Application and Synthesis of Propofol

Propofol is derivative of phenol. It is a short-acting intravenous anesthetic and it belongs to the national banned drugs. The effect of general anesthetics (propofol and volatile anesthetics) on pulmonary outcome after lung resection surgery with one-lung ventilation (OLV) is yet undetermined. We evaluated the effect of intravenous anesthesia (propofol) and volatile anesthesia (sevoflurane or desflurane) regimens on postoperative pulmonary complications (PPCs) in patients undergoing lung resection surgery.

Figure 1 the molecular formula of propofol

Application and research

Propofol is a common sedative anesthetic for painless endoscopy, characterized by quick effect and short action time, but the inhibitory effect on respiratory circulation is its fatal disadvantage. In clinical practice, opiates are commonly used while bronchoscopy is conducted to reduce the dosage of propofol. However, the combined administration of propofol and opiates is more likely to cause respiratory inhibition in the elder patients and the propofol circulation fluctuates greatly. The ideal sedative method should increase the patient cooperation, shorten rehabilitation time, and improve endoscopist satisfaction. The important goals of anesthesiologists are the approaches to minimal cognitive dysfunction, rapid recovery and obtaining the psychological function levels as those before anesthesia[1]. 

Propofol has recently been attracted increasing attention for its anti-tumor property in cancers, including colorectal cancer (CRC). However, the anti-tumor molecular determinants of propofol largely remain to be elucidated. The levels of circRNA poly(A) binding protein nuclear 1 (circ-PABPN1, hsa_circ_0031288), microRNA (miRNA)-638 and serine and arginine-rich factor 1 (SRSF1) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell viability, colony formation, apoptosis, invasion, and migration were detected by the Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, transwell, and woundhealing assays, respectively. Animal studies were used to evaluate the biological action of circ-PABPN1 in the propofol-mediated anti-CRC effect. Targeted relationships among circ-PABPN1, miR-638 and SRSF1 were validated by dual-luciferase reporter assays. 

Our data showed the anti-tumor activity of propofol in CRC, as evidenced by the repression in cell viability, colony formation, invasion, migration and the promotion in cell apoptosis in vitro, as well as the suppression in tumor growth in vivo. Circ-PABPN1 was overexpressed in CRC tissues and cells, and propofol down-regulated circ-PABPN1 in a dose-dependent manner. Moreover, circ-PABPN1 was a functional effector of propofol in suppressing CRC development in vitro and in vivo. Circ-PABPN1 directly targeted miR-638, and SRSF1 was a direct target of miR-638. Propofol repressed CRC development in vitro by up-regulating miR-638 or downregulating SRSF1. Furthermore, propofol regulated SRSF1 expression by the circ-PABPN1/miR-638 axis in CRC cells.Their current findings identified the circ-PABPN1/miR-638/SRSF1 axis as a novel anti-tumor mechanism of propofol in CRC, providing a new rationale for developing propofol as a promising therapeutic agent for CRC[2].

The effect of general anesthetics (propofol and volatile anesthetics) on pulmonary outcome after lung resection surgery with one-lung ventilation (OLV) is yet undetermined. We evaluated the effect of intravenous anesthesia (propofol) and volatile anesthesia (sevoflurane or desflurane) regimens on postoperative pulmonary complications (PPCs) in patients undergoing lung resection surgery. 

This prospective, randomized controlled trial enrolled 555 adult patients scheduled for lung resection surgery with OLV. Participants were randomized to 1 of 3 general anesthetic regimens (propofol, sevoflurane, or desflurane). Standard anesthesia and ventilation protocols were followed in all groups. The primary outcome was a composite of PPCs in the first 7 postoperative days. Secondary outcomes included the severity of PPCs and major postoperative complications classification. Intergroup difference in the primary outcome was assessed for significance using the Pearson χ2 test. Of 837 patients who were assessed for eligibility, 555 were randomized and 545 were analyzed. One hundred and seventy-nine patients were assigned to the propofol group, 182 in the sevoflurane group, and 184 in the desflurane group. The incidence of PPCs did not differ between the combined volatile anesthetics (sevoflurane and desflurane) group and the propofol group (21.9% vs 24.0%; odds ratio, 0.89; 95% confidence interval, 0.58-1.35; P = .570). The PPCs grade and Clavien-Dindo scores did not differ significantly across groups. In patients undergoing lung resection surgery with OLV, general anesthesia with volatile anesthetics (sevoflurane or desflurane) did not reduce PPCs compared with propofol. No difference in secondary outcomes was observed[3].

Synthesis research

The crude product of propofol widely adopts high pressure synthesis method. The advantages of this method are low cost and high yield. The disadvantage is that it reacts under high pressure conditions, the risk factor is relatively large, and the requirements for equipment are high. Based on the above advantages and disadvantages, the process route is carried out. Improved. The new process is carried out under normal pressure conditions, the risk factor is greatly reduced, and the yield, purity, and color are not affected. And improved in the later refining method, the cost is greatly reduced, the refined waste liquid can be recycled and reused, and the discharge of industrial waste liquid is reduced. The synthetic route is as follows:

Figure of process synthesis route

The synthesis method of this process takes a relatively long time, but compared with high-pressure reaction, the risk factor is lower. The refining method is easier to operate than vacuum distillation, and has low cost, high purity, gas chromatography detection purity >99.9%, high performance liquid chromatography detection product Purity>99.5%, refined waste liquid can be reused, reducing waste liquid discharge.

reference

1.Ma J J, Xiong W, Guo D Z , et al. Effects of Sevoflurane-Propofol-Balanced Anesthesia on Flash Visual Evoked Potential Monitoring in Spine Surgery: A Randomized Noninferiority Trial.[J]. Anesthesia and analgesia,2021.

2.Zhao A X, Liu Y C. Propofol suppresses colorectal cancer development by the circ-PABPN1/miR-638/SRSF1 axis[J]. Analytical Biochemistry,2021,631.

3.Li X F, Hu J R, Wu Y, et al. Comparative Effect of Propofol and Volatile Anesthetics on Postoperative Pulmonary Complications After Lung Resection Surgery: A Randomized Clinical Trial.[J]. Anesthesia and analgesia,2021,133(4).