How to identify compounds and impurities contained in them

Abstract

The present invention relates to a method for identifying a compound and impurities contained therein.

Description

[Technical Field]

[0001] This application claims the benefit of the filing date of Korean Patent Application No. 10-2022-0117306, filed with the Korean Intellectual Property Office on September 16, 2022, the entire contents of which are incorporated herein by reference.

[0002] The present invention relates to a method for identifying compounds and impurities contained therein. [Background technology]

[0003] In recent years, antibacterial properties have been required for a variety of products, including household goods and hygiene products.

[0004] The required level of antibacterial properties and the requirements for materials that provide antibacterial properties vary depending on the material of the product that requires antibacterial properties and the state of final use. For example, the nature of the material that provides antibacterial properties and the level of antibacterial properties vary depending on the amount of antibacterial material used in the product and the materials used together.

[0005] However, since the antibacterial product contains unintended decomposition products or intermediate products that are not the intended target due to the high temperature process required during the manufacturing process, it is difficult to obtain a highly pure product.

[0006] Therefore, there is a need to develop a method that can identify whether an antibacterial material suitable for application to various products contains decomposition products or impurities that are not the target of the product. Summary of the Invention [Problem to be solved by the invention]

[0007] The present invention relates to a method for identifying compounds and impurities contained therein. [Means for solving the problem]

[0008] One embodiment of the present invention provides a compound comprising a quaternary ammonium structure having an acrylate or methacrylate group, the compound having a turbidity of less than 120 as determined by Method 1 below.

[0009] [Method 1] A 20 wt % aqueous solution of the compound is analyzed by UV / Vis spectroscopy to measure the absorbance Abs for light with a wavelength of 290 nm, and the turbidity Tb is calculated from the measured absorbance Abs using the following formula 1.

[0010] [Formula 1] Abs=0.00309Tb+0.04946

[0011] Another embodiment of the present invention provides a method for identifying impurities in a compound containing a quaternary ammonium structure having an acrylate group or a methacrylate group, wherein the impurities are identified by at least one of the following methods 1' to 3':

[0012] [Method 1'] A 20 wt % aqueous solution of the compound was analyzed by UV / Vis spectroscopy to measure the absorbance Abs for light with a wavelength of 290 nm, and the turbidity Tb was calculated from the measured absorbance Abs using the following formula 1. If the calculated turbidity Tb is 120 or higher, the presence of impurities was confirmed.

[0013] [Formula 1] Abs=0.00309Tb+0.04946

[0014] [Method 2'] The compound is dissolved in a mixed solution containing acetonitrile and water in a volume ratio of 5:5 and analyzed by HPLC / CAD. If a peak of 100 mV or more is detected between 4 and 9 minutes, the presence of impurities is confirmed.

[0015] [Method 3'] The compound is dissolved in DMF and analyzed by GPC / RI-DMF. If a peak of 10 mV or more is detected between 10 and 18 minutes, the presence of an impurity is confirmed. [Effects of the Invention]

[0016] Compounds according to some embodiments of the present invention have the advantage of being free of or containing few impurities.

[0017] The compounds according to some embodiments of the present invention have the advantage of having excellent antibacterial activity.

[0018] The method for checking impurities according to some embodiments of the present invention makes it easy to check whether a target impurity is present.

[0019] The method for checking impurities according to some embodiments of the present invention can be applied to quality control such as QC (Quality Control).

[0020] The method for identifying impurities according to some embodiments of the present invention has the advantage of being rapid in duration. [Brief explanation of the drawings]

[0021] [Figure 1] FIG. 1 shows UV / Vis measurements according to some embodiments of the present invention. [Figure 2] FIG. 1 shows HPLC / CAD results according to some embodiments of the present invention. [Figure 3] FIG. 1 shows HPLC / CAD results according to some embodiments of the present invention. [Figure 4] FIG. 1 shows GPC / RI-DMF results according to some embodiments of the present invention. [Figure 5] FIG. 1 shows GPC / RI-DMF results according to some embodiments of the present invention. [Figure 6] FIG. 1 shows GPC / RI-CHCl3 measurement results according to some embodiments of the present invention. [Figure 7] FIG. 1 shows GPC / RI-CHCl3 measurement results according to some embodiments of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0022] The present invention will be described in detail below.

[0023] One embodiment of the present invention provides a compound comprising a quaternary ammonium structure having an acrylate or methacrylate group, the compound having a turbidity of less than 120 as determined by Method 1 below.

[0024] [Method 1] A 20 wt % aqueous solution of the compound is analyzed by UV / Vis spectroscopy to measure the absorbance Abs for light with a wavelength of 290 nm, and the turbidity Tb is calculated from the measured absorbance Abs using the following formula 1.

[0025] [Formula 1] Abs=0.00309Tb+0.04946

[0026] According to one embodiment of the present specification, the above formula 1 is derived via the following method A.

[0027] [Method A] Five turbidity standard solutions (0, 1, 10, 100, and 1,000 NTU) were analyzed by UV / Vis spectroscopy (Agilent 8453, 200-1,100 nm, 2 nm resolution, 1 mm cuvette) to determine the absorbance of light at a wavelength of 290 nm. An empty cuvette cell was used as the reference for the measurement. A calibration curve (Equation 1) was derived from the absorbance in the range from 0 NTU to 1,000 NTU. (NTU: Nephelometric Turbidity Unit, water quality standard: 1 NTU)

[0028] According to one embodiment of the present invention, in the method 1, when the turbidity is 120 or more, it can be determined that a large amount of impurities is contained, and when the turbidity is 40 or more and less than 120, it can be determined that some impurities are contained. As an example, when the turbidity is 40 or more and less than 120, it can be determined that some impurities are contained in sample numbers 3 to 6 in the examples described below.

[0029] According to one embodiment of the present invention, the turbidity of the compound is less than 40. Preferably, when the turbidity Tb in Method 1 is less than 40, the absence of impurities can be confirmed. As an example, Sample Nos. 1 and 2 in the Examples described below, which have a turbidity Tb of less than 40, can be determined to have no or very few impurities.

[0030] On the other hand, when the turbidity Tb is 120 or more, it can be confirmed that the compound contains a very large amount of impurities. As an example, sample No. 7 in the Examples described below, which has a turbidity Tb of 120 or more, can be determined to contain a very large amount of impurities.

[0031] According to one embodiment of the present invention, the lower limit of the turbidity of the compound is not limited and may be 0 or more.

[0032] According to one embodiment of the present invention, when the turbidity of the compound satisfies the requirement of less than 120, the antibacterial activity can be improved.

[0033] According to one embodiment of the present invention, in order to make the turbidity of the compound satisfy the above range, i.e., to reduce the concentration of impurities, the synthesis conditions of the compound can be adjusted, or purification can be performed during or after the synthesis.

[0034] Specifically, in order to reduce the impurity concentration, the synthesis may be carried out at a temperature of 20°C to 80°C for 3 to 30 hours during compound production. More specifically, the synthesis may be carried out at a temperature of 40°C to 70°C for 4 to 25 hours. More specifically, the synthesis may be carried out for 4 to 20 hours.

[0035] To reduce the impurity concentration, a polymerization inhibitor may be used in an amount of 0.001 to 0.05 equivalents, specifically 0.001 to 0.01 equivalents, per equivalent of reactant during compound production.

[0036] In addition, in order to reduce the impurity concentration, the reaction solution and the precipitation solution may be used at a volume ratio of 1:1 to 1:30 (reaction solution:precipitation solution), specifically, 1:3 to 1:20, during precipitation for compound production.

[0037] In one embodiment of the present invention, the polymerization inhibitor and the precipitating solution can be any material commonly used in the art without any limitations.

[0038] According to one embodiment of the present invention, the impurity may be a polymer containing the compound having a quaternary ammonium structure with an acrylate group or a methacrylate group and / or a polymer containing units derived from the compound having a quaternary ammonium structure with an acrylate group or a methacrylate group. For example, the impurity may be a homopolymer of the compound.

[0039] According to one embodiment of the present invention, when the compound is subjected to the following method 2, no peak of 100 mV or more is detected within 4 to 9 minutes.

[0040] [Method 2] The compound is dissolved in a mixed solution containing acetonitrile and water in a volume ratio of 5:5, and analyzed by HPLC / CAD (High Performance Liquid Chromatography / Charged Aerosol Detector).

[0041] In this case, the method 2 may be carried out according to the following specific conditions.

[0042] -Column: Capcellpak CN, 4.6mmID x 150mmL, 5μm, Shiseido First mobile phase: acetonitrile / trichloroacetic acid = 100 / 0.1 (v / v, %) Second mobile phase: H2O / trichloroacetic acid = 100 / 0.1 (v / v, %) -Flow rate: 1mL / min -Injection volume: 5μL -Progress time: 15 minutes

[0043] According to one embodiment of the present invention, the method 2 may use a sample in which 1 mg of the compound is dissolved in 1 mL of the mixed solution. That is, the method 2 is performed using a sample with a concentration of 1 mg / mL (compound / mixed solution).

[0044] According to one embodiment of the present invention, a compound containing a quaternary ammonium structure having an acrylate or methacrylate group that does not contain impurities does not exhibit a peak of 100 mV or more between 4 and 9 minutes when subjected to Method 2. On the other hand, when impurities are present, a peak of 100 mV or more between 4 and 9 minutes when subjected to Method 2. Based on this, if a peak of 100 mV or more is detected between 4 and 9 minutes when subjected to Method 2, it can be confirmed that the sample further contains impurities in addition to the compound containing a quaternary ammonium structure having an acrylate or methacrylate group.

[0045] According to one embodiment of the present invention, when impurities are present, a peak of 125 mV or more is detected in 4 to 9 minutes when Method 2 is used.

[0046] According to one embodiment of the present invention, when the compound is subjected to the method 2, no peak of 50 mV or more is detected within 4 to 9 minutes.

[0047] According to one embodiment of the present invention, when the compound is subjected to the method 2, no peak is detected between 4 and 9 minutes, or a peak of less than 50 mV is detected.

[0048] According to one embodiment of the present invention, when the compound is subjected to the method 2, no peak of 100 mV or more is detected within 4 to 12 minutes.

[0049] According to one embodiment of the present invention, when the compound is subjected to the method 2, a peak is detected in 1 to 3 minutes.

[0050] According to one embodiment of the present invention, when the compound is subjected to the method 2, a peak of 100 mV or more is detected within 1 to 3 minutes.

[0051] According to one embodiment of the present invention, when the compound is subjected to the method 2, peaks are detected in 1 to 3 minutes, and one or more of the detected peaks are 100 mV to 5,000 mV.

[0052] In the present invention, the magnitude of a peak refers to the magnitude of the highest point of the peak. For example, the detection of a peak of 100 mV or more between 1 and 3 minutes means that the highest point of the peak present between 1 and 3 minutes is 100 mV or more.

[0053] According to one embodiment of the present invention, when the above-mentioned method 2 is used, a compound for which no peak of 100 mV or more is detected between 4 and 9 minutes exhibits an effect of improving antibacterial activity.

[0054] According to one embodiment of the present invention, in order to prevent a peak of 100 mV or more from being detected at 4 to 9 minutes, i.e., to reduce the concentration of impurities, the synthesis conditions of the compound can be adjusted or purification can be performed during or after the synthesis process when using Method 2. Specific synthesis conditions for this purpose are the same as those described above for Method 1.

[0055] According to one embodiment of the present invention, when the compound is subjected to the following method 3, no peak of 10 mV or more is detected within 10 to 18 minutes.

[0056] [Method 3] The compound is dissolved in DMF and analyzed by GPC / RI-DMF (Gel Permeation Chromatography / Refractive Index-DMF).

[0057] In this case, the method 3 may be carried out according to the following specific conditions.

[0058] -Column: PLgel column -1st mobile phase: DMF / 0.01M LiBr -Flow rate: 1mL / min -Injection volume: 100μL -Progress time: 35 minutes

[0059] According to one embodiment of the present invention, a sample in which 5 mg of a compound is dissolved in 1 mL of DMF (dimethylformamide) can be used in Method 3. That is, measurement is performed in Method 3 using a sample with a concentration of 5 mg / mL (compound / mixed solution).

[0060] According to one embodiment of the present invention, a compound containing a quaternary ammonium structure having an acrylate or methacrylate group that does not contain impurities does not exhibit a peak of 10 mV or more between 10 and 18 minutes when subjected to Method 3. On the other hand, when impurities are present, a peak of 10 mV or more between 10 and 18 minutes when subjected to Method 3. Based on this, if a peak of 10 mV or more is detected between 10 and 18 minutes when subjected to Method 3, it can be confirmed that the sample further contains impurities in addition to the compound containing a quaternary ammonium structure having an acrylate or methacrylate group.

[0061] According to one embodiment of the present invention, when the compound is subjected to Method 3, no peak of 5 mV or more is detected between 10 and 18 minutes.

[0062] According to one embodiment of the present invention, when the compound is subjected to Method 3, no peak is detected between 10 and 18 minutes.

[0063] According to one embodiment of the present invention, when a sample containing impurities is subjected to Method 3, a peak of 10 mV or more is detected in 10 to 18 minutes.

[0064] According to one embodiment of the present invention, the upper limit of the peak detected from a sample containing impurities is not limited, but may be, for example, 500 mV or less. For example, when a sample containing impurities is subjected to Method 3, a peak of 10 mV or more and 500 mV or less is detected in 10 to 18 minutes.

[0065] According to one embodiment of the present invention, the method 3 may involve dissolving a sample in DMF at a concentration of 5 mg / ml (sample / DMF), shaking the mixture for approximately 10 to 14 hours, and then measuring the resultant by GPC / RI-DMF.

[0066] According to one embodiment of the present invention, when the above-mentioned method 3 is used, a compound for which no peak of 10 mV or more is detected between 10 and 18 minutes exhibits an effect of improving antibacterial activity.

[0067] According to one embodiment of the present invention, in order to prevent a peak of 10 mV or more from being detected between 10 and 18 minutes, i.e., to reduce the concentration of impurities, the synthesis conditions of the compound can be adjusted or purification can be performed during or after the synthesis in Method 3. Specific synthesis conditions for this purpose are the same as those described above for Method 1.

[0068] According to one embodiment of the present invention, the compound is represented by the following Chemical Formula 1:

[0069] [ka]

[0070] In the above Chemical Formula 1, R1 to R3 are the same or different and each independently represents a hydrogen atom or a methyl group; R4 to R6 are the same or different and each independently represents an alkyl group; L is an alkylene group.

[0071] According to one embodiment of the present invention, R1 is hydrogen or a methyl group.

[0072] According to one embodiment of the present invention, R2 is hydrogen or a methyl group.

[0073] According to one embodiment of the present invention, R3 is hydrogen or a methyl group.

[0074] According to one embodiment of the present invention, R2 and R3 are hydrogen, and R1 is hydrogen or a methyl group.

[0075] According to one embodiment of the present invention, the L is an alkylene group having 1 to 30 carbon atoms.

[0076] According to one embodiment of the present invention, the L is an alkylene group having 1 to 10 carbon atoms.

[0077] According to one embodiment of the present invention, the L is an alkylene group having 1 to 5 carbon atoms.

[0078] According to one embodiment of the present invention, L is a methylene group, an ethylene group, a propylene group, or a butylene group.

[0079] According to one embodiment of the present invention, the R2 and R3 are hydrogen, the R1 is hydrogen or a methyl group, and the L is an alkylene group having 1 to 30 carbon atoms.

[0080] According to one embodiment of the present invention, the R2 and R3 are hydrogen, the R1 is hydrogen or a methyl group, and the L is an alkylene group having 1 to 10 carbon atoms.

[0081] According to one embodiment of the present invention, R2 and R3 are hydrogen, R1 is hydrogen or a methyl group, and L is a methylene group, an ethylene group, a propylene group, or a butylene group.

[0082] According to one embodiment of the present invention, R4 to R6 are the same or different and each independently represent an alkyl group having 1 to 30 carbon atoms.

[0083] According to one embodiment of the present invention, any one of R4 to R6 is an alkyl group having 5 to 30 carbon atoms, and the rest are the same or different and each independently an alkyl group having 1 to 30 carbon atoms.

[0084] According to one embodiment of the present invention, any one of R4 to R6 is an alkyl group having 5 to 30 carbon atoms, and the rest are the same or different and each independently an alkyl group having 1 to 20 carbon atoms.

[0085] According to one embodiment of the present invention, any one of R4 to R6 is an alkyl group having 5 to 30 carbon atoms, and the rest are the same or different and each independently an alkyl group having 1 to 15 carbon atoms.

[0086] According to one embodiment of the present invention, any one of R4 to R6 is an alkyl group having 5 to 20 carbon atoms, and the rest are the same or different and each independently an alkyl group having 1 to 30 carbon atoms.

[0087] According to one embodiment of the present invention, any one of R4 to R6 is an alkyl group having 5 to 20 carbon atoms, and the rest are the same or different and each independently an alkyl group having 1 to 20 carbon atoms.

[0088] According to one embodiment of the present invention, any one of R4 to R6 is an alkyl group having 5 to 20 carbon atoms, and the rest are the same or different and each independently an alkyl group having 1 to 10 carbon atoms.

[0089] According to one embodiment of the present invention, any one of R4 to R6 is an alkyl group having 5 to 20 carbon atoms, and the rest are the same or different and each independently an alkyl group having 1 to 4 carbon atoms.

[0090] According to one embodiment of the present invention, R2 and R3 are hydrogen, R1 is hydrogen or a methyl group, L is an alkylene group having 1 to 30 carbon atoms, any of R4 to R6 is an alkyl group having 5 to 30 carbon atoms, and the remainder of R4 to R6 are the same or different and each independently is an alkyl group having 1 to 30 carbon atoms.

[0091] According to one embodiment of the present invention, R2 and R3 are hydrogen, R1 is hydrogen or a methyl group, L is an alkylene group having 1 to 20 carbon atoms, any of R4 to R6 is an alkyl group having 5 to 20 carbon atoms, and the remainder of R4 to R6 are the same or different and each independently is an alkyl group having 1 to 20 carbon atoms.

[0092] According to one embodiment of the present invention, R2 and R3 are hydrogen, R1 is hydrogen or a methyl group, L is an alkylene group having 1 to 10 carbon atoms, any of R4 to R6 is an alkyl group having 5 to 20 carbon atoms, and the remainder of R4 to R6 are the same or different and each independently an alkyl group having 1 to 15 carbon atoms.

[0093] According to one embodiment of the present invention, the compound is any one selected from the following compounds 1 to 10.

[0094] [ka] [ka]

[0095] According to one embodiment of the present invention, the compound containing a quaternary ammonium structure having an acrylate or methacrylate group exhibits cationic properties and may exist in the form of a salt with a group exhibiting anionic properties. In this case, the group exhibiting anionic properties is not particularly limited, and materials known in the art may be used as long as they do not impair the purpose of the antibacterial resin. For example, the group exhibiting anionic properties may be a halogen-based anion or a sulfonate-based anion, and specifically, Br- It may be, but is not limited to this.

[0096] According to one embodiment of the invention, the compound is an antibacterial compound, i.e., the compound exhibits antibacterial properties.

[0097] In one embodiment of the present specification, the antimicrobial resin exhibits antimicrobial activity against at least one of gram-positive bacteria, gram-negative bacteria, and fungi.

[0098] In this specification, Gram-positive bacteria is a general term for bacteria that stain purple when stained by the Gram staining method. The cell walls of Gram-positive bacteria are composed of multiple layers of peptidoglycan, and after staining with a basic dye such as crystal violet, they retain their purple color even when treated with ethanol.

[0099] In one embodiment of the present specification, the Gram-positive bacterium is selected from Enterococcus faecalis, Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecium, and Lactobacillus lactis. Specifically, the Gram-positive bacterium is any one selected from the above-mentioned examples, but is not limited thereto.

[0100] As used herein, Gram-negative bacteria are a collective term for bacteria that stain red when stained with the Gram staining method, and instead of having a cell wall with a relatively small amount of peptidoglycan compared to Gram-positive bacteria, have an outer membrane composed of lipid polysaccharides, lipid proteins, and / or other complex polymeric substances.

[0101] In one embodiment of the present specification, the Gram-negative bacterium is selected from Proteus mirabilis, Escherichia coli, Salmonella typhi, Pseudomonas aeruginosa, and Vibrio cholerae. Specifically, the Gram-negative bacterium is any bacterium selected from the above-mentioned examples, but is not limited thereto.

[0102] In one embodiment of the present specification, the fungus may be, but is not limited to, Candida albicans.

[0103] In this specification, "exhibiting antibacterial properties" means that the antibacterial activity measured based on the following method 4, that is, the bacteriostatic reduction rate, is 90% or more.

[0104] According to one embodiment of the present specification, the antibacterial resin has an antibacterial activity of 90% or more against any strain selected from the group consisting of gram-positive bacteria, gram-negative bacteria, and fungi, as measured by the following method 4.

[0105] [Method 4] 1 g of sample was placed in a 250 mL Erlenmeyer flask, and 50 mL of phosphate-buffered saline (PBS) inoculated with the bacterial strain was poured into it. This was then cultured for 1 hour in a shaking incubator maintained at 35°C. The culture solution was diluted and smeared on an agar medium plate. Serial dilutions were performed to enable colony counting, using a 0.9 wt.% NaCl solution. After calculating the initial microbial concentration (C0, CFU / mL) taking into account the dilution concentration, the antibacterial activity was calculated using the following equation 1.

[0106]

number

[0107] In one embodiment of the present specification, the sample used in the method 4 is a sample containing the compound.

[0108] In one embodiment of the present specification, when carrying out the method 4, the standard strain of E. coli ATCC25922 is used.

[0109] In one embodiment of the present specification, when carrying out the method 4, the strain is 1.5 × 10 5 CFU / ml ~ 3 x 10 5 Use by inoculating CFU / ml.

[0110] In one embodiment of the present specification, the antibacterial resin has an antibacterial activity of 90% or more against Gram-positive bacteria as measured by the above method 4.

[0111] In one embodiment of the present specification, the compound has an antibacterial activity of 90% or more against Gram-negative bacteria as measured by the above method 4.

[0112] In one embodiment of the present specification, the compound has an antibacterial activity of 90% or more against fungi as measured by the above method 4.

[0113] According to one embodiment of the present specification, the antibacterial activity is 92% or more, 94% or more, 96% or more, 98% or more, 99% or more, or 99.8% or more. The upper limit of the antibacterial activity is not particularly limited, and is, for example, 100% or less or less than 100%.

[0114] Since the above strains of gram-positive bacteria, gram-negative bacteria and fungi can cause various diseases when they come into contact with each other, as well as secondary infections, it is preferable to use a single compound that exhibits antibacterial properties against all of the above gram-positive bacteria, gram-negative bacteria and fungi.

[0115] One embodiment of the present invention provides a method for identifying impurities in a compound containing a quaternary ammonium structure having an acrylate group or a methacrylate group, the method being carried out by at least one of the following methods 1' to 3':

[0116] [Method 1'] A 20 wt % aqueous solution of the compound was analyzed by UV / Vis spectroscopy to measure the absorbance Abs for light with a wavelength of 290 nm, and the turbidity Tb was calculated from the measured absorbance Abs using the following formula 1. If the calculated turbidity Tb is 120 or higher, the presence of impurities was confirmed.

[0117] [Formula 1] Abs=0.00309Tb+0.04946

[0118] [Method 2'] The compound is dissolved in a mixed solution containing acetonitrile and water in a volume ratio of 5:5 and analyzed by HPLC / CAD. If a peak of 100 mV or more is detected between 4 and 9 minutes, the presence of impurities is confirmed.

[0119] [Method 3'] The compound is dissolved in DMF and analyzed by GPC / RI-DMF. If a peak of 10 mV or more is detected between 10 and 18 minutes, the presence of an impurity is confirmed.

[0120] Here, the method 2' may be carried out according to the following specific conditions.

[0121] -Column: Capcellpak CN, 4.6mmID x 150mmL, 5μm, Shiseido First mobile phase: acetonitrile / trichloroacetic acid = 100 / 0.1 (v / v, %) Second mobile phase: H2O / trichloroacetic acid = 100 / 0.1 (v / v, %) -Flow rate: 1mL / min -Injection volume: 5μL -Progress time: 15 minutes

[0122] In this case, the method 3' may be carried out according to the following specific conditions.

[0123] -Column: PLgel column -1st mobile phase: DMF / 0.01M LiBr -Flow rate: 1mL / min -Injection volume: 100μL -Progress time: 35 minutes

[0124] According to one embodiment of the present invention, the impurity may be a polymer containing the compound having a quaternary ammonium structure with an acrylate group or a methacrylate group and / or a polymer containing units derived from the compound having a quaternary ammonium structure with an acrylate group or a methacrylate group. For example, the impurity may be a homopolymer of the compound.

[0125] In general, compounds containing a quaternary ammonium structure having an acrylate or methacrylate group have very high solubility in water or organic solvents, making it easy to confirm their structure using standard solution 1H NMR spectroscopy. On the other hand, polymers containing compounds containing a quaternary ammonium structure having an acrylate or methacrylate group and polymers containing units derived from compounds containing a quaternary ammonium structure having an acrylate or methacrylate group have low solubility in water or organic solvents, making it difficult to confirm their structure using solution NMR spectroscopy. In other words, when a compound containing a quaternary ammonium structure having an acrylate or methacrylate group is mixed with impurities, it is difficult to determine whether or not the impurities are present in the solution NMR spectroscopy.

[0126] The method for identifying impurities according to the present invention has the advantage that impurities can be easily identified even when the compound containing a quaternary ammonium structure having an acrylate group or methacrylate group and the impurities are mixed together.

[0127] Furthermore, while methods such as solid NMR require long experimental times, the method of the present invention for checking impurities does not require such long times, which has the advantage that it can also be applied to quality control (QC).

[0128] For example, homopolymer impurities may be generated during the scale-up synthesis of the compound, and the above-described method for identifying the impurities allows for a simple and rapid evaluation of the grade according to the amount of the impurities.

[0129] According to one embodiment of the present invention, the above-mentioned explanation for Method 1 can be applied to Method 1' used in the impurity confirmation method, the above-mentioned explanation for Method 2 can be applied to Method 2', and the above-mentioned explanation for Method 3 can be applied to Method 3'.

[0130] One embodiment of the present invention provides a composition comprising the aforementioned compound.

[0131] According to one embodiment of the invention, the composition is an antibacterial composition.

[0132] According to one embodiment of the present invention, the composition may consist of the aforementioned compound, for example, a compound containing a quaternary ammonium structure having an acrylate or methacrylate group, and having a turbidity of less than 120 as determined by Method 1.

[0133] According to one embodiment of the present invention, the composition may contain the aforementioned compounds and the aforementioned impurities. For example, the composition may consist of compounds containing a quaternary ammonium structure having an acrylate group or a methacrylate group, the compounds having a turbidity of less than 120 and the compounds having a turbidity of 120 or more as determined by Method 1.

[0134] According to one embodiment of the present invention, the composition may further contain additives in addition to the compound.

[0135] According to one embodiment of the present invention, the additive may be an additive that exhibits antibacterial effects.

[0136] According to one embodiment of the present invention, the additive may be any substance used in the art without any limitation.

[0137] In the present invention, when a member (layer) is said to be "located on" another member (layer), this includes not only the case where a member (layer) is in contact with the other member, but also the case where another member (layer) exists between the two members (layers).

[0138] In the present invention, when a part is said to "comprise" a certain component, this does not mean that it excludes other components, but that it may further include other components, unless otherwise specified. [Example]

[0139] Hereinafter, the present invention will be described in detail with reference to examples in order to specifically explain the present invention. However, the examples of the present invention can be modified in various different forms, and the scope of the present invention should not be construed as being limited to the examples described below. The examples of the present invention are provided to more completely explain the present invention to those skilled in the art.

[0140] <Production Example A> Synthesis of Compound A-1. Synthesis of Compound 1, Compound 2, and Compound 3

[0141] [ka]

[0142] Step 1. (1) 0.1 mol of 2-(dibutylamino)ethanol (DBAE), 0.1 mol of trimethylamine, and 0.001 mol of hydroquinone were added to 100 mL of tetrahydrofuran (THF) (solvent). (2) While stirring the materials, 0.1 mol of acryloyl chloride was added dropwise onto the reaction solution (room temperature). (3) Stirred for 2 hours. (4) After removing the triethylamine salt by filtration, the solvent was removed using a rotary evaporator. (5) Vacuum dried at 83°C to 87°C.

[0143] Step 2. (1) The product of Step 1 and 1-bromooctane (production of compound 1), 1-bromodecane (production of compound 2), or 1-bromododecane (production of compound 3) were dissolved in acrylonitrile (solvent) at a ratio of 1:1 to a concentration of 50 wt%. (2) Next, p-methoxyphenol, a polymerization inhibitor, was added (ratio to reactants: 1:0.001 eq). (3) The reaction was carried out at 50°C for 20 hours. (4) The mixture was precipitated in methyl t-butyl ether (MTBE) (MTBE: reaction solution = 15:1) and then filtered. (5) Vacuum dried at 45°C.

[0144] A-2. Synthesis of Compound 4

[0145] [ka]

[0146] Step 1 (1) 0.1 mol of 2-(dioctylamino)ethanol (DOAE), 0.1 mol of trimethylamine, and 0.001 mol of hydroquinone were added to 100 mL of THF (solvent). (2) While stirring the materials, 0.1 mol of acryloyl chloride was added dropwise onto the reaction solution (room temperature). (3) Stirred for 2 hours. (4) After removing the triethylamine salt by filtration, the solvent was removed using a rotary evaporator. (5) Vacuum dried at 83°C to 87°C.

[0147] Step 2 (1) The product of Step 1 and 1-bromooctane were dissolved in acrylonitrile (solvent) at a ratio of 1:1 to 50 wt%. (2) Next, p-methoxyphenol, a polymerization inhibitor, was added (ratio to reactants: 1:0.001 eq). (3) The reaction was carried out at 50°C for 20 hours. (4) The mixture was precipitated in methyl t-butyl ether (MTBE) (MTBE: reaction solution = 15:1) and then filtered. (5) Vacuum dried at 45°C.

[0148] A-3. Synthesis of Compound 5

[0149] [ka]

[0150] Step 1. (1) 0.1 mol of 2-(dihexylamino)ethanol (DHAE), 0.1 mol of trimethylamine, and 0.001 mol of hydroquinone were added to 100 mL of THF (solvent). (2) While stirring the above materials, 0.1 mol of methacryloyl chloride was added dropwise onto the reaction solution (room temperature). (3) Stirred for 2 hours. (4) After removing the triethylamine salt by filtration, the solvent was removed using a rotary evaporator. (5) Vacuum dried at 83°C to 87°C.

[0151] Step 2. (1) The product of Step 1 and 1-bromodecane were dissolved in acrylonitrile (solvent) at a ratio of 1:1 at 50 wt%. (2) Next, p-methoxyphenol, a polymerization inhibitor, was added (ratio to reactants: 1:0.001 eq). (3) The reaction was carried out at 50°C for 20 hours. (4) The mixture was precipitated in methyl t-butyl ether (MTBE) (MTBE: reaction solution = 15:1) and then filtered. (5) Vacuum dried at 45°C.

[0152] A-4. Synthesis of Compound 6

[0153] [ka]

[0154] Step 1. (1) 0.1 mol of 2-(butylhexylamino)ethanol (BHAE), 0.1 mol of trimethylamine, and 0.001 mol of hydroquinone were added to 100 mL of THF (solvent). (2) While stirring the materials, 0.1 mol of methacryloyl chloride was added dropwise onto the reaction solution (room temperature). (3) Stirred for 2 hours. (4) After removing the triethylamine salt by filtration, the solvent was removed using a rotary evaporator. (5) Vacuum dried at 83°C to 87°C.

[0155] Step 2. (1) The product of Step 1 and 1-bromodecane were dissolved in acrylonitrile (solvent) at a ratio of 1:1 at 50 wt%. (2) Next, p-methoxyphenol, a polymerization inhibitor, was added (ratio to reactants: 1:0.001 eq). (3) The reaction was carried out at 50°C for 20 hours. (4) The mixture was precipitated in methyl t-butyl ether (MTBE) (MTBE: reaction solution = 15:1) and then filtered. (5) Vacuum dried at 45°C.

[0156] A-5. Synthesis of Compound 7

[0157] [ka]

[0158] Step 1. (1) 0.1 mol of 2-(butyloctylamino)ethanol (BOAE), 0.1 mol of trimethylamine, and 0.001 mol of hydroquinone were added to 100 mL of THF (solvent). (2) While stirring the materials, 0.1 mol of methacryloyl chloride was added dropwise onto the reaction solution (room temperature). (3) Stirred for 2 hours. (4) After removing the triethylamine salt by filtration, the solvent was removed using a rotary evaporator. (5) Vacuum dried at 83°C to 87°C.

[0159] Step 2. (1) The product of Step 1 and 1-bromodecane were dissolved in acrylonitrile (solvent) at a ratio of 1:1 at 50 wt%. (2) Next, p-methoxyphenol, a polymerization inhibitor, was added (ratio to reactants: 1:0.001 eq). (3) The reaction was carried out at 50°C for 20 hours. (4) The mixture was precipitated in methyl t-butyl ether (MTBE) (MTBE: reaction solution = 15:1) and then filtered. (5) Vacuum dried at 45°C.

[0160] A-6. Synthesis of Compound 8

[0161] [ka]

[0162] Step 1. (1) 0.1 mol of 2-(butyldecylamino)ethanol (BDAE), 0.1 mol of trimethylamine, and 0.001 mol of hydroquinone were added to 100 mL of THF (solvent). (2) While stirring the materials, 0.1 mol of acryloyl chloride was added dropwise onto the reaction solution (room temperature). (3) Stirred for 2 hours. (4) After removing the triethylamine salt by filtration, the solvent was removed using a rotary evaporator. (5) Vacuum dried at 83°C to 87°C.

[0163] Step 2. (1) The product of Step 1 and 1-bromodecane were dissolved in acrylonitrile (solvent) at a ratio of 1:1 at 50 wt%. (2) Next, p-methoxyphenol, a polymerization inhibitor, was added (ratio to reactants: 1:0.001 eq). (3) The reaction was carried out at 50°C for 20 hours. (4) The mixture was precipitated in methyl t-butyl ether (MTBE) (MTBE: reaction solution = 15:1) and then filtered. (5) Vacuum dried at 45°C.

[0164] A-7. Synthesis of Compound 9

[0165] [ka]

[0166] Step 1. (1) 0.1 mol of 2-(dibutylamino)butanol (DBAB), 0.1 mol of trimethylamine, and 0.001 mol of hydroquinone were added to 100 mL of THF (solvent). (2) While stirring the materials, 0.1 mol of acryloyl chloride was added dropwise onto the reaction solution (room temperature). (3) Stirred for 2 hours. (4) After removing the triethylamine salt by filtration, the solvent was removed using a rotary evaporator. (5) Vacuum dried at 83°C to 87°C.

[0167] Step 2. (1) The product of Step 1 and 1-bromooctane were dissolved in acrylonitrile (solvent) at a ratio of 1:1 to 50 wt%. (2) Next, p-methoxyphenol, a polymerization inhibitor, was added (ratio to reactants: 1:0.001 eq). (3) The reaction was carried out at 50°C for 20 hours. (4) The mixture was precipitated in methyl t-butyl ether (MTBE) (MTBE: reaction solution = 15:1) and then filtered. (5) Vacuum dried at 45°C.

[0168] A-8. Synthesis of Compound 10

[0169] [ka]

[0170] Step 1. (1) 0.1 mol of 2-(dioctylamino)butanol (DOAB), 0.1 mol of trimethylamine, and 0.001 mol of hydroquinone were added to 100 mL of THF (solvent). (2) While stirring the materials, 0.1 mol of acryloyl chloride was added dropwise onto the reaction solution (room temperature). (3) Stirred for 2 hours. (4) After removing the triethylamine salt by filtration, the solvent was removed using a rotary evaporator. (5) Vacuum dried at 83°C to 87°C.

[0171] Step 2. (1) The product of Step 1 and 1-bromooctane were dissolved in acrylonitrile (solvent) at a ratio of 1:1 to 50 wt%. (2) Next, p-methoxyphenol, a polymerization inhibitor, was added (ratio to reactants: 1:0.001 eq). (3) The reaction was carried out at 50°C for 20 hours. (4) The mixture was precipitated in methyl t-butyl ether (MTBE) (MTBE: reaction solution = 15:1) and then filtered. (5) Vacuum dried at 45°C.

[0172] In the synthesis example described above, a static precipitation method was used in which the reactants were added to a nonsolvent, but a reverse precipitation method in which the nonsolvent is added to the reactants can also be used. Furthermore, the ratio of MTBE to the reaction solution may be other than 15:1, such as 12:1 or 26:1.

[0173] <Production Example B> Sample production When compound 3 was produced in step 2 (3) of Production Example A-1, the reaction time was set to 4 hours, 8 hours, 10 hours, 12 hours, 16 hours, 20 hours, and 24 hours, respectively. The products were collected and named samples 1 to 7, respectively.

[0174] <Example> Example 1. Turbidity measurement The UV / Vis of Samples 1 to 7 produced in Production Example B using Method 1 of the present invention was measured, and the results are shown in Figure 1. The measured absorbance (Abs) was converted into turbidity using the following equation 1, and the values ​​are shown in Table 1 below.

[0175] [Formula 1] Abs=0.00309Tb+0.04946

[0176] Specifically, the turbidity was measured by UV / Vis spectroscopy analysis under the following conditions.

[0177] 1) UV / Vis spectroscopy measurement 500 mg of each of Samples 1 to 7 was placed in a vial and diluted with distilled water to prepare a 20 wt% aqueous solution. The absorbance at 290 nm was measured by UV / Vis spectroscopy (Agilent 8453, 200-1100 nm, 2 nm resolution, 1 mm cuvette). DI water was used as a reference for the measurements.

[0178] 2) Derivation of turbidity calculation formula (formula 1) Five turbidity standard solutions (0, 1, 10, 100, and 1000 NTU) were analyzed by UV / Vis spectroscopy (Agilent 8453, 200-1100 nm, 2 nm resolution, 1 mm cuvette) to determine the absorbance at 290 nm wavelength. An empty cuvette was used as a reference for the measurements.

[0179] A calibration curve (Equation 1) was derived from absorbance in the range of 0 NTU to 1,000 NTU. (NTU: Nephelometric Turbidity Unit, water quality standard: 1 NTU)

[0180] [Formula 1] Abs=0.00309Tb+0.04946 (Abs: absorbance, Tb: turbidity)

[0181] 3) Turbidity calculation for samples 1 to 7 The absorbances of Samples 1 to 7 confirmed in 1) above were introduced into Equation 1 to derive the turbidity.

[0182] [Table 1]

[0183] From Table 1, it can be seen that as the polymerization progresses and the amount of homopolymer relative to the compound increases (from Sample 1 to Sample 7), the turbidity improves. Specifically, Samples 1 and 2, which had a short polymerization time and produced little homopolymer, had converted turbidities of less than 40. Furthermore, Samples 3 to 6, which had intermediate polymerization times, produced a small amount of homopolymer and had turbidities of 40 or more and less than 120. On the other hand, Sample 7, which had a long polymerization time and produced a large amount of homopolymer, had a turbidity of 120 or more.

[0184] This shows that the level of impurities can be confirmed by measuring turbidity using Method 1 and Equation 1.

[0185] Example 2. HPLC / CAD measurement The impurities in Sample 1 and Sample 6 were confirmed using Method 2 of the present invention.

[0186] Specifically, HPLC / CAD was measured under the following conditions.

[0187] -Column: Capcellpak CN, 4.6mmID x 150mmL, 5μm, Shiseido First mobile phase: acetonitrile / trichloroacetic acid = 100 / 0.1 (v / v, %) Second mobile phase: H2O / trichloroacetic acid = 100 / 0.1 (v / v, %) -Flow rate: 1mL / min -Injection volume: 5μL -Progress time: 15 minutes

[0188] Figure 2 shows the HPLC / CAD measurement results for Sample 1. Since the measurement in Figure 2 contained no impurities other than Compound 3, it can be seen that two or more peaks were detected only between 1 and 3 minutes, and no peaks were detected between 4 and 9 minutes.

[0189] Figure 3 shows the HPLC / CAD measurement results for Sample 6. Sample 6 used in Figure 3 contains Compound 3 and impurities, and it can be seen that two or more peaks were detected between 1 and 3 minutes, as well as a peak of 100 mV or more between 4 and 9 minutes.

[0190] Example 3. GPC / RI-DMF measurement Using Method 3 of the present invention, impurities in Sample 1 and Sample 7 were identified.

[0191] Specifically, GPC / RI-DMF was measured under the following conditions.

[0192] -Column: PLgel column -1st mobile phase: DMF / 0.01M LiBr -Flow rate: 1mL / min -Injection volume: 100μL -Progress time: 35 minutes

[0193] FIG. 4 shows the results of GPC / RI-DMF measurement of sample 1, and FIG. 5 shows the results of GPC / RI-DMF measurement of sample 7.

[0194] Figure 4 shows the results of measurements taken with Sample 1, which contains the compound and a trace amount of homopolymer, and Figure 5 shows the results of measurements taken with Sample 7, which contains the compound and a large amount of homopolymer. In both Figures 4 and 5, it can be seen that a peak of 10 mV or more was detected between 10 and 18 minutes. This confirmed that even if only a trace amount of homopolymer (impurity) is contained in the compound, it is possible to detect whether or not the impurity is present by GPC / RI-DMF measurement as in Method 3.

[0195] Comparative example 1.GPC / RI-CHCl3 measurement In Example 3, GPC / RI-CHCl3 was measured for Sample 1 and Sample 6 using CHCl3 instead of DMF.

[0196] FIG. 6 shows the measurement results of Compound 3 produced in Production Example A-1, and FIG. 7 shows the measurement results of Sample 6 by GPC / RI-CHCl3.

[0197] It can be seen from Figure 6 that a peak of 20 mV or more was detected between 18 and 22 minutes when the compound of the present invention was measured using GPC / RI-CHCl3. On the other hand, it can be seen from Figure 7 that no peak was detected between 18 and 22 minutes. Sample 6 contains the compound and impurities, and a peak of 20 mV or more should have been detected between 18 and 22 minutes as in Figure 6. However, since no such peak was detected in Figure 7, it was confirmed that GPC / RI-CHCl3 is not suitable for detecting impurities.

[0198] Example 4. Antibacterial activity measurement One gram of sample was placed in a 250 mL Erlenmeyer flask, and 50 mL of phosphate-buffered saline (PBS) inoculated with E. coli ATCC 25922 standard strain was added. This was then cultured for 1 hour in a shaking incubator maintained at 35°C. The culture solution was diluted and smeared on an agar medium plate. Serial dilutions were performed to enable colony counting, using a 0.9 wt.% NaCl solution. The initial microbial concentration (C0, CFU / mL) was calculated taking the dilution concentration into account, and the antibacterial activity was calculated using the following equation 1.

[0199]

number

[0200] In Table 2 below, the control is a bacterial inoculated culture medium to which no sample was added, and is a measure of whether the bacteria had grown properly. In Example 4-1 and Comparative Example 4-1 below, the reliability of the experiment was confirmed through the control in Table 2 below before the experiment was carried out.

[0201] [Table 2]

[0202] When the results in Table 2 are summarized with Table 1, it can be seen that samples with low turbidity have high antibacterial activity.

[0203] This confirms that the lower the content of impurities, the lower the turbidity and the more improved the antibacterial activity.

Claims

1. A composition comprising a compound represented by the following chemical formula 1: A composition having a turbidity of less than 120 as derived by Method 1 below: 【Chemistry 1】 In the above Chemical Formula 1, R1 to R3 are the same or different and each independently represents a hydrogen atom or a methyl group; any one of R4 to R6 is an alkyl group having 5 to 30 carbon atoms, and the rest are the same or different and each independently is an alkyl group having 1 to 30 carbon atoms; L is an alkylene group having 1 to 30 carbon atoms. [Method 1] A 20 wt % aqueous solution of the compound was analyzed by UV / Vis spectroscopy to measure the absorbance Abs for light with a wavelength of 290 nm, and the turbidity Tb was calculated from the measured absorbance Abs using the following equation 1. [Formula 1] Abs=0.00309Tb+0.04946

2. 10. The composition of claim 1, wherein the turbidity is less than 40.

3. The composition according to claim 1, wherein when the composition is subjected to the following method 2, no peak of 100 mV or more is detected within 4 to 9 minutes: [Method 2] The compound is dissolved in a mixed solution containing acetonitrile and water in a volume ratio of 5:5 and analyzed by HPLC / CAD.

4. The composition according to claim 3, wherein a peak is detected in 1 to 3 minutes when the composition is subjected to method 2.

5. The composition according to claim 1, wherein when the composition is subjected to the following method 3, no peak of 10 mV or more is detected between 10 and 18 minutes: [Method 3] The compound is dissolved in DMF and analyzed by GPC / RI-DMF.

6. 2. The compound according to claim 1, wherein R2 and R3 are hydrogen, R1 is hydrogen or a methyl group, and L is an alkylene group having 1 to 30 carbon atoms.

7. The composition according to claim 1, wherein the compound is any one selected from the following compounds 1 to 10: 【Chemistry 2】 【Transformation 3】

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