Compound quaternary ammonium salt disinfectant for sterile environment and preparation method of compound quaternary ammonium salt disinfectant

Abstract

According to the compound quaternary ammonium salt disinfectant for the sterile environment and the preparation method thereof, the benzalkonium chloride, the polyhexamethylene biguanide hydrochloride and the plant polysaccharide are compounded to form the positively charged plant polysaccharide compound disinfectant under the action of the sodium sulfite or the potassium sulfite by utilizing a compound synergistic principle, so that the compound quaternary ammonium salt disinfectant for the sterile environment is obtained. Positive charges are promoted to penetrate through cell walls of bacterial biofilms, so that an excellent bactericidal effect is achieved; the sodium hyaluronate, the enhancer and the glycerol are cooperatively used, so that sodium ions are combined with dehydrogenation groups in polysaccharide and hydroxyl groups, carboxyl groups and the like of other components to form a relatively stable internal net-shaped structure, and the situation that quaternary ammonium salt reacts with metal ions in the environment to reduce the disinfection effect is effectively avoided; meanwhile, the sodium hyaluronate and the glycerol are used for enhancing the compatibility of all the components, and the moisturizing effect of the components is fully utilized, so that the hand sanitizer is not only suitable for disinfection of object surfaces and space environments in a sterile environment, but also can be used for disinfection of hands of a human body.

Description

Technical Field

[0001] The invention belongs to the technical field of disinfectants, and specifically relates to a quaternary ammonium salt compound disinfectant and a preparation method thereof. Background Art

[0002] With the development of society, people's safety awareness has gradually increased, and they pay more attention to daily antibacterial disinfection, which has led to the research and development of bactericidal disinfectants. At present, common disinfectants include chlorine-containing disinfectants, alcohol disinfectants, peroxide disinfectants, aldehyde disinfectants, quaternary ammonium disinfectants, iodine disinfectants, phenol disinfectants and guanidine disinfectants.

[0003] Although the above-mentioned disinfectants have the effect of killing bacteria and viruses, they still have different disadvantages. For example, chlorine-containing disinfectants and peracetic acid disinfectants are much more corrosive to the surface of metal objects than other products. Chlorine-containing disinfectants are also prone to corrode the skin due to strong oxidation and bleaching effects, and cannot be used directly in clinical practice. Peroxide disinfectants require high concentrations to achieve disinfection effects, so they cannot be stored stably for a long time and need to be freshly prepared before use, which limits their use; alcohol disinfectants are flammable and explosive, and are dangerous to store and use; aldehyde disinfectants, iodine disinfectants and phenol disinfectants have large toxic side effects. Quaternary ammonium salts and guanidine disinfectants have the advantages of stable performance, low toxicity, non-flammability and explosion, low corrosion to metals, and low odor. However, quaternary ammonium salt disinfectants have a narrow antibacterial spectrum and cannot kill hydrophilic viruses and bacterial spores. Long-term use alone is prone to drug resistance. When used for disinfection on metal surfaces, they are sensitive to metal ions such as calcium and magnesium, and their bactericidal activity is reduced. At the same time, they are easily affected by factors such as natural light, oxygen and moisture, and the various components of the solution interact with each other, causing discoloration, affecting the use effect and appearance. Although guanidine disinfectants have a broad antibacterial spectrum, they are similar to quaternary ammonium salt disinfectants and are low-efficiency cationic disinfectants. They can only be used for disinfection and cannot kill bacterial spores. In addition, the guanidine content is relatively high. The content of polyhexamethylene biguanide in existing compound disinfectants is higher than 0.25%.

[0004] Plant polysaccharides are polymers formed by connecting multiple monosaccharide molecules through glycosidic bonds, and are one of the main components of plant cell walls. Modern research shows that plant polysaccharides have pharmacological effects such as immunomodulation, anti-tumor, antioxidant and anti-aging, as well as unique processing properties such as thickening, stabilization, and thermal gelation. Therefore, they are often used as active ingredients in the fields of medicine and health foods or as additives in food processing. At present, few disinfectants use plant polysaccharides, especially algae polysaccharides and plant polysaccharides extracted from medicinal and edible raw materials. Therefore, the application of plant polysaccharides still has certain limitations.

[0005] As we all know, a sterile environment refers to a situation in which there are no nutrient cells, spores or spores of any living microorganisms in the environment. Therefore, a sterile environment requires strict control of endotoxins and microorganisms, and therefore has high requirements for disinfectants entering the environment. Ordinary disinfectants directly entering the sterile clean area will cause secondary pollution.

[0006] In summary, it is necessary to develop a new type of disinfectant that has a long-lasting, stable bactericidal effect, is safe and non-toxic, can act on the surface of objects and the human body, and can especially meet the requirements of sterile environment disinfection, and the preparation process is safe, environmentally friendly, simple and easy. Summary of the invention

[0007] Based on this, in response to the shortcomings of the prior art, the present invention provides a disinfectant that can kill common bacteria, hydrophilic viruses and bacterial spores, has long-lasting and stable bactericidal effect, is safe and non-toxic, has a wide source of raw materials, and a safe and environmentally friendly preparation process. It is particularly suitable for use on human hands, object surfaces and space environments in a sterile environment.

[0008] The technical solutions of the present invention include the following: A compound quaternary ammonium salt disinfectant for use in a sterile environment, characterized in that it comprises the following components in percentage by weight: 0.14% to 0.16% benzalkonium chloride, 0.07% to 0.09% polyhexamethylene biguanide hydrochloride, 0.3% to 0.4% glycerol, 0.2% to 0.3% sodium hyaluronate, 3% to 4% plant polysaccharides, 0.5% to 1% inorganic stabilizer, 0% to 0.2% enhancer, and the balance being water for injection.

[0009] Furthermore, the plant polysaccharide is one or more of Schisandra chinensis polysaccharide, Ligustrum lucidum polysaccharide, Cassia seed polysaccharide and Schizonepeta tenuifolia polysaccharide; the inorganic stabilizer is one of sodium sulfite and potassium sulfite; and the enhancer is one or both of sodium hexametaphosphate and sodium trimetaphosphate.

[0010] Furthermore, the preparation method includes the following: Step 1: After proper amount of water for injection, sodium hyaluronate, enhancer, glycerin and inorganic stabilizer are mixed evenly, plant polysaccharide, benzalkonium chloride and polyhexamethylene biguanide hydrochloride are added in sequence, and after the reaction is complete, a mixed system is formed, and coarse filtration is performed to obtain a concentrated solution; Step 2: Add the remaining water for injection to the concentrated solution, circulate it, and then filter it to obtain the compound quaternary ammonium salt disinfectant; Step 3: The disinfectant obtained above is filled, packaged and irradiated to obtain the final product.

[0011] Furthermore, the water for injection described in step 1 is 60% to 70% of the formula amount; the reaction temperature is 40°C to 50°C, and the time is 30min to 45min; and the pore size of the filter membrane for the coarse filtration is 0.45μm.

[0012] Furthermore, the cycle time in step 2 is 30 minutes to 1 hour; and the pore size of the filter membrane in the fine filtration is 0.2 μm.

[0013] Furthermore, the intensity of the irradiation in step 3 is 21 kGy~34 kGy.

[0014] Compared with the prior art, the present invention has the following advantages and beneficial effects: 1) The present invention utilizes the principle of compound synergism, takes benzalkonium chloride, polyhexamethylene biguanide hydrochloride and plant polysaccharides as main active ingredients, and uses sodium hyaluronate, a strengthener and glycerol in coordination, so that benzalkonium chloride and polyhexamethylene biguanide hydrochloride react with plant polysaccharides, and metal cations form bonds with dehydrogenation groups in polysaccharides and hydroxyl groups, carboxyl groups and the like of other components, thereby generating a positively charged internal network structure, which can effectively inhibit the aggregation and sedimentation of components such as polysaccharides in the disinfectant, and at the same time avoid the reaction of quaternary ammonium salts with metal ions in the environment to reduce the disinfection effect, thereby achieving long-lasting disinfection ability; 2) The present invention uses sodium hyaluronate and glycerol to enhance the compatibility of the components in the disinfectant solution and give full play to its moisturizing effect, so that when the disinfectant is used for hand disinfection, it can still keep the skin moisturized and avoid dry skin peeling and desquamation; 3) The present invention adopts double filtration to effectively remove impurities and microorganisms in the raw materials, and through the control of the production environment and irradiation treatment of the product, the product meets the requirements of low endotoxin and sterility, and can directly enter the sterile environment to avoid secondary contamination.

[0015] 4) The raw materials used in the present invention are widely available and the preparation process is simple. The prepared disinfectant can react with the negatively charged polysaccharides in the bacterial biofilm cells, promote the positive charge to penetrate the cell wall, and kill common bacteria, hydrophilic viruses and bacterial spores. It has the advantages of excellent bactericidal effect, broad antibacterial spectrum, safety and non-toxicity, and is particularly suitable for disinfection of human hands, object surfaces and space environments in sterile environments. DETAILED DESCRIPTION

[0016] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments. Example

[0017] 1. Concentrated preparation and filtration: Add 65% of the formula amount of water for injection, sodium hyaluronate, sodium hexametaphosphate, glycerol, and sodium sulfite in the concentrated preparation tank in sequence, stir until completely dissolved, then add the formula amount of seaweed polysaccharide, benzalkonium chloride and polyhexamethylene biguanide hydrochloride in sequence, and react at 45°C for 40 minutes; after the reaction is completed, filter through 0.45μm coarse filtration to obtain a concentrated solution; 2. Dilution and fine filtration: The concentrated solution after coarse filtration is poured into the dilution tank, and the remaining water for injection is added. After circulating for 45 minutes, it is finely filtered through 0.2μm to obtain the compound quaternary ammonium salt disinfectant; 3. Filling, packaging and irradiation: After filling and packaging, the compound quaternary ammonium salt disinfectant is irradiated under 28kGy to obtain the final product.

[0018] The preparation methods of the compound quaternary ammonium salt disinfectants of Examples 2 to 4 are substantially the same as those of Example 1. The differences in the formulations and process parameters of Examples 1 to 4 are detailed in Table 1 below:

[0019] Comparative Examples 1 to 5 Comparative Examples 1 to 5 were prepared using the same process as Example 1, and their formulas are shown in Table 2:

[0020] Comparative Example 6 Comparative Example 6 is the same as Example 1 except that the polysaccharide is aloe polysaccharide.

[0021] Comparative Example 7 Comparative Example 7 uses the same formula as Example 1, and its production process does not undergo fine filtration and irradiation treatment.

[0022] The test results of Examples 1 to 4 and Comparative Examples 1 to 7 are as follows: 1. Air sterilization performance test According to the 2002 edition of the Technical Specifications for Disinfection, the bactericidal effect of disinfectant on natural bacteria in the air was tested; Bacillus subtilis spore tablets were used as biological indicators and placed in 8 locations in the test space (about 60m 3 ), the amount of disinfectant is equivalent to 10ml / m 3 , the sporicidal effect of the disinfectant was investigated, and the results are shown in Table 3 below:

[0023] It can be seen from the data in the above table that the compound quaternary ammonium salt product prepared by the formula of Examples 1 to 4 and Comparative Example 7 has a bactericidal effect of more than 90% on natural bacteria and can kill spores, and its effect is much better than the two-component compound disinfectant formed by quaternary ammonium salts and biguanides. The addition of plant polysaccharides can effectively improve the disinfection effect of the two-component compound disinfectant when glycerol, sodium hyaluronate and sulfite are added, but the effect of a single addition is much less than that of adding each component at the same time, and the disinfection effect of seawater algae polysaccharides is better than that of aloe polysaccharides.

[0024] 2. Sterilization performance test of object surface According to the 2002 edition of the Technical Specifications for Disinfection, the sterilization effect of the disinfectant on conventional bacteria and spores on the surface of objects was tested. The results are detailed in Tables 4-5 below:

[0025]

[0026] It can be seen from the data in the above table that the compound quaternary ammonium salt product prepared by the formula of Examples 1 to 4 and Comparative Example 7 has a good sterilization effect on Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Bacillus subtilis, and its effect is much better than that of Comparative Examples 1 to 6, indicating that the formula of the present technical solution is better than the beneficial effects brought by the two-component compound disinfectant and other single ingredients, and the disinfection effect of using seawater algae polysaccharides is better than that of aloe polysaccharides.

[0027] 3. On-site hand disinfection performance test According to the 2002 edition of the Technical Specifications for Disinfection, the disinfection effect of the disinfectant on the hands for 10 minutes and the skin comfort after use were tested. The results are shown in Table 6 below:

[0028] 4. Stability performance test According to the 2002 edition of the Technical Specifications for Disinfection and the 2020 edition of the Chinese Pharmacopoeia, the stability of the disinfectant after being stored at 37°C and 75% for 3 months was tested with appearance, effective ingredient decline rate, sterility and bacterial endotoxin as indicators. The results are detailed in Table 7:

[0029] From the data in the above table, it can be seen that: 1) in terms of product appearance, the disinfectants prepared in Examples 1 to 4 and Comparative Examples 6 to 7 are clear and precipitate-free, which is much better than Comparative Examples 1 to 5; 2) in terms of the decrease rate of the active ingredients benzalkonium chloride and polyhexamethylene biguanide salt, Examples 1 to 4 ≤ Comparative Example 7 ≤ Comparative Example 6 < Comparative Example 5 < Comparative Examples 3 to 4 < Comparative Examples 1 to 2. In summary, it can be seen that the product prepared by the formula of the scheme of the present invention is not easy to change in appearance and active ingredients during storage, and its effect is much better than the addition of a single ingredient, and the disinfection effect of seawater microalgae polysaccharides is better than that of aloe polysaccharides.

[0030] Secondly, it can be seen from the sterility and bacterial endotoxin indicators that, except for Comparative Example 7, the sterility and bacterial endotoxin of the products prepared in Examples 1 to 4 and Comparative Examples 1 to 6 all meet the requirements, indicating that the disinfectant prepared by the technology of the present invention can meet the requirements of sterility and low endotoxin, and can be directly used for disinfection in a sterile environment.

[0031] 5. Safety performance test According to the 2002 edition of the Technical Specification for Disinfection, Example 1 was tested for metal corrosion, acute oral toxicity, multiple skin irritation, and mutagenicity. The results are shown in Tables 8 to 9 below:

[0032] It can be seen from the data in Tables 8 and 9 above that the disinfectant product prepared by the technology of the present invention is safe, non-toxic and has low metal corrosion.

Claims

1. A compound quaternary ammonium salt disinfectant for use in a sterile environment, characterized in that: The invention comprises the following components in percentage by weight: 0.14% to 0.16% benzalkonium chloride, 0.07% to 0.09% polyhexamethylene biguanide hydrochloride, 0.3% to 0.4% propylene glycol, 0.2% to 0.3% sodium hyaluronate, 3% to 4% plant polysaccharides, 0.5% to 1% inorganic stabilizer, 0% to 0.2% enhancer, and the balance is water for injection.

2. The compound quaternary ammonium salt disinfectant according to claim 1, characterized in that The plant polysaccharide is one or more of Schisandra polysaccharide, Ligustrum lucidum polysaccharide, Cassia seed polysaccharide and Schizonepeta tenuifolia polysaccharide; the inorganic stabilizer is one of sodium sulfite and potassium sulfite; the enhancer is one or both of sodium hexametaphosphate and sodium trimetaphosphate.

3. A compound quaternary ammonium salt disinfectant for use in a sterile environment according to claim 1 or 2, characterized in that: The preparation method thereof comprises the following steps: Step 1: After proper amount of water for injection, sodium hyaluronate, enhancer, glycerin and inorganic stabilizer are mixed evenly, plant polysaccharide, benzalkonium chloride and polyhexamethylene biguanide hydrochloride are added in sequence, and after the reaction is complete, a mixed system is formed, and coarse filtration is performed to obtain a concentrated solution; Step 2: Add the remaining water for injection to the concentrated solution, circulate it, and then filter it to obtain the compound quaternary ammonium salt disinfectant; Step 3: The disinfectant obtained above is filled, packaged and irradiated to obtain the final product.

4. A compound quaternary ammonium salt disinfectant for use in a sterile environment according to claim 3, characterized in that: The water for injection described in step 1 is 60% to 70% of the formula amount; the reaction temperature is 40°C to 50°C and the time is 30min to 45min; the filter membrane pore size of the coarse filtration is 0.45μm.

5. A compound quaternary ammonium salt disinfectant for use in a sterile environment according to claim 3, characterized in that: The cycle time in step 2 is 30 minutes to 1 hour; the pore size of the filter membrane in the fine filtration is 0.2 μm.

6. A compound quaternary ammonium salt disinfectant for use in a sterile environment according to claim 3, characterized in that: The intensity of the irradiation described in step 3 is 21 kGy~34 kGy.

7. A compound quaternary ammonium salt disinfectant for use in a sterile environment according to claims 1 to 6, which can be used for disinfection of human hands, object surfaces and spaces in a sterile environment.

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