Analysis of the source of ethylene oxide sterilization residues in medical devices.(II)

Second, the analysis of sterilizing residues.

The production process of ethylene oxide is divided into chlorol and oxidation. The chlorool method is the early production method of ethylene oxide. There are two main reaction processes: the first step: C2H4-HClO-CH2-CH2OH; The interstitonal product during the reaction is 2-chloroethanol (CH2Cl-CH2OH). Due to the backward technology of chlorol, serious pollution of the environment, coupled with the product of serious corrosion of equipment, most manufacturers have been phased out. The oxidation method is divided into the air method and the oxygen method. Depending on the purity of the oxygen, the production consists of two main reaction processes: the first step: 2C2H4 and O2 -2C2H4O; At present, the industrial production of ethylene oxide mainly uses the direct oxidation process of ethylene, which is silver-based catalyst. Therefore, the production process of ethylene oxide is a factor in the evaluation of 2-chloroethanol after sterilization.

The confirmation and development of ethylene oxide sterilization process is carried out in accordance with the relevant provisions of GB/T 16886.7-2015 standard, and most of the residues after sterilization are present in the original form according to the physicochemical properties of ethylene oxide. The factors affecting the residual amount mainly include the adsorption of ethylene oxide, packaging material and thickness of medical devices, temperature and humidity before and after sterilization, the time of sterilization and the time of analysis, storage conditions, etc., and the above factors determine the escape capacity of ethylene oxide. It has been reported in the literature that the concentration of ethylene oxide sterilization is usually selected at 300-1000 mg. L-1. The loss factors of ethylene oxide include: adsorption of medical devices, hydrolysis in certain humidity conditions, etc. The concentration is 500-600 mg. L-1 is relatively cost-effective, reduces the consumption of ethylene oxide and the residue on the sterilized articles, saving the cost of sterilization.

Chlorine is widely used in the chemical industry and many products are closely related to us. It can be used as an intermediate, such as vinyl chloride, or as a final product, such as bleach. At the same time, chlorine also exists in the air, water and other environment, the harm to the human body is also obvious. Therefore, when the relevant medical devices are sterilized by ethylene oxide, we should consider the comprehensive analysis of the production, sterilization, storage and other links of the product, and take appropriate measures to control the residual amount of 2-chloroethanol.

There are literature reports that the average daily dose of 2-chloroethanol to patients should not exceed 9 mg, and the residual amount of 2-chloroethanol reached nearly 150 ?g/chip after 72 hours of analysis, with reference to the short-term contact devices specified in the standard sg/T16886.7-2015, the average daily dose of 2-chloroethanol to patients should not exceed 9 mg, and its residue should be well below the limits in the standard.

The residual amount of ethylene oxide and 2-chloroethanol in 3 stitchneedles were determined by study, the material was nylon threaded stitching needles, the result of ethylene oxide was undetected, and the result of 2-chloroethanol was 53.7 sg.g-1. YY 0167-2005 provides for non-absorbent surgical stitches for ethylene oxide detection limits, 2-chloroethanol is not specified. Sutures have a lot of industrial water in the production process. China's surface water four types of water quality is applicable to general industrial protection areas and human non-direct contact water areas, generally by bleaching powder treatment, can control algae and microorganisms in the water, for sterilization and health prevention. Its main active ingredient is calcium hypochlorite, which is produced by chlorine gas through limestone. Calcium hypochlorite is easily degraded in the air, the main reaction siphons are: Ca (ClO) 2 plus CO2-H2O-CaCO3-2HClO. The hypochloric acid is easily decomposed into hydrochloric acid and water under light, the main reaction is: 2HClO plus light - 2HCl-O2. Chlorine negative ions are easily adsorbed in the suture line, and under a certain weak acidic or weak alkaline environment, ethylene oxide open ring and its production of 2-chlorinethanol.

It has been reported in the literature that the residual 2-chlorine ethanol from artificial crystal samples was extracted with acetone ultrasound, and the gas chromatography-mass spectrometry method was measured, but it was not detected. YY0290.8-2008 "Ophthalmological Optics Artificial Crystals Part 8: Basic Requirements", the artificial crystal sepsis on the 2-chloroethanol residue should not exceed 2.0 sg per day, the total amount of each crystal should not exceed 5.0 sg. The GB/T16886.7-2015 standard mentions that 2-chloroethanol residues cause four times as much eye toxicity as the same level of ethylene oxide.

In summary, in evaluating the residuals of medical devices after sterilization of ethylene oxide, the focus should be on ethylene oxide and 2-chlorine ethanol, but the residuals should be analyzed according to the actual comprehensive analysis.

In the process of sterilization of medical devices, some of the raw materials used in single-use medical devices or packaging materials include PVC, PVC resin in the processing due to the decomposition of resin will also produce a very small amount of vinyl chloride monomer. GB10010-2009 Medical soft PVC pipe specified that the content of vinyl chloride monomer can not exceed 1 ?g.g-1. Vinyl chloride is easily polymerized under the action of catalyst (peroxide, etc.) or light and heat, and the production of PVC is collectively referred to as vinyl chloride resin. Polyvinyl chloride exposure to more than 100 degrees C or exposure to ultraviolet radiation can have the possibility of hydrogen chloride gas escape. Then the combination of hydrogen chloride gas in the package and ethylene oxide produces a certain amount of 2-chloroethanol.

Ethylene glycol, stable in nature, not easy to volatilize. The oxygen atoms in ethylene oxide are belted with two isolated pairs of electrons, which are strongly hydrophilic and are more likely to produce ethylene glycol when co-existing with negative chloride ions. For example: C2H4O, NaCl,H2O-CH2Cl-CH2OH-NaOH. This process reacts with a weak alkaline end and a strong alkaline end, and the incidence of this reaction is low. The higher incidence is ethylene oxide water-generating glycol: C2H4O-H2O-CH2OH-CH2OH, and the water-co-operation of ethylene oxide inhibits its binding with free chlorine negative ions.

In the production, sterilization, storage, transportation, use and so on, if negative chloride ions are introduced, there is a possibility of cycloethylene and its reaction to produce 2-chloroethanol. Since the chlorinol method has been eliminated in the production process, the inter-product 2-chloroethanol will not appear in the direct oxidation method. In the production of medical devices, some raw materials have strong adsorption properties for ethylene oxide and 2-chloroethanol, so the control of its residuemustbe be considered when analyzing after sterilization. In addition, in the production of medical devices, raw materials, additives, reaction inhibitors and other inorganic salts in the form of chlorides, in sterilization, must take into account ethylene oxide in acidic or alkaline conditions open ring, SN2 reaction, combined with free chlorine chloride to produce 2-chlorinethanol.

At present, the common detection of ethylene oxide, 2-chloroethanol, ethylene glycol method sesame. Ethylene oxide can also be supplied with red sulphate test liquid contrast color method for testing, but its disadvantage is that the authenticity of the test results are affected by the experimental conditions of more factors, such as ensuring that the experimental ambient temperature of 37 degrees C is constant to control the reaction of ethylene glycol, after color treatment to be measured liquid placement time. Therefore, in qualified laboratories, proven methodological validation (including accuracy, precision, linearity, sensitivity, etc.) is of reference to quantitative testing of residues.