WO2019233377A1 - 一种新型氨基酸自组装超分子聚合物及其制备方法和应用 - Google Patents

一种新型氨基酸自组装超分子聚合物及其制备方法和应用 Download PDF

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WO2019233377A1
WO2019233377A1 PCT/CN2019/089819 CN2019089819W WO2019233377A1 WO 2019233377 A1 WO2019233377 A1 WO 2019233377A1 CN 2019089819 W CN2019089819 W CN 2019089819W WO 2019233377 A1 WO2019233377 A1 WO 2019233377A1
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alanine
lauroyl
alanyl
amino acid
salt
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PCT/CN2019/089819
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English (en)
French (fr)
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张健
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苏州欧丽特生物医药有限公司
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Priority claimed from CN201810562174.5A external-priority patent/CN108653025A/zh
Priority claimed from CN201810562200.4A external-priority patent/CN108752420B/zh
Priority claimed from CN201810562197.6A external-priority patent/CN108451783A/zh
Application filed by 苏州欧丽特生物医药有限公司 filed Critical 苏州欧丽特生物医药有限公司
Priority to JP2021517890A priority Critical patent/JP7391397B2/ja
Priority to US16/972,465 priority patent/US11540993B2/en
Priority to EP19815207.6A priority patent/EP3805249A4/en
Publication of WO2019233377A1 publication Critical patent/WO2019233377A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
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    • A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
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    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
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    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/925—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of animal origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9706—Algae
    • A61K8/9717—Rhodophycota or Rhodophyta [red algae], e.g. Porphyra
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/107—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides
    • C07K1/1072—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups
    • C07K1/1077—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length by chemical modification of precursor peptides by covalent attachment of residues or functional groups by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/06—Dipeptides
    • C07K5/06008—Dipeptides with the first amino acid being neutral
    • C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
    • C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
    • C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
    • C08G69/08—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from amino-carboxylic acids
    • C08G69/10—Alpha-amino-carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D1/00—Detergent compositions based essentially on surface-active compounds; Use of these compounds as a detergent
    • C11D1/02—Anionic compounds
    • C11D1/04—Carboxylic acids or salts thereof
    • C11D1/10—Amino carboxylic acids; Imino carboxylic acids; Fatty acid condensates thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/10—General cosmetic use
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/30—Characterized by the absence of a particular group of ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41—Particular ingredients further characterized by their size
    • A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/48—Thickener, Thickening system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/524—Preservatives

Definitions

  • the invention belongs to the technical field of amino acid-type surfactant preparation, and particularly relates to a method and application for preparing a novel amino acid self-assembling supramolecular polymer.
  • Surfactants are an indispensable component in many fields such as daily chemical industry, agriculture, and pharmaceutical industry. There are dozens of surfactants currently used in the market, but the main commonly used are sodium dodecylbenzenesulfonate (SLS), sodium lauryl alcohol polyoxyethylene ether sulfate (AES), and sodium lauryl sulfate ( K12). Since these three surfactants have been used for decades or even hundreds of years, their negative effects have gradually emerged during their use, and their impact on human safety and the environment is often reported.
  • SLS sodium dodecylbenzenesulfonate
  • AES sodium lauryl alcohol polyoxyethylene ether sulfate
  • K12 sodium lauryl sulfate
  • surfactants such as saccharide alkyl glycosides (APG), amino acid surfactants, such as lauroyl-L-glutamic acid, lauroyl glycine, lauroyl sarcosine and the like.
  • APG saccharide alkyl glycosides
  • amino acid surfactants such as lauroyl-L-glutamic acid, lauroyl glycine, lauroyl sarcosine and the like.
  • APG saccharide alkyl glycosides
  • amino acid surfactants such as lauroyl-L-glutamic acid, lauroyl glycine, lauroyl sarcosine and the like.
  • N-lauroyl-L-alanine self-assembled polymer can be formed at a certain content of lauric acid, but the previous method patent did not obtain the polymer, and the polymer effect is superior to the effect of the method patent compound. Therefore, the present invention N-lauroyl-L-alanyl-L-alanine self-assembled supramolecular polymer was prepared.
  • N-lauroyl-L-alanyl-L-alanine self-assembled supramolecular polymer is a new type of amino acid self-assembled supramolecular polymer synthesized on the basis of in-depth research on N-lauroyl-L-alanine Compounds with the basic properties of N-lauroyl-L-alanine. However, because it has an additional set of hydrogen bonds, the entire structure is more stable and difficult to split. And the addition of an L-alanine makes the entire chain longer, which is similar to the length of stearic acid.
  • N-lauroyl-L-alanyl-L-alanine itself is derived from biological materials, it has natural safety and biodegradability, so it has more applications and has huge changes to the human living environment. .
  • the self-assembled supramolecular polymer N-lauroyl-L-alanyl-L-alanine sodium salt has two groups of hydrogen bonds, and the two-dimensional planar structure formed by it has stronger structural connectivity and forms a network. The structure is not easily broken. And a single molecule adds an L-alanine, which makes the chain of the single molecule longer, which is similar to the length of sodium stearate of eighteen carbons, and thus has stronger detergency and encapsulation.
  • a novel amino acid self-assembled supramolecular polymer was synthesized on the basis of studying N-lauroyl-L-alanine. Compared with existing surfactants and even N-lauroyl-L-alanine, the compound shows more effective decontamination and bacteriostatic performance, and can be well applied in the fields of daily chemical industry, agriculture and medicine.
  • a novel amino acid self-assembling supramolecular polymer proposed in accordance with the present invention has the following structure:
  • a new type of monomer for amino acid self-assembling supramolecular polymer has the following structure:
  • R is selected from H, Na or K.
  • the invention also relates to a novel amino acid self-assembling supramolecular polymer, which is characterized in that N-lauroyl-L-alanyl-L-alanine is used as a basic unit to self-assemble into a supramolecular polymer through hydrogen bonding.
  • Weight average molecular weight data is between 50-50 million.
  • the polymer is substantially free of lauric acid, which means that lauric acid is not detectable by HPLC.
  • the invention also relates to a novel sodium salt of an amino acid self-assembling supramolecular polymer, which has the following structure:
  • n represents the number of molecules of N-lauroyl-L-alanyl-L-alanine to form a self-assembled polymer.
  • the invention also discloses a novel sodium salt of a novel amino acid self-assembling supramolecular polymer, which uses N-lauroyl-L-alanyl-L-alanine sodium as a basic unit and self-assembles into a supramolecular through hydrogen bonding. Polymers with weight average molecular weight data between 50 and 5 million.
  • a method for preparing the above-mentioned compound according to the present invention is as follows:
  • a solvent, L-alanyl-L-alanine and a catalyst were added to the crude N-lauroyl-L-alanyl-L-alanine and stirred under certain conditions, and then cooled and filtered. The obtained solid was washed After drying, N-lauroyl-L-alanyl-L-alanine self-assembled supramolecular polymer is obtained.
  • the solvent is selected from the group consisting of acetone, methanol, ethanol, acetonitrile, tetrahydrofuran, or a mixed solvent of the above-mentioned solvent and water.
  • the catalyst is selected from one or more of sulfuric acid, p-toluenesulfonic acid, and an emulsifier.
  • the stirring conditions are: a temperature of 25 ° C. to 100 ° C., a pressure of 5 kg to 50 kg, and a time of 1-3 h.
  • the method for preparing crude N-lauroyl-L-alanyl-L-alanine includes the following steps:
  • L-alanyl-L-alanine and a metal inorganic base are dissolved in a mixed solution of distilled water and an organic solvent and stirred to obtain an L-alanyl-L-alanine salt solution;
  • the metal inorganic base in the step (1) is selected from one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.
  • the organic solvent in the step (1) is selected from one or more of acetone, methanol, ethanol, acetonitrile, and tetrahydrofuran.
  • stirring conditions in the step (2) are: a temperature of 5-50 ° C, and a time of 1-3h.
  • the concentration of the genus inorganic base in the step (2) is 30-80%.
  • the metal inorganic base in the step (2) is selected from one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.
  • a method for preparing a compound as described above includes the following steps:
  • step 1 of the foregoing method according to the present invention the amount of pentan-2-one added is 80-100 mL, the amount of activated carbon added is 1-3 g, and the amount of organic solvent added is 80-100 mL.
  • the molar ratio of the N-lauroyl-L-alanine and the chlorinating reagent is (1-1.5): 5
  • the The chlorinating agent may be one or more of dichlorosulfoxide, phosphorus trichloride, triphosgene, and N-chlorosuccinimide.
  • the metal inorganic base in the step (2) is selected from one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.
  • the organic solvent in the step (2) is selected from one or more of acetone, methanol, ethanol, acetonitrile, and tetrahydrofuran.
  • stirring conditions in the step (3) are: a temperature of 5-50 ° C, and a time of 1-3h.
  • the inorganic metal base in the step (3) is selected from one or more of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.
  • the object of the present invention and its technical problems are also achieved by the following technical solutions.
  • the compound obtained according to the above-mentioned preparation method according to the present invention is used as a surfactant in applications in the field of daily chemical, agriculture, and medicine.
  • the object of the present invention and its technical problems are also achieved by the following technical solutions.
  • the compounds proposed according to the present invention are used as surfactants in the fields of daily chemical, agriculture, and medicine.
  • a supramolecular amino acid proposed according to the present invention wherein the supramolecular amino acid is obtained by hydrogen bonding between N-lauroyl-L-alanyl-L-alanine monomers obtained by the preparation method as described above. Connection formed.
  • the method for preparing a novel amino acid self-assembling supramolecular polymer according to the present invention has simple process steps, is made by condensing natural lauric acid and L-alanyl-L-alanine, and is stable under normal conditions. It is non-toxic and harmless to the human body. It enters the human body and naturally degrades into lauric acid and L-alanine quickly. The degradation products are natural products, which can be recycled, and the reaction conditions are mild, suitable for industrial production.
  • the weight percent content of lauric acid in the self-assembled supramolecular N-lauroyl-L-alanyl-L-alanine prepared according to the method of the present invention is between 0.0001% and 0.02%, and it basically does not contain
  • the content of lauric acid, that is, lauric acid has no effect on the structure and properties of N-lauroyl-L-alanyl-L-alanine, which effectively avoids the effect of lauric acid on product quality.
  • the self-assembled supramolecular N-lauroyl-L-alanyl-L-alanine obtained according to the method of the present invention has a three-dimensional network structure and has strong adsorption of organic matters such as oil stains.
  • the pH during use is 6 ⁇ 7, more suitable for human pH requirements, more than 90% exist in the form of sodium salt, the remaining part in the form of acid, coexist in two-dimensional and three-dimensional manner, endowed with strong washing ability, adsorption bacteria, pesticides, odor and other properties.
  • the self-assembled supramolecular N-lauroyl-L-alanyl-L-alanine prepared according to the method of the present invention has stable structural properties and has supramolecular properties.
  • the molecules are in solution due to various gels Factors such as hydrogen bonding, electrostatic forces, hydrophobic forces, and ⁇ - ⁇ interactions drive liquid components to rest, forming an amino acid with a three-dimensional network space structure, which has physical sterilization, odor removal, and pesticide removal.
  • Residue and other characteristics It has a good bacteriostatic rate, and it can reach 100% against E.
  • a new type of amino acid self-assembling supramolecular polymer prepared according to the method of the present invention exists in the form of numerous pillars, and there are huge gaps between the molecules, which can encapsulate organic substances such as drug molecules, pesticide residues and tiny inorganic substances. Particles.
  • N-lauroyl-L-alanyl-L-alanine can encapsulate drug molecules, slowly release the active ingredients of drugs under the action of enzymes, and play the role of a slow-release agent.
  • Applications in the field of pesticides On the other hand, N-lauroyl-L-alanyl-L-alanine can encapsulate pesticides and prevent pesticides from penetrating into the plants.
  • N-lauroyl-L-alanyl-L-alanine In the field of cosmetics, N-lauroyl-L-alanyl-L- The combination of alanine and natural oils will change the physical properties of oils and oils, which are close to the oils secreted by the human body and have a good experience. N-lauroyl-L-alanyl-L-alanine can wrap the active ingredients of cosmetics, so that the active ingredients are not easily oxidized and inactivated, and the particles are evenly dispersed and suspended in the cosmetic system.
  • FIG. 1 is a structure of a monomer of a compound of the present invention.
  • Example 2a is a chemical reaction formula for preparing crude N-lauroyl-L-alanyl-L-alanine according to the synthesis method in Example 1 of the present invention
  • 2b is a chemical reaction formula of a crude N-lauroyl-L-alanyl-L-alanine according to the synthesis method in Example 4 of the present invention
  • 2c is a chemical reaction formula of a crude N-lauroyl-L-alanyl-L-alanine according to the synthesis method in Example 5 of the present invention
  • 2d is a chemical reaction formula for preparing a crude N-lauroyl-L-alanyl-L-alanine according to the synthesis method in Example 7 of the present invention.
  • FIG. 3 is a nuclear magnetic spectrum of an N-lauroyl-L-alanyl-L-alanine self-assembled supramolecular polymer obtained according to the synthesis method in Example 1 of the present invention; where ppm is one million molecules A unit of chemical shift.
  • 4a is a structure formation diagram of an N-lauroyl-L-alanyl-L-alanine monomer formed by a synthesis method according to Example 1 of the present invention to form a supramolecular amino acid;
  • FIG. 4b is a structure formation diagram of the N-lauroyl-L-alanyl-L-alanine monomer formed by the synthesis method in Example 1 of the present invention to form a supramolecular amino acid.
  • 5a is an 10,000-times electron microscope image of N-lauroyl-L-alanyl-L-alanine obtained according to the synthesis method in Example 1 of the present invention
  • 5b is an 20,000-times electron microscope image of N-lauroyl-L-alanyl-L-alanine obtained according to the synthesis method in Example 1 of the present invention
  • 5c is an 50,000-times electron microscope image of N-lauroyl-L-alanyl-L-alanine obtained according to the synthesis method in Example 1 of the present invention.
  • FIG. 6 is a diagram illustrating the formation process of N-lauroyl-L-alanyl-L-alanine further forming a supramolecular amino acid sodium salt obtained according to the synthesis method in Example 1 of the present invention.
  • Example 7 is a mass spectrum of an N-lauroyl-L-alanyl-L-alanine self-assembled supramolecular polymer obtained according to the synthesis method in Example 1 of the present invention.
  • ACQ method ACQ method
  • the inventors found that the polymer formed by the self-assembly of N-lauroyl-L-alanyl-L-alanine monomers through hydrogen bonding can be substantially free or non-existent through specific methods. Contains lauric acid, and can form an elastic void-containing structure, which can cure oily substances; when the polymer forms a salt with a base, the polymer salt can also be used as a surfactant. Based on this, the present invention has been completed.
  • the polymer or a salt thereof provided by the present invention is substantially free or free of lauric acid
  • lauric acid refers to, for example, the use of a high-performance liquid chromatography (equipped with a UV detector; a column: ODS-2HYPERSIL C18250 * 4.6mm 5 ⁇ m) ; Mobile phase vacuum filtration and degassing device and 0.45 ⁇ m organic filter membrane) lauric acid is not detected, that is, the content of lauric acid does not affect the properties and structure of N-lauroyl-L-alanyl-L-alanine. Or it means that the molecular ion peak characteristics of lauric acid cannot be detected in the obtained mass spectrum by mass spectrometry.
  • the mass spectrum shown in FIG. 7 is obtained by an Agilent 1200/6220 LC / MS.
  • the N-lauroyl-L-alanyl-L-alanine salt involved in the present invention is N-lauroyl-L-alanyl-L-alanine and / or N-lauroyl-L- Alanyl-L-alanine potassium. It may also be a salt formed of N-lauroyl-L-alanine with a basic amino acid, such as a salt formed with arginine, histidine, lysine, and the like.
  • the invention provides an amino acid self-assembling supramolecular polymer or a salt thereof, the polymer is formed by hydrogen bonding between N-lauroyl-L-alanyl-L-alanine monomers; the polymerization
  • the substance is substantially free or free of lauric acid.
  • N-lauroyl-L-alanyl-L-alanine monomer or a salt thereof is a compound having the following structure:
  • R is selected from H, Na or K.
  • N-lauroyl-L-alanyl-L-alanine monomers are connected through hydrogen bonding to form a structure as shown in formula (I):
  • the weight average molecular weight of the amino acid self-assembling supramolecular polymer provided by the present invention is between 50-50 million, and its melting point is 148-150 ° C.
  • the present invention also provides a salt of the above-mentioned amino acid self-assembling supramolecular polymer, the salt formed by the polymer and a base; the base includes an inorganic base and an organic base.
  • the inorganic base is selected from sodium hydroxide, potassium hydroxide, or lithium hydroxide.
  • the organic base is a natural basic amino acid (arginine, lysine or histidine).
  • an amino acid self-assembling supramolecular polymer sodium salt is provided, which is a hydrogen bond between N-lauroyl-L-alanyl-L-alanine monomers. A connection is formed; the polymer sodium salt is substantially free or free of lauric acid.
  • N-lauroyl-L-alanyl-L-alanine monomers are connected through hydrogen bonding to form a structure as shown in formula (II):
  • n 8-20000; n N-lauroyl-L-alanyl-L-alanine sodiums are sequentially connected through hydrogen bonding in the same plane, or n N-lauroyl-L-alanine sodium They are connected in sequence by hydrogen bonds and end-to-end by hydrogen bonds to form a columnar shape.
  • the weight average molecular weight of the sodium salt of the amino acid self-assembled supramolecular polymer provided is between 50-50 million.
  • the present invention also provides a composition containing the amino acid self-assembling supramolecular polymer or a salt thereof provided by the present invention, and N-lauroyl-L-alanine monoamine without or with lauric acid.
  • the polymer or salt thereof formed by hydrogen bonding between the monomers based on the total weight of the composition, wherein the polymer or salt thereof formed by hydrogen bonding between N-lauroyl-L-alanine monomers
  • the weight percentage is between 0-60%.
  • N-lauroyl-L-alanine monomers are connected through hydrogen bonding to form a structure as shown in formula (I '):
  • the maximum solubility of the sodium salt of the polymer is 15w / v%, which is determined by the solubility method ("Chinese Pharmacopoeia” (2015 edition). ), That is, a maximum of 15 grams of self-assembled polymerized sodium N-lauroyl-L-alanine dissolved per 100 ml of water at 25 ° C and 1 atmosphere.
  • N-lauroyl-L-alanine monomers can also be connected by hydrogen bonding to form a structure as shown in formula (II '):
  • n is the number of molecules of N-lauroyl-L-alanine forming a self-assembled supramolecular polymer
  • n N-lauroyl-L-alanine sodiums are sequentially connected in the same plane through hydrogen bonding, or n N-lauroyl-L-alanine sodiums are connected sequentially through hydrogen bonding and end-to-end hydrogen bonding is used to form a Columnar.
  • the weight average molecular weight of the polymer sodium salt as shown in formula II ′ is between 28 and 770,000; from this, it can be inferred that the n ranges from 10 to 3000, and the solubility of the obtained sodium salt in water does not exceed 15 g / 100ml.
  • the invention provides a method for preparing an amino acid self-assembling supramolecular polymer.
  • the method includes the following steps:
  • L-alanyl-L-alanine and a metal inorganic base are dissolved in a mixed solution of distilled water and an organic solvent and stirred to obtain an L-alanyl-L-alanine salt solution;
  • lauryl chloride and a metal inorganic base are sequentially added to the L-alanyl-L-alanine salt solution obtained above so that the pH of the reaction system is 8-10, and then the stirring is continued under certain conditions to obtain a paste.
  • N-lauroyl-L-alanyl-L-alanine salt N-lauroyl-L-alanyl-L-alanine salt
  • a solvent, L-alanyl-L-alanine and a catalyst are added to the crude N-lauroyl-L-alanyl-L-alanine obtained above, and stirred under certain conditions.
  • the amino acid self-assembling supramolecular polymer provided by the present invention is obtained.
  • the volume ratio of the distilled water and the organic solvent in the first step is 1: (1-1.5).
  • the molar ratio of L-alanyl-L-alanine to the metal inorganic base in the first step is 1: (1-1.5).
  • the metal inorganic base in the first step is selected from one or two or more of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.
  • the organic solvent in the first step is selected from one or two or more of acetone, methanol, ethanol, acetonitrile, and tetrahydrofuran.
  • the molar ratio of lauroyl chloride to L-alanyl-L-alanine in the second step is (0.8-1): 1.
  • the stirring conditions in the second step are: a temperature of 5-50 ° C, and a time of 1-3 hours.
  • the concentration of the metal inorganic base in the second step is 30-80%; the metal inorganic base is selected from one of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate. One or two or more.
  • the second step is to add N-lauroyl-L-propyl to the L-alanyl-L-alanine salt solution obtained in the first step at 5-50 ° C.
  • the N-lauroyl-L-alanyl chloride in acetone solution is a mixture of N-lauroyl-L-alanine and dichlorosulfoxide for 1-3 hours, and then The excess dichlorosulfoxide was distilled off, and after cooling, pentan-2-one and activated carbon were added, followed by decolorizing filtration and distillation under reduced pressure. The remaining dichlorosulfoxide was taken away, and water acetone was continuously added to dissolve N-lauroyl-L- Acyl chloride in alanine to give N-lauroyl-L-alanyl chloride in acetone.
  • the molar ratio of N-lauroyl-L-alanine and dichlorosulfoxide is (1-1.5): 5.
  • the obtained N-lauroyl-L-alanyl-L-alanine methyl ester and a metal inorganic base are dissolved in a mixed solution of distilled water and an organic solvent to react. After 4-8 hours, the excess organic solvent was distilled off after the reaction was completed to obtain a paste of N-lauroyl-L-alanyl-L-alanine.
  • the molar ratio of the N-lauroyl-L-alanyl-L-alanine methyl ester to the inorganic base of the metal is 1: (1-1.5);
  • the inorganic base is selected from one or two or more kinds of sodium hydroxide, potassium hydroxide, sodium carbonate, and potassium carbonate.
  • the volume ratio of the distilled water and the organic solvent is 1: (3-7); the organic solvent is selected from one or two or more of acetone, methanol, ethanol, and acetonitrile.
  • the N-lauroyl-L-alanyl-L-alanine methyl ester is a mixture of L-alanine methyl ester hydrochloride and a water-soluble organic base (selected from One or more of triethylamine, pyridine, triethanolamine) and N-lauroyl-L-alanyl chloride are dissolved in acetone and reacted under certain conditions (reaction at 0-5 ° C for 3-7 hours) , And then raised to room temperature to continue the reaction for 4-6 hours. After the reaction, the excess acetone was distilled off to obtain the N-lauroyl-L-alanyl chloride.
  • a water-soluble organic base selected from One or more of triethylamine, pyridine, triethanolamine
  • the hydrochloric acid concentration in the third step is 5-15%.
  • the solvent in the fourth step is selected from the group consisting of acetone, methanol, ethanol, acetonitrile, tetrahydrofuran, or a mixed solvent made of the solvent and water.
  • the catalyst in the fourth step is selected from one or two or more of sulfuric acid, p-toluenesulfonic acid, and an emulsifier.
  • the N-lauroyl-L-alanyl-L-alanine crude product, solvent, L-alanyl-L-alanine, catalyst described in the fourth step above The mixed molar ratio is 1: (5-10) :( 0.1-0.2) :( 0.001-0.1).
  • the stirring conditions described in the fourth step are: a temperature of 25 ° C. to 100 ° C., a pressure of 5 kg to 50 kg, and a time of 1-3 hours.
  • the fourth step is cooled and filtered after stirring, and the obtained solid is washed and dried to obtain N-lauroyl-L-alanyl-L-propyl which is substantially free of lauric acid. Self-assembling polymer.
  • the amino acid self-assembling supramolecular polymer or a salt thereof provided by the present invention can be widely used in the daily chemical field, agriculture, or the pharmaceutical industry, such as, but not limited to, used in the preparation of toothpaste, skin care composition, laundry liquid, soap, laundry Powder, dishwashing liquid, facial mask, etc.
  • a crude solvent of N-lauroyl-L-alanyl-L-alanine was added with a mixed solvent of water and acetone, L-alanyl-L-alanine and p-toluenesulfonic acid, of which N-lauroyl -L-alanyl-L-alanine crude, a mixed solvent of water and acetone, L-alanine, p-toluenesulfonic acid is added in a molar ratio of 1: 7.5: 0.2: 0.002 and the temperature is 60 ° C Stir for 2h under the pressure of 27kg, so that a small amount of lauric acid is completely consumed, and then cooled and filtered.
  • the obtained solid is washed twice with pure water and finally dried at 100 ° C to obtain N-lauroyl-L- Alanyl-L-alanine self-assembling polymer.
  • FIG. 3 shows the obtained NMR spectrum of N-lauroyl-L-alanyl-L-alanine.
  • FIG. 7 is a mass spectrum of the obtained N-lauroyl-L-alanyl-L-alanine.
  • a crude solvent of N-lauroyl-L-alanyl-L-alanine was added with a mixed solvent of water and acetone, L-alanyl-L-alanine and p-toluenesulfonic acid, of which N-lauroyl -L-alanyl-L-alanine crude, a mixed solvent of water and acetone, L-alanine, p-toluenesulfonic acid is added in a molar ratio of 1: 10: 0.2: 0.002 and the temperature is 25 ° C Stir at a pressure of 50 kg for 3 hours, so that a small amount of lauric acid is completely consumed, and then cooled and filtered. The obtained solid is washed twice with pure water and finally dried at 70 ° C to obtain N-lauroyl-L- Alanyl-L-alanine self-assembling polymer.
  • the mass of the obtained N-lauroyl-L-alanyl-L-alanine self-assembled polymer was 32.35 g, the yield was 94.72%, and the melting point was 148-150 ° C.
  • N-lauroyl-L-alanyl-L-alanine a mixed solvent of water and ethanol, L-alanyl-L-alanine and p-toluenesulfonic acid are added, of which N-lauroyl -L-alanyl-L-alanine crude, mixed solvent of water and ethanol, L-alanyl-L-alanine, p-toluenesulfonic acid is added in a molar ratio of 1: 5: 0.2: 0.001
  • the mixture was stirred for 1 h at a temperature of 100 ° C and a pressure of 5 kg, so that a small amount of lauric acid was completely consumed, and then cooled and filtered.
  • the obtained solid was washed twice with pure water and finally dried at 130 ° C to obtain N. -Lauryl-L-alanyl-L-alanine self-assembling polymer.
  • the mass of the obtained N-lauroyl-L-alanyl-L-alanine self-assembled polymer was 29.15 g, the yield was 85.35%, the content of lauric acid could not be detected, and the melting point was 148-150 ° C.
  • a crude solvent of N-lauroyl-L-alanyl-L-alanine was added with a mixed solvent of water and acetone, L-alanyl-L-alanine and p-toluenesulfonic acid, of which N-lauroyl -L-alanyl-L-alanine crude, a mixed solvent of water and acetone, L-alanine, p-toluenesulfonic acid is added in a molar ratio of 1: 10: 0.2: 0.002 and the temperature is 25 ° C Stir at a pressure of 50 kg for 3 hours, so that a small amount of lauric acid is completely consumed, and then cooled and filtered. The obtained solid is washed twice with pure water and finally dried at 70 ° C to obtain N-lauroyl-L- Alanyl-L-alanine self-assembling polymer.
  • the mass of the obtained N-lauroyl-L-alanyl-L-alanine self-assembled polymer was 31.1 g, the yield was 90.7%, the lauric acid content could not be detected, and the melting point was 148-150 ° C.
  • a crude solvent of N-lauroyl-L-alanyl-L-alanine was added with a mixed solvent of water and acetone, L-alanyl-L-alanine and p-toluenesulfonic acid, of which N-lauroyl -L-alanyl-L-alanine crude, a mixed solvent of water and acetone, L-alanine, p-toluenesulfonic acid is added in a molar ratio of 1: 10: 0.2: 0.002 and the temperature is 25 ° C Stir at a pressure of 50 kg for 3 hours, so that a small amount of lauric acid is completely consumed, and then cooled and filtered. The obtained solid is washed twice with pure water and finally dried at 70 ° C to obtain N-lauroyl-L- Alanyl-L-alanine self-assembling polymer.
  • the mass of the obtained N-lauroyl-L-alanyl-L-alanine self-assembled polymer was 31.6 g, the yield was 92.3%, the lauric acid content could not be detected, and the melting point was 148-150 ° C.
  • a crude solvent of N-lauroyl-L-alanyl-L-alanine was added with a mixed solvent of water and acetone, L-alanyl-L-alanine and p-toluenesulfonic acid, of which N-lauroyl -L-alanyl-L-alanine crude, a mixed solvent of water and acetone, L-alanine, p-toluenesulfonic acid is added in a molar ratio of 1: 10: 0.2: 0.002 and the temperature is 25 ° C Stir at a pressure of 50 kg for 3 hours, so that a small amount of lauric acid is completely consumed, and then cooled and filtered. The obtained solid is washed twice with pure water and finally dried at 70 ° C to obtain N-lauroyl-L- Alanyl-L-alanine self-assembling polymer.
  • the mass of the obtained N-lauroyl-L-alanyl-L-alanine self-assembled polymer was 29.95 g, the yield was 87.72%, the content of lauric acid could not be detected, and the melting point was 148-150 ° C.
  • a crude solvent of N-lauroyl-L-alanyl-L-alanine was added with a mixed solvent of water and acetone, L-alanyl-L-alanine and p-toluenesulfonic acid, of which N-lauroyl -L-alanyl-L-alanine crude, a mixed solvent of water and acetone, L-alanine, p-toluenesulfonic acid is added in a molar ratio of 1: 10: 0.2: 0.002 and the temperature is 25 ° C Stir at a pressure of 50 kg for 3 hours, so that a small amount of lauric acid is completely consumed, and then cooled and filtered. The obtained solid is washed twice with pure water and finally dried at 70 ° C to obtain N-lauroyl-L- Alanyl-L-alanine self-assembling polymer.
  • the mass of the obtained N-lauroyl-L-alanyl-L-alanine self-assembled polymer was 31.9 g, the yield was 93.4%, the lauric acid content could not be detected, and the melting point was 148-150 ° C.
  • a crude solvent of N-lauroyl-L-alanyl-L-alanine was added with a mixed solvent of water and acetone, L-alanyl-L-alanine and p-toluenesulfonic acid, of which N-lauroyl -L-alanyl-L-alanine crude, a mixed solvent of water and acetone, L-alanine, p-toluenesulfonic acid is added in a molar ratio of 1: 10: 0.2: 0.002 and the temperature is 25 ° C Stir at a pressure of 50 kg for 3 hours, so that a small amount of lauric acid is completely consumed, and then cooled and filtered. The obtained solid is washed twice with pure water and finally dried at 70 ° C to obtain N-lauroyl-L- Alanyl-L-alanine self-assembling polymer.
  • the mass of the obtained N-lauroyl-L-alanyl-L-alanine self-assembled polymer was 32.4 g, the yield was 94.9%, the lauric acid content could not be detected, and the melting point was 148-150 ° C.
  • a crude solvent of N-lauroyl-L-alanyl-L-alanine was added with a mixed solvent of water and acetone, L-alanyl-L-alanine and p-toluenesulfonic acid, of which N-lauroyl -L-alanyl-L-alanine crude, a mixed solvent of water and acetone, L-alanine, p-toluenesulfonic acid is added in a molar ratio of 1: 10: 0.2: 0.002 and the temperature is 25 ° C Stir at a pressure of 50 kg for 3 hours, so that a small amount of lauric acid is completely consumed, and then cooled and filtered. The obtained solid is washed twice with pure water and finally dried at 70 ° C to obtain N-lauroyl-L- Alanyl-L-alanine self-assembling polymer.
  • the mass of the obtained N-lauroyl-L-alanyl-L-alanine self-assembled polymer was 30.9 g, the yield was 90.5%, the content of lauric acid could not be detected, and the melting point was 148-150 ° C.
  • FIG. 4a is a structure formation diagram of an amino acid self-assembling supramolecular polymer N-lauroyl-L-alanyl-L-alanine monomer forming a supramolecular amino acid obtained according to the synthesis method in Example 1 of the present invention
  • FIG. 4b is a structure formation diagram of the N-lauroyl-L-alanyl-L-alanine monomer formed by the synthesis method in Example 1 of the present invention to form a supramolecular amino acid.
  • the N-lauroyl-L-alanyl-L-alanine produced by this process basically does not contain the impurity lauric acid.
  • the N-lauroyl synthesized in the process -L-alanyl-L-alanine can form three groups of hydrogen bonds, with an alkane structure of eleven carbon chains at each end.
  • the lipophilic end and the lipophilic end are chain-like, End to end are connected to form a circle.
  • the hydrogen bonds and oil and oil are miscible with each other to form a columnar molecular cluster.
  • the columnar molecular clusters are stacked indefinitely to form a special spatial structure-called supramolecular amino acids.
  • the columnar molecular clusters are infinitely superimposed to form a special spatial structure. Due to the existence of two or more configurations, there will be a certain angle deviation during superposition, and branch chains will be formed during superposition.
  • 5a, 5b, and 5c respectively show the N-lauroyl-L-alanyl-L-alanine self-assembled polymer obtained by the synthesis method in Example 1 of the present invention at 10,000 times, 20,000 times, and 50000 times electron micrograph. As shown in Figures 5a, 5b, and 5c, the formation principle and structure of N-lauroyl-L-alanyl-L-alanine monomers to form supramolecular amino acids are better proved.
  • the supramolecular amino acid further reacts with sodium hydroxide to form a sodium salt structure of the supramolecular amino acid as shown in FIG. 6.
  • the sodium salt structure is hydrophilic on one side and lipophilic on the other.
  • the molecules are connected by hydrogen bonding to obtain a special two-dimensional network regular arrangement. Because the carbon chain length is similar to stearic acid, it has a very Strong ability to combine with oil, can be used as a main surfactant.
  • the present invention used N-caproyl-L-alanyl-L-alanine to conduct structural research under the same conditions.
  • the above three-dimensional network structure was not found, and it is speculated that it may be N-caproyl-L -The length of the carbon chain of alanyl-L-alanine is short, and the loop between the lipophilic ends of the two molecules cannot be formed.
  • the carbon chain of the lipophilic group is between 12-18, and Fatty acyl-L-alanyl-L-alanine formed by L-alanyl-L-alanine can also be formed by intermolecular hydrogen bonding and oil-oil compatibility under the condition of removing fatty acids.
  • the above spatial structure Once this structure is very stable, experiments have shown that adding a small amount of fatty acid below 10% will not destroy the stability and performance of the existing structure.
  • the N-lauroyl-L-alanyl-L-alanine self-assembled polymer solution synthesized according to the method of the present invention has obvious effects on E. coli, Staphylococcus aureus and Candida albicans.
  • the inhibitory effect was 100% after N-lauroyl-L-alanyl-L-alanine solution was applied to E.coli for 2 minutes, and the original solution was treated with S. aureus for 2 minutes. 100% inhibition rate can be achieved; the inhibition rate can also reach 100% for 3 minutes on Candida albicans; the original solution can also reach 100% for 2 minutes on P. aeruginosa.
  • Example 1 the difference between Example 1 and Comparative Example 1 lies only in the replacement of the N-lauroyl-L-alanyl-L-alanine self-assembled polymer with the N-lauroyl-L-alanine self-assembled polymer. All other conditions remained the same as in Example 1.
  • N-lauroyl-L-alanyl-L-alanine self-assembling polymer of the present invention has a bacteriostatic effect than N-lauroyl-L-alanine
  • the advantages of assembly polymers are more obvious.
  • the N-lauroyl-L-alanyl-L-alanine self-assembled polymer of the present invention has an unexpected inhibitory effect on bacteriostasis.
  • the size of bacteria is usually 0.5 to 5 ⁇ m, and the lauric acid-free N-lauroyl-L-alanyl-L-alanine self-assembled polymer is used in the present invention.
  • the space between the pillars of the structure and the pillars is also micron, so it can remove the bacterial package, so it can be said to produce nano-scale foam micropores.
  • the surface-active substance N-lauroyl-L-alanyl-L-alanine self-assembled polymer solution used in the present invention has a significant removal effect on methamidophos and acephate After 2 minutes, the removal rate of methamidophos can reach 90.6%; the removal rate of paramethion can reach 93.2%, and the effect is obvious.
  • Example 2 the difference between Comparative Example 2 and Example 2 is only that the N-lauroyl-L-alanyl-L-alanine self-assembled polymer is replaced with the N-lauroyl-L-alanine self-assembled polymer.
  • other conditions were kept the same as in Example 2.
  • N-lauroyl-L-alanyl-L-alanine self-assembled polymer of the present invention has a better effect on pesticide removal than N-lauroyl-L-alanine
  • the advantages of acid self-assembling polymers are more obvious.
  • the method for preparing the self-assembled supramolecular polymer N-lauroyl-L-alanyl-L-alanine of the present invention has simple process steps, mild reaction conditions, and is suitable for industrial production.
  • the self-assembled supramolecular polymer N-lauroyl-L-alanyl-L-alanine prepared according to the method of the present invention has high purity, and the lauric acid content cannot be detected by HPLC, which effectively prevents lauric acid from affecting product quality. Impact.
  • the obtained N-lauroyl-L-alanyl-L-alanine has stable structural properties; has a good bacteriostatic rate, and is effective against Escherichia coli, Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa.
  • the inhibition rate can reach 100%; it can effectively remove pesticide residues, the removal rate of methamidophos can reach 90.6%, and the removal rate of paramethion phosphate can reach 93.2%; meanwhile, it has good deodorizing performance,
  • the fields, agriculture, and pharmaceutical industries can all have very good applications.
  • the total weight parts of the amino acid toothpaste paste in the examples are all 100.
  • the composition and specific content of each substance in the toothpaste are shown in Table 5:
  • the total weight parts of the amino acid toothpaste paste in the examples are all 100.
  • the composition and specific content of each substance in the toothpaste are shown in Table 6:
  • the specific steps include: putting 10 g of water, 37.5 g of sorbitol, 0.2 g of sodium saccharin, 2 g of polyethylene glycol-400, 5 g of glycerol, and 0.4 g of sodium benzoate into an aqueous solution. Paste machine.
  • Examples 5-13 were all prepared by the method described in Example 4, and will not be described in detail in the examples.
  • the amino acid toothpaste prepared according to the formula in Example 4-13 different weight parts of amino acid surfactants were used, and repeated formulation tests were repeated. 100 volunteers with frequent toothache and gum bleeding were entrusted to evaluate the effect. The use frequency is once a day in the morning and one in the evening, and the dosage is about 1g of paste / each time, each brushing time is about 5min. The obtained results show that toothpaste containing amino acid surface active ingredients has obvious analgesic, anti-inflammatory and anti-gingival bleeding effects. From the two aspects of taste and deodorization, the weight ratio of amino acid surface active ingredients to the toothpaste paste is 0.1. -25% is more suitable, the optimization is 0.5-10%, and the best optimization is 1-5%.
  • the amino acid surface active ingredient accounts for 1-5% by weight of the drug toothpaste paste
  • the toothpaste's efficacy and taste are in the best balance, and the oral odor is removed to the best level.
  • eating fruits immediately after brushing does not affect the consumption.
  • the taste of fruit does not feel bitter and dry.
  • Natural oil blend contains 40% grape seed oil, 37.2% sunflower seed oil and 22.8% aloe oil.
  • the specific preparation steps according to Formula 1 shown in Table 7 include: adding 57% natural oil mixture and 40% corn starch to a mixer and homogenizing to disperse the particles first.
  • the particles in the oil dispersion were then heated to 83-86 ° C while mixing.
  • 3% N-lauroyl-L-alanyl-L-alanine self-assembling polymer was added to the mixer while heating.
  • the sample was heated and kept at 73-86 ° C for 5-10 min. It is then cooled to a temperature between 65-72 ° C while remaining miscible.
  • the sample was then poured into a 30 ml volume to obtain a skin care composition, which was stored and used for evaluation.
  • the methods for preparing the skin care composition in Formulas 2-6 adopt the same method as in Formula 1, and are not repeated here.
  • oil-insoluble particles such as starch, TiO 2 , mica, boron nitride particles (Caress BN02 from Kobo), and an oil-miscible liquid such as glycerin.
  • the natural oil mixture components used in Formulas 1-6 are all the same, which include 40% grape seed oil, 37.2% sunflower seed oil, and 22.8% aloe oil. The results showed that the compositions obtained from all the formulations shown in Table 3 were stable at room temperature and in an oven at 48 ° C without any particle separation problems.
  • the laundry liquid prepared according to Formula 1 in Table 8 was tested by the Suzhou Product Quality Supervision and Inspection Institute.
  • the detergency is greater than or equal to that of the standard laundry liquid.
  • the obtained samples have a detergency greater than that of the standard laundry.
  • the detergent liquid formulated according to Formula 2 was tested by Suzhou Product Quality Supervision and Inspection Institute, and the detergency was less than that of standard laundry detergent.
  • N-lauroyl-L-alanyl-L-alanine self-assembled polymer and N-lauroyl-L-alanine self-assembled polymer salt in alkaline aqueous system can be used as clean surface Active agent, this surfactant is mild, non-irritating, strong oil control, more suitable for sensitive skin.

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Abstract

本发明公开了一种新型氨基酸自组装超分子聚合物及其制备和应用，该自组装超分子化合物为N-月桂酰-L-丙氨酰-L-丙氨酸或其盐，其盐包括N-月桂酰-L-丙氨酰-L-丙氨酸钠和N-月桂酰-L-丙氨酰-L-丙氨酸钾。本发明公开的聚合物具有更有效的抑菌、去农药等效果，可广泛应用于日化、农业和医药行业。本发明还公开了三种制备该化合物的方法。所述的方法得到的产物产率高，适于工业化生产。

Description

一种新型氨基酸自组装超分子聚合物及其制备方法和应用 技术领域
本发明属于氨基酸型表面活性剂制备技术领域，具体地，涉及一种新型氨基酸自组装超分子聚合物的制备方法和应用。
背景技术
表面活性剂是日化行业、农业、医药行业等许多领域必不可少的组成部分。目前市场使用的表面活性剂有几十种之多，但常用的主要以十二烷基苯磺酸钠(SLS)、月桂醇聚氧乙烯醚硫酸酯钠(AES)和月桂醇硫酸酯钠(K12)为主。由于这三大表面活性剂使用历史已有几十年甚至上百年，在使用的过程中它的负面影响已逐步显现出来，对人体的安全和环境的影响经常报道。
其它的表面活性剂，如糖类的烷基糖苷(APG)，氨基酸表面活性剂，如月桂酰-L-谷氨酸、月桂酰甘氨酸、月桂酰肌氨酸等。虽然它们属于生物物质为基础的表面活性剂，具有安全性高，生物降解性好和优良的肤感，也越来越受到人们的关注，但由于这类的表面活性剂去污能力较差，很少单独作为主表面活性剂来使用，常需与其它主表面活性剂来配合使用，没有从根本上解决日化主表面活性剂在安全性和生物降解性上的负面问题。
N-月桂酰-L-丙氨酸自组装聚合物在月桂酸一定含量下可以形成，而之前的方法专利得不到聚合物，且聚合物效果优于方法专利化合物的效果，因此，本发明制备得到N-月桂酰-L-丙氨酰-L-丙氨酸自组装超分子聚合物。
N-月桂酰-L-丙氨酰-L-丙氨酸自组装超分子聚合物是在深入研究N-月桂酰-L-丙氨酸的基础上合成的一种新型氨基酸自组装超分子聚合物，具有N-月桂酰-L-丙氨酸的基本性质。但是，由于它多了一组氢键，使得整个结构更加稳定，不易分裂。并且多了一个L-丙氨酸使得整个链更长，与硬脂酸的长度相仿，具有比N-月桂酰-L-丙氨酸更强的与油污相结合的能力，形成的环具有更大的空间，能包裹更多的有机分子化合物及生物物质，从而改变被包裹物质的一些物理性质及化学性质。由于N-月桂酰-L-丙氨酰-L-丙氨酸本身来源于生物物质的材料，具有天然的安全性及生物降解性，因而具有更多的 应用，对人类生活环境具有巨大的改变。
自组装超分子聚合物N-月桂酰-L-丙氨酰-L-丙氨酸的钠盐由于具有二组氢键，它形成的二维平面结构具有更强的结构连接性，形成网状结构不易破裂。并且单个分子增加了一个L-丙氨酸，使得单个分子的链更长，与十八碳的硬脂酸钠的长度相仿，从而具有更强的去污能力及包裹性。
发明内容
为了获得具有良好的生物可降解性、去污能力强的表面活性剂，本发明在研究N-月桂酰-L-丙氨酸的基础上合成了一种新型氨基酸自组装超分子聚合物，该化合物相对于现有的表面活性剂甚至N-月桂酰-L-丙氨酸，表现出更有效的去污、抑菌性能，能够很好的应用于日化行业、农业及医药行业等领域。
本发明的目的及解决其技术问题采用以下的技术方案来实现。依据本发明提出的一种新型氨基酸自组装超分子聚合物具有如下结构：
Figure PCTCN2019089819-appb-000001
一种新型氨基酸自组装超分子聚合物的单体，具有如下结构：
Figure PCTCN2019089819-appb-000002
其中，R选自H、Na或K。
本发明还涉及一种新型氨基酸自组装超分子聚合物，其特征在于以N-月桂酰-L-丙氨酰-L-丙氨酸为基本单元，通过氢键自组装成为超分子聚合物，重均分子量数据介于5000-500万之间。
所述聚合物基本不含月桂酸，基本不含是指月桂酸用HPLC检测不出。
本发明还涉及一种新型氨基酸自组装超分子聚合物的钠盐，结构如下：
Figure PCTCN2019089819-appb-000003
其中n表示N-月桂酰-L-丙氨酰-L-丙氨酸钠形成自组装聚合物的分子个数。
本发明还公开了一种新型氨基酸自组装超分子聚合物的钠盐，其以N-月桂酰-L-丙氨酰-L-丙氨酸钠为基本单元，通过氢键自组装成为超分子聚合物，其重均分子量数据介于5000-500万之间。
本发明的目的及解决其技术问题还采用以下的技术方案来实现。依据本发明提出的一种制备如上所述化合物的方法如下：
将N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入溶剂、L-丙氨酰-L-丙氨酸和催化剂并在一定条件下搅拌，之后冷却过滤，所得固体经洗涤后烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装超分子聚合物。
在根据本发明的前述的方法中，其中所述溶剂选自丙酮、甲醇、乙醇、乙腈、四氢呋喃或上述溶剂与水制成的混合溶剂。
在根据本发明的前述的方法中，其中所述催化剂选自硫酸、对甲苯磺酸、乳化剂中的一种或更多种。
在根据本发明的前述的方法中，其中所述N-月桂酰-L-丙氨酰-L-丙氨酸粗品、溶剂、L-丙氨酰-L-丙氨酸、催化剂的摩尔比为1:(5-10):(0.1-0.2):(0.001-0.1)。
在根据本发明的前述的方法中，其中所述搅拌条件为：温度25℃-100℃，压力5kg-50kg，时间1-3h。
制备N-月桂酰-L-丙氨酰-L-丙氨酸粗品，所述方法包括以下步骤：
(1)将L-丙氨酰-L-丙氨酸与金属无机碱溶于蒸馏水和有机溶剂的混合溶液中搅拌均匀得到L-丙氨酰-L-丙氨酸盐溶液；
(2)向上述得到的L-丙氨酰-L-丙氨酸盐溶液中依次加入月桂酰氯和金属无机碱，然后在一定条件下继续搅拌，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐；
(3)将上述得到的糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐酸化，逐渐析出白色固体，冷却后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
在根据本发明的前述的方法中，其中所述步骤(1)中所述L-丙氨酰-L-丙氨酸与金属无机碱的摩尔比为1:(1-1.5)。
在根据本发明的前述的方法中，其中所述步骤(1)中所述金属无机碱选自氢氧化钠、氢氧化钾、碳酸钠、碳酸钾中的一种或更多种。
在根据本发明的前述的方法中，其中所述步骤(1)中所述有机溶剂选自丙 酮、甲醇、乙醇、乙腈、四氢呋喃中的一种或更多种。
在根据本发明的前述的方法中，其中所述步骤(1)中所述蒸馏水和有机溶剂的体积比为1:(1-1.5)。
在根据本发明的前述的方法中，其中所述步骤(2)中所述月桂酰氯与L-丙氨酰-L-丙氨酸的投料摩尔比为(0.8-1):1。
在根据本发明的前述的方法中，其中所述步骤(2)中所述搅拌条件为：温度5-50℃，时间1-3h。
在根据本发明的前述的方法中，其中所述步骤(2)中所述属无机碱浓度为30-80％。
在根据本发明的前述的方法中，其中所述步骤(2)中所述金属无机碱选自氢氧化钠、氢氧化钾、碳酸钠、碳酸钾中的一种或更多种。
本发明的目的及解决其技术问题还采用以下的技术方案来实现。依据本发明提出的一种制备如上所述化合物的方法，所述方法包括以下步骤：
(1)将N-月桂酰-L-丙氨酸和氯化试剂混合反应，冷却后加入戊-2-酮和活性炭依次经脱色过滤、减压蒸馏，继续加入有机溶剂，溶解N-月桂酰-L-丙氨酸中的酰氯，得N-月桂酰-L-丙氨酰氯的溶液；
(2)将L-丙氨酸与金属无机碱溶于蒸馏水和有机溶剂的混合溶液中搅拌均匀得到L-丙氨酸盐溶液；
(3向上述得到的L-丙氨酸盐溶液中加入步骤(1)中得到的N-月桂酰-L-丙氨酰氯的丙酮溶液和金属无机碱，然后在一定条件下继续搅拌，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐；
(4)将上述得到的糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐酸化，逐渐析出白色固体，冷却后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品；
(5)将N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入溶剂、L-丙氨酰-L-丙氨酸和催化剂并在一定条件下搅拌，之后冷却过滤，所得固体经洗涤后烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装超分子聚合物。
在根据本发明的前述的方法中步骤1中，戊-2-酮的加入量为80-100mL，活性炭加入量为1-3g，有机溶剂的加入量为80-100mL。
在根据本发明的前述的方法中，其中所述步骤(1)中，所述N-月桂酰-L-丙氨酸和氯化试剂的摩尔比为(1-1.5):5，所述的氯化试剂可以是二氯亚砜、三氯化磷、三光气、N-氯代丁二酰亚胺中的一种或更多种。
在根据本发明的前述的方法中，其中所述步骤(2)中所述L-丙氨酸与金属无机碱的摩尔比为1:(1-1.5)。
在根据本发明的前述的方法中，其中所述步骤(2)中所述金属无机碱选自氢氧化钠、氢氧化钾、碳酸钠、碳酸钾中的一种或更多种。
在根据本发明的前述的方法中，其中所述步骤(2)中所述有机溶剂选自丙酮、甲醇、乙醇、乙腈、四氢呋喃中的一种或更多种。
在根据本发明的前述的方法中，其中所述步骤(2)中所述蒸馏水和有机溶剂的体积比为1:(1-1.5)。
在根据本发明的前述的方法中，其中所述步骤(3)中所述N-月桂酰-L-丙氨酰氯的丙酮溶液与L-丙氨酸的投料摩尔比为(0.8-1):1。
在根据本发明的前述的方法中，其中所述步骤(3)中所述搅拌条件为：温度5-50℃，时间1-3h。
在根据本发明的前述的方法中，其中所述步骤(3)中所述无机金属碱浓度30-80％。
在根据本发明的前述的方法中，其中所述步骤(3)中所述无机金属碱选自氢氧化钠、氢氧化钾、碳酸钠、碳酸钾中的一种或更多种。
本发明的目的及解决其技术问题还采用以下的技术方案来实现。依据本发明提出的根据如上所述的制备方法得到的化合物，用作表面活性剂，在日化领域、农业、医药行业的应用。
本发明的目的及解决其技术问题还采用以下的技术方案来实现。依据本发明提出的根据如上所述的化合物，用作表面活性剂，在日化领域、农业、医药 行业的应用。
本发明的目的及解决其技术问题还采用以下的技术方案来实现。依据本发明提出的一种超分子氨基酸，其中所述超分子氨基酸是由如上所述的制备方法得到的N-月桂酰-L-丙氨酰-L-丙氨酸单体之间通过氢键连接形成的。
与现有技术相比，本发明具有有益的技术效果：
1、本发明的一种新型氨基酸自组装超分子聚合物的制备方法工艺步骤简单，是用天然的月桂酸和L-丙氨酰-L-丙氨酸缩合而成的，在常态下稳定存在，对人体无毒无害，进入人体和自然也很快降解成月桂酸和L-丙氨酸，降解产物又是天然产品，可循环利用，并且反应条件温和，适于工业化生产。
2、根据本发明的方法制备得到的自组装超分子N-月桂酰-L-丙氨酰-L-丙氨酸中月桂酸重量百分含量介于0.0001％-0.02％之间，基本不含有月桂酸，即月桂酸的含量对N-月桂酰-L-丙氨酰-L-丙氨酸的结构和性能不产生影响，有效的避免了月桂酸对产品质量的影响。
3、根据本发明的方法得到的自组装超分子N-月桂酰-L-丙氨酰-L-丙氨酸是一个三维网状结构，具有强吸附油污等有机物，在使用中pH取6～7，更适合人体pH要求，90％以上以钠盐形式存在，其余部分以酸的形式存在，以二维和三维的方式共存，赋予了强的洗涤能力，吸附细菌、农药、气味等性能。
4、根据本发明的方法制备得到的自组装超分子N-月桂酰-L-丙氨酰-L-丙氨酸结构性能稳定，并具有超分子的性质，分子在溶液中由于各种凝胶因素存在，如氢键、静电力、疏水力以及π-π的相互作用，驱动液体成分静止，形成一种具有三维立体网络空间结构的氨基酸，这样就具有了物理除菌、除气味、除农药残留等特性：具有良好的抑菌率，对大肠杆菌、金黄色葡萄球菌、白假丝酵母菌以及铜绿假单胞菌的抑制率均可达到100％；有效去除农药残留，对甲胺磷的去除率可达90.6％，对乙酰甲胺磷的去除率可达93.2％；同时具有良好的除异味性能。
5、根据本发明的方法制备得到的一种新型氨基酸自组装超分子聚合物是一个以无数柱状体的形式存在，分子之间存在巨大的空隙，能包裹有机物 如药物分子、农药残留及微小无机颗粒。在医药领域应用上，N-月桂酰-L-丙氨酰-L-丙氨酸能包裹药物分子，在酶的作用下缓慢释放药物有效成分，起到缓释剂的作用；在农药领域应用上，N-月桂酰-L-丙氨酰-L-丙氨酸能包裹农药，防止农药渗透，进入到植物内部；在化妆品领域应用上，N-月桂酰-L-丙氨酰-L-丙氨酸与天然油脂结合后会改变油脂的物理性能，贴近人体自身分泌的油脂，具有良好的体验感。N-月桂酰-L-丙氨酰-L-丙氨酸能包裹化妆品活性物质，这样使活性物质不易氧化、失活，还可使颗粒均匀分散，悬浮于化妆品体系内。
附图说明
图1为本发明的化合物的单体的结构。
图2a为根据本发明的实施例1中的合成方法制备N-月桂酰-L-丙氨酰-L-丙氨酸粗品的化学反应式；
图2b为根据本发明的实施例4中的合成方法制备N-月桂酰-L-丙氨酰-L-丙氨酸粗品的化学反应式；
图2c为根据本发明的实施例5中的合成方法制备N-月桂酰-L-丙氨酰-L-丙氨酸粗品的化学反应式；
图2d为根据本发明的实施例7中的合成方法制备N-月桂酰-L-丙氨酰-L-丙氨酸粗品的化学反应式。
图3为根据本发明的实施例1中的合成方法得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装超分子聚合物的核磁谱图；其中，ppm为百万分子一化学位移的单位。
图4a为根据本发明的实施例1中的合成方法得到的N-月桂酰-L-丙氨酰-L-丙氨酸单体形成超分子氨基酸的结构形成图；
图4b为根据本发明的实施例1中的合成方法得到的N-月桂酰-L-丙氨酰-L-丙氨酸单体形成超分子氨基酸的结构形成图。
图5a为根据本发明的实施例1中的合成方法得到的N-月桂酰-L-丙氨酰-L- 丙氨酸的10000倍电镜图；
图5b为根据本发明的实施例1中的合成方法得到的N-月桂酰-L-丙氨酰-L-丙氨酸的20000倍电镜图；
图5c为根据本发明的实施例1中的合成方法得到的N-月桂酰-L-丙氨酰-L-丙氨酸的50000倍电镜图。
图6为根据本发明的实施例1中的合成方法得到的N-月桂酰-L-丙氨酰-L-丙氨酸进一步形成超分子氨基酸钠盐的形成过程图。
图7为根据本发明的实施例1中的合成方法得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装超分子聚合物的质谱图；其中，
Counts vs Mass-to-Chorge(m/z)
Sample Name:ZZXF(P161014Y)样品名称：ZZXF(P161014Y)
Inj Vol:进样体积
Data filename：ZZXF(P161014Y)-02.d数据文件名：ZZXF(P161014Y)-02.d
Position：位置
Injposition：进样位置
ACQ method：ACQ方法
Instrument Name:仪器名称
Sample Type:样品型号
Comment:评论
User name:用户名
IRM Calibration Status:IRM校准数据
Acquired Time:精确时间
Success:成功
PM：下午。
具体实施方式
发明人经过广泛而深入的研究，发现可通过特定的方法可以使N-月桂酰-L-丙氨酰-L-丙氨酸单体通过氢键自组装形成的聚合物中基本不含或不含月桂酸，并且可形成有弹性含空隙的结构，这种结构可固化油类物质；当聚合物与碱成盐后，聚合物盐又可作为表面活性剂。在此基础上，完成了本发明。
如本文所用，“本发明提供的聚合物或其盐基本不含或不含月桂酸”是指例如采用高效液相色谱仪(配有紫外检测器；色谱柱：ODS-2HYPERSIL C18250*4.6mm 5μm；流动相真空抽滤脱气装置及0.45μm有机滤膜)检测不到月桂酸，即月桂酸的含量不影响N-月桂酰-L-丙氨酰-L-丙氨酸的性质和结构。或是指通过质谱测定，获得的质谱图中检测不出月桂酸的分子离子峰特征。例如但不限于，通过Agilent 1200/6220液质联用仪获得如图7所示的质谱图。
本发明中涉及的N-月桂酰-L-丙氨酰-L-丙氨酸盐为N-月桂酰-L-丙氨酰-L-丙氨酸钠和/或N-月桂酰-L-丙氨酰-L-丙氨酸钾。也可以是N-月桂酰-L-丙氨酸同碱性氨基酸形成的盐，例如同精氨酸、组氨酸、赖氨酸等形成的盐。
聚合物或其盐
本发明提供一种氨基酸自组装超分子聚合物或其盐，所述聚合物是N-月桂酰-L-丙氨酰-L-丙氨酸单体之间通过氢键连接形成；所述聚合物基本不含或不含月桂酸。
所述N-月桂酰-L-丙氨酰-L-丙氨酸单体或其盐是具有如下结构的化合物：
Figure PCTCN2019089819-appb-000004
其中，R选自H、Na或K。
所述N-月桂酰-L-丙氨酰-L-丙氨酸单体之间通过氢键连接可形成如式(Ⅰ)所示的结构：
Figure PCTCN2019089819-appb-000005
本发明提供的氨基酸自组装超分子聚合物的重均分子量介于5000-500万之间，其熔点为148-150℃。
本发明还提供上述氨基酸自组装超分子聚合物的盐，所述盐为聚合物与碱形成；所述碱包括无机碱和有机碱。
在一优选例中，所述无机碱选自氢氧化钠、氢氧化钾、或氢氧化锂。
在一优选例中，所述有机碱为天然碱性氨基酸(精氨酸、赖氨酸或组氨酸)。
在本发明的一种实施方式中，提供一种一种氨基酸自组装超分子聚合物钠盐，是N-月桂酰-L-丙氨酰-L-丙氨酸钠单体之间通过氢键连接形成；所述聚合物钠盐基本不含或不含月桂酸。
所述N-月桂酰-L-丙氨酰-L-丙氨酸钠单体之间通过氢键连接可形成如式(Ⅱ)所示的结构：
Figure PCTCN2019089819-appb-000006
其中，n为8-20000；n个N-月桂酰-L-丙氨酰-L-丙氨酸钠在同一平面通过氢键依次连接，或n个N-月桂酰-L-丙氨酸钠通过氢键依次连接且首尾通过氢键连接以形成一柱状。
提供的氨基酸自组装超分子聚合物钠盐的重均分子量介于5000-500万之间。
本发明还提供一种组合物，所述组合物中含有本发明提供的氨基酸自组装超分子聚合物或其盐，和不含或不含月桂酸的N-月桂酰-L-丙氨酸单体之间通过氢键连接形成的聚合物或其盐，以组合物的总重量计，其中N-月桂酰-L-丙氨酸单体之间通过氢键连接形成的聚合物或其盐的重量百分含量介于0-60％之间。
所述N-月桂酰-L-丙氨酸单体之间通过氢键连接可形成如式(Ⅰ＇)所示的结构：
Figure PCTCN2019089819-appb-000007
其重均分子量介于2000-500万之间，其熔点为82-84℃；该聚合物的钠盐的最大溶解度为15w/v％，通过溶解度方法测定(《中国药典》(2015年版)凡例)，即在25℃，1个大气压下，每100ml水中溶解的自组装的聚合的N-月桂酰-L-丙氨酸钠最多为15克。
所述N-月桂酰-L-丙氨酸钠单体之间通过氢键连接也可形成如式(Ⅱ＇)所示的结构：
Figure PCTCN2019089819-appb-000008
Figure PCTCN2019089819-appb-000009
其中n表示N-月桂酰-L-丙氨酸钠形成自组装超分子聚合物的分子个数
n个N-月桂酰-L-丙氨酸钠在同一平面通过氢键依次连接，或n个N-月桂酰-L-丙氨酸钠通过氢键依次连接且首尾通过氢键连接以形成一柱状。
如式Ⅱ＇所示的聚合物钠盐的重均分子量介于2800-77万之间；由此可以推断n在10至3000在范围内，所得的钠盐在水中的溶解度不超过15克/100ml。
聚合物或其盐的制备方法
本发明提供一种氨基酸自组装超分子聚合物的制备方法，所述方法包括步骤：
第一步，将L-丙氨酰-L-丙氨酸与金属无机碱溶于蒸馏水和有机溶剂的混合溶液中搅拌均匀得到L-丙氨酰-L-丙氨酸盐溶液；
第二步，向上述得到的L-丙氨酰-L-丙氨酸盐溶液依次加入月桂酰氯和金属无机碱使得反应体系的pH＝8-10，然后在一定条件下继续搅拌，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐；
第三步，将上述得到的糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐酸化至pH＝3-4，逐渐析出白色固体，然后在冰浴下放置1-3小时后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品；
第四步，在上述得到的N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入溶剂、L-丙氨酰-L-丙氨酸和催化剂，并在一定条件下搅拌，得到本发明提供的氨基酸自 组装超分子聚合物。
在本发明的一种实施方式中，上述第一步中所述蒸馏水和有机溶剂的体积比为1：(1-1.5)。
在本发明的一种实施方式中，上述第一步中所述L-丙氨酰-L-丙氨酸与金属无机碱的摩尔比为1:(1-1.5)。
在本发明的一种实施方式中，上述第一步中所述金属无机碱选自氢氧化钠、氢氧化钾、碳酸钠、碳酸钾中的一种或两种以上。
在本发明的一种实施方式中，上述第一步中所述有机溶剂选自丙酮、甲醇、乙醇、乙腈、四氢呋喃中的一种或两种以上。
在本发明的一种实施方式中，上述第二步中所述月桂酰氯与L-丙氨酰-L-丙氨酸的投料摩尔比为(0.8-1):1。
在本发明的一种实施方式中，上述第二步中所述搅拌条件为：温度5-50℃，时间1-3小时。
在本发明的一种实施方式中，上述第二步中所述金属无机碱浓度为30-80％；所述金属无机碱选自氢氧化钠、氢氧化钾、碳酸钠、碳酸钾中的一种或两种以上。
在本发明的一种实施方式中，上述第二步在5-50℃下，向第一步得到的L-丙氨酰-L-丙氨酸盐溶液中加入N-月桂酰-L-丙氨酰氯的丙酮溶液和金属无机碱使得反应体系的pH＝8-10，然后在一定条件下继续搅拌，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在本发明的一种实施方式中，所述N-月桂酰-L-丙氨酰氯的丙酮溶液是将N-月桂酰-L-丙氨酸和二氯亚砜混合反应1-3小时，然后蒸除过量的二氯亚砜，冷却后加入戊-2-酮和活性炭依次经脱色过滤、减压蒸馏，带走剩余的二氯亚砜，继续加入水丙酮，溶解N-月桂酰-L-丙氨酸中的酰氯，得到N-月桂酰-L-丙氨酰氯的丙酮溶液。所述N-月桂酰-L-丙氨酸和二氯亚砜的摩尔比为(1-1.5):5。
在本发明的一种实施方式中，上述第二步将得到的N-月桂酰-L-丙氨酰-L-丙氨酸甲酯和金属无机碱溶于蒸馏水和有机溶剂的混合溶液中反应4-8小时，待反应结束后蒸去多余的有机溶剂，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在本发明的一种实施方式中，所述N-月桂酰-L-丙氨酰-L-丙氨酸甲酯与金属无机碱的投料摩尔比为1:(1-1.5)；所述金属无机碱选自氢氧化钠、氢氧化钾、碳酸钠、碳酸钾中的一种或两种以上。
在本发明的一种实施方式中，所述蒸馏水和有机溶剂的体积比为1:(3-7)；所述有机溶剂选自丙酮、甲醇、乙醇、乙腈中的一种或两种以上。
在本发明的一种实施方式中，所述N-月桂酰-L-丙氨酰-L-丙氨酸甲酯是将L-丙氨酸甲酯盐酸盐和水溶性有机碱(选自三乙胺、吡啶、三乙醇胺中的一种或两种以上)以及N-月桂酰-L-丙氨酰氯溶于丙酮中，在一定条件下反应(在0-5℃反应3-7小时)，然后升至室温继续反应4-6小时，反应结束后蒸去多余的丙酮而得到；所述N-月桂酰-L-丙氨酰氯是将将N-月桂酰-L-丙氨酸和三光气溶于氯仿中并加入少量催化剂(选自二甲基甲酰胺、吡啶、1-甲基吡咯烷酮、1-甲基哌啶、1-乙基哌啶中的一种或两种以上)反应(氯仿与催化剂的体积比为(200-300):(1-10)，在30-50℃反应4-8小时)，然后蒸去多余的氯仿而得到；所述N-月桂酰-L-丙氨酸和三光气的投料摩尔比为(1-1.5):0.3；所述L-丙氨酸甲酯盐酸盐、水溶性有机碱和N-月桂酰-L-丙氨酰氯的投料摩尔比为(0.8-1):(0.8-1):1。
在本发明的一种实施方式中，上述第三步中所述盐酸浓度为5-15％。
在本发明的一种实施方式中，上述第四步中所述溶剂选自丙酮、甲醇、乙醇、乙腈、四氢呋喃或上述溶剂与水制成的混合溶剂。
在本发明的一种实施方式中，上述第四步中所述催化剂选自硫酸、对甲苯磺酸、乳化剂中的一种或两种以上。
在本发明的一种实施方式中，上述第四步中所述N-月桂酰-L-丙氨酰-L-丙氨酸粗品、溶剂、L-丙氨酰-L-丙氨酸、催化剂的混合摩尔比为1:(5-10):(0.1-0.2):(0.001-0.1)。
在本发明的一种实施方式中，上述第四步中所述搅拌条件为：温度25℃-100℃，压力5kg-50kg，时间1-3小时。
在本发明的一种实施方式中，上述第四步在搅拌后冷却过滤，所得固体经洗涤后烘干，即得到基本不含月桂酸的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物。
聚合物或其盐的用途
本发明提供的氨基酸自组装超分子聚合物可用于固化油类物质，其盐可用作表面活性剂。
本发明提供的氨基酸自组装超分子聚合物或其盐可在日化领域、农业、或医 药行业中广泛使用，例如但不限于，用于制备牙膏、皮肤护理组合物、洗衣液、香皂、洗衣粉、洗洁精、面膜等。
下面结合附图和实施例对本发明作进一步的阐述，应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解，在阅读了本发明讲授的内容之后本领域技术人员可以对本发明做各种改动或修改，这些等价同样落于本申请所附权利要求书所限定的范围。
实施例1 N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物的合成
实例1
常温下，在2L的三口烧瓶中，将16.0g(0.1mol)L-丙氨酰-L-丙氨酸和4..0g(0.1mol)氢氧化钠溶于450mL蒸馏水和450mL丙酮的混合溶液中搅拌均匀得到L-丙氨酰-L-丙氨酸钠溶液。
在25℃的条件下，向L-丙氨酰-L-丙氨酸盐溶液中缓慢滴加21.9g(0.1mol)月桂酰氯，再滴加50％的氢氧化钠溶液使得反应体系的pH＝9，滴加完毕后，在25℃下继续搅拌2h，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐中加入盐酸酸化至pH＝3-4，逐渐析出白色固体，然后在冰浴下放置2h后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
在N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入水和丙酮的混合溶剂、L-丙氨酰-L-丙氨酸和对甲苯磺酸，其中，N-月桂酰-L-丙氨酰-L-丙氨酸粗品、水和丙酮的混合溶剂、L-丙氨酸、对甲苯磺酸按照摩尔比1:7.5:0.2:0.002的量加入并在温度为60℃、压力为27kg的条件下搅拌2h，使得少量的月桂酸完全消耗完，之后冷却过滤，所得固体再用纯水洗涤两次，最后在100℃下烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物。
所得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物质量为30.5g，产率为89.3％，月桂酸含量检测不出，熔点148～150℃。图3为所得到的N-月桂酰-L- 丙氨酰-L-丙氨酸的核磁谱图。图7为所得到的N-月桂酰-L-丙氨酰-L-丙氨酸的质谱图。
经试验发现，如果上述反应在常压下条件搅拌，经检测反应体系中还存在少量的月桂酸，最后的产品不能获得N-月桂酰-L-丙氨酰-L-丙氨酸聚合物。
实例2
常温下，在2L的三口烧瓶中，将16.0g(0.1mol)L-丙氨酰-L-丙氨酸和6.0g(0.15mol)氢氧化钾溶于450mL蒸馏水和450mL乙腈的混合溶液中搅拌均匀得到L-丙氨酰-L-丙氨酸钠溶液。
在25℃的条件下，向L-丙氨酰-L-丙氨酸盐溶液中缓慢滴加17.52g(0.08mol)月桂酰氯，再滴加30％的氢氧化钠溶液使得反应体系的pH＝9，滴加完毕后，在50℃下继续搅拌0.5h，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐中加入盐酸酸化至pH＝3-4，逐渐析出白色固体，然后在冰浴下放置3h后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
在N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入水和丙酮的混合溶剂、L-丙氨酰-L-丙氨酸和对甲苯磺酸，其中，N-月桂酰-L-丙氨酰-L-丙氨酸粗品、水和丙酮的混合溶剂、L-丙氨酸、对甲苯磺酸按照摩尔比1:10:0.2:0.002的量加入并在温度为25℃、压力为50kg的条件下搅拌3h，使得少量的月桂酸完全消耗完，之后冷却过滤，所得固体再用纯水洗涤两次，最后在70℃下烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物。
所得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物质量为32.35g，产率为94.72％，熔点148～150℃。
实例3
常温下，在2L的三口烧瓶中，将16.0g(0.1mol)L-丙氨酰-L-丙氨酸和4.0g(0.1mol)氢氧化钾溶于450mL蒸馏水和600mL乙腈的混合溶液中搅拌均匀得到L-丙氨酰-L-丙氨酸钠溶液。
在25℃的条件下，向L-丙氨酰-L-丙氨酸盐溶液中缓慢滴加21.9g(0.1mol) 月桂酰氯，再滴加80％的氢氧化钠溶液使得反应体系的pH＝9，滴加完毕后，在5℃下继续搅拌3.5h，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐中加入盐酸酸化至pH＝3-4，逐渐析出白色固体，然后在冰浴下放置1h后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
在N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入水和乙醇的混合溶剂、L-丙氨酰-L-丙氨酸和对甲苯磺酸，其中，N-月桂酰-L-丙氨酰-L-丙氨酸粗品、水和乙醇的混合溶剂、L-丙氨酰-L-丙氨酸、对甲苯磺酸按照摩尔比1:5:0.2:0.001的量加入并在温度为100℃、压力为5kg的条件下搅拌1h，使得少量的月桂酸完全消耗完，之后冷却过滤，所得固体再用纯水洗涤两次，最后在130℃下烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物。
所得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物质量为29.15g，产率为85.35％，月桂酸含量检测不出，熔点148～150℃。
实例4
常温下，在500mL的三颈烧瓶中，将27.1g(0.1mol)N-月桂酰-L-丙氨酸和69.48g(0.5mol)二氯亚砜混合反应2h。反应结束后蒸除过量的二氯亚砜，冷却后加入100mL戊-2-酮和2g活性炭依次进行脱色过滤、减压蒸馏，带走剩余的二氯亚砜。继续加入100mL无水丙酮溶解N-月桂酰-L-丙氨酸中的酰氯，得N-月桂酰-L-丙氨酰氯的丙酮溶液。
常温下，在2L的三口烧瓶中，将8.9g(0.1mol)L-丙氨酸和4.0g(0.1mol)氢氧化钠溶于450mL蒸馏水和450mL丙酮的混合溶液中搅拌均匀得到L-丙氨酸钠溶液。
在25℃的条件下，向L-丙氨酸盐溶液中缓慢滴加0.1mol上述得到的N-月桂酰-L-丙氨酰氯的丙酮溶液，再滴加50％的氢氧化钠溶液使得反应体系的pH＝9，滴加完毕后，在25℃下继续搅拌2h，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐中加入盐酸酸化至pH＝3-4，逐渐 析出白色固体，然后在冰浴下放置2h后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
在N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入水和丙酮的混合溶剂、L-丙氨酰-L-丙氨酸和对甲苯磺酸，其中，N-月桂酰-L-丙氨酰-L-丙氨酸粗品、水和丙酮的混合溶剂、L-丙氨酸、对甲苯磺酸按照摩尔比1:10:0.2:0.002的量加入并在温度为25℃、压力为50kg的条件下搅拌3h，使得少量的月桂酸完全消耗完，之后冷却过滤，所得固体再用纯水洗涤两次，最后在70℃下烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物。
所得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物质量为31.1g，产率为90.7％，月桂酸含量检测不出，熔点148～150℃。
实例5
常温下，在250mL的三颈烧瓶中，氮气保护下，将27.1g(0.1mol)N-月桂酰-L-丙氨酸和4.53g(0.033mol)三氯化磷加热到90度，反应2-3h。反应结束后分离掉亚磷酸，冷却到室温。继续加入100mL无水丙酮溶解N-月桂酰-L-丙氨酸中的酰氯，得N-月桂酰-L-丙氨酰氯的丙酮溶液。
常温下，在2L的三口烧瓶中，将8.9g(0.1mol)L-丙氨酸和4.0g(0.1mol)氢氧化钠溶于450mL蒸馏水和450mL丙酮的混合溶液中搅拌均匀得到L-丙氨酸钠溶液。
在25℃的条件下，向L-丙氨酸盐溶液中缓慢滴加0.1mol上述得到的N-月桂酰-L-丙氨酰氯的丙酮溶液，再滴加50％的氢氧化钠溶液使得反应体系的pH＝9，滴加完毕后，在25℃下继续搅拌2h，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐中加入盐酸酸化至pH＝3-4，逐渐析出白色固体，然后在冰浴下放置2h后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
在N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入水和丙酮的混合溶剂、L-丙氨酰-L-丙氨酸和对甲苯磺酸，其中，N-月桂酰-L-丙氨酰-L-丙氨酸粗品、水和丙酮的 混合溶剂、L-丙氨酸、对甲苯磺酸按照摩尔比1:10:0.2:0.002的量加入并在温度为25℃、压力为50kg的条件下搅拌3h，使得少量的月桂酸完全消耗完，之后冷却过滤，所得固体再用纯水洗涤两次，最后在70℃下烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物。
所得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物质量为31.6g，产率为92.3％，月桂酸含量检测不出，熔点148～150℃。
实例6
常温下，在1L的三颈烧瓶中，将40.65g(0.15mol)N-月桂酰-L-丙氨酸和69.48g(0.5mol)二氯亚砜混合反应3h。反应结束后蒸除过量的二氯亚砜，冷却后加入120mL戊-2-酮和1g活性炭依次进行脱色过滤、减压蒸馏，带走剩余的二氯亚砜。继续加入80mL无水丙酮，溶解N-月桂酰-L-丙氨酸的酰氯，得N-月桂酰-L-丙氨酰氯的丙酮溶液。
常温下，在2L的三口烧瓶中，将8.9g(0.1mol)L-丙氨酸和4.0g(0.1mol)氢氧化钾溶于450mL蒸馏水和600mL乙腈的混合溶液中搅拌均匀得到L-丙氨酸钠溶液。
在25℃的条件下，向L-丙氨酸盐溶液中缓慢滴加0.1mol上述得到的N-月桂酰-L-丙氨酰氯的丙酮溶液，再滴加80％的氢氧化钠溶液使得反应体系的pH＝9，滴加完毕后，在5℃下继续搅拌3.5h，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐中加入盐酸酸化至pH＝3-4，逐渐析出白色固体，然后在冰浴下放置1h后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
在N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入水和丙酮的混合溶剂、L-丙氨酰-L-丙氨酸和对甲苯磺酸，其中，N-月桂酰-L-丙氨酰-L-丙氨酸粗品、水和丙酮的混合溶剂、L-丙氨酸、对甲苯磺酸按照摩尔比1:10:0.2:0.002的量加入并在温度为25℃、压力为50kg的条件下搅拌3h，使得少量的月桂酸完全消耗完，之后冷却过滤，所得固体再用纯水洗涤两次，最后在70℃下烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物。
所得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物质量为29.95g，产率为87.72％，月桂酸含量检测不出，熔点148～150℃。
实例7
在1L的三口烧瓶中，将27.1g(0.1mol)N-月桂酰-L-丙氨酸和9.9g(0.033mol)三光气(C 3Cl 6O 3)溶于200mL氯仿和5mL DMF(二甲基甲酰胺)的混合溶液中，在40℃下磁力搅拌反应6h，反应后蒸去剩余的氯仿，得到N-月桂酰-L-丙氨酰氯。
在1L的三口烧瓶中，将13.95g(0.1mol)L-丙氨酸甲酯盐酸盐和10.1g(0.1mol)三乙胺以及23.55g(0.1mol)N-月桂酰-L-丙氨酰氯溶于500mL丙酮中，在0℃下磁力搅拌反应2h，然后升至室温继续磁力搅拌反应5h，待反应结束后，蒸去剩余的丙酮，得到N-月桂酰-L-丙氨酰-L-丙氨酸甲酯。
在1L的三口烧瓶中，将35.6g(0.1mol)N-月桂酰-L-丙氨酰-L-丙氨酸甲酯和7.2g(0.3mol)氢氧化锂溶于500mL甲醇和100mL水的混合溶液中，磁力搅拌反应6h，待反应结束后蒸去甲醇，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐中加入10％盐酸酸化至pH＝3-4，逐渐析出白色固体，然后在冰浴下放置2h后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
在N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入水和丙酮的混合溶剂、L-丙氨酰-L-丙氨酸和对甲苯磺酸，其中，N-月桂酰-L-丙氨酰-L-丙氨酸粗品、水和丙酮的混合溶剂、L-丙氨酸、对甲苯磺酸按照摩尔比1:10:0.2:0.002的量加入并在温度为25℃、压力为50kg的条件下搅拌3h，使得少量的月桂酸完全消耗完，之后冷却过滤，所得固体再用纯水洗涤两次，最后在70℃下烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物。
所得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物质量为31.9g，产率为93.4％，月桂酸含量检测不出，熔点148～150℃。
实例8
在1L的三口烧瓶中，将40.65g(0.15mol)N-月桂酰-L-丙氨酸和9.9g(0.033mol)三光气(C 3Cl 6O 3)溶于400mL氯仿和1mL吡啶的混合溶液中，在50℃下磁力搅拌反应4h，反应后蒸去剩余的氯仿，得到N-月桂酰-L-丙氨酰氯。
在1L的三口烧瓶中，将11.16g(0.08mol)L-丙氨酸甲酯盐酸盐和7.91g(0.1mol)吡啶以及23.55g(0.1mol)N-月桂酰-L-丙氨酰氯溶于700mL丙酮中，在5℃下磁力搅拌反应3h，然后升至室温继续磁力搅拌反应4h，待反应结束后，蒸去剩余的丙酮，得到N-月桂酰-L-丙氨酰-L-丙氨酸甲酯。
在1L的三口烧瓶中，将35.6g(0.1mol)N-月桂酰-L-丙氨酰-L-丙氨酸甲酯和5.6g(0.1mol)氢氧化钾溶于300mL乙醇和100mL水的混合溶液中，磁力搅拌反应4h，待反应结束后蒸去甲醇，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐中加入15％盐酸酸化至pH＝3-4，逐渐析出白色固体，然后在冰浴下放置1h后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
在N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入水和丙酮的混合溶剂、L-丙氨酰-L-丙氨酸和对甲苯磺酸，其中，N-月桂酰-L-丙氨酰-L-丙氨酸粗品、水和丙酮的混合溶剂、L-丙氨酸、对甲苯磺酸按照摩尔比1:10:0.2:0.002的量加入并在温度为25℃、压力为50kg的条件下搅拌3h，使得少量的月桂酸完全消耗完，之后冷却过滤，所得固体再用纯水洗涤两次，最后在70℃下烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物。
所得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物质量为32.4g，产率为94.9％，月桂酸含量检测不出，熔点148～150℃。
实例9
在1L的三口烧瓶中，将27.1g(0.15mol)N-月桂酰-L-丙氨酸和9.9g(0.033mol)三光气(C 3Cl 6O 3)溶于700mL氯仿和10mL 1-甲基哌啶的混合溶液中，在30℃下磁力搅拌反应8h，反应后蒸去剩余的氯仿，得到N-月桂酰-L-丙氨酰氯。
在1L的三口烧瓶中，将11.16g(0.08mol)L-丙氨酸甲酯盐酸盐和8.1g(0.08mol)三乙胺以及23.55g(0.1mol)N-月桂酰-L-丙氨酰氯溶于300mL丙酮中，在3℃下磁力搅拌反应7h，然后升至室温继续磁力搅拌反应6h，待反应结束后，蒸去剩余的丙酮，得到N-月桂酰-L-丙氨酰-L-丙氨酸甲酯。
在1L的三口烧瓶中，将35.6g(0.1mol)N-月桂酰-L-丙氨酰-L-丙氨酸甲酯和20g(0.5mol)氢氧化钠溶于700mL乙醇和100mL水的混合溶液中，磁力搅拌反应8h，待反应结束后蒸去甲醇，得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐。
在糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐中加入5％盐酸酸化至pH＝3-4，逐渐析出白色固体，然后在冰浴下放置3h后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
在N-月桂酰-L-丙氨酰-L-丙氨酸粗品中加入水和丙酮的混合溶剂、L-丙氨酰-L-丙氨酸和对甲苯磺酸，其中，N-月桂酰-L-丙氨酰-L-丙氨酸粗品、水和丙酮的混合溶剂、L-丙氨酸、对甲苯磺酸按照摩尔比1:10:0.2:0.002的量加入并在温度为25℃、压力为50kg的条件下搅拌3h，使得少量的月桂酸完全消耗完，之后冷却过滤，所得固体再用纯水洗涤两次，最后在70℃下烘干，即得N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物。
所得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物质量为30.9g，产率为90.5％，月桂酸含量检测不出，熔点148～150℃。
实施例2 N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物的结构特征
图4a为根据本发明的实施例1中的合成方法得到的氨基酸自组装超分子聚合物N-月桂酰-L-丙氨酰-L-丙氨酸单体形成超分子氨基酸的结构形成图；图4b为根据本发明的实施例1中的合成方法得到的N-月桂酰-L-丙氨酰-L-丙氨酸单体形成超分子氨基酸的结构形成图。根据上述核磁谱图、质谱图可以看出，采用本工艺所生产的N-月桂酰-L-丙氨酰-L-丙氨酸基本不含有杂质月桂酸，工艺中合成得到的N-月桂酰-L-丙氨酰-L-丙氨酸可以形成三组氢键，两端各有十一个碳链的烷烃结构，根据油油相溶原则，亲油端与亲油端链条式契合，首尾相连接， 形成一个圆环。圆环与圆环之间又通过氢键及油油相溶，无限叠加形成柱状分子簇。柱状分子簇又无限叠加形成特殊的空间结构—称为超分子氨基酸。
柱状分子簇又无限叠加形成特殊的空间结构，由于存在二个或者二个以上的构型，在叠加时会有一定角度的偏差，在叠加时会形成支链。图5a、5b和5c分别示出了根据本发明的实施例1中的合成方法得到的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物的10000倍、20000倍以及50000倍电镜图。如图5a、5b和5c所示，更好的证明了N-月桂酰-L-丙氨酰-L-丙氨酸单体形成超分子氨基酸的形成原理及结构。
在上述超分子氨基酸形成之后，超分子氨基酸进一步与氢氧化钠反应生成如图6所示的超分子氨基酸的钠盐结构。根据图6所示，其钠盐结构一面亲水，一面亲油，分子间通过氢键相连接，得到一个特殊的二维网状规则排列结构，由于碳链长度与硬脂酸相仿，具有很强的跟油污相结合的能力，可作为主表面活性剂使用。
月桂酸的存在会破坏N-月桂酰-L-丙氨酰-L-丙氨酸之间氢键的无限连接形成，实验验证含有月桂酸的N-月桂酰-L-丙氨酰-L-丙氨酸，得不到上述的电镜图。所以本工艺解决了杂质月桂酸的残留问题，使得N-月桂酰-L-丙氨酰-L-丙氨酸之间易于形成氢键，无限连接，具有特殊性能。本工艺有效的解决了杂质月桂酸的残留破坏N-月桂酰-L-丙氨酰-L-丙氨酸结构，并进一步影响破坏N-月桂酰-L-丙氨酰-L-丙氨酸性能的问题，使得N-月桂酰-L-丙氨酰-L-丙氨酸之间易于形成氢键，无限连接，具有特殊性能。
在进一步实验中，本发明用N-葵酰-L-丙氨酰-L-丙氨酸在相同条件下进行了结构研究，未发现上述三维网状结构，推测可能是N-葵酰-L-丙氨酰-L-丙氨酸的碳链长度短，两个分子的亲油端之间不能成环，同样，由此可以推测亲油基团的碳链在12-18之间，与L-丙氨酰-L-丙氨酸形成的脂肪酰-L-丙氨酰-L-丙氨酸，在除去脂肪酸的条件下，通过分子间的氢键及油油相溶，也可以形成上述空间结构。这个结构一旦形成很稳定，实验证明，再少量添加脂肪酸10％以下，不会破坏已有结构的稳定性和性能应用。
实施例3 N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物的应用
实例1 N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物对细菌的抑制作用评价
取根据实施例1的方法合成的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物10g加入水中，加10％的氢氧化钠水溶液中和至pH＝6～7，配制成100mL的水溶液。取5mL原液，将此溶液分别浸泡预先接种了金黄色葡萄糖球菌、大肠杆菌、铜绿假单胞菌、白假丝酵母菌、铜绿假单胞菌等常见的细菌于果盘上，作用一定时间，用清水冲洗一次，然后测定果盘上的细菌残留。检测结果如表1：
表1：N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物的抑菌作用分析
Figure PCTCN2019089819-appb-000010
Figure PCTCN2019089819-appb-000011
由以上数据可以看出，根据本发明方法合成的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物溶液对大肠杆菌、金黄色葡萄球菌和白假丝酵母菌具有明显的抑制作用，在原液即N-月桂酰-L-丙氨酰-L-丙氨酸溶液作用于大肠杆菌2min后，其抑制率可达到100％；而原液作用于金黄色葡萄球菌2min后，就可达到100％的抑制率；作用于白假丝酵母菌3min抑制率也同样可以达到100％；原液作用于铜绿假单胞菌2min，抑制率同样能够达到100％。
对比实例1 N-月桂酰-L-丙氨酸自组装聚合物对细菌的抑制作用评价
同样的条件下，检测N-月桂酰-L-丙氨酸自组装聚合物的抑菌效果，见于如下表2中所示：
其中，实例1与对比实例1的区别仅在于将N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物替换成N-月桂酰-L-丙氨酸自组装聚合物，其他条件均保持与实例1中一致。
表2 N-月桂酰-L-丙氨酸自组装聚合物对细菌的抑制效果
Figure PCTCN2019089819-appb-000012
Figure PCTCN2019089819-appb-000013
通过对比表1和表2可以看出，本发明的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物其抑菌效果较N-月桂酰-L-丙氨酸自组装聚合物优势更明显。基于以上的数据可以说明，本发明的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物对抑菌具有意想不到的抑制效果。
根据本领域公知常识可知，细菌大小通常在0.5～5μm，而本发明所用的基本不含月桂酸的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物形成的超分子结构的柱团与柱团之间的空隙也是微米级的，所以能够将细菌包裹去除，所以可以称为能够产生纳米级的泡沫微孔。
实例2 N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物对农药的去除效果评价
取100g事先喷洒过农药甲胺磷和乙酰甲胺磷的绿叶蔬菜(大青菜)两份，一份直接用清水1L浸泡，然后取出检测其蔬菜叶子上的农药残留，称为清洗前。另一份使用根据实施例3的方法合成的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物配制的溶液来清洗，称为清洗后。操作如下描述：
取根据实施例1的方法合成的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物10g加入水中，加10％的氢氧化钠水溶液中和至pH＝6～7，配制成100mL的水溶液。取5mL原液，将另一份事先喷洒过农药甲胺磷和乙酰甲胺磷的绿叶蔬菜(大青菜)100g，剪碎，浸泡在上述溶液中2分钟，取出后用500mL清水冲洗，然后取出检测其蔬菜叶子上的农药残留。表3示出了清洗前后的农药数据残留对比：
表3：N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物对农药的去除效果分析
序号 检验项目 清洗前mg/kg 清洗后mg/kg 去除率％
1 甲胺磷 17.26 1.51 90.6
2 乙酰甲胺磷 39.53 2.67 93.2
根据以上数据可以看出，本发明所使用的表面活性物质N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物溶液对甲胺磷和乙酰甲胺磷具有明显的去除作用，作用2min后，对甲胺磷的去除率可达到90.6％；对乙酰甲胺磷的去除率可达到93.2％，效果明显。
对比实例2 N-月桂酰-L-丙氨酸自组装聚合物对农药的去除效果评价
同样的条件下，检测N-月桂酰-L-丙氨酸自组装聚合物的抑菌效果，见于如下表4中所示：
其中，对比实例2与实例2的区别仅在于将N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物替换成N-月桂酰-L-丙氨酸自组装聚合物进行对农药的去除效果评价，其他条件均保持与实例2中一致。
表4 N-月桂酰-L-丙氨酸自组装聚合物对农药的去除效果
序号 检验项目 清洗前mg/kg 清洗后mg/kg 去除率％
1 甲胺磷 16.06 5.68 64.63
2 乙酰甲胺磷 38.48 9.75 74.66
通过对比表3和表4可以看出，本发明的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物其对农药去除的效果较N-月桂酰-L-丙氨酸自组装聚合物优势更明显。
基于以上可知，本发明的自组装超分子聚合物N-月桂酰-L-丙氨酰-L-丙氨酸的制备方法工艺步骤简单，反应条件温和，适于工业化生产。根据本发明的方法制备得到的自组装超分子聚合物N-月桂酰-L-丙氨酰-L-丙氨酸纯度高，月桂酸含量HPLC检测不出来，有效的避免了月桂酸对产品质量的影响。所得到的N-月桂酰-L-丙氨酰-L-丙氨酸结构性能稳定；具有良好的抑菌率， 对大肠杆菌、金黄色葡萄球菌、白假丝酵母菌以及铜绿假单胞菌的抑制率均可达到100％；有效去除农药残留，对甲胺磷的去除率可达90.6％，对乙酰甲胺磷的去除率可达93.2％；同时具有良好的除异味性能，在日化领域、农业、医药行业均可以有很好的应用。
实施例4-8
实施例中氨基酸牙膏膏体的总重量份数均为100。牙膏中各物质组成以及具体含量如表5所示：
表5：牙膏中各物质组成及含量
Figure PCTCN2019089819-appb-000014
实施例9-13
实施例中氨基酸牙膏膏体的总重量份数均为100。牙膏中各物质组成以及具体含量如表6所示：
表6：牙膏中各物质组成及含量
Figure PCTCN2019089819-appb-000015
根据实施例4的配方制备牙膏，具体步骤包括：将10g水、37.5g山梨(糖)醇、0.2g糖精钠、2g聚乙二醇-400、5g甘油、0.4g苯甲酸钠制成水溶液置于制膏机中。然后将4g羧甲基纤维素、35g水合硅石、0.2g邹波角叉菜提取物、0.1g甘草提取物以及0.1g马齿苋提取物混合后加入制膏机，搅拌研磨20-30min直至膏体均匀为止，然后真空脱泡；将4.4gN-月桂酰-L-丙氨酰-L-丙氨酸钠聚合物、1g食用香精(薄荷香型)、0.1g CI42090依次加入制膏机中，搅拌研磨10-15min至膏体均匀，然后脱泡，即得氨基酸牙膏。
实施例5-13均采用实施例4中所述方法制备，在实施例中就不再具体赘述。
根据实施例4-13中的配方量制得的氨基酸牙膏，取不同重量份数的氨基酸表面活性剂，重复进行多次配方试验，分别委托100名经常牙痛和牙龈出血的志愿者进行效果评价，使用频率为每日早、晚各一次，用量约1g膏体/每次，每次刷牙时间约5min。得到的结果表明含有氨基酸表面活性成分的牙膏具有明显的镇痛、消炎和防止牙龈出血的功效，并且从使用口感和去味两方面评价，氨基酸表面活性成分占该牙膏膏体的重量比为0.1-25％比较适宜，优化为0.5-10％，最佳优化为1-5％。当氨基酸表面活性成分占该药物牙膏膏体的重量比为1-5％时，牙膏的药效与口感处于最佳平衡，而且去除口腔异味达到最佳水平，同时刷牙后立马吃水果不影响食用水果时的味道，不会觉得苦和干涩。
实施例14 N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物在皮肤护理上的 应用
表7：皮肤护理组合物组成原料及重量百分比含量
Figure PCTCN2019089819-appb-000016
Figure PCTCN2019089819-appb-000017
*天然油混合物包含有40％的葡萄籽油、37.2％的向日葵籽油和22.8％的芦荟油。
根据表7所示的配方1的具体制备步骤包括：将57％天然油混合物和40％玉米淀粉加入到混合器中并匀化以使颗粒首先分散。然后将油分散体中的颗粒加热至83-86℃同时混合。在加热的同时将3％N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物加入到混合器中。样品加热并保持在73-86℃下保持5-10min。然后将其冷却至65-72℃之间的温度，同时保持可混合。然后将样品倒入体积为30ml的罐中即得皮肤护理组合物，保存并用于评估。其中，配方2-6中的皮肤护理组合物制备方法均采用与配方1中一样的方法，在此不再赘述。
根据以上实施例得到的皮肤护理组合物，其中原料中添加了不同种类及含量的颗粒物。结果表明，颗粒物的加入除了增加了油的粘度之外，N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物也可用于将固体有机/无机颗粒或油混合液体如甘油稳定地悬浮在增稠的天然油中以获得额外的皮肤益处。
使用四种油不溶性颗粒，例如淀粉、TiO 2、云母、氮化硼颗粒(来自Kobo的Caress BN02)以及一种油可混合液体如甘油。配方1-6中所用天然油混合物组分均一样，即包含40％的葡萄籽油、37.2％的向日葵籽油和22.8％的芦荟油。结果显示，表3中所示的所有配方得到的组合物在室温下和48℃烘箱中都是稳定的，没有任何颗粒分离问题。而配方7中使用了月桂酰丙氨酸(含月桂酸2％以上)代替了配方1中的N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物，用以对比试验，结果发现所得到组合物在48℃烘箱中48小时后不稳定 的，有冒油现象。
实施例15超分子氨基酸在洗衣液中应用实例
表8氨基酸洗衣液
Figure PCTCN2019089819-appb-000018
按照表8配方1所配成的洗衣液，经苏州市产品质量监督检验所检测，去污力大于等于标准洗衣液去污力，所得样品对JB01、JB02、JB03污布去污力大于标准洗衣液对JB01、JB02、JB03污布去污力。而按照配方2所配成的洗衣液，经苏州市产品质量监督检验所检测，去污力小于标准洗衣液去污力。
实施例16超分子氨基酸和N-月桂酰-L-丙氨酸形成的自组装聚合物构 成的表面活性剂在洗面奶中应用实例
表9超分子氨基酸洗面奶
Figure PCTCN2019089819-appb-000019
Figure PCTCN2019089819-appb-000020
N-月桂酰-L-丙氨酰-L-丙氨酸自组装聚合物和N-月桂酰-L-丙氨酸自组装聚合物在碱性水相体系形成的盐，可以作为清洁的表面活性剂，该表面活性剂温和，无刺激性，控油性强，对于敏感肌肤更加适用。
此外，本领域的技术人员能够理解，尽管在此所述的一些实施例包括其它实施例中所包括的某些特征而不是其它特征，但是不同实施例的特征的组合意味着处于本发明的范围之内并且形成不同的实施例。例如，在下面的权利要求书中，所要求保护的实施例的任意之一都可以以任意的组合方式来使用。

Claims (49)

  1. 一种氨基酸自组装超分子聚合物或其盐，所述聚合物是N-月桂酰-L-丙氨酰-L-丙氨酸单体之间通过氢键连接形成；以聚合物或其盐的总重量计，所述聚合物或其盐中月桂酸重量百分含量低于0.02％，优选低于0.01％。
  2. 如权利要求1所述的氨基酸自组装超分子聚合物或其盐，其特征在于，所述N-月桂酰-L-丙氨酰-L-丙氨酸单体之间通过氢键连接形成如式(Ⅰ)所示的结构：
    Figure PCTCN2019089819-appb-100001
  3. 如权利要求1所述的氨基酸自组装超分子聚合物或其盐，其特征在于，所述聚合物的重均分子量介于5000-500万之间。
  4. 如权利要求1所述的氨基酸自组装超分子聚合物或其盐，其特征在于，所述聚合物基本不含或不含月桂酸。
  5. 如权利要求1所述的氨基酸自组装超分子聚合物或其盐，其特征在于，所述聚合物的熔点为148-150℃。
  6. 如权利要求1-5任一项所述的氨基酸自组装超分子聚合物或其盐，其特征在于，所述盐为聚合物与碱形成；所述碱包括无机碱和有机碱。
  7. 一种新型氨基酸自组装超分子聚合物钠盐，其特征在于，是N-月桂酰-L-丙氨酰-L-丙氨酸钠单体之间通过氢键连接形成；所述聚合物钠盐中月桂酸基本不含或不含月桂酸。
  8. 如权利要求7所述的氨基酸自组装超分子聚合物钠盐，其特征在于，所述N-月桂酰-L-丙氨酰-L-丙氨酸钠单体之间通过氢键连接形成如式(Ⅱ)所示的结构：
    Figure PCTCN2019089819-appb-100002
    其中，n为8-20000；n个N-月桂酰-L-丙氨酰-L-丙氨酸钠在同一平面通过氢键依次连接，或n个N-月桂酰-L-丙氨酸钠通过氢键依次连接且首尾通过氢键连 接以形成一柱状。
  9. 如权利要求7所述的氨基酸自组装超分子聚合物钠盐，其特征在于，氨基酸自组装超分子聚合物钠盐的重均分子量介于5000-500万之间。
  10. 一种新型氨基酸自组装超分子聚合物的制备方法，其特征在于，所述方法包括步骤：
    将N-月桂酰-L-丙氨酰-L-丙氨酸粗品、溶剂、L-丙氨酰-L-丙氨酸和催化剂混合、搅拌后得到N-月桂酰-L-丙氨酰-L-丙氨酸自组装超分子聚合物。
  11. 如权利要求10所述的方法，其特征在于，所述N-月桂酰-L-丙氨酰-L-丙氨酸粗品通过如下步骤制备得到：
    (1)将L-丙氨酰-L-丙氨酸与金属无机碱溶于蒸馏水和有机溶剂的混合溶液中搅拌均匀得到L-丙氨酰-L-丙氨酸盐溶液；
    (2)向上述得到的L-丙氨酰-L-丙氨酸盐溶液中依次加入月桂酰氯和金属无机碱，继续搅拌得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐；
    (3)将上述得到的糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐酸化，逐渐析出白色固体，冷却后过滤，得到N-月桂酰-L-丙氨酰-L-丙氨酸粗品。
  12. 如权利要求11所述的方法，其特征在于，步骤(1)中所述L-丙氨酰-L-丙氨酸与金属无机碱的摩尔比为1:(1-1.5)；所述金属无机碱选自氢氧化钠、氢氧化钾、碳酸钠、碳酸钾中的一种或两种以上；所述有机溶剂选自丙酮、甲醇、乙醇、乙腈、四氢呋喃中的一种或两种以上；所述蒸馏水和有机溶剂的体积比为1:(1-1.5)。
  13. 如权利要求11所述的方法，其特征在于，步骤(2)中所述月桂酰氯与L-丙氨酰-L-丙氨酸的投料摩尔比为(0.8-1):1；所述搅拌条件为：温度5-50℃，时间1-3小时；所述属无机碱浓度为30-80％；所述金属无机碱选自氢氧化钠、氢氧化钾、碳酸钠、碳酸钾中的一种或两种以上。
  14. 如权利要求11所述的方法，其特征在于，所述溶剂选自丙酮、甲醇、乙醇、乙腈、四氢呋喃或上述溶剂与水制成的混合溶剂；所述催化剂选自硫酸、对甲苯磺酸、乳化剂中的一种或两种以上；所述N-月桂酰-L-丙氨酰-L-丙氨酸粗 品、溶剂、L-丙氨酰-L-丙氨酸、催化剂的摩尔比为1:(5-10):(0.1-0.2):(0.001-0.1)；所述搅拌条件为：温度25℃-100℃，压力5kg-50kg，时间1-3小时。
  15. 如权利要求11所述的方法，其特征在于，步骤(2)中向步骤(1)得到的L-丙氨酰-L-丙氨酸盐溶液中加入N-月桂酰-L-丙氨酰氯的溶液和金属无机碱，继续搅拌得到糊状的N-月桂酰-L-丙氨酰-L-丙氨酸盐；
    所述N-月桂酰-L-丙氨酰氯的溶液通过下述步骤得到：
    将N-月桂酰-L-丙氨酸和氯化试剂混合反应，冷却后加入戊-2-酮和活性炭依次经脱色、过滤、减压蒸馏，继续加入有机溶剂，溶解N-月桂酰-L-丙氨酸中的酰氯，得N-月桂酰-L-丙氨酰氯的溶液。
  16. 如权利要求15所述的方法，其特征在于，所述N-月桂酰-L-丙氨酸和氯化试剂的摩尔比为(1-1.5):5；所述的氯化试剂为二氯亚砜、三氯化磷、三光气、N-氯代丁二酰亚胺中的一种或两种以上。
  17. 一种新型氨基酸自组装超分子聚合物或其盐，其特征在于，所述聚合物通过如权利要求10-16任一项所述的方法制备得到。
  18. 一种如权利要求1-6任一项所述的氨基酸自组装超分子聚合物或其盐的用途，其特征在于，用作表面活性剂。
  19. 一种如权利要求7-9任一项所述的氨基酸自组装超分子聚合物钠盐的用途，其特征在于，用作表面活性剂。
  20. 如权利要求18或19所述的用途，其特征在于，所述表面活性剂用于日化领域、农业、医药行业。
  21. 一种组合物，其特征在于，所述组合物中含有如权利要求1-10任一项所述的氨基酸自组装超分子聚合物或其盐，和N-月桂酰-L-丙氨酸单体之间通过氢键连接形成的聚合物或其盐，以组合物的总重量计，其中N-月桂酰-L-丙氨酸单体之间通过氢键连接形成的聚合物或其盐的重量百分含量介于0-60％之间。
  22. 一种氨基酸牙膏，包含摩擦剂、保湿剂、增稠剂和表面活性剂，所述的表面活性剂选自N-月桂酰-L-丙氨酰-L-丙氨酸或其盐、或如权利要求1-10任一项所述的氨基酸自组装超分子聚合物或其盐；以牙膏的总重量计，其中含有表面活性剂0.1-25％，摩擦剂10-50％，保湿剂5-40％，增稠剂0.1-6％。
  23. 如权利要求22所述的氨基酸牙膏，其特征在于，所述的摩擦剂选自水合硅石、碳酸钙以及磷酸氢钙中的一种或几种的混合。
  24. 如权利要求22所述的氨基酸牙膏，其特征在于，所述的保湿剂选自山梨(糖)醇、聚乙二醇-400、甘油以及丙二醇中的一种或几种的混合。
  25. 如权利要求22所述的氨基酸牙膏，其特征在于，所述的增稠剂选自羧甲基纤维素、黄原胶、卡拉胶、卡姆胶、泊洛沙姆407以及硅酸铝镁中的一种或几种的混合。
  26. 如权利要求22-25任一项所述的氨基酸牙膏，其特征在于，所述氨基酸牙膏还包含如下重量百分比的物质：甜味剂0.1-0.3％，香精0.5-1.5％，水5-10％，中草药提取物0.3-0.5％，防腐剂0.3-0.5％，着色剂0.05-0.15％。
  27. 如权利要求26所述的氨基酸牙膏，其特征在于，所述的甜味剂选自糖精钠、木糖醇以及赤藓糖醇中的一种或几种的混合。
  28. 如权利要求26所述的氨基酸牙膏，其特征在于，所述的中草药提取物选自邹波角叉菜提取物、甘草提取物以及马齿苋提取物中的一种或几种的混合。
  29. 如权利要求26所述的氨基酸牙膏，其特征在于，所述的防腐剂选自苯甲酸钠、羟苯甲酯、三氯羟苯醚/共聚体以及生物溶菌酶中的一种或几种的混合。
  30. 如权利要求26所述的氨基酸牙膏，其特征在于，所述的着色剂选自CI77019、CI77891、CI42090、云母、二氧化钛、亮蓝中的一种或几种的混合。
  31. 如权利要求22所述的氨基酸牙膏，其特征在于，所述的氨基酸牙膏中不含十二烷基硫酸钠。
  32. 一种制备权利要求22-31任一项所述的氨基酸牙膏的方法，其特征在于，所述方法包括以下步骤：
    (1)将水、甜味剂、防腐剂、保湿剂制成水溶液置于制膏机中；
    (2)将增稠剂、摩擦剂、中草药提取物混合后加入制膏机，搅拌研磨直至膏体均匀为止，然后真空脱泡；
    (3)将表面活性剂、香精、着色剂依次加入制膏机中，搅拌研磨至膏体均匀，然后脱泡，即得氨基酸牙膏；所述表面活性剂选自N-月桂酰-L-丙氨酰-L-丙氨酸或其盐、或如权利要求1-10任一项所述的氨基酸自组装超分子聚合物或其盐。
  33. 皮肤护理组合物，以相对于其总重量计，所述的组合物包含：
    油类             50-95重量％；
    表面活性剂       0.5-30重量％；以及
    悬浮颗粒              0-45重量％
    所述表面活性剂选自N-月桂酰-L-丙氨酰-L-丙氨酸或其盐、或如权利要求1-10任一项所述的氨基酸自组装超分子聚合物或其盐。
  34. 如权利要求33所述的皮肤护理组合物，其特征在于，所述油类选自凝固点在-50℃-6℃之间的天然油、合成油或其混合物。
  35. 如权利要求33所述的皮肤护理组合物，其特征在于，所述天然油包括植物油和动物油。
  36. 如权利要求33所述的皮肤护理组合物，其特征在于，所述植物油包括葡萄籽油、向日葵籽油、霍霍巴油、芦荟油、橄榄油、亚麻籽油、红花籽油、大豆油、杏仁油、茶油或其任意混合物。
  37. 如权利要求33所述的皮肤护理组合物，其特征在于，所述动物油包括马油和绵羊油。
  38. 如权利要求33所述的皮肤护理组合物，其特征在于，所述合成油包括新癸酸异癸酯和新戊二醇二庚酸酯。
  39. 如权利要求33所述的皮肤护理组合物，其特征在于，所述油类的含量为65重量％。
  40. 如权利要求33所述的皮肤护理组合物，其特征在于，所述油类的含量为85重量％。
  41. 如权利要求33所述的皮肤护理组合物，其特征在于，所述表面活性剂中不含月桂酸。
  42. 如权利要求33所述的皮肤护理组合物，其特征在于，所述悬浮颗粒的粒度小于30μm。
  43. 如权利要求33所述的皮肤护理组合物，其特征在于，所述悬浮颗粒的粒度小于15μm。
  44. 如权利要求33所述的皮肤护理组合物，其特征在于，所述悬浮颗粒的粒度小于5μm。
  45. 如权利要求33所述的皮肤护理组合物，其特征在于，所述悬浮颗粒选自油不溶性的固体颗粒或油不混溶液体。
  46. 如权利要求45所述的皮肤护理组合物，其特征在于，所述油不溶性的固体颗粒包括云母、淀粉、氧化锌、二氧化钛、滑石粉和有机硅弹性体。
  47. 如权利要求45所述的皮肤护理组合物，其特征在于，所述油不混溶液体包括甘油、水和多元醇。
  48. 制备权利要求33-47中任一项所述的皮肤护理组合物的方法，其特征在于，所述方法包括以下步骤：
    (1)将油类、表面活性剂和悬浮颗粒按照重量百分比为(50-95％)：(0.5-30％)：(0-45％)的量混合后在82-87℃下搅拌反应，待表面活性剂全部溶于所述油类后将混合物搅拌冷却至65-72℃；所述表面活性剂选自N-月桂酰-L-丙氨酰-L-丙氨酸或其盐、或如权利要求1-10任一项所述的氨基酸自组装超分子聚合物或其盐；
    (2)将上述得到的混合物冷却至室温，即得皮肤护理组合物。
  49. 一种氨基酸洗衣液，其特征在于，包含表面活性剂；所述所述表面活性剂选自N-月桂酰-L-丙氨酰-L-丙氨酸或其盐、或如权利要求1-9任一项所述的氨基酸自组装超分子聚合物或其盐；所述氨基酸表面活性剂的重量比为0.1-25％。
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