Supramolecular amino acid or its salt, and its production and application

Abstract

The present invention provides a method for producing N-long-chain acyl amino acid dipeptides, supramolecular amino acids and corresponding salts, which can control the occurrence of structural rearrangement and the content of long-chain fatty acids. The present invention also provides supramolecular amino acids and their salts, as well as their applications in fields such as daily chemicals.

Description

[Technical field]

[0001] The present invention relates to the technical field of producing amino acid-based surfactants, and more particularly to a supramolecular amino acid or a salt thereof, and the production and application thereof. [Background technology]

[0002] Surfactants are an essential component in many fields, such as the daily chemical industry, agriculture, and pharmaceutical industry. Currently, there are dozens of types of surfactants in use on the market, but the most commonly used are mainly sodium dodecylbenzenesulfonate (SLS), sodium laureth polyoxyethylene ether sulfate (AES), and sodium laureth sulfate (K12). These three surfactants have been used for decades, and in some cases hundreds of years, so their adverse effects gradually appear during use, and their impact on human safety and the environment has often been reported.

[0003] Other surfactants include, for example, alkyl glycosides (APG) of sugars, amino acid surfactants such as lauroyl-L-glutamic acid, lauroyl glycine, and lauroyl sarcosine. These surfactants are increasingly attracting attention because they are made from biomass, are highly safe, biodegradable, and gentle on the skin, but because they have low dirt removal capabilities, they are rarely used alone as mainstream surfactants and are often used in combination with other mainstream surfactants. Therefore, they do not fundamentally solve the safety and biodegradability shortcomings of mainstream surfactants contained in everyday chemicals.

[0004] Long-chain acyl amino acids such as lauroylalanine are being studied. The synthesis process is currently dominated by the reaction of fatty acid chlorides with the amino groups of amino acids in industrial production. This reaction is also called the Schotten-Baumann condensation reaction, and this typical reaction can cause multiple side reactions such as hydrolysis of fatty acid chlorides and anhydride formation.

[0005] On the other hand, the higher fatty acids produced by hydrolysis of the acid chloride in this reaction are structurally similar to the product long-chain acyl amino acids, and the difference in carbon chain length is small, so it is extremely difficult to remove them efficiently and at low cost using conventional separation methods. However, the presence of higher fatty acid impurities affects the quality of the product, so the removal of higher fatty acids and the reduction of the content of higher fatty acid impurities are important.

[0006] The article "Synthesis and Performance Study of Sodium N-Lauroylalanine", Chen Lili et al., Printing and Dyeing Auxiliaries, Vol. 26, No. 4, April 2009, discusses the synthesis conditions in detail and points out that the hydrolysis of lauroyl chloride is very likely to occur, and many conditions such as solvent, pH, reaction temperature, etc. affect the hydrolysis of lauroyl chloride, and even if the conditions are optimized, the yield is only about 85%.

[0007] According to previous research, it was found that in the Schotten-Baumann reaction, it is difficult to avoid the hydrolysis of long-chain acid chlorides, and it is also difficult to remove long-chain fatty acids such as lauric acid produced by hydrolysis. In addition, in the Schotten-Baumann reaction, in addition to long-chain fatty acids, multiple impurities are introduced, such as impurities from the anhydride formation reaction, acetone and its aldol condensation products such as diacetone alcohol and isopropylideneacetone, and esters (when using alcohol solvents). Although the purity can be increased by several processes such as elution, filtration, and recrystallization, how to effectively and inexpensively control the content of long-chain fatty acids remains a topic for research.

[0008] In the 1990s, Kao improved the Schotten-Baumann reaction to synthesize N-long-chain acyl-β-alanine by reacting β-alanine with fatty acid halide in the presence of potassium hydroxide, using water as the reaction solvent and a reaction temperature of 25-60°C, and then reacting the resulting salt with a strong acid at 60-90°C. However, this method has two problems. First, it produces N-long-chain acyl-β-alanine instead of N-long-chain acyl-L-alanine (or N-long-chain acyl α-alanine). β-alanine does not have a branched chain, and α-alanine has a methyl branched chain, but the two have different steric hindrances and reaction conditions, so this method is not versatile and has problems when applied to amino acids with branched chains. Second, the acid addition process of this method is relatively high at 60-90°C, and the reaction system is water, so the hydrolysis of the acid chloride is intense and difficult to control effectively. The general Schotten-Baumann condensation reaction reduces the hydrolysis of the acid chloride just by choosing a lower temperature.

[0009] Similarly, Ajinomoto Co. has also attempted to improve the Schotten-Baumann condensation reaction and has disclosed a method for producing a cleaning composition containing an N-acylamino acid type anionic surfactant, which includes the following steps (1) to (3): (1) reacting a halogenated fatty acid with an amino acid; (2) adding an acid to the reaction mixture and controlling the pH to 1 to 5 and the temperature to 50 to 100°C; and (3) separating the organic layer from the aqueous layer and neutralizing the organic layer with a base to obtain an organic layer. This method mainly solves the problem of desalting by forming an organic layer and an aqueous layer and separating the organic layer. However, this method uses an anionic surfactant, and similarly has problems in that the hydrolysis of the acid chloride is intense and difficult to effectively control.

[0010] The product obtained by the above method contains a large amount of higher fatty acid impurities, but higher fatty acids such as lauric acid do not show peaks when detected by high performance liquid chromatography (with a UV detector), so they cannot be detected by conventional detection methods. Because the detection of higher fatty acid impurities was overlooked, it was not recognized that the product contained a large amount of higher fatty acid impurities, and there was also a problem with the calculation of the purity of the product (higher fatty acid impurities were incorrectly calculated in the final product). Currently, there are studies such as CN105675749B, CN106442829B, and CN106596768B that recognize this problem, but they only consider how to detect remaining higher fatty acids and do not mention at all how to efficiently remove higher fatty acids.

[0011] Meanwhile, long-chain acyl amino acid dipeptide is a well-known concept, and long-chain acyl glycyl glycine, long-chain acyl glutamyl glutamic acid, etc. have been produced, and the prior art has attempted to introduce N-long-chain acyl amino acid dipeptide or its salt into a cleaning composition. For example, CN100448968C discloses a related detergent composition, but the preparation method thereof involves mixing amino acid, lauric acid and a base solution, and heating in a nitrogen stream at 180°C for 1.5 hours, which requires a very high temperature for the reaction, and the conditions are strict, making it unfavorable for large-scale industrial production. CN105683151B discloses an aqueous solution containing N-long-chain acyl acidic amino acid and / or its salt and a method for preparing the same, but although the method is relatively mild, it requires the use of Celite®, and a large amount of sodium chloride and sodium glutamate salt remain in the product, and at the same time, the scope of application is narrow, and it is only suitable for the preparation of N-long-chain acyl acidic amino acid.

[0012] Theoretically, N-long chain acyl amino acid dipeptide or its salt can be prepared by the Schotten-Baumann reaction between an acid chloride derived from an N-long chain acyl amino acid and an amino acid, or by the reaction of an amino acid dipeptide such as glutamyl glutamic acid with an acid chloride. The above methods have at least two problems. One is that the cost of preparing the dipeptide is high and the yield is low. The other is that it is not generally compatible, and in the case of amino acids such as L-alanine that contain branched chains or have relatively large steric hindrance, N-long chain acyl-L-alanine dipeptide cannot be prepared smoothly by the Schotten-Baumann reaction.

[0013] Therefore, a method for obtaining relatively high and even higher content dipeptide products that is efficient, suitable for large-scale industrial production, and low cost is an urgent issue to be researched.

[0014] On the other hand, although amino acid surfactants are known, the dirt removing ability of such surfactants is low, and they are rarely used alone as mainstream surfactants. How to obtain amino acid surfactants with strong dirt removing ability and how to obtain amino acid surfactants with new structural features are urgent issues that need to be researched.

[0015] The inventors of the present application have studied in detail the amino acid self-assembled supramolecules or salts thereof with novel structural features in the prior applications CN108752228A, CN110804188A, WO2019233375A1, WO2019233377A1, etc., and the relevant contents are incorporated herein by reference. The manufacturing process of the above prior applications requires the use of catalysts, the reaction pressure is 5-50KG, and the dipeptide content in the product is low, but the present invention seeks other solutions to be more suitable for industrialized production.

[0016] For industrial production, a simpler method is expected, which can control the occurrence of self-organization, promote the restructuring of the structure, and control the content of long-chain fatty acids and / or dipeptides (for example, the reaction of lauroyl chloride with sodium alanine, where the dipeptide is lauroylalanylalanine). It is also desirable to obtain a new amino acid surfactant that has strong dirt removal power and can be used as a mainstream surfactant. Summary of the Invention [Problem to be solved by the invention]

[0017] In view of the above problems, in one aspect, the object of the present invention is to provide a production method which can easily obtain an N-long-chain acyl amino acid dipeptide and / or a salt thereof (also referred to as a long-chain acyl amino acid dipeptide and / or a salt thereof) and a composition containing the dipeptide and / or a salt thereof, and which can easily control the content of the long-chain acyl amino acid dipeptide and / or a salt thereof in the composition, has a simple process, is low cost, and can easily be industrially produced.

[0018] In another aspect, the object of the present invention is to provide a convenient method for controlling the content of long-chain fatty acid impurities formed in the Schotten-Baumann reaction or the reaction of an amino acid with a long-chain acid halide, in which various water-soluble impurities such as salts, amino acids, etc. are also removed.

[0019] In a further aspect, the present invention provides a method for separating components in a solid mixture using differences in melting points based on the principle of separating long chain fatty acids and N-long chain acyl amino acids.

[0020] In a further aspect, the object of the present invention is to provide a simple method for producing a supramolecular amino acid having properties different from those of generally commercially available long-chain acyl amino acids. The supramolecular amino acid or its salt according to the present invention is an amino acid product produced based on the process method of the present invention, and a specific structure is formed under specific conditions, and therefore, it is defined herein as a supramolecular amino acid or its salt based on its characteristics.

[0021] In the last aspect, after treatment with the specific process of the present invention, the content of impurities in the product, particularly the content of long-chain fatty acids (also called higher fatty acids, which usually have a long chain of 8 to 22 carbon atoms), sodium halides (such as sodium chloride), and amino acids, can be controlled to be extremely low. [Means for solving the problem]

[0022] Specifically, the solution of the present invention is as follows.

[0023] [1] A method for producing an N-long-chain acyl amino acid dipeptide and / or a salt thereof, or a composition containing an N-long-chain acyl amino acid dipeptide and / or a salt thereof, comprising a step of reacting an amino acid and / or a salt thereof with a long-chain acid halide, wherein after the reaction, the pH value of the system is less than 8, preferably a pH value of 7.5 or less, more preferably a pH value of 7 or less, and most preferably a pH value of 5 to 6.5.

[0024] [2] A method for producing an N-long-chain acyl amino acid dipeptide and / or a salt thereof, or a composition containing an N-long-chain acyl amino acid dipeptide and / or a salt thereof, comprising a step of reacting an amino acid and / or a salt thereof with a long-chain acid halide in the presence of a base, wherein the molar ratio of the amino acid to the base in the entire reaction process is 3:1 to 1:2, preferably 2:1 to 1:1.8, more preferably 1.7:1 to 1:1.7, and most preferably 1.5:1 to 1:1.5.

[0025] [3] According to the method of the above [1] or [2], the long-chain acid halide is added to the amino acid and / or its salt, and when the long-chain acid halide is added, it is not necessary to control the reaction solution to be basic, and preferably, it is not necessary to control the reaction solution to be kept at a pH value of 8 or more; Alternatively, when adding the long-chain acid halide, there is no need to simultaneously add a base or control the rate of addition of the base to maintain the pH value of the system; Alternatively, the difference in pH value of the system before and after adding the long-chain acid halide is 2 or more, preferably 3 or more, more preferably 4 or more.

[0026] [4] According to the method of any one of the above [1] to [3], after reacting the amino acid and / or its salt with the long-chain acid halide, the weight percentage of the N-long-chain acylamino acid dipeptide and / or its salt in the product is 3% or more, preferably 5% or more, more preferably 8% or more, and most preferably 10% or more.

[0027] [5] According to the method according to any one of the above [1] to [4], the method includes: (1) a production step of reacting a raw material containing an amino acid with a raw material containing a base to produce an amino acid salt solution; and (2) a production step of adding a long-chain acid halide to the amino acid salt solution obtained above, or adding a long-chain acid halide and a base to the amino acid salt solution obtained above, and satisfies one or more of the following conditions: a. the pH value of the amino acid salt solution produced in step (1) is 7.5-14, preferably 8-12, more preferably 9-11, and after the reaction in step (2), the pH value of the system is less than 8, preferably 7.5 or less, even more preferably 7 or less, and most preferably 5-6.5; b. In the entire reaction system of step (1) and step (2), the molar ratio of amino acid to base is 3:1 to 1:2, preferably 2:1 to 1:1.8, more preferably 1.7:1 to 1:1.7, and most preferably 1.5:1 to 1:1.5; c. The pH value of the amino acid salt solution obtained in step (1) is higher than the pH value of the system obtained after reacting the amino acid salt with the long-chain acid halide in step (2), and the difference between the two is 2 or more, preferably 3 or more, and more preferably 4 or more.

[0028] [6] According to the method according to any one of the above [1] to [5], the reaction of the amino acid and / or its salt with the long-chain acid halide satisfies one or more of the following conditions: a. the reaction is carried out in the presence of water or a mixed solution of water and a hydrophilic organic solvent, the hydrophilic organic solvent is one or more selected from acetone, methanol, ethanol, isopropanol, sec-butanol, tert-butanol, acetonitrile, and tetrahydrofuran, preferably acetone, and the volume ratio of water to the hydrophilic organic solvent is preferably 1:(0 to 2); b. the temperature of the reaction is 35° C. or less, preferably 30° C. or less; c. The molar ratio of the amino acid and / or its salt to the long-chain acid halide is greater than 1, preferably 2:1 to 1.1:1, and more preferably 1.5:1 to 1.2:1.

[0029] [7] The method according to any one of the above [1] to [6], further comprising a step of acidifying the product obtained by reacting the amino acid and / or its salt with the long-chain acid halide to obtain a crude N-long-chain acyl amino acid product, preferably having a pH value of 1 to 4, more preferably 1 to 2 after acidification.

[0030] [8] According to any one of the methods described above in [1] to [7], wherein the method satisfies one or more of the following conditions: a. the amino acid is one or more selected from glycine, alanine, glutamic acid, sarcosine, aspartic acid, leucine, isoleucine, valine, threonine, proline, phenylalanine, arginine, and lysine; b. the long-chain acyl group in the long-chain acid halide is derived from a saturated or unsaturated, straight-chain or branched-chain fatty acid having 8 to 22 carbon atoms; c. The base is one or more selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, and ammonia.

[0031] [9] According to the method according to [8] above, wherein the method satisfies one or more of the following conditions: a. the amino acid is selected from alanine, glycine, glutamic acid, sarcosine, arginine or lysine, preferably L-alanine; b. the long chain acid halide is one or more selected from octanoyl chloride, decanoyl chloride, undecanoyl chloride, lauroyl chloride, myristoyl chloride, pentadecanoyl chloride, palmitoyl chloride, stearoyl chloride, oil chloride, linoleyl chloride, isostearoyl chloride, coconut oil fatty acid chloride, palm oil fatty acid chloride, preferably coconut oil fatty acid chloride or lauroyl chloride, most preferably lauroyl chloride; c. The base is selected from sodium hydroxide or potassium hydroxide.

[0032]

[10] A method for removing impurities from a crude product of N-long-chain acyl amino acid, comprising the steps of mixing the crude product of N-long-chain acyl amino acid with a solvent, optionally stirring, controlling the temperature T of the system after mixing to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the N-long-chain acyl amino acid, the solvent being water or an organic solvent or a mixed solution of water and an organic solvent, and performing a solid-liquid separation operation after controlling the temperature of the system.

[0033]

[11] According to the method described in

[10] above, the solid-liquid separation is carried out under the action of centrifugal force or pressure, and preferably, during the solid-liquid separation, separation is promoted using a solvent at a constant temperature as a medium, and the solvent at a constant temperature refers to a solvent that controls the temperature T to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the N-long-chain acyl amino acid, and the solvent is water or an organic solvent, or a mixed solution of water and an organic solvent.

[0034]

[12] According to the method according to

[11] above, wherein the solid-liquid separation satisfies one or more of the following conditions: a. In the solid-liquid separation, a solvent as a medium is brought into contact with the crude product, and under the action of centrifugal force or pressure, the solvent carries away impurities to promote separation; b. During solid-liquid separation, the solvent as a medium is provided by injection; c. The amount of the solvent used as a medium during solid-liquid separation is 0.5 times or more the mass of the crude product of N-long-chain acyl amino acid; d. Solid-liquid separation should be performed using an industrial centrifuge or filter press, preferably a filtering centrifuge equipped with a filtering mesh or filter cloth.

[0035]

[13] According to the method of the above

[11] or

[12] , wherein the temperature T of the solvent as the medium has a plurality of temperature stages, and preferably the temperature of the latter stage is equal to or higher than the temperature of the former stage; Preferably, the temperature of the first stage is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 15°C, and the temperature of at least one subsequent stage is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 15°C and equal to or lower than the melting point of the N-long-chain acyl amino acid; More preferably, the temperature of the first stage is controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain fatty acid +10°C, and the temperature of at least one subsequent stage is controlled to be above the melting point of the long-chain fatty acid +20°C and below the melting point of the N-long-chain acyl amino acid.

[0036]

[14] According to the method of the above

[11] or

[12] , when only water is used as a solvent when preparing the crude product of N-long-chain acyl amino acid, or the content of long-chain fatty acid impurities in the crude product of N-long-chain acyl amino acid is 10% wt or more, the temperature T of the solvent as a medium has multiple temperature stages, and the temperature of the first stage is controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain fatty acid + 6 ° C, and the temperature of at least one subsequent stage is controlled to be above the melting point of the long-chain fatty acid + 15 ° C and below the melting point of the N-long-chain acyl amino acid; More preferably, the temperature of the first stage is controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain fatty acid +3°C, and the temperature of at least one subsequent stage is controlled to be above the melting point of the long-chain fatty acid +20°C and below the melting point of the N-long-chain acyl amino acid.

[0037]

[15] According to the method described in

[11] or

[12] above, the temperature T of the solvent as a medium has a plurality of temperature stages, the temperature of the first stage is controlled to 60°C or lower, and the temperature of at least one subsequent stage is controlled to 60°C or higher, more preferably the temperature of the first stage is controlled to 50-60°C, and the temperature of at least one subsequent stage is controlled to 65-70°C.

[0038]

[16] According to the method according to any one of the above

[10] to

[15] , the solid-liquid separation is further performed n times (n≧1) after the first solid-liquid separation, and preferably the temperature of the next solid-liquid separation is equal to or higher than the temperature of the previous solid-liquid separation; The specific steps of each solid-liquid separation are as follows: mix the solid obtained after the previous solid-liquid separation with a solvent, and optionally stir; control the temperature Tn of the mixed system to be equal to or higher than the melting point of the long-chain fatty acid and lower than the melting point of the N-long-chain acyl amino acid; and then carry out a solid-liquid separation operation; the solvent is water or an organic solvent, or a mixture of water and an organic solvent; Alternatively, the solid obtained after the previous solid-liquid separation is mixed with a solvent, and optionally stirred, and the temperature Tn of the system is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the N-long-chain acyl amino acid. Then, a solid-liquid separation operation is carried out, and during the solid-liquid separation, the separation is promoted by using a solvent with a constant temperature as a medium. The constant temperature solvent refers to a solvent that controls the temperature Tn to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the N-long-chain acyl amino acid, and the solvent is water or an organic solvent, or a mixed solution of water and an organic solvent.

[0039]

[17] According to the method of the above

[16] , in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 15 ° C., and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 15 ° C. and equal to or lower than the melting point of the N-long-chain acyl amino acid; More preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 10°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 20°C and equal to or lower than the melting point of the N-long-chain acylamino acid.

[0040]

[18] According to the method described in

[16] above, here, three or more solid-liquid separations are performed, and in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 8°C, in at least one intermediate solid-liquid separation, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 8°C and equal to or lower than the melting point of the long-chain fatty acid + 18°C, and in the final solid-liquid separation, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 24°C and equal to or lower than the melting point of the N-long-chain acyl amino acid.

[0041]

[19] According to the method described in

[16] above, when only water is used as a solvent when producing a crude product of N-long-chain acyl amino acid, or when the content of long-chain fatty acid impurities in the crude product of N-long-chain acyl amino acid is 10% or more, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 6°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 15°C and equal to or lower than the melting point of the N-long-chain acyl amino acid; More preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 3°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 20°C and equal to or lower than the melting point of the N-long-chain acylamino acid.

[0042]

[20] According to the method described in

[16] above, in the first solid-liquid separation, the temperature T is controlled to 60°C or lower, and in at least one solid-liquid separation among the subsequent n solid-liquid separations, the temperature Tn is controlled to 60°C or higher, more preferably in the first solid-liquid separation, the temperature T is controlled to 50 to 60°C, and in at least one solid-liquid separation among the subsequent n solid-liquid separations, the temperature Tn is controlled to 65 to 70°C.

[0043]

[21] According to the method of any one of the above

[10] to

[20] , wherein the crude N-long-chain acyl amino acid is a commercially available N-long-chain acyl amino acid; Alternatively, it is a crude product of the N-long-chain acyl amino acid according to any one of the above [7] to [9], or an N-long-chain acyl amino acid having a weight percentage of long-chain fatty acids of 5% or more; Alternatively, a crude product of N-long-chain acyl amino acid produced by a method comprising the steps of: (1) reacting a raw material containing an amino acid with a raw material containing a base to produce an amino acid salt solution; (2) adding a long-chain acid halide and optionally a base to the amino acid salt solution obtained above to obtain an N-long-chain acyl amino acid salt; and (3) acidifying the N-long-chain acyl amino acid salt obtained above, Alternatively, the crude product of N-long-chain acyl amino acid is produced by a method including the steps of reacting an amino acid and / or a salt thereof with a long-chain acid halide in the presence of a base to obtain an N-long-chain acyl amino acid salt, acidifying the obtained N-long-chain acyl amino acid salt to gradually precipitate a solid, allowing it to stand, subjecting it to solid-liquid separation, and optionally washing and drying to obtain a crude product of N-long-chain acyl amino acid.

[0044]

[22] According to the method of any one of

[10] to

[21] above, the long-chain fatty acid is a saturated or unsaturated, straight-chain or branched-chain fatty acid having 8 to 22 carbon atoms, the N-long-chain acyl group in the N-long-chain acyl amino acid is derived from the saturated or unsaturated, straight-chain or branched-chain fatty acid having 8 to 22 carbon atoms, and the amino acid in the N-long-chain acyl amino acid is glycine, alanine, glutamic acid, sarcosine, aspartic acid, leucine, isopropyl alcohol, ... The organic solvent is one or more selected from the group consisting of soleucine, valine, threonine, proline, phenylalanine, arginine and lysine, and the organic solvent is an organic solvent that is slightly soluble, poorly soluble or insoluble in long-chain fatty acids and N-long-chain acyl amino acids, where the above-mentioned "slightly soluble, poorly soluble or insoluble" means that the solubility of the long-chain fatty acids and N-long-chain acyl amino acids in the organic solvent at 20°C is less than 1 g / 100 g, preferably less than 0.01 g / 100 g, and more preferably less than 0.001 g / 100 g.

[0045]

[23] According to any one of the methods of

[22] above, wherein the long chain fatty acid is one or more selected from caprylic acid, capric acid, undecanoic acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, isostearic acid, coconut oil fatty acid, palm oil fatty acid, preferably coconut oil fatty acid or lauric acid, most preferably lauric acid; Correspondingly, the N-long-chain acyl group in the above-mentioned N-long-chain acyl amino acid is one or more selected from octanoyl group, decanoyl group, undecanoyl group, lauroyl group, myristoyl group, pentadecanoyl group, palmitoyl group, stearoyl group, oleoyl group, linoleoyl group, isostearoyl group, coconut oil fatty acid acyl group, palm oil fatty acid acyl group, preferably coconut oil fatty acid acyl group or lauroyl group, most preferably lauroyl group; The amino acid in said N-long chain acyl amino acid is derived from alanine, glycine, glutamic acid, sarcosine, arginine or lysine, preferably L-alanine.

[0046]

[24] A method for separating components in a solid mixture by utilizing the difference in melting point, the method comprising: (a) adding a solvent to the solid mixture; (b) controlling the temperature T of the system after adding the solvent to be equal to or higher than the melting point of the low melting point component and equal to or lower than the melting point of the high melting point component; and (c) controlling the temperature of the system and then performing a solid-liquid separation operation, the solvent being slightly soluble, slightly soluble or insoluble in the components to be separated (i.e., the high melting point component and the low melting point component to be separated), the slightly soluble, slightly soluble or insoluble meaning that the solubility of the components to be separated in the solvent at 20°C is less than 1 g / 100 g, preferably less than 0.01 g / 100 g, more preferably less than 0.001 g / 100 g, the boiling point of the solvent is equal to or higher than the melting point of the low melting point component, and the temperature T of the system is equal to or lower than the boiling point of the solvent.

[0047]

[25] According to the method of the above

[24] , wherein the melting point difference between the components to be separated is 10°C or more, preferably 20°C or more, more preferably 30°C or more; And / or the weight percentage of the low melting point component is 50% or less, preferably 40% or less, more preferably 30% or less.

[0048]

[26] According to the method of the above 24 or 25, wherein the solid-liquid separation is carried out under the action of centrifugal force or pressure, and preferably, during the solid-liquid separation, separation is promoted using a solvent of a constant temperature as a medium, and the solvent of the constant temperature refers to a solvent that controls the temperature T to be equal to or higher than the melting point of the low-melting point component and lower than the melting point of the high-melting point component, and the solvent is a solvent that is slightly soluble, difficult to soluble or insoluble in the components to be separated.

[0049]

[27] According to any one of the methods described in

[24] to

[26] above, wherein the solid-liquid separation satisfies one or more of the following conditions: a. In solid-liquid separation, a solvent as a medium is brought into contact with the mixture to be separated, and under the action of centrifugal force or pressure, the solvent carries away the low melting point components to promote separation; b. During solid-liquid separation, the solvent as a medium is provided by injection; c. When separating solid and liquid, the amount of solvent used as a medium is at least 0.5 times the mass of the mixture to be separated; d. Solid-liquid separation should be performed using an industrial centrifuge or filter press, preferably a filtering centrifuge equipped with a filtering mesh or filter cloth.

[0050]

[28] According to the method of the above

[26] or

[27] , wherein the temperature T of the solvent as the medium has a plurality of temperature stages, and preferably the temperature of the latter stage is equal to or higher than the temperature of the former stage; Preferably, the temperature of the first stage is controlled to be equal to or higher than the melting point of the low melting component and equal to or lower than the melting point of the low melting component +10° C., and the temperature of at least one subsequent stage is controlled to be equal to or higher than the melting point of the low melting component +10° C. and equal to or lower than the melting point of the high melting component; More preferably, the temperature of the first stage is controlled to be above the melting point of the low melting component and below the melting point of the low melting component +10°C, and the temperature of at least one subsequent stage is controlled to be above the melting point of the low melting component +20°C and below the melting point of the high melting component.

[0051]

[29] According to the method of the above

[26] or

[27] , wherein the weight percentage of the low-melting-point component is 10% to 40%, preferably 15% to 30%, the temperature T of the solvent as a medium has a plurality of temperature stages, and the temperature of the first stage is controlled to be equal to or higher than the melting point of the low-melting-point component and equal to or lower than the melting point of the low-melting-point component + 6°C, and the temperature of at least one subsequent stage is controlled to be equal to or higher than the melting point of the low-melting-point component + 15°C and equal to or lower than the melting point of the high-melting-point component; More preferably, the temperature of the first stage is controlled to be above the melting point of the low melting point component and below the melting point of the low melting point component +3°C, and the temperature of at least one subsequent stage is controlled to be above the melting point of the low melting point component +20°C and below the melting point of the high melting point component.

[0052]

[30] According to the method according to any one of the above

[24] to

[29] , the solid-liquid separation is further performed n times (n≧1) after the first solid-liquid separation, and preferably the temperature of the next solid-liquid separation is equal to or higher than the temperature of the previous solid-liquid separation; The specific steps of each solid-liquid separation are: mixing the solid obtained after the previous solid-liquid separation with a solvent, optionally stirring, controlling the temperature Tn of the system after mixing to be equal to or higher than the melting point of the low melting point component and equal to or lower than the melting point of the high melting point component, and then performing a solid-liquid separation operation, the solvent being a solvent that is slightly soluble, poorly soluble or insoluble in the components to be separated; Alternatively, the solid obtained after the previous solid-liquid separation is mixed with a solvent, and optionally stirred, and the temperature Tn of the system is controlled to be equal to or higher than the melting point of the low melting point component and equal to or lower than the melting point of the high melting point component. Then, a solid-liquid separation operation is carried out, and during the solid-liquid separation, the separation is promoted using a solvent at a constant temperature as a medium. The constant temperature solvent refers to a solvent that controls the temperature Tn to be equal to or higher than the melting point of the low melting point component and equal to or lower than the melting point of the high melting point component, and the solvent is a solvent that is slightly soluble, difficult to dissolve, or insoluble in the components to be separated.

[0053]

[31] According to the method described in

[30] above, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component + 10°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component + 10°C and equal to or lower than the melting point of the high-melting point component; Preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component +10°C, and in at least one solid-liquid separation among the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component +20°C and equal to or lower than the melting point of the high-melting point component.

[0054]

[32] According to the method described in

[30] above, here, three or more solid-liquid separations are performed, and in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component + 8°C, in at least one intermediate solid-liquid separation, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component + 8°C and equal to or lower than the melting point of the low-melting point component + 18°C, and in the final solid-liquid separation, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component + 24°C and equal to or lower than the melting point of the high-melting point component.

[0055]

[33] According to the method described in

[30] above, wherein the weight percentage of the low melting point component is 10% to 40%, preferably 15% to 30%, and in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low melting point component and equal to or lower than the melting point of the low melting point component + 6°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the low melting point component + 15°C and equal to or lower than the melting point of the high melting point component; More preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component +3°C, and in at least one solid-liquid separation among the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component +20°C and equal to or lower than the melting point of the high-melting point component.

[0056]

[34] A method for producing a supramolecular amino acid, comprising a step of removing impurities from a crude product of the N-long-chain acyl amino acid described in any one of

[10] to

[23] above, and reconstructing the structure during the impurity removal process.

[0057]

[35] A supramolecular amino acid produced by the method described in

[34] above.

[0058]

[36] According to the supramolecular amino acid described in

[35] above, the weight percentage of the long-chain fatty acid is 5% or less, preferably 3% or less, and most preferably 0.5% to 3%; And / or, the weight percentage of N-long-chain acyl amino acid dipeptide is 3% or more, preferably 5% or more, more preferably 8% or more, and most preferably 10% or more.

[0059]

[37] A supramolecular amino acid, comprising an N-long-chain acyl amino acid, an N-long-chain acyl amino acid dipeptide self-assembled supramolecular structure, and the weight percentage of the N-long-chain acyl amino acid dipeptide is 3% or more, preferably 5% or more, more preferably 8% or more, and most preferably 10% or more.

[0060]

[38] According to the supramolecular amino acid described in

[37] above, the supramolecular amino acid has a medium dipeptide content, and the weight percentage of N-long-chain acyl amino acid dipeptide is 5% or more, preferably 10% or more and less than 15%; Alternatively, it is a supramolecular amino acid with a high dipeptide content, and the weight percentage of N-long-chain acyl amino acid dipeptide is 15% or more, preferably 20% or more.

[0061]

[39] According to the supramolecular amino acid described in the above

[37] or

[38] , the weight percentage of the long-chain fatty acid is 5% or less, preferably 3% or less, and most preferably 0.5% to 3%.

[0062]

[40] According to the supramolecular amino acid according to any one of the above

[35] to

[39] , the supramolecular amino acid is subjected to mass spectrometry detection, and the detection conditions are mass spectrometry AB4500, mass spectrometry system Q1SCAN, ionization method ESI(-), scan range m / z = 200 to 600, and a characteristic ion peak in the mass spectrometry spectrum in the range of 541 to 545; And / or, high performance liquid chromatography detection is performed on the supramolecular amino acid, and the detection conditions are as follows: a high performance liquid chromatograph equipped with a UV detector is used, the column is ODS-2 HYPERSIL C18 250×4.6 mm 5 μm, the wavelength is 210 nm, the mobile phase is methanol: 20 mmol / L potassium dihydrogen phosphate buffer solution at pH 3.0 = 70:30 (v / v), and the peak group includes 3 or 4 peaks in the retention time range of 30 to 45 minutes in the chromatogram.

[0063]

[41] According to the supramolecular amino acid according to any one of

[35] to

[40] above, one or more of the following conditions are satisfied: a. the microdomain of the supramolecular amino acid solid powder is columnar, rod-like, linear or rope-like; b. the supramolecular amino acid has an initial melting temperature of 78°C or higher and a final melting temperature of 87°C or higher, preferably an initial melting temperature of 80°C or higher and a final melting temperature of 90°C or higher, as detected by a capillary; c. the DSC peak value (Peak temperature) of the supramolecular amino acid is 86°C or higher, preferably 88°C or higher, more preferably 90°C or higher; d. the number average molecular weight of the supramolecular amino acid sodium salt is between 5,000 and 250,000, preferably between 10,000 and 150,000, and more preferably between 15,000 and 100,000.

[0064]

[42] According to the supramolecular amino acid according to any one of

[35] to

[41] above, one or more of the following conditions are satisfied: a. After washing the arm with 8% arginine-neutralized supramolecular amino acid aqueous solution for 60 minutes, the moisture content of the stratum corneum is greater than that of the stratum corneum before washing; b. The aqueous solution of the supramolecular amino acid salt is easy to rinse and has no false slippage; c. Referring to GB / T 29679-2013 test, the amount of bubbles at 0 min in the supramolecular amino acid salt solution with a mass percentage concentration of supramolecular amino acid of 0.5% is greater than 130 mm, preferably greater than 150 mm, more preferably greater than 160 mm; the amount of bubbles at 0 min in the supramolecular amino acid salt solution with a mass percentage concentration of supramolecular amino acid of 0.05% is greater than 40 mm, preferably greater than 60 mm, more preferably greater than 80 mm.

[0065]

[43] According to the supramolecular amino acid according to any one of

[35] to

[42] above, one or more of the following conditions are satisfied: a The N-long-chain acyl group in the N-long-chain acyl amino acid and the N-long-chain acyl amino acid dipeptide is one or more selected from an octanoyl group, a decanoyl group, an undecanoyl group, a lauroyl group, a myristoyl group, a pentadecanoyl group, a palmitoyl group, a stearoyl group, an oleoyl group, a linoleoyl group, an isostearoyl group, a coconut oil fatty acid acyl group, and a palm oil fatty acid acyl group, preferably a coconut oil fatty acid acyl group or a lauroyl group, and most preferably a lauroyl group; b) The amino acid in the N-long chain acyl amino acid or N-long chain acyl amino acid dipeptide is one or more selected from glycine, alanine, glutamic acid, sarcosine, aspartic acid, leucine, isoleucine, valine, threonine, proline, phenylalanine, arginine, and lysine, preferably alanine, glycine, glutamic acid, sarcosine, arginine, or lysine, and most preferably L-alanine; c. The long chain fatty acid is one or more selected from caprylic acid, capric acid, undecanoic acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, isostearic acid, coconut oil fatty acid, palm oil fatty acid, preferably coconut oil fatty acid or lauric acid, most preferably lauric acid.

[0066]

[44] According to the supramolecular amino acid described in any one of

[35] to

[43] above, the N-long-chain acyl amino acid is N-lauroyl-L-alanine, the N-long-chain acyl amino acid dipeptide is N-lauroyl-L-alanyl-L-alanine, and the long-chain fatty acid is lauric acid.

[0067]

[45] A supramolecular amino acid salt, which is formed from the supramolecular amino acid according to any one of the above

[35] to

[44] and a base.

[0068]

[46] According to the supramolecular amino acid salt described in

[45] above, the base is one or more selected from inorganic bases, organic amines, and basic amino acids.

[0069]

[47] According to the supramolecular amino acid salt described in

[46] above, the inorganic base is one or more selected from sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate, preferably sodium hydroxide or potassium hydroxide, the organic amines are selected from amines and alkanolamines, and the basic amino acid is one or more selected from arginine, lysine, and histidine, preferably arginine or lysine.

[0070]

[48] ​​Use of the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] , wherein the supramolecular amino acid and / or salt thereof is used in a cleaning composition, a detergent composition, a cosmetic composition or a care composition.

[0071]

[49] Use of the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] , wherein the supramolecular amino acid and / or salt thereof is used as a surfactant or an emulsifier.

[0072]

[50] Use of the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] , wherein the supramolecular amino acid and / or salt thereof is used for adsorption of oil or dirt, or adsorption of bacteria, or for sterilization, deodorization, or removal of pesticide residues.

[0073]

[51] Use of the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] , wherein the supramolecular amino acid and / or salt thereof is used in detergent, toothpaste, laundry detergent, soap, powder laundry detergent, dishwashing detergent, mask, shampoo, shower gel, facial cleanser, makeup remover, mouthwash, shaving supplies, hand wash, cleaning lotion, or cleaning cream.

[0074]

[52] A cleaning composition comprising the supramolecular amino acid and / or a salt thereof according to any one of

[35] to

[47] above, preferably an arginine salt or a lysine salt of the supramolecular amino acid.

[0075]

[53] According to the cleaning composition according to

[52] above, wherein the cleaning composition is a detergent, a laundry detergent, a soap, a powder laundry detergent, a dishwashing detergent, a mask, a shampoo, a shower gel, a facial cleanser, a makeup remover, a mouthwash, a shaving product, a hand wash, a cleaning lotion or a cleaning cream.

[0076]

[54] A toothpaste comprising the supramolecular amino acid and / or a salt thereof according to any one of

[35] to

[47] above, preferably an arginine salt or a lysine salt of the supramolecular amino acid.

[0077]

[55] A cosmetic composition comprising the supramolecular amino acid and / or a salt thereof according to any one of

[35] to

[47] above, preferably an arginine salt or a lysine salt of the supramolecular amino acid.

[0078]

[56] A toothpaste comprising an abrasive, a humectant, a thickener, and a surfactant, the weight percentages of each of which based on the total weight of the toothpaste are as follows: Surfactant 0.1-25%, Friction agent 10~50%, Moisturizer 5-40%, Thickener 0.1-6%, The surfactant comprises the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] , and preferably 50 wt % or more, more preferably 80 wt % or more, and even more preferably 100 wt % of the surfactant is the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] .

[0079]

[57] A skin care composition comprising an oil, a surfactant, and suspended particles, the weight percentages of each being as follows: Oil content 50~95%, Surfactant 0.5-30%, Suspended particles 0-45%, The surfactant comprises the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] , and preferably 50 wt % or more, more preferably 80 wt % or more, and even more preferably 100 wt % of the surfactant is the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] .

[0080]

[58] A laundry detergent comprising a surfactant, a fabric softener, a chelating agent, deionized water, a preservative, and a fragrance, the weight percentages of each material being as follows: Surfactant 5-50%, Fabric softener 0.1-3%, Chelating agent 0.1-5%, Deionized water 50-90%, Preservatives 0.1-6%, Fragrance 0.1~2%, The surfactant comprises the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] , and preferably 50 wt % or more, more preferably 80 wt % or more, and even more preferably 100 wt % of the surfactant is the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] .

[0081]

[59] A powder laundry detergent comprising a surfactant, a friction agent, and the weight percentages of each material are as follows: Surfactant 10-50%, Friction agent 50~90%, The surfactant comprises the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] , and preferably 50 wt % or more, more preferably 80 wt % or more, and even more preferably 100 wt % of the surfactant is the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] .

[0082]

[60] A dishwashing detergent comprising a surfactant, deionized water, a thickener, glycerin, a preservative, and a fragrance, the weight percentages of each material being as follows: Surfactant 5-20%, Deionized water 70-90%, Thickener 1-2%, Glycerin 5-10%, Preservatives 0.1-6%, Fragrance 0.1~2%, The surfactant comprises the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] , and preferably 50 wt % or more, more preferably 80 wt % or more, and even more preferably 100 wt % of the surfactant is the supramolecular amino acid and / or salt thereof according to any one of the above

[35] to

[47] . Effect of the Invention

[0083] Compared with the prior art, the present invention has the following beneficial technical effects: 1. The present inventors have unexpectedly discovered that by controlling conditions such as the pH value and the amount of base added, it is possible to produce long-chain acylamino acid dipeptides and / or salts thereof, as well as compositions containing the dipeptides, at low cost.

[0084] 2. The present invention proposes an innovative method for efficiently removing impurities from long-chain acylamino acids, which does not require catalysts or pressure and operates under mild conditions. Based on this principle, the separation of components in a solid mixture is achieved by making innovative use of the difference in melting points of the components to be separated and a solvent at a specific temperature.

[0085] 3. The temperature of the solvent can be controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain acyl amino acid, which helps to remove impurities and control the reorganization of the structure of the long-chain acyl amino acid to form a product with a specific structure. It is the first time that the appropriate separation temperature is screened according to the melting points of the long-chain fatty acid and the long-chain acyl amino acid, and this method has a positive effect.

[0086] 4. In conventional refining operations, products are often washed with room temperature or low temperature solvents, but this does not take into consideration that removing some low melting point impurities at a relatively low temperature first allows the subsequent solid-liquid separation to withstand higher temperatures. Therefore, the present invention performs multiple solid-liquid separations and / or temperature gradient treatments to more effectively remove impurities.

[0087] 5. At the same time as the solid-liquid separation, the separation is promoted by using a constant temperature intermediate solvent, the temperature of the intermediate solvent is controlled to be above the melting point of the long-chain fatty acid and below the melting point of the N-long-chain acyl amino acid, and the intermediate solvent is continuously sprayed / washed (especially sprayed under centrifugal force or pressure conditions) and separated, which effectively removes impurities while promoting the restructuring of the N-long-chain acyl amino acid structure to form a product with a specific structure. A filtration centrifuge equipped with a filtering mesh or filter cloth constantly shakes off the solution during centrifugation, similar to the elution of a washing machine, and a product with a reconstructed structure is obtained by mixing the intermediate solvent at a constant temperature.

[0088] 6. Conventional post-treatment of Schotten-Baumann condensation reaction requires washing or recrystallization using organic solvents such as petroleum ether, isopropanol, and ethanol. However, the present invention can treat the reaction with water only by rational control of the treatment temperature and / or centrifugal force, which is extremely significant from the viewpoints of environmental protection and cost.

[0089] 7. According to the method of the present invention, the content of long-chain fatty acids can be reasonably controlled, the content of dipeptide (take the reaction of lauroyl chloride with sodium alanine as an example, the dipeptide is lauroylalanylalanine) can be adjusted, and the product with a dipeptide content of more than 20% can be easily obtained.

[0090] 8. The supramolecular amino acid or salt thereof obtained by the method of the present invention has a special structure and is capable of adsorbing organic matter such as oil and dirt, and has a high ability to remove oil and dirt.

[0091] 9. The supramolecular amino acid or salt thereof prepared by the method of the present invention is structurally stable, has supramolecular characteristics, and has a special spatial structure, therefore it has properties such as physical sterilization, deodorization, and removal of pesticide residues. It has a good bacterial inhibition rate, and the inhibition rates against Escherichia coli, Staphylococcus aureus, and Candida albicans can all reach 100%, effectively removing pesticide residues, and has a high removal rate against both methylamine-phosphorus and acetomethylamine-phosphorus, as well as good deodorizing performance.

[0092] 10. Due to their special structure, supramolecular amino acids can combine with grease to form a "solid" / cream that does not stick to hands and can be easily removed. They also have a cleaning power within the pH range of 5-14, making them very versatile. [Brief description of the drawings]

[0093] [Figure 1] This is a high performance liquid chromatogram of the Example 33# sample. [Diagram 2] This is a high performance liquid chromatogram of the Example 503# sample. [Diagram 3] This is a high performance liquid chromatogram of Example 604# sample. [Figure 4] The spectra were collected in full scan mode in ESI negative ion mode. [Diagram 5] 1 is a lauric acid standard curve for Method 1. [Figure 6]1 is an SIR spectrum of a sample solution of Example 1. [Figure 7] 2 is a lauric acid standard curve for Method 2. [Figure 8] 1 is a spectrum and integral diagram of the PDA channel of the sample solution of Example 1. [Figure 9] 1 shows the spectrum and integral plot of the QDa full scan channel of the sample solution of Example 1. [Figure 10] 1 is a DSC analysis of the sample of Example 1. [Figure 11] DSC analysis of Example 502# sample. [Figure 12] FIG. 5 is a DSC analysis of Example 501# sample after initial solid-liquid separation. [Figure 13] FIG. 13 is DSC analysis of Example 501# sample after the second solid-liquid separation. [Figure 14] FIG. 13 is DSC analysis of Example 501# sample after the third solid-liquid separation. [Figure 15] FIG. 5 is DSC analysis of Example 503# sample after initial solid-liquid separation. [Figure 16] FIG. 13 is DSC analysis of Example 503# sample after the second solid-liquid separation. [Figure 17] FIG. 13 is DSC analysis of Example 503# sample after the third solid-liquid separation. [Figure 18] Example 502# Scanning electron micrographs of crude product, where 18a is a 200x scanning electron micrograph, 18b is a 500x scanning electron micrograph, and 18c is a 2000x scanning electron micrograph. [Figure 19] 19A-19C are scanning electron micrographs of the crude product of Example 501# after washing, where 19a is a 200x scanning electron micrograph, 19b is a 1000x scanning electron micrograph, and 19c is a 2000x scanning electron micrograph. [Figure 20a] This is a double quantum filtered (DQ-filtered) hydrogen spectrum. [Figure 20b] This is a double quantum filtered (DQ-filtered) hydrogen spectrum. [Figure 20c] 2D 1H-1H DQ-SQ two-dimensional spectrum. [Figure 20d] This is the 13C CP spectrum. [Figure 20e] 2D 13C-1H FSLG-HETCOR spectrum. [Figure 21] 1 is a mass spectrometry spectrum of a sample of Example 6. [Figure 22] This is a diagram showing the effects of a makeup experiment. [Figure 23] FIG. 2 shows changes in water content of the stratum corneum. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0094] In one embodiment, a method for producing a long-chain acylamino acid dipeptide and / or a salt thereof at low cost and a method for producing a composition containing said dipeptide are provided. Long-chain acylamino acid dipeptide refers to a long-chain acylaminoacylamino acid, typically long-chain acylglycylglycine, long-chain acylglutamylglutamic acid, long-chain acylalanylalanine, etc.

[0095] Specifically, the production method includes a step of reacting an amino acid and / or a salt thereof with a long-chain acid halide, and the pH value of the system after the reaction (meaning only the system after the amino acid and / or a salt thereof is reacted with the long-chain acid halide) is less than 8, preferably 7.5 or 7 or less, more preferably 3, 3.5, 4, 4.5 or 5 or more, and 7, 6.9, 6.8, 6.7, 6.6, 6.5 or less than 6. The pH value is preferably 5 to 7, and most preferably 5 to 6.5.

[0096] In the conventional Schotten-Baumann reaction, the condensation of acid halides and amines is believed to be carried out by the conventional reaction mechanism, in which the amine first performs nucleophilic addition / substitution on the acid halide as a nucleophile to form an amide cation intermediate, which is then deprotonated under basic conditions to obtain the amide product, so the pH value of the system must be 8 or higher during the entire reaction process. The reaction activity of amines depends on their basicity, and the stronger the basicity, the faster the reaction rate. If the system is not controlled to be basic, the amine substrate may be protonated by the Bronsted acid by-product generated in the system and lose its activity.

[0097] [ka]

[0098] The present invention unexpectedly found that unless the pH value of the reaction system is controlled to 8 or more, the pH value of the reaction system will decrease with the continuous dropwise addition of acid halide, and that controlling the pH value after completion of the reaction to less than 8, for example less than 7.5, particularly less than 7 or less than 7, is advantageous for the production of long-chain acylamino acid dipeptide and / or a salt thereof.

[0099] In general, the final pH value of the reaction system can be controlled by controlling the amount of base added. Research has been conducted that includes a step of reacting an amino acid and / or its salt with a long-chain acid halide in the presence of a base, and the molar ratio of the amino acid to the base in the entire reaction process is 3:1 to 1:2 (the amino acid salt is converted into the molar ratio of the amino acid to the base), preferably 2:1 to 1:2, more preferably 1.9:1 or 1.8:1 or 1.7:1 or 1.6:1 or 1.5:1 or 1.4:1 or The molar ratio is 1.3:1 or 1.2:1 or 1.1:1 or less and 1:1.9 or 1:1.8 or 1:1.7 or 1:1.6 or 1:1.5 or 1:1.4 or 1:1.3 or 1:1.2 or 1:1.1 or 1:1 or more, for example, the molar ratio is 2:1 to 1:1.8 or 1.8:1 to 1:1.8 or 1.7:1 to 1:1.7, more preferably 1.5:1 to 1:1.5, and most preferably 1.4:1 to 1:1.4. The molar ratio of amino acids to bases refers to the molar ratio of the total amount of amino acids to the total amount of bases.

[0100] The base may be added in one or more portions, or may be added alone or together with the long-chain acid halide to the reaction system. The long-chain acid halide may be added in one or more portions to the reaction system. However, the present invention does not necessarily require that the pH value of the reaction be kept basic even if the base and / or acid halide are added in multiple portions.

[0101] Furthermore, with regard to the production method of the present invention, the conditions under which a long-chain acid halide is added to an amino acid and / or a salt thereof, and the reaction solution does not need to be controlled to be basic when the long-chain acid halide is added, are preferably such that there is no need to control the pH value of the reaction solution to be 8 or higher, or there is no need to add a base simultaneously with the addition of the long-chain acid halide to maintain the pH value, or there is no need to control the dropwise addition rate or amount of a base such as sodium hydroxide to maintain the pH value of the system, or the difference in pH value of the system before and after the addition of the long-chain acid halide is 2 or more, preferably 3, 4, 5, or 6 or more. That is, instead of controlling the pH value as in the conventional Schotten-Baumann reaction, the pH value of the reaction system is gradually lowered as the reaction proceeds.

[0102] By controlling the amount of specific base added (molar ratio of amino acid to base) and / or pH value, the present invention makes it very easy to obtain a large amount of dipeptide product, and preferably, after reacting amino acid and / or its salt with long-chain acid halide, the weight percentage of N-long-chain acyl amino acid dipeptide in the product is 3% or more, preferably 4%, 5%, 6%, 7%, 8%, 9% or 10% or more.

[0103] In one embodiment, after the condensation reaction of the acid halide with the amino acid, the dipeptide content is moderate, i.e., the weight percentage of the N-long-chain acylamino acid dipeptide and / or its salt is 5% or more, preferably 8% or more, more preferably 10% or more and less than 15%.

[0104] In one embodiment, after the condensation reaction of the acid halide with the amino acid, the dipeptide content is high, i.e., the weight percentage of N-long chain acyl amino acid dipeptide and / or its salt is 15% or more, preferably 20% or more.

[0105] In a preferred embodiment, a method for producing a long-chain acyl amino acid dipeptide and / or its salt or related composition includes the steps of: (1) reacting a raw material containing an amino acid with a raw material containing a base to produce an amino acid salt solution; and (2) adding a long-chain acid halide to the amino acid salt solution obtained above, or adding a long-chain acid halide and a base to the amino acid salt solution obtained above, and satisfies one or more of the following conditions: a. the pH value of the amino acid salt solution produced in step (1) is 7.5 to 14, preferably 8 or 8.5 or 9 or 9.5 or more, and 13.5 or 13 or 12.5 or 12 or 11.5 or 11 or less, preferably 8 to 12, more preferably 9 to 11; and after the reaction in step (2), the pH value of the system is less than 8, for example 7.5 or less, preferably 7 or less or less than 7, even more preferably 3, 3.5, 4, 4.5 or 5 or more, and the pH value is 7, 6.9, 6.8, 6.7, 6.5 or 6 or less, preferably 5 to 7, most preferably 5 to 6.5, for example about 6; b. In the entire reaction system of step (1) and step (2), the molar ratio of amino acid to base is 3:1 to 1:2, preferably 2:1 to 1:1.8, and preferably 1.9:1 or 1.8:1 or 1.7:1 or 1.6:1 or 1.5:1 or 1.4:1 or 1.3:1 or 1.2:1 or 1.1:1 or less and 1:1.9 or 1:1.8 or 1:1.7 or 1:1.6 or 1:1.5 or 1:1.4 or 1:1.3 or 1:1.2 or 1:1.1 or 1:1 or more, and the molar ratio of amino acid to base is more preferably 1.8:1 to 1:1.8, preferably 1.7:1 to 1:1.7, and most preferably 1.5:1 to 1:1.5 or 1.4:1 to 1:1.4; c. The pH value of the amino acid salt solution obtained in step (1) is higher than the pH value of the system obtained after reacting the amino acid salt with the long-chain acid halide in step (2), and the difference between the two is 2 or more, preferably 3, 4, 5, or 6 or more.

[0106] If the amount of base added is too large or the pH value after the reaction is too high, the composition of the reaction product is similar to that obtained in the general Schotten-Baumann reaction, that is, the product is mainly long-chain acyl amino acids (peptides), and the content of long-chain acyl amino acid dipeptides is very low (generally less than 2%, even 0). If the amount of base added is too small, precipitation occurs quickly when the acid halide is dropped, and the hydrolysis of the acid halide becomes intense, the reaction cannot proceed efficiently, and the yield is also reduced. Therefore, it is advantageous to include a specific amount of base as above, and it is preferable to simultaneously satisfy the above conditions a, b, and c.

[0107] In one preferred embodiment, the reaction of the amino acid and / or its salt with the long chain acid halide satisfies one or more of the following conditions: a. the reaction is carried out in the presence of water or a mixed solution of water and a hydrophilic organic solvent, the hydrophilic organic solvent is one or more selected from acetone, methanol, ethanol, isopropanol, sec-butanol, tert-butanol, acetonitrile, and tetrahydrofuran, preferably acetone, and the volume ratio of water to the hydrophilic organic solvent is preferably 1:(0-2), preferably 1:(0.8-1.5); b. the temperature of the reaction is 35° C. or less, preferably 30° C. or less; c. The molar ratio of the amino acid and / or its salt to the long-chain acid halide is greater than 1, preferably 2:1 to 1.1:1, and more preferably 1.5:1 to 1.2:1.

[0108] It is preferable that conditions a, b, and c are satisfied simultaneously.

[0109] When the reaction of amino acid and / or its salt with long-chain acid halide is carried out using water as a medium, for example, first dissolving amino acid and base in water and stirring uniformly, and then adding long-chain acid halide thereto, this reaction system is more environmentally friendly, but the hydrolysis of long-chain acid halide is relatively large, reaction impurities increase, and yield decreases.When the mixed solution of water and hydrophilic organic solvent is used as a medium, the hydrolysis of long-chain acid halide can be well controlled with the increase in the amount of hydrophilic organic solvent, but if the amount of hydrophilic organic solvent added is too large, it is disadvantageous in terms of environment and cost, and is also disadvantageous in the progress of the reaction, leading to a decrease in yield, etc.

[0110] The reaction temperature is preferably controlled to a low temperature, for example, 40°C or less, preferably 35°C or 30°C or less, and for example, the temperature can be controlled to 20-30°C throughout the reaction. If the temperature is too high, hydrolysis of the acid halide increases. Of course, if the temperature is too low, the reactivity becomes poor, and the temperature is preferably controlled to 10°C or more.

[0111] In order to promote the production of dipeptides, the molar ratio of the amino acid and / or its salt to the long-chain acid halide is preferably greater than 1. Of course, the more the amino acid, the better; if there is too much amino acid, the reaction cannot be sufficient and the post-treatment pressure increases; therefore, the molar ratio of the amino acid and / or its salt to the long-chain acid halide is preferably 2, 1.9, 1.8, 1.7, 1.6, 1.5 or 1.4 or less, and 1, 1.1, 1.2, 1.3 or more, for example, 2:1 to 1.1:1, more preferably 1.5:1 to 1.2:1.

[0112] Furthermore, the above-mentioned production method further includes a step of acidifying the product obtained after reacting the amino acid and / or its salt with the long-chain acid halide to obtain a crude product of N-long-chain acyl amino acid, preferably having a pH value of 1 or 2 or more, and a pH value of 3 or 4 or less, more preferably a pH value of 1 to 2 after acidification. The above-mentioned crude product refers to a product containing impurities such as long-chain fatty acids and sodium chloride. For the composition, the crude product contains both long-chain acyl amino acids and long-chain acyl amino acid dipeptides.

[0113] The above product can be further purified using known processes or the impurity removal process of the present invention described below to obtain a composition containing long-chain acyl amino acids and long-chain acyl amino acid dipeptides and related supramolecular amino acids, which can also be separated to obtain long-chain acyl amino acid dipeptides.

[0114] In a preferred embodiment, the amino acid is one or more selected from glycine, alanine, glutamic acid, sarcosine, aspartic acid, leucine, isoleucine, valine, threonine, proline, phenylalanine, arginine, lysine. More preferably, the amino acid is selected from alanine, glycine, glutamic acid, sarcosine, arginine or lysine, most preferably L-alanine.

[0115] In a preferred embodiment, the long-chain acyl group in the long-chain acid halide is derived from a saturated or unsaturated, straight-chain or branched-chain fatty acid having 8 to 22 carbon atoms. More preferably, the long-chain acid halide is one or more selected from octanoyl chloride, decanoyl chloride, undecanoyl chloride, lauroyl chloride, myristoyl chloride, pentadecanoyl chloride, palmitoyl chloride, stearoyl chloride, oil chloride, linoleyl chloride, isostearoyl chloride, coconut oil fatty acid chloride, and palm oil fatty acid chloride, preferably coconut oil fatty acid chloride or lauroyl chloride, and most preferably lauroyl chloride.

[0116] In one preferred embodiment, the base is one or more selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonia, more preferably the base is selected from sodium hydroxide or potassium hydroxide.

[0117] In one embodiment, a method for removing impurities from N-long chain acyl amino acids is provided, and in the process of removing impurities using the method, the structure is reconstructed to form a supramolecular amino acid with a specific structure.

[0118] The above-mentioned impurity removal method includes the steps of mixing the crude N-long-chain acyl amino acid with a solvent (the solvent may be added to the crude N-long-chain acyl amino acid, or the crude N-long-chain acyl amino acid may be added to the solvent, and after mixing, it is called "system"), optionally stirring, and controlling the temperature T of the system to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the N-long-chain acyl amino acid, and the above-mentioned solvent is water or an organic solvent, or a mixed solution of water and an organic solvent. From the viewpoint of the cost of industrial production and the environment, it is more preferable to use only water as the solvent.

[0119] The reason for selecting the specific temperature is that the melting points of N-long-chain acyl amino acids and long-chain fatty acids are different. As shown in FIG. 11, taking lauroylalanine as an example, the corresponding peak value of lauric acid in the figure is 42.46°C, and the peak value of lauroylalanine (crude product) is 78.95°C. When the temperature is controlled to be above the melting point of long-chain fatty acids such as lauric acid, the impurities of the long-chain fatty acids can be melted and the long-chain fatty acids can be better removed. When the temperature is controlled to be below the melting point of N-long-chain acyl amino acids, the melting of N-long-chain acyl amino acids can be avoided. If the temperature is too high, no solid-liquid separation will occur after the solid melts, and only by selecting a specific temperature, a solid-liquid two-phase can be formed. It is the first time that an appropriate impurity removal temperature is selected according to the melting points of long-chain fatty acids and long-chain acyl amino acids, and the method has a positive effect on the efficient removal of impurities, the formation of a specific spatial structure, and the performance of the product.

[0120] The above-mentioned mixing of N-long chain acyl amino acid crude product and solvent includes the case where the crude product itself contains a solvent in addition to the case where the solvent is added separately.For example, in the typical case where the crude product itself contains a solvent, after acidification with hydrochloric acid / sulfuric acid, no solid-liquid separation is carried out, and no separate addition of a solvent is required at this time, and a solvent can be added optionally, and still meets the condition of "mixing N-long chain acyl amino acid crude product and solvent".

[0121] Preferably, the removal of impurities is primarily to remove water-soluble impurities such as long chain fatty acids (such as lauric acid) and salts, unreacted amino acids, and the like.

[0122] The above-mentioned crude product of N-long-chain acyl amino acid is a commercially available N-long-chain acyl amino acid, or a crude product of N-long-chain acyl amino acid obtained by the Schotten-Baumann reaction of amino acid and / or its salt with long-chain acid halide, or a crude product containing the above-mentioned dipeptide. The above-mentioned crude product refers to a product containing impurities such as long-chain fatty acid and sodium chloride.

[0123] The N-long-chain acyl amino acid referred to in "below the melting point of N-long-chain acyl amino acid" is the same as the N-long-chain acyl amino acid referred to in "crude product of N-long-chain acyl amino acid", and all are derived from long-chain fatty acid, that is, the above-mentioned N-long-chain acyl amino acid, crude product of N-long-chain acyl amino acid, and long-chain fatty acid have the same "long chain". For example, in the case of crude product of lauroyl alanine, controlling the temperature T of the system to "above the melting point of long-chain fatty acid and below the melting point of N-long-chain acyl amino acid" means controlling the temperature T of the system to "above the melting point of lauric acid and below the melting point of lauroyl alanine". Similarly, in the case of crude product of lauroyl glutamic acid, controlling the temperature T of the system to "above the melting point of lauric acid and below the melting point of lauroyl glutamic acid", and in the case of crude product of lauroyl sarcosine, controlling the temperature T of the system to "above the melting point of lauric acid and below the melting point of lauroyl sarcosine".

[0124] In the case of controlling the temperature T of the system, the overall purpose is to control the temperature. It can be in various forms, for example, adding a solvent to the reaction vessel / container, then adding the N-long-chain acyl amino acid crude product, and then heating to raise the temperature to above the melting point of the long-chain fatty acid and below the melting point of the N-long-chain acyl amino acid. It can also be adding a solvent with a certain temperature (optionally heated), such as solvent / hot water, after adding the N-long-chain acyl amino acid crude product to the reaction vessel / container, and then controlling the temperature to above the melting point of the long-chain fatty acid and below the melting point of the N-long-chain acyl amino acid.

[0125] Stirring can achieve more uniform mixing, and of course other operations that have the same mixing effect as stirring can also be used. In consideration of the mixing effect, stirring or other similar operations are preferred.

[0126] Alternatively, an amino acid is mixed in while adding a solvent to the crude N-long-chain acyl amino acid, or an amino acid solution such as an aqueous amino acid solution is added to the crude N-long-chain acyl amino acid, thereby controlling the temperature of the entire system to be above the melting point of the long-chain fatty acid and below the melting point of the N-long-chain acyl amino acid.

[0127] After controlling the temperature of the above system, a solid-liquid separation operation (initial solid-liquid separation) is carried out.

[0128] In a preferred embodiment, the solid-liquid separation is carried out under the action of centrifugal force or pressure. Preferably, the solid-liquid separation is also promoted by using a constant temperature solvent, the constant temperature solvent being a solvent that controls the temperature T to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the N-long-chain acyl amino acid, and the solvent is water or an organic solvent or a mixed solution of water and an organic solvent. From the viewpoint of the cost of industrial production and the environment, it is more preferable to use only water as the solvent.

[0129] In the present invention, the solvent as a medium is abbreviated as "mediating solvent".Regarding the temperature of the mediating solvent, for example, in the case of crude lauroyl sarcosine, the temperature T of the mediating solvent should be controlled to be above the melting point of lauric acid and below the melting point of lauroyl sarcosine, and in the case of crude lauroyl alanine, the temperature T of the mediating solvent should be controlled to be above the melting point of lauric acid and below the melting point of lauroyl alanine.

[0130] For ease of understanding, "promoting separation using a solvent at a constant temperature" is similar to elution in conventional chemical separation, but is different from elution. Specifically, at the above constant temperature, the crude product is separated into two solid-liquid phases (above the melting point of long-chain fatty acid, impurities of long-chain fatty acid melt to form a liquid phase, and N-long-chain acyl amino acid is a solid phase), and after the intermediate solvent contacts the crude product, the liquid phase can be gradually removed (preferably under the action of centrifugal force or pressure). That is, the treatment with the intermediate solvent means contacting the crude product with the intermediate solvent, such as a method of washing the product / crude product, a method of spraying the product / crude product, etc.

[0131] Preferably, during solid-liquid separation, the solvent as a medium is continuously in contact with the crude product, and under the action of centrifugal force or pressure, the carrier solvent is removed and at the same time, impurities are carried away with it to facilitate separation.

[0132] Preferably, the solid-liquid separation is treated with the intermediate solvent at the same time. The above "solid-liquid separation is treated with the intermediate solvent at the same time" means that at least one stage of solid-liquid separation is treated while performing solid-liquid separation. Taking the solid-liquid separation operation by a centrifuge as an example, after transferring the mixed solution of the crude product and the solvent to the centrifuge, the centrifuge is started, the liquid is first separated, and then the injection device is turned on to inject the intermediate solvent such as hot water, and the centrifuge does not stop centrifuging at the same time as the injection, or after transferring the mixed solution to the centrifuge, the centrifuge is started, and when the centrifugation is started, the injection device is turned on to inject the intermediate solvent such as hot water, and the centrifuge does not stop centrifuging at the same time as the injection. The present invention has surprisingly found that at least one stage of centrifugation and intermediate solvent treatment operations are performed simultaneously, and in this special operating environment, it is more advantageous for the formation of a specific spatial structure by supramolecular amino acids, and the product shows excellent performance.

[0133] The preferred method of using the intermediate solvent during solid-liquid separation is by spraying, that is, the intermediate solvent is sprayed onto the crude product to achieve the purpose of continuous contact with the crude product, and the amount of intermediate solvent used each time is at least 0.5 times the mass of the crude product, preferably 0.5 to 3 times, more preferably 1 to 2 times. If the amount is too small, the treatment effect is low, and if the amount is too large, water and electricity resources are wasted and the product is easily worn.

[0134] Furthermore, the above-mentioned intermediate solvent treatment is carried out under the action of centrifugal force or pressure. Treatment under the action of centrifugal force means that solid-liquid separation is carried out by centrifugal force when treating with a solvent (spraying / washing, etc.), and is most typically carried out inside a centrifuge, and since the centrifuge is also operating when treating with an intermediate solvent (spraying / washing, etc.), an environment of centrifugal force action is provided. Treatment under the action of pressure means that solid-liquid separation is carried out by pressure when treating with a solvent, and is possible with any device / equipment that can apply pressure, and is most typically carried out inside a filter press, and since the filter press is also operating during treatment, an environment of pressure action is provided.

[0135] Further, a centrifuge or a filter press is used for solid-liquid separation. Here, the centrifuge is particularly preferably an industrial centrifuge. In particular, a filter-type centrifuge equipped with a filter mesh or filter cloth is preferred.

[0136] From the viewpoints of better removing impurities and favoring structural reconstruction, it is preferable to use multiple temperature steps / temperature gradient treatments, or to carry out n (n≧1) further solid-liquid separations after the initial solid-liquid separation.

[0137] In one preferred embodiment, there are multiple temperature steps ("mediating solvent temperature gradient process" or "temperature gradient process") in the temperature T of the mediating solvent. Preferably, the temperature of the first step is controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain fatty acid +15°C, and the temperature of at least one subsequent step is controlled to be above the melting point of the long-chain fatty acid +15°C and below the melting point of the N-long-chain acyl amino acid, more preferably, the temperature of the first step is controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain fatty acid +10°C, and the temperature of at least one subsequent step is controlled to be above the melting point of the long-chain fatty acid +20°C and below the melting point of the N-long-chain acyl amino acid.

[0138] Preferably, three or more (including three) temperature stages are used, with the temperature of the first stage being controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain fatty acid +8°C, the temperature of at least one intermediate stage being controlled to be above the melting point of the long-chain fatty acid +8°C and below the melting point of the long-chain fatty acid +18°C, and the temperature of the final stage being controlled to be above the melting point of the long-chain fatty acid +24°C and below the melting point of the N-long-chain acyl amino acid.

[0139] Preferably, when only water is used as the solvent in preparing the crude product of N-long-chain acyl amino acid, or the content of long-chain fatty acid impurities in the crude product of N-long-chain acyl amino acid is more than 10%, the temperature T of the intermediate solvent has multiple temperature stages, and the temperature of the first stage is controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain fatty acid + 6 ° C, and the temperature of at least one subsequent stage is controlled to be above the melting point of the long-chain fatty acid + 15 ° C and below the melting point of the N-long-chain acyl amino acid; more preferably, the temperature of the first stage is controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain fatty acid + 3 ° C, and the temperature of at least one subsequent stage is controlled to be above the melting point of the long-chain fatty acid + 20 ° C and below the melting point of the N-long-chain acyl amino acid.

[0140] The reason for using gradient treatment with multiple temperature stages is that the temperature resistance of the entire crude product gradually improves with the decrease in the content of impurities (for example, as can be seen from Figures 11 to 14, the peak value gradually shifts to the right after each treatment). If a higher temperature is used at the beginning, most of the product will melt, and if a temperature that is too low is used, the long-chain fatty acid impurities cannot melt and the long-chain fatty acids cannot be efficiently removed. First, a temperature that is low but higher than the melting point of the long-chain fatty acid is used to remove some impurities first, and the temperature resistance of the system after treatment is improved to a certain extent. In this case, a higher treatment temperature can be used to remove more impurities, and then the treatment temperature can be further improved. When the content of crude product impurities is high, the temperature resistance of the system is low and when the temperature is too high, the entire product shows a paste-like shape, and the solids gradually dissolve, which is unfavorable for filtration and separation, so it is preferable that the initial treatment temperature is close to the melting point of the long-chain fatty acid. Otherwise, if the temperature is not properly controlled and the starting temperature is too high, the excess long-chain fatty acids will melt easily, and these long-chain fatty acids will further dissolve the N-long-chain acyl amino acids as a "solvent", ultimately resulting in a decrease in the product yield.

[0141] When the long-chain fatty acid contained in the long-chain acylamino acid is lauric acid, since the melting point of lauric acid is about 44° C., in some related embodiments, the temperature T of the intermediate solvent has multiple temperature stages, and the temperature of the first stage is controlled to 60° C. or lower, preferably 44 to 60° C., more preferably 50 to 60° C., and even more preferably 55 to 58° C. The temperature of at least one subsequent stage is controlled to 60° C. or higher, preferably 65° C. or higher, or 60 to 95° C., 62 to 90° C., 65 to 80° C., 65 to 77° C., 65 to 75° C., more preferably 65 to 70° C., or 66 to 68° C.

[0142] Regarding controlling the temperature of at least one subsequent stage to 60°C or higher, for example, when there are three temperature stages in total, the temperature of the first stage may be controlled to 50-60°C, for example 50°C, the temperature of the second stage may be controlled to 60°C or higher, for example 65°C, and the temperature of the third stage may be controlled to 60°C or higher, for example 70°C; the temperature of the first stage may be controlled to 50-60°C, for example 50°C, the temperature of the second stage may be controlled to 50-60°C, for example 50°C, and the temperature of the third stage may be controlled to 60°C or higher, for example 65°C; the temperature of the first stage may be controlled to 50-60°C, for example 50°C, the temperature of the second stage may be controlled to 60°C or higher, for example 65°C, and the temperature of the third stage may be controlled to 50-60°C, for example 60°C. It is preferable to control the temperature of the first stage to 50-60°C, and then use a gradually increased temperature.

[0143] For example, when there are four temperature stages in total, the temperature of the first stage may be controlled to 50 to 60 ° C, the temperature of the second stage may be controlled to 60 ° C or more, the temperature of the third stage may be controlled to 60 ° C or more, and the temperature of the fourth stage may be controlled to 60 ° C or more; the temperature of the first stage may be controlled to 50 to 60 ° C, the temperature of the second stage may be controlled to 50 to 60 ° C, the temperature of the third stage may be controlled to 60 ° C or more, and the temperature of the fourth stage may be controlled to 60 ° C or more; the temperature of the first stage may be controlled to 50 to 60 ° C, the temperature of the second stage may be controlled to 60 ° C or more, the temperature of the third stage may be controlled to 50 to 60 ° C, and the temperature of the fourth stage may be controlled to 60 ° C or more. More preferably, the temperature is 50 to 60 ° C in the first one or two stages, and then 60 ° C or more.

[0144] For all the above embodiments, more preferably, the temperature of all stages is gradually increased or gradually increased overall (although some temperatures of intermediate stages can be basically the same), that is, the processing temperature of the later stages is higher than that of the earlier stages. Preferably, there are 3, 4, 5 or 6 or more temperature stages, which can generally be selected according to the content of impurities and the convenience, cost and efficiency of processing, and usually, 3 temperature stages are more preferred.

[0145] In order to fully achieve the effect of removing impurities, the carrier solvent should be turned over from time to time during the treatment to ensure that the carrier solvent is in contact with the solid as much as possible.

[0146] In another preferred embodiment, after the first solid-liquid separation, further n (n≧1) solid-liquid separations are carried out. The specific steps of each solid-liquid separation are to mix the solid obtained after the previous solid-liquid separation with a solvent, optionally stir, and control the temperature Tn of the system after mixing to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the N-long-chain acyl amino acid, and then carry out a solid-liquid separation operation, and the solvent is water or an organic solvent, or a mixed solution of water and an organic solvent.

[0147] Alternatively, the specific step of solid-liquid separation is to mix the solid obtained after the previous solid-liquid separation with a solvent, optionally stirring, and control the temperature Tn of the system to be above the melting point of the long-chain fatty acid and below the melting point of the N-long-chain acyl amino acid, and then perform a solid-liquid separation operation. During the solid-liquid separation, a constant temperature solvent is used as a medium to promote the separation, and the constant temperature solvent refers to a solvent that controls the temperature Tn to be above the melting point of the long-chain fatty acid and below the melting point of the N-long-chain acyl amino acid. The intermediate solvent is water or an organic solvent, or a mixed solution of water and an organic solvent. From the viewpoint of the cost and environment of industrialized production, it is more preferable to use only water as the intermediate solvent. For the content related to the intermediate solvent, the above description can be referred to, and the description will be omitted here.

[0148] Each solid-liquid separation operation is independent of each other, that is, the above two types of solid-liquid separation can be independently selected and combined. For example, in some solid-liquid separation operations, a solvent at a constant temperature can be used as a medium to promote separation, and in other solid-liquid separation operations, a medium solvent can be used.

[0149] Preferably, the intermediate solvent is used simultaneously with each solid-liquid separation, and more preferably, the intermediate solvent is used by injection during solid-liquid separation.

[0150] The temperature T or Tn of the system after mixing the solid and the solvent, and the temperature T or Tn of the intermediate solvent may be the same or different from each other as long as they are within a limited temperature range. For example, in the initial solid-liquid separation, the temperature T of the system after mixing the solid and the solvent may be different from the temperature T of the subsequent intermediate solvent, but from the viewpoints of convenience of operation and convenience of control, they are preferably the same.

[0151] In the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid +15°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid +15°C and equal to or lower than the melting point of the N-long-chain acylamino acid, more preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid +10°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid +20°C and equal to or lower than the melting point of the N-long-chain acylamino acid.

[0152] Unless otherwise specified, in the present invention, in each solid-liquid separation, the system temperature and the intermediate solvent temperature are in the same temperature range (when an intermediate solvent is used), and for example, when the system temperature Tn is controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain fatty acid + 15° C., the intermediate solvent temperature Tn is similarly controlled to be above the melting point of the long-chain fatty acid and below the melting point of the long-chain fatty acid + 15° C. From the viewpoint of operational convenience, preferably, the above two Tn are not only in the same temperature range, but also have basically the same values ​​(temperature error is allowed).

[0153] Preferably, three or more solid-liquid separations (including three) are performed, the temperature of the first solid-liquid separation is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 8°C, the temperature of at least one intermediate solid-liquid separation is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 8°C and equal to or lower than the melting point of the long-chain fatty acid + 18°C, and the temperature of the final solid-liquid separation is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 24°C and equal to or lower than the melting point of the N-long-chain acylamino acid.

[0154] Preferably, when only water is used as a solvent in producing the crude product of N-long-chain acyl amino acid, or when the content of long-chain fatty acid impurities in the crude product of N-long-chain acyl amino acid is 10% or more, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 6°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 15°C and equal to or lower than the melting point of the N-long-chain acyl amino acid; more preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 3°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 20°C and equal to or lower than the melting point of the N-long-chain acyl amino acid.

[0155] In some embodiments, when the long-chain fatty acid is lauric acid, in the first solid-liquid separation, the temperature T is controlled to 60° C. or lower, and in at least one solid-liquid separation among the subsequent n solid-liquid separations, the temperature Tn is controlled to 60° C. or higher. More preferably, in the first solid-liquid separation, the temperature T is controlled to 50 to 60° C., and in at least one solid-liquid separation among the subsequent n solid-liquid separations, the temperature Tn is controlled to 65 to 70° C.

[0156] In all the above embodiments, more preferably, the temperature of each solid-liquid separation is basically gradually increased, that is, the temperature of the next solid-liquid separation is higher than that of the previous solid-liquid separation. Preferably, 3, 4, 5 or 6 or more solid-liquid separations are carried out, which can generally be selected according to the content of impurities and the ease, cost and efficiency of processing, and generally, 3 solid-liquid separations are more preferred.

[0157] In all of the above-mentioned forms for removing impurities, when the solvent is an organic solvent or a mixed solution of water and an organic solvent, the organic solvent is preferably an organic solvent in which the long-chain fatty acid and the long-chain acyl amino acid are slightly soluble, poorly soluble or insoluble, where the above-mentioned slightly soluble, poorly soluble or insoluble means that the solubility of the long-chain fatty acid and the N-long-chain acyl amino acid in the organic solvent at 20°C is less than 1 g / 100 g, preferably less than 0.01 g / 100 g, more preferably less than 0.001 g / 100 g. For example, the organic solvent may be petroleum ether or acetone.

[0158] The inventors unexpectedly found that in order to properly control the temperature of the first solid-liquid separation, some impurities (such as low melting point impurities) can be selectively filtered out, and if the temperature is raised after these impurities are filtered out, the whole system can withstand a higher temperature without becoming pasty, and therefore, in terms of better removing impurities, the temperature can be appropriately raised in the subsequent solid-liquid separation step (conventional purification operations often wash / elute with normal temperature or low temperature solvents without considering this point). However, the higher the temperature, the better; if it is too high, it will still directly melt the solid. Specifically, the preferred temperature ranges vary slightly depending on the types of long-chain fatty acids and long-chain acyl amino acids.

[0159] In at least one solid-liquid separation, the temperature Tn of the solvent / system is controlled to 60°C or more, which can be understood as follows. For example, when a total of three solid-liquid separations are performed, the temperature of the first step may be controlled to 50-60°C, for example 50°C, the temperature of the second step may be controlled to 60°C or more, and the temperature of the third step may be controlled to 60°C or more; the temperature of the first step may be controlled to 50-60°C, for example 50°C, the temperature of the second step may be controlled to 50-60°C, for example 50°C, and the temperature of the third step may be controlled to 60°C or more; the temperature of the first step may be controlled to 50-60°C, the temperature of the second step may be controlled to 60°C or more, and the temperature of the third step may be controlled to 50-60°C. Preferably, the temperature of the first step is controlled to 50-60°C, and a temperature that is preferably gradually increased thereafter is used. For details of similar definitions and related principles, please refer to the above mediator solvent temperature gradient treatment section.

[0160] The n solid-liquid separation and the intermediate solvent temperature gradient treatment may be performed simultaneously, or only one of them may be performed. From the viewpoint of operational convenience, only n solid-liquid separations may be performed.

[0161] In one embodiment, the present invention provides a method for separating components in a solid mixture by utilizing the difference in melting point, considering that the separation of N-long-chain acyl amino acid from long-chain fatty acid utilizes the difference in melting point between the two and the use of a solvent at a constant temperature to promote the mixture to form a solid-liquid two-phase. This principle is widely applicable to the separation of components in a solid mixture, so that the present invention provides a method for separating components in a solid mixture by utilizing the difference in melting point. This method belongs to a completely new separation method that is different from conventional methods such as evaporation, distillation, crystallization, filtration, solvent extraction, absorption, adsorption, column chromatography, dialysis, permeation, and ultrafiltration.

[0162] With regard to the separation of a solid mixture, if the content of one of its components is so low that it is considered an impurity, the separation therefor corresponds to an impurity removal process.

[0163] The solid mixture according to the present invention does not have to be a completely dry solid mixture, but may contain organic solvents, water, and is typically a crude product after a chemical reaction.

[0164] The present invention is particularly suitable for separating multi-component mixtures with similar physical properties, such as components with similar solubilities, components that form azeotropes, or components that are compatible after melting, which are difficult to separate using traditional separation methods, can be achieved by using the method of the present invention.

[0165] In the prior art, although there are some examples of separation utilizing the difference in melting point, they are mainly used for crystal separation (such as CN102423542B), crystal separation + solubility separation (such as CN106590939B), or direct separation and discharge after melting (such as CN111039776A), and do not involve the mixture being treated with a solvent at a certain temperature to form a solid-liquid two-phase, and then performing solid-liquid separation, or performing solid-liquid separation with the assistance of an intermediate solvent.

[0166] Specifically, the present invention provides a method for separating a high-melting point component and a low-melting point component in a solid mixture by utilizing the difference in melting points, the method comprising: (a) adding a solvent to the mixture; (b) controlling the temperature T of the system after adding the solvent to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the high-melting point component; and (c) controlling the temperature of the system and then performing a solid-liquid separation operation, wherein the solvent is slightly soluble, slightly soluble or insoluble in the components to be separated (i.e., the high-melting point component and the low-melting point component to be separated), and the above-mentioned slightly soluble, slightly soluble or insoluble means that the solubility of the components to be separated in the solvent at 20°C is less than 1 g / 100 g, preferably 0.01 g / 100 g, more preferably 0.001 g / 100 g, and the boiling point of the solvent is equal to or higher than the melting point of the low-melting point component, and the system temperature T is equal to or lower than the boiling point of the solvent.

[0167] Here, the mixture is composed of a high melting point component and a low melting point component, and is not limited to two components, and may be, for example, two to three high melting point components or two to three low melting point components. "Temperature T is equal to or higher than the melting point of the low melting point component" means that temperature T is equal to or higher than the melting points of all low melting point components, and "temperature T is equal to or lower than the melting point of the high melting point component" means that temperature T is equal to or lower than the melting points of all high melting point components. For ease of understanding, assume that the mixture contains four components A, B, C, and D, whose melting points are 34°C, 44°C, 54°C, and 64°C, respectively, and when separating D from the other components, the low melting point components are A, B, and C, the high melting point component is D, and the temperature T is set to 54°C or higher and 64°C or lower. When separating A, B from C, D, the low melting point components are A and B, the high melting point components are C and D, and the temperature T is set to 44°C or higher and 54°C or lower. Of course, after separating A, B and C, D, the method of the present invention can still be used to separate A, B into A and B, and C, D into C and D. Preferably, a two-component separation is used.

[0168] Preferably, the melting point difference between the components to be separated is 10° C. or more, more preferably 15° C., 20° C., 25° C., 30° C. or 35° C. or more. When there are multiple low-melting point components and multiple high-melting point components, the melting point difference between the components to be separated refers to the difference between the highest melting point among the low-melting point components and the lowest melting point among the high-melting point components.

[0169] Preferably, the weight percentage of the low melting point component is 50% or less, more preferably 45%, 40%, 35%, 30%, 25%, 20%, 15%, 10% or 5% or less, said weight percentages being based on the total mixture.

[0170] Preferably, the solid-liquid separation is carried out under the action of centrifugal force or pressure, more preferably, the solid-liquid separation is promoted by a constant-temperature solvent, the constant-temperature solvent refers to a solvent that controls the temperature T to be equal to or higher than the melting point of the low melting point component and equal to or lower than the melting point of the high melting point component, and the intermediate solvent is a solvent that is slightly soluble, poorly soluble or insoluble in the components to be separated, and the slightly soluble, poorly soluble or insoluble means that the solubility of the components to be separated in the solvent at 20°C is less than 1g / 100g, preferably 0.01g / 100g, more preferably less than 0.001g / 100g. The intermediate solvent may refer to the relevant description in other embodiments.

[0171] Preferably, the solid-liquid separation satisfies one or more of the following conditions: a. In solid-liquid separation, a solvent as a medium is brought into contact with the mixture to be separated, and under the action of centrifugal force or pressure, the solvent carries away the low-melting point components together to promote separation; b. During solid-liquid separation, the solvent as a medium is provided by injection; c. During solid-liquid separation, the amount of solvent used as a medium is at least 0.5 times the mass of the solid mixture to be separated; d. Solid-liquid separation should be performed using an industrial centrifuge or filter press, preferably a filtering centrifuge equipped with a filtering mesh or filter cloth.

[0172] In one embodiment, the temperature T of the solvent as the medium has a plurality of temperature stages, and preferably the temperature of the latter stage is equal to or higher than the temperature of the former stage.

[0173] Preferably, the temperature of the first stage is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component +10°C or +15°C (if the difference in melting points between the high-melting point component and the low-melting point component is large, select +15°C or lower), and the temperature of at least one subsequent stage is controlled to be equal to or higher than the melting point of the low-melting point component +10°C or +15°C (if the difference in melting points between the high-melting point component and the low-melting point component is large, select +15°C or higher) and equal to or lower than the melting point of the high-melting point component; more preferably, the temperature of the first stage is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component +10°C, and the temperature of at least one subsequent stage is controlled to be equal to or higher than the melting point of the low-melting point component +20°C and equal to or lower than the melting point of the high-melting point component.

[0174] Preferably, when the weight percentage of the low-melting point component is 10% to 40%, particularly 15% to 30%, there are multiple temperature stages in the temperature T of the solvent as a medium, and the temperature of the first stage is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component +6°C, and the temperature of at least one subsequent stage is controlled to be equal to or higher than the melting point of the low-melting point component +15°C and equal to or lower than the melting point of the high-melting point component, and more preferably, the temperature of the first stage is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component +3°C, and the temperature of at least one subsequent stage is controlled to be equal to or higher than the melting point of the low-melting point component +20°C and equal to or lower than the melting point of the high-melting point component.

[0175] In one embodiment, after the first solid-liquid separation, n (n≧1) more solid-liquid separations are carried out, and preferably the temperature of the next solid-liquid separation is equal to or higher than the temperature of the previous solid-liquid separation.

[0176] The specific steps of each solid-liquid separation are to mix the solid obtained after the previous solid-liquid separation with a solvent, optionally stir, control the temperature Tn of the system after the mixing to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the high-melting point component, and then perform the solid-liquid separation operation.

[0177] Alternatively, the solid obtained after the previous solid-liquid separation is mixed with a solvent, and optionally stirred, and the temperature Tn of the system is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the high-melting point component. Then, a solid-liquid separation operation is performed, and the separation is promoted by using a constant-temperature solvent during the solid-liquid separation. The constant-temperature solvent is a solvent that controls the temperature Tn to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the high-melting point component.

[0178] In each solid-liquid separation, the solvent (including the intermediate solvent) is a solvent that is slightly soluble, slightly soluble or insoluble in the components to be separated, and the above-mentioned slightly soluble, slightly soluble or insoluble means that the solubility of the components to be separated in the solvent at 20°C is less than 1 g / 100 g, preferably less than 0.01 g / 100 g, more preferably less than 0.001 g / 100 g.

[0179] Preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component +10°C or +15°C (if the difference in melting points between the high and low melting point components and the low-melting point component is large, +15°C or lower is selected), and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component +10°C or +15°C and equal to or lower than the melting point of the high-melting point component, preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting point component +10°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component +20°C and equal to or lower than the melting point of the high-melting point component.

[0180] Preferably, three or more solid-liquid separations are performed, and in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component +8°C, in at least one intermediate solid-liquid separation, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component +8°C and equal to or lower than the melting point of the low-melting point component +18°C, and in the final solid-liquid separation, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component +24°C and equal to or lower than the melting point of the high-melting point component.

[0181] Preferably, when the weight percentage of the low-melting point component is 10% to 40%, particularly 15% to 30%, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component +6°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component +15°C and equal to or lower than the melting point of the high-melting point component, more preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting point component and equal to or lower than the melting point of the low-melting point component +3°C, and in at least one solid-liquid separation of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting point component +20°C and equal to or lower than the melting point of the high-melting point component.

[0182] The conditions "multiple solid-liquid separations" and "the temperature T of the intermediate solvent has multiple temperature stages" may be satisfied simultaneously, or only one of them may be satisfied.

[0183] In each of the above embodiments, the crude product of N-long chain acyl amino acid may be a commercially available N-long chain acyl amino acid, as long as it is any N-long chain acyl amino acid available on the market, without being limited to a specific specification. Some commercially available N-long chain acyl amino acids have high nominal purity, but in reality they still contain a lot of impurities, and since lauric acid is not absorbed in the ultraviolet region, they are not detected by conventional liquid chromatography (with a UV detector), and there is a high possibility that the purity will be calculated inaccurately. The impurities can be better analyzed by a combination of high performance liquid chromatography-mass spectrometry or high performance liquid chromatography with a specific detector, etc. When the commercially available N-long chain acyl amino acid is treated according to each of the above embodiments, impurities can be further removed, structural reconstruction occurs, and a product with a specific structure (supermolecular amino acid with a specific structure) can be formed.

[0184] In each of the above embodiments, the crude N-long-chain acyl amino acid is produced by a method including the steps of: (1) reacting a raw material containing an amino acid with a raw material containing a base to produce an amino acid salt solution; (2) adding a long-chain acid halide and optionally a base to the amino acid salt solution obtained above to obtain an N-long-chain acyl amino acid salt; and (3) acidifying the N-long-chain acyl amino acid salt obtained above.

[0185] After the acidification in step (3), a crude product may be obtained by performing a solid-liquid separation operation such as filtration / centrifugation, or the crude product may be used as it is without performing solid-liquid separation. Preferably, solid-liquid separation is performed.

[0186] Alternatively, the crude N-long-chain acyl amino acid is produced by a method including the steps of reacting an amino acid and / or a salt thereof with a long-chain acid halide in the presence of a base to obtain an N-long-chain acyl amino acid salt, acidifying the obtained N-long-chain acyl amino acid salt to gradually precipitate a solid, allowing it to stand and then subjecting it to solid-liquid separation, and optionally washing and drying to obtain the crude N-long-chain acyl amino acid.

[0187] Alternatively, the crude N-long-chain acyl amino acid can be produced by a method including the steps of: (1) dissolving an amino acid and a base in a mixed solution of water and an organic solvent, and stirring the mixture to obtain an amino acid salt solution; (2) adding a long-chain acid halide and a base to the amino acid salt solution obtained above, and then continuing to stir to obtain an N-long-chain acyl amino acid salt; and (3) acidifying the N-long-chain acyl amino acid salt obtained above to gradually precipitate a solid, which is allowed to stand, separated into solid and liquid, and optionally washed and dried to obtain a crude N-long-chain acyl amino acid.

[0188] Furthermore, the crude product of N-long chain acyl amino acid is (1) dissolving an amino acid and a metal inorganic base in a mixed solution of water and an organic solvent, and stirring the mixture to obtain an amino acid salt solution; (2) adding long-chain acid chloride and metal inorganic base to the amino acid salt solution obtained above in order, and then continuing to stir to obtain N-long-chain acyl amino acid salt; (3) The N-long-chain acyl amino acid salt obtained above is acidified to gradually precipitate a solid, which is then allowed to stand and then subjected to solid-liquid separation by filtration, centrifugation or the like to obtain a crude product of the N-long-chain acyl amino acid.

[0189] From the viewpoint of favoring complete reaction of the long-chain acid chloride, the molar ratio of the amino acid to the long-chain acid chloride administered is 1:1 or more, preferably 1.2:1 or more.

[0190] Furthermore, the crude product of the N-long-chain acyl amino acid is (1) dissolving an amino acid and a metal inorganic base in a mixed solution of water and an organic solvent, and stirring the mixture to obtain an amino acid salt solution; (2) adding a long-chain acid chloride and a metal inorganic base in this order to the amino acid salt solution obtained above, and then continuing to stir the mixture at 0 to 50°C (preferably at a low temperature of, for example, 0 to 25°C) to obtain an N-long-chain acyl amino acid salt; (3) acidifying the N-long-chain acyl amino acid salt obtained above to gradually precipitate a solid, then leaving it at 0 to 30°C, for example in an ice bath, for 1 to 5 hours, and filtering / centrifuging to obtain a crude product of N-long-chain acyl amino acid.

[0191] Here, the molar ratio of the amino acid and the metal inorganic base described in step (1) is 1: (1 to 1.5). The metal inorganic base is one or more selected from sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.

[0192] The volume ratio of water to the organic solvent described in step (1) is 1:(1 to 1.5). The concentration of the metal inorganic base described in step (2) is 30 to 80%.

[0193] The metal inorganic base described in step (2) is one or more selected from sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate. The amount of the metal inorganic base added is controlled so that the pH value of the reaction system is 8 to 10.

[0194] The long-chain acid chloride described in step (2) is one or more selected from octanoyl chloride, decanoyl chloride, undecanoyl chloride, lauroyl chloride, myristoyl chloride, pentadecanoyl chloride, palmitoyl chloride, stearoyl chloride, oil chloride, linoleyl chloride, isostearoyl chloride, coconut oil fatty acid chloride, and palm oil fatty acid chloride, preferably coconut oil fatty acid chloride or lauroyl chloride, and most preferably lauroyl chloride.

[0195] In one embodiment, a method for producing a supramolecular amino acid is provided, and a method for producing a composition containing the supramolecular amino acid is further provided, and the supramolecular amino acid produced by the above method has a structure and performance different from that of generally commercially available long-chain acyl amino acids.

[0196] Specifically, the crude N-long-chain acyl amino acid product (regardless of whether it contains a dipeptide) undergoes an impurity removal step according to the above embodiment, and structural reconstitution occurs during the impurity removal process to form a supramolecular amino acid having a specific structure.

[0197] The weight percentage of long-chain fatty acids in the above supramolecular amino acids is 5% or less. Considering that it is difficult to completely remove long-chain fatty acids by a mild process and is cost-disadvantageous, the weight percentage of long-chain fatty acids is preferably 4%, 3% or 2% or less, 0.1%, 0.2% or 0.5% or more, and most preferably 0.5% to 3%.

[0198] The present invention further provides a supramolecular amino acid comprising N-long chain acyl amino acid, N-long chain acyl amino acid dipeptide self-assembled supramolecular structure, the weight percentage of N-long chain acyl amino acid dipeptide is 3% or more, preferably 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14% or 15% or more.

[0199] In one embodiment, the dipeptide has a moderate content, ie, the weight percentage of N-long chain acyl amino acid dipeptides is 5% or more, preferably 8% or more, more preferably 10% or more and less than 15%.

[0200] In one embodiment, the dipeptide has a high content, ie, the weight percentage of N-long chain acyl amino acid dipeptides is 15% or more, preferably 20% or more.

[0201] The weight percentage of long-chain fatty acids in the above supramolecular amino acids is 5% or less. Considering that it is difficult to completely remove long-chain fatty acids by a mild process and is cost-disadvantageous, the weight percentage of long-chain fatty acids is preferably 4%, 3% or 2% or less, 0.1%, 0.2%, 0.5% or 1% or more, and most preferably 0.5% to 3%.

[0202] Preferably, the supramolecular amino acid of the present invention is subjected to mass spectrometry detection, and the detection conditions are mass spectrometry AB4500, mass spectrometry system Q1SCAN, ionization method ESI(-), scanning range m / z = 200 to 600, and a characteristic ion peak in the mass spectrometry spectrum in the range of 541 to 545.

[0203] Preferably, the supramolecular amino acid of the present invention is subjected to high performance liquid chromatography detection, and the detection conditions are as follows: a high performance liquid chromatograph equipped with a UV detector is used; the column is ODS-2 HYPERSIL C18 250×4.6 mm 5 μm, the wavelength is 210 nm, the mobile phase is methanol: 20 mmol / L potassium dihydrogen phosphate buffer solution at pH 3.0 = 70:30 (v / v); and the peak group includes 3 or 4 peaks in the range of retention time 30 to 45 min in the high performance liquid chromatogram.

[0204] Preferably, the morphology of the microdomains of the supramolecular amino acid solid powder is columnar, rod-like, linear, or rope-like.

[0205] Preferably, the supramolecular amino acid has an initial melting temperature detected by capillary of 75°C or higher, preferably 78°C or higher, more preferably 80°C or higher. The final melting temperature is 87°C or higher, preferably 90°C or higher, more preferably 92°C or higher. The final melting temperature of the conventional Schotten-Baumann reaction product is 77-84°C, while the final melting temperature of the supramolecular amino acid of the present invention can reach 87°C or higher, and the final melting temperature increases with increasing dipeptide content.

[0206] Preferably, the supramolecular amino acid product has a DSC peak temperature of 86° C. or higher, preferably 88° C. or higher, more preferably 90° C. or higher in a DSC analysis, and the DSC peak temperature shifts to the right with increasing dipeptide content.

[0207] Preferably, the number average molecular weight of the supramolecular amino acid sodium salt is between 5,000 and 250,000, and preferably the number average molecular weight is 6,000, 7,000, 8,000, 9,000, 10,000, 11,000, 12,000, 13,000, 14,000, 15,000, 16,000, 17,000, 18,000, 19,000, 20,000 or more and 240, 000, 230,000, 220,000, 210,000, 200,000, 190,000, 180,000, 170,000, 160,000, 150,000, 140,000, 130,000, 120,000, 110,000 or less, more preferably between 10,000 and 150,000, and most preferably between 15,000 and 100,000.

[0208] In the present invention, unless otherwise specified, the long-chain fatty acid is a saturated or unsaturated, straight-chain or branched-chain fatty acid having 8 to 22 carbon atoms. Preferred specific examples include one or more selected from caprylic acid, capric acid, undecanoic acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, isostearic acid, coconut oil fatty acid, and palm oil fatty acid, preferably coconut oil fatty acid or lauric acid, and most preferably lauric acid.

[0209] The amino acid may be one or more selected from glycine, alanine, glutamic acid, sarcosine, aspartic acid, leucine, isoleucine, valine, threonine, proline, phenylalanine, arginine, and lysine. Preferred are alanine, glycine, glutamic acid, sarcosine, arginine, and lysine, and most preferred is L-alanine in alanine. The amino acids mentioned herein also refer to crude products of long-chain acyl amino acids / amino acids derived from long-chain acyl amino acids (i.e., crude products of the long-chain acyl amino acids / amino acids for synthesizing the crude products of the long-chain acyl amino acids / long-chain acyl amino acids).

[0210] The N-long-chain acyl group in the crude N-long-chain acyl amino acid / N-long-chain acyl amino acid product is derived from a saturated or unsaturated, straight-chain or branched-chain fatty acid having 8 to 22 carbon atoms. Preferably, the N-long-chain acyl group is one or more selected from an octanoyl group, a decanoyl group, an undecanoyl group, a lauroyl group, a myristoyl group, a pentadecanoyl group, a palmitoyl group, a stearoyl group, an oleoyl group, a linoleoyl group, an isostearoyl group, a coconut oil fatty acid acyl group, and a palm oil fatty acid acyl group, preferably a coconut oil fatty acid acyl group or a lauroyl group, and most preferably a lauroyl group.

[0211] The long chain in the above-mentioned N-long-chain acyl amino acid crude product / N-long-chain acyl amino acid is the same as the long chain in the above-mentioned long-chain fatty acid.

[0212] In all embodiments, the supramolecular amino acid salt is composed of a supramolecular amino acid and a base. The base is not particularly limited, and includes inorganic bases and organic bases. Specifically, inorganic bases such as basic metals such as sodium and potassium, or basic earth metals such as magnesium and calcium, organic amines such as amines and alkanolamines, or organic bases such as basic amino acids such as lysine, arginine, and histidine are used. These bases may be used alone or in combination of two or more.

[0213] As inorganic bases, sodium hydroxide and potassium hydroxide are particularly preferred, especially sodium hydroxide. As organic bases, basic amino acids are particularly preferred, especially arginine or lysine.

[0214] The inventors unexpectedly found that when basic amino acid such as arginine is reacted with supramolecular amino acid to form salt, in practical application, foam is more dense, rich and more durable, feels soft when used, has high elasticity, and has better cleaning power.In addition, when lysine is reacted with supramolecular amino acid to form salt, it has very good solubility, high system stability, and the foam is the most stable.

[0215] The present invention further provides a supramolecular amino acid salt prepared by the above supramolecular amino acid and a basic amino acid. The basic amino acid is selected from arginine, lysine, and histidine, and preferably arginine and lysine. The supramolecular amino acid salt can be used as a cleaning agent, an emulsifier, a care composition, and a cosmetic.

[0216] The present invention further provides a supramolecular amino acid or a salt thereof prepared by the above-mentioned embodiments. The supramolecular amino acid or a salt thereof is used as a surfactant or an emulsifier.

[0217] The above-mentioned supramolecular amino acid or its salt can be used in the manufacture of detergent compositions, toothpastes, care compositions, laundry detergents, soaps, powdered laundry detergents, dishwashing detergents, masks, shampoos, shower gels, facial cleansers, makeup removers, mouthwashes, shaving supplies, hand washes, cleaning lotions, cleaning creams, etc.

[0218] Due to its special spatial structure, the above supramolecular amino acid or its salt has many uses, and can be used for adsorbing oil and dirt or bacteria. It can also be used for disinfection, deodorization, and removal of pesticide residues.

[0219] The present invention provides amino acid dishwashing detergent, amino acid laundry detergent, amino acid toothpaste, skin care composition, amino acid soap, amino acid powder laundry detergent, amino acid mask, amino acid shampoo, amino acid shower gel, amino acid face wash, and supramolecular amino acid or salt thereof including the above. Each amino acid product described in the present invention is named simply because it contains a supramolecular amino acid and / or a salt thereof, and is not particularly limited.

[0220] The present invention provides a toothpaste comprising a friction agent, a moisturizing agent, a thickening agent and a surfactant. The surfactant comprises the supramolecular amino acid and / or a salt thereof, and the surfactant is 0.1-25 wt%, the friction agent 10-50 wt%, the moisturizing agent 5-40 wt%, and the thickening agent 0.1-6 wt% based on the total weight of the toothpaste. Alternatively, the surfactant is entirely composed of the supramolecular amino acid and / or a salt thereof of the present invention, or the amino acid surfactant is entirely composed of the supramolecular amino acid and / or a salt thereof of the present invention. Preferably, 20 wt% or more, more preferably 30, 40, 50, 60, 70, 80 or 90 wt% or more, even more preferably 100 wt% of the surfactant is the supramolecular amino acid and / or a salt thereof of the present invention.

[0221] The friction agent is one or more selected from hydrated silica, calcium carbonate, and calcium hydrogen phosphate. The humectant is one or more selected from sorbitol, polyethylene glycol-400, glycerin, and propylene glycol. The thickener is one or more selected from carboxymethylcellulose, xanthan gum, carrageenan, caramel gum, poloxamer 407, and magnesium aluminum silicate.

[0222] The toothpaste further comprises weight percentages of 0.1-0.3% sweetener, 0.5-1.5% flavor, 5-10% water, 0.3-0.5% herbal extract, 0.3-0.5% preservative, and 0.05-0.15% colorant. Here, the sweetener is one or more combinations selected from sodium saccharin, xylitol, and erythritol. The herbal extract is one or more combinations selected from paprika extract, licorice extract, and purslane extract. The preservative is one or more combinations selected from sodium benzoate, hydroxybenzyl ester, trichlorohydroxyphenyl ether / copolymer, and biosoluble enzyme. The colorant is one or more combinations selected from CI77019, CI77891, CI42090, CI19140, mica, titanium dioxide, and brilliant blue. The amino acid toothpaste does not contain sodium dodecyl sulfate.

[0223] The method for producing the toothpaste includes the steps of: (1) preparing an aqueous solution of water, a sweetener, a preservative, and a humectant, and feeding the solution into a paste-making machine; (2) mixing a thickener, a friction agent, and a Chinese herbal extract, and then feeding the mixture into the paste-making machine, stirring and grinding the mixture until the paste is uniform, and then degassing the mixture in a vacuum; and (3) sequentially feeding a surfactant, a flavoring, and a coloring agent into the paste-making machine, stirring and grinding the mixture until the paste is uniform, and then degassing the mixture to obtain toothpaste.

[0224] The present invention provides a skin care composition comprising, by total weight thereof: Oil content 50~95wt%, Surfactant 0.5-30wt%, Suspended particles: 0-45wt%.

[0225] The surfactant comprises the supramolecular amino acid and / or its salt. Alternatively, the surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention, or the amino acid surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention. Preferably, 20wt% or more of the surfactant is the supramolecular amino acid and / or its salt of the present invention, more preferably 30, 40, 50, 60, 70, 80 or 90wt% or more, and even more preferably 100wt% is the supramolecular amino acid and / or its salt of the present invention.

[0226] The oil is selected from natural oils, synthetic oils, or mixtures thereof, each having a freezing point between -50°C and 6°C. The natural oils include vegetable oils and animal oils. The vegetable oils include grape seed oil, sunflower seed oil, jojoba oil, aloe oil, olive oil, linseed oil, safflower seed oil, soybean oil, almond oil, tea oil, or any mixtures thereof. The animal oils include horse oil and lanolin. The synthetic oils include isodecyl neodecanoate and neopentyl glycol diheptanoate.

[0227] The oil content is 65wt% or 85wt%.

[0228] The particle size of the suspended particles is less than 30 μm, preferably less than 15 μm, more preferably less than 5 μm.

[0229] The suspended particles are selected from oil-insoluble solid particles or oil-immiscible liquids, where the oil-insoluble solid particles include mica, starch, zinc oxide, titanium dioxide, talc powder and silicone elastomers, and the oil-immiscible liquids include glycerin, water and polyols.

[0230] A method for producing the above skin care composition includes the steps of: (1) mixing an oil, a surfactant, and suspended particles in the weight percentages of (50-95%):(0.5-30%):(0-45%), reacting them with stirring at 82-87°C, and stirring and cooling the mixture to 65-72°C after all the surfactant has dissolved in the oil; and (2) cooling the mixture obtained above to room temperature to obtain a skin care composition.

[0231] The present invention provides a laundry detergent comprising a surfactant, a softener, a chelating agent, deionized water, a preservative and a fragrance, the weight percentages of each of the materials in the laundry detergent being as follows: Surfactant 5-50%, Fabric softener 0.1-3%, Chelating agent 0.1-5%, Deionized water 50-90%, Preservatives 0.1-6%, Fragrance 0.1~2%, The surfactant comprises the supramolecular amino acid and / or its salt. Alternatively, the surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention, or the amino acid surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention. Preferably, 20wt% or more of the surfactant is the supramolecular amino acid and / or its salt of the present invention, more preferably 30, 40, 50, 60, 70, 80 or 90wt% or more, and even more preferably 100wt% is the supramolecular amino acid and / or its salt of the present invention.

[0232] The present invention provides a soap comprising a surfactant, a fatty acid, glycerin, a softening agent, a chelating agent, a filler, and deionized water, the weight percentages of each material in the soap being as follows: Surfactant 10-50%, Fatty acids 0.1~7%, Glycerin 0.1-5%, Fabric softener 0.1-6%, Chelating agent 0.1-1%, Filler 10-40%, 1-5% deionized water.

[0233] The surfactant comprises the supramolecular amino acid and / or its salt. Alternatively, the surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention, or the amino acid surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention. Preferably, 20wt% or more of the surfactant is the supramolecular amino acid and / or its salt of the present invention, more preferably 30, 40, 50, 60, 70, 80 or 90wt% or more, and even more preferably 100wt% is the supramolecular amino acid and / or its salt of the present invention.

[0234] The present invention provides a powder laundry detergent comprising a surfactant and a friction agent, the weight percentages of each substance in the amino acid powder laundry detergent being as follows: Surfactant 10-50%, Friction agent 50~90%, The surfactant comprises the supramolecular amino acid and / or its salt. Alternatively, the surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention, or the amino acid surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention. Preferably, 20wt% or more of the surfactant is the supramolecular amino acid and / or its salt of the present invention, more preferably 30, 40, 50, 60, 70, 80 or 90wt% or more, and even more preferably 100wt% is the supramolecular amino acid and / or its salt of the present invention.

[0235] The present invention provides a dishwashing detergent comprising a surfactant, deionized water, a thickener, glycerin, a preservative and a fragrance, wherein the weight percentages of each substance in the amino acid dishwashing detergent are as follows: Surfactant 5-20%, Deionized water 70-90%, Thickener 1-2%, Glycerin 5-10%, Preservatives 0.1-6%, Fragrance 0.1~2%, The surfactant comprises the supramolecular amino acid and / or its salt. Alternatively, the surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention, or the amino acid surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention. Preferably, 20wt% or more of the surfactant is the supramolecular amino acid and / or its salt of the present invention, more preferably 30, 40, 50, 60, 70, 80 or 90wt% or more, and even more preferably 100wt% is the supramolecular amino acid and / or its salt of the present invention.

[0236] The present invention provides a mask comprising a surfactant, deionized water, glycerin, a preservative and a fragrance, the weight percentages of each of the materials in the mask being as follows: Surfactant 0.1-5% Deionized water 50-90%, Glycerin 1-10%, Preservatives 0.1-2%, Fragrance 0.1~2%, The surfactant comprises the supramolecular amino acid and / or its salt. Alternatively, the surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention, or the amino acid surfactant is entirely composed of the supramolecular amino acid and / or its salt of the present invention. Preferably, 20wt% or more of the surfactant is the supramolecular amino acid and / or its salt of the present invention, more preferably 30, 40, 50, 60, 70, 80 or 90wt% or more, and even more preferably 100wt% is the supramolecular amino acid and / or its salt of the present invention.

[0237] The present invention will be further described below in conjunction with the drawings and examples, and it should be understood that these examples are merely illustrative of the present invention and do not limit the scope of the present invention. In addition, after reading the above disclosure of the present invention, those skilled in the art may make various variations and modifications to the present invention, and it should be understood that these equivalent forms are also included in the scope of the claims attached to this application. EXAMPLES

[0238] The present invention will be further described below with reference to specific examples. Production Example: Synthesis of N-lauroyl-L-alanine crude product Manufacturing Example 1 At room temperature, in a 1000L reactor, 89kg (1Kmol) of L-alanine and 40kg (1Kmol) of sodium hydroxide were dissolved in a mixture of 150L of distilled water and 150L of acetone, and stirred uniformly to obtain an L-alanine sodium solution.

[0239] Under the condition of 20°C, 175 kg (0.8 Kmol) of lauroyl chloride was gradually added dropwise to the L-alanine sodium solution, and then 50% sodium hydroxide solution was added dropwise so that the pH of the reaction system became 9. After the addition was completed, the mixture was stirred at 20°C for 1.5 hours to obtain a paste-like N-lauroyl-L-alanine salt.

[0240] Hydrochloric acid was added to the paste-like N-lauroyl-L-alanine salt to acidify it to pH=3-4, and a white solid was gradually precipitated. The mixture was then left in an ice bath for 3 hours and then filtered to obtain a crude N-lauroyl-L-alanine product.

[0241] Manufacturing Example 2 At room temperature, in a 1000L reaction vessel, 89 kg (1 Kmol) of L-alanine and 56 kg (1 Kmol) of potassium hydroxide were dissolved in a mixed solution of 150 L of distilled water and 150 L of acetone, and the solution was stirred uniformly to obtain an L-alanine potassium solution.

[0242] Under the condition of 20°C, 218.7 kg (1 Kmol) of lauroyl chloride was gradually added dropwise to the L-alanine salt solution, and 50% potassium hydroxide solution was also added dropwise so that the pH of the reaction system became 9. After the addition was completed, the mixture was stirred at 20°C for 2 hours to obtain a paste-like N-lauroyl-L-alanine salt.

[0243] Hydrochloric acid was added to the paste-like N-lauroyl-L-alanine salt to acidify it to pH=3-4, and a white solid was gradually precipitated. The mixture was then left in an ice bath for 2 hours and then filtered to obtain a crude N-lauroyl-L-alanine product.

[0244] Production Example 3 At room temperature, in a 1000L three-neck flask, 89Kg (1Kmol) of L-alanine and 106Kg (1Kmol) of sodium carbonate were dissolved in a mixed solution of 150L of distilled water and 150L of acetone, and the solution was stirred uniformly to obtain an L-alanine sodium solution.

[0245] Under the condition of 20°C, 218.7 kg (1 Kmol) of lauroyl chloride was gradually added dropwise to the L-alanine salt solution, and 30% sodium hydroxide solution was also added dropwise so that the pH of the reaction system became 8. After the addition was completed, the mixture was stirred at 20°C for 3.5 hours to obtain a paste-like N-lauroyl-L-alanine salt.

[0246] Hydrochloric acid was added to the paste-like N-lauroyl-L-alanine salt to acidify it to pH=3-4, and a white solid was gradually precipitated. The mixture was then left in an ice bath for 3 hours and then filtered to obtain a crude N-lauroyl-L-alanine product.

[0247] Example Composition / Crude Product Containing N-Lauroylalanylalanine (N-Lauroylalanine Dipeptide) Example 14# 100g of water, 79g of acetone, 60g of alanine, and 20g of plate-shaped base were added to a reaction vessel and stirred uniformly. Next, 100g of lauroyl chloride was added dropwise. The reaction temperature was controlled at 20-30°C. After the addition was completed, the pH became about 6-7. The mixture was kept warm for 20 minutes, hydrochloric acid was added dropwise to adjust the pH to 1-2, and the mixture was filtered.

[0248] Example 20# 100 g of water, 79 g of acetone, 77 g of alanine, and 20 g of plate-shaped base were added to a reaction vessel and stirred uniformly. Next, 100 g of lauroyl chloride was added dropwise and the reaction temperature was controlled at 20 to 30°C. After the addition was completed, the pH became about 6 to 7. The mixture was kept warm for 20 minutes, hydrochloric acid was added dropwise to adjust the pH to 1 to 2, and the mixture was filtered.

[0249] Example 27# 100g of water, 79g of acetone, 53g of alanine, and 20g of plate-shaped base were added to a reaction vessel and stirred uniformly. Next, 100g of lauroyl chloride was added dropwise. The reaction temperature was controlled at 20-30°C. After the addition was completed, the pH became about 6-7. The mixture was kept warm for 20 minutes, hydrochloric acid was added dropwise to adjust the pH to 1-2, and the mixture was filtered.

[0250] Example 31# 275 g of water, 216 g of acetone, 122.2 g of alanine, and 20 g of plate-shaped base were added to a reaction vessel and stirred uniformly. Then, 100 g of lauroyl chloride was added dropwise and the reaction temperature was controlled at 20 to 30°C. After the addition was completed, 10 g of plate-shaped base was added, the mixture was kept warm for 20 minutes, hydrochloric acid was added dropwise to adjust the pH to 1 to 2, and the mixture was filtered.

[0251] Example 33# 500 g of water, 390 g of acetone, 49 g of alanine, and 100 g of plate-shaped base were added to a reaction vessel and stirred uniformly. Next, 500 g of lauroyl chloride was added dropwise. The reaction temperature was controlled at 20 to 30°C. After the addition was completed, the mixture was kept warm for 20 minutes, hydrochloric acid was added dropwise to adjust the pH to 1 to 2, and the mixture was filtered.

[0252] Example 501# 100 kg of water, 140 kg of acetone, 110 kg of alanine, and 120 kg of liquid base (32%) were added to a reaction vessel and stirred uniformly. Then, 180 kg of lauroyl chloride was added dropwise and the reaction temperature was controlled at 42°C. After the addition was completed, the pH became about 5, and hydrochloric acid was added to adjust the pH to 1 to 2. Then, the mixture was filtered and washed with pure water.

[0253] Example 502# 550 kg of water, 110 kg of alanine, and 125 kg of liquid base (32%) were added to a reaction vessel and stirred uniformly. Then, 180 kg of lauroyl chloride was added dropwise. The reaction temperature was controlled at 27°C. After the addition was completed, the pH became about 5. Hydrochloric acid was further added to adjust the pH to 1-2. Then, the mixture was filtered and washed with pure water.

[0254] Example 503# 100 kg of water, 140 kg of acetone, 97 kg of alanine, and 150 kg of liquid base (32%) were added to a reaction vessel, and then 180 kg of lauroyl chloride was added dropwise. The reaction temperature was controlled at 30°C. After the addition was completed, the pH became 5-6. Hydrochloric acid was then added to adjust the pH to 1-2, and the mixture was then filtered and washed with pure water.

[0255] Example 601# 100 kg of water, 90 kg of acetone, 103 kg of alanine, and 160 kg of liquid base (32%) were added to a reaction vessel and stirred uniformly. Then, 180 kg of lauroyl chloride was added dropwise. The reaction temperature was controlled to about 25°C, and hydrochloric acid was added to adjust the pH to 1 to 2. The mixture was then filtered and washed with pure water.

[0256] Example 602# 100 kg of water, 140 kg of acetone, 103 kg of alanine, and 145 kg of liquid base (32%) were added to a reaction vessel and stirred uniformly. Next, 90 kg of lauroyl chloride was added dropwise, the reaction temperature was controlled to about 25°C, and 90 kg of lauroyl chloride and 51.5 kg of liquid base (32%) were further added. Next, hydrochloric acid was added so as to adjust the pH to 1 to 2, and then the mixture was filtered and washed with pure water.

[0257] Example 603# 100 kg of water, 140 kg of acetone, 103 kg of alanine, and 145 kg of liquid base (32%) were added to a reaction vessel and stirred uniformly. Next, 135 kg of lauroyl chloride was added dropwise. The reaction temperature was controlled to about 25°C. 45 kg of lauroyl chloride and 50 kg of liquid base (32%) were added dropwise at the same time. Next, hydrochloric acid was added so as to adjust the pH to 1 to 2, and then the mixture was filtered and washed with pure water.

[0258] Example 604# Into the reactor, add 100kg of water, 140kg of acetone, 81kg of alanine, and 150kg of liquid base (32%), and stir evenly. Then, add 90kg of acid chloride dropwise. After the addition is completed, add 90kg of lauroyl chloride and 50kg of liquid base (32%). Then, add hydrochloric acid to adjust the pH to 1-2. Control the temperature of the whole process at 20-30°C. Then, filter and wash with pure water.

[0259] [Table 1-1]

[0260] [Table 1-2] *1. Measure the pH value using pH test paper. *2. Peptide refers to lauroylalanine. *3. Dipeptide refers to lauroylalanylalanine.

[0261] Experimental results show that when the amount of sodium hydroxide is small, precipitation gradually occurs at the beginning of the reaction (e.g., 31#), and the yield decreases. When excessive sodium hydroxide is added (e.g., 33#), the pH is above 8 during the entire reaction process, which is unfavorable to the production of dipeptide. The reaction temperature is preferably below 35°C, otherwise the hydrolysis of acid chloride increases and the yield decreases (e.g., 501#). Water or a mixed solution of water and an organic solvent can be selected as the reaction solvent, and when only water is used as the reaction solvent (e.g., 502#), a high dipeptide content can still be obtained, but the yield decreases.

[0262] [Measurement of peptide and dipeptide content] The content was measured using the following "Method II. High performance liquid chromatography method," and the measurement results are shown in Table I.

[0263] Typical spectra are shown in Figure 1 (Example 33#), Figure 2 (Example 503#), and Figure 3 (Example 604#). From this, it was found that when the pH after the completion of the addition of lauroyl chloride is controlled to 8 or more (conventional process), a peak group having 1 to 2 peaks appears in the retention time range of 30 to 40 min in the high performance liquid chromatogram (Figure 1). When the pH after the completion of the addition of lauroyl chloride is controlled to 8 or less, a peak group having 3 to 4 peaks appears in the retention time range of 30 to 40 min (Figures 2 and 3).

[0264] Example: Removal of impurities and formation of specific structure supramolecular amino acids Example 1 In the reactor, the N-lauroyl-L-alanine crude product obtained in Preparation Example 1 is mixed with water, stirred uniformly, heated to increase the temperature, and the temperature of the entire system is controlled at 55°C. Then, the mixture is transferred to a filtration centrifuge (with a filtration mesh) to carry out the first solid-liquid separation. First, the mixture is centrifuged to remove the liquid component, then the injection device is opened, and hot water of 55°C is injected to treat the solid. During the treatment, the centrifuge is still in operation, that is, the mixture is centrifuged while being treated, and the total amount of hot water treated is 0.5 tons. After the hot water runs out, the centrifugation is stopped.

[0265] Water is added to the reactor, and then the solid after centrifugation is transferred to the reactor, stirred and heated to increase the temperature, and the temperature of the entire system is controlled at 65°C. Then it is transferred to a filtration centrifuge to perform a second solid-liquid separation. First, it is centrifuged to remove the liquid components, and then the injection device is opened and 65°C hot water is injected to treat the solid. During the treatment, the centrifuge is still in operation, that is, it is centrifuged while being treated, and the total amount of hot water is 0.5 tons. After the hot water runs out, the centrifugation is stopped.

[0266] Add water to the reactor, then transfer the solid to the reactor, stir and heat to raise the temperature, and control the temperature of the entire system to 65°C. Then transfer to a filtration centrifuge to carry out the third solid-liquid separation. First, centrifuge to remove the liquid components, then open the injection device and inject 65°C hot water to treat the solid. During the treatment, the centrifuge is still in operation, that is, centrifuge while treating. The total amount of hot water is 0.5 tons. After the hot water is gone, the centrifuge is stopped and dried to obtain supramolecular amino acid.

[0267] [Measurement of lauric acid content] Method 1. Ultra-high performance liquid chromatography-mass spectrometry (ACQUITY I-Class_PDA_QDa) Chromatography Equipment: ACQUITY I-Class Chromatography column: ACQUITY UPLCR BEH, C18 2.1 x 50 mm, 1.7 μm Mobile phase A: 10mM NH4FA in water, Mobile phase B: ACN Column temperature: 40°C, sample chamber temperature: 10°C, injection volume: 4μL Solution preparation: Solvent: Methanol -Lauric acid standard solution: lauric acid 1-50μg / mL, - Sample solution: 0.5 mg / mL of the supramolecular amino acid product of Example 1.

[0268] mass spectrometry Mass spectrometry system: QDa Ionization method: ESI (-), capillary voltage: 0.8 kV, cone voltage: 20 V, probe temperature: 600°C, scanning method: -SIR: lauric acid: 199.28 (exact mass: 200.18), -Full scan: 50~500.

[0269] Confirmation of lauric acid: In the ESI anion mode, a spectrum (m / z = 50-500) in full scan mode was collected and shown in Figure 4. Lauric acid parent ion m / z = 199.28, [MH]-. Rt = 1.59 min. In the subsequent quantitative analysis, m / z 199.28 was used as the parent ion, and the chromatographic peak area of ​​the SIR was obtained.

[0270] Linearity and range: Good linearity within the range of 1 to 50 μg / mL of lauric acid, R2=0.999549. The standard curve is shown in FIG.

[0271] The content of lauric acid in the sample solution of Example 1 was 0.010122 mg / mL, as determined by quantitative analysis with a standard curve using the external standard method. The relevant SIR spectrum is shown in FIG.

[0272] Method 2. Ultra-high performance liquid chromatography Equipment: Waters UPLC H-Class, Detector: PDA detector Chromatography column: Waters XBridgeR, C18 3.0 x 100 mm, 3.5 μm Mobile phase: Methanol: 0.1% H3PO4 = 80:20 Column temperature: 35°C, sample chamber temperature: not set, injection volume: 1μL Solution preparation: Solvent: Methanol Lauric acid standard solution: lauric acid 1000 to 20000 mg / L, standard curve shown in FIG.

[0273] The test results are recorded in Table II.

[0274] [Table 2]

[0275] [Lauroylalanine and lauroylalanylalanine content] Method I. Ultra-high performance liquid chromatography-UV-mass spectrometry (ACQUITY I-Class_PDA_QDa) Chromatography Equipment: ACQUITY I-Class Chromatography column: ACQUITY UPLCR BEH, C18 2.1 x 50 mm, 1.7 μm Wavelength: 210nm Mobile phase A: 0.1% FA and 5 mM NH4FA in water, Mobile phase B: ACN Column temperature: 40°C, sample chamber temperature: 10°C, injection volume: 2μL Solution preparation: Solvent: Methanol - Sample solution: 3 mg / mL of the supramolecular amino acid product of Example 1.

[0276] mass spectrometry Mass spectrometry system: QDa Ionization method: ESI(-), Capillary voltage: 0.8kV, Cone voltage: 20V, Probe temperature: 600℃, Scan method: -Full scan: 50~500 Full scan signals were collected in ESI anion mode (m / z = 50-500). At a wavelength of 210 nm, only two distinct chromatographic peaks were observed, whereas in the QDa full scan, three distinct chromatographic peaks were observed.

[0277] In the spectral integration of the PDA channel, the contents of lauroylalanylalanine (dipeptide) and lauroylalanine in the sample were 3.05% and 96.95%, respectively, as calculated by Empower, as shown in Figure 8. It should be noted that the normalized contents only considered compounds with absorption at a wavelength of 210 nm.

[0278] The spectrum integral of the QDa full scan channel is shown in Figure 9. The contents of lauroylalanylalanine (dipeptide) and lauroylalanine in the sample were 4.83% and 91.51%, respectively, according to Empower calculation. It should be noted that the normalized contents did not take into account the different ionization efficiencies of different compounds.

[0279] Method II. High-Performance Liquid Chromatography The high performance liquid chromatography method was used to recognize and identify lauroylalanine and lauroylalanylalanine using a UV detector. By comparing the retention times of lauroylalanine and lauroylalanylalanine standards, lauroylalanine and lauroylalanylalanine in the samples were recognized and quantified by the area normalization method.

[0280] Instrumentation: High-performance liquid chromatograph with UV detector; Chromatography column: ODS-2 HYPERSIL C18 250 x 4.6 mm, 5 μm, Wavelength: 210nm Mobile phase: methanol: 20 mmol / L potassium dihydrogen phosphate buffer solution (pH 3.0) = 70:30 (v / v) Column temperature: 30°C, injection volume: 2 μL.

[0281] Sample measurement: After adjusting the instrument parameters according to the chromatography conditions and stabilizing the baseline of the instrument, inject 20μL of the standard solution and the sample solution into the chromatography column, and record the chromatograms of the lauroylalanine standard solution and the sample solution. Qualify the chromatographic peaks of lauroylalanine and lauroylalanylalanine in the sample based on the retention time of the standard solution, and use the area normalization method to measure the content of the test substance according to the peak area of ​​the sample.

[0282] The test results are recorded in Table III.

[0283] [Table 3]

[0284] [DSC analysis] Equipment: Differential scanning calorimeter DSC2500, Experimental conditions: A certain amount of dry sample was weighed, a hole was made in the lid, and the sample was not tableted. Temperature range: -50℃~150℃ Heating rate: 10℃ / min.

[0285] The results of DSC analysis of the product of Example 1 are shown in FIG.

[0286] Example 2 In the reactor, the N-lauroyl-L-alanine crude product obtained in Preparation Example 2 is mixed with water, stirred uniformly, heated to increase the temperature, and the temperature of the entire system is controlled at 50°C. Then, the mixture is transferred to a filtration centrifuge (with a filtration mesh) to carry out the first solid-liquid separation. At the same time as the separation operation, the injection device is opened, and hot water of 50°C is injected to treat the solid. At the same time, the centrifuge is still in operation, that is, centrifugal separation is carried out while treating, the total amount of hot water is 0.5 tons, and the centrifugation is stopped after the hot water is gone.

[0287] The solid was transferred to the reactor, water was added to the reactor, stirred, and heated to raise the temperature, and the temperature of the entire system was controlled at 60°C. It was then transferred to a filtration centrifuge to perform a second solid-liquid separation. During centrifugation, the injection device was opened and 60°C hot water was injected to treat the solid. During treatment, the centrifuge was still in operation, that is, centrifugal separation was performed while treating. The total amount of hot water was 0.5 tons. The centrifugation was stopped after the hot water was gone.

[0288] The solid is transferred to a reactor, water is added to the reactor, stirred, heated, and the temperature of the entire system is controlled to 68°C, and then transferred to a filtration centrifuge to carry out the third solid-liquid separation. During separation, the injection device is opened, and 68°C hot water is injected to treat the solid. During treatment, the centrifuge is still in operation, that is, centrifugal separation is carried out while treating. The total amount of hot water is 0.5 tons. After the hot water is gone, the centrifugation is stopped and the product is dried to obtain supramolecular amino acid.

[0289] Example 3 According to the method of preparation example 3, obtain N-lauroyl-L-alanine crude product, add hot water therein, control the temperature of hot water to about 60°C, stir, heat and increase the temperature, control the temperature of the whole system to 60°C, then transfer to filtration type centrifuge (with filtration mesh) to carry out the first solid-liquid separation, first centrifuge to remove liquid components, then open the injection device, inject 60°C hot water to treat solids, while processing, the centrifuge is still in operation, that is, centrifuge while processing, the total amount of hot water is 0.5 tons, and centrifuge is stopped after hot water is gone.

[0290] Add water to the reactor, then transfer the solid to the reactor, stir and heat to raise the temperature, and control the temperature of the entire system to 70°C. Then transfer to a filtration centrifuge to carry out a second solid-liquid separation. First, centrifuge to remove liquid components, then open the injection device and inject 70°C hot water to treat the solid. During the treatment, the centrifuge is still in operation, that is, centrifuge while treating. The total amount of hot water is 0.5 tons. After the hot water is gone, the centrifuge is stopped and dried to obtain supramolecular amino acid.

[0291] Example 4 At room temperature, in a 1000L reactor, 89kg (1Kmol) of L-alanine and 40kg (1Kmol) of sodium hydroxide were dissolved in a mixture of 150L of distilled water and 150L of acetone, and stirred uniformly to obtain an L-alanine sodium solution.

[0292] Under the condition of 20°C, 175 kg (0.8 Kmol) of lauroyl chloride was gradually added dropwise to the L-alanine salt solution, and 50% sodium hydroxide solution was further added dropwise so that the pH of the reaction system became 9. After the addition was completed, the mixture was stirred at 20°C for 1.5 hours to obtain a paste-like N-lauroyl-L-alanine salt.

[0293] Hydrochloric acid was added to the paste-like N-lauroyl-L-alanine salt to acidify it to pH=3-4, and a white solid was gradually precipitated. The mixture was then allowed to stand in an ice bath for 3 hours.

[0294] The temperature was then raised, the temperature was controlled at 50°C, and the mixture was stirred, and then transferred to a filtering centrifuge (with filtering mesh) to carry out the first solid-liquid separation. The mixture was first centrifuged to remove the liquid components, and then the injection device was opened and 50°C hot water was injected to treat the solids. During the treatment, the centrifuge was still in operation, that is, the mixture was centrifuged while being treated, and the total amount of hot water was 0.5 tons. After the hot water ran out, the centrifugation was stopped.

[0295] Water is added to the reaction kettle, then the solid is transferred to the reaction kettle, stirred and heated to increase the temperature, and the temperature of the entire system is controlled at 60°C. Then it is transferred to a filtration centrifuge to perform a second solid-liquid separation. First, it is centrifuged to remove the liquid components, and then the injection device is opened and 60°C hot water is injected to treat the solid. During the treatment, the centrifuge is still in operation, that is, it is centrifuged while being treated, and the total amount of hot water is 0.5 tons. After the hot water runs out, the centrifugation is stopped.

[0296] Water is added to the reaction kettle, then the solid is transferred to the reaction kettle, stirred and heated to increase the temperature, and the temperature of the entire system is controlled at 65°C. Then it is transferred to a filtration centrifuge to perform the third solid-liquid separation. First, the liquid components are removed by centrifugation, and then the injection device is opened and 65°C hot water is injected to treat the solid. During the treatment, the centrifuge is still in operation, that is, the centrifuge is performed while treating, and the total amount of hot water is 0.5 tons. After the hot water runs out, the centrifuge is stopped.

[0297] Add water to the reactor, then transfer the solid to the reactor, stir and heat to raise the temperature, and control the temperature of the entire system to 65°C. Then transfer to a filtration centrifuge to carry out the fourth solid-liquid separation. During separation, open the injection device and inject 65°C hot water to treat the solid. During treatment, the centrifuge is still in operation, that is, centrifugal separation is carried out while treating. The total amount of hot water is 0.5 tons. After the hot water is gone, the centrifugation is stopped and dried to obtain supramolecular amino acid.

[0298] Example 5 A portion of the dipeptide-containing crude product obtained in Example 503# was taken, and 50°C hot water was added to control the temperature of the entire system at 50°C, and then transferred to an industrial centrifuge to carry out the first solid-liquid separation. It was first centrifuged to remove the liquid components, and then the injection device was opened and 50°C hot water was injected to treat the solids, and while the treatment was being carried out, the centrifuge was still in operation, that is, it was centrifuged while being treated.

[0299] The solids in the centrifuge were transferred to a reaction vessel, 60°C hot water was added, stirred, and the temperature of the entire system was controlled at 60°C, and then transferred to an industrial centrifuge for the second solid-liquid separation. The solids were first centrifuged to remove the liquid components, and then the injection device was opened and 60°C hot water was injected to treat the solids. During the treatment, the centrifuge was still in operation.

[0300] The solid was transferred to the reactor, 70 ° C hot water was added, stirred, and the temperature of the whole system was controlled at 70 ° C, and then transferred to an industrial centrifuge to perform the third solid-liquid separation. First, the liquid components were removed by centrifugation, and then the injection device was opened and 70 ° C hot water was injected to treat the solid. During the treatment, the centrifuge was still in operation. After the treatment hot water was gone, the centrifugation was stopped and the supramolecular amino acid was obtained.

[0301] Example 6 A portion of the dipeptide-containing crude product obtained in Example 503# was taken, and hot water at 50°C was added to control the temperature of the entire system at 50°C, and then it was transferred to an industrial centrifuge to perform the first solid-liquid separation.

[0302] The solid in the centrifuge was transferred to a reaction vessel, and hot water at 60°C was added, stirred, and the temperature of the entire system was controlled at 60°C. The solid was then transferred to an industrial centrifuge for a second solid-liquid separation.

[0303] The solid was transferred to a reaction vessel, and 70°C hot water was added, stirred, and the temperature of the entire system was controlled at 70°C. It was then transferred to an industrial centrifuge for a third solid-liquid separation. After the hot water for treatment was gone, the centrifugation was stopped, and the supramolecular amino acid was obtained by drying.

[0304] Example 7 The dipeptide-containing crude product obtained in Example 502# was treated according to a method similar to that in Example 6, where the difference was that the temperature of the first solid-liquid separation of the 502# sample was 46°C, the temperature of the second solid-liquid separation was 50°C, and the temperature of the third solid-liquid separation was 60°C.

[0305] Example 8 The dipeptide-containing crude products obtained in Examples 501#, 601-604# were treated according to a method similar to that in Example 5 or Example 6.

[0306] [Measurement of lauric acid content] It was detected by the above-mentioned Method 2 (ultra-high performance liquid chromatography method), and the test results were recorded in Table IV.

[0307] [Table 4] *All test samples were subjected to a drying process and then the lauric acid content was measured.

[0308] From the above experimental results, it was found that after the conventional sample was treated three times (three solid-liquid separations), the lauric acid content was less than 5%, and that when separation was promoted using a solvent at a constant temperature (e.g., Example 5), the removal effect of lauric acid was more excellent.

[0309] 502# The crude product has a high impurity content, so the first solid-liquid separation needs to be performed at a low temperature. After three solid-liquid separations, the lauric acid content is still above 5%. However, it is obvious that the lauric acid content decreases significantly after processing. In the subsequent steps, the number of solid-liquid separations can be increased or a constant temperature solvent can be used to promote separation, thereby controlling the lauric acid content to below 5%.

[0310] [DSC analysis] Using the same detection method as above, DSC analysis was performed on the product of Example 502#, and the results are shown in Figure 11.

[0311] For the product of Example 501#, the results of DSC analysis of the product after 1 to 3 hot water treatments (solid-liquid separation) are shown in Figures 12 to 14, respectively. For the product of Example 503#, the results of DSC analysis of the product after 1 to 3 hot water treatments (treatment method according to Example 6) are shown in Figures 15 to 17, respectively.

[0312] From the experimental results, when there was a large amount of lauric acid impurities and no treatment was performed (e.g., the product of Example 502#), the DSC had one peak (Peak temperature, the same below) at around 78°C. When treated (e.g., the products of Example 501# and Example 503#), the DSC had a peak at 86°C or higher, and as the number of treatments (number of solid-liquid separations) increased, the peak gradually shifted to the right and the peak value became larger. In contrast, the higher the dipeptide content, the higher the peak value (Peak temperature) after treatment.

[0313] [Melting point analysis] After three solid-liquid separations, the melting point test samples were taken, and the test method used was a capillary. The results were recorded in Table V.

[0314] [Table 5] * 1 The table records the temperatures of the samples from initial melting to final melting. * 2 The sample melting point of WO2019233375A1 should be 82-84°C, but the 86-88°C stated in its priority document CN108752228A (201810562220.1) is an error (deviation due to uncalibrated system temperature system), which the inventors corrected in WO2019233375A1.

[0315] The test results showed that the higher the dipeptide content, the higher the melting point value. The melting point values ​​(final melting temperature) of the high dipeptide content products of the present invention were all above 87°C.

[0316] [Morphological analysis] Figure 18 shows the morphology of the microdomains of the crude product of Example 502#. When only water was used as the solvent, the product obtained was an assembly of columnar, rod-shaped, linear or rope-shaped units. Figure 19 shows the morphology of the microdomains of the crude product of Example 501# after washing. It was found that the basic unit was rod-shaped.

[0317] [Solid-state nuclear magnetic analysis] Instrument model: Bruker AVANCE III HD WB400 solid-state nuclear magnetic resonance spectrometer.

[0318] Experimental method: carbon cross-polarization experiment. Cross-polarization contact time 1.5 ms, sampling time 25 ms, relaxation waiting time 5 s, cumulative 1024 times. The experimental sample is the product of Example 6.

[0319] In the double quantum filtered hydrogen spectrum (DQ-filtered) experiments (Figures 20a and 20b), the carboxy hydrogen signal was preserved and was highly intense, suggesting that the local motion of the corresponding group was restricted and hydrogen bonds were formed, and the broad peak at 8.6 ppm was estimated to be an ammonia peak.

[0320] 2D 1 H- 1 In the H DQ-SQ two-dimensional spectrum (FIG. 20c), the carboxy hydrogen had a strong autocorrelation peak, indicating the presence of other carboxy groups in the vicinity of the carboxy group, and it was presumed that hydrogen bonds exist between the carboxy groups.

[0321] 13 In the C CP spectrum (Fig. 20d), five peaks corresponding to three carboxyl groups and two amide structures appeared at C=O. From the peak shape, it was estimated that the aggregation state of the structural molecules in the 1:1 reaction was more regular.

[0322] 2D 13 C- 1The H FSLG-HETCOR spectrum (FIG. 20e) serves to indicate the carbon spectrum and to confirm the relationship between the amino and carboxy groups.

[0323] [Mass spectrometry] Mass spectrometry AB4500 Mass spectrometry system: Q1SCAN Ionization method: ESI(-), Scan range: m / z=200-600 Experimental sample: the product of Example 6.

[0324] From Figure 21, a characteristic ion peak is observed at 543, which indicates that two molecules of lauroylalanine are associated (the molecular weight of lauroylalanine is 271.4, and the characteristic ion peak at 543 is considered to represent two molecules of lauroylalanine associated). The research team of the present invention proposes that when lauric acid exists, it destroys the association of two molecules of lauroylalanine, and when lauric acid is removed or the content is reduced to a certain limit, the carboxyl groups of two lauroylalanines are linked by hydrogen bonds, and each has an alkane structure with 11 carbon chains at both ends, and according to the similar compatibility principle, the lipophilic ends are linked by chains, and the heads and tails are linked to form a ring, and the rings are infinitely overlapped to form a columnar molecular cluster due to hydrogen bonds and similar compatibility, and the columnar molecular clusters are infinitely overlapped to form a special spatial structure called supramolecular amino acid.

[0325] [ka]

[0326] [GPC analysis] The experimental samples were the sodium salt of the product of Example 6 and the sodium salt of the crude (before treatment) of Example 502#.

[0327] Test equipment and conditions: Pump: waters1515 Detector: waters2414 Chromatography column: PL aquagel-OH MIXED-H Mobile phase: Sodium acetate Flow rate: 0.5mL / min Standard product: PEG / PEO After weighing, an aqueous solution of sodium hydroxide was added dropwise and thoroughly stirred to obtain a sodium salt.

[0328] Test results: Sodium salt of the product of Example 6: Number average molecular weight was 28,000.

[0329] Example 502# Sodium salt of crude product (before treatment): No peaks were detected, suggesting the absence of large molecules. The reason for this result was that 502# crude product contained more than 25 wt% lauric acid.

[0330] Comparative Example 1 At room temperature, in a 1L reaction vessel, 89g (1mol) of L-alanine and 40g (1mol) of sodium hydroxide were dissolved in a mixture of 150mL of distilled water and 150mL of acetone, and stirred uniformly to obtain an L-alanine sodium solution.

[0331] Under the condition of 20°C, 175 g (0.8 mol) of lauroyl chloride was gradually added dropwise to the L-alanine salt solution, and 50% sodium hydroxide solution was added dropwise so that the pH of the reaction system became 9. After the addition was completed, the mixture was stirred at 20°C for 3 hours to obtain a paste-like N-lauroyl-L-alanine salt.

[0332] Hydrochloric acid was added to the paste-like N-lauroyl-L-alanine salt to acidify it to pH = 1 to 2, and the salt was further eluted several times with water and petroleum ether, suction filtered, and dried to obtain N-lauroyl-L-alanine as a white powdery solid.

[0333] Comparative Example 2 The synthesis was performed with reference to First report of phase selective gelation of oil from oil / water mixtures. Possible implications toward containing oil spills, Santanu Bhattacharya, Chem. Commun., 2001, 185-186. Lauroylalanine methyl ester (formula is as follows) was hydrolyzed in methanol in the presence of 1 equivalent of 1M NaOH, the temperature of hydrolysis was controlled at 5°C, and after 2 hours, it was centrifuged at low temperature and dried to obtain N-lauroyl-L-alanine.

[0334] [ka]

[0335] Applications of supramolecular amino acids For experiments on bacterial inhibition, pesticide removal, deodorization, etc., and for manufacturing methods of products such as toothpaste and laundry detergent, refer to the prior application WO2019 / 233375A1, the main difference being that the long-chain acyl amino acid is replaced with the supramolecular amino acid of the present invention.

[0336] Application example 1: Evaluation of the antibacterial effect of supramolecular amino acids a. Treatment of fruit plates 10g of N-lauroyl-L-alanine supramolecules synthesized by the method of Example 1 was added to water, and 10% aqueous sodium hydroxide solution was added to neutralize the pH to 6-7, to prepare 100mL of aqueous solution. 5mL of the original solution (i.e., the solution after neutralization with sodium hydroxide) was taken, and fruit plates inoculated with common bacteria such as Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans were immersed in the original solution, and after a certain period of time, the fruit plates were washed once with clean water, and the bacterial residues in the fruit plates were measured. The detection results are shown in Table 1.

[0337] [Table 6]

[0338] As can be seen from the above data, the N-lauroyl-L-alanine supramolecular solution synthesized by the method of the present invention has obvious inhibitory effect on Escherichia coli, Staphylococcus aureus and Candida albicans. After the original solution is acted on Escherichia coli for 2 minutes, the inhibition rate can reach 98.5%, and after 5 minutes, the inhibition rate can reach 100%. After the original solution is acted on Staphylococcus aureus for 2 minutes, the inhibition rate can reach 100%, and after 5 minutes, the inhibition rate can reach 100%.

[0339] b. Bacterial inhibition experiment The N-lauroyl-L-alanine supramolecules synthesized by the method of Example 1 were neutralized with sodium hydroxide and arginine, respectively, to prepare a 10% aqueous solution (10% LA, prepared with sterilized deionized water). After being left for one month, no microorganisms were detected in either the material neutralized with sodium hydroxide or arginine, suggesting that 10% LA itself does not produce bacteria and has a certain degree of bacterial inhibition.

[0340] Application example 2: Evaluation of pesticide removal effect by supramolecular amino acids Two portions of 100g of green and yellow vegetables (large leafy vegetables) that had been sprayed with the pesticides methylamine-phosphorus and acetomethylamine-phosphorus in advance were taken out, one portion was immersed in 1L of clean water as is, and then removed to detect the pesticide residues on the vegetable leaves, which is called "before washing." The other portion was washed with a solution prepared by the N-lauroyl-L-alanine supramolecules synthesized by the method of Example 1, which is called "after washing." The operation is as follows.

[0341] 10g of N-lauroyl-L-alanine supramolecules synthesized by the method of Example 1 was taken and added to water, and 10% aqueous sodium hydroxide solution was added to neutralize the pH to 6-7, to prepare 100mL of aqueous solution. 5mL of the original solution was taken, and 100g of another part of green and yellow vegetables (large leaf vegetables) that had been sprayed with the pesticides methylamine-phosphorus and acetomethylamine-phosphorus in advance was finely cut, immersed in the above solution for 2 minutes, and then washed with 500mL of clean water after removal, and the pesticide residues on the vegetable leaves were detected. Table 2 shows a comparison of the pesticide data residues before and after washing.

[0342] [Table 7]

[0343] From the above data, it can be seen that the N-lauroyl-L-alanine supramolecular solution used in the present invention has obvious removal effect on methylamine-phosphorus and acetomethylamine-phosphorus. After acting for 2 minutes, the removal rate of methylamine-phosphorus can reach 76.19%, and the removal rate of acetomethylamine-phosphorus can reach 86.37%, and the effect is obvious.

[0344] Application example 3: Evaluation of the effect of supramolecular amino acids in removing unpleasant flavors a. Deodorization experiment 10 g of the N-lauroyl-L-alanine supramolecules synthesized by the method of Example 1 was added to water, and 10% aqueous sodium hydroxide solution was added to neutralize the pH to 6 to 7, to prepare 100 mL of an aqueous solution. 5 mL of the original solution was taken and applied to 10 mm of cotton cloth with an unpleasant taste (smell, oily smell, bad smell, etc.). 2 The cotton cloth was immersed in the above solution for 2 minutes, then taken out, washed with water, and dried. As a result, all the unpleasant tastes on the cotton cloth were eliminated, which shows that the N-lauroyl-L-alanine supramolecule synthesized by the method of the present invention has good unpleasant taste elimination effect.

[0345] b. Deodorization experiment 10 g of N-lauroyl-L-alanine supramolecules synthesized by the method of Example 1 was taken and added to water, and 10% aqueous sodium hydroxide solution was added to neutralize the pH to 6-7, to prepare 100 mL of aqueous solution (undiluted solution). Deodorizing evaluation was performed by five experts. The specific procedure was to take a small amount of crab egg oil and apply it to the arm, after which three experts rubbed their arms with the undiluted solution (rubbed twice), and two experts rubbed their arms with clean water (rubbed twice), and each expert independently evaluated the odor remaining on the arm. If a strong crab egg oil odor remained, it was given 1 point, if it was a faint odor, it was given 2-4 points, and if there was almost no odor, it was given 5 points.

[0346] [Table 8]

[0347] Application example 4: Application of supramolecular amino acids in skin care

[0348] [Table 9-1]

[0349] [Table 9-2] *Natural oil blend contains 40% Grape Seed Oil, 37.2% Sunflower Seed Oil and 22.8% Aloe Oil.

[0350] The experiment was repeated according to the compounding method of the prior application WO2019 / 233375A1, with the main difference being that the long-chain acyl amino acid was replaced with the supramolecular amino acid of the present invention. The specific manufacturing steps according to compounding method 1 shown in Table 4 include the following: 57% natural oil mixture and 40% corn starch were added to the mixer and homogenized to first disperse the particles. Then, the particles in the oil dispersion were heated to 83-86°C. At the same time as heating, 3% N-lauroyl-L-alanine supramolecules were added to the mixer. The sample was heated and held at 73-86°C for 5-10 min. Then, it was cooled to a temperature between 65-72°C and simultaneously maintained to be mixable. Next, the sample was poured into a tank with a volume of 30 mL to obtain a skin care composition, which was then stored for evaluation. Here, the manufacturing methods of the skin care compositions of compounding methods 2-6 are all the same as compounding method 1, so the description thereof will be omitted here.

[0351] The skin care compositions obtained in the above examples are made by adding different kinds and contents of particulate matter to the raw materials.The results show that the addition of particles not only increases the viscosity of oil, but also N-lauroyl-L-alanine supramolecules can be used to stably suspend solid organic / inorganic particles or oil mixture liquids such as glycerin in thickened natural oils to obtain additional skin benefits.

[0352] For example, four oil-insoluble particles, such as starch, TiO2, mica, boron nitride particles (Caress BN02 from Kobo), and one oil-miscible liquid, such as glycerin, were used. The components of the natural oil mixtures used in formulations 1-6 were all similar, i.e., they contained 40% grape seed oil, 37.2% sunflower seed oil, and 22.8% aloe oil. The results showed that the compositions obtained by formulations 1-6 shown in Table 4 were stable at both room temperature and in a drying box at 48°C, and did not have any particle separation problems.

[0353] Application example 5: Application of supramolecular amino acids in toothpaste (1) The experiments were repeated according to the formulation methods of the prior application WO2019 / 233375A1, with the main difference being that the long-chain acyl amino acids were replaced with the supramolecular amino acids of the present invention (formulation methods 1 to 5).

[0354] (2) The supramolecular amino acid of the present invention was neutralized with arginine, and a toothpaste manufacturing experiment was conducted (Formulation Method 6).

[0355] The composition and specific content of each substance in toothpaste are shown in Table 5. N-lauroyl-L-alanine supramolecular sodium salt is prepared by reacting the N-lauroyl-L-alanine supramolecule of Example 1 with sodium hydroxide.

[0356] [Table 10]

[0357] The toothpaste was prepared by the formula method 1, and the specific steps include the following: 10g water, 37.5g sorbitol, 0.2g sodium saccharin, 2g polyethylene glycol-400, 5g glycerin, and 0.4g sodium benzoate were prepared into an aqueous solution, and then put into a paste making machine. Then, 4g carboxymethylcellulose, 35g hydrated silica, 0.2g paprika extract, 0.1g licorice extract, and 0.1g purslane extract were mixed and added to the paste making machine, and the paste was ground for 20-30min while stirring until the paste was uniform, and then vacuum degassed, and 4.4g N-lauroyl-L-alanine supramolecular sodium salt, 1g edible flavor (mint flavor type), and 0.1g CI42090 were added to the paste making machine in sequence, and the paste was ground for 10-15min while stirring until the paste was uniform, and then degassed, to obtain amino acid toothpaste. Formulations 2 to 5 used similar manufacturing methods.

[0358] The toothpaste was prepared by the blending method 6, and the specific steps include the following: 10g water, 35g sorbitol, 0.2g trichlorogalactose, 2g polyethylene glycol-400, 6g glycerin, and 0.4g sodium benzoate were mixed into an aqueous solution and then put into a paste making machine. Then, 5g carboxymethylcellulose, 35g hydrated silica, and 0.2g paprika extract were mixed and then put into a paste making machine, and the mixture was ground with stirring for 20-30min until the paste was uniform, and then vacuum degassed, and 3g N-lauroyl-L-alanine supramolecules, 2g arginine, 1g edible flavor, 0.1g CI42090, and 0.1g CI19140 were added to the paste making machine in sequence, and the mixture was ground with stirring for 10-15min until the paste was uniform, and then degassed, to obtain an amino acid toothpaste.

[0359] The amino acid toothpaste provided by the present invention is safe and all tests meet the standards. By neutralizing N-lauroyl-L-alanine supramolecules with arginine, the final toothpaste produced is milder, safer and has a better taste.

[0360] Application example 6: Cleaning power experiment of supramolecular amino acids a. Detergency evaluation Five testers applied three sets of color makeup (lipstick + eyeliner) to the arms of each tester, ensuring that the area of ​​color makeup was as large as possible and that there was no difference in the shade. Next, each tester washed the product with the aqueous solution (weighed at 1 g) shown in Table 6, and finally rinsed the product with tap water (the cleaning power was judged comprehensively based on the scores of the five testers).

[0361] [Table 11] * Cleaning power is rated as 5 is best, 1 is worst and 3 is average.

[0362] b. Application of supramolecular amino acids in laundry detergents

[0363] [Table 12]

[0364] When the laundry detergents prepared by Formulation Methods 1 and 4 were tested, JB01, JB02, and JB03 all passed (the stain removal power of the samples for JB01, JB02, and JB03 was greater than that of the standard laundry detergent for JB01, JB02, and JB03). When the laundry detergent prepared by Formulation Method 2 was tested, JB01 passed, while JB02 and JB03 did not pass. When the laundry detergent prepared by Formulation Method 3 was tested, JB01, JB02, and JB03 all failed to pass.

[0365] Application Example 7 Supramolecular amino acid neutralization test <a. Product experiment of Example 1> Test process ((1) The supramolecular amino acid of Example 1 was neutralized with arginine. (2) The supramolecular amino acid of Example 1 was neutralized with sodium hydroxide. (3) The supramolecular amino acid of Example 2 was neutralized with arginine. (4) The supramolecular amino acid of Example 2 was neutralized with sodium hydroxide.) The specific manufacturing process is as follows. Take two 500 g beakers, weigh them with an electronic balance, record the beaker weights respectively, weigh the corresponding deionized water for each process and put it into the beakers, and place a water bath pot and heat it to 75 °C - 80 °C. Measure the water temperature in the beaker with a thermometer, and after confirming that it is 75 °C - 80 °C, add the weighed supramolecular amino acid of Example 1 respectively. When starting stirring, add the weighed arginine to beaker (1) and the weighed 10% sodium hydroxide aqueous solution to beaker (2) respectively. Stir for 1 min each. Cool beakers (1) and (2) to 25 °C with running tap water. Weigh with an electronic balance, and replenish the water volatilized during the trial production of the two beakers to 100% respectively with deionized water after cooling. Measure the pH of the products (1) and (2) in the beakers, observe the appearance, and confirm the smell.

[0366] (3) and (4) were manufactured according to the above method, except that the supramolecular amino acid of Example 1 was changed to the supramolecular amino acid of Example 2.

[0367] Detergency test 1) Four sets of colored makeup were drawn on the arms of the same tester, specifically, lipstick was applied 4 times and eyeliner was applied 4 times. The area of the colored makeup was ensured to be as large as possible, and the shades were made to have no difference.

[0368] 2) Next, they were washed with the aqueous solutions (1 g weighed) of (1), (2), (3), and (4) respectively.

[0369] 3) They were rinsed with tap water. The experimental results are shown in Figure 22.

[0370] All the test results were recorded in Table 8.

[0371]

Table 13

[0372] <b. Comparative experiment of the product of Example 1 (LA-I) and the product of Example 6 (LA-II)> Arrangement of sample samples:

[0373]

Table 14

[0374] Explanation: The neutralization of 1 to 6 above is calculated in equimolar amounts. Taking 5% LA-II + NaOH as an example, it means that LA-II is neutralized with equimolar NaOH, and 5% LA-II means that the mass percentage of LA-II is 5%. Lysine neutralization method: After neutralizing lysine hydrochloride with NaOH, this aqueous solution is used to neutralize with LA. Foaming test

[0375] The foaming test was carried out with reference to step 6.2.6 of "GB / T 29679-2013 Shampoo·Cream Shampoo". The difference was that 5 g of the above sample sample (i.e., 5% LA solution after neutralization) was taken, 445 g of distilled water was added, and 50 g of hard water was further added to make the mass percentage concentration of the final test solution of supramolecular amino acid 0.05%. The test results are shown in Table 9.

[0376] [Table 15]

[0377] From the above test results, the aqueous solution after neutralization with LA-II foams easier and is relatively strong, and the foam is denser, compared to LA-I. In terms of foaming properties, the foaming properties of "lysine neutralization" are superior to those of "arginine neutralization", and both are better than "NaOH neutralization". The defoaming of "NaOH neutralization" is faster than that of "arginine neutralization", and "lysine neutralization" is relatively the strongest.

[0378] Application Example 8 Application of salt formation by supramolecular amino acids and basic amino acids in facial cleansers

[0379] [Table 16]

[0380] The experiment was repeated according to the compounding method of the prior application WO2019 / 233375A1, the main difference being that the long-chain acyl amino acid was replaced with the supramolecular amino acid of the present invention. The facial cleanser prepared by the compounding method described in Table 10 is gentle and non-irritating, and is more suitable for sensitive skin. The reason is that the salt composed of N-lauroyl-L-alanine supramolecule and arginine is a cleaning surfactant that is non-irritating to human skin, and its excellent performance ultimately leads to excellent performance of the facial cleanser.

[0381] Application Example 9: Application of supramolecular amino acids in facial cleansing foam

[0382] [Table 17]

[0383] [Table 18]

[0384] Due to the excellent detergency and foam expression of the LA-II formulation, it is possible to achieve the same effect as the LA-I formulation without adding any other surfactants or cleaning agents other than LA.

[0385] Application example 10: Efficacy evaluation test of supramolecular amino acid bath foam Evaluation method: Measurement of water content in the stratum corneum The inside of the arm was washed with bath foam, and the moisture content of the stratum corneum was measured without any application (before using the sample).Then, using the sample, the moisture content of the skin was measured before washing and 5 minutes, 15 minutes, 30 minutes, and 60 minutes after washing, and the moisture retention was evaluated using the change before and after washing as an index.Five subjects were allowed to adapt to an environment of room temperature 22°C / humidity 50%RH for more than 20 minutes before conducting the test without application.

[0386] How to use the sample: After foaming, the sample was applied to the inside of the arm for 1 minute and then washed off with water 10 times.

[0387] Equipment used: Skin moisture meter Corneometer CM 825 (Courage+Khazaka, Germany).

[0388] The formulations are recorded in Table 12, and the test results are shown in Figure 23 (average value for 5 subjects).

[0389] [Table 19] *The amount of each ingredient added is expressed as a weight percentage.

[0390] In the commercially available product blending method, TEA-cocoyl glutamate is used as an amino acid surfactant, and various moisturizers such as butylene glycol, glycerin, diglycerin, and sorbitol are further blended in, whereas the LA-I blending method and LA-II blending method of the present invention are aqueous solutions neutralized with arginine, and have excellent moisturizing performance without adding any moisturizers. The LA-II blending method is superior to commercially available products that contain added moisturizers, and the superiority of the performance of the LA-II blending method becomes more apparent over time.

[0391] Furthermore, when the LA-I formulation method was supplemented with the same amounts of butylene glycol, glycerin, diglycerin, and sorbitol as in the commercial product formulation method, a clear improvement in moisturizing performance was observed, indicating that the biological moisturizing performance of the present invention is excellent, and the performance can be further improved by further blending a moisturizing agent.

[0392] Application example 11 Qualitative application test Due to their special structure, supramolecular amino acids can bind with grease to form a "solid" / cream that does not stick to hands and can be easily removed. They also have cleaning power within the pH range of 5-14, making them very versatile.

[0393] The sodium salt of the supramolecular amino acid of Example 1 (LA-I) and the sodium salt of the supramolecular amino acid of Example 6 (LA-II) were prepared into 10% and 12% aqueous solutions, respectively, and applied to daily life such as the surface of a rice cooker, the surface of a range hood, the oil drawer of a range hood, a countertop, dishwashing, laundry washing, deodorization, and toilets.

[0394] The foam yield from the 12% LA aqueous solution was more abundant, more thorough, and had better cleaning power than the 10% LA foam.

[0395] The surface of the rice cooker, especially the buttons, was sticky, so I wiped the oily parts of the surface of the rice cooker with a wet rag or paper towel, wiped it several times, and then wiped it again with a cleaning cloth, and it became clean, non-sticky, had no unpleasant taste, and no residual bubbles.

[0396] Ordinary dishwashing cleaners are less effective on the surfaces of kitchen counters and range hoods, but when washed with 12% LA-I or LA-II, the cleaning power is excellent and the irritation to the hands is low, so there is generally no need to wash again. After adding an aqueous solution of LA-I or LA-II to the range hood drawer, the fluidity becomes high (it is easier to pour), making cleaning easier.

[0397] It washes dishes with 10% LA, produces abundant foaming, is non-sticky on hands, leaves no cleaning agent behind, rinses dishes easily, and is water-saving and environmentally friendly.

[0398] The 10% LA was used to clean the dirt on the inner walls of the toilet, which gave a great experience. After pouring in an appropriate amount, it was possible to clean and deodorize the toilet by brushing it several times with a toilet brush.

[0399] In addition, those skilled in the art should understand that some embodiments described herein include certain features included in other embodiments and do not include other features, but that combinations of features from different embodiments are within the scope of the present invention and form different embodiments. For example, in the following claims, any one of the claimed embodiments can be used in any combination.

Claims

1. A method for producing an N-long-chain acyl amino acid dipeptide and / or a salt thereof or a composition containing an N-long-chain acyl amino acid dipeptide and / or a salt thereof, wherein: It includes the step of reacting an amino acid and / or a salt thereof with a long-chain acid halide, and after the reaction, the pH value of the system is less than 8, preferably the pH value is 7.5 or less, more preferably the pH value is 7 or less, and most preferably the pH value is 5 to 6.5; or, It includes the step of reacting an amino acid and / or a salt thereof with a long-chain acid halide in the presence of a base, and throughout the reaction process, the molar ratio of the amino acid to the base is 3:1 to 1:2, preferably 2:1 to 1:1.8, more preferably 1.7:1 to 1:1.7, and most preferably 1.5:1 to 1:1.

5.

2. According to the method described in Claim 1 above, wherein when adding a long-chain acid halide to the amino acid and / or a salt thereof, it is not necessary to control the reaction solution to be maintained basic, and preferably, it is not necessary to control the pH value of the reaction solution to be maintained at 8 or above, or when adding a long-chain acid halide, it is not necessary to add a base simultaneously or control the dropping rate of the base to maintain the pH value of the system, or before and after adding the long-chain acid halide, the difference in the pH value of the system is 2 or more, preferably 3 or more, more preferably 4 or more.

3. According to the method described in Claim 1 or 2 above, wherein: (1) a production step of reacting a raw material containing an amino acid with a raw material containing a base to produce an amino acid salt solution; and (2) adding a long-chain acid halide to the amino acid salt solution obtained above, or adding a long-chain acid halide and a base to the amino acid salt solution obtained above, and further satisfying one or more of the following conditions: a. The pH value of the amino acid salt solution produced in step (1) is 7.5 to 14, preferably the pH value is 8 to 12, more preferably the pH value is 9 to 11, and after the reaction in step (2), the pH value of the system is less than 8, preferably the pH value is 7.5 or less, more preferably the pH value is 7 or less, and most preferably the pH value is 5 to 6.5; b. Throughout the reaction systems of steps (1) and (2), the molar ratio of the amino acid to the base is 3:1 to 1:2, preferably 2:1 to 1:1.8, more preferably 1.7:1 to 1:1.7, and most preferably 1.5:1 to 1:1.5; c. The pH value of the amino acid salt solution obtained in step (1) is greater than the pH value of the system after reacting the amino acid salt with the long-chain acid halide in step (2), and the difference between the two is 2 or more, preferably 3 or more, more preferably 4 or more.

4. According to the method described in claim 1 or 2 above, here, the method further includes a step of acidifying the product after reacting an amino acid and / or its salt with a long-chain acid halide to obtain a crude N-long-chain acyl amino acid product. Preferably, the pH value after acidification is 1 to 4, more preferably the pH value is 1 to 2.

5. According to the method described in claim 1 or 2 above, here, the above method satisfies one or more of the following conditions: a. The amino acid is one or more selected from glycine, alanine, glutamic acid, sarcosine, aspartic acid, leucine, isoleucine, valine, threonine, proline, phenylalanine, arginine, lysine. b. The long-chain acyl group in the long-chain acid halide is derived from a saturated or unsaturated straight-chain or branched-chain fatty acid having 8 to 22 carbon atoms. c. The base is one or more selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, ammonia.

6. A method for removing impurities from a crude product of N-long-chain acyl amino acid, here, the crude product of N-long-chain acyl amino acid and a solvent are mixed, optionally stirred, and the temperature T of the system after mixing is controlled to be not lower than the melting point of the long-chain fatty acid and not higher than the melting point of the N-long-chain acyl amino acid. The above solvent is water or an organic solvent or a mixed solution of water and an organic solvent, and after controlling the temperature of the system, a solid-liquid separation operation is included.

7. According to the method described in claim 6 above, here, the above solid-liquid separation is carried out under the action of centrifugal force or pressure. Preferably, during solid-liquid separation, a solvent at a certain temperature is used as a medium to promote separation. The solvent at the above certain temperature refers to a solvent that controls the temperature T to be not lower than the melting point of the long-chain fatty acid and not higher than the melting point of the N-long-chain acyl amino acid. The solvent is water or an organic solvent or a mixed solution of water and an organic solvent.

8. According to the method described in claim 7 above, here, there are multiple temperature stages for the temperature T of the solvent as the medium. Preferably, the temperature in the later stage is not lower than the temperature in the previous stage. Preferably, the temperature in the first stage is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 15°C, and the temperature in at least one subsequent stage is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 15°C and equal to or lower than the melting point of the N-long-chain acyl amino acid. More preferably, the temperature in the first stage is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 10°C, and the temperature in at least one subsequent stage is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 20°C and equal to or lower than the melting point of the N-long-chain acyl amino acid.

9. According to the method described in claim 6 above, here, after the first solid-liquid separation, solid-liquid separation is further performed n times (n ≥ 1), and preferably the temperature of the next solid-liquid separation is equal to or higher than the temperature of the previous solid-liquid separation. The specific steps of each solid-liquid separation are as follows: The solid obtained after the previous solid-liquid separation is mixed with the solvent, and optionally stirred. The temperature Tn of the system after mixing is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the N-long-chain acyl amino acid. Then, a solid-liquid separation operation is performed. The above solvent is water, an organic solvent, or a mixed solution of water and an organic solvent. Alternatively, the solid obtained after the previous solid-liquid separation is mixed with the solvent, and optionally stirred. The temperature Tn of the system is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the N-long-chain acyl amino acid. Then, a solid-liquid separation operation is performed. During the solid-liquid separation, separation is promoted through a solvent at a certain temperature. The above solvent at a certain temperature refers to a solvent that controls the temperature Tn to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the N-long-chain acyl amino acid. The solvent is water, an organic solvent, or a mixed solution of water and an organic solvent.

10. According to the method described in claim 9 above, here, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 15°C. In at least one of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 15°C and equal to or lower than the melting point of the N-long-chain acyl amino acid. More preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the long-chain fatty acid and equal to or lower than the melting point of the long-chain fatty acid + 10°C. In at least one of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the long-chain fatty acid + 20°C and equal to or lower than the melting point of the N-long-chain acyl amino acid.

11. According to the method described in any one of claims 6 to 10 above, here, the crude product of the N-long-chain acyl amino acid is a commercially available N-long-chain acyl amino acid. Alternatively, it is a crude product of N-long-chain acyl amino acid according to claim 4, Alternatively, it is an N-long-chain acyl amino acid with a weight percentage of long-chain fatty acid of 5% or more, Alternatively, it is a crude product of N-long-chain acyl amino acid produced by a method comprising: (1) reacting a raw material containing an amino acid with a raw material containing a base to produce an amino acid salt solution; (2) adding a long-chain acid halide and optionally a base to the amino acid salt solution obtained above to obtain an N-long-chain acyl amino acid salt; and (3) acidifying the N-long-chain acyl amino acid salt obtained above. Alternatively, it is a crude product of N-long-chain acyl amino acid produced by a method comprising reacting an amino acid and / or its salt with a long-chain acid halide in the presence of a base to obtain an N-long-chain acyl amino acid salt, acidifying the obtained N-long-chain acyl amino acid salt, gradually precipitating a solid, subjecting it to solid-liquid separation after standing, optionally washing and drying to obtain a crude product of N-long-chain acyl amino acid.

12. According to the method of claim 6, wherein the long-chain fatty acid is a saturated or unsaturated straight-chain or branched-chain fatty acid having 8 to 22 carbon atoms, the N-long-chain acyl group in the N-long-chain acyl amino acid is derived from the saturated or unsaturated straight-chain or branched-chain fatty acid having 8 to 22 carbon atoms, the amino acid in the N-long-chain acyl amino acid is one or more selected from glycine, alanine, glutamic acid, sarcosine, aspartic acid, leucine, isoleucine, valine, threonine, proline, phenylalanine, arginine, lysine, and the organic solvent is an organic solvent that is slightly soluble, hardly soluble or insoluble in the long-chain fatty acid and the N-long-chain acyl amino acid, and the slight solubility, hardly solubility or insolubility means that the solubility of the long-chain fatty acid and the N-long-chain acyl amino acid in the organic solvent at 20 °C is less than 1 g / 100 g, preferably less than 0.01 g / 100 g, more preferably less than 0.001 g / 100 g.

13. A method for separating components in a solid mixture by utilizing the difference in melting points, wherein the method comprises: (a) adding a solvent to the solid mixture; (b) after adding the solvent, controlling the temperature T of the system to be equal to or higher than the melting point of the low-melting component and lower than the melting point of the high-melting component; (c) after controlling the temperature of the system, performing a solid-liquid separation operation, wherein the solvent is a solvent that is slightly soluble, hardly soluble or insoluble in the components to be separated (i.e., the high-melting component and the low-melting component to be separated), and the slight solubility, hardly solubility or insolubility means that the solubility of the component to be separated in the solvent at 20 °C is less than 1 g / 100 g, preferably less than 0.01 g / 100 g, more preferably less than 0.001 g / 100 g, and the boiling point of the solvent is equal to or higher than the melting point of the low-melting component and the temperature T of the system is lower than the boiling point of the solvent.

14. According to the method described in claim 13 above, wherein the solid-liquid separation is performed under the action of centrifugal force or pressure, and preferably, during the solid-liquid separation, a solvent at a constant temperature is used as a medium to promote the separation, and the solvent at the constant temperature refers to the solvent that controls the temperature T to be equal to or higher than the melting point of the low-melting component and lower than the melting point of the high-melting component, and the solvent is a solvent that is slightly soluble, hardly soluble or insoluble in the components to be separated.

15. According to the method described in claim 13 above, wherein after the first solid-liquid separation, n more times (n ≥ 1) of solid-liquid separation are performed, and preferably the temperature of the next solid-liquid separation is equal to or higher than the temperature of the previous solid-liquid separation. The specific steps of each solid-liquid separation are: mixing the solid obtained after the previous solid-liquid separation with the solvent, optionally stirring, controlling the temperature Tn of the system after mixing to be equal to or higher than the melting point of the low-melting component and lower than the melting point of the high-melting component, and then performing a solid-liquid separation operation, wherein the solvent is a solvent that is slightly soluble, hardly soluble or insoluble in the components to be separated. Alternatively, mixing the solid obtained after the previous solid-liquid separation with the solvent, optionally stirring, controlling the temperature Tn of the system to be equal to or higher than the melting point of the low-melting component and lower than the melting point of the high-melting component, and then performing a solid-liquid separation operation, and during the solid-liquid separation, a solvent at a constant temperature is used as a medium to promote the separation, and the solvent at the constant temperature refers to the solvent that controls the temperature Tn to be equal to or higher than the melting point of the low-melting component and lower than the melting point of the high-melting component, and the solvent is a solvent that is slightly soluble, hardly soluble or insoluble in the components to be separated.

16. According to the method described in claim 15, here, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting component and equal to or lower than the melting point of the low-melting component + 10 °C. In at least one of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting component + 10 °C and equal to or lower than the melting point of the high-melting component. Preferably, in the first solid-liquid separation, the temperature T is controlled to be equal to or higher than the melting point of the low-melting component and equal to or lower than the melting point of the low-melting component + 10 °C. In at least one of the subsequent n solid-liquid separations, the temperature Tn is controlled to be equal to or higher than the melting point of the low-melting component + 20 °C and equal to or lower than the melting point of the high-melting component.

17. A supramolecular amino acid, here, containing an N-long-chain acyl amino acid and an N-long-chain acyl amino acid dipeptide self-assembled supramolecular structure, and the weight percentage of the N-long-chain acyl amino acid dipeptide is 3% or more, preferably 5% or more, more preferably 8% or more, and most preferably 10% or more.

18. According to the supramolecular amino acid described in claim 17, here, it is a supramolecular amino acid with a medium dipeptide content, and the weight percentage of the N-long-chain acyl amino acid dipeptide is 5% or more, preferably 10% or more and less than 15%. Or, it is a supramolecular amino acid with a high dipeptide content, and the weight percentage of the N-long-chain acyl amino acid dipeptide is 15% or more, preferably 20% or more.

19. According to the supramolecular amino acid described in claim 17 or 18, here, it satisfies one or more of the following conditions: a. Perform mass spectrometry detection on the supramolecular amino acid. As the detection conditions, mass spectrometry AB4500, mass spectrometry system Q1SCAN, ionization method ESI(-), scanning range m / z = 200 - 600, and it has an ion peak characteristic of the mass spectrometry spectrum in the range of 541 - 545. b. Perform high-performance liquid chromatography detection on the supramolecular amino acid. As the detection conditions, a high-performance liquid chromatograph equipped with a UV detector is used for the instrument. The column is ODS-2 HYPERSIL C18 250×4.6 mm 5 μm, the wavelength is 210 nm, the mobile phase is methanol: 20 mmol / L potassium dihydrogen phosphate buffer solution with pH 3.0 = 70:30 (v / v), and it is a peak group containing 3 or 4 peaks in the range of the retention time of 30 - 45 min in the chromatogram. c. The morphology of the microdomains of the supramolecular amino acid solid powder exhibits a columnar, rod-shaped, linear, or cord-like shape. d. The supramolecular amino acid has an initial melting temperature detected by a capillary of 78 °C or higher and a final melting temperature of 87 °C or higher, preferably an initial melting temperature of 80 °C or higher and a final melting temperature of 90 °C or higher. e. The DSC peak value (Peak temperature) of the supramolecular amino acid is 86 °C or higher, preferably 88 °C or higher, more preferably 90 °C or higher. f. The number average molecular weight of the sodium salt of the supramolecular amino acid is between 5,000 and 250,000, preferably between 10,000 and 150,000, and more preferably between 15,000 and 100,000.

20. According to the supramolecular amino acid described in claim 17 or 18, herein satisfying one or more of the following conditions: a. The N-long-chain acyl group in the N-long-chain acyl amino acid and N-long-chain acyl amino acid dipeptide is one or more selected from an octanoyl group, a decanoyl group, an undecanoyl group, a lauroyl group, a myristoyl group, a pentadecanoyl group, a palmitoyl group, a stearoyl group, an oleoyl group, a linoleoyl group, an isostearoyl group, a coconut oil fatty acid acyl group, and a palm oil fatty acid acyl group, preferably a coconut oil fatty acid acyl group or a lauroyl group, and most preferably a lauroyl group. b. The amino acid in the N-long-chain acyl amino acid and N-long-chain acyl amino acid dipeptide is one or more selected from glycine, alanine, glutamic acid, sarcosine, aspartic acid, leucine, isoleucine, valine, threonine, proline, phenylalanine, arginine, and lysine, preferably alanine, glycine, glutamic acid, sarcosine, arginine, or lysine, and most preferably L-alanine. c. The long-chain fatty acid is one or more selected from caprylic acid, capric acid, undecanoic acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, isostearic acid, coconut oil fatty acid, and palm oil fatty acid, preferably coconut oil fatty acid or lauric acid, and most preferably lauric acid.

Images