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Rationale: Ethylene oxide (EO) sterilization is commonly employed for the sterilization of medical devices and has a very high market share. However, EO and its metabolite ethylene chlorohydrin (ECH) are toxic to humans. In compliance with the classification and residue limits of medical devices defined by ISO 10993-7, our study established two extraction methods for the testing of EO and ECH., Methods: The first method involves simulated-use extraction using water as the extraction solvent. While the second, exhaustive extraction, directly extracts sample through headspace sampling analysis. Gas chromatography-tandem mass spectrometry in multiple reaction monitoring mode was utilized, requiring only 16 min. Then, the developed method was applied to assess 10 commercially available medical devices sterilized by EO., Results: In simulated-use extraction, calibration curves were evaluated in the range of 1-100 and 5-500 μg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 85.0% to 95.2% and from 94.8% to 102.4%. In exhaustive extraction, calibration curves spanned 0.5-50 and 2-200 μg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 101.6% to 102.1% for EO and from 98.1% to 102.2% for ECH. After analysis of the 10 commercially available medical devices, two cotton swabs were found to have ECH of 35.1 and 28.4 μg per device, and four medical devices were found to have EO with concentration below the limit of quantification. Meanwhile, we found that the EO internal standard (propylene oxide) recommended by ISO 10993-7 had interference problems with other similar substances and was not suitable as an internal standard for EO., Conclusions: This study offers a sensitive and straightforward analytical approach to EO and ECH residues in a variety of medical devices. In addition, the results show that the EO or ECH content of these types of medical devices in our study falls below the regulatory limits, therefore instilling confidence among consumers regarding their safe use., (© 2024 John Wiley & Sons Ltd.)

A "one-step" strategy has been demonstrated for the tunable synthesis of multifunctional aliphatic polycarbonates (APCs) with ethylene oxide (EO), ethylene carbonate (EC), and cyclohexene oxide (CHO) side groups by the copolymerization of 4-vinyl-1-cyclohexene diepoxide with carbon dioxide under an aminotriphenolate iron/PPNBz (PPN = bis(triphenylphosphine)-iminium, Bz = benzoate) binary catalyst. By adjusting the PPNBz-to-iron complex ratio and incorporating auxiliary solvents, the content of functional side groups can be tuned within the ranges of 53-75% for EO, 18-47% for EC, and <1-7% for CHO. The yield and molecular weight distribution of the resulting multifunctional APCs are affected by the viscosity of the polymerization system. The use of tetrahydrofuran as an auxiliary solvent enables the preparation of narrow-distribution polycarbonates at high conversion. This work presents a novel perspective for the preparation of tailorable multifunctional APCs.

Biodegradable shape memory polymers provide unique regenerative medicine approaches in minimally invasive surgeries. Once heated, thermally responsive shape memory polymer devices can be compressed, programmed to fit within a small profile, delivered in the cold programmed state, and expanded when heated to body temperature. We have previously developed a biodegradable shape memory elastomer (SME), poly(glycerol dodecanedioate) (PGD), with transition temperatures near 37°C exhibiting nonlinear elastic properties like numerous soft tissues. Using SMEs in the clinic requires disinfection and sterilization methods that conserve physiochemical, thermomechanical, and shape recovery properties. We evaluated disinfection protocols using 70% ethanol and UV254 nm for research applications and ethylene oxide (EtO) gas sterilization for clinical applications. Samples disinfected with ethanol for 0.5 and 1 min showed no changes in physiochemical material properties, but after 15 min showed slower recovery rates than controls (p < .05). EtO sterilization at 54.4°C decreased transition temperatures and shape recovery rate compared to EtO sterilization at 37.8°C (p < .01) and controls (p < .05). Aging samples for 9 months in a vacuum desiccator significantly reduced shape recovery, and the recovery rate in EtO sterilized samples compared to controls (p < .001). Cytotoxicity testing (ISO-10993.5C:2012) revealed media extractions from EtO sterilized samples, sterilized at 37.8°C, and high-density polyethylene negative control samples exhibit lower cytotoxicity (IC50) than Ethanol 1 min, UV 2 h, and EtO 54.4°C. Cell viability of NIH3T3 fibroblasts on sterilized surfaces was equivalent on EtO 37.7°C, EtO 54.4°C and Ethanol sterilized substrates. Finally, chromogenic bacterial endotoxin testing showed endotoxin levels were below the FDA prescribed levels for devices contacting blood and lymphatic tissues for ethanol 1 min, UV 120 min, EtO 37.7°C, EtO 54.4°C. These findings outline various disinfection and sterilization processes for research and pre-clinical application and provide a pathway for developing custom sterilization cycles for the translation of biomedical devices utilizing PGD shape memory polymers., (© 2022 Wiley Periodicals LLC.)

Reactions of oxirane ring opening provide a powerful tool for regio- and stereoselective synthesis of polyfunctional and heterocyclic compounds, widely used in organic chemistry and drug design. Cyclooctane, alongside other medium-sized rings, is of interest as a novel molecular platform for the construction of target-oriented leads. Additionally, cyclooctane derivatives are well known to be prone to transannular reactions, which makes them a promising object in the search for novel approaches to polycyclic structures. In the present work, a series of cyclooctanediones was studied in Corey-Chaykovsky reactions, and novel spirocyclic bis(oxiranes) containing cyclooctane core, namely, 1,5-dioxadispiro[2.0.2.6]dodecane and 1,8-dioxadispiro[2.3.2.3]dodecane, were synthesized. Ring opening of the obtained bis(oxiranes) upon treatment with sodium azide was investigated, and it was found that the reaction path is determined by the reciprocal orientation of oxygen atoms in the oxirane moieties. Diastereomers of the bis(oxiranes) with cis -orientation underwent independent ring opening, supplying corresponding diazidodiols, while in the case of stereoisomers with trans -orientation, domino-like reactions occurred, including intramolecular nucleophilic attack and the formation of a novel three- or six-membered O-containing ring. Summarily, a straightforward approach to polyfunctional compounds containing cyclooctane or oxabicyclo[3.3.1]nonane cores, employing bis(oxiranes), was elaborated.

Ensuring the sterility of life science products plays a pivotal role in the healthcare sector. Gamma irradiation and ethylene oxide sterilization are two commonly applied methods for the sterilization of medical devices, packaging components and Active Pharmaceutical Ingredients (API) for medicinal products. Focussed studies on the effects of sterilization processes on APIs remain limited. In this research study, five APIs, frequently used in sterile ophthalmic preparations were subjected to both gamma irradiation and ethylene oxide under different process conditions. The following APIs of GMP quality were selected: dexamethasone, aciclovir, tetracycline hydrochloride, triamcinolone and methylprednisolone. Analyses were performed using High Performance Liquid Chromatography equipped with UV detection and the effect of sterilization conditions on the APIs was evaluated by the assay and related substances test prescribed by the European Pharmacopoeia (Ph. Eur.). It was concluded that exposure to ethylene oxide resulted in compliance with Ph. Eur. for all APIs. While dexamethasone and methylprednisolone did not meet the requirement for the Ph. Eur. after exposure to gamma irradiation, the other three APIs did meet the requirement under the specified irradiation conditions. Subsequent optimization of sterilization parameters positively influenced the compliance to the Ph. Eur. requirements., Competing Interests: Declaration of Competing Interest Sterigenics has no conflict of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The 'ethylene glycol ethers' (EGE) are a broad family of solvents and hydraulic fluids produced through the reaction of ethylene oxide and a monoalcohol. Certain EGE derived from methanol and ethanol are well known to cause toxicity to the testes and fetotoxicity and that this is caused by the common metabolites methoxy and ethoxyacetic acid, respectively. There have been numerous published claims that EGE fall into the category of 'endocrine disruptors' often without substantiated evidence. This review systematically evaluates all of the available and relevant in vitro and in vivo data across this family of substances using an approach based around the EFSA/ECHA 2018 guidance for the identification of endocrine disruptors. The conclusion reached is that there is no significant evidence to show that EGE target any endocrine organs or perturb endocrine pathways and that any toxicity that is seen occurs by non-endocrine modes of action., (Copyright © 2022 The Author. Published by Elsevier Inc. All rights reserved.)

Recyclable aqueous two-phase systems with thermo-responsive phase-forming materials have been employed to separate macromolecules; however, these systems have achieved very limited separation efficiency for small molecules, such as antibiotics. In this study, aqueous two-phase systems composed of the ethylene oxide/propylene oxide copolymer and water were developed to extract alkaline antibiotics from the fermentation broth. In the aqueous two-phase systems with an ethylene oxide ratio of 20 and propylene oxide ratio of 80, the partition coefficients of tylosin and spiramycin reached 16.87 and 20.39, respectively, while the extraction recoveries were 70.67 and 86.70%, respectively. Coupled with mechanism analysis, we demonstrated the feasibility of extracting alkaline antibiotics using this aqueous two-phase system, especially for 16-membered macrolide antibiotics. The molecular dynamic simulation was employed to visualize the process of dual-phase formation and the partition behavior of antibiotics in an aqueous two-phase system. The dynamic simulation revealed the binding energy between the antibiotic and ethylene oxide/propylene oxide copolymers, which provides a simple indicator for screening suitable antibiotics in aqueous two-phase systems. Our recyclable aqueous two-phase systems provide a robust approach for the extraction of 16-membered macrolide antibiotics with ease of operation and high recovery rates, which is appropriate for large-scale extraction in the fermentation industry., (© 2021 Wiley-VCH GmbH.)

This study evaluated the performance of a new O 3 /H 2 O 2 mixed gas sterilization instrument for killing microorganisms and inactivating bacterial endotoxin at low temperatures. Sterility assurance level was achieved by an over 6-log reduction of Geobacillus stearothermophilus ATCC 12980, and the decimal reduction value was 0.77 min in sterilization mode. A reduction of over 3 logs in Limulus amebocyte lysate coagulation activity of purified endotoxin from Escherichia coli was observed after treatment in endotoxin-inactivation mode. The same inactivation ability was observed when treating dried bacterial cells. Biomaterials made of polymer or metal did not exhibit cytotoxicity after gas exposure at O 3 concentrations below 200 ppm. As the results of human cell-based pyrogen testing, significant amounts of endotoxin that were over the limit for medical devices contacting cerebrospinal fluid (2.15 EU/device) were detected on scissors washed with a washer-disinfector and sterilized with ethylene oxide or autoclaving. In contrast, endotoxin decreased to 0.29 ± 0.05 EU/device after O 3 /H 2 O 2 mixed gas sterilization in endotoxin-inactivation mode. Compared to conventional gas sterilization methods, O 3 /H 2 O 2 mixed gas has high sterilization ability and a strong capacity to inactivate endotoxin. It is expected that this sterilization technology will improve the safety of reusable medical devices and utensils for regenerative medicine., (© 2021 Wiley Periodicals LLC.)