China since the 1980s the introduction of foreign chlorine dioxide products and began to study its production process, after more than a decade of time, not only has the domestic chlorine dioxide products, and the production process has improved greatly, the chlorine dioxide as an oxidizing disinfectant out of the problem has also had a considerable understanding of the application of chlorine dioxide. With the wide application of the product, promote the development of the product dosage form, there are chlorine dioxide generator, stable chlorine dioxide, as well as tablets and other solid chlorine dioxide products. Now the chlorine dioxide used for disinfection of the dosage form is summarized below.
1. Chlorine dioxide generator
1.1 The nature and preparation of chlorine dioxide
Chlorine dioxide is an oxide of chlorine, with an irritating odor similar to chlorine, molecular formula ClO2, molecular weight of 67.457, melting point -59 ° C, boiling point of 11 ° C, exists in the form of a gas at room temperature, for a kind of yellowish green gas. When the concentration increases, the color changes to orange-red, gas chlorine dioxide is extremely unstable. Chlorine dioxide is soluble in water, solubility at 20 ° C for 107.98 mg / L, can be made into an unstable liquid, its liquid and gas on the temperature, pressure and light are more sensitive, when the content of the air is higher than 10%, the spark can be detonated [1], chlorine dioxide is an unstable compound in water can be turned into HClO2 and HClO3.3., about 2-10% per day at room temperature The dissociation rate of [2], so it is not conducive to the preparation and transportation of large quantities, generally more in the use of the site now prepared.
Chlorine dioxide generator preparation of chlorine dioxide methods are mainly electrolysis and chemical methods, electrolysis is widely used in the diaphragm electrolysis, salt as raw material, under the action of the electric field to generate a mixture of chlorine dioxide containing sodium hypochlorite, hydrogen peroxide, ozone, the concentration of chlorine dioxide is generally only 10-30% or so, most of the chlorine gas. Chemical method mainly with sodium chlorate and sodium chlorite as raw materials for the two types of chlorine dioxide generation method. In the sodium chlorate method of production of chlorine dioxide process, if the chlorine ion as a reducing agent, the produced chlorine dioxide has the disadvantage of low purity, while the sodium chlorite method of chlorine dioxide has a high proportion of the general in more than 90%.
1.2 Equipment and sterilization performance
The generators introduced from abroad are mainly Tetraralent, Rio Lindo, Germany's Prominent, etc., Li Lingwen et al [3] reported the synergistic sterilization effect of chlorine dioxide synergistic disinfector of Tetraralent, which utilizes electrolysis of the salt solution, and at the same time generates chlorine dioxide, chlorine gas, ozone and hydrogen peroxide, which are dissolved in water and synergistically sterilized, and its sterilizing effect is superior to any of the above mentioned disinfectants.The experimental results also indicate that the electrolysis voltage, current, electrolyte concentration and effective area of anode of electrolysis tank have an effect on the gas production of the sterilizer. Huan Pengcheng et al [4] on the United States Vulcan Rio Linda T140 chlorine dioxide generator for disinfection effect observation, the generator generates chlorine dioxide concentration can be adjusted in 2000-300mg / L, kill Escherichia coli, Staphylococcus aureus 1mg / L 3 minutes, kill Bacillus subtilis black variant spores 125mg / L 5 minutes, destroy HBsAg 125mg/L 2 minutes, the lowest concentration of energy experiments for 400 mg/L, 25% and 50% calf serum to protect the bacterial solution, then the bactericidal effect can be affected, the generator at a low concentration (10mg/L), on the copper sheet, carbon steel sheet, aluminum sheet is mildly corrosive, on the stainless steel sheet is basically non-corrosive.
Domestic chlorine dioxide generator development faster, the process is gradually mature [5]. At present, there have been used to produce chlorine dioxide through electrolysis of table salt and sodium chlorate and sodium chlorite method of production of positive and negative pressure chlorine dioxide generator, some of which have been awarded a national patent. Ren Qingwei [6] according to the electrolysis method of preparation of chlorine dioxide mixed disinfection solution of the working principle and operating characteristics, the use of single-chip computer technology and residual chlorine detector, the realization of chlorine dioxide disinfection equipment, salt, alkali and operation of the whole process of regulation of automatic control, greatly improving the efficiency of disinfection and safe operation of the equipment. Chlorine dioxide produced by chemical method of higher content, Shi Lai-shun et al [7] developed a chemical method of chlorine dioxide generator, by iodine amount of chlorine dioxide composite disinfectant solution prepared by the generator determined that the effective chlorine content of 3246.1 mg / L. Detected by UV spectrophotometer and infrared spectrophotometer, the solution contains chlorine dioxide and chlorine, of which chlorine dioxide accounted for 60% -70% of the aqueous solution to the microorganisms. The killing effect of the aqueous solution on microorganisms, containing 4.5-5.0 mg/L active ingredient of Staphylococcus aureus, Escherichia coli and Candida albicans in the water for 1-2 minutes, containing 90 mg/L active ingredient of Bacillus subtilis black variant spores in the role of 5 minutes, the killing rate of 99.9% or more. Containing 400 mg/L active ingredient can destroy HBsAg antigenicity in 5 minutes. Chlorine dioxide generator chlorine dioxide disinfectant performance is more unstable [8], stored for 3 days, the degradation rate of 14.05%, such as the disinfectant solution plus analytical purity of sodium hydroxide, the PH value adjusted to 11.80, airtight and protected from light, stored at room temperature (18 ° C - 25 ° C) 18 months, the degradation rate of only 3.31%.
1.3 in the application of disinfection
At present, chlorine dioxide generator is mainly used for drinking water disinfection and sewage treatment, etc., the traditional drinking water disinfection of chlorine disinfectant in the treatment of raw water will have a large number of halogenated hydrocarbons, including THMs, such as chloroform, as well as chlorinated phenols and dichloroacetonitrile, and other organohalogenated compounds [9][10][11], chloroform has been recognized as a carcinogen by the U.S. National Institute of Oncology [11], chloroform is a carcinogenic substance [11]. Institute of Oncology [12], chlorophenols and dichloroacetonitrile are also carcinogenic or mutagenic, and chlorine dioxide is a strong oxidizing agent. Oxidative degradation of organic matter in water will not produce chlorinated products like chlorine disinfectant, chlorine dioxide used as a substitute for chlorine as a water treatment studies have shown that [13], chlorine treatment of the water after the content of trihalomethanes than the use of chlorine dioxide is 100% higher, therefore, the use of chlorine dioxide can greatly reduce the generation of chloroform, and in addition, it also oxidizes the iron, manganese, magnesium ions in water, as well as sulfur compounds. Does not react with phenols in water, does not produce unpleasant odor [14], so chlorine dioxide is a promising alternative to chlorine water disinfectant. At present, more and more developed countries in Europe has been chlorine dioxide sterilization effect is better than chlorine, the Yangtze River water plus chlorine dioxide 0.5 mg / L, the role of 30 minutes. Minhang water into the 1.0-1.5 mg / L, the role of 30 minutes, can meet the disinfection standards, the number of bacteria & lt; 30 / ml, or even undetectable, and can be better in addition to iron, manganese, phenol in the water. Basically no trihalomethanes generated in the water, in addition to a strong role in reducing the odor of the water. Chlorine dioxide in drinking water disinfection dosage according to the water quality and different, such as the first water through the activated carbon filtration, etc., the dosage is only 0.2 mg / L, such as natural water is added to 2.0 mg / L amount.
Chlorine dioxide is used in sewage treatment, in addition to disinfection, but also can be used to destroy the taste and smell of compounds, control the growth of algae in the water, remove turbidity, improve flocculation and remove color, etc., the amount of dosage to meet the national sewage discharge standards.
2. Stabilized chlorine dioxide solution
2.1 The nature and preparation of stabilized chlorine dioxide
Stabilized chlorine dioxide solution will be dissolved in chlorine dioxide gas containing sodium carbonate, sodium percarbonate, sodium borate, sodium borates and other stabilizers, the usual concentration of 10% or less of a colorless, tasteless and transparent aqueous solution, non-flammable, non-volatile, stable chlorine dioxide. Does not have bactericidal ability, only through the activation (acidification) reaction to make the solution of chlorine dioxide re-released to have a strong bactericidal ability, after activation of 2% aqueous solution PH value is acidic, specific gravity of 1.03 -1.04 (20 ° C), the aqueous solution was light yellow, activation of the solution is unstable, stored for a day the content of the 80% can be reduced [16], it is desirable to be used now.
The domestic production of stabilized chlorine dioxide is mostly a chemical method, with sodium chlorate as the raw material of the chemical method has a large number of production processes, the reducing agent is mostly hydrochloric acid, sulfur dioxide, methanol, etc., the method of low cost, and there is also a sodium chlorite as the raw material of the production method.
In order to improve the stability of chlorine dioxide activation speed and activation rate, the domestic activator has made a lot of research, the activator is divided into a short period of time all the release of the immediate activator, such as hydrochloric acid, phosphoric acid, and other strong acids and slow release of slow-acting activator, mainly citric acid and other weak acids, and the experiments have proved that, the use of citric acid as an activator, generally only 60% of the chlorine dioxide can be activated due to the active chlorine dioxide release is incomplete, there are still more toxic chlorite in the solution, while with hydrochloric acid, the activation rate of chlorine dioxide can be increased to more than 95 [17]. In order to improve the inconvenience of the use of liquid activator, the country also has a solid activator development, the experimental results show that the activation of oxalic acid plus aluminum trichloride solid activator with the use of hydrochloric acid has the same effect [18], usually stabilized liquid and activator volume ratio of 10:1 activation.
2.2 Sterilization performance
Stabilized chlorine dioxide is a broad-spectrum, highly efficient disinfectant that kills bacterial propagules, spores, fungi and viruses [19]. Wang Fuyu et al [20] on the disinfection effect of stabilized chlorine dioxide solution for the observation results are 2.0 mg / L concentration of 1 minute, can make the contaminated Escherichia coli reduced by 5-6 logarithmic values (kill rate of 99.999%-99.9999%) and kill the E. coli phage f2, JiuXiJuan et al [21] reported that with a stabilized chlorine dioxide with a concentration of 50 mg / L 1 minute, can completely kill E. coli, can be used to kill the bacteria, fungi, and virus [19]. Jiu Xijuan et al.[21] reported that the stabilized chlorine dioxide with 50 mg/L for 1 minute could completely kill Escherichia coli and Staphylococcus aureus, and the killing rate of Bacillus subtilis black variant spores with 500 mg/L for 30 minutes was 100%, and it could completely destroy the antigenicity of HBsAg. Chlorine dioxide is also effective in killing Mycobacterium tuberculosis, and it has been reported that at 20°C, chlorine dioxide can kill all 106 Mycobacterium tuberculosis in 10-20 minutes [22]. Acting with a concentration of 1100 mg/L for 5 minutes can kill Mycobacterium tuberculosis on endoscopes [23]. Wei Lanfen et al [24] on the content of 2.55%, PH value of 6.0 chlorine dioxide solution for the microbial killing effect and metal corrosion test, the results of 160 mg / L concentration of Escherichia coli 10 minutes to 200 mg / L concentration of Staphylococcus aureus role of 2 minutes, the rate of killing are up to 100%, so that stainless steel on the destruction of the antigenicity of HBsAg need to 3200 mg / L role of 20 minutes. 400 mg / L concentration can kill Mycobacterium tuberculosis on the endoscope [23]. / L role of 20 minutes. 400 mg / L chlorine dioxide solution, aluminum, copper, carbon steel immersion for 72 hours, are heavy corrosion, stainless steel has a moderate corrosion, the solution to kill microorganisms required for the concentration of the role of time is higher because the authors believe that it may be related to the higher pH value of the solution. 57 times, humidity coefficient (Q10) is 1.63, the disinfectant in acidic (PH3-5) conditions sterilization effect is better, PH value & gt; 7 when the bactericidal effect of a significant decline [25]. Stabilized chlorine dioxide acute toxicity and irritation experiments [26] for the mouse oral LD50>10000mg/kg, is actually non-toxic substances, containing chlorine dioxide 9.7-11.4 mg/L solution on the rabbit skin and mucous membranes of the eye 48 hours of irritation points for 0, is non-irritating. Stable chlorine dioxide products produced in Shanghai can also achieve the basic LD50>5000mg/kg, skin irritation index>0.4, negative results of the micronucleus test.
2.3 Application
In 1985, the United States agreed to use chlorine dioxide as a disinfectant for food processing equipment, and in 1987, it was approved to be used as a disinfectant for environmental surfaces in food processing plants. China has also been approved for use in the food industry pipeline, equipment containers, tableware disinfection, using a concentration of 250 mg / L.
In the field of health care, the United States has been approved for use in hospitals, laboratories and pharmaceutical environments in the biocide, to be our country has also been approved for use in the above sectors of the environmental surface disinfection of the body, but also for the disinfection of corrosion-resistant medical devices such as thermometers, dilatation, oxygen humidification cylinders, test tubes, slides, etc. to respirators, respiratory equipment and other medical equipment.
In addition, in 1996, China has developed GB2760-1996 food additives use of health standards, will be included in the stabilized state of chlorine dioxide in the food additives, "preservative", used in fruits and vegetables, "preservative", and the use of chlorine dioxide in food additives, "preservative", "preservative", "preservative", "preservative", "preservative", "preservative", "preservative", "preservative", "preservative", "preservative" and "preservative". ", used in the preservation of fruits and vegetables, fish processing industry, the maximum use of 0.2-1.0 mg / L.
3. Solid chlorine dioxide disinfectant
3.1 Formulations and preparation
Solid chlorine dioxide products, including powders, tablets, and binary packaging form of the product.
Most of the solid chlorine dioxide to sodium chlorite as the main raw material, the existing sodium chlorite and acidic activator preparation of chlorine dioxide binary packaging products, there is also a sodium chlorite solution adsorbed to the sodium salt of bentonite clay or chlorine dioxide gas adsorption to the formation of adsorption of chlorine dioxide formulations on the carrier of calcium silicate, silicon dioxide, talcum powder, sodium percarbonate powder, and so on, and in addition there is still a solid chlorine dioxide with a non-adsorption type There is also a production process for non-adsorbed chlorine dioxide solid disinfectants. Jiang Xingjin [27] with solid mixed acid activation of sodium chlorite production of chlorine dioxide, the results alone with solid organic acids such as citric acid, oxalic acid, etc. activation of sodium chlorite in the chlorine dioxide is only 29% -56%, and such as organic acids mixed with inorganic acidic salts, the ratio of 1:1-9, the activation rate of up to 90% or more, in fact, with the oxalic acid and AlCl3.6H2O mixing of the best results. The authors also on the activation of the appropriate amount of water and activation of the best time to make observations, the results of the amount of water for the solid organic acid 10 times, placed for 10 minutes the best.
3.2 Bactericidal performance
Chlorine dioxide activation rate and bactericidal effect shows [28], activation and PH value is related. PH & lt; 0.5, can be quickly released activation of chlorine dioxide, PH & gt; 0.5 chlorine dioxide release rate slows down, the activation is incomplete, the bactericidal ability of the weak. Jia Songshu [28] reported binary packaging chlorine dioxide disinfection effect: product chlorine dioxide content of an average of 6.74%, 54 ° C 14 days after storage content of an average of 6.736%, no significant change. With 7.5 mg / L solution for 5 minutes can kill Escherichia coli, Staphylococcus aureus, Candida albicans 150 mg / L for 5 minutes to kill the rate of 100%, the black variant of Bacillus subtilis spores with 60 mg / L role in 10 minutes, the killing rate of 100%. With 200 mg / L solution diluted to 20 mg / mL of purified HBsAg 5 minutes of action can be antigenically destroyed, 200 mg / L solution of stainless steel has mild corrosion, copper, aluminum has moderate corrosion, in addition to the damage to rubber products for observation, the results of the latex tube immersed in the concentration of 200 mg / L solution for many times, its fracture strength and elongation at break has decreased, but there is no significant difference (P<). Significant difference (P<0.05), and no swelling, hardening, sticking, discoloration and other changes.
3.3 Application of disinfection
Solid chlorine dioxide is easy to store and transport, but it must be activated before use, and pay attention to the current use, the use of the same range of liquid stabilized chlorine dioxide.
4. Conclusion
To sum up, the current chlorine dioxide agent research and application is constantly expanding and in-depth, the current chlorine dioxide generator, stable chlorine dioxide solution, as well as solid chlorine dioxide powder or tablets have a strong microbial killing effect, due to the disinfection process without carcinogenic substances, non-toxic and harmless to the human body, has a wide range of prospects for application. However, because chlorine dioxide is a new type of disinfectant, especially in the process of research and application of new dosage forms, there are still a lot of issues that deserve to be continued and further in-depth research, for example, to improve the activation rate of stable and solid chlorine dioxide, reduce the corrosive properties of the metal as well as the establishment of a rapid test method of the content of the field when used, and we expect to make better achievements in the application of chlorine dioxide through the efforts of the study