CN110313489B - Antiseptic and bactericidal wet wipes and preparation method and application thereof - Google Patents

Abstract

The invention provides an antiseptic or mildew inhibitor for wet tissues, which comprises lauroyl arginine ethyl ester (LAE) and ion pair derivatives thereof. The invention also provides a method for preparing the preservative or mildew preventive for the wet tissue and the preservative or mildew preventive for the wet tissue prepared by the method. The preservative or mildew preventive for the wet tissue has the characteristics of being natural, non-toxic, efficient in bacteriostasis, easy to degrade and environment-friendly.

Description

Antiseptic and bactericidal wet wipes and preparation method and application thereof

technical field

The present invention relates to anti-corrosion and sterilization type wet wipes, in particular to anti-corrosion and sterilization type wet wipes containing lauroyl arginine ethyl ester and its derivatives (ion-pair compounds), the lauroyl arginine ethyl ester and its ion-pair derivatives It has an antibacterial effect, which can help wet wipes to exert their moisturizing function and also exert an antibacterial and antiseptic effect.

Background technique

With the continuous improvement of people's living standards, people's consumption of wet wipes is also increasing, and there are more and more varieties of wet wipes. From hotel wipes, car wipes, makeup remover wipes, facial mask wipes to children's hygiene wipes, etc., the production scale of wipes has also been expanded from manual workshops to automatic production lines. As far as the many occasions and functions of wet wipes are concerned, all wet wipe manufacturers are required to strictly sterilize the wet wipes during the production process of wet wipes, and at the same time, they must also have a good anti-corrosion and anti-mildew effect during the storage process. .

Although wet wipes are disinfection products, their process does not include disinfection. Once they are contaminated during production, storage and transportation, many harmful microorganisms will be attached to the wet wipes. After consumers use the contaminated wet towels, it may cause diarrhea, skin diseases, or other diseases in severe cases.

Due to the difficulty of anti-corrosion and mildew prevention of wet wipes, many domestic wet wipes manufacturers have experienced a lot of losses due to serious excess of microbes in wet wipes, odor and mildew. In order to prevent the reproduction of microorganisms on wet wipes, many companies have adopted the method of adding preservatives to the preparation solution to ensure that the products meet the national hygiene standards during the shelf life.

Chinese invention patent application 2012104006385, "An antiseptic and antifungal agent composition for wet wipes and its production method" discloses a kind of compound with 2-methylisothiazolinone (MIT) and/or 5-chloro-2-methyl Wipes with isothiazolinone (CMIT) and/or bronopol (Bropol) as preservatives. The invention scientifically combines the functions of sterilization, anti-corrosion and anti-mildew through the above-mentioned compatibility, and can protect the wet wipes from being polluted by microorganisms by adding them alone, so that the product has stronger anti-corrosion and anti-mildew effects, forming an anti-microbial hazard. best composition. However, the anti-preservative is still aimed at using toxic compounds to kill microorganisms, in order to overcome the drug resistance problem that often occurs in existing wet wipes, and long-term use still has an impact on the human body and the environment.

In the Chinese patent text whose publication number is CN101416843A, a method for making a smoke-proof and dust-proof wet towel has been disclosed. , Polyhexamethylene biguanide, distilled water and peppermint liquid are mixed to make a solution; 2. Disinfect the selected towel at high temperature; 3. Soak the disinfected towel in a solvent with a good proportion, and take it out; 4. Pack the removed towel into an aluminized film bag for sterile sealing. In this patent, bisimidazolidinyl urea is used as one of the preservative components, which will release formaldehyde. At the same time, several preservatives need to be added separately, which is very inconvenient to use. It is difficult to dissolve iodopropynyl butylcarbamate even in propylene glycol. , requires a long stirring and dissolving time, and at the same time, the towel pretreatment requires high temperature disinfection, which consumes energy and increases the production process.

In the Chinese patent text with the publication number of CN102613 935A, an aromatic disinfectant wipe and a preparation method thereof have been disclosed. The steps are to mix quantitative 2-bromo-2-nitropropanediol, benzethonium chloride, tetrahydrate Sodium borate and essence are made into a disinfectant mixed solution, and then the disinfectant mixed droplets are wetted on the carrier paper towel, and the dripping amount is 1.5 ml per gram of paper towel, and the paper towel is moistened to obtain an aromatic disinfectant wipe; this method uses tetrahydrate As a preservative component, sodium octaborate is a commonly used wood preservative and is a fungicide that cannot be in contact with the human body, thus affecting the application of its wet wipes products.

Therefore, the current research on natural non-toxic wet wipes preservatives or antifungal agents has become a research hotspot in wet wipes products.

Ethyl lauroylarginate (LAE) is an organic compound formed by the condensation of fatty acid and dibasic amino acid. It is a white hygroscopic solid with stable chemical properties in the range of pH 3 to 7, melting point of 50 to 58, At this temperature, 247g of LAE can be dispersed in 1kg of water, and its partition coefficient in water and oil is greater than 10, that is, it mainly exists in the water phase. The study found that lauroyl arginine ethyl ester LAE has the characteristics of strong antibacterial ability, low biological toxicity, good metabolism in vivo, and high compatibility with the environment. Among them, the most representative feature is that lauroyl arginine ethyl ester has no residue in metabolism. Relevant studies have shown that lauroyl arginine ethyl ester can be rapidly metabolized naturally in humans and animals, and is first hydrolyzed into lauroyl arginine. (LAS) and ethanol, which is then hydrolyzed to the naturally occurring dietary components lauric acid and arginine, which is further metabolized to carbon dioxide and water, and arginine, which is metabolized to ornithine, urea, and carbon dioxide. All primary metabolites and final products produced during the metabolism of lauroyl arginine ethyl ester are non-toxic and harmless, and are the same as the metabolites in the body of the food ingested by humans and animals daily. In 2005, the US FDA approved LAE as a GRAS (generally recognized as safe) food additive, and in 2007, it passed the safe food certification of the European Food Safety Authority (EFSA). Among them, LAE is licensed as a preservative in more than 20 kinds of food and fresh agricultural products.

Chinese patent application CN201710056593, titled "An antiseptic and preservative for fruits and vegetables and its preparation method and application", discloses a composition containing lauroyl arginine ethyl ester hydrochloride and sodium methylparaben as the main active ingredients. As a preservative and preservative for fruits and vegetables, it can effectively inhibit the growth of bacteria that cause fruits and vegetables to rot. However, the single antibacterial effect of high concentration sodium methylparaben (2000μg/ml) in this invention is stronger than that of low concentration LAE (1000μg/ml), because it has a phenolic hydroxyl structure, and its antibacterial performance is far stronger than Benzoic acid and sorbic acid, so on the premise of ensuring the preservative performance, this method clearly points out that the use of sodium methylparaben instead of LAE will help reduce the dosage and cost of preservatives.

Chinese patent application CN201510748675, the title of the invention is "method of using lauroyl arginine ethyl ester to inhibit alcohol fermentation contaminating microorganisms" discloses a method for using lauroyl arginine ethyl ester to inhibit alcohol fermentation contaminating microorganisms. Salt compounds, added to the fermentation broth of Saccharomyces cerevisiae at a concentration of less than 50 μg/ml, can effectively inhibit the growth of lactic acid bacteria and control the growth of other polluting microorganisms. However, the bacteriostat slightly affected yeast growth to some extent and resulted in a 0.6% reduction in alcohol production.

Chinese patent application CN201610466729, the name of the invention is "a mild baby shampoo and bath bubble" discloses a mild baby shampoo and bath bubble, which is based on the characteristics of the baby's hair and skin texture, using cocoyl glutamic acid dimethicone Sodium, cocamidopropyl betaine and sodium hydroxypropyl sulfonate lauryl glucoside cross-linked polymer are compounded as surfactant system, and camellia seed oil, alpha-glucan oligosaccharide/inulin compound are selected As a conditioning ingredient, wild chrysanthemum extract and lauroyl arginine ethyl ester HCl are compounded as a preservative system. In the invention, the raw materials cooperate with each other, and the cleaning effect is good, mild and non-irritating.

At present, there is no report on the use of LAE and its derivatives for antiseptic and sterilizing wipes.

SUMMARY OF THE INVENTION

The prior invention does not teach the use of a single LAE component as a mildew inhibitor for antiseptic and germicidal wet wipes, nor does it disclose the appropriate concentration of LAE as a mildew inhibitor for antiseptic and germicidal wet wipes. Therefore, on the one hand, the present invention utilizes the antibacterial effect of LAE as a preservative, and uses it for the first time in the research of antiseptic and bactericidal wet wipes, and determines its suitable concentration through experiments, so as to achieve effective antibacterial and disease prevention effects at the same time. , the negative impact on the environment is small, and the toxic and side effects are low. On the other hand, on the basis of the above research, according to the fact that lauroyl arginine ethyl ester LAE has strong antibacterial ability, low biological toxicity, good metabolism in vivo, high compatibility with the environment, and does not react with other compounds at room temperature. According to the characteristics of LAE, LAE is further improved to obtain a new type of derivative, that is, the condensation reaction of LAE and organic acid salt is carried out to obtain the LAE ion-pair compound. The ion-pair compound, as a preservative component of antiseptic and sterilizing wet wipes, has the advantages of better bacteriostatic effect and lower dosage than LAE, thereby being more conducive to the preparation of natural non-toxic and stable antiseptic and sterilizing wet wipes.

The first object of the present invention is to provide the use of lauroyl arginine ethyl ester LAE as a preservative or antifungal agent for wet wipes.

In one embodiment, the LAE includes a lauroyl arginine ethyl ester compound (LAE compound) represented by formula (I) or a hydrate or a pharmaceutically acceptable salt thereof.

in,

X is halogen or HSO ₄ ; preferably, Br, Cl or HSO ₄ ;

R ₁ is a straight-chain saturated fatty acid or an oxyacid containing 8-14 carbon atoms; preferably, a straight-chain oxyacid containing 12 carbon atoms;

R ₂ is a straight-chain or branched-chain fatty acid or aromatic group containing 1-18 carbon atoms; preferably, a straight-chain saturated fatty acid containing 2 carbon atoms;

_R3 is one of the following structures:

The range of n is 0-4.

In a preferred embodiment, the X is Cl, the compound shown in the formula (I) is lauroyl arginine ethyl ester hydrochloride (LAEHCl), and its structural formula is shown in the following formula (II):

Wherein, the mass percentage concentration of the LAE in the base solution of the wet tissue preservative or antifungal agent is 0.001-2%; preferably, it is 0.001-0.01%, 0.01-0.1%, 0.05-0.1%, 0.1-0.2 %, 0.1-1%, 1-2% or 1.5-2%; further preferably, it is 0.01-0.1% or 0.05-0.1%.

The second object of the present invention is to provide the use of the LAE ion pair compound for preparing a preservative or antifungal agent for wet wipes, wherein the LAE ion pair compound has the structural formula shown in the following formula (III):

Wherein, the RCOO ^- organic acid or salt is selected from salicylic acid, formic acid, ammonium formate, calcium formate, acetic acid, sodium diacetate, propionic acid, ammonium propionate, sodium propionate, calcium propionate, butyric acid with antibacterial activity Acid, Sodium Butyrate, Lactic Acid, Benzoic Acid, Sodium Benzoate, Sorbic Acid, Sodium Sorbate, Potassium Sorbate, Fumaric Acid, Citric Acid, Potassium Citrate, Sodium Citrate, Calcium Citrate, Tartaric Acid, Malic Acid, Phosphoric Acid , sodium carbonate, oxalic acid or carbonic acid. In a preferred embodiment, the organic acid salt is selected from the group consisting of niacin, tartaric acid, oxalic acid.

Wherein, the mass percentage concentration of the LAE ion-pair compound in the base solution of the wet tissue preservative or antifungal agent is 0.001-2%; 0.1-0.2%, 0.1-1%, 1-2% or 1.5-2%; further preferably, 0.01-0.1% or 0.05-0.1%.

The third object of the present invention is to provide a method for preparing a preservative or antifungal agent for wet wipes containing the above-mentioned LAE ion-pair compound, the steps comprising:

(1) heating and dissolving the compound shown in formula (II), then adding organic acid salt solution;

(2) fully stirring and mixing, and under the condition of heating, reaction obtains LAE ion pair compound, and described reaction is shown in following reaction formula:

Wherein, the RCOO ^- organic acid or salt is selected from salicylic acid, formic acid, ammonium formate, calcium formate, acetic acid, sodium diacetate, propionic acid, ammonium propionate, sodium propionate, calcium propionate, butyric acid with antibacterial activity Acid, Sodium Butyrate, Lactic Acid, Benzoic Acid, Sodium Benzoate, Sorbic Acid, Sodium Sorbate, Potassium Sorbate, Fumaric Acid, Citric Acid, Potassium Citrate, Sodium Citrate, Calcium Citrate, Tartaric Acid, Malic Acid, Phosphoric Acid , sodium carbonate, oxalic acid or carbonic acid;

(3) after fully reacting, cooling room temperature, vacuum drying after purification, thereby preparing the lauroyl arginine ethyl ester organic acid ion pair compound shown in formula (III);

(4) In the container, add the base solution at normal temperature and normal pressure, and add the above-mentioned LAE ion-pair compound, and after fully stirring by pump circulation, the antiseptic or antifungal agent of the wet tissue is obtained.

In step (1), the temperature of the heating and dissolving is 50°C-100°C; preferably, it is 90°C.

In step (2), the temperature of the reaction is 50°C-100°C; preferably, it is 90°C.

In step (2), the reaction time is 50°C-100°C; preferably, it is 90°C.

In step (3), the vacuum drying conditions are 50°C-100°C; preferably, it is 60°C.

In step (4), the container is preferably a container made of stainless steel or an inert material.

In one embodiment, wherein the RCOO ^- organic acid or salt is selected from the group consisting of salicylic acid, formic acid, ammonium formate, calcium formate, acetic acid, sodium diacetate, propionic acid, ammonium propionate, sodium propionate with antibacterial activity , calcium propionate, butyric acid, sodium butyrate, lactic acid, benzoic acid, sodium benzoate, sorbic acid, sodium sorbate, potassium sorbate, fumaric acid, citric acid, potassium citrate, sodium citrate, calcium citrate, Tartaric acid, malic acid, phosphoric acid, sodium carbonate, oxalic acid or carbonic acid. In a preferred embodiment, the organic acid salt is selected from sodium nicotinate, sodium tartrate, and sodium oxalate.

In another embodiment, the preparation method of the RCOO ^- organic acid salt is as follows: adding the organic acid to a methanol solution, adding an appropriate amount of NaOH, stirring at room temperature until a white solid is precipitated, suction filtration and washing with methanol to obtain organic acid salts.

The fourth object of the present invention is to provide a preservative or antifungal agent for wet wipes containing the above-mentioned LAE or its ion-pair compound as a bacteriostatic agent or preservative, which contains the LAE ion-pair compound in a mass percentage concentration of 0.001-2% ; preferably, it is 0.001-0.01%, 0.01-0.1%, 0.05-0.1%, 0.1-0.2%, 0.1-1%, 1-2% or 1.5-2%; further preferably, it is 0.01-0.1%, 0.05-0.1% LAE ion pair compound.

Terms and Definitions:

Ethyl lauroylarginate (LAE) is an organic compound formed by the condensation of fatty acid and dibasic amino acid. It is a white hygroscopic solid with stable chemical properties in the pH range of 3 to 7. At this temperature, 247g of LAE can be dispersed in 1kg of water, and its partition coefficient in water and oil is greater than 10, that is, it mainly exists in the water phase. The study found that lauroyl arginine ethyl ester LAE has the characteristics of strong antibacterial ability, low biological toxicity, good metabolism in vivo, and high compatibility with the environment. The most representative feature is that there is no residue in the metabolism of lauroyl arginine ethyl ester. Relevant studies have shown that lauroyl arginine ethyl ester can be rapidly metabolized naturally in humans and animals to generate lauric acid and arginine. Metabolized to ornithine, urea, carbon dioxide and water. All primary metabolites and final products produced during the metabolism of lauroyl arginine ethyl ester are non-toxic and harmless, and are the same as the metabolites in the body of the food that humans and animals ingest daily.

The present invention improves the derivatives of LAE, and breaks through the traditional thinking for the development of derivatives, that is, it is no longer limited to selecting suitable forms of acids, bases, and salts/esters traditionally suitable for LAE, or performing acid, base, The treatment of salt or esterification group, but creative selection of an acid group that can enhance the antibacterial synergistic effect of LAE, and unconventionally combine the two into new derivatives through strong intermolecular ionic bonds, That is, an ion-pair compound, thereby significantly improving the use of LAE derivatives in preservatives or antifungal agents for wet wipes.

technical effect

The advantages of the mildew-proof adhesive of the present invention are:

The creative use of LAE and its ion pair derivatives to replace the bacteriostatic agents and preservatives in wet wipes, while retaining the advantages of low cost, simple production process and good stability of traditional wet wipes, also has a significant bacteriostatic effect. It has the advantages of single and simple preparation, no harm to human body, easy to be catabolized by biological, easy to store for a long time and the like.

Description of drawings

Figure 1: ESI mass spectrum of the cation B+ molecular ion peak of the LAE ion-pair compound;

Figure 2: ESI mass spectrum of the anion A-molecular ion peak of the LAE nicotinic acid ion-pair compound;

Figure 3: Peak shape and chemical shift diagram of 1H-NMR of LAE;

Figure 4: Peak shape and chemical shift diagram of 1H-NMR of nicotinic acid;

Figure 5: Peak shape and chemical shift diagram of 1H-NMR of LAE nicotinic acid ion pair;

Figure 6: ESI mass spectrum of the anion A-molecular ion peak of the LAE tartrate ion-pair compound.

Detailed ways

In conjunction with the following specific embodiments and accompanying drawings, the present invention will be further described in detail, and the protection content of the present invention is not limited to the following embodiments. Variations and advantages that can occur to those skilled in the art without departing from the spirit and scope of the inventive concept are included in the present invention, and the appended claims are the scope of protection. Processes, conditions, reagents, experimental methods, etc., for implementing the present invention, except for the content specifically mentioned below, are general knowledge and common knowledge in the art, and the present invention has no particular limitation.

Embodiment 1: the preparation method of lauroyl arginine ethyl ester hydrochloride and nicotinic acid synthetic ion pair compound

Dissolve 2.0 g of sodium nicotinate (purchased from Tixiai (Shanghai) Chemical Industry Development Co., Ltd.) in 50 mL of water to prepare a sodium nicotinate salt solution (A); 6.8 g of lauroyl arginine ethyl ester hydrochloride Dissolved in 40 mL of water, heated to 90°C, until all the lauroyl arginine ethyl ester hydrochloride was dissolved to prepare an aqueous solution of lauroyl arginine ethyl ester hydrochloride (B); The saline solution (A) was slowly added to the aqueous lauroyl arginine ethyl ester hydrochloride solution (B), stirred continuously, reacted for 2 hours, cooled to room temperature, filtered, fully washed with purified water, and the precipitate was vacuum-dried at 60°C, That is, 7.6 g of nicotinic acid ion-pair compound was obtained.

Example Analysis of Molecular Formula and Molecular Weight of Compounds with Dilauroyl Arginine Ethyl Ester Nicotinic Acid Ion Pair

The molecular formula of the compound obtained by mass spectrometry, ¹ H-NMR, and ¹³ C-NMR spectral analysis is:

1. Mass Spectrometry (ESI) Analysis

The m/z=385.3 of the cation B ⁺ molecular ion peak, see Figure 1;

Anion A ^- molecular ion peak m/z=122.1, see Figure 2.

The theoretical calculated value of nicotinic acid ion to the cation in the compound is 507.4, and the measured value is in good agreement with the theoretical value.

2. NMR analysis

Lauroyl arginine ethyl ester hydrochloride (see Figure 3), ¹ H-NMR of nicotinic acid (see Figure 4), and ¹ H-NMR of LAE nicotinic acid ion-pair compound (see Figure 5) were compared. Since the LAE ion-pair compound is in the process of salt formation, the peak shape and chemical shift of lauroyl arginine ethyl ester in this ion-pair compound do not change much, but all hydrogens on nicotinic acid have shift changes, and its spectral characteristics are similar to Compared with the original inorganic acid salt (ie LAE hydrochloride), the distance between the two parts of the acid and the base is closer and has an impact. Therefore, it has a corresponding change compared with the original LAE and its hydrochloride. It is not a simple acid-base two. Partial superposition, such as when the precipitate was washed with purified water, has changed the solubility, indicating a strong interaction between all hydrogen nuclei of ethyl lauroyl arginine and nicotinic acid through strong ionic bond formation stable single compound structure.

Embodiment three: the preparation method of lauroyl arginine ethyl ester hydrochloride and tartaric acid synthetic ion pair compound

2.0 g of tartaric acid (purchased from Tixiai (Shanghai) Chemical Industry Development Co., Ltd.) was dissolved in 50 mL of methanol, an equivalent of NaOH was added, stirred at room temperature until a white solid was precipitated, suction filtered and washed three times with 30 mL of methanol to obtain sodium tartrate. . Dissolve sodium tartrate in 50 mL of water to prepare an aqueous solution of sodium tartrate (A); dissolve 5.6 g of lauroyl arginine ethyl ester hydrochloride in 40 mL of water, and heat to 90°C until lauroyl arginine ethyl ester salt All the acid salts were dissolved to make lauroyl arginine ethyl ester hydrochloride aqueous solution (B); at 90°C, the sodium tartrate aqueous solution (A) was slowly added to lauroyl arginine ethyl ester hydrochloride aqueous solution ( In B), keep stirring, react for 2 hours, cool to room temperature, filter, fully wash the precipitate with pure water, and dry the precipitate under vacuum at 60°C to obtain 6.3 g of tartaric acid ion pair compound.

Example Four: Analysis of Molecular Weight of Compounds by Lauroyl Arginine Ethyl Ester Tartaric Acid Ion

Mass spectrometry (ESI) analysis of cation B ⁺ molecular ion peak m/z = 385.3 (see Figure 1)

Anion A ^- m/z of molecular ion peak = 149.0 (see Figure 6)

The theoretical calculated value of nicotinic acid ion to the cation in the compound is 534.3, and the measured value is in good agreement with the theoretical value.

Embodiment 5: the preparation method of lauroyl arginine ethyl ester hydrochloride and oxalic acid synthetic ion pair compound

Dissolve 1.0 g of oxalic acid (purchased from Discovery Co., Ltd.) in 50 mL of methanol, add an equivalent of NaOH, stir at room temperature until a white solid is precipitated, filter with suction and wash with 30 mL of methanol for three times to obtain sodium oxalate. Dissolve sodium oxalate in 50 mL of water to prepare a sodium oxalate aqueous solution (A); dissolve 4.7 g of lauroyl arginine ethyl ester hydrochloride in 40 mL of water, and heat to 90°C until lauroyl arginine ethyl ester salt The sodium oxalate solution (A) was slowly added to the lauroyl arginine ethyl ester hydrochloride aqueous solution (B) at 90°C. In B), stirring continuously, reacting for 2 hours, cooling to room temperature, filtering, fully washing the precipitate with pure water, and drying the precipitate under vacuum at 60° C. to obtain 5.0 g of the oxalic acid ion pair compound.

According to the method of Example 2, NMR analysis and ESI analysis were carried out. The results showed that the spectral characteristics of the ion-pair compound were not simply the superposition of two parts of acid and base, and the distance between the two parts of acid and base was close, which had an impact, and its spectral data was the same as the original one. Compared with LAE and its hydrochloride, corresponding changes have occurred. For example, when the precipitate is washed with purified water, the solubility has changed, which indicates that there is a strong interaction between all the hydrogen nuclei of lauroyl arginine ethyl ester and oxalic acid, And formed a stable single compound structure through strong ionic bonds.

Embodiment 6: the preparation method of lauroyl arginine ethyl ester hydrochloride and carbonic acid synthetic ion pair compound

Dissolve 1.0 g of sodium carbonate (purchased from Discovery Co., Ltd.) in 50 mL of water to prepare a sodium carbonate aqueous solution (A); dissolve 4.0 g of lauroyl arginine ethyl ester hydrochloride in 40 mL of water, and heat to 90°C until Lauroyl arginine ethyl ester hydrochloride is completely dissolved to make lauroyl arginine ethyl ester hydrochloride aqueous solution (B); the sodium carbonate aqueous solution (A) is slowly added to lauroyl arginine at 90°C The ethyl ester hydrochloride aqueous solution (B) was continuously stirred, reacted for 2 hours, cooled to room temperature, filtered, fully washed with purified water, and the precipitate was vacuum-dried at 60°C to obtain 4.0 g of carbonate ion pair compound.

According to the method of Example 2, NMR analysis and ESI analysis were carried out. The results showed that the spectral characteristics of the ion-pair compound were not simply the superposition of two parts of acid and base, and the distance between the two parts of acid and base was close, which had an impact, and its spectral data was the same as the original one. Compared with LAE and its hydrochloride, there are corresponding changes, which indicates that all hydrogen nuclei of lauroyl arginine ethyl ester have strong interactions with carbonic acid, and form a stable single compound structure through strong ionic bonds.

Example 7: Determination of minimum inhibitory concentration (MIC) of lauroyl arginine ethyl ester ion-pair compound in vitro

Principle and purpose: According to the micro-broth dilution method stipulated by CLSI, after co-incubating the drug and bacteria in a 96-well plate for 24 hours, the minimum drug concentration that inhibits the growth of bacteria is the minimum inhibitory concentration of the drug.

Method: Lauroyl arginine ethyl ester hydrochloride (LAE hydrochloride) and the organic acid ion pair of lauroyl arginine ethyl ester prepared above were used twice in tryptone soybean broth medium (TSB). Diluted to different concentrations, the drug and bacteria were mixed and incubated in a 96-well plate, and a blank control medium CK1 without bacteria, a medium CK2 supplemented with LAE (1000 μg/ml), and a normal growth control medium CK3 without drugs were set up. . The 96-well plate was incubated in a 37°C incubator for 24 hours, and the absorbance value at 625 nm of each well was measured. Wells with OD ₆₂₅ values consistent with the blank control were considered to have no significant bacterial growth. The lowest concentration of drug without obvious growth of bacteria is the minimum inhibitory concentration MIC (Minimal Inhibitory Concentration) of LAE to bacteria.

The results of the comparison of the antibacterial activities of the prepared various LAE derivatives (ion-pair compounds) with respect to the original LAE compounds are shown in Table 1 below.

Table 1 In vitro antibacterial effects of LAE and its ion-pair compounds against two bacteria

Wherein, the percentage value in brackets ( ) represents the mass percentage of each additive in the reaction system.

Result analysis:

(1) Most of the ion-pair compounds maintain the same antibacterial activity against Escherichia coli, especially the antibacterial activity of oxalate ion-pair compounds increases;

(2) Most of the ion-pair compounds maintain the same antibacterial activity against Staphylococcus aureus, the antibacterial activity of carbonate ion-pair compounds decreases, and the antibacterial activity of niacin ion-pair compounds increases significantly;

Conclusion: The ion-pair compounds of LAE derivatives do not inhibit the antibacterial activity of the original LAE of a single component, but are beneficial to the antibacterial activity on the contrary. Among them, the nicotinic acid ion-pair compound produced a significant bacteriostatic effect on Staphylococcus aureus.

Example 8: Test the antibacterial effect of sanitary wet wipes by standing method

The formula mixture of antifungal agent and bactericide for sanitary wipes as shown in Table 2 was prepared using conventional methods. Except for H ₂ O ₂ which was expressed by volume, other components were expressed as mass percentage (%). Among them, the control 1-2 is antifungal agent (Niplatin) and bactericide (Debio ^™ S207), and the negative control is blank water.

Cut a white towel into 10 x 10 cm pieces, and immerse them in the solutions of formulations 1-4 and controls 1-2 for 20 minutes. Drain to about 35% humidity. Then put it in a sterile hygienic bag, seal it, and store it at room temperature for 1 year. To speed up the test, it can also be stored at a constant temperature of 35-40°C for 60 days.

Then, according to the method of "Sanitary Standard for Disposable Sanitary Products GB15979-2002", the number of colonies of the wet wipes was tested.

The results are shown in Table 2.

Table 2

+++: Out of detection range.

Result analysis:

The test results of the antibacterial effect showed that 0.05% LAE acetate ion pair has achieved a combined antibacterial effect close to the antifungal agent niplatin and the fungicide Debio ^TM S207, but better than the antifungal effect of using niplatin alone.

Although in the above experiments, the 0.2% dose group had the highest combined effect of bacteriostasis and mildew resistance, and from the patent application submitted by the applicant earlier (invention title: "Lauroyl arginine ethyl ester derivatives and use as animals for According to the in vitro cell test data of "Use of Antibacterial Agents", Application No.: 201810648982.3), a concentration of 0.0032% has produced a bacteriostatic effect, and an increase in the dose of LAE and its derivatives within a certain range can improve the bacteriostatic and antifungal effects. , but the bacteriostatic effect was not significantly improved compared to the 0.1% dose group, indicating that the dose range of 0.01%-0.2% has met the production needs

In addition, according to the current national standard "Sanitary Standard for Disposable Sanitary Products GB15979-2002", if the total number of bacterial colonies is less than 20 within the specified concentration and action time, and Escherichia coli, pathogenic pus, and fungi shall not be detected. , then it means that the sanitary wipes meet the hygiene regulations. Although increasing the addition amount of LAE and its derivatives will correspondingly increase the bacteriostatic and antifungal rates, but too high an antibacterial rate means more residues, which is not conducive to human health. Even so, since the bacteriostatic ingredients of LAE and its derivatives of the present invention are natural, environmentally friendly and non-toxic ingredients, high-dose addition and use still have the advantage of being friendly and friendly to the human body compared with traditional chemical bacteriostatic agents, and Compared with the traditional combined use of antifungal agent and bactericide, the present invention uses a single LAE and its derivatives to have the combined effect of antifungal and bactericidal.

Therefore, considering the production cost and actual production needs, the mass percentage concentration of LAE and its ion pair as the active ingredient for mildew and sterilization of sanitary wipes is 0.01-1% or 0.1-1% or 1-2% or 1.5- 2%, preferably an effective concentration of 0.01-0.1%, most preferably 0.05%, can effectively prevent and treat disease, and meet the needs of production.

Claims (8)

1. Use of the LAE ion-pair compound for preparing a preservative or antifungal agent for wet wipes, wherein the LAE ion-pair compound has the structural formula shown in the following formula (III):

Wherein ^, the organic acid salt of described RCOO- is selected from acetate, nicotinate, oxalate with antibacterial activity; And, The LAE ion-pair compounds are prepared by the following condensation reactions: (1) heating and dissolving the compound shown in formula (II), then adding the organic acid salt solution of RCOO-;

(2) fully stirring and mixing, and a condensation reaction occurs under the condition of heating to 90 ° C to obtain the LAE ion-pair compound, and the condensation reaction is shown in the following reaction formula:

(3) After fully reacting, cooling to room temperature, washing and purifying with pure water, and then vacuum drying to prepare a purified LAE ion-pair compound. 2. The use according to claim 1, wherein the mass percentage concentration of the LAE ion-pair compound in the base solution of the wet tissue preservative or antifungal agent is 0.001-2%. 3. The use according to claim 1 or 2, wherein the organic acid salt of RCOO- is selected from nicotinate and oxalate. 4. the preparation method of the preservative of a wet tissue or antifungal agent, is characterized in that, comprises the following steps: (1) heating and dissolving the compound shown in formula (II), then adding the organic acid salt solution of RCOO-;

(2) fully stirring and mixing, and under the condition of heating to 90 ° C, the ion-pair compound is produced by the following condensation reaction formula;

Wherein, the organic acid salt of described RCOO- is selected from acetate, nicotinate, oxalate with antibacterial activity; (3) after fully reacting, cooling to room temperature, washing and purifying with pure water and then vacuum drying, thereby preparing the purified LAE ion-pair compound; (4) In the container, add the matrix solution at normal temperature and normal pressure, and add the above-mentioned LAE ion-pair compound, and after fully stirring by pump circulation, the antiseptic or antifungal agent of the wet tissue is obtained. 5. method as claimed in claim 4, is characterized in that, the preparation method of the organic acid salt of described RCOO- is: described organic acid is added in methanol solution, and add appropriate amount of NaOH, stir at room temperature until separate out white solid , filtered with suction and washed with methanol to obtain an organic acid salt. 6. A preservative or anti-mildew for wet wipes containing the LAE ion-pair compound as described in any one of the uses of claims 1-3, or the LAE ion-pair compound in the method of claim 4 or 5 The agent is characterized in that it contains the LAE ion pair compound with a concentration of 0.001-2% by mass. 7. The antiseptic or antifungal agent for wet wipes according to claim 6, characterized in that, it comprises a mass percentage concentration of 0.001-0.01%, 0.01-0.1%, 0.05-0.1%, 0.1-0.2%, 0.1% -1%, 1-2% or 1.5-2% LAE ion pair compound. 8 . The preservative or antifungal agent for wet wipes according to claim 7 , characterized in that, it comprises LAE ion-pair compounds with a concentration of 0.01-0.1% and 0.05-0.1% by mass. 9 .

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