Quaternary ammonium salt disinfectants in China

With the outbreak of the new coronavirus pneumonia in early 2020, "disinfection and sterilization" has almost become a daily necessity, and the supply of disinfectant products is also in short supply. Disinfectants are chemical agents that can effectively control or kill bacteria, fungi, viruses, algae and other microorganisms. According to their mechanism of action, they can be divided into oxidizing and non-oxidizing bactericides. Oxidizing bactericides kill bacteria by inactivating active enzymes in bacteria or direct oxidation by their strong oxidizing properties. The main products are generally chlorine and peroxide preparations, which have the advantages of strong bactericidal power, easy availability of raw materials, and simple use; However, such preparations will have strong irritation and oxidative corrosion on human skin, respiratory mucosa and eyes during production and use, and are prone to burning and explosion accidents during storage and transportation; such preparations are generally used alone , It is difficult to be used to prepare detergents with sterilization function. Non-oxidizing bactericides include non-oxidizing compounds such as chlorophenols, organic aldehydes, quaternary ammonium salts, biguanides, etc. Among them, quaternary ammonium salts are an important category. Such bactericides are a kind of broad-spectrum, high-efficiency and low-toxicity The fungicide is widely used in daily life and industrial fields. Quaternary ammonium salt disinfectants played a key role in cleaning products such as sterilizing laundry detergent and sterilizing hand sanitizer that provided medical staff and the people with washing, disinfection, and sterilization guarantees in the fight against the epidemic.

The development process and sterilization mechanism of quaternary AMMONIUM salt

As early as the 1930s, quaternary ammonium salt as a fungicide began to attract people’s attention. However, until the mid-1980s, the development of quaternary ammonium salt products had not achieved large-scale development in China, mainly due to the preparation season. The raw material of ammonium salt-alkyl tertiary amine failed to achieve domestic production. During the "Seventh Five-Year Plan" period, the scientific and technological research project undertaken by the China Daily Chemical Institute successfully developed the internationally leading "fatty alcohol one-step tertiary amine" process, breaking the foreign monopoly, after which the quaternary ammonium salt can develop rapidly in China.

The development of quaternary ammonium salt fungicides has now derived seven generations of products, the first generation of fungicides benzalkonium chloride/bromide (Zerminer/Syndactyl); the second generation is the first-generation derivative; the third-generation fungicide is double long Chain quaternary ammonium salt (DDAC); the fourth-generation fungicide is a compound of the first and third generations; the fifth-generation fungicide is a gemini quaternary ammonium salt; the sixth-generation fungicide is a polyquaternary ammonium salt; the seventh-generation fungicide is a third and sixth-generation compound . The mechanism of action of this kind of bactericides is mainly that positively charged cations adsorb negatively charged bacteria and gather on the cell wall, resulting in a compartmental barrier effect, causing the growth of bacteria to be inhibited and death; at the same time, their hydrophobic groups interact with the hydrophilic groups of bacteria. , Change the permeability of the membrane, and then undergo lysis, destroy the cell structure, and cause cell lysis and death (Figure 1). It has high efficiency, low toxicity, is not easily affected by pH changes, has a long-lasting bactericidal activity, and has a strong peeling effect on the mucus layer, stable chemical properties, good dispersion and corrosion inhibition, and also has algae killing and flocculation Features.

Status of Quaternary Ammonium Fungicide Products

Quaternary ammonium salts have been used as fungicides for nearly a hundred years. After research and development, there are now a variety of quaternary ammonium salts (single-chain and double-chain compounds) fungicides and sanitary products. Because of its low concentration and effectiveness, small side effects, colorless, odorless, low toxicity and safety, it is widely used as a sterilization and disinfectant for surgical operations and medical equipment, a sterilization and algicide for industrial circulating water treatment, and a treatment agent for oilfield water reinjection , Forestry and construction industry preservatives, household personal, public health and hard surface cleaning and disinfectants, livestock disinfection and cleaning agents, meat, eggs and other food processing equipment cleaning and disinfection agents, and used in the preparation of Sterilizing washing products such as laundry detergent and hand sanitizer.

At present, the mature quaternary ammonium bactericides in the domestic market include: single chain type (alkyl trimethyl chloride/ammonium bromide 1231-1831), benzyl type (alkyl dimethyl benzyl chloride/ammonium bromide 1227) , 1427, etc.), double-chain type (Didecyldimethyl chloride/ammonium bromide DDAC/B), pyridines (tetradecyl-2-methylpyridinium ammonium bromide, etc.).

Development of new varieties of quaternary ammonium salt fungicides

Some traditional quaternary ammonium salt antibacterial agents will have a certain degree of drug resistance due to long-term use. By changing the structure of hydrophobic groups, hydrophilic groups and counterions, many new quaternary ammonium salts can be derived. In recent years, researchers have continuously developed some new varieties of quaternary ammonium salts, and improved the bactericidal effect and avoided the development of drug resistance through the compound synergy of different fungicides.

(1) New counter ion quaternary ammonium salt

This type of quaternary ammonium salt is obtained by using the green chemical raw material "Dimethyl Carbonate" as a quaternizing agent. The anion part is no longer limited to halogen ions. Almost all inorganic acids and organic acid radicals can be used as counter ions of quaternary ammonium salts. , Which greatly enriches the varieties of quaternary ammonium salts. Compared with traditional quaternary ammonium salts, the new counter-ion quaternary ammonium salts have a stronger bactericidal effect (such as didecyldimethyl methyl/ethyl/ammonium propionate at 5 ppm The antibacterial rate against Staphylococcus aureus and Escherichia coli at a concentration of 100%), the toxicity and irritation are lower, and the problem of bacterial resistance caused by the long-term use of traditional quaternary ammonium salts is solved. China National Institute of Daily Chemicals took the Lead in developing this process technology and has the capacity for large-scale production.

(2) Containing hydroxyethyl or hydroxypropyl quaternary ammonium salt

Hydroxyethyl/hydroxypropyl quaternary ammonium salt (Didecylmethylhydroxyethyl/hydroxypropylammonium chloride DEQ/DPQ) is a quaternary ammonium salt with a new structure, which is a typical functional species and a traditional quaternary ammonium salt Upgraded products. It has excellent disinfection and sterilization properties (inhibition rate of Staphylococcus aureus and E. coli can reach 100% at a concentration of 10 ppm), low ecotoxicity, good compatibility with the environment, and good compatibility. The Chinese Academy of Daily Chemicals has developed a green and efficient preparation process technology. This technology has no three wastes emissions, short reaction time, low temperature and pressure. At present, hydroxyethyl quaternary ammonium salt has realized industrial production.

(3) Gemini quaternary ammonium salt

Gemini quaternary ammonium salt has two positively charged nitrogen ions and two long-chain hydrophobic groups in the molecular structure. Because there are two quaternary ammonium cations in one molecule, the charge density is higher, which enhances its resistance to bacteria. Effective adsorption on the cell surface, thereby changing the permeability of the cell wall, has stronger antibacterial and antifungal activity than typical monoquaternary ammonium salts. Traditional alkyl gemini quaternary ammonium salts have limited use due to poor biodegradability. Researchers from the Chinese Academy of Daily Chemicals introduced amide groups into the alkyl chain, which not only improved the biodegradability, but also improved the bactericidal and antibacterial properties (10 The inhibitory rate against Staphylococcus aureus and Escherichia coli can reach 100% at the concentration of ppm), and the process has also been industrialized.

(4) Polyquaternium

Polyquaternary ammonium bactericides are obtained by polymerizing monomers with bactericidal active functional groups, or by grafting small molecules with bactericidal functions on the polymer matrix, and can be divided into water-soluble and water-insoluble Compared with ordinary quaternary ammonium salts, polyquaternary ammonium salt bactericides prolong the effect of antibacterial agents and reduce environmental pollution. At the same time, they also have the functions of flocculation and corrosion inhibition. It avoids the problems of toxicity, residual toxicity, irritation and safety in use, and is a kind of disinfectant with good prospects.

(5) Quaternary ammonium salt compound products

Because the bactericidal effect of a single quaternary ammonium salt is limited in certain use environments, and long-term use alone can produce drug resistance, researchers have found that the synergistic effect of compound quaternary ammonium salt will have a more excellent broad-spectrum bactericidal effect. The effect and many other advantages, such as: prolonging the sterilization cycle, expanding the antibacterial spectrum and antibacterial range, reducing the use concentration, preventing bacteria from developing resistance, etc. Studies have shown that the first and third-generation compounds, the fourth-generation fungicides, are 4-20 times higher than the previous three generations. It is believed that the combination of traditional quaternary ammonium salt and new quaternary ammonium salt and other types of surfactants or bactericides can also achieve synergistic effect to improve the bactericidal effect.

Concluding remarks

After nearly a century of development, quaternary ammonium salt disinfectants have become an important variety. The future development directions are:

(1) Develop and apply a new structure quaternary ammonium salt disinfection product with broad spectrum, high efficiency, low toxicity, wide application range and environmental safety;

(2) Strengthen the development of compound formula technology, so that different ingredients can play a synergistic and complementary sterilization effect, overcome the sterilization weakness of a single component, and reduce costs;

(3) Strengthen the research on the new use and compound sterilization mechanism of old chemicals, and guide the development of new products.