Use of polyether-modified siloxanes as virucidal agents

Abstract

The application discloses application of polyether modified siloxane as a virus disinfectant and belongs to the technical field of disinfectants. The application of the polyether modified siloxane as the virus disinfectant is to mix the polyether modified siloxane with a solvent or other substances uniformly, and then spray the polyether modified siloxane on an environment or an animal body surface to be disinfected; the pore size of the polyether modified siloxane is 10-100 nm. The pore size of the polyether modified siloxane is limited to 10-100 nm, so that the polyether modified siloxane can play a special role in fixing and killing viruses. The polyether modified siloxane can be used as the virus disinfectant alone or mixed with ethanol, isopropyl alcohol, glycerol and / or water to be used as the virus disinfectant. The virus disinfectant has small toxicity and low irritancy, and meets various standards of disinfectants.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of disinfectants, in particular to the application of polyether-modified siloxane as a virus disinfectant. BACKGROUND

[0002] In the current general practice, the main method for killing viruses in the environment is chemical disinfection, and the chemicals used mainly include aldehydes, ethylene oxide, halogens, alcohols, phenols, guanidines, quaternary ammonium salts, peroxides, etc. When killing viruses on the surface of animals (fur, skin, mucous membrane), it is necessary to ensure efficient inactivation, while also considering animal safety, low stress, and no residual toxicity. The current mainstream approach can be summarized as a physical-chemical synergistic strategy, in which the physical method mainly includes warm water flushing, high-pressure spraying, ultraviolet irradiation, dry heat or hot air, which can inactivate most of the capsid viruses. The commonly used safe formulations for animals (pets) mainly include five categories: slightly acidic hypochlorite water, complex quaternary ammonium salt, iodophor, peroxyacetic acid, and organic acid compound, etc. The core is to avoid the use of phenol, aldehyde and other irritating or toxic preparations, and to strictly follow the label concentration and action time. After disinfection, it is best to use warm water close to the body temperature of the animal for flushing to prevent stress.

[0003] However, for the killing of viruses in the environment, it is required to have safety, low irritation, low corrosion, environmental protection, easy degradation, and no residue. For the killing of viruses on the surface of animals, it is more required to have safety, no irritation, no corrosion, environmental protection, easy degradation, no residue, and easy use. However, the traditional chemical or antiviral drugs currently have the following problems: they can be absorbed through the skin or mucous membrane into the blood circulation, causing potential toxicity or irritation to the body; viruses have developed partial or complete drug resistance mutations, and the effect decreases after long-term or repeated use; the drugs themselves have poor spreadability and poor stability, making it difficult to form effective coverage on complex surfaces, resulting in the inability to fully exert the killing effect. Polyether siloxane is a kind of surface active material with extremely small molecular size (1.5-7.5 nm), which has hydrophilicity, low surface tension and strong penetration. It has been widely used in cosmetics, polyurethane foam, plastic modification, fabric finishing, washing and industrial defoaming fields. In addition, polyether-modified siloxane has been applied as a pesticide and fungicide, and its functionality and safety have been proven by application and evidence.

[0004] CN118216516A proposes to use polyether modified siloxane as a pesticide and fungicide. Its specific use is: after mixing polyether modified siloxane with ethanol, isopropyl alcohol, glycerol and deionized water uniformly, it is sprayed in the environment or animal body surface that needs to be disinfected; wherein the pore size of the polyether modified siloxane is strictly controlled in the range of 10-100 nm, and this specific size enables it to play a special role in fixing and killing bacteria and insect bodies. In addition, the application form of the polyether modified siloxane is flexible, which can be used as a bactericide and insecticide alone, or mixed with the above-mentioned ethanol, isopropyl alcohol, glycerol and deionized water to play a role. Test verification shows that this bactericide and insecticide can be directly applied to the animal body surface or the environment, and can be in direct contact with the body, even if it is attached to the skin, it will not cause irritation or harm to the skin.

[0005] CN111802409A discloses a broad-spectrum antiviral and antibacterial disinfectant, which contains 1-50 parts of N-alkyl propyl glycine, 10-50 parts of active matrix material, 1-100 parts of film-forming agent, 1-100 parts of thickening agent, 1-10 parts of plant extract agent, 1-10 parts of solubilizing agent and 1-10 parts of cooling agent by weight. The active matrix material is a mixture of carrageenan and chitosan sulfate. This broad-spectrum antiviral and antibacterial disinfectant has excellent bactericidal and bacteriostatic effect, and the effective duration is long, and it has no toxicity and harm to the human body. In the bactericidal range, it shows strong killing effect on many viruses such as novel coronavirus, hepatitis virus, HIV, avian influenza virus, influenza A virus, and bovine virus, as well as common pathogenic bacteria such as Escherichia coli, cryptococcus, enteritis salmonella, white candida, and staphylococcus aureus.

[0006] The existing disinfectants have their own limitations, such as insufficient killing effect on viruses or limited range, and long onset time. Therefore, it is of great significance to develop a broad-spectrum, high-efficiency, environmentally friendly and less irritating to human / animal disinfectant. SUMMARY

[0007] In view of the above-mentioned defects of the prior art, the technical problem to be solved by the present application is to provide an application of polyether modified siloxane as a virus disinfectant.

[0008] Some viruses (such as influenza virus, new coronavirus, herpes virus, etc.) have a layer of "lipid envelope" on their surface. This layer of envelope is not only a protective structure of the virus, but also a key tool for its adsorption to host cells (through glycoprotein on the envelope). The polyether-modified siloxane has both "hydrophobicity of siloxane" and "hydrophilicity of polyether". Its molecules can penetrate and adsorb to the surface of the lipid envelope of the virus, forming a tight wrapping layer; or after wrapping, the envelope may be broken due to physical tension, and the envelope is a necessary structure for the survival of enveloped viruses. After the envelope is broken, the nucleic acid inside the virus will be exposed and degraded by enzymes in the environment, and finally inactivated; even if the envelope is not directly broken, the tight wrapping layer will cover the adsorption proteins on the surface of the virus, so that it cannot combine with the receptors on the surface of the host cells. The polyether-modified siloxane kills viruses through a unique physical rigid network structure, and its core mechanism is physical wrapping and mechanical restraint, rather than traditional chemical or biological action. After spraying, a 3D rigid siloxane bundle network with a pore size of about 100 nm (adjustable to 15-60 nm) is formed. This pore size is smaller than the diameter of most viruses (such as influenza virus, herpes virus, etc.), which can physically capture them like a "spider web". The wrapped viruses will struggle violently, and their struggle energy will be quickly consumed, leading to their inactivation. This process can be completed within a few seconds to a few minutes, and the effect is rapid. After about 14 days, the network structure will automatically degrade into "silica flowers" (fine dust) with a diameter of about 500 μm and settle. The degradation products will not enter the body circulation and will not cause environmental residues and pollution.

[0009] The application of the polyether-modified siloxane as a virus disinfectant comprises mixing 1-10% of the polyether-modified siloxane, 0-50% of ethanol, 0-50% of isopropyl alcohol, 0-10% of glycerol, and the rest of water, and then spraying them on the environment or animal body surface to be disinfected.

[0010] The pore size of the polyether-modified siloxane is 10-100 nm.

[0011] Further, the pore size of the polyether-modified siloxane is 10-30 nm.

[0012] Further, the pore size of the polyether-modified siloxane is 30-50 nm.

[0013] Further, the pore size of the polyether-modified siloxane is 50-80 nm.

[0014] Further, the pore size of the polyether-modified siloxane is 80-100 nm.

[0015] Further, the viruses targeted by the application of the polyether-modified siloxane as a virus disinfectant include environmental viruses and animal body surface viruses.

[0016] But the surface of non-enveloped viruses has no lipid envelope, only the internal nucleic acid is wrapped by "protein shell", the shell structure is hard and stable, and the physical wrapping mechanism has limited effect on direct inactivation. Therefore, the application also provides a virus disinfectant, in addition to adding polyether modified siloxane, modified chitosan is also added, after carboxymethylation of chitosan, grafting with modified monomer is carried out, and modified chitosan with hydrophobic chain and quaternary ammonium salt is obtained, the quaternary ammonium group with positive electricity is adsorbed on the surface of the virus with negative electricity, and the long alkyl chain can be inserted into the hydrophobic region of the virus, so that the virus membrane structure is broken and the content is leaked, so that the virus is inactivated. Modified chitosan can effectively deal with enveloped viruses and non-enveloped viruses, and the physical destruction mechanism makes it difficult for viruses to develop drug resistance through variation. And its target is the unique structure of the virus, which is very safe to mammalian cell membrane. Chitosan itself has good biocompatibility and is easy to degrade.

[0017] The application of polyether modified siloxane as a virus disinfectant specifically includes the following steps, in parts by weight:

[0018] S1, 1-2 parts of modified chitosan are added to 5-10 parts of ethanol, mixed with 1-3 parts of fumed silica under shearing, and dried to obtain composite particles;

[0019] S2, 1-2 parts of polyvinylpyrrolidone are added to a mixture of 40-50 parts of water and glycerol, and then 2-4 parts of composite particles and 0.1-1 parts of silicone surfactant are uniformly dispersed to obtain an aqueous phase;

[0020] S3, 2-8 parts of polyether modified siloxane are added to a mixture of 30-50 parts of ethanol and isopropanol, uniformly mixed, then added to the aqueous phase, stirred uniformly, and then sprayed on the environment or animal body surface to be disinfected;

[0021] The pore size of the polyether modified siloxane is 10-100 nm. The preparation method of the modified chitosan includes the following steps:

[0022] X1, dimethylaminoethyl methacrylate and bromododecane are added to isopropanol, heated to 50-60 DEG C, reacted in the dark under nitrogen atmosphere for 24-48 h, cooled to room temperature after the reaction is completed, and the modified monomer is obtained after post-treatment;

[0023] X2, the chitosan is dispersed in isopropanol and alkalized by adding alkali, then a chloroacetic acid solution is added, heated to 50-60 DEG C, stirred for 3-5 h, then the pH is adjusted to neutral by adding acid, and the obtained solid is added to 30-50 times the volume of water, mixed with modified monomer and ammonium persulfate, heated to 60-70 DEG C, reacted under nitrogen atmosphere for 6-8 h, cooled to room temperature, and the modified chitosan is obtained after post-treatment.

[0024] Further, the mass ratio of the dimethylaminoethyl methacrylate and bromododecane, isopropyl alcohol is 1:1-2:4-10.

[0025] Further, the mass ratio of the chitosan, isopropyl alcohol, sodium hydroxide, and chloroacetic acid is 1:5-10:1-3:2-3.

[0026] Further, the mass ratio of the solid obtained after post-processing, modified monomer, and ammonium persulfate is 1:1-3:0.1-0.2.

[0027] Preferably, the preparation method of the modified chitosan comprises the following steps:

[0028] X1, dimethylaminoethyl methacrylate and bromododecane are added to isopropyl alcohol, the mass ratio of dimethylaminoethyl methacrylate, bromododecane, and isopropyl alcohol is 1:1-2:4-10, and the temperature is raised to 50-60℃, and the reaction is carried out in the dark under a nitrogen atmosphere for 24-48h, and then the temperature is cooled to room temperature, and the modified monomer is obtained after post-processing;

[0029] X2, chitosan is dispersed in isopropyl alcohol and alkali is added for alkalization, and then a chloroacetic acid solution is added, the mass ratio of chitosan, isopropyl alcohol, sodium hydroxide, and chloroacetic acid is 1:5-10:1-3:2-3, the temperature is raised to 50-60℃ and stirred for 3-5h, and then acid is added to adjust the pH to neutral, the solid obtained after post-processing is added to 30-50 times the volume of water, mixed with modified monomer and ammonium persulfate, the mass ratio of the solid obtained after post-processing, modified monomer, and ammonium persulfate is 1:1-3:0.1-0.2, the temperature is raised to 60-70℃, and the reaction is carried out under a nitrogen atmosphere for 6-8h, and then the temperature is cooled to room temperature to obtain the modified chitosan after post-processing.

[0030] Advantages of the present application:

[0031] The pore size of the polyether-modified siloxane is limited to 10-100nm, which can play a special role in fixing and killing viruses; the polyether-modified siloxane can be used as a virus killer alone, or mixed with ethanol, isopropyl alcohol, glycerol, and deionized water to be used as a virus killer, which has low toxicity and low irritation, and meets various specifications of disinfectants. DETAILED DESCRIPTION

[0032] The preparation method of the polyether-modified siloxane with a pore size of 10-30nm is described in CN118216516B, Example 1.

[0033] The preparation method of the polyether-modified siloxane with a pore size of 30-50nm is described in CN118216516B, Example 2.

[0034] The preparation method of polyether-modified siloxane with a pore size of 50-80 nm is described in Example 3 of CN118216516B.

[0035] The preparation method of polyether-modified siloxane with a pore size of 80-100 nm is described in Example 4 of CN118216516B.

[0036] The preparation method of polyether-modified siloxane with a pore size of 1-8 nm is described in Comparative Example 1 of CN118216516B.

[0037] Polyvinylpyrrolidone, type: Sokalan K30 P, from BASF.

[0038] Silicone surfactant, type: DC-193, from Dow Chemical.

[0039] Example 1, application of polyether-modified siloxane as a virus disinfectant, 10% of polyether-modified siloxane with a pore size of 10-30 nm and 90% of deionized water are sequentially introduced into a mixer and mixed.

[0040] Example 2, application of polyether-modified siloxane as a virus disinfectant, 10% of polyether-modified siloxane with a pore size of 30-50 nm and 90% of deionized water are sequentially introduced into a mixer and mixed.

[0041] Example 3, application of polyether-modified siloxane as a virus disinfectant, 10% of polyether-modified siloxane with a pore size of 50-80 nm and 90% of deionized water are sequentially introduced into a mixer and mixed.

[0042] Example 4, application of polyether-modified siloxane as a virus disinfectant, 10% of polyether-modified siloxane with a pore size of 80-100 nm and 90% of deionized water are sequentially introduced into a mixer and mixed.

[0043] Example 5, application of polyether-modified siloxane as a virus disinfectant, specifically including the following steps, in parts by weight:

[0044] S1, add 1 part of modified chitosan to 5 parts of ethanol, mix with 2 parts of fumed silica under 2000 rpm shear, and dry to obtain composite particles;

[0045] S2, add 1 part of polyvinylpyrrolidone to 45 parts of 50wt% glycerol aqueous solution, then add 2 parts of composite particles and 1 part of silicone surfactant to disperse uniformly to obtain an aqueous phase;

[0046] S3, 8 parts of polyether modified siloxane with a pore size of 80-100 nm were added to a mixture of 21 parts of ethanol and 22 parts of isopropanol, mixed uniformly, and then added to the aqueous phase. The mixture was introduced into a mixer and mixed uniformly.

[0047] The preparation method of the modified chitosan comprises the following steps:

[0048] X1, dimethylaminoethyl methacrylate and bromododecane were added to isopropanol, the mass ratio of dimethylaminoethyl methacrylate, bromododecane and isopropanol was 1:1.5:8, and the temperature was raised to 60°C. The reaction was carried out in the dark under a nitrogen atmosphere for 36 hours. After the reaction was completed, the temperature was cooled to room temperature, and the product was precipitated in 0°C diethyl ether. After filtration, washing and drying, the modified monomer was obtained;

[0049] X2, chitosan was dispersed in isopropanol and 40wt% sodium hydroxide aqueous solution was added. Alkalization was carried out at 60°C for 1h. Then 40wt% chloroacetic acid isopropanol solution was added. The mass ratio of chitosan, isopropanol, sodium hydroxide and chloroacetic acid was 1:8:2:2.5. The temperature was raised to 60°C and stirred for 4h. Then acetic acid was added to adjust the pH to 7. The product was added to 5 times the volume of ethanol. After filtration, washing and drying, the solid was added to 40 times the mass of water. The product was mixed with modified monomer and ammonium persulfate. The mass ratio of the solid, modified monomer and ammonium persulfate was 1:2:0.1. The temperature was raised to 70°C and the reaction was carried out under a nitrogen atmosphere for 6h. After cooling to room temperature, the product was added to 5 times the volume of acetone. After filtration, washing, dialysis and drying, the modified chitosan was obtained.

[0050] In Comparative Example 1, polyether modified siloxane was used as a virus disinfectant. 10wt% polyether modified siloxane with a pore size of 1-8nm and 90% deionized water were introduced into a mixer in sequence and mixed uniformly.

[0051] In Comparative Example 2, polyether modified siloxane was used as a virus disinfectant. The specific steps included the following:

[0052] S1, 1 part of chitosan was added to 5 parts of ethanol, and 2 parts of fumed silica was mixed under shearing. After drying, the composite particles were obtained;

[0053] S2, 1 part of polyvinylpyrrolidone was added to 45 parts of 50wt% glycerol aqueous solution. Then 2 parts of composite particles and 1 part of silicone surfactant were added and dispersed uniformly to obtain an aqueous phase;

[0054] S3, 8 parts of polyether modified siloxane with a pore size of 80-100 nm were added to a mixture of 21 parts of ethanol and 22 parts of isopropanol, mixed uniformly, and then added to the aqueous phase. The mixture was stirred uniformly, and then sprayed on the environment or animal body surface to be disinfected.

[0055] Test Example 1, after the virucides in the examples and the control example were configured into a 0.3% solution, reference ISO 18184-2019 "Textiles - Determination of the antiviral activity of textiles", at room temperature for 15 min, to evaluate the inactivation effect of each group of samples on respiratory syncytial virus A (RSV-A). The specific method is: the RSV-A virus liquid containing high titer (10 6.5 TCID 50 ) was uniformly dropped on a sterile dust-free cloth to prepare a virus slide. After the virus liquid was completely absorbed, the experimental group used different sample solutions to completely cover the slide for action, 3 repeats were set for each concentration; the control group was not treated. After the action was completed, 1 mL of serum-free medium was used to elute the slide to recover the virus. Then, the recovered virus liquid was serially diluted 10 times with serum-free medium until 10 -6 gradient. The virus liquid of each dilution was inoculated into a 96-well plate, 4 replicate wells were set for each dilution, and Hep2 cell suspension was added for co-culture. The cell plate was placed in a 37°C, 5% CO2 incubator for 3-4d, and the cytopathic effect (CPE) was observed and recorded daily. Finally, the half tissue infective dose (TCID 50 ) of each group was calculated according to the Reed-Muench formula, and the virus titer of the experimental group and the control group was compared to calculate the killing logarithm value and the killing rate, so as to evaluate the inactivation effect of the sample. The results are shown in Table 1.

[0056] Table 1

[0057]

[0058] As can be seen from Table 1, the sample has good killing effect on RSV-A. The polyether-modified siloxane kills viruses by a unique physical rigid network structure, the core mechanism of which is physical wrapping and mechanical restraint, rather than traditional chemical or biological action. After spraying, a 3D rigid siloxane bundle network with different pore sizes is formed. The pore size is smaller than the diameter of most viruses (such as influenza virus, herpes virus, etc.), which can physically capture them like a "spider web", and the struggling energy of the wrapped viruses is quickly consumed, resulting in loss of activity. This process can be completed within a few seconds to a few minutes, and the effect is rapid. After about 14d, the network structure will automatically degrade into "silica flowers" (fine dust) with a diameter of about 500μm and settle. The degradation products will not enter the body circulation, nor will they cause environmental residues and pollution.

[0059] The killing logarithm value of Example 5 is higher than other examples, which is 3.74. The inactivation of virus is not linear but exponential. The difference is undoubtedly significant. The killing logarithm value increases by 1, which means the number of surviving virus decreases by 10 times. The amount of virus required for many virus infections is low (i.e. "infectious dose"). If the number of surviving viruses decreases from 20 to 2, the probability of infection will be greatly reduced. For high-risk groups (such as the elderly, infants, and patients), this may be the difference between "being infected" and "not being infected".

[0060] In Example 5, in addition to adding polyether-modified siloxane, modified chitosan is also added. After carboxymethylation of chitosan, grafting with modified monomers is carried out to obtain modified chitosan with hydrophobic chains and quaternary ammonium salt. The positively charged quaternary ammonium groups are adsorbed on the negatively charged virus surface, and the long alkyl chain can insert into the hydrophobic region of the virus. The chitosan skeleton and the high molecular characteristics enable it to form a persistent antibacterial film on the surface. The combined action of multiple mechanisms causes the virus membrane structure to rupture and the contents to leak, thereby inactivating. Modified chitosan can effectively deal with both enveloped viruses and non-enveloped viruses. The physical destruction mechanism makes it difficult for viruses to develop drug resistance through mutation.

[0061] Test Example 2: Toxicology experiments were conducted on the disinfectants of the examples and the control examples. The toxicology experiments were conducted in accordance with the relevant provisions of 2.3 of the "Disinfection Technical Specifications" (2002 edition). The results of the toxicology experiments are shown in Table 2 below.

[0062] Table 2

[0063]

[0064] As can be seen from Table 2, the virus disinfectant obtained by the present application has low toxicity and no skin irritation, and meets the requirements of the disinfection specifications in all aspects.

[0065] The above describes in detail the preferred embodiments of the present application. It should be understood that those skilled in the art can make many modifications and changes without creative labor based on the concept of the present application. Therefore, any technical solution obtained by logical analysis, reasoning or limited experiments based on the existing technology according to the concept of the present application shall be within the protection scope determined by the claims.

Claims

1. The application of polyether-modified siloxane as a virus disinfectant, characterized in that, Mix 1-10% by weight of polyether-modified siloxane, 0-50% ethanol, 0-50% isopropanol, 0-10% glycerin, and the remainder water, and then spray the mixture onto the environment or animal body surface to be disinfected. The polyether-modified siloxane has a pore size of 80-100 nm.

2. The application of the polyether-modified siloxane as described in claim 1 as a virus disinfectant, characterized in that, Includes the following steps, in parts by weight: S1. Add 1-2 parts of modified chitosan to 5-10 parts of ethanol, mix with 1-3 parts of fumed silica under shear, and dry to obtain composite particles. S2. Add 1-2 parts of polyvinylpyrrolidone to a mixture of 40-50 parts of water and glycerin, then add 2-4 parts of composite particles and 0.1-1 parts of organosilicon surfactant and disperse evenly to obtain an aqueous phase; S3. Add 2-8 parts of polyether-modified siloxane to a mixture of 30-50 parts of ethanol and isopropanol, mix well, then add to the aqueous phase, stir well, and then spray on the environment or animal body surface to be disinfected. The polyether-modified siloxane has a pore size of 80-100 nm.

3. The application of the polyether-modified siloxane as described in claim 2 as a virus disinfectant, characterized in that, The method for preparing the modified chitosan includes the following steps: X1. Dimethylaminoethyl methacrylate and bromododecane were added to isopropanol. The mass ratio of dimethylaminoethyl methacrylate to bromododecane and isopropanol was 1:1-2:4-10. The mixture was heated to 50-60℃ and reacted under a nitrogen atmosphere in the dark for 24-48 hours. After the reaction was completed, the mixture was cooled to room temperature and post-treated to obtain the modified monomer. X2. Chitosan is dispersed in isopropanol and alkalized with alkali, then chloroacetic acid solution is added. The mass ratio of chitosan to isopropanol, sodium hydroxide, and chloroacetic acid is 1:5-10:1-3:2-3. The mixture is heated to 50-60℃ and stirred for 3-5 hours. The pH is then adjusted to neutral by adding acid. The solid obtained after post-treatment is added to 30-50 times its volume of water and mixed with modified monomers and ammonium persulfate. The mass ratio of the solid obtained after post-treatment to modified monomers and ammonium persulfate is 1:1-3:0.1-0.

2. The mixture is heated to 60-70℃ and reacted under a nitrogen atmosphere for 6-8 hours. After cooling to room temperature, modified chitosan is obtained through post-treatment.

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