Preparation Of New Enoxaparin Sodium Bone Cement And Its Biomechanical Study

Pulmonary embolism includes pulmonary thromboembolism(PTE),fat embolism,amniotic fluid embolism,air embolism,etc.PTE is the most common type of pulmonary embolism,accounting for more than 90% of pulmonary embolism.If not treated,it may cause Serious consequences even death.According to prospective studies,the incidence of PTE in acute trauma and orthopedic surgery is 0.46%,after diagnosis of PTE.The mortality rate is as high as 12.7%.At present,the most commonly used drug for prevention and treatment of PTE is low molecular weight heparin.Preoperative subcutaneous injection of low molecular weight heparin can prevent deep vein thrombosis,but it will increase the risk of intraoperative bleeding,while the wound continues to ooze and the hemostasis time is prolonged.The risk of subcutaneous oozing and infection in the posterior wound is also increased.Therefore,orthopedic surgeons generally stop using anticoagulant drugs within 12 hours before and after orthopedic surgery to reduce the risk of intraoperative and postoperative bleeding.However,the risk of thromboembolism is increased after discontinuation of anticoagulant drugs.Therefore,how to effectively intervene in this anticoagulation blank window to prevent thrombosis and reduce intraoperative and postoperative bleeding is an important problem to be solved in orthopedic surgery.Among the diseases such as joint replacement,vertebroplasty,bone metastases and bone defects,polymethylmethacrylate(PMMA)bone cement is an important material widely used.By applying bone cement,the prosthesis can be firmly fixed to the bone tissue to fill and anchor between the prosthesis and the bone.PMMA bone cement consists of two parts,a liquid phase and a solid phase,wherein the main component of the liquid phase is methyl methacrylate monomer and the solid phase is polymethyl methacrylate powder.When the solid phase is mixed with the liquid phase during use,polymerization can occur,and during the polymerization of the monomer,a certain pore structure can be formed,and some water-soluble drugs can remain in the pore structure,and after being implanted into the human body,It is gradually released in the body fluid environment,so PMMA bone cement can be used as a carrier for drug release.Enoxaparin Sodium(ES)is a low molecular weight heparin that is widely used in clinical practice.Its antithrombotic and anticoagulant activities are separate,and its main feature is its anti-Xa activity relative to anticoagulant factor IIa,ie,antithrombin activity,and local application does not cause thrombocytopenia.We try to prepare a new enoxaparin sodium bone cement mixed with enoxaparin sodium to achieve local anticoagulation and precise treatment,without stopping the low molecular weight heparin drugs before surgery to reduce the circumference.Hemorrhage during the operation period reduces the risk of thromboembolism.At present,the research focus at home and abroad are focused on the clinical application of antibiotic bone cement in the treatment of infection and the related research on drug-loading calcium phosphate cement.So far,relevant literatures and reports on new enoxaparin bone cement have not been retrieved in foreign literature databases.The aim of this study was to conduct a preliminary study on the development and biomechanics of the new enoxaparin sodium bone cement to determine whether the new enoxaparin sodium bone cement meets the biomechanical requirements for clinical application,and to explore enoxaparin by different mixing methods.The biomechanical effect of sodium addition to bone cement lays the foundation for further experiments on the new enoxaparin sodium bone cement.Part 1 Preparation and biomechanical study of new enoxaparin sodium polymethylmethacrylate bone cementObjective: To explore the preparation of new enoxaparin sodium bone cement and its biomechanical study.Methods: The enoxaparin sodium injection was mixed with polymethyl-methacrylate(PMMA)bone cement at different doses and divided in seven different mass fractions: A(blank group),B(4000AxaIU),C(8000AxaIU),D(12000AxaIU),and E(16000AxaIU),F(20000AxaIU),G(24000AxaIU).In the environment of temperature 23±1 °C,aseptic,relative humidity higher than 40%(operating room environment),the final setting time was measured by standard Vicat instrument.According to the ISO5833:2002 "Implants for surgery-Acrylic resin cement",we made the cemented cylinder specimens and cuboid specimens.After measurement and X-ray irradiation inspection,each group of 10 samples was selected.The compressive strength,flexural strength and flexural modulus were measured on the electronic material universal test machine.Results: The Statistical analysis showed no statistical difference for the results of final setting time.The biomechanical results showed that the compressive strength,flexural strength and flexural modulus of the A-G group decreased with the increase of the dose of enoxaparin sodium for injection.After 4 weeks,the A-E group were not significantly different from those in advance.The lowest values of compressive strength,flexural strength and flexural modulus of each group are higher than international standards.Summary: The enoxaparin sodium injection can be added to the PMMA bone cement.When it is not higher than 8000 AxaIU,it will not have a significant effect on the mechanical properties of the bone cement,which fulfills the biomechanical requirements of clinical application.Part 2 Effect of different mixing modes of enoxaparin sodium on biomechanics of bone cementObjective: To explore the biomechanical effects of enoxaparin sodium added to PMMA bone cement in different mixing modes.Methods: The enoxaparin sodium for injection was mixed with polymethylmethacrylate(PMMA)bone cement according to different dosages and different mixing methods.Group A was used as blank control group without enoxaparin sodium.B(8000AxaIU)group,C(16000AxaIU)group and the D(24000AxaIU)group were added as a control group in a powder mixture.The E(8000AxaIU)group,F(16000AxaIU)group and G(24000Axa IU)group were used as experimental groups to dissolve the enoxaparin sodium for injection.Then add to the PMMA bone cement.In the operating room environment,according to the International Organization for Standardization,made Bone cement cylinder specimens and cuboid specimens.After vernier caliper measurement and X-ray irradiation detection,5 experiments of each set of test pieces were selected for experiment.The compressive strength and the four-point bending test were measured on an electronic material universal testing machine.Results: The compressive strength and the four-point bending test of the experimental group E,F and G were significantly lower than those of the control group.The difference was statistically significant.The lowest values were(57.17±1.15)MPa,(67.93±0.55).)MPa,(19.2 ± 0.114)GPa.Summary: The addition of enoxaparin sodium to PMMA bone cement in a liquid mixture will significantly affect the biomechanical properties of bone cement and does not meet the requirements of clinical application.Conclusion:1.The enoxaparin sodium powder for injection can be added to the PMMA bone cement.When it is not higher than 8000 AxaIU,it will not have a significant effect on the mechanical properties of the bone cement.The difference is not statistically significant.In the experimental design group,the lowest values of compressive strength,flexural strength and flexural modulus(83.75±0.42)MPa,(86.65±0.62)MPa,and(2.11±0.119)GPa were higher than international standards.Provisions that meet the biomechanical requirements for clinical applications.2.Dissolving enoxaparin sodium for injection and then mixing with bone cement will significantly reduce the mechanical properties of bone cement.It proves that mixing the liquid with PMMA bone cement will obviously affect the biomechanical properties of bone cement,which is not in line with clinical application.