CN115089504A

CN115089504A - Novel cosmetic compositions, process for their preparation and their use

Info

Publication number: CN115089504A
Application number: CN202210503192.2A
Authority: CN
Inventors: 易正芳; 邵婷; 仇文卫; 刘明耀
Original assignee: East China Normal University
Current assignee: East China Normal University
Priority date: 2018-06-22
Filing date: 2019-06-24
Publication date: 2022-09-23
Also published as: CN110403846A

Abstract

The present invention provides a preservative for cosmetics, which comprises lauroyl arginine ethyl ester (LAE) ion pair derivative. The invention also provides a method for preparing the cosmetics containing the preservative and a cosmetic composition prepared by the method. The preservative of the cosmetic composition has the characteristics of being natural, non-toxic, efficient and bacteriostatic, easy to degrade and environment-friendly.

Description

Novel cosmetic compositions, process for their preparation and their use

The application is a divisional application of Chinese invention patent application with the application date of 2019, 6 and 24 months and the application number of 201910548558.6, and the invention name of the invention is 'novel cosmetic composition and a preparation method and application thereof'.

Technical Field

The invention relates to a cosmetic composition, in particular to a cosmetic composition containing lauroyl arginine ethyl ester derivatives (ion pair compounds), wherein the lauroyl arginine ethyl ester ion pair has an antibacterial effect, can help the cosmetic composition to exert cosmetic functions, and can also keep the composition stable and exert the antibacterial effect.

Background

The cosmetic is a chemical industrial product or a fine chemical product which is applied to any part of the surface of a human body, such as skin, hair, nails, lips and teeth, by smearing, spraying or the like, so as to achieve the purposes of cleaning, maintaining, beautifying, decorating and changing the appearance, or correcting the odor of the human body and keeping a good state.

Because the cosmetics contain a plurality of organic nutrient components, in order to prevent the nutrient components from generating bacteria to cause deterioration of the cosmetics, the preservative is added into the cosmetics to inhibit the growth and reproduction of bacteria and fungi and avoid the deterioration of the cosmetics, thereby maintaining freshness and persistence.

The preservative is wide in variety and mainly comprises a chemical preservative and a natural preservative, and the effects of the preservatives mainly comprise:

(1) inhibiting the growth and reproduction of microorganisms, keeping the stable property of the cosmetic, preventing the cosmetic from going bad after being used after being uncovered, and prolonging the preservation time;

(2) cosmetics with high moisture content have a high demand for preservatives, such as lotions, milky lotions, and the like; closer to ointment or waxy cosmetics, the more difficult it is for microbes to survive, and the relatively smaller the need for preservatives.

(3) In the production of cosmetics, several preservatives are usually compounded, so that the effects of expanding an antibacterial range, improving the drug effect, resisting secondary pollution and the like are achieved. The common antiseptic in cosmetics comprises benzoic acid, sodium benzoate, phenoxyethanol, Methylisothiazolinone (MIT), salicylic acid, sorbic acid, p-hydroxy-phenyl potassium acid ester, resorcinol, and boric acid. With the development of society, the development of natural nontoxic preservatives has become a research focus in a plurality of fields including cosmetics and foods.

Although a proper amount of preservative is nontoxic to human bodies, even trace components can affect human bodies after long-term use. For example, phenoxyethanol, is a common preservative in cosmetics, typically at concentrations of 0.5% to 1% in cosmetics. Phenoxyethanol is toxic at moderate concentrations and can have effects on the brain and nervous system. For another example, the maximum amount of paraben preservatives in cosmetics is 0.4% for a single ester and 0.8% for a mixed ester. It has been reported that excessive use of parabens in cosmetics causes contact dermatitis.

Other common anti-mold agents used in cosmetics are listed below:

therefore, the addition amount of the currently commonly used preservative is slightly high, and how to keep the minimum addition amount (for example, less than 0.05%, even less than 0.01%) while ensuring the bacteriostatic and mildewproof effects becomes a research hotspot for developing preservatives for cosmetics.

Lauroyl arginine Ethyl ester (LAE) is an organic matter formed by condensing fatty acid and dibasic amino acid, is a white hygroscopic solid, is stable in chemical property within the pH range of 3-7, has a melting point of 50-58 ℃, can be dispersed in 1kg of water at the temperature of 247g, has a distribution coefficient of more than 10 in water and oil, and mainly exists in a water phase. Research finds that the lauroyl arginine ethyl ester LAE has the characteristics of strong antibacterial ability, low biotoxicity, good in-vivo metabolism effect and high environmental compatibility. The lauroyl arginine ethyl ester is metabolized without residue, and related researches show that the lauroyl arginine ethyl ester can be rapidly and naturally metabolized in human bodies and animal bodies to generate lauric acid and arginine, and further be metabolized into 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 of food which is ingested daily by human and animals in vivo.

In 2005, LAE was approved by FDA as a GRAS (generally recognized as safe) food additive in the united states, approved by European Food Safety Administration (EFSA) for safe food certification in 2007, and listed as a standard of food additive general law by 2011 international committee on food code, and is approved as a preservative for 20 kinds of foods and fresh agricultural products.

Chinese patent invention 200980104596.7, "use of cationic surfactants to protect against dental erosion" discloses the use of LAE as a cationic surfactant in the form of an orally used composition such as a dry powder mixture of confectionary, candy, tablet, lozenge, lollipop, chews, jelly, gum, drops or powdered drinks intended for dissolution, wherein the LAE compound is present in the composition at a concentration of 0.001 to 5% by weight, preferably 0.001 to 2% by weight. In the composition, the presence of LAE produces a microbial effect and provides a source of neutralizing plaque acids, which is highly effective.

Chinese patent 201480081262.3 entitled mouthwash composition containing peroxide source and N-acetyl-L-arginine alkyl ester salt discloses LAE and its salt and hydrogen peroxide (H) ₂ O ₂ ) A proportioned mouthwash wherein the LAE and its salt is present in the composition in a concentration of 0.05 to 0.4% by weight, preferably 0.1 to 0.3% by weight, is capable of having a dual effect of an effective whitening activity and an antimicrobial activity, and the effect is capable of maintaining the whitening activity and the antimicrobial activity over time.

Chinese patent application CN201280027864, entitled "cosmetic or dermatological sunscreen formulation with improved water resistance", discloses the use of LAE for the preparation of a cosmetic or dermatological sunscreen formulation comprising, in addition to a UV filter, an emulsifier polyglycerol-10 stearate.

In summary, research on LAE has been carried out in the prior art, but no related report on the use of LAE, even LAE derivatives, for antisepsis and anti-mildew of cosmetics is found.

Disclosure of Invention

One principle of the invention is that according to the characteristics that lauroyl arginine ethyl ester LAE has strong antibacterial ability, low biological toxicity, good in vivo metabolism effect, high environmental compatibility and no reaction with other compounds at normal temperature, the LAE is further improved to obtain a novel derivative, namely, LAE and organic acid salt are subjected to condensation reaction, so that an LAE ion pair compound is obtained. The ion pair compound is used as a bacteriostatic agent and a preservative component in cosmetics, and has the advantages of better bacteriostatic effect and lower dosage compared with LAE, thereby being more beneficial to preparing natural and environment-friendly cosmetic preservatives.

Accordingly, a first object of the present invention is to provide the use of a LAE ion pair compound for the preparation of a cosmetic composition, wherein the LAE ion pair compound has the following formula (III):

wherein, the RCOO ^- The 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, 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 having antibacterial activity. In a preferred embodiment, the organic acid salt is selected from the group consisting of nicotinic acid, tartaric acid, oxalic acid.

In any of the above embodiments, the cosmetic composition is a cream, lotion, cleanser, makeup remover, makeup emulsion, mask, lipstick, mousse, nail polish, or the like.

Wherein the LAE ion pair compound is 0.0030-1% by mass in the cosmetic composition; preferably, 0.0030-0.01, 0.01-1%; more preferably, it is 0.0032 to 0.01%, 0.01 to 0.05%, 0.05 to 0.1%.

It is a third object of the present invention to provide a method for preparing a cosmetic composition containing the above LAE ion pair compound, comprising the steps of:

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

(2) fully stirring and uniformly mixing, and reacting to generate a LAE ionic compound under the condition of heating, wherein the reaction is shown as the following reaction formula:

(3) After full reaction, cooling to room temperature, purifying and then drying in vacuum to prepare the lauroyl arginine ethyl ester organic acid ion pair compound shown in the formula (III);

(4) dissolving the LAE ion pair compound in an organic solvent in a container to obtain an ion pair compound mother solution;

(5) adding the mother solution into cosmetic composition matrix at room temperature, and stirring to obtain cosmetic composition.

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

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

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

In the step (3), the vacuum drying condition is 50-100 ℃; preferably, it is 60 ℃.

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

In the step (4), the organic solvent is methanol, ethanol or the like.

In one embodiment, wherein said RCOO ^- The 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, 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 having antibacterial activity. In a preferred embodiment, the organic acid is selected from the group consisting of nicotinic acid, tartaric acid, oxalic acid.

In another embodiment, the RCOO ^- The preparation method of the organic acid salt comprises the following steps: adding the organic acid into a methanol solution, adding a proper amount of NaOH, stirring at room temperature until a white solid is separated out, carrying out suction filtration, and washing with methanol to obtain the organic acid salt.

It is a fourth object of the present invention to provide a cosmetic composition comprising the above LAE ion-pair compound or prepared by the above method.

In any of the above embodiments, wherein the LAE ion pair compound is present in the cosmetic composition at a concentration of 0.0030 to 0.01, 0.01 to 1% by weight. In a preferred embodiment, the LAE ion pair compound is present in the cosmetic composition in a concentration of 0.0032 to 0.01%, 0.01 to 0.05%, 0.05 to 0.1% by weight.

Terms and definitions:

lauroyl arginine Ethyl ester (LAE) is an organic matter formed by condensing fatty acid and dibasic amino acid, is a white hygroscopic solid, is stable in chemical property within the pH range of 3-7, has a melting point of 50-58 ℃, can be dispersed in 1kg of water at the temperature of 247g, has a distribution coefficient of more than 10 in water and oil, and mainly exists in a water phase. Research finds that the lauroyl arginine ethyl ester LAE has the characteristics of strong antibacterial ability, low biotoxicity, good in-vivo metabolism effect and high environmental compatibility. The most representative characteristic is that no residue is left in the metabolism of lauroyl arginine ethyl ester, and related researches show that the lauroyl arginine ethyl ester can be rapidly and naturally metabolized in human bodies and animal bodies to generate lauric acid and arginine which are further metabolized into ornithine, urea, carbon dioxide and water. All primary metabolites and final metabolites produced during the metabolism of lauroyl arginine ethyl ester are non-toxic and harmless, and are the same as the metabolites of food ingested daily by humans and animals in the body.

The invention improves the derivatives of the LAE, breaks through the traditional thought of the development of the derivatives, namely, the traditional thought is not limited to selecting the proper forms of acid, alkali and salt/ester which are traditionally suitable for the LAE, or treating the LEA with acid, alkali, salt or esterification groups, but creatively selects an acid radical group which can enhance the bacteriostatic synergistic effect of the LAE, and combines the acid radical group and the acid radical group into a new derivative, namely an ion pair compound, through strong intermolecular ionic bonds, so that the application of the LAE derivative in the cosmetic composition is remarkably improved.

Technical effects

The cosmetic composition of the invention has the advantages that:

the LAE ion pair compound is creatively used to replace bacteriostatic agents and preservatives in the cosmetic composition, and the traditional cosmetic composition has the advantages of low cost, simple preparation process and good stability, and meanwhile has the advantages of remarkable bacteriostatic effect, single component, simple preparation, no harm to human bodies, easiness in catabolism, easiness in long-term storage and the like.

Drawings

FIG. 1: ESI mass spectrum of cation B + molecular ion peak of LAE ion pair compound;

FIG. 2 is a schematic diagram: ESI mass spectrum of anion A-molecular ion peak of LAE nicotinic acid ion pair compound;

FIG. 3: peak shape and chemical shift pattern of 1H-NMR of LAE;

FIG. 4 is a schematic view of: 1H-NMR peak shape and chemical shift pattern of nicotinic acid;

FIG. 5: peak shape and chemical shift pattern by 1H-NMR of LAE nicotinic acid ion pair;

FIG. 6: ESI mass spectrum of LAE tartrate ion on the anion A-molecule ion peak of the compound.

Detailed Description

The present invention will be described in further detail with reference to the following specific examples and drawings, and the present invention is not limited to the following examples. Variations and advantages that may occur to those skilled in the art are intended to be included within the invention without departing from the spirit and scope of the inventive concept, and the scope of the invention is to be determined by the appended claims. The procedures, conditions, reagents, experimental methods and the like for carrying out the present invention are general knowledge and common general knowledge in the art except for the contents specifically mentioned below, and the present invention is not particularly limited.

The first embodiment is as follows: preparation method of ion pair compound synthesized by lauroyl arginine ethyl ester hydrochloride and nicotinic acid

Dissolving 2.0g of sodium nicotinate (purchased from Taishiai (Shanghai) chemical industry development Co., Ltd.) in 50mL of water to prepare a sodium nicotinate saline solution (A); dissolving 6.8g of lauroyl arginine ethyl ester hydrochloride in 40mL of water, heating to 90 ℃ until the lauroyl arginine ethyl ester hydrochloride is completely dissolved to prepare lauroyl arginine ethyl ester hydrochloride aqueous solution (B); slowly adding the sodium nicotinate aqueous solution (A) into the lauroyl arginine ethyl ester hydrochloride aqueous solution (B) at 90 ℃, continuously stirring, reacting for 2 hours, cooling to room temperature, filtering, fully washing the precipitate with purified water, and performing vacuum drying on the precipitate at 60 ℃ to obtain 7.6g of the nicotinic acid ion pair compound.

Example analysis of molecular formula and molecular weight of dilauroyl arginine ethyl ester nicotinic acid ion pair compound

By mass spectrometry, ¹ H-NMR、 ¹³ The compound obtained by C-NMR spectroscopy has the formula:

1. mass Spectrometry (ESI) analysis

Cation B ⁺ The molecular ion peak has m/z 385.3, see fig. 1;

anion A ^- The molecular ion peak has m/z of 122.1, see fig. 2.

The theoretical calculation of the nicotinic acid ion for the cation in the compound is 507.4, and the actual measurement value is consistent with the theoretical value.

NMR analysis

Extracting lauroyl arginine ethyl ester hydrochloride (see FIG. 3), nicotinic acid ¹ H-NMR (see FIG. 4) and of LAE Niacin ion-pair Compounds ¹ H-NMR (see FIG. 5). In the salt forming process of the LAE ion pair compound, the peak shape and chemical shift of lauroyl arginine ethyl ester in the ion pair compound are not changed greatly, but all hydrogen on nicotinic acid has shift change, the spectral characteristics of the LAE ion pair compound are closer to the spatial distance of two acid and alkali parts compared with the original inorganic acid salt (namely LAE hydrochloride), and influence is generated, so that the LAE ion pair compound generates corresponding change compared with the original LAE and the hydrochloride thereof, and is not simple superposition of the two acid and alkali parts, for example, the solubility is changed when pure water is used for washing precipitates, which shows that strong interaction is generated between all hydrogen nuclei of the lauroyl arginine ethyl ester and the nicotinic acid, and a stable single compound structure is formed through strong ionic bonds.

Example three: preparation method of ion pair compound synthesized by lauroyl arginine ethyl ester hydrochloride and tartaric acid

2.0g of tartaric acid (purchased from Chi-Seai (Shanghai) chemical industry Co., Ltd.) was dissolved in 50mL of methanol, and an equivalent amount of NaOH was added thereto, and the mixture was stirred at room temperature until a white solid was precipitated, and then the solution was filtered under suction and washed with 30mL of methanol three times to obtain a tartaric acid sodium salt. Dissolving sodium tartrate salt in 50mL of water to prepare a sodium tartrate salt aqueous solution (A); dissolving 5.6g of lauroyl arginine ethyl ester hydrochloride in 40mL of water, heating to 90 ℃ until the lauroyl arginine ethyl ester hydrochloride is completely dissolved to prepare lauroyl arginine ethyl ester hydrochloride aqueous solution (B); slowly adding the tartaric acid sodium salt aqueous solution (A) into the lauroyl arginine ethyl ester hydrochloride aqueous solution (B) at 90 ℃, continuously stirring, reacting for 2 hours, cooling to room temperature, filtering, fully washing the precipitate with purified water, and drying the precipitate in vacuum at 60 ℃ to obtain 6.3g of the tartaric acid ion pair compound.

Examples analysis of molecular weight of Compound by Tetralauroyl arginine Ethyl ester tartrate ion

Mass Spectrometry (ESI) analysis of cation B ⁺ Molecular ion peak m/z 385.3 (see fig. 1)

Anion A ^- Molecular ion peak m/z 149.0 (see FIG. 6)

The theoretical calculation of the niacin ion for the cation in the compound was 534.3, and the observed value coincided with the theoretical value.

Example five: preparation method for synthesizing ion pair compound by using lauroyl arginine ethyl ester hydrochloride and oxalic acid

Oxalic acid (purchased from research Co., Ltd.) 1.0g was dissolved in 50mL of methanol, and an equivalent amount of NaOH was added thereto, and the mixture was stirred at room temperature until a white solid precipitated, which was then subjected to suction filtration and washed with 30mL of methanol three times to obtain an oxalic acid sodium salt. Dissolving sodium oxalate in 50mL of water to prepare sodium oxalate aqueous solution (A); dissolving 4.7g of lauroyl arginine ethyl ester hydrochloride in 40mL of water, heating to 90 ℃ until the lauroyl arginine ethyl ester hydrochloride is completely dissolved to prepare lauroyl arginine ethyl ester hydrochloride aqueous solution (B); slowly adding the sodium oxalate salt aqueous solution (A) into the lauroyl arginine ethyl ester hydrochloride aqueous solution (B) at 90 ℃, continuously stirring, reacting for 2 hours, cooling to room temperature, filtering, fully washing the precipitate with purified water, and drying the precipitate in vacuum at 60 ℃ to obtain 5.0g of the oxalate ion pair compound.

The results of NMR analysis and ESI analysis according to the method of example two show that the ion pair compound is not a simple superposition of two acid and base parts, which are closely spaced and affect the compound, and the spectral data of the ion pair compound has a corresponding change compared with the original LAE and its hydrochloride, for example, the solubility of the compound is changed when the precipitate is washed with purified water, which shows that all hydrogen nuclei of lauroyl arginine ethyl ester have strong interaction with oxalic acid and form a stable single compound structure through strong ionic bonds.

Example six: preparation method of ion pair compound synthesized by lauroyl arginine ethyl ester hydrochloride and carbonic acid

1.0g of sodium carbonate (purchased from research Co., Ltd.) was dissolved in 50mL of water to prepare an aqueous sodium carbonate solution (A); dissolving 4.0g of lauroyl arginine ethyl ester hydrochloride in 40mL of water, heating to 90 ℃ until the lauroyl arginine ethyl ester hydrochloride is completely dissolved to prepare lauroyl arginine ethyl ester hydrochloride aqueous solution (B); slowly adding the sodium carbonate aqueous solution (A) into the lauroyl arginine ethyl ester hydrochloride aqueous solution (B) at 90 ℃, continuously stirring, reacting for 2 hours, cooling to room temperature, filtering, fully washing the precipitate with purified water, and drying the precipitate in vacuum at 60 ℃ to obtain 4.0g of the carbonate ion pair compound.

The results of NMR analysis and ESI analysis according to the method of example two show that the ion pair compound is not a simple superposition of two acid and base parts with close spatial distance, and the influence is generated, and the spectral data of the ion pair compound is changed correspondingly compared with the original LAE and hydrochloride thereof, which indicates that all hydrogen nuclei of lauroyl arginine ethyl ester generate strong interaction with carbonic acid and form a stable single compound structure through strong ionic bonds.

Example seven: determination of lauroyl arginine ethyl ester ion pair compound Minimum Inhibitory Concentration (MIC) in vitro

The principle and the purpose are as follows: according to the microbubult dilution method specified by CLSI, the minimum drug concentration at which bacterial growth is inhibited after 24h of co-incubation of the drug with bacteria in a 96-well plate is the minimum inhibitory concentration of the drug.

The method comprises the following steps: lauroyl arginine ethyl ester hydrochloride (LAE) and the pair of lauroyl arginine ethyl ester organic acid ions prepared above are respectively diluted to different concentrations by Trypticase Soy Broth (TSB), the medicine and the bacteria are mixed and incubated in a 96-well plate, and a blank culture medium CK1 without bacteria, a culture medium CK2 added with LAE (1000 mu g/ml) and a normal growth control culture medium CK3 without the medicine are additionally arranged. The absorbance at 625nm of each well was measured after incubating the 96-well plate in a 37 ℃ incubator for 24 h. OD with blank control ₆₂₅ Wells with consistent values were considered to have no significant growth of bacteria. The lowest concentration of drug at which bacteria do not significantly grow is the minimum Inhibitory concentration mic (minimum inhibition concentration) of LAE to bacteria.

The results of comparing the antibacterial activity of various LAE derivatives (ion pair compounds) prepared with respect to the original LAE compound are shown in table 1 below.

TABLE 1 in vitro antibacterial Effect of LAE and its ion-pair Compounds on two bacteria

Comparison of	Escherichia coli	Staphylococcus aureus
			LAE	16	8
LAE nicotinic acid ion pair	16	4
			LAE tartrate ion pair	16	8
LAE oxalate ion pair	8	8
			LAE carbonate ion pair	16	16

And (4) analyzing results:

(1) most of the LAE ion pair compound keeps the same antibacterial activity to escherichia coli, and especially the antibacterial activity of the LAE oxalic acid ion pair compound is increased;

(2) most of the LAE ion pair compounds keep the same antibacterial activity to staphylococcus aureus, the antibacterial activity of LAE carbonate ions to the compounds is reduced, and the antibacterial activity of LAE nicotinic acid ions to the compounds is obviously improved;

and (4) conclusion: ion pair compounds of LAE derivatives do not inhibit the antibacterial activity of the original LAE in a single composition, but are beneficial to the antibacterial activity. Wherein, the nicotinic acid ion pair compound has obvious bacteriostatic effect on staphylococcus aureus.

Example eight: testing of the Effect of LAE ion on the mildew resistance of Compounds on cosmetic products

Principle of

The test simulates the potential for contamination by high intensity microorganisms during the manufacture and use of cosmetics and the optimum conditions for microbial growth in nature, and tests whether a preservative effect can be provided to a cosmetic product by adding the preservative to a sample at a specific concentration.

1. Preparation of bacterial liquid

Staphylococcus aureus was inoculated into the culture broth and cultured at 37 ℃ for 24 hours. Inoculating Aspergillus niger to the culture medium of the delta liquid, and culturing at 25 deg.C for 6 days. The two are respectively prepared into a certain amount of bacterial suspensions.

2. Formulated cosmetic product

A cleansing liquid (100ml) was prepared according to Table 2, for a total of 6 formulations and a control, in which the preservative was phenoxyethanol.

TABLE 2

Note: the LAE ion pair is LAE hydrochloric acid ion pair

3. Test for bacteriostatic efficacy

Weighing a certain amount of cosmetic, respectively inoculating 10000(cfu/g) staphylococcus aureus and 1000000(cfu/g) aspergillus niger, fully stirring uniformly, and standing for 12h, 1d, 2d, 7d, 14d and 28d for determination. The bacteria were counted using lecithin-Tween 80-nutrient agar, and control was performed using plain agar. The results are shown in tables 3 to 4.

TABLE 3

TABLE 4

And (4) analyzing results:

the antibacterial effect detection result shows that the LAE ion pair in the concentration range of 0.005-0.1% generates or basically generates the expected mildew-proof effect on the makeup remover, wherein the difference between the mildew-proof effect of 0.01% and the mildew-proof effect of 0.05% is not large, and the mildew-proof effect is slightly lower than the mildew-proof effect of 0.1%.

The preservative phenoxyethanol control had a concentration of only 0.5% to produce essentially a mold-proof effect, whereas a concentration of 0.1% had failed to produce any effect on the cosmetic. Phenoxyethanol is considered toxic at moderate concentrations and can have effects on the brain and nervous system. Obviously, the LAE ion with the concentration range of 0.01-0.05% has lower toxicity to human body and better inhibition capability to bacteria compared with the over-high addition amount.

The negative water control did not have any mildew-resistant effect.

Although the bacteriostatic effect was highest in the 0.1% dose group in the above test, and from the test data of the applicant's previously filed patent application (title of the invention: "use of lauroyl arginine ethyl ester derivative as antibacterial agent for animals", application No. 201810648982.3), the increase in the dose of LAE and its derivative in a certain range could improve the bacteriostatic effect, but the bacteriostatic effect was not significantly improved with respect to the 0.05% dose group, indicating that the 0.01% -0.05% dose range has satisfied the production requirement.

In addition, according to the once-adding antiseptic challenge test and evaluation standard recommended by CTFA, the inoculation amount of the mold and the bacteria at the beginning of the test is 10000(cfu/g) and 1000000(cfu/g), and the mildew preventive can be considered to have the mildew-proof function on the cosmetics if the mold is reduced by 90% on the 7 th day, the bacteria is reduced by 99.9% on the 7 th day, and the average number is continuously reduced within 28 days. If the addition amount of LAE and derivatives thereof is increased, although the bacteriostatic rate is correspondingly increased, too high bacteriostatic rate means more residues and is not beneficial to human health. Even so, because the bacteriostatic agent components of the LAE and the derivatives thereof belong to natural, environment-friendly and nontoxic components, the bacteriostatic agent has the advantage of being friendly to human bodies when being added and used in high dosage compared with the traditional chemical bacteriostatic agent and the traditional mildew preventive.

Therefore, in view of production cost and actual production requirements, the LAE and its ion pair are effective in mildew resistance at a concentration of 0.0030 to 0.01, 0.01 to 1% by mass as an active ingredient of the cosmetic composition, wherein the effective concentration of 0.01 to 0.05%, most preferably 0.05%, meets the production requirements.

Claims

Use of a LAE ion pair compound for the preparation of a cosmetic composition, characterized in that the LAE ion pair compound is prepared by reacting:

(1) dissolving the compound shown in the formula (II) in water, heating to 90 ℃ until the compound is completely dissolved, and then slowly adding tartrate, carbonate or oxalate solution at 90 ℃;

(2) fully stirring and uniformly mixing, and reacting under the condition of heating to 90 ℃ to obtain an LAE ion pair compound;

(3) after sufficient reaction, the reaction mixture is cooled to room temperature, and is fully washed and purified by purified water and then dried in vacuum, thereby preparing the purified LAE ion pair compound.
2. The use according to claim 1, wherein the oxalate solution is added in step (1).
3. Use according to claim 1, wherein the cosmetic composition is a cream, lotion, cleanser, makeup remover, makeup emulsion, mask, lipstick, mousse, nail varnish.
4. The use according to claim 1, wherein the LAE ion pair compound is present in the cosmetic composition in a concentration of from 0.0030% to 1% by weight.
5. The use according to claim 4, wherein the LAE ion pair compound is present in the cosmetic composition at a concentration of 0.0030% to 0.01% and 0.01% to 1% by weight.
6. The use according to claim 5, wherein the LAE ion pair compound is present in the cosmetic composition at a concentration of 0.0032 to 0.01%, 0.01 to 0.05%, 0.05 to 0.1% by weight.