CN106588701A - Amino acid derivative and preparation method and application thereof - Google Patents

Abstract

The invention provides salts formed from fatty acyl amino acid esters and fatty acyl amino acids and a forming method of the salts that have inhibitory or killing effect for microorganisms. These derivatives also have the properties such as high performance, mildness, and broad-spectrum baceriostasis, and are widely applicable to the products, such as foods, drinks, feeds, home care products, and personal care products. The salts formed from fatty acyl amino acid esters and fatty acyl amino acids according to the invention are liquids that are convenient to add and use, and the salts have good inhibitory effect for common microorganisms, may replace traditional preservatives, and have the advantages of high safety, low irritation, reduced allergy and toxicity risk, low degrading difficulty, good environmental friendliness and the like.

Description

A kind of amino acid derivative, preparation method and application thereof

technical field

The invention relates to an amino acid derivative, a preparation method, and the application of the derivative as a microbial inhibitor in food, feed, home care and personal care products.

Background technique

Preservatives are used in food, feed, cosmetics and furniture care products. The main function is to inhibit the growth and reproduction of microorganisms, so as to prolong the storage time of products and inhibit product spoilage. With the rapid development of cosmetics, food and other industries, choosing a safe and efficient anti-corrosion system is a matter of great concern to current policies, regulations, consumers and researchers.

Many traditional preservatives have been proven to have certain negative effects. For example, DMDMH will release formaldehyde, the chlorine in Casson series can stimulate certain skin types, Bropol may produce carcinogen nitrosamines, and IPBC may cause ingestion Adding iodine, triclosan has a negative impact on the environment. As for parabens, their benzene rings may accumulate in adipose tissue or show some ability to mimic the female hormone estrogen in certain test systems.

The regulations on the use of preservatives are becoming more and more strict, and the use of isoxazolones, formaldehyde releasers, and paraben preservatives is increasingly restricted. More and more stringent cosmetics regulations, the improvement of consumers' safety awareness, misunderstandings about preservatives, safety and other factors, these series of changes have led to a significant decline in the total use of traditional preservatives, and the development of new preservatives is urgently needed. application.

Lauroyl arginine ethyl ester hydrochloride is a kind of safe and effective preservative, which is used in the preservation of preserved food and cosmetics; it is approved by the FAO/WHO Joint Expert Committee on Food Additives (JECFA) ; In addition, lauroyl arginine ethyl ester hydrochloride also complies with the relevant regulations of the European Union, Australia, Canada and New Zealand and other countries and regions.

Lauroyl arginine ethyl ester hydrochloride is a white powder, which is not conducive to adding to the formula. Its melting point is 50-58 °C. When adding to the formula, it is necessary to heat and melt the solid in advance or use a solvent to dissolve it, and then add it to the In the formula system, it is very troublesome to add it. In addition, even if it is dissolved in a solvent, its solubility is very limited. For example, the maximum solubility in glycerin is only about 20%.

The invention provides an arginine ethyl ester derivative, which has a low melting point and is a clear and transparent liquid at room temperature, can be easily dissolved in common solvents such as glycerin, and has a solubility of up to 70%, and can be very conveniently used in food, Medicines and cosmetics.

Contents of the invention

The purpose of the present invention is to provide a salt formed by fatty acylamino acid ester and fatty acylamino acid. This kind of derivative is in liquid form, has better inhibitory or killing effect on microorganisms, and can be conveniently and widely used in food and beverages. , medicine, home care and personal care products.

The salt formed by the fatty acylamino acid and the fatty acylamino acid ester provided by the invention has a good inhibitory effect on common microorganisms and can replace traditional preservatives.

The compound of the present invention has the advantages of natural origin, high safety, low irritation, reduced risk of allergy and toxicity, easy degradation, environmental friendliness and the like.

The technical solution provided by the invention: a method of using fatty acylamino acid ester and fatty acyl amino acid to form a salt, after the fatty acyl amino acid ester and fatty acyl amino acid are formed into a salt, the antibacterial effect is significantly enhanced.

The salt formed by the fatty acylamino acid ester and the fatty acylamino acid described in the present invention, the method of the salt having an inhibitory or killing effect on microorganisms, the specific steps are:

(1) Dissolution: Dissolve fatty acylamino acid ester in solvent and heat to 50-55°C to dissolve;

(2) Salt formation: Add fatty acyl amino acid to the fatty acyl amino acid ester solution obtained in step (1), mix and stir until clear and transparent;

(3) Distill the salt compounded in step (2) under reduced pressure to remove the solvent.

In the step (1), the fatty acylamino acid ester has the chemical structure (a) ~ (d), which can be one or a combination of several general formulas (a) ~ (d):

I. Arginine derivatives and common salts thereof, the general structure of which is as formula (a):

(a)

Wherein, R ₁ is methyl, ethyl, propyl or butyl; R ₂ is a fatty acyl group with 6-22 carbon atoms;

II. Ornithine derivatives and common salts thereof, the general structure of which is shown in formula (b):

(b)

Wherein, R ₁ is methyl, ethyl, propyl or butyl; R ₂ is a fatty acyl group with 6-22 carbon atoms;

III. Lysine derivatives and common salts thereof, the general structural formula of which is formula (c):

(c)

Wherein, R ₁ is methyl, ethyl, propyl or butyl; R ₂ is a fatty acyl group with 6-22 carbon atoms;

IV. Histidine derivatives and common salts thereof, the general structural formula of which is formula (d):

(d)

Wherein, R ₁ is methyl, ethyl, propyl or butyl; R ₂ is a fatty acyl group with 6-22 carbon atoms.

The solvent in step (1) is water or ethanol;

The fatty acylamino acid in step (2) can be a combination of one or more substances, formed by condensation of fatty acids and amino acids with 5-21 carbon atoms, wherein the amino acids are selected from alanine, arginine, Partic acid, cysteine, glutamine, glutamic acid, histidine, isoleucine, glycine, asparagine, leucine, lysine, methionine, phenylalanine, Proline, Serine, Threonine, Tryptophan, Tyrosine, Valine.

The antibacterial system of the salt formed by the fatty acylamino acid ester and the fatty acylamino acid of the present invention is evaluated and tested.

① Antiseptic challenge test: The salt system formed by compounding fatty acylamino acid ester and fatty acyl amino acid is added to the formula of skin care products, and the antiseptic challenge test is carried out on the formula solutions added with different salts according to the EU standard BP2002 XVIC antiseptic effect test method.

②Minimum inhibitory concentration test: The antiseptic effect test was carried out on the salt system formed by the compound of fatty acyl amino acid ester and fatty acyl amino acid and ethyl lauroyl arginate. Antiseptic effect test strains are shown in Table 1:

③ Patch test: Skin allergy test was carried out for the salt system formed by the compound of fatty acylamino acid ester and fatty acyl amino acid and ethyl lauroyl arginate.

The salt system formed by compounding in the present invention has good compatibility with general cosmetic raw materials, and has good compoundability with other components such as surfactants, oils, solvents, antioxidants, etc., and can be mixed evenly with cosmetic raw materials After emulsification, it can make ointment, cream, milk and other bases fine and uniform, without stratification and water seepage for long-term storage, and the dosage form is stable.

The above content of the present invention will be further described in detail through the specific implementation of the examples below, but not limited to the following examples. The present invention includes the above technical ideas, and various replacements or changes made according to common technical knowledge and customary means in this field shall be included in the scope of the present invention.

detailed description

In order to better understand the essence of the invention, the content of the invention will be described in detail below through examples, but the content of the invention is not limited thereto. The fatty acylamino acids and fatty acylamino acid esters used in the following examples are all self-made.

Example 1

(1) Weigh 76.9g (0.2mol) of ethyl lauroyl arginate, add 30mL of ethanol, and heat to dissolve in a water bath at 60°C;

(2) Add 0.1mol lauroyl glutamic acid into (1), stir and mix evenly to obtain a salt system;

(3) Distill the system obtained in (2) under reduced pressure to remove ethanol;

(4) The obtained product, ethyl lauroyl arginate lauroyl glutamate, is a yellow liquid with a freezing point of 14°C.

Example 2

(1) Weigh 0.1mol propyl cocoyl lysine, add 30mL ethanol, and heat to dissolve in a water bath at 60°C;

(2) Add 0.1mol lauroyl glycine to (1), stir and mix evenly to obtain a salt system;

(3) Distill the system obtained in (2) under reduced pressure to remove ethanol;

(4) The obtained product, cocoyl lysine propyl ester lauroyl glycinate, is a yellow liquid with a freezing point of 18°C.

Example 3

(1) Weigh 0.1mol of ethyl lauroyl ornithine, add 30mL of ethanol, and heat in a water bath at 60°C to dissolve;

(2) Add 0.1mol lauroyl sarcosine to (1), stir and mix evenly to obtain a salt system;

(3) Distill the system obtained in (2) under reduced pressure to remove ethanol;

(4) The obtained product, ethyl lauroyl ornithine lauroyl sarcosinate, is a yellow transparent liquid with a melting point of 13°C.

Example 4

(1) Weigh 0.2mol of ethyl lauroyl histidine, add 30mL of ethanol, and heat to dissolve in a water bath at 60°C;

(2) Add 0.1mol of lauroyl aspartic acid into (1), stir and mix evenly to obtain a salt system;

(3) Distill the system obtained in (2) under reduced pressure to remove ethanol;

(4) The obtained product lauroyl histidine ethyl ester lauroyl aspartate is a yellow liquid with a freezing point of 10°C.

Example 5

(1) Weigh 0.1mol butyl cocoyl arginate, add 30mL ethanol, and heat to dissolve in a 60°C water bath;

(2) Add 0.1mol palmitoylproline to (1), stir and mix evenly to obtain a salt system;

(3) Distill the system obtained in (2) under reduced pressure to remove ethanol;

(4) The obtained product, butyl cocoyl arginate palmitoyl proline salt, is a colorless liquid with a freezing point of 11°C.

Example 6

(1) Weigh 0.1mol of palmitoyl lysine methyl ester, add 30mL of ethanol, and heat to dissolve in a water bath at 60°C;

(2) Add 0.1 mol of octanoyl tyrosine to (1), stir and mix evenly to obtain a salt system;

(3) Distill the system obtained in (2) under reduced pressure to remove ethanol;

(4) The obtained product, palmitoyl lysine methyl ester octyl tyrosinate, is a light yellow liquid with a freezing point of 16°C.

Example 7

(1) Weigh 0.1mol butyl stearyl histidine, add 30mL ethanol, and heat to dissolve in a water bath at 60°C;

(2) Add 0.1mol decyl alanine to (1), stir and mix evenly to obtain a salt system;

(3) Distill the system obtained in (2) under reduced pressure to remove ethanol;

(4) The obtained product octadecyl histidine butyl ester decyl alaninate is a colorless transparent liquid with a freezing point of 15°C.

Example 8

(1) Weigh 0.1mol hexylornithine propyl ester, add 30mL ethanol, and heat to dissolve in a 60°C water bath;

(2) Add 0.1mol lauroyl valine to (1), stir and mix evenly to obtain a salt system;

(3) Distill the system obtained in (2) under reduced pressure to remove ethanol;

(4) The obtained product, hexylornithine propyl ester lauroyl valine salt, is a colorless transparent liquid with a freezing point of 18°C.

Example 9

(1) Weigh 0.1mol of eicosyl arginine methyl ester, add 30mL of ethanol, and heat to dissolve in a water bath at 60°C;

(2) Add 0.1mol cocoyl leucine to (1), stir and mix evenly to obtain a salt system;

(3) Distill the system obtained in (2) under reduced pressure to remove ethanol;

(4) The obtained product eicosyl arginine methyl ester cocoyl leucine salt is a yellow liquid with a freezing point of 12°C.

Example 10

(1) Weigh 0.1 mol of ethyl hexadecanyl histidine, add 30 mL of ethanol, and heat in a water bath at 60°C to dissolve;

(2) Add 0.1mol behenylserine to (1), stir and mix evenly to obtain a salt system;

(3) Distill the system obtained in (2) under reduced pressure to remove ethanol;

(4) The obtained product hexadecyl histidine ethyl ester behenyl serinate is a yellow clear liquid with a freezing point of 12°C.

The sample codes of fatty acylamino acid esters, fatty acylamino acids and the resulting salt systems corresponding to Examples 1-10 are shown in Table 2:

Example 11

The above-mentioned bacteriostatic salt system was subjected to a product formulation experiment, and the formulations are shown in Table 3 to Table 6.

Example 12

For the bacteriostatic salt system of Examples 1-10, an antiseptic challenge experiment was carried out for screening and verification. After 7 days of fungal culture and 28 days of antibacterial investigation, the results are judged in Table 7 to Table 10. The unit of the test results of the bacteria, mold and yeast inhibition experiments is CFU/ml.

Antibacterial experiments show that the salt system formed by the compounding of fatty acylamino acid esters and fatty acylamino acids has a significant inhibitory effect on bacteria, molds, and yeasts.

Example 13

Cosmetics-related microorganisms (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Pseudomonas cepacia, Candida albicans) were tested against the antibacterial salt system and lauroyl arginine ethyl ester (LAE) in Examples 1-10. , Aspergillus niger, Malassezia furfur) minimum inhibitory concentration (MIC) value test (unit: ug/mL):

Compared with ethyl lauroyl arginine hydrochloride, the MIC values of each antibacterial system against different microorganisms were all lower, indicating that the antibacterial system had a more significant inhibitory effect on microorganisms.

Example 14

A patch test was performed on the salt system samples obtained in Examples 1-10, and compared with lauroyl arginine ethyl ester hydrochloride (LAE). The patch test results are shown in Table 12.

Patch tests showed that fatty acylamino acid esters and fatty acylamino acid salt systems were less irritating than ethyl lauroyl arginate hydrochloride.

Claims (10)

1. the invention provides a kind of fatty acylamino-acid ester and amino acid derivativges obtained by fatty amic acid reaction.

2. according to described in claim 1, using fatty acylamino-acid ester and amino acid derivativges obtained by fatty amic acid, It is characterized in that：

(1) with relatively low freezing point, be intended to than the fusing point of fatty acylamino-acid ester and fatty amic acid it is low, can be very square Just in being added to formula, without the need for heating；

(2) with extraordinary solubility, be soluble in polyalcohol, such as glycerine, ethylene glycol, propane diols, butanediol, pentanediol, oneself Glycol etc.；

(3) Miscibility is good, and the other products with formula system, such as surfactant, emulsifying agent have higher compatibility, Can widely use.

3. according to described in claim 1 using fatty acylamino-acid ester and fat amic acid into salt method, its concrete step Suddenly it is：

(1) dissolve：0.1mol fat acylamino-acid esters are dissolved in into solvent, 50-55 DEG C of dissolving is heated to；

(2) into salt：0.1mol fat amic acids are added to step（1）In the fatty acylamino-acid ester solution of gained, mix To clear；

(3) by step（2）The salt vacuum distillation that middle compounding is formed, removes solvent.

4., according to described in claim 1, compound to be formed to microorganism tool using fatty acylamino-acid ester and fatty amic acid There is the salt of suppression or killing action, it is characterised in that fatty acylamino-acid ester has the chemical constitution of (a) ~ (d), Ke Yiwei The combination of one or more in formula (a) ~ (d)：

I. arginine derivative and its common salt, its general structure such as formula (a)：

(a)

Wherein, R₁It is methyl, ethyl, propyl group or butyl；R₂Be carbon number be 6-22 fatty acyl group；

II. ornithine derivative and its common salt, its general structure such as formula (b)：

(b)

Wherein, R₁It is methyl, ethyl, propyl group or butyl；R₂Be carbon number be 6-22 fatty acyl group；

III. lysine derivative and its common salt, its general structure such as formula (c)：

(c)

Wherein, R₁It is methyl, ethyl, propyl group or butyl；R₂Be carbon number be 6-22 fatty acyl group；

IV. histidine derivative and its common salt, its general structure such as formula (d)：

(d)

Wherein, R₁It is methyl, ethyl, propyl group or butyl；R₂Be carbon number be 6-22 fatty acyl group.

5., according to described in claim 1, react to be formed to microorganism tool using fatty acylamino-acid ester and fatty amic acid There is the salt of suppression or killing action, it is characterised in that fatty amic acid is by the aliphatic acid and amino acid that carbon number is 5-21 Condensation is formed, and can be the combination of one or more fatty amic acid, and wherein amino acid is selected from alanine, arginine, asparagus fern Propylhomoserin, cysteine, glutamine, glutamic acid, histidine, isoleucine, glycine, asparagine, leucine, lysine, Methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, valine.

6. according to fatty acylamino-acid ester described in claim 2 and fatty amic acid into salt method, it is characterised in that step Suddenly（1）Middle solvent for use is water or ethanol.

7. the amino acid derivativges described in claim 1-6 are applied to food, beverage as the purposes for suppressing microorganism.

8. the amino acid derivativges described in claim 1-6 are applied to feed as the purposes for suppressing microorganism.

9. the amino acid derivativges described in claim 1-6 are applied to household care products as the purposes for suppressing microorganism.

10. the amino acid derivativges described in claim 1-6 are applied to use in personal care as the purposes for suppressing microorganism Product.