Enoxaparin sodium

Scheme 1-preparation steps of Enoxaparin Sodium

Preparation of Heparin Benzyl Chloride Salt: Dissolve sodium heparin in pure water, then add benzyl chloride ammonium solution. Allow the reaction to proceed at room temperature for 1-3 hours. After the reaction, centrifuge, wash the precipitate with water, and obtain heparin benzyl chloride salt.

Elution of Heparin Benzyl Chloride Salt: At room temperature, dissolve heparin benzyl chloride salt in N,N-dimethylformamide. After loading the sample, wash with a mixture of dichloromethane and ethanol, then elute with 1.5 mol/L sodium chloride solution. The elution endpoint is when the UV absorption curve at 263 nm stabilizes at the baseline. Collect the eluted heparin benzyl chloride salt solution.

Preparation of Heparin Benzyl Ester: Add benzyl chloride to the heparin benzyl chloride salt eluate. Perform esterification at 30-40°C for 20-40 hours. After completion, cool to room temperature, add sodium acetate in methanol to precipitate, separate the precipitate, wash with methanol, and dry to obtain heparin benzyl ester.

Preparation of Enoxaparin Sodium: Dissolve heparin benzyl ester in purified water, stir at 60°C, and add sodium hydroxide. React for 30-60 minutes, adjust pH to 6-8 with hydrochloric acid, filter, add sodium chloride solution, and then add four volumes of methanol. Let it sit for 12-24 hours, collect the precipitate, and dissolve it in ten volumes of purified water. After complete dissolution, add hydrogen peroxide, react for 6-12 hours, filter, add sodium chloride, and add four volumes of methanol. Dry to obtain Enoxaparin Sodium.

Case Study 1-Enoxaparin Sodium Combo Therapy in Severe Preeclampsia: Retrospective Study

To observe the effect of enoxaparin sodium combined with magnesium sulfate in the treatment of severe preeclampsia on newborns. A retrospective analysis was conducted on clinical data of 80 patients with severe preeclampsia admitted to Hefei Second People's Hospital from January 2019 to December 2020. Treatment records indicated 40 cases received magnesium sulfate alone (single group) and 40 cases received enoxaparin sodium combined with magnesium sulfate (combination group). Levels of D-dimer, soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PLGF), newborn Apgar scores, gestational weeks, and incidence of adverse reactions were compared before and after treatment. After treatment, the combination group showed significantly lower levels of D-dimer, sFlt-1, and adverse reaction rates compared to the single group (P<0.05). PLGF levels, newborn Apgar scores, and gestational weeks were significantly higher in the combination group compared to the single group (P<0.05). Compared to magnesium sulfate alone, the combination of enoxaparin sodium and magnesium sulfate in the treatment of severe preeclampsia effectively regulates cytokine levels in patients, improves pregnancy outcomes, and enhances newborn Apgar scores. The low incidence of adverse reactions indicates that this treatment regimen is safe and effective.

Case Study 2-Influence of Enoxaparin sodium on Intestinal Microcirculation in Lipopolysaccharide-Induced Septic Rats

During severe sepsis or septic shock, activation of the inflammatory and coagulation systems can lead to microcirculatory dysfunction and microvascular thrombosis, ultimately resulting in multiple organ dysfunction and death. Enoxaparin can inhibit factor Xa and reduce endothelial damage. This study aimed to investigate the effect of enoxaparin on intestinal microcirculation in endotoxemic rats. Thirty male Wistar rats were divided into three groups: sham-operated (OP), lipopolysaccharide (LPS), and LPS + Enoxaparin groups. The rats underwent a midline laparotomy to exteriorize a segment of the terminal ileum for microcirculation examination using a full-field laser perfusion imager and sidestream dark field video microscope, assessing the mucosa, muscle, and Peyer's patch. In the LPS and LPS + Enoxaparin groups, 15 mg/kg LPS was administered intravenously to induce endotoxemia, and 400 IU/kg enoxaparin sodium was also administered in the LPS + Enoxaparin group. At 240 minutes, the mean arterial pressure was significantly higher in the LPS + Enoxaparin group compared to the LPS group (93 ± 9 versus 64 ± 16 mm Hg, P < 0.001). Microcirculatory blood flow intensity was higher in the LPS + Enoxaparin group compared to the LPS group: mucosa (1085 ± 215 versus 617 ± 214 perfusion units [PU], P < 0.001); muscle (760 ± 202 versus 416 ± 223 PU, P = 0.001); and Peyer's patch (1,116 ± 245 versus 570 ± 280 PU, P < 0.001). Enoxaparin inhibited the reduction in perfused small vessel density and increase in microcirculatory heterogeneity induced by LPS. Enoxaparin can prevent intestinal microcirculatory dysfunction in endotoxemic rats by preventing microvascular thrombosis formation and maintaining normal mean arterial pressure.

Notes: Comparison of total small vessel density (TSVD), perfused small vessel density (PSVD), and heterogeneity index (HI) of the terminal ileum at 240 minutes. Groups: 1) Sham OP group, 2) LPS group, and 3) LPS + Enoxaparin group. *P < 0.05 compared to Sham OP group; †P < 0.05 compared to LPS + Enoxaparin group. HI, heterogeneity index; LPS, lipopolysaccharide; PSVD, perfused small vessel density; TSVD, total small vessel density. (Yeh YC.,2012)

Enoxaparin sodium is a low molecular weight heparin that functions similarly to standard heparin but with more specific and defined effects.

Inhibition of Thrombin: Enoxaparin sodium exerts its anticoagulant effect by enhancing the inhibition of thrombin by antithrombin III. Antithrombin III is a crucial natural anticoagulant in the blood that inhibits thrombin, thereby reducing the formation of blood clots.

Inhibition of Factor Xa: Enoxaparin sodium also strongly inhibits factor Xa, a key enzyme in the coagulation cascade responsible for converting prothrombin to thrombin. By inhibiting factor Xa activity, enoxaparin sodium effectively reduces thrombin formation and thus decreases blood clot formation.

Inhibition of Cell Adhesion: Enoxaparin sodium can reduce the expression of surface adhesion molecules (such as VCAM-1 and ICAM-1) on endothelial cells, thereby decreasing the adhesion and infiltration of white blood cells, further lowering the risk of inflammation and thrombosis.

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