CN121203164A

CN121203164A - Supramolecular aggregates, their preparation methods, and cosmetic compositions containing them

Info

Publication number: CN121203164A
Application number: CN202410820747.5A
Authority: CN
Inventors: 李臻; 吴艳; 高映虹; 曹丰; 姚继宗; 李雨峰; 王小永; 周奂君
Original assignee: ELC Management LLC
Current assignee: ELC Management LLC
Priority date: 2024-06-24
Filing date: 2024-06-24
Publication date: 2025-12-26
Also published as: WO2026001245A1

Abstract

The present disclosure relates generally to the field of supramolecular chemistry, and in particular to novel supramolecular aggregates, methods of making the same, and cosmetic compositions containing the same.

Description

Supermolecule aggregate, method for preparing the same, and cosmetic composition comprising the same

Technical Field

Background

Azelaic acid, also known as azaleic acid (Azelaic acid), having the molecular formula C ₉H₁₆O₄, is widely used in the cosmetic field due to its excellent antibacterial properties. However, azelaic acid has very little solubility in water, and only about 2 to 3g of azelaic acid can be dissolved per liter of water, which makes it difficult to prepare water-based cosmetics. And because the melting point is as high as 131-134 ℃, the melting point can be melted at a higher temperature in the heating process, which increases the complexity of the preparation process and the energy consumption.

Various attempts have been made to increase the water solubility of azelaic acid. CN113248364a discloses a method for solubilising azelaic acid comprising compounding using an alkaline substance. CN112624918a discloses a method for forming supermolecular co-crystals by reacting azelaic acid with an organic compound containing an amino group such as pyridine carboxamide. CN117567763a discloses a supramolecular system formed by azelaic acid, lactic acid and panthenol. However, the methods in CN113248364A and CN112624918a are prone to azelaic acid decomposition due to the alkaline environment, and there are concerns about stability as well as reduced efficacy. Further, lactic acid used in the method described in CN117567763a may damage the skin barrier after long-term use, and the skin becomes fragile and is easily affected by external harmful substances. This in turn also causes skin inflammation or other skin problems. Accordingly, there is a need for improvements and developments in the art.

Disclosure of Invention

The present invention has been made to solve the problems occurring in the prior art, and an object of the present invention is to provide a novel azelaic acid supermolecule aggregate which can improve the solubility of azelaic acid in water and has good stability without causing the above-mentioned skin problems even after long-term use.

As a result of intensive studies on a method for forming azelaic acid supramolecular aggregates, the present inventors have unexpectedly found that azelaic acid and a heterocyclic amino acid represented by the following general formula (I) can form a novel supramolecular aggregate which can improve the solubility of azelaic acid in water and is excellent in stability without causing skin inflammation or other skin problems even after long-term use.

In a first aspect, the present disclosure provides a supramolecular aggregate formed from azelaic acid and at least one heterocyclic amino acid of formula (I),

Wherein R ₁ and R ₂ each independently represent hydrogen or hydroxy, and at least one of R ₁ and R ₂ represents hydrogen, and

Wherein the powder X-ray diffraction pattern of the aggregate comprises characteristic peaks at 5.7 ° ± 0.2 ° and 21.8 ° ± 0.2 °.

According to some embodiments, the powder X-ray diffraction pattern of the aggregate further comprises at least 2, preferably at least 4, characteristic peaks ：8.5°±0.2°、9.4°±0.2°、16.7°±0.2°、17.6°±0.2°、18.5°±0.2°、19.4°±0.2°、20.3°±0.2°、21.1°±0.2°、23.0°±0.2°、23.6°±0.2°、27.3°±0.2° and 28.3 ° ± 0.2 ° at 2Θ as described below.

According to some embodiments, the powder X-ray diffraction pattern of the aggregate further comprises at least 2, preferably at least 4, characteristic peaks at 16.6 ° ± 0.2 °, 17.5 ° ± 0.2 °, 19.3 ° ± 0.2 ° and 22.9 ° ± 0.2 °.

According to some embodiments, the powder X-ray diffraction pattern of the aggregate further comprises at least 2, preferably at least 4, characteristic peaks ：8.3°±0.2°、9.3°±0.2°、16.5°±0.2°、17.4°±0.2°、18.0°±0.2°、18.4°±0.2°、19.0°±0.2°、22.8°±0.2°、23.4°±0.2°、27.1°±0.2° and 28.1 ° ± 0.2 ° at 2Θ as described below.

According to some embodiments, the powder X-ray diffraction pattern of the aggregate comprises characteristic peaks ：5.7°±0.2°、8.5°±0.2°、9.4°±0.2°、16.7°±0.2°、17.6°±0.2°、18.5°±0.2°、19.4°±0.2°、20.3°±0.2°、21.1°±0.2°、21.8°±0.2°、23.0°±0.2°、23.6°±0.2°、27.3°±0.2° and 28.3 ° ± 0.2 ° at 2Θ described below.

According to some embodiments, the powder X-ray diffraction pattern of the aggregate comprises characteristic peaks at 5.5 ° ± 0.2 °, 16.6 ° ± 0.2 °, 17.5 ° ± 0.2 °, 19.3 ° ± 0.2 °, 21.7 ° ± 0.2 ° and 22.9 ° ± 0.2 °.

According to some embodiments, the powder X-ray diffraction pattern of the aggregate comprises characteristic peaks ：5.5°±0.2°、8.3°±0.2°、9.3°±0.2°、16.5°±0.2°、17.4°±0.2°、18.0°±0.2°、18.4°±0.2°、19.0°±0.2°、21.7°±0.2°、22.8°±0.2°、23.4°±0.2°、27.1°±0.2° and 28.1 ° ± 0.2 ° at 2Θ described below.

According to some embodiments, the heterocyclic amino acid is proline or hydroxyproline, preferably proline.

According to some embodiments, the molar ratio of azelaic acid to proline is 1:5-5:1, preferably 1:2-2:1, more preferably 1:1-2:1.

According to some embodiments, the aggregate exhibits 1 endothermic peak in its DSC profile at a temperature of 76 ℃ to 86 ℃.

According to some embodiments, the aggregate further exhibits 1 endothermic peak in its DSC profile at a temperature of 94 ℃ to 103 ℃.

According to some embodiments, the aggregate has only one endothermic peak in its DSC profile at a temperature of 78 ± 2 ℃.

In a second aspect, the present disclosure further provides a method of preparing a supramolecular aggregate from azelaic acid and a heterocyclic amino acid comprising the steps of:

1) Azelaic acid and at least one heterocyclic amino acid shown in the following general formula (I) are mixed according to a molar ratio of 1:5-5:1, preferably 1:2-2:1, more preferably 1:1-2:1, and more preferably 1:1 to obtain a mixture;

2) The mixture is subjected to liquid-assisted milling or cooling crystallization to obtain supramolecular aggregates.

According to some embodiments, the liquid-assisted milling is performed using a lower saturated alkyl alcohol as the milling liquid, wherein the ratio of the volume of the lower saturated alkyl alcohol to the mass of the mixture is 0.1 to 0.5ml/g.

According to some embodiments, the lower saturated alkyl alcohol is ethanol.

In a third aspect, the present disclosure further provides a cosmetic composition comprising the supramolecular aggregates described in the present disclosure.

According to some embodiments, the composition further comprises at least one active ingredient selected from the group consisting of surfactants, humectants, non-volatile oils, antioxidants, UV screening agents, anti-inflammatory agents, natural extracts, ferments, vitamins, skin conditioning agents, preservatives, thickeners, and mixtures thereof.

Other subjects and features, aspects and advantages of the present invention will become more apparent upon reading the following description and examples.

Drawings

The accompanying drawings are included to provide a further understanding of embodiments of the disclosure, and are incorporated in and constitute a part of this specification. They are used in conjunction with the following detailed description of the present invention to illustrate but not to limit the embodiments of the present disclosure. In the drawings:

figure 1 shows DSC profiles of azelaic acid and L-proline as starting materials, and supramolecular aggregates prepared by different starting material ratios and preparation methods.

Figure 2 shows powder X-ray diffraction patterns of azelaic acid and L-proline as starting materials, and supramolecular aggregates prepared by different starting material ratios and preparation methods.

FIG. 3 shows powder X-ray diffraction patterns of azelaic acid and L-lysine as raw materials, and the supramolecular aggregate prepared in comparative example 1.

Detailed Description

I. Definition of the definition

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. To the extent that the term definition in the present specification conflicts with the meaning commonly understood by one of ordinary skill in the art to which this disclosure pertains, the definition in the present specification controls.

Throughout this disclosure, the term "comprising" should be interpreted to cover all the specifically mentioned features as well as optional, additional, unspecified features. As used herein, use of the term "comprising" also discloses embodiments (i.e., "consisting of") that do not have features other than the ones specifically mentioned.

Unless otherwise indicated, all numbers expressing quantities of ingredients and so forth used in the specification and claims are to be understood as being modified by the term "about" and have the meaning conventionally known in the art such as within 10% of the indicated number (e.g., "about 100-220" means 90-242, "about 10" means 9-11). Accordingly, unless indicated otherwise, the numerical values and parameters set forth herein are approximations that may vary depending upon the desired purposes. At the very least, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Furthermore, the scope described in the present disclosure and claims is intended to include the entire scope specifically, not just the endpoints. For example, a range of 0 to 10 is intended to disclose all integers between 0 to 10, such as 1, 2, 3, 4, and any two values thereof forming subranges, etc., all fractions between 0 to 10, such as 1.5, 2.3, 4.57, 6.1113, and any two values thereof forming subranges, etc., and endpoints 0 and 10.

The term "supramolecular aggregates" as used herein means aggregates composed of two or more molecules bound together by intermolecular interactions, such as hydrogen bonds, pi-pi stacking, van der Waals forces, and other non-covalent bonds.

The term "co-crystal" as used herein is a morphological description of an aggregate of supramolecules and refers to a crystal formed by two or more different molecules joined together in a fixed stoichiometric ratio by non-covalent bonds within the same lattice.

The term "liquid-assisted milling" as used herein is sometimes also referred to as "wet milling," which is a technique that involves the addition of small amounts of solvents and milling of the raw materials to form crystals.

The term "cooling crystallization", sometimes referred to herein as "cooling crystallization", is a technique that includes heating a raw material solution to a temperature that is reduced after sufficient dissolution to supersaturate the solution to precipitate crystals.

Supramolecular aggregates

Supramolecular aggregates refer to complex, organized aggregates formed by intermolecular interactions of two or more molecules, which maintain a certain integrity and have defined microscopic and macroscopic properties. These intermolecular interactions may include weak interactions of non-covalent bonds such as electrostatic interactions, hydrogen bonds, coordination bonds, van der Waals forces, pi-pi conjugation, hydrophobic interactions, and the like.

The application of supermolecular technology in the cosmetic field has been increasingly widespread due to the important pushing action on raw material development and product upgrading. However, according to the techniques so far, not all molecules can form supramolecular aggregates, and the selection of suitable target molecules for forming azelaic acid supramolecular aggregates still presents difficulties.

According to a first aspect, the present disclosure provides a supramolecular aggregate formed from azelaic acid and at least one heterocyclic amino acid of formula (I),

Azelaic acid is a dicarboxylic acid obtained by replacing one hydrogen atom on any two carbon atoms of heptane with a carboxyl group. Because heptane has seven carbon atoms and the substitution sites can vary, a variety of possible azelaic acid isomers are produced. These isomers will differ based on the position of the carboxyl group on the heptane carbon chain. Azelaic acid as used herein is intended to encompass all such isomers.

In a preferred embodiment, the azelaic acid is in particular 1, 9-azelaic acid. As the 1, 9-azelaic acid, commercially available ones can be used. For example, azelaic acid supplied under the trade name Azelaic acid from Leyan (hereinafter, sometimes simply referred to as azo) is particularly used in the present disclosure.

In the present disclosure, the heterocyclic amino acid used to form the supramolecular aggregate with azelaic acid has an α -imino acid structure represented by the general formula (I).

In some embodiments, the heterocyclic amino acid is a heterocyclic amino acid of formula (I) wherein R ₁ and R ₂ are both hydrogen atoms, i.e., proline. The proline may be any one of L-proline, D-proline and DL-proline.

In some embodiments, the heterocyclic amino acid is a heterocyclic amino acid of formula (I) wherein either of R ₁ and R ₂ is hydroxy, i.e., hydroxyproline. Depending on the chiral structure, hydroxyproline includes cis-3-hydroxy-L-proline, cis-4-hydroxy-L-proline, trans-3-hydroxy-L-proline and trans-4-hydroxy-L-proline.

In some embodiments, the heterocyclic amino acid used in the present disclosure may be any of L-proline, D-proline, cis-3-hydroxy-L-proline, cis-4-hydroxy-L-proline, trans-3-hydroxy-L-proline, trans-4-hydroxy-L-proline.

In some embodiments, a heterocyclic amino acid in the present disclosure may be a combination of two or more of L-proline, D-proline, cis-3-hydroxy-L-proline, cis-4-hydroxy-L-proline, trans-3-hydroxy-L-proline, and trans-4-hydroxy-L-proline.

L-proline is one of the twenty amino acids used in human synthetic proteins. It has not only functions of moisturizing, improving dermal sensation, inhibiting skin pigmentation, etc., but also has an extremely low risk factor of 1, so that it is not easy to occur such as breaking skin barrier even after long-term use, causing skin to become fragile and causing skin inflammation, etc. Thus, in a preferred embodiment, the heterocyclic amino acid used in the present disclosure is preferably L-proline.

In some embodiments, the molar ratio of azelaic acid to proline in the supramolecular aggregate is 1:5 to 5:1, preferably 1:2 to 2:1, more preferably 1:1 to 2:1.

Without wishing to be bound by theory, it is believed that by having an α -imino acid structure, the heterocyclic amino acids in the present disclosure may intermolecular interact with two carboxyl groups in azelaic acid to form a co-crystal and thereby increase the solubility of azelaic acid and reduce its irritation to skin. Moreover, the proline used to form supramolecular aggregates with azelaic acid in the present disclosure is neutral due to the α -imino acid structure and does not constitute an alkaline environment. Thus, there is no concern in that the alkaline environment makes azelaic acid easily decomposed, resulting in stability problems of reduced efficacy.

In some embodiments, the solubility of azelaic acid is increased by at least 15%, preferably 17%, more preferably 19%, by forming supramolecular aggregates.

The expression "solubility of azelaic acid is increased by at least XX%" as used herein means that the solubility of azelaic acid in water in supramolecular aggregates formed from azelaic acid and heterocyclic amino acids is increased by at least XX% relative to the solubility of azelaic acid monomers in water in solubility assays using shake flask methods and ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) described below.

The term "XX%" as used herein means a specific percentage value of increased solubility of azelaic acid.

In some embodiments, the solubility of azelaic acid in supramolecular aggregates formed from azelaic acid and heterocyclic amino acids is increased by at least 16%, 17%, or 18% relative to the solubility of azelaic acid itself in water in a solubility assay using shake flask and ultra high performance liquid chromatography-mass spectrometry (UPLC-MS) as described below. In some embodiments, the solubility of azelaic acid can be increased by 19% by forming supramolecular aggregates.

In some embodiments, the supramolecular aggregates formed by azelaic acid and at least one heterocyclic amino acid of formula (I) in the present disclosure are co-crystals.

It has been found that the use of certain conditions (e.g., different preparation methods and/or different azelaic acid/proline stoichiometry) can result in different supramolecular aggregates, including supramolecular aggregate I, supramolecular aggregate II, and supramolecular aggregate III described herein, which can exhibit one or more of the advantageous properties described herein.

Supermolecular aggregate I

In some embodiments, supramolecular aggregate I has a powder X-ray diffraction (hereinafter sometimes PXRD) pattern substantially as shown in fig. 2C. The 2θ angles observed in PXRD for supramolecular aggregate I are shown in table 1 below.

TABLE 1

Angle/2 theta
	5.7
8.5
	9.4
16.7
	17.6
18.5
	19.4
20.3
	21.1
21.8
	23.0
23.6
	27.3
28.3

In some embodiments, supramolecular aggregate I has a PXRD pattern comprising at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 peaks at the 2θ angles, the relative intensities in the PXRD pattern being as shown in figure 2C.

It should be understood that the relative intensities may vary depending on a number of factors, including sample preparation, mounting, and instrumentation and analytical procedures and settings for obtaining spectra. The relative peak intensities and peak assignments may vary within experimental errors.

In some embodiments, the peak assignments listed herein, including supramolecular aggregate I, can vary by ± 0.2 degrees or ± 0.1 degrees 2θ. In some embodiments, the peak assignments listed herein, including supramolecular aggregate I, can vary by ± 0.2 degrees 2θ. In some embodiments, the peak assignments listed herein, including supramolecular aggregate I, can vary by ± 0.1 degrees 2θ.

In some embodiments, supramolecular aggregate I has a DSC (differential scanning calorimetry) curve substantially as shown in figure 1D. In some embodiments, supramolecular aggregate I is characterized by an endotherm occurring at about 78 ℃, as determined by DSC. In some embodiments, supramolecular aggregate I is characterized by an endotherm that occurs at about 78±2 ℃ (e.g., ,78±1.9℃、78±1.8℃、78±1.7℃、78±1.6℃、78±1.5℃、78±1.4℃、78±1.3℃、78±1.2℃、78±1.1℃、78±1℃、78±0.9℃、78±0.8℃、78±0.7℃、78±0.6℃、78±0.5℃、78±0.4℃、78±0.3℃、78±0.2℃、 or 78±0.1 ℃), as determined by DSC.

In some embodiments of supramolecular aggregate I, at least one or all of the following (a) to (d) apply:

(a) The supramolecular aggregate I has a PXRD pattern comprising peaks at 5.7 ° ± 0.2 °, 16.7 ° ± 0.2 °, 17.6 ° ± 0.2 °, 21.8 ° ± 0.2 °, 23.0 ° ± 0.2 °, or PXRD patterns :5.7°±0.2°、8.5°±0.2°、9.4°±0.2°、16.7°±0.2°、17.6°±0.2°、18.5°±0.2°、19.4°±0.2°、20.3°±0.2°、21.1°±0.2°、21.8°±0.2°、23.0°±0.2°、23.6°±0.2°、27.3°±0.2° and 28.3 ° ± 0.2 ° comprising peaks at 2 theta.

(B) Supramolecular aggregate I has a PXRD pattern substantially as shown in figure 2C.

(C) Supramolecular aggregate I is characterized by an endotherm occurring at about 78 ℃, as determined by DSC.

(B) Supramolecular aggregate I has a DSC curve substantially as shown in figure 1D.

Supramolecular aggregate II

In some embodiments, the supramolecular aggregates formed by azelaic acid and at least one heterocyclic amino acid of formula (I) in the present disclosure are supramolecular aggregates II.

In some embodiments, supramolecular aggregate II has a PXRD pattern substantially as shown in figure 2B. The 2θ angles observed in PXRD for supramolecular aggregate II are shown in table 2 below.

TABLE 2

Angle/2 theta
	5.5
16.6
	17.5
19.3
	21.7
22.9

In some embodiments, supramolecular aggregate II has a PXRD pattern comprising at least 2, at least 3, at least 4, at least 5, or all peaks at the 2θ angles, the relative intensities in the PXRD pattern being as shown in figure 2B.

In some embodiments, the peak assignments listed herein, including supramolecular aggregate II, can vary by ± 0.2 degrees or ± 0.1 degrees 2θ. In some embodiments, the peak assignments listed herein, including supramolecular aggregate II, can vary by ± 0.2 degrees 2θ. In some embodiments, the peak assignments listed herein, including supramolecular aggregate II, can vary by ± 0.1 degrees 2θ.

In some embodiments, supramolecular aggregate II has a DSC (differential scanning calorimetry) curve substantially as shown in figure 1F. In some embodiments, supramolecular aggregate II is characterized by two endotherms occurring at about 85 ℃ and 103 ℃, as determined by DSC. In some embodiments, supramolecular aggregate II is characterized by two endotherms occurring at about 85±2 ℃ (e.g., ,85±1.9℃、85±1.8℃、85±1.7℃、85±1.6℃、85±1.5℃、85±1.4℃、85±1.3℃、85±1.2℃、85±1.1℃、85±1℃、85±0.9℃、85±0.8℃、85±0.7℃、85±0.6℃、85±0.5℃、85±0.4℃、85±0.3℃、85±0.2℃、 or 85±0.1 ℃) and 103±2 ℃ (e.g., ,103±1.9℃、103±1.8℃、103±1.7℃、103±1.6℃、103±1.5℃、103±1.4℃、103±1.3℃、103±1.2℃、103±1.1℃、103±1℃、103±0.9℃、103±0.8℃、103±0.7℃、103±0.6℃、103±0.5℃、103±0.4℃、103±0.3℃、103±0.2℃、 or 103±0.1 ℃), as determined by DSC.

In some embodiments of supramolecular aggregate II, at least one or all of the following (a) to (d) apply:

(a) The supramolecular aggregate II has a PXRD pattern containing peaks at 5.5 ° ± 0.2 °, 16.6 ° ± 0.2 °, 17.5 ° ± 0.2 °, 21.7 ° ± 0.2 °, 22.9 ° ± 0.2 °, or 5.5 ° ± 0.2 °, 16.6 ° ± 0.2 °, 17.5 ° ± 0.2 °, 19.3 ° ± 0.2 °, 21.7 ° ± 0.2 °, and 22.9 ° ± 0.2 °.

(B) Supramolecular aggregate II has a PXRD pattern substantially as shown in figure 2B.

(C) Supramolecular aggregate II is characterized by two endotherms occurring at about 85 ℃ and 103 ℃, as determined by DSC.

(D) Supramolecular aggregate II has a DSC curve substantially as shown in figure 1F.

Supermolecular aggregate III

In some embodiments, the supramolecular aggregates formed by azelaic acid and at least one heterocyclic amino acid of formula (I) in the present disclosure are supramolecular aggregates III.

In some embodiments, supramolecular aggregate III has a PXRD pattern substantially as shown in figure 2D. The 2θ angles observed in PXRD for supramolecular aggregate III are shown in table 2 below.

TABLE 3 Table 3

Angle/2 theta
	5.5
8.3
	9.3
16.5
	17.4
18.0
	18.4
19.0
	21.7
22.8
	23.4
27.1
	28.1

In one embodiment, supramolecular aggregate III has a PXRD pattern comprising at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, or at least 10 peaks at the 2θ angles, the relative intensities in the PXRD pattern being as shown in figure 2D.

In some embodiments, the peak assignments listed herein, including supramolecular aggregate III, can vary by ± 0.2 degrees or ± 0.1 degrees 2θ. In some embodiments, the peak assignments listed herein, including supramolecular aggregate III, can vary by ± 0.2 degrees 2θ. In some embodiments, the peak assignments listed herein, including supramolecular aggregate III, can vary by ± 0.1 degrees 2θ.

In some embodiments, supramolecular aggregate III has a DSC profile substantially as shown in figure 1C. In some embodiments, supramolecular aggregate III is characterized by two endotherms occurring at about 77 ℃ and 95 ℃, as determined by DSC. In some embodiments, supramolecular aggregate III is characterized by two endotherms occurring at about 77±2 ℃ (e.g., ,77±1.9℃、77±1.8℃、77±1.7℃、77±1.6℃、77±1.5℃、77±1.4℃、77±1.3℃、77±1.2℃、77±1.1℃、77±1℃、77±0.9℃、77±0.8℃、77±0.7℃、77±0.6℃、77±0.5℃、77±0.4℃、77±0.3℃、77±0.2℃、 or 77±0.1 ℃) and 95±2 ℃ (e.g., ,95±1.9℃、95±1.8℃、95±1.7℃、95±1.6℃、95±1.5℃、95±1.4℃、95±1.3℃、95±1.2℃、95±1.1℃、95±1℃、95±0.9℃、95±0.8℃、95±0.7℃、95±0.6℃、95±0.5℃、95±0.4℃、95±0.3℃、95±0.2℃、 or 95±0.1 ℃), as determined by DSC.

In some embodiments of supramolecular aggregate III, at least one or all of the following (a) to (d) apply:

(a) The supramolecular aggregate II has a PXRD pattern containing peaks at 5.5 ° ± 0.2 °, 16.5 ° ± 0.2 °, 17.4 ° ± 0.2 °, 21.7 ° ± 0.2 °, 22.8 ° ± 0.2 °, or PXRD patterns :5.5°±0.2°、8.3°±0.2°、9.3°±0.2°、16.5°±0.2°、17.4°±0.2°、18.0°±0.2°、18.4°±0.2°、19.0°±0.2°、21.7°±0.2°、22.8°±0.2°、23.4°±0.2°、27.1°±0.2° and 28.1 ° ± 0.2 ° containing peaks at 2 theta.

(B) Supramolecular aggregate III has a PXRD pattern substantially as shown in figure 2D.

(C) Supramolecular aggregate III is characterized by two endotherms occurring at about 77 ℃ and 95 ℃, as determined by DSC.

(D) Supramolecular aggregate III has a DSC profile substantially as shown in figure 1C.

III preparation method

According to a second aspect, the present disclosure provides a method of preparing a supramolecular aggregate comprising the steps of:

1) Azelaic acid and at least one heterocyclic amino acid shown in the following general formula (I) are mixed according to a molar ratio of 1:2-2:1 to obtain a mixture;

It should be noted that the same definitions as above will be adopted below for the same features as those described in the above "ii. Supramolecular aggregates", for example, "azelaic acid", "heterocyclic amino acid represented by formula (1), and the like.

The ratio of the starting materials has an important influence on the formation of supramolecular aggregates of azelaic acid, including an improvement in stability, uniformity of crystallization and solubility of azelaic acid. In order to obtain supramolecular aggregates with the desired stability, crystallization uniformity and improved solubility of azelaic acid, it is necessary to control the raw material ratio.

The present disclosure can form a supramolecular aggregate by setting the molar ratio of azelaic acid to the heterocyclic amino acid represented by the general formula (I) in a range of 1:5 to 5:1, preferably 1:2 to 2:1, more preferably 1:1 to 2:1. Preferably, the molar ratio of azelaic acid to the heterocyclic amino acid of formula (I) may be set at 1:1 to obtain excellent effects, including more homogeneous crystallization and more improved solubility of azelaic acid.

As a method for producing the supramolecular aggregate, any one of liquid-assisted milling and cooling crystallization methods may be used. However, the liquid-assisted milling method is preferably used because it can form more homogeneous crystals. Liquid-assisted milling involves the addition of a small amount of solvent and milling of the feedstock. The solvent to be used is not particularly limited as long as it promotes the interaction between the raw materials and allows them to more easily form supramolecular aggregates. In some embodiments, liquid assisted milling comprises adding a good solvent for azelaic acid and a heterocyclic amino acid of formula (I). As such a good solvent, a lower alkyl alcohol, for example, a C1-C5 alkyl monohydric alcohol, preferably a C2-C3 alkyl alcohol, more preferably methanol, ethanol or propanol, and most preferably ethanol, may be used.

The amount of the solvent (polishing liquid) added in the liquid-assisted polishing may be set to about 0.1 to 0.5ml/g in terms of the ratio of the volume of the lower saturated alkyl alcohol to the mass of the mixture of azelaic acid and the heterocyclic amino acid represented by the formula (I). Without wishing to be bound by theory, it is believed that the addition of too much solvent in liquid-assisted milling may result in too low a concentration of the starting materials in the solution, thereby reducing the chance of interactions between the starting materials, making the formation of a co-crystal difficult. Conversely, if the amount of solvent is too small, the raw materials may not be sufficiently dissolved or dispersed in the solvent, which may also limit interactions between the raw materials, thereby impeding the formation of eutectic crystals.

The polishing method in the liquid-assisted polishing is not particularly limited. The grinding may be performed manually using a mortar or may be performed using a grinding device such as a grinder.

In some embodiments, the liquid-assisted milling is performed using a lower saturated alkyl alcohol as the milling liquid, wherein the ratio of the volume of the lower saturated alkyl alcohol to the mass of the mixture of azelaic acid and the heterocyclic amino acid of formula (I) is 0.1 to 0.5mL/g.

In some embodiments, the liquid-assisted milling is performed using ethanol as milling liquid, wherein the ratio of the volume of ethanol to the mass of the mixture of azelaic acid and heterocyclic amino acid is 0.1 to 0.5ml/g, preferably the heterocyclic amino acid is proline.

IV cosmetic composition

According to a third aspect, the present disclosure provides a cosmetic composition comprising the above-described supramolecular aggregate.

It should be noted that the same definitions as above will be adopted below for the same features as those described in the above "ii. Supermolecule aggregate" or "iii. Preparation method", for example, "azelaic acid", "heterocyclic amino acid represented by formula (1), and the like.

The cosmetic composition may be in solid, semi-solid or liquid form, and may be in solution, emulsion, suspension or anhydrous form. If in solution or suspension, the composition may comprise about 1 to 99.9%, preferably about 5 to 95%, more preferably about 10 to 90% water. In the case of emulsion, the composition may comprise about 1 to 99%, preferably about 5 to 90%, more preferably about 10 to 85% water and about 1 to 99%, preferably about 5 to 90%, more preferably about 5 to 75% oil. If in anhydrous form, the composition may comprise about 10 to 99% oil and 10 to 99% curative.

In one embodiment, the supramolecular aggregate is present in the cosmetic composition in an amount of 0.01% to 50%, more preferably 0.05% to 20%, more preferably 0.1% to 10% by weight of azelaic acid relative to the total amount of the composition.

The cosmetic composition may further comprise at least one cosmetically acceptable active ingredient, such as moisturizers, antioxidants, UV screening agents, anti-inflammatory agents, preservatives, vitamins, skin conditioners, stabilizers, particularly for preventing or reducing excessive sebum, acne, wrinkles, fine lines, dry skin, photoaging and inflammation, as long as the objects of the present disclosure are achieved. Other cosmetically acceptable ingredients that may be mentioned include oils, thickeners, pH adjusters, or any other ingredient typically formulated into cosmetics or pharmaceuticals. The following subsections provide non-limiting examples of some of these components.

A. Humectant type

The compositions of the present disclosure may contain one or more humectants. If present, they may comprise about 0.1% to 75%, preferably about 0.2% to 70%, more preferably about 0.5% to 40% by weight of the total composition. Examples of suitable humectants include ethylene glycol, sugar, hyaluronic acid, sodium hyaluronate, and the like. Preferably, the humectant used in the compositions of the present disclosure is a C1-6, preferably C2-4, alkyl diol, most particularly butanediol.

B. Antioxidant agent

The compositions of the present disclosure may contain one or more antioxidants. If present, they may comprise about 0.001 to 20%, preferably about 0.005 to 15%, more preferably about 0.010 to 10% by weight of the total composition.

Non-limiting examples of antioxidants that may be used in the compositions of the present disclosure include acetylcysteine, ascorbyl polypeptide, ascorbyl dipalmitate, ascorbyl methylsilanol pectate, ascorbyl palmitate, ascorbyl stearate, BHA, BHT, t-butylhydroquinone, cysteine HCl, dipentyl hydroquinone, di-t-butylhydroquinone, dicetyl thiodipropionate, disodium ascorbyl sulfate, dilauryl thiodipropionate, ditridecyl thiodipropionate, dodecyl gallate, erythroic acid, ascorbate, ethyl ferulate, ferulic acid, gallate, hydroquinone, and combinations thereof isooctylthioglycolate, kojic acid, magnesium ascorbate, magnesium ascorbyl phosphate, methylsilanol ascorbate, natural plant antioxidants (e.g., green tea or grape seed extract), nordihydroguaiaretic acid, octyl gallate, phenylthioglycolate, potassium sulfite, propyl gallate, quinones, rosmarinic acid, sodium ascorbate, sodium bisulfite, sodium erythorbate, sodium metabisulfite, sodium sulfite, superoxide dismutase, sodium thioglycolate, sorbitol furfural, thiodiglycol, thiodiethanolamide, thiodiglycolic acid, thioglycolate, thiolactic acid, thiosalicylic acid, and tris (nonylphenyl) phosphite.

UV screening agent

The compositions of the present disclosure may contain one or more UV screening agents. The UV screening agent, if present, may comprise about 0.1% to 50%, preferably about 0.5% to 40%, more preferably about 1% to 35% by weight of the total composition.

Non-limiting examples of UV screening agents include chemical UVA screening agents such as dibenzoylmethane compounds, di-camphorsulfonic acid derivatives, and the like, or UVB screening agents such as phenylbenzimidazole sulfonic acid, 2-ethylhexyl 2-cyano-3, 3-diphenylacrylate, ethylhexyl methoxycinnamate, benzophenone derivatives, menthyl salicylate derivatives, and the like, or physical screening agents in particulate form. The addition of a masking agent to the composition provides additional protection to the skin during daylight hours and enhances the effect of the whitening active on the skin.

The compositions of the present disclosure may be formulated to have a certain SPF (sun protection factor) value, ranging from about 1 to 50, even 50+, depending on the type and dosage of UV screening agent, as desired. Calculation of SPF values is well known in the art.

D. Anti-inflammatory agent

The compositions of the present disclosure may contain one or more anti-inflammatory agents. The anti-inflammatory agent, if present, may comprise about 0.001% to 5%, preferably about 0.01% to 2%, more preferably about 0.1% to 1% by weight of the total composition.

Non-limiting examples of anti-inflammatory agents include steroidal anti-inflammatory agents and non-steroidal anti-inflammatory agents. The steroid anti-inflammatory agent may be hydrocortisone. So-called "natural" anti-inflammatory agents are also useful. For example, bisabolol, aloe vera, manjistha (extracted from Rubia plants, particularly Rubia cordifolia), and Guggal (extracted from Umbelliferae plants, particularly myrrh indicum), cola extract, chamomile, and sea whip extract may also be used.

Inclusion of an anti-inflammatory agent in the composition will enhance skin appearance benefits by, for example, contributing to uniformity and acceptable skin tone and/or color.

E. Preservative agent

The compositions of the present disclosure may contain one or more preservatives. The anti-inflammatory agent, if present, may comprise about 0.001% to 8%, preferably about 0.01% to 6%, more preferably about 0.05% to 5% by weight of the total composition.

Non-limiting examples of preservatives that may be used in the compositions of the present disclosure include quaternary ammonium preservatives, such as polyquaternium-1 and benzalkonium halides (e.g., benzalkonium chloride ("BAC") and benzalkonium bromide), parabens (e.g., methylparaben and propylparaben), phenoxyethanol, benzyl alcohol, chlorobutanol, phenol, sorbic acid, thimerosal, or combinations thereof.

F. Vitamins

The compositions of the present disclosure may contain one or more vitamins. Vitamins, if present, may comprise about 0.001% to 20%, preferably about 0.005% to 15%, more preferably about 0.1% to 10% by weight of the total composition.

Non-limiting examples of vitamins that may be used in the compositions of the present disclosure include tocopherols or derivatives thereof, such as tocopheryl acetate, tocopheryl ferulate, tocopheryl polyether-5, tocopheryl polyether-10, tocopheryl polyether-12, tocopheryl polyether-18, tocopheryl polyether-50, tocopherols, tocopheryl alcohol esters, tocopheryl linoleate, tocopheryl nicotinate, tocopheryl succinate dioleyl tocopheryl methylsilanol, ascorbic acid or derivatives thereof, such as ascorbyl palmitate, magnesium ascorbyl phosphate, vitamin a or derivatives thereof, such as retinol palmitate, or vitamin D, K, B or derivatives thereof.

G. Conditioning agent

The compositions of the present disclosure may contain one or more skin/hair conditioning agents. The skin conditioning agent, if present, may comprise about 0.001% to 10%, preferably about 0.01% to 5%, more preferably about 0.1% to 2% by weight of the total composition.

Non-limiting examples of skin/hair conditioning agents that can be used in the compositions of the present disclosure include RNA-Na (sodium ribonucleic acid), vitamin B5 derivatives such as panthenol, dexpanthenol, pantethine, lauroyl lysine, hydrolyzed keratin, and hydrolyzed wheat protein.

H. Stabilizing agent

The compositions of the present disclosure may contain one or more stabilizers. The stabilizer, if present, may comprise about 0.001% to about 10%, preferably about 0.01% to about 5%, more preferably about 0.1% to about 2% by weight of the total composition.

Non-limiting examples of stabilizers useful in the compositions of the present disclosure include sodium gluconate, sodium phytate, disodium EDTA, trisodium EDTA, tetrasodium EDTA.

I. surface active agent

The compositions of the present disclosure may contain one or more surfactants, especially when in emulsion form. However, such surfactants may be used if the composition is also a solution, suspension or anhydrous. The surfactant, if present, may comprise about 0.01 to 30%, preferably about 0.05 to 25%, more preferably about 0.1 to 20% by weight of the total composition.

Non-limiting examples of surfactants that may be used in the compositions of the present disclosure include nonionic organic surfactants such as Oleth-3, oleth-5, oleth-3 phosphate, choleth-24, ceteth-24, methyl glucitol polyether-20, glycerol polyether-26, PEG-75, silicone or silane-based surfactants such as PEG-1 dimethicone, PEG-4 dimethicone, PEG-8 dimethicone, PEG-12 dimethicone, PEG-20 dimethicone, bis-PEG-18 methyl ether dimethicone, dimethicone copolyol, cetyl dimethicone copolyol, and the like.

J. Thickening agent

Suitable thickeners may be incorporated into the compositions of the present disclosure. If present, the recommended range may be about 0.01% to 30%, preferably about 0.1% to 20%, more preferably about 0.5% to 15% of the total weight of the composition.

Non-limiting examples of thickeners useful in the compositions of the present disclosure include animal, vegetable, mineral, silicone or synthetic waxes, silica, silicate, silica silicone and alkali or alkaline earth metal derivatives thereof, silicone elastomers such as vinyl dimethicone/methyl polysiloxane silsesquioxane cross-linked polymers, polysaccharides such as agar, agarose, hyaluronic acid, hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, pectin, sclerotium gum, xanthan gum, dehydrogenated xanthan gum, pectin, trehalose, gelatin, and the like.

K. Oil (oil)

In the case where the compositions of the present disclosure are in the form of solutions, suspensions, anhydrous, particularly emulsions, the compositions may contain oily components. The oily component is required for skin moisturizing and protective properties. Suitable oils include volatile silicones such as Dow Corning 244, 245, 344 and 200 fluids, volatile paraffins such as pentane, hexane, heptane, decane, dodecane, tetradecane, tridecane and C8-20 isoparaffins as disclosed in U.S. Pat. Nos.3,439,088 and 3,818,105, both of which are incorporated herein by reference, mono-, di-and tri-esters such as hexyl laurate, butyl isostearate, diisostearyl malate, neopentyl glycol dioctate, tributyl citrate, triisostearyl citrate, hydrocarbon oils such as mineral oil, pentahydro squalene, squalane and the like.

The amount of these ingredients can be selected by one skilled in the art depending on the end use of the cosmetic composition. Those of skill in the art will appreciate that compositions according to the present disclosure may comprise a total of about 20% -98%, preferably about 30% -90%, more preferably about 40% -80% of one or more additional cosmetically acceptable ingredients.

The cosmetic composition may be in any form. Suitable forms include, but are not limited to, solid, liquid, gel, lotion, cream, hard gel stick, roller ball, mousse, aerosol spray, pad coating, and film forming formulations.

The cosmetic compositions of the present disclosure may also find wide application in the fields of personal care, food, dietary supplements, and pharmaceuticals, among others.

The present disclosure is not limited to these embodiments, but may be modified by a person skilled in the art within the scope of the appended claims. The present disclosure also covers any embodiment in which technical means disclosed in different embodiments are combined within its technical scope.

Examples

The following examples are given as non-limiting illustrations of the present disclosure.

1. Sample preparation and characterization

The supramolecular aggregates prepared were characterized by DSC, PXRD and elemental analysis using the following procedure.

DSC

DSC analysis was performed using a HCT-1 thermal analyzer. The test is carried out on samples with a weight of 3-5 mg by heating at a heating rate of 5 DEG Cmin ^-1 in a temperature range of 40-200 ℃ under nitrogen atmosphere.

PXRD

Powder X-ray diffraction (PXRD) analysis was performed using a rotating anode X-ray powder diffractometer equipped with Cu kaThe source was operated at 40kV and 40 mA. And collecting the PXRD map at an angle step of 1 degree/min within the range of 5-50 degrees of 2 theta.

Elemental analysis

Elemental analysis was performed using a vario EL cube elemental analyzer to determine the composition of the supramolecular aggregates produced. Specifically, the sample was completely burned. The mass of the three products (CO ₂,H₂O,N₂) after oxidative combustion was measured by an elemental analyzer, and the contents of the three elements (C, H, N) in the sample were measured, respectively.

The main raw materials, trade names and suppliers used are listed in Table 1.

TABLE 4 raw material information

INCI name	Abbreviations (abbreviations)	Trade name	Suppliers (suppliers)
				Azelaic acid	AZA	Azelaic acid	Leyan
Proline (proline)	Pro	L-proline	Sigma-Aldrich
				Ethanol	EtOH	Absolute ethyl alcohol	ShanghaiLingfengChemical
Lysine	Lys	L-lysine	Macklin

EXAMPLE 1 preparation of supramolecular aggregate A

Supramolecular aggregates a (azo-Pro (1:1)) were prepared using a liquid-assisted milling method. More specifically, 376mg (2 mmol) of azelaic acid and 230mg (2 mmol) of L-proline were ground in a mortar for 30min after adding 0.2mL of ethanol, to obtain supramolecular aggregate A as microcrystalline powder. The resulting product was dried in an oven at 50 ℃ for 5 hours to remove residual solvent and ground into a fine powder for further analysis.

EXAMPLE 2 preparation of supramolecular aggregate A

Supramolecular aggregates a (azo-Pro (1:1)) were prepared using a cooling crystallization method. More specifically, 188mg (1 mmol) of AZA and 115mg (1 mmol) of L-Pro were dissolved in 4mL of EtOH at a molar ratio of 1:1 to give a saturated solution. The saturated solution was heated to 45 ℃ and held at that temperature for 30min with stirring to ensure complete dissolution of the starting materials. After complete dissolution, stirring was stopped and the system was cooled slightly to room temperature. After further cooling to-7 ℃, the system was left to stand for 6 hours. The crystals produced were collected and dried under vacuum at 50 ℃ for 24 hours to give pure form.

Examples 3-4 preparation of supramolecular aggregates B and C

Supermolecular aggregate B (AZA-Pro (2:1)) and supermolecular aggregate C (AZA-Pro (1:2)) were prepared using the same method as in example 1, except that the amounts of AZA and Pro were adjusted according to the descriptions in Table 5 below.

Table 5. Amounts of raw materials and crystallization method in examples 1-4.

Comparative example 1 preparation of supramolecular aggregate D

Supramolecular aggregates D (azo-Lys (1:1)) were prepared using a liquid-assisted milling method. More specifically, 376mg (2 mmol) of azelaic acid and 292mg (2 mmol) of L-lysine were ground in a mortar for 30min after adding 0.2mL of ethanol, to obtain supramolecular aggregate D as microcrystalline powder. The resulting product was dried in an oven at 50 ℃ for 5 hours to remove residual solvent and ground into a fine powder for further analysis.

FIGS. 1 and 2 show DSC and PXRD results of the starting materials AZA and Pro, respectively, and the supramolecular aggregates prepared in examples 1-4. Fig. 3 shows PXRD results of starting materials azo and Lys, and the supramolecular aggregates prepared in comparative example 1.

Table 6 below shows DSC endotherm peaks of starting materials AZA and Pro, and supramolecular aggregates prepared in examples 1-4.

Table 6.

	Endothermic peak
		AZA	103°C
Pro	219°C
		Example 1	78°C
Example 2	75°C,103°C
		Example 3	77°C,95°C
Example 4	86°C,103°C

As shown in FIG. 1, the melting temperatures of AZA and L-Pro were 103℃and 219℃respectively. Supermolecular aggregate A prepared in a molar ratio of 1:1 using liquid-assisted milling in example 1 showed only very pronounced endothermic peaks at 78℃in distinction to AZA and Pro. This phenomenon indicates that a homogeneous supramolecular aggregate (supramolecular aggregate I) was formed in example 1. In contrast, the supramolecular aggregate a prepared using the cooling crystallization method in example 2 at a molar ratio of 1:1 showed a weak endothermic peak at 75 ℃ and also showed an endothermic peak corresponding to AZA at 103 ℃. This suggests that liquid assisted milling is more suitable for eutectic formation between AZA and Pro than cooling crystallization.

Furthermore, supramolecular aggregate B prepared using liquid-assisted milling in a molar ratio of 2:1 in example 3 showed the presence of an endothermic peak, with the 1 st endothermic peak being pronounced, representing the melting point of the co-crystal (77 ℃) and the 2 nd endothermic peak being weak, corresponding to the interaction between AZA and Pro (95 ℃). This indicates that the eutectic formation (supramolecular aggregate II) in example 3 is more sufficient. Furthermore, supramolecular aggregate C prepared at a molar ratio of 1:2 using liquid-assisted milling in example 4 also showed 2 endothermic peaks. The 1 st endotherm (86 ℃) was weaker and the 2 nd endotherm corresponded to the melting point of AZA (103 ℃). This indicates insufficient eutectic formation in example 4 (supermolecule aggregate III).

Table 7 below shows the raw materials azo and Pro, and PXRD data from the co-crystals of example 1, example 3 and example 4.

Table 7.

As can be seen from fig. 2 and table 7, the supramolecular aggregate I obtained in example 1 exhibited distinct characteristic peaks from AZA and Pro at least at 2θ of 5.7 °, 20.3 ° and 21.8 °, indicating the formation of eutectic crystals. The supermolecular aggregates II and III in examples 3 and 4 each present distinct characteristic peaks from AZA and Pro at least at 2 theta of 5.5 DEG and 21.7 DEG, indicating the formation of a eutectic.

On the other hand, as shown in FIG. 3, AZA-Lys supermolecules prepared under the same conditions as in example 1 did not show clear diffraction peaks, except that L-lysine was used instead of L-proline, indicating that AZA and Lys failed to form a co-crystal.

In addition, the results of elemental analysis showed that the measured contents of carbon, hydrogen, and nitrogen elements in the supramolecular aggregates prepared in examples 1 to 4 and comparative example 1 were closer to their theoretical values, indicating that the supramolecular aggregates with different molar ratios were successfully prepared.

2. Solubility test

Solubility testing was performed using shake flask and ultra high performance liquid chromatography-mass spectrometry (UPLC-MS). Specifically, an excess of sample corresponding to 30mg of AZA was dispersed in a test tube containing 1.5mL of distilled water, respectively. The dispersion was placed in a water bath and sonicated continuously for 30 minutes. The dispersion was then centrifuged at 6000rpm for 50 minutes. In addition, AZA concentration in the supernatant of the AZA starting material and the supramolecular aggregate of example 1 was assessed by UPLC-MS.

UPLC-MS analysis was performed using Waters UPLC/MS (Waters ACQUITY I class-TQS micro MS detector) and C18 reverse phase column (Phenomenex Prodigy ODS-3 column; 5 μm, 150X 4.6mm inside diameter). The mobile phase consists of acetonitrile and formic acid water solution. The gradient flow rate of the mobile phase was set to 0.6mL/min. Column temperature, sample injection volume and detection m/z were set to 40 ℃,5 μl and 187>125 (negative), respectively. The AZA calibration curve is linear (r ² is greater than or equal to 0.995) within the concentration range of 0.2-20 mug/mL.

As shown in Table 8 below, the solubility of AZA in distilled water increased by a factor of about 1.19, increasing from 2352ppm of AZA as the starting material to 2795ppm of supramolecular aggregates.

TABLE 8 solubility in water

3. Formulation of

Example 5 and comparative examples 2-3 were prepared according to the formulations shown in table 9.

TABLE 9 formulations of example 5 and comparative examples 2-3

As a result, the formulations of comparative example 2 and comparative example 3 had a problem that AZA was not completely dissolved, which was not observed in example 5.

Therefore, the supermolecule aggregate obtained by the invention can be used for preparing water-based cosmetics with higher AZA content.

Although the present disclosure and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the disclosure as defined by the appended claims. Furthermore, the scope of the present application is not intended to be limited to the particular embodiments of the process, machine, manufacture, composition of matter, means, methods and steps described in the specification. One of ordinary skill in the art will readily appreciate from the disclosure that processes, machines, manufacture, compositions of matter, means, methods, or steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the present disclosure. Accordingly, the appended claims are intended to include within their scope such processes, machines, manufacture, compositions of matter, means, methods, or steps.

Claims

1. Supramolecular aggregates formed by azelaic acid and at least one heterocyclic amino acid of formula (I),

Wherein the powder X-ray diffraction pattern of the aggregate comprises peaks at 5.7 DEG + -0.2 DEG and 21.8 DEG + -0.2 DEG at 2 theta.

2. The supramolecular aggregate of claim 1, wherein said powder X-ray diffraction pattern further comprises at least 2, preferably at least 4 characteristic peaks ：8.5°±0.2°、9.4°±0.2°、16.7°±0.2°、17.6°±0.2°、18.5°±0.2°、19.4°±0.2°、20.3°±0.2°、21.1°±0.2°、23.0°±0.2°、23.6°±0.2°、27.3°±0.2° and 28.3 ° ± 0.2 ° at 2Θ.

3. The supramolecular aggregate of claim 1, wherein said powder X-ray diffraction pattern further comprises at least 2, preferably at least 4, characteristic peaks at 16.6 ° ± 0.2 °, 17.5 ° ± 0.2 °, 19.3 ° ± 0.2 ° and 22.9 ° ± 0.2 °.

4. The supramolecular aggregate of claim 1, wherein said powder X-ray diffraction pattern further comprises at least 2, preferably at least 4, characteristic peaks ：8.3°±0.2°、9.3°±0.2°、16.5°±0.2°、17.4°±0.2°、18.0°±0.2°、18.4°±0.2°、19.0°±0.2°、22.8°±0.2°、23.4°±0.2°、27.1°±0.2° and 28.1 ° ± 0.2 ° at 2Θ.

5. The supramolecular aggregate of any of claims 1-4, wherein the heterocyclic amino acid is proline or hydroxyproline, preferably proline.

6. Supramolecular aggregate according to any of claims 1-5, wherein the molar ratio of azelaic acid to proline is 1:5-5:1, preferably 1:2-2:1, more preferably 1:1-2:1.

7. The supramolecular aggregate of any of claims 1-6, wherein the aggregate exhibits 1 endothermic peak in its DSC curve at a temperature of 76-86 ℃.

8. The supramolecular aggregate of claim 7, wherein said aggregate further exhibits 1 endothermic peak in its DSC curve at a temperature of 94 ℃ to 103 ℃.

9. A process for preparing supramolecular aggregates from azelaic acid and heterocyclic amino acids comprising the steps of:

1) Azelaic acid and at least one heterocyclic amino acid shown in the following general formula (I) are mixed according to a molar ratio of 1:2-2:1, preferably 1:1-2:1, more preferably 1:1 to obtain a mixture;

10. The method according to claim 9, wherein the liquid-assisted milling is performed using a lower saturated alkyl alcohol as the milling liquid, wherein the ratio of the volume of the lower saturated alkyl alcohol to the mass of the mixture is 0.1 to 0.5ml/g.

11. The method according to claim 9 or 10, wherein the lower saturated alkyl alcohol is ethanol.

12. The method according to any one of claims 9 to 11, wherein the heterocyclic amino acid is proline or hydroxyproline, preferably proline.

13. Cosmetic composition comprising the supramolecular aggregate according to any one of claims 1 to 8.

14. The cosmetic composition of claim 13, wherein the composition further comprises at least one active ingredient selected from the group consisting of moisturizers, antioxidants, UV screens, anti-inflammatory agents, preservatives, vitamins, skin conditioners, stabilizers, and mixtures thereof.