Supramolecular assemblies, compositions containing the same, and methods for producing the same.

Abstract

This disclosure provides a supramolecular assembly comprising at least one pyridinylformamide compound and at least one hydroxy fatty acid, wherein the pyridinylformamide compound and the hydroxy fatty acid are bound together by non-covalent bonds. This disclosure further provides cosmetic compositions comprising the supramolecular assembly. Methods for preparing the supramolecular assembly are also provided.

Description

[Technical Field]

[0001] This disclosure generally relates to supramolecular assemblies and their applications in cosmetic and personal care products. More specifically, this disclosure relates to supramolecular assemblies comprising at least one pyridinylformamide compound and at least one hydroxy fatty acid, compositions comprising the same, and methods for producing the same. [Background technology]

[0002] Hydroxy fatty acids refer to fatty acids that have one or more hydroxyl groups at the carbon positions in the long chain of the fatty acid molecule. The hydroxyl groups in hydroxy fatty acid molecules confer special properties to the fatty acid, resulting in higher reactivity and great value in cosmetics, personal care, food, nutritional supplements, and pharmaceuticals. Hydroxy fatty acids can be used in cosmetics as surfactants, emulsifiers, stabilizers, conditioners, antioxidants, etc., and can also be used in the pharmaceutical industry as antibacterial, anti-inflammatory, and antitumor active substances. However, hydroxy fatty acids have extremely low solubility in water, which greatly limits their application in cosmetics or pharmaceuticals. Currently, commercially available cosmetics or pharmaceuticals containing hydroxy fatty acids as active substances generally have drawbacks such as low content, insufficient transdermal permeability, slow onset of action, and / or unsatisfactory effects. To meet market and consumer demands, it is desirable to develop novel derivative or improved products based on hydroxy fatty acids that can overcome one or more of these drawbacks.

[0003] From such expectations, supramolecular chemistry has been applied upstream in the development of cosmetic raw materials. Supramolecular chemistry has expanded the scope of chemistry and enabled the design and development of smart and functional materials. Conventional synthetic molecules are covalently bonded molecules or macromolecules, while supramolecular complexes contain non-covalent bonds in the association of two or more building blocks held together by intermolecular bonds such as hydrogen bonds, dipole-dipole interactions, van der Waals forces, cation-π interactions, π-π bonds, CH / π interactions, or hydrophobic effects, and exhibit inclusion, selectivity, and other functionalities. The application of supramolecular chemistry has significantly increased the diversity of the components of cosmetic raw materials and provided new pathways for improving properties such as the solubility, bioavailability, stability, and effectiveness of these materials.

[0004] Therefore, there is a need for novel active materials modified by supramolecular chemistry that exhibit improved solubility and functionality and can consequently increase the effectiveness of products containing the active materials.

Summary of the Invention

[0005] Therefore, one objective of the present disclosure is to provide a supramolecular assembly having improved properties with respect to the individual components contained therein.

[0006] Another objective of the present disclosure is to provide a method for preparing a supramolecular assembly according to the present disclosure.

[0007] Yet another objective of the present disclosure is to provide a composition containing a supramolecular assembly according to the present disclosure, particularly a cosmetic and / or personal care composition for topical application.

[0008] Yet another objective of the present disclosure is to provide a non-therapeutic method for caring for, protecting, and / or making up keratinous substances such as the skin.

[0009] The inventors have found that one or more of these objectives can be achieved by the following aspects.

[0010] In one aspect, the present disclosure provides a supramolecular assembly comprising at least one pyridinylformamide compound and at least one hydroxy fatty acid, wherein the pyridinylformamide compound and the hydroxy fatty acid are assembled by non-covalent bonds.

[0011] According to certain embodiments, the non-covalent bonds may include hydrogen bonds, non-covalent electrostatic interactions, and van der Waals forces. According to certain embodiments, the molar ratio of the pyridinylformamide compound to the hydroxy fatty acid may range from about 1:10 to about 10:1, preferably from about 1:8 to about 8:1, more preferably from about 1:5 to about 5:1, even more preferably from about 1:2 to about 2:1, and most preferably about 1:1.

[0012] According to certain embodiments, the pyridinylformamide compound may be selected from the group consisting of picolinamide, nicotinamide, isonicotinamide, and combinations thereof.

[0013] According to certain embodiments, the hydroxy fatty acid may be a C6-C24 saturated straight-chain fatty acid having one or two hydroxy groups, preferably a C12-C18 saturated straight-chain fatty acid having one hydroxy group.

[0014] According to certain embodiments, the hydroxy fatty acid may be selected from the group consisting of hydroxylauric acid, hydroxystearic acid, dihydroxystearic acid, and combinations thereof, and more preferably selected from the group consisting of 2-hydroxylauric acid, 10-hydroxystearic acid, and 12-hydroxystearic acid.

[0015] In another aspect, the present disclosure provides a method for preparing the supramolecular assembly according to the present invention, comprising: a) mixing starting materials in a solvent to obtain a mixture, heating the mixture to a first temperature, and maintaining the heating until the starting materials are completely dissolved to obtain a transparent system; b) A step of cooling the system to a second temperature and leaving the system at the second temperature to generate crystals, wherein the second temperature is -20°C or higher and at least 15°C, preferably at least 25°C, and more preferably at least 35°C lower than the first temperature. The present invention provides a method comprising the steps of: c) collecting the crystals obtained in step b), optionally purifying them, and obtaining a supramolecular assembly.

[0016] According to one embodiment, in step a), the first temperature may be in the range of about 30°C to about 70°C, preferably about 35°C to about 60°C, and more preferably about 40°C to about 50°C. According to one embodiment, in step b), the system may be left for 1 to 10 hours, preferably 2 to 8 hours, and more preferably 4 to 6 hours.

[0017] According to one embodiment, the method of the present disclosure may further include n intermediate cooling steps between step a) and step b), wherein the system is cooled to an intermediate temperature and left for 1 to 10 hours, preferably 1 to 6 hours, more preferably 1 to 3 hours, the intermediate temperature being at least 10°C lower than the first temperature or the intermediate temperature of the previous intermediate cooling step, and at least 10°C higher than the second temperature, and n being 1, 2, 3, 4, or 5, preferably 2, 3, or 4, more preferably 2 or 3.

[0018] According to one embodiment, n is 1, the first temperature is in the range of approximately 35°C to approximately 65°C, the intermediate temperature of the intermediate cooling process is in the range of approximately 15°C to approximately 25°C, and the second temperature is in the range of approximately -5°C to approximately 5°C.

[0019] According to another embodiment, n is 2, the first temperature is in the range of about 35°C to about 65°C, the intermediate temperature of the first intermediate cooling step is in the range of about 25°C to about 35°C, the intermediate temperature of the second intermediate cooling step is in the range of about 15°C to about 25°C, and the second temperature is in the range of about -5°C to about 5°C.

[0020] In yet another embodiment, n is 3, the first temperature is in the range of about 35°C to about 65°C, the intermediate temperature of the first intermediate cooling step is in the range of about 25°C to about 35°C, the intermediate temperature of the second intermediate cooling step is in the range of about 15°C to about 25°C, the intermediate temperature of the third intermediate cooling step is in the range of about 0°C to about 5°C, and the second temperature is in the range of about -10°C to about -5°C.

[0021] According to one embodiment, the collection in step c) can be achieved by any suitable solid-liquid separation process, such as filtration. According to one embodiment, the purification in step c) can be carried out by any suitable purification process, such as vacuum drying, for a period of 5 to 48 hours, preferably 10 to 24 hours, at a temperature of about 20°C to about 70°C, preferably about 40°C to about 50°C.

[0022] According to one embodiment, in step a), the starting material may comprise at least one pyridinylformamide compound and at least one hydroxy fatty acid. According to a preferred embodiment, the molar ratio of the pyridinylformamide compound to the hydroxy fatty acid in the starting material may be in the range of about 1:10 to about 10:1, preferably about 1:8 to about 8:1, more preferably about 1:5 to about 5:1, even more preferably about 1:2 to about 2:1, and most preferably about 1:1. According to a preferred embodiment, the pyridinylformamide compound may be selected from the group consisting of picolinamide, nicotinamide, isonicotinamide, and combinations thereof. According to a preferred embodiment, the hydroxy fatty acid may be selected from the group consisting of hydroxylauric acid, hydroxystearic acid, dihydroxystearic acid, and combinations thereof, and more preferably from the group consisting of 2-hydroxylauric acid, 10-hydroxystearic acid, and 12-hydroxystearic acid.

[0023] According to one embodiment, the solvent may be selected from the group consisting of ethanol, n-propanol, isopropanol, methanol, acetone, propanediol, and acetic acid, citric acid, and phosphate buffer, as well as mixtures thereof with each other or with water, preferably ethanol and mixtures thereof with water. According to another embodiment, the solvent may be selected from the group consisting of ethyl acetate, butyl acetate, n-butanol, and mixtures thereof.

[0024] In a further embodiment, the present disclosure provides compositions comprising supramolecular assemblies according to the present invention, in particular cosmetic compositions for topical application.

[0025] According to one embodiment, the supramolecular aggregate is present in the composition in an amount of about 0.0001% to about 50% by weight, preferably about 0.001% to about 20% by weight, more preferably about 0.01% to about 10% by weight, and most preferably about 0.1% to about 2% by weight, relative to the total weight of the composition.

[0026] In a further aspect of the present invention, the present invention provides a non-therapeutic method for caring for, protecting and / or makeuping keratinous substances, which includes topical application of the composition according to the present invention to keratinous substances such as skin.

[0027] In a further embodiment, the present disclosure provides the use of the supramolecular aggregate or cosmetic composition according to the present invention for improving the condition of keratinous substances such as skin.

[0028] These solutions are based on the remarkable discovery that supramolecular assemblies prepared from pyridinylformamide compounds and hydroxy fatty acids by programmed cooling methods exhibit synergistic effects in terms of functionality, such as substantially improved solubility in water and antioxidant properties, compared to insoluble hydroxy fatty acids.

[0029] Other advantages of this disclosure will become clearer by reading the following description and examples. [Brief explanation of the drawing]

[0030] For a more complete understanding of this disclosure, the following description is referenced herein together with the attached drawings. [Figure 1] Figure 1 shows the FT-IR spectra of NAM, 10-HSA, and the supramolecular assemblies of Examples 3, 4, and 5, respectively. [Figure 2] Figure 2 shows the XRD patterns of NAM, 10-HSA, and the supramolecular assemblies of Examples 3, 4, and 5, respectively. [Figure 3] Figure 3 shows the DSC profiles of NAM, 10-HSA, and the supramolecular assemblies of Examples 3, 4, and 5, respectively. [Modes for carrying out the invention]

[0031] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art in which this disclosure pertains. If any definition of a term herein conflicts with the meaning generally understood by those skilled in the art in which this disclosure pertains, the definition provided herein shall prevail.

[0032] Unless otherwise specified, all figures used in this specification and the claims, such as quantities of components, molecular weights and other properties, and reaction conditions, should be understood in all cases to be modified by the term "approximately." Therefore, unless otherwise indicated, the numerical parameters described in the following specification and the appended claims are approximations that may vary depending on the desired properties to be obtained by this disclosure. At a minimum, each numerical parameter should be interpreted by applying common rounding techniques, taking into account at least the number of significant figures reported. Furthermore, the ranges described in this disclosure and the claims are intended to include the entire range, not just the endpoints. For example, a range described as 0 to 10 is intended to disclose all integers between 0 and 10, such as 1, 2, 3, 4, etc., all fractions between 0 and 10, such as 1.5, 2.3, 4.57, 6.1113, etc., and the endpoints 0 and 10.

[0033] Although the numerical ranges and parameters representing the broad scope of the present invention are approximations, the numerical values ​​shown in specific embodiments are intended to be reported accurately, taking into account the measurement methods. However, any numerical value inherently contains a certain error that inevitably arises from the standard deviation found in each of those test measurements.

[0034] It should be understood that the reference to one or more process steps does not preclude the existence of additional process steps before or after the combined enumerated steps, or intervening process steps between those explicitly identified steps. Furthermore, the names of process steps, components, or other aspects of information disclosed or claimed in this application, using letters, numbers, etc., are a convenient means of identifying individual activities or components, and the enumerated letters may be arranged in any order unless otherwise indicated.

[0035] As used herein, the singular forms “a,” “an,” and “the” refer to multiple objects unless the context explicitly indicates otherwise. For example, a reference to a Cn alcohol equivalent is intended to include multiple types of Cn alcohol equivalents. Thus, even the use of language such as “at least one” in a given position is not intended to imply that other uses of “a,” “an,” and “the” exclude multiple objects unless the context explicitly indicates otherwise.

[0036] As used herein, the term “comprising” should be interpreted as encompassing all specifically mentioned features and any optional additional unspecified features. As used herein, the use of the term “comprising” also discloses embodiments that consist of no features other than those specifically mentioned (i.e., “consisting of”).

[0037] As used herein, the term "and / or" when used in a list of two or more items means that any one of the listed items may be used alone, or any combination of two or more of the listed items may be used. For example, if a composition is described as containing components A, B, and / or C, the composition may contain only A, only B, only C, a combination of A and B, a combination of A and C, a combination of B and C, or a combination of A, B, and C.

[0038] As used herein, the terms “supramolecular assembly” or “supramolecular complex” may be used interchangeably and refer to molecular self-assembly in which two or more compounds interact with each other through various weak intermolecular interactions, such as hydrogen bonding, dipole-to-dipole interactions, van der Waals forces, cation-π interactions, π-π bonds, CH / π interactions, or hydrophobic effects, resulting in the formation of an intermolecular complex having enhanced or different functionalities compared to each individual molecule, such as water solubility.

[0039] As used herein, the term “keratinous substance” is intended to include mucous membranes such as skin, hair, and lips.

[0040] As used herein, "room temperature" means a temperature of approximately 25°C.

[0041] All percentages in this disclosure refer to weight percentages unless otherwise specified.

[0042] supramolecular assembly The supramolecular assemblies of this disclosure comprise at least one pyridinylformamide compound and at least one hydroxy fatty acid, wherein the pyridinylformamide compound and the hydroxy fatty acid are assembled by non-covalent bonds.

[0043] While we do not wish to be bound by any particular theory, it is proposed herein that intermolecular interactions, such as hydrogen bonding interactions between the components of pyridinylformamide compounds and hydroxy fatty acids, lead to the formation of supramolecular assemblies, which are involved in the observation of enhanced functionality of the supramolecular assemblies and improved solubility of water-insoluble or poorly soluble active ingredients.

[0044] Hydroxy fatty acids The supramolecular assemblies of this disclosure may contain at least one hydroxy fatty acid.

[0045] Suitable hydroxy fatty acids may have a carbon chain length of C6 or more, for example, a carbon chain length of C6 to C24, preferably a carbon chain length of C12 to C18.

[0046] For the purposes of the present invention, the hydroxy fatty acid may be linear or branched, preferably linear, and saturated or unsaturated, preferably saturated.

[0047] For the purposes of the present invention, the fatty acid may have one or two hydroxyl groups, preferably one hydroxyl group.

[0048] For the purposes of the present invention, the aliphatic fatty acid is preferably substituted by a hydroxyl molecule between the C6 and C12 positions, preferably at the C10 position.

[0049] Suitable hydroxy fatty acids for use in the present invention may be selected from hydroxylauric acid, hydroxystearic acid, dihydroxystearic acid, and combinations thereof, for example, 2-hydroxylauric acid, 10-hydroxystearic acid, and 12-hydroxystearic acid.

[0050] 10-hydroxystearic acid is particularly preferred.

[0051] 10-Hydroxystearic acid can be formed from 10-hydroxydecanoic acid by dehydration and oxidation using copper chloride and hydrogen peroxide. Alternatively, 10-hydroxystearic acid can be synthesized by recombinant cells engineered to express the gene for this molecule. The fatty acid can also be produced by corynebacterium glutamicum when grown on a medium containing glucose as the sole carbon source. A commercially available product of 10-hydroxystearic acid is, for example, the product sold by DSM Nutritional Products Ltd. under the brand name "BEAUACTIVE".

[0052] Pyridinylformamide compounds The supramolecular assemblies of this disclosure may comprise at least one pyridinylformamide compound.

[0053] As used herein, the term "pyridinylformamide compound" refers to the following formula:

[0054] [ka] This refers to certain compounds having and their N-substituted derivatives, where R is -CONH2.

[0055] N-substituted derivatives include nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR).

[0056] Pyridinylformamide compounds suitable for use in the present invention can be selected from the group consisting of picolinamide, nicotinamide, isonicotinamide, and combinations thereof.

[0057] Nicotinamide is particularly preferred.

[0058] Nicotinamide, also known as niacinamide, is a physiologically active amide of vitamin B3 that inhibits melanosome migration and inhibits melanin synthesis in keratinocytes. This reduces skin pigmentation and enhances skin whitening. A commercially available product containing nicotinamide is, for example, the product sold by DSM Nutritional Products Ltd. under the brand name "NIACINAMIDE PC / B3 FRESH".

[0059] In one particular embodiment, the molar ratio of the pyridinylformamide compound to the hydroxy fatty acid in the supramolecular assembly is in the range of about 1:10 to about 10:1, preferably about 1:8 to about 8:1, more preferably about 1:5 to about 5:1, even more preferably about 1:2 to about 2:1, and most preferably about 1:1.

[0060] In a particular embodiment, the supramolecular assembly of the Disclosure comprises or comprises at least one pyridinylformamide compound and at least one hydroxy fatty acid. In a particular embodiment, the supramolecular assembly of the Disclosure comprises or comprises 10-hydroxystearic acid and nicotinamide interacting with each other via intermolecular interactions, such as hydrogen bonding forces, non-covalent electrostatic interactions, and van der Waals forces.

[0061] In a particular embodiment, the supramolecular assembly of the present disclosure is formed from nicotinamide and 10-hydroxystearic acid in a 1:1 molar ratio. The supramolecular assembly has X-ray powder diffraction peaks at 2θ angles of approximately 8.4°, 9.7°, 10.1°, 11.0°, 14.7°, 16.9°, 19.5°, 20.5°, 21.2°, 22.2°, 22.6°, 23.3°, and 24.1°. The DSC thermogram of the supramolecular assembly shows an endothermic peak at approximately 84°C.

[0062] In another specific embodiment, the supramolecular assembly of the present disclosure is formed from nicotinamide and 10-hydroxystearic acid in a 2:1 molar ratio. The supramolecular assembly has X-ray powder diffraction peaks at 2θ angles of approximately 8.4°, 9.7°, 10.1°, 11.1°, 12.7°, 14.8°, 15.1°, 16.9°, 19.6°, 20.5°, 21.3°, 22.2°, 22.7°, 23.3°, 25.4°, 25.8°, 27.3°, 29.9°, 37.0°, and 38.7°. The DSC thermogram of the supramolecular assembly shows an endothermic peak at approximately 84°C.

[0063] In yet another specific embodiment, the supramolecular assembly of the present disclosure is formed from nicotinamide and 10-hydroxystearic acid in a 1:2 molar ratio. The supramolecular assembly has X-ray powder diffraction peaks at 2θ angles of approximately 8.4°, 9.7°, 10.2°, 11.1°, 12.7°, 14.8°, 15.1°, 16.9°, 19.5°, 20.6°, 21.2°, 22.3°, 22.7°, 23.3°, 24.3°, 24.6°, 29.9°, 34.3°, and 38.8°. The DSC thermogram of the supramolecular assembly shows an endothermic peak at approximately 84°C.

[0064] Supramolecular self-assemblies in which pyridinylformamide compounds and hydroxy fatty acids interact with each other through various non-covalent intermolecular interactions such as hydrogen bonding forces, non-covalent electrostatic interactions, and van der Waals forces result in the formation of intermolecular assemblies that have enhanced or distinct functionalities for each individual molecule, including, for example, water solubility, antioxidant properties, stability, and transdermal permeability.

[0065] Preparation method Methods for preparing supramolecular assemblies include, but are not limited to, the hot-melt method, programmed cooling method, solvent evaporation method, and ball mill method.

[0066] In one embodiment, the supramolecular assembly of the present disclosure is prepared by solvent evaporation, and this method is a) A step of dissolving the starting material in a solvent to obtain a saturated solution, b) A step of evaporating / drying the solution until a substantial amount of solvent is removed from the solution and a crystalline form is formed, c) optionally includes a step of purifying the crystalline form obtained in step b) to obtain a supramolecular aggregate in a pure form.

[0067] In another embodiment, the supramolecular assemblies of the present disclosure are prepared by a hot-melt method, which is: a) A step of heating the starting material to a temperature higher than the melting point of the starting material to produce a mixed molten product, b) A step of cooling the mixed molten material obtained in step a) to provide it in a solid form, c) optionally includes a step of purifying the solid form obtained in step b) to obtain a pure form of supramolecular aggregate.

[0068] In yet another embodiment, the supramolecular aggregates of the present disclosure are prepared by ball milling or solid milling, the method of which a) A step of providing the starting material in stoichiometric quantities, b) Optionally, a step of partially wetting the starting material with a small amount of solvent such as methanol, ethanol, or isopropanol, c) A step of crushing the starting material under crystallization conditions to obtain solid-phase crystals, d) The process includes a step of recovering the crystals obtained in step c) and optionally purifying them.

[0069] In one preferred embodiment, the supramolecular assemblies of the present disclosure are prepared by a programmed cooling method, which is: a) A step of mixing the starting materials in a solvent to obtain a mixture, heating the mixture to a first temperature and maintaining it until the starting materials are completely dissolved and a transparent system is obtained, b) A step of cooling the system to a second temperature and leaving the system at the second temperature to generate crystals, wherein the second temperature is at least 15°C, preferably at least 25°C, and more preferably at least 35°C lower than the first temperature. c) The step of collecting the crystals obtained in step b) and optionally purifying them to obtain a supramolecular assembly.

[0070] The programmed cooling method may further include an intermediate cooling step between step a) and step b), where the system is cooled to an intermediate temperature and left for 1 to 10 hours, preferably 1 to 6 hours, more preferably 1 to 3 hours, where the intermediate temperature is at least 10°C lower than the first temperature or the intermediate temperature of the previous intermediate cooling step, and at least 10°C higher than the second temperature, and n is 1, 2, 3, 4, or 5, preferably 2, 3, or 4, more preferably 2 or 3.

[0071] In step a) of the programmed cooling method, the first temperature may be in the range of about 30°C to about 70°C, preferably about 35°C to about 60°C, and more preferably about 40°C to about 50°C. In step b) of the programmed cooling method, the system may be left for 1 to 10 hours, preferably 2 to 8 hours, and more preferably 4 to 6 hours. Recovery in step c) can be achieved by any suitable solid-liquid separation process, such as filtration. Purification in step c) can be carried out by any suitable purification process, such as vacuum drying, for a period of 5 to 48 hours, preferably 10 to 24 hours, at a temperature of about 20°C to about 70°C, preferably about 40°C to about 50°C.

[0072] In one embodiment, suitable solvents for use in the process of the present disclosure include any suitable polar or nonpolar solvent that is liquid under the conditions of the method and capable of dissolving the starting material, such as various hydrocarbons, alcohols, carboxylic acids, esters, ketones, acetals, ethers, and water.

[0073] Polar solvents used herein include those with up to 100% water solubility and a polarity index greater than about 5.0, such as water, acetic acid, methanol, ethanol, n-propanol, isopropanol, propanediol, glycerol, dimethyl sulfoxide, dimethylformamide, acetonitrile, acetone, dioxane, tetrahydrofuran, or acetic acid, citric acid, phosphate buffer, or mixtures thereof in different proportions. This list is not intended to limit the solvents used, but considering safety for cosmetic or pharmaceutical applications, water, ethanol, n-propanol, isopropanol, methanol, acetone, propanediol, as well as acetic acid, citric acid, and phosphate buffer are preferred.

[0074] Nonpolar organic solvents used herein include those with less than 30% water solubility and a polarity index of 0 to about 5.0, such as ethyl acetate, butyl acetate, n-butanol, diethyl ether, hexane, 2-butanone, chloroform, 1,2-dichloroethane, benzene, xylene, methyl-t-butyl ether, toluene, carbon tetrachloride, trichloroethylene, cyclohexane, pentane, and heptane, or mixtures thereof in different proportions. This list is not intended to limit the solvents used, but ethyl acetate, butyl acetate, and n-butanol are preferred in consideration of safety for cosmetic or pharmaceutical applications.

[0075] A mixed solvent of ethanol and water is particularly preferred.

[0076] In one embodiment, the method for preparing the supramolecular assemblies of the present disclosure may be a seed crystal addition process with or without the addition of exogenous seed crystals. Conventional seed crystal addition processes involve adding exogenous seed crystals, originating from other sources such as solvent evaporation, to the system to initiate crystallization. Preferably, the method of the present disclosure is a self-seed crystal addition process without the addition of exogenous seed crystals.

[0077] In one particular embodiment, a programmed cooling method for preparing a supramolecular assembly is: a) A step of mixing the starting materials in a solvent and stirring to obtain a mixture, heating the mixture to a first temperature in the range of approximately 35°C to approximately 65°C, and maintaining it until the starting materials are completely dissolved and a transparent system is obtained, b) Once completely dissolved, stop stirring, cool the system to an intermediate temperature in the range of approximately 15°C to 25°C, and leave the system at this temperature for 1 to 6 hours to generate a seed crystal doping system. c) A step of further cooling the system to a second temperature in the range of approximately -5°C to approximately 5°C, and leaving the system at the second temperature for 1 to 10 hours to generate crystals, d) The step of recovering the crystals obtained in step c) and optionally purifying them to obtain a pure form of the supramolecular assembly.

[0078] In another specific embodiment, a programmed cooling method for preparing a supramolecular assembly is, a) A step of mixing the starting materials in a solvent and stirring to obtain a mixture, heating the mixture to a first temperature in the range of approximately 35°C to approximately 65°C, and maintaining it until the starting materials are completely dissolved and a transparent system is obtained, b) After complete dissolution, stopping the stirring, cooling the system to a first intermediate temperature in the range of approximately 25°C to approximately 35°C, and leaving the system at the first intermediate temperature for 1 to 3 hours, wherein the first intermediate temperature is at least 10°C lower than the first temperature. c) A step of further cooling the system to a second intermediate temperature in the range of approximately 15°C to approximately 25°C, and leaving the system at the second intermediate temperature for 1 to 3 hours to generate a seed crystal doped system, wherein the second intermediate temperature is at least 10°C lower than the first intermediate temperature. d) A step of further cooling the system to a second temperature in the range of approximately -5°C to approximately 5°C, and leaving the system at the second temperature for 1 to 10 hours to generate crystals, e) The process includes recovering the crystals obtained in step d) and optionally purifying them to obtain a pure form of the supramolecular assembly.

[0079] In yet another specific embodiment, a programmed cooling method for preparing a supramolecular assembly is, a) A step of mixing the starting materials in a solvent and stirring to obtain a mixture, heating the mixture to a first temperature in the range of approximately 35°C to approximately 65°C, and maintaining it until the starting materials are completely dissolved and a transparent system is obtained, b) After complete dissolution, stopping the stirring, cooling the system to a first intermediate temperature in the range of approximately 25°C to approximately 35°C, and leaving the system at the first intermediate temperature for 1 to 3 hours, wherein the first intermediate temperature is at least 10°C lower than the first temperature. c) A step of further cooling the system to a second intermediate temperature in the range of approximately 15°C to approximately 25°C, and leaving the system at the second intermediate temperature for 1 to 3 hours to generate a seed crystal doped system, wherein the second intermediate temperature is at least 10°C lower than the first intermediate temperature. d) A step of further cooling the system to a third intermediate temperature in the range of approximately 0°C to approximately 5°C, and leaving the system at the third intermediate temperature for 1 to 3 hours, wherein the third intermediate temperature is at least 15°C lower than the second intermediate temperature. e) A step of further cooling the system to a second temperature in the range of approximately -10°C to approximately -5°C, and leaving the system at the second temperature for 1 to 10 hours to generate crystals, f) includes the step of recovering the crystals obtained in step d) and optionally purifying them to obtain a pure form of the supramolecular assembly.

[0080] In one preferred embodiment, the present disclosure provides a supramolecular assembly comprising at least one pyridinylformamide compound and at least one hydroxy fatty acid, wherein the pyridinylformamide compound and the hydroxy fatty acid are bound together by non-covalent forces. Supramolecular assemblies are a) A step of mixing starting materials in a solvent to obtain a mixture, heating the mixture to a first temperature and maintaining it until the starting materials are completely dissolved and a transparent system is obtained, wherein the starting materials comprise at least one pyridinylformamide compound and at least one hydroxy fatty acid. b) A step of cooling the system to a second temperature and leaving the system at the second temperature to generate crystals, wherein the second temperature is -20°C or higher and at least 15°C, preferably at least 25°C, and more preferably at least 35°C lower than the first temperature. c) The step of collecting the crystals obtained in step b) and optionally purifying them to obtain a supramolecular assembly.

[0081] In a further embodiment, the method preferably further includes n intermediate cooling steps between step a) and step b), where the system is cooled to an intermediate temperature and left for 1 to 10 hours, preferably 1 to 6 hours, more preferably 1 to 3 hours, the intermediate temperature being at least 10°C lower than the first temperature or the intermediate temperature of the previous intermediate cooling step, and at least 10°C higher than the second temperature, where n is 1, 2, 3, 4, or 5, preferably 2, 3, or 4, more preferably 2 or 3.

[0082] Cosmetic composition The cosmetic compositions of this disclosure include supramolecular assemblies having the definitions and preferences defined above.

[0083] Cosmetic compositions may be in solid, semi-solid, or liquid form, and may be in solution, emulsion, suspension, or anhydrous form. When in solution or suspension form, the composition may contain about 1 to 99.9%, preferably about 5 to 95%, more preferably about 10 to 90% water. When in emulsion form, the composition may contain 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. When in anhydrous form, the composition may contain about 10 to 99% oil and 10 to 99% solidifying agent.

[0084] Cosmetic compositions may include skincare products such as face, hand, and foot care products; acne treatment products, shaving products, cleansing products; powders, antiperspirants; hair remover products, teeth whitening products, color makeup products such as makeup bases, foundations, eyeshadows, eyeliners, and blushes; sunscreen products; and insect repellents.

[0085] In one embodiment, the supramolecular aggregate is present in the cosmetic composition in an amount of about 0.0001% to about 50% by weight, preferably about 0.001% to about 20% by weight, more preferably about 0.01% to about 10% by weight, and most preferably about 0.1% to about 2% by weight, relative to the total weight of the composition.

[0086] Provided that the beneficial effects of the supramolecular assemblies of this disclosure are not affected, the compositions of this disclosure may further include at least one cosmetically acceptable medium, such as additives, excipients, diluents, and / or other active ingredients, as detailed below.

[0087] A. Moisturizer The compositions of this disclosure may contain one or more humectants. If present, they may be in the range of about 0.1 to 75%, preferably about 0.5 to 70%, more preferably about 0.5 to 40%. Examples of suitable humectants include glycols and sugars. Suitable glycols are polyethylene glycols in monomeric or polymeric form having 4 to 10 repeating ethylene oxide units, such as polyethylene glycols and polypropylene glycols such as PEG4 to PEG10, and C 1~6 Alkylene glycols, such as propylene glycol, butylene glycol, and pentylene glycol, are also suitable. Suitable sugars are also suitable humectants, some of which are polyhydric alcohols. Examples of such sugars include glucose, fructose, honey, hydrogenated honey, inositol, maltose, mannitol, maltitol, sorbitol, sucrose, xylitol, and xylose. Urea is also suitable. Preferably, the humectant used in the compositions of this disclosure is C 1~6 Preferably C 2~4 Alkylene glycol, more specifically butylene glycol.

[0088] B. Plant extracts The compositions of this disclosure may contain one or more additional plant extracts other than roselle extract. If present, the proposed range is about 0.0001 to 20%, preferably about 0.0005 to 15%, and more preferably about 0.001 to 10%. Suitable plant extracts include yeast fermentation extracts, Padina pavonica extracts, Thermus thermophilis fermentation extracts, Camelina sativa seed oil, Boswellia serrata extracts, olive extracts, Acacia dealbata extracts, Acer saccharinum (sugar maple), Acidopholus, Acorus, Aesculus, Agaricus, Agave, Agrimonia, algae, aloe, citrus fruits, Brassica, cinnamon, oranges, apples, blueberries, cranberries, peas, pears, lemons, limes, peas, seaweed, caffeine, green tea, chamomile, willow bark, mulberry, poppy, and extracts from plants (herbs, roots, flowers, fruits, seeds) such as flowers, fruits, and vegetables, including those listed on pages 1646-1660 of the CTFA Cosmetic Ingredient Handbook, Eighth Edition, Volume 2.Further examples include, but are not limited to, Glycyrrhiza glabra, Salix nigra, Macrocycstis pyrifera, Pyrus malus, Saxifraga sarmentosa, Vitis vinifera, Morus nigra, Scutellaria baicalensis, Anthemis nobilis, Salvia sclarea, Rosmarinus officianalis, Citrus limonum, Panax ginseng, Siegesbeckia orientalis, Fructus mume, Ascophyllum nodosum, Glycine soja extract, Beta vulgaris, Haberlea rhodopensis, Polygonum cuspidatum, Citrus aurantium dulcis, Vitis vinifera, Selaginella tamariscina, Humulus lupulus, Citrus reticulata Peel, Punica granatum, Asparagopsis, Curcuma Examples include longa, Menyanthes trifoliata, Helianthus annuus, Hordeum vulgare, Cucumis sativus, Evernia prunastri, Evernia furfuracea, Kola acuminata, and mixtures thereof.

[0089] C. Surfactants The compositions of this disclosure may contain one or more surfactants, particularly when in emulsion form. However, such surfactants may also be used when the composition is a solution, suspension, or anhydrous. If present, the surfactant may be in the range of about 0.001 to 30% by weight, preferably about 0.005 to 25% by weight, and more preferably about 0.1 to 20% by weight of the total composition. Suitable surfactants may be silicones, or organic, nonionic, anionic, amphoteric, or zwitterionic.

[0090] 1. Organic nonionic surfactants The compositions of this disclosure may contain one or more nonionic organic surfactants. Suitable nonionic surfactants include alkoxylated alcohols or ethers formed by the reaction of an alcohol with an alkylene oxide, usually ethylene oxide or propylene oxide. Suitable alcohols include monovalent, divalent, or polyvalent short-chain (C) 1~6 ) Alcohol, cholesterol, aromatic or aliphatic saturated or unsaturated fats (C 12~40 Examples include alcohol.

[0091] Cholesterol, or aromatic or aliphatic saturated or unsaturated fatty alcohols having 6 to 40 carbon atoms, preferably about 10 to 30, more preferably about 12 to 22 carbon atoms, are preferred. Examples include oleyl alcohol, cetearyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, and behenyl alcohol. Examples of such components include oleth 2-100, steareth 2-100, beheneth 5-30, ceteareth 2-100, ceteth 2-100, and cholesterol 2-100, where the number range refers to the number of repeating ethylene oxide units; for example, ceteth 2-100 means ceteth with a number of repeating ethylene oxide units in the range of 2 to 100. Derivatives of alkoxylated alcohols, such as their phosphate esters, are also preferred.

[0092] Some preferred organic nonionic surfactants include oleth-3, oleth-5, oleth-3 phosphate, choleth-24, and ceteth-24.

[0093] Alkoxylated alcohols formed from monovalent, divalent, or polyvalent short-chain alcohols, such as those having about 1 to 6 carbon atoms, are also preferred. Examples include glucose, glycerin, or their alkylated derivatives. Examples include glycereth-2-100, gluceth-2-100, and methyl gluceth-2-100. Methyl gluceth-20 and glycereth-26 are more preferred.

[0094] Other types of alkoxylated alcohols are suitable surfactants, including ethylene oxide polymers with a variable number of repeating EO groups, commonly referred to as PEG-12 to PEG-200. PEG-75 is more preferred, and can be purchased from Dow Chemical under the trade name Carbowax PEG-3350.

[0095] Other suitable nonionic surfactants include alkoxylated sorbitan and alkoxylated sorbitan derivatives. For example, alkoxylation of sorbitan, particularly ethoxylation, provides polyalkoxylated sorbitan derivatives. Esterification of polyalkoxylated sorbitan provides sorbitan esters such as polysorbates. For example, polyalkoxylated sorbitan is C 6~30 Preferably C 12~22 These components can be esterified with fatty acids. Examples of such components include polysorbate 20-85, sorbitan oleate, sorbitan sesquioleate, sorbitan palmitate, sorbitan sesquiisostearate, and sorbitan stearate.

[0096] 2. Silicone or silane surfactant Various types of silicone or silane-based surfactants are also suitable. Examples include PEG-dimethicone, which is a polyethylene glycol-substituted dimethicone containing organosiloxanes substituted with ethylene oxide or propylene oxide groups, such as PEG-1 dimethicone, PEG-4 dimethicone, PEG-8 dimethicone, PEG-12 dimethicone, and PEG-20 dimethicone, among others.

[0097] Silanes substituted with ethoxy groups, propoxy groups, or both, such as various types of PEG methyl ether silanes like bis-PEG-18 methyl ether dimethyl silane, are also preferred.

[0098] Further examples of silicone-based surfactants include those with common names such as dimethicone copolyol and cetyl dimethicone copolyol.

[0099] D. Biological materials The compositions of this disclosure may contain various types of biological materials, such as cell-derived materials, fermentation materials, etc. If present, such materials may be present in an amount of about 0.001 to 30%, preferably about 0.005 to 25%, and more preferably about 0.01 to 20%. Examples include cellular RNA or DNA, or fragments of probiotic microorganisms. RNA fragments are particularly preferred.

[0100] E. Thickening agents Suitable thickeners may be incorporated into the compositions of the present disclosure. If present, the proposed range is about 0.01 to 30% by weight, preferably about 0.1 to 20% by weight, and more preferably about 0.5 to 15% by weight of the total composition.

[0101] Examples of thickeners include animal, plant, mineral, silicone, or synthetic waxes that may have a melting point in the range of approximately 30 to 150°C. Examples of such waxes include waxes produced by Fischer-Tropsch synthesis, such as polyethylene or synthetic waxes; or waxes made from bayberry, candelilla, ozokerite, acacia, beeswax, ceresin, cetyl esters, flower waxes, citrus waxes, carnauba wax, jojoba wax, wood wax, polyethylene, microcrystalline waxes, rice bran, lanolin wax, mink, montane, bayberry, ouricury, ozokerite, palm kernel wax, paraffin, avocado wax, apple wax, shellac wax, salvia wax, spent grain wax, grape wax, and their polyalkylene glycol derivatives, such as PEG-6-20 beeswax or PEG-12 carnauba wax; or fatty acids or fatty alcohols containing their esters, such as hydroxystearic acid (e.g., 12-hydroxystearic acid), tristearin, and tribehenin.

[0102] Silica, silicates, silylated silica, and their alkali metal or alkaline earth metal derivatives are also suitable as thickeners. These silicas and silicates are generally found in particulate form and include silica, silylated silica, and magnesium aluminum silicate.

[0103] Silicone elastomers can also be used as thickeners. Such elastomers are formed by addition curing in the presence of a platinum metal catalyst, reacting a SiH-containing diorganosiloxane with an organopolysiloxane having terminally olefin unsaturated or alpha-omegadiene hydrocarbon. Such elastomers may also be formed by other reaction methods, such as condensation curing of an organopolysiloxane composition via a dehydrogenation reaction between a hydroxyl-terminated diorganopolysiloxane and a SiH-containing diorganopolysiloxane or alpha-omegadiene in the presence of an organotin compound, or by condensation curing of an organopolysiloxane composition using a condensation reaction between a hydroxyl-terminated diorganopolysiloxane and a hydrolyzable organosiloxane in the presence of an organotin compound or titanate ester. They may also be formed by other reaction methods, such as peroxide curing of a thermocurable organopolysiloxane composition in the presence of an organic peroxide catalyst.

[0104] One type of elastomer that may be suitable can be prepared by addition curing of an organopolysiloxane or alpha-omegadiene having at least two lower alkenyl groups in each molecule, and an organopolysiloxane having at least two silicon-bonded hydrogen atoms in each molecule, and a platinum catalyst. The lower alkenyl groups, such as vinyl, can be located at any position in the molecule, but terminal olefin unsaturation at one or both ends of the molecule is preferred. The molecular structure of this component may be linear, branched linear, cyclic, or network. These organopolysiloxanes are exemplified by methylvinylsiloxane, methylvinylsiloxane-dimethylsiloxane copolymer, dimethylvinylsiloxy-terminated dimethylpolysiloxane, dimethylvinylsiloxy-terminated dimethylsiloxane-methylphenylsiloxane copolymer, dimethylvinylsiloxy-terminated dimethylsiloxane-diphenylsiloxane-methylvinylsiloxane copolymer, trimethylsiloxy-terminated dimethylsiloxane-methylvinylsiloxane copolymer, trimethylsiloxy-terminated dimethylsiloxane-methylphenylsiloxane-methylvinylsiloxane copolymer, dimethylvinylsiloxy-terminated methyl(3,3,3-trifluoropropyl)polysiloxane, and dimethylvinylsiloxy-terminated dimethylsiloxane-methyl(3,3,-trifluoropropyl)siloxane copolymer, decadiene, octadiene, heptadiene, hexadiene, pentadiene, or tetradiene, or tridiene.

[0105] Curing proceeds by an addition reaction between silicon-bonded hydrogen atoms in dimethylmethylhydrogensiloxane and siloxane or alpha-omegadiene under catalytic conditions using the catalyst described herein. To form a highly crosslinked structure, the methylhydrogensiloxane must contain at least two silicon-bonded hydrogen atoms in each molecule to optimize its function as a crosslinking agent.

[0106] Catalysts used in the addition reactions of silicon-bonded hydrogen atoms and alkenyl groups include, specifically, chloroplatinic acid (possibly dissolved in an alcohol or ketone, and this solution optionally aged), chloroplatinic acid-olefin complexes, chloroplatinic acid-alkenylsiloxane complexes, chloroplatinic acid-diketone complexes, platinum black, and supported platinum.

[0107] Examples of silicone elastomers suitable for use in the compositions of this disclosure may be in powder form, or may be dispersed or solubilized in a solvent such as a volatile or non-volatile silicone, or in a silicone-compatible vehicle such as a paraffinic hydrocarbon or ester. Examples of silicone elastomer powders include vinyl dimethicone / methicone silsesquioxane crosslinked polymers such as Shin-Etsu's KSP-100, KSP-101, KSP-102, KSP-103, KSP-104, and KSP-105; hybrid silicone powders containing fluoroalkyl groups such as Shin-Etsu's KSP-200, which is a fluorosilicone elastomer; hybrid silicone powders containing phenyl groups such as Shin-Etsu's KSP-300, which is a phenyl-substituted silicone elastomer; and Dow Coming's DC9506. Examples of silicone elastomer powders dispersed in a silicone-compatible vehicle include dimethicone / vinyl dimethicone crosslinked polymers supplied by various suppliers, including trade names 9040 or 9041 from Dow Corning Corporation, SFE839 from GE Silicones, or KSG-15, 16, and 18 from Shin-Etsu Silicones. KSG-15 has the CTFA name Cyclopentasiloxane / Dimethicone / Vinyl Dimethicone Crosslinked Polymer. KSG-18 has the INCI name Phenyl Trimethicone / Dimethicone / Phenyl Vinyl Dimethicone Crosslinked Polymer. Silicone elastomers can also be purchased from Grant Industries under the trade name Gransil. Furthermore, silicone elastomers having long-chain alkyl substitutions, such as lauryl dimethicone / vinyl dimethicone crosslinked polymers supplied by Shin Etsu under the trade names KSG-31, KSG-32, KSG-41, KSG-42, KSG-43, and KSG-44, are also suitable.Crosslinked organopolysiloxane elastomers useful in this disclosure and processes for producing them are further described in U.S. Patent No. 4,970,252 to Sakuta et al., issued November 13, 1990; U.S. Patent No. 5,760,116 to Kilgour et al., issued June 2, 1998; U.S. Patent No. 5,654,362 to Schulz, Jr. et al., issued August 5, 1997; and Japanese Patent Application Publication No. 61-18708, assigned to Pola Kasei Kogyo KK, each of which is incorporated herein by reference in whole.

[0108] Polysaccharides can be suitable aqueous thickeners. Examples of such polysaccharides include naturally derived materials such as agar, agarose, Alcaligenes-producing polysaccharides, algin, alginic acid, acacia gum, amylopectin, chitin, dextran, cellulose gum, gelatin, gellan gum, hyaluronic acid, hydroxyethylcellulose, methylcellulose, ethylcellulose, pectin, sclerotium gum, xanthan gum, trehalose, and gelatin.

[0109] Furthermore, different types of synthetic polymer thickeners are also suitable. One example is an acrylic polymer thickener composed of monomers A and B, where A is selected from the group consisting of acrylic acid, methacrylic acid, and mixtures thereof, and B is selected from the group consisting of C1-22 alkyl acrylates, C1-22 alkyl methacrylates, and mixtures thereof. Examples of acrylic polymer solutions include those sold by Seppic, Inc. under the trade name Sepigel® or under the trade name Aristoflex®.

[0110] Acrylic polymer thickeners that are copolymers of monomers A, B, and C are also suitable, where A and B are as defined above, and C is given by the following general formula:

[0111] [ka] having, wherein Z is -(CH2) m where m is 1 - 10, n is 2 - 3, o is 2 - 200, and R is C 10~30 a linear or branched alkyl. Examples of the above secondary thickeners are copolymers where A and B are defined as above, C is CO, and n, o, and R are as defined above. An example of such a secondary thickener is the acrylate / stearyl - 20 methacrylate copolymer sold by Rohm & Haas under the trade name Acrysol ICS - 1.

[0112] Also preferred are acrylate - based anionic amphiphilic polymers containing at least one hydrophilic unit and at least one allyl ether unit containing a fatty chain. The hydrophilic unit contains an ethylenically unsaturated anionic monomer, more specifically a vinyl carboxylic acid such as acrylic acid, methacrylic acid, or a mixture thereof, and the allyl ether unit containing a fatty chain has the following formula: CH2=CR’CH2OB n R corresponding to the monomer of, wherein R’ represents H or CH3, B represents an ethyleneoxy radical, n is an integer in the range of zero or 1 - 100, and R preferably represents a hydrocarbon radical selected from alkyl radicals, arylalkyl radicals, aryl radicals, alkylaryl radicals, and cycloalkyl radicals containing 8 - 30 carbon atoms, preferably 10 - 24 carbon atoms, and more specifically 12 - 18 carbon atoms. In this case, R’ represents H, n is equal to 10, and R is stearyl (C 18) Those representing radicals are more preferred. This type of anionic amphiphilic polymer is described and prepared in U.S. Patents 4,677,152 and 4,702,844, both of which are incorporated herein by reference in their entirety. Among these anionic amphiphilic polymers, particularly those formed from 20-60% by weight of acrylic acid and / or methacrylic acid, 5-60% by weight of lower alkyl methacrylate, 2-50% by weight of the aforementioned fatty chain-containing allyl ether, and 0-1% by weight of a crosslinking agent which is a well-known copolymerizable polyethylene unsaturated monomer, such as diallyl phthalate, allyl (meth)acrylate, divinylbenzene, (poly)ethylene glycol dimethacrylate, and methylenebisacrylamide. One commercially available example of such polymers is a crosslinked terpolymer of polyethylene glycol (having 10 EO units) ether of methacrylic acid, ethyl acrylate, stearyl alcohol, or steareth-10, particularly those marketed by Allied Colloids under the names SALCARE SC80 and SALCARE SC90, which are aqueous emulsions containing 30% crosslinked terpolymer of methacrylic acid, ethyl acrylate, and steareth-10 allyl ether (40 / 50 / 10).

[0113] Acrylate copolymers such as polyacrylate-3, which is a copolymer of methacrylic acid, methyl methacrylate, methylstyrene isopropyl isocyanate, and PEG-40 behenate monomer; polyacrylate-10, which is a copolymer of sodium acryloyldimethyltaurate, sodium acrylate, acrylamide, and vinylpyrrolidone monomer; or polyacrylate-11, which is a copolymer of sodium acryloyldimethylacryloyldimethyltaurate, sodium acrylate, hydroxyethyl acrylate, lauryl acrylate, butyl acrylate, and acrylamide monomer are also preferred.

[0114] Crosslinked acrylate polymers, such as acrylate / C10-30 alkyl acrylate crosslinked polymers, are also preferred. These polymers may have one or more substituted long-chain alkyl (6-40, 10-30, etc.) groups among the acrylic groups. For example, a copolymer of C10-30 alkyl acrylate and one or more monomers of acrylic acid, methacrylic acid, or simple esters thereof, is crosslinked with an allyl ether of sucrose or an allyl ether of pentaerythritol. Such polymers are commonly sold under the trade names Carbopol or Pemulen and have the CTFA name carbomer.

[0115] One particularly preferred type of aqueous thickener is an acrylate polymer thickener marketed by Clariant under the Aristoflex trademark, such as Aristoflex AVL; in which the same polymer found in Aristoflex AVC;AVC, which is an ammonium acryloyldimethyltaurate / VP copolymer, is dispersed in a mixture containing caprylic / capric triglyceride, trilaureth-4, and polyglyceryl-2 sesquiisostearate, or Aristoflex HMB, which is an ammonium acryloyldimethyltaurate / beheneth-25 methacrylate crosslinked polymer.

[0116] Various polyethylene glycol (PEG) derivatives with a degree of polymerization ranging from 1,000 to 200,000 are also suitable as thickeners. Such components are indicated by the degree of polymerization in thousands following "PEG," for example, PEG-45M, which means PEG having 45,000 repeating ethylene oxide units. Examples of suitable PEG derivatives include PEG 2M, 5M, 7M, 9M, 14M, 20M, 23M, 25M, 45M, 65M, 90M, 115M, 160M, and 180M.

[0117] Polyglycerin, which is a repeating glycerin portion having 15 to 200 repeating portions, preferably in the range of about 20 to 100, is also suitable. Examples of suitable polyglycerins include those having CTFA names such as polyglycerin-20 and polyglycerin-40.

[0118] F.Oil If the compositions of this disclosure are in emulsion form, the compositions will contain an oil phase. The oily component is desirable for skin moisturizing and protective properties. Suitable oils include, but are not limited to, silicones, esters, vegetable oils, and synthetic oils as described herein. The oils may be volatile or non-volatile and are preferably in the form of a liquid that can be injected at room temperature. The term "volatile" means that the oil has a measurable vapor pressure or a mercury vapor pressure of at least about 2 mm at 20°C. The term "non-volatile" means that the oil has a mercury vapor pressure of less than about 2 mm at 20°C.

[0119] 1. Volatile oils Suitable volatile oils generally have a viscosity in the range of about 0.5 to 5 centistokes at 25°C and include linear silicones, cyclic silicones, paraffinic hydrocarbons, or mixtures thereof.

[0120] (a) Volatile silicones Cyclic silicones are a type of volatile silicone that can be used in compositions. Such silicones are represented by the following general formula:

[0121] [ka] The formula has the following characteristics, where n = 3 to 6, preferably 4, 5, or 6.

[0122] Linear volatile silicones, for example, the following general formula: (CH3)3Si-O-[Si(CH3)2-O] n -Si(CH3)3 Those having are also preferable, where n = 0, 1, 2, 3, 4, or 5, preferably 0, 1, 2, 3, or 4.

[0123] Cyclic and linear volatile silicones are available from various commercial sources, including Dow Corning Corporation and General Electric. Dow Corning's linear volatile silicones are marketed under the trade names Dow Corning 244, 245, 344, and 200 fluid. These fluids include hexamethyldisiloxane (viscosity 0.65 centistoke (abbreviated as cst)), octamethyltrisiloxane (1.0 cst), decamethyltetrasiloxane (1.5 cst), dodecamethylpentasiloxane (2 cst), and mixtures thereof, all viscosity measurements taken at 25°C.

[0124] Suitable branched volatile silicones include alkyl trimethicones such as methyl trimethicone, and branched volatile silicones having the following general formula:

[0125] [ka]

[0126] Methyltrimethicone, with a viscosity of 1.5 centistokes at 25°C, can be purchased from Shin-Etsu Silicones under the trade name TMF-1.5.

[0127] (b) Volatile paraffinic hydrocarbons Various straight-chain or branched paraffinic hydrocarbons having 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 carbon atoms, more preferably 8 to 16 carbon atoms, are also suitable. Suitable hydrocarbons include pentane, hexane, heptane, decane, dodecane, tetradecane, tridecane, and C, as disclosed in U.S. Patents No. 3,439,088 and No. 3,818,105, both of which are incorporated herein by reference.8~20 Isoparaffin is one example.

[0128] Preferred volatile paraffinic hydrocarbons have a molecular weight of 70-225, preferably 160-190, a boiling point range of 30-320, preferably 60-260°C, and a viscosity of less than about 10 cst. at 25°C. Such paraffinic hydrocarbons are available from EXXON under the trademark ISOPARS and from Permethyl Corporation. Suitable C 12 Isoparaffin is manufactured by Permethyl Corporation under the trade name Permethyl 99A. Various types of C are available on the market. 16 Isoparaffins, such as isohexadecane (which has the trade name Permethyl R), are also preferred.

[0129] 2. Non-volatile oils Various non-volatile oils are also suitable for use in the compositions of this disclosure. Non-volatile oils generally have a viscosity greater than about 5 to 10 centistokes at 25°C, and may range in viscosity up to about 1,000,000 centipoise at 25°C. Examples of non-volatile oils include, but are not limited to, the following.

[0130] (a) Ester Suitable esters are mono-, di-, and triesters. The composition may contain one or more esters selected from the group, or mixtures thereof.

[0131] (i) monoester A monoester is defined as an ester formed by the reaction of a monocarboxylic acid having the formula R-COOH (wherein R is a linear or branched saturated or unsaturated alkyl group having 2 to 45 carbon atoms, or a phenyl group) with an alcohol having the formula R-OH (wherein R is a linear or branched saturated or unsaturated alkyl group having 2 to 30 carbon atoms, or a phenyl group). Both the alcohol and the acid may be substituted with one or more hydroxyl groups. Either the acid or the alcohol, or both, may be a “fatty” acid or alcohol, having about 6 to 30 carbon atoms, more preferably 12, 14, 16, 18, or 22 carbon atoms, in a linear or branched, saturated or unsaturated form. Examples of monoester oils that may be used in the compositions of this disclosure include hexyl laurate, butyl isostearate, hexadecyl isostearate, cetyl palmitate, isostearyl neopentanoate, stearyl heptanoate, isostearyl isononanoate, stearyl lactate, stearyl octanoate, stearyl stearate, and isononyl isononanoate.

[0132] (ii) Diester Suitable diesters are reaction products of a dicarboxylic acid with an aliphatic or aromatic alcohol, or an aliphatic or aromatic alcohol having at least two substituted hydroxyl groups with a monocarboxylic acid. The dicarboxylic acid may contain 2 to 30 carbon atoms and may be linear or branched, saturated or unsaturated. The dicarboxylic acid may be substituted with one or more hydroxyl groups. The aliphatic or aromatic alcohol may also contain 2 to 30 carbon atoms and may be linear or branched, saturated or unsaturated. Preferably, one or more of the acids or alcohols are fatty acids or alcohols, i.e., containing 12 to 22 carbon atoms. The dicarboxylic acid may also be an alpha hydroxy acid. The ester may be in dimer or trimer form. Examples of diester oils that may be used in the compositions of this disclosure include diisostearyl malate, neopentyl glycol dioctanoate, dibutyl sebacate, dicetearyl dimer dilinoleate, dicetyl adipate, diisocetyl adipate, diisononyl adipate, diisostearyl dimer dilinoleate, diisostearyl fumarate, diisostearyl malate, and dioctyl malate.

[0133] (iii) Triester Suitable triesters include reaction products of tricarboxylic acids with aliphatic or aromatic alcohols, or reaction products of aliphatic or aromatic alcohols having three or more substituted hydroxyl groups with monocarboxylic acids. Similar to the mono- and diesters described above, the acids and alcohols contain 2 to 30 carbon atoms, may be saturated or unsaturated, linear or branched, and may be substituted with one or more hydroxyl groups. Preferably, one or more of the acids or alcohols are fatty acids or alcohols containing 12 to 22 carbon atoms. Examples of triesters include trialaxidine, tributyl citrate, triisostearyl citrate, and tri-C citrate. 12~13Examples include alkyl groups, tricaprylin, tricaprylyl citrate, tridecyl behenate, trioctyldodecyl citrate, tridecyl behenate, esters of arachidonic acid, citric acid, or behenate, or tridecyl cocoate, tridecyl isononanoate, etc.

[0134] Suitable esters for use in the compositions of this disclosure are further described under the classification "Esters" in the CTFA Cosmetic Ingredient Dictionary and Handbook, Eleventh Edition, 2006, the entire text of which is incorporated herein by reference.

[0135] (b) Hydrocarbon oils It may be desirable to incorporate one or more non-volatile hydrocarbon oils into the compositions of this disclosure. Suitable non-volatile hydrocarbon oils include paraffinic hydrocarbons and olefins, preferably those having about 20 or more carbon atoms. An example of such hydrocarbon oil is C 24~28 Olefin, C 30~45 Olefin, C 20~40 Examples include isoparaffins, hydrogenated polyisobutene, polyisobutene, polydecene, hydrogenated polydecene, mineral oil, pentahydrosqualene, squalene, squalane, and mixtures thereof. In one preferred embodiment, such hydrocarbons have a molecular weight in the range of about 300 to 1000 daltons.

[0136] (c) Glyceryl esters of fatty acids Synthetic or naturally occurring fatty acid glyceryl esters or triglycerides are also suitable for use in this composition. Both plant and animal sources may be used. Examples of such oils include castor oil, lanolin oil, and C. 10~18Examples include triglycerides, caprylic / capric triglycerides, sweet peach oil, apricot kernel oil, sesame oil, camelina sativa oil, tamanu seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, ink oil, olive oil, coconut oil, illipe oil, rapeseed oil, soybean oil, grapeseed oil, sunflower seed oil, and walnut oil.

[0137] Furthermore, synthetic or semi-synthetic glyceryl esters of fatty acid monoglycerides, diglycerides, and triglycerides, which are modified natural fats or oils, as well as monoesters, diesters, or triesters of polyols such as glycerin, are also preferred. In one example, fat (C 12~22 Carboxylic acids react with one or more repeating glyceryl groups, glyceryl stearate, diglyceryl diisostearate, polyglyceryl-3 isostearate, polyglyceryl-4 isostearate, polyglyceryl-6 ricinoleate, glyceryl dioleate, glyceryl diisotearate, glyceryl tetraisostearate, glyceryl trioctanoate, diglyceryl distearate, glyceryl linoleate, glyceryl myristate, glyceryl isostearate, PEG castor oil, PEG glyceryl oleate, PEG glyceryl stearate, PEG glyceryl tauroate, etc.

[0138] (d) Non-volatile silicones Non-volatile silicone oils (both water-soluble and water-insoluble) are also suitable for use in this composition. Such silicones preferably have a viscosity in the range of about 5 to 800,000 cst at 25°C, preferably 20 to 200,000 cst. Suitable water-insoluble silicones include amine-functional silicones such as amodimethicone.

[0139] For example, such non-volatile silicones can be expressed by the following general formula:

[0140] [ka] It may have, where R and R' are each independently C 1~30 A is a linear or branched, saturated or unsaturated alkyl, phenyl, or aryl, or trialkylsiloxy, where x and y are each independently 1 to 1,000,000, provided that at least one of x or y is present, and A is an alkylsiloxy end-cap unit. A is a methylsiloxy end-cap unit, particularly trimethylsiloxy, and R and R' are each independently C 1~30 Linear or branched alkyl, phenyl, or trimethylsiloxy, more preferably C 1~22 The R is alkyl, phenyl, or trimethylsiloxy, most preferably methyl, phenyl, or trimethylsiloxy, and the resulting silicone is preferably dimethicone, phenyl dimethicone, diphenyl dimethicone, phenyl trimethicone, or trimethylsiloxyphenyl dimethicone. Another example is that at least one R is fatty alkyl (C 12 , C 14 , C 16 , C 18 , C 20 , or C 22 Examples of alkyl dimethicones include cetyl dimethicone, where R is methyl and A is a trimethylsiloxy end cap unit, however such alkyl dimethicones are liquids that can be injected at room temperature. Phenylen trimethicone can be purchased from Dow Corning Corporation under the trade name 556 Fluid. Trimethylsiloxyphenyl dimethicone can be purchased from Wacker-Chemie under the trade name PDM-1000. Cetyl dimethicone, also called liquid silicone wax, can be purchased from Dow Corning as Fluid 2502, or from DeGussa Care & Surface Specialties under the trade names Abil Wax 9801 or 9814.

[0141] G. Sunscreen It may also be desirable to include one or more sunscreens in the compositions of this disclosure. Such sunscreens may include chemical UVA or UVB sunscreens or physical sunscreens in particulate form. Including sunscreens in compositions containing whitening active ingredients will provide additional protection to the skin during the day and enhance the effectiveness of the whitening active ingredients on the skin. If present, the sunscreen may be present in an amount of about 0.1 to 50%, preferably about 0.5 to 40%, and more preferably about 1 to 35%.

[0142] 1. UVA chemical sunscreen If desired, the composition may contain one or more UVA sunscreens. The term "UVA sunscreen" means a compound that blocks UV radiation in the wavelength range of approximately 320–400 nm. A preferred UVA sunscreen has the following formula:

[0143] [ka] This is a dibenzoylmethane compound, where R1 is H, OR, and NRR, and each R is independently H, C 1~20 It is a linear or branched alkyl group, R2 is H or OH, and R3 is H or C 1~20 It is a linear or branched alkyl group.

[0144] R1 is OR, and R is C 1~20 A linear or branched alkyl group, preferably methyl, where R2 is H and R3 is C 1~20 Linear or branched alkyl groups are preferred, more preferably butyl groups.

[0145] Examples of suitable UVA sunscreen compounds for this general formula include 4-methyldibenzoylmethane, 2-methyldibenzoylmethane, 4-isopropyldibenzoylmethane, 4-tert-butyldibenzoylmethane, 2,4-dimethyldibenzoylmethane, 2,5-dimethyldibenzoylmethane, 4,4'-diisopropylbenzoylmethane, 4-tert-butyl-4'-methoxydibenzoylmethane, 4,4'-diisopropylbenzoylmethane, 2-methyl-5-isopropyl-4'-methoxydibenzoylmethane, and 2-methyl-5-tert-butyl-4'-methoxydibenzoylmethane. 4-tert-butyl-4'-methoxydibenzoylmethane, also known as avobenzone, is particularly preferred. Avobenzone is commercially available from Givaudan-Roure under trade name Parsol® 1789 and from Merck & Co. under trade name Eusolex® 9020.

[0146] Other types of UVA sunscreens include dicamphor sulfonic acid derivatives such as ecamsule, a sunscreen sold under the trade name Mexoryl®, which has the following formula: terephthalylidene dicamphor sulfonic acid.

[0147] [ka]

[0148] The composition may contain about 0.001 to 20% by weight, preferably 0.005 to 5% by weight, and more preferably about 0.005 to 3% by weight of a UVA sunscreen composition. In preferred embodiments of this disclosure, the UVA sunscreen is avobenzone and is present in an amount of about 3% by weight or less of the total composition.

[0149] 2. UVB chemical sunscreens The term "UVB sunscreen" refers to compounds that block UV radiation in the wavelength range of approximately 290–320 nm. Various UVB chemical sunscreens exist, including alpha-cyano-beta,beta-diphenylacrylates, such as those described in U.S. Patent No. 3,215,724, which is incorporated herein by reference in whole. One specific example of an alpha-cyano-beta,beta-diphenylacrylate is octocrylene, which is 2-ethylhexyl 2-cyano-3,3-diphenylacrylate. In certain cases, a composition may contain octocrylene in an amount of about 10% by weight or less of the total composition. Preferred amounts range from about 0.001% to 10% by weight. Octocrylene can be purchased from BASF under the trade name Uvinul® N-539.

[0150] Other suitable sunscreens include the benzylidene camphor derivatives described in U.S. Patent No. 3,781,417, which are incorporated herein by reference in their entirety. Such benzylidene camphor derivatives have the following general formula:

[0151] [ka] The formula contains, where R is p-tolyl or styryl, preferably styryl. 4-methylbenzylidene camphor, a lipid-soluble UVB sunscreen compound sold by Merck under the trade name Eusolex 6300, is particularly preferred.

[0152] The following general formula:

[0153] [ka] Cinnamate derivatives having are also preferred, where R and R1 are each independently C 1~20 It is a linear or branched alkyl group. R is methyl, and R1 is branched C 1~10Preferably, the compound is a C8 alkyl group. A preferred compound is ethylhexyl methoxycinnamate, also known as octoxynate or octyl methoxycinnamate. The compound can be purchased from Givaudan Corporation under the trade name Parsol® MCX, or from BASF under the trade name Uvinul® MC 80.

[0154] Mono-, di-, and triethanolamine derivatives of such methoxycinnamates, including diethanolamine methoxycinnamate, are also preferred. Synoxates, which are aromatic ether derivatives of the above compounds, are also acceptable. If present, the synoxates should be found in an amount of about 3% by weight or less of the total composition.

[0155] The following general formula:

[0156] [ka] Various benzophenone derivatives having the same properties are also suitable as UVB shielding agents, where R to R9 are each independently H, OH, NaO3S, SO3H, SO3Na, Cl, R'', OR'', and R'' is C 1~20 The alkyl group is linear or branched. Examples of such compounds include benzophenone 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. Particularly preferred are benzophenone 3 (also called oxybenzone), benzophenone 4 (also called surisobenzone), benzophenone 5 (surisobenzone sodium), etc. Benzophenone 3 is the most preferred.

[0157] The following general formula:

[0158] [ka] Certain menthyl salicylate derivatives having the formula are also preferred, where R1, R2, R3, and R4 are each independently H, OH, NH2, or C 1~20The alkyl group is linear or branched. It is particularly preferable that R1, R2, and R3 are methyl and R4 is hydroxyl or NH2, and the compound is named homomenthyl salicylate (also known as homosalate) or menthyl anthranilate. Homosalate is commercially available from Merck under the trademark Eusolex® HMS, and menthyl anthranilate is commercially available from Haarmann & Reimer under the trademark Heliopan®. If present, homosalate should be found in an amount of about 15% by weight or less of the total composition.

[0159] Various aminobenzoic acid derivatives are given by the following general formula:

[0160] [ka] A suitable UVB absorber comprising the following, wherein R1, R2, and R3 are each independently substituted with H and C, which may be substituted with one or more hydroxyl groups. 1~20 It is a linear or branched alkyl group. R1 is H or C 1~8 It is a linear or branched alkyl group, and R2 and R3 are H or C. 1~8 Linear or branched alkyl groups are particularly preferred. PABA, ethylhexyldimethyl PABA (padimate O), and ethyldihydroxypropyl PABA are particularly preferred. If present, padimate O should be found in an amount of about 8% by weight or less of the total composition.

[0161] Salicylate derivatives are also acceptable UVB absorbers. Such compounds have a general formula, where R is a linear or branched alkyl group, and include derivatives of the above compounds formed from mono-, di-, or triethanolamine. Octyl salicylate, TEA-salicylate, DEA-salicylate, and mixtures thereof are particularly preferred.

[0162] Generally, the amount of UVB chemical sunscreen present may be in the range of about 0.001 to 45% by weight of the total composition, preferably 0.005 to 40% by weight, and more preferably about 0.01 to 35% by weight.

[0163] If desired, the compositions of the present disclosure may be formulated to have a specific SPF (Sun Protection Factor) value in the range of about 1 to 50, preferably about 2 to 45, and most preferably about 5 to 30. The calculation of SPF values ​​is well known in the art.

[0164] H. Vitamins and antioxidants It may be desirable to incorporate one or more vitamins or antioxidants into the compositions of this disclosure. If present, the proposed range is about 0.001 to 20%, preferably about 0.005 to 15%, and more preferably about 0.010 to 10%. Preferably, such vitamins, vitamin derivatives, and / or antioxidants function to scavenge free radicals in the form of singlet oxygen. Examples of such vitamins include tocopherol or its derivatives, e.g., tocopherol acetate, tocopherol ferulate; ascorbic acid or its derivatives, e.g., ascorbyl palmitate, magnesium ascorbyl phosphate; vitamin A or its derivatives, e.g., retinyl palmitate; or vitamins D, K, B, or their derivatives.

[0165] As those skilled in the art will understand, compositions containing supramolecular assemblies according to this disclosure may further comprise one or more additional cosmetic-acceptable media in an amount of about 0.001 to 99% by weight, preferably about 0.01 to 90% by weight, more preferably about 0.1 to 70% by weight, and most preferably about 1 to 50% by weight of the total composition.

[0166] The preparation of the above cosmetic compositions and others can be achieved by referring to any of the cosmetic formulation guidebooks and industry journals available in the cosmetics industry. These references provide standard formulations that can be modified by adding or substituting the supramolecular complexes of this disclosure into the formulations. Suitable guidebooks include Cosmetics and Toiletries Magazine Vol. 111 (March, 1996), Formulary: Ideas for Personal Care; Croda, Inc., Parsippany, NJ (1993), and Cosmeticon: Cosmetic Formulary, BASF, which are incorporated herein by reference in their entirety. The cosmetic compositions may be in any form. Preferred forms include, but are not limited to, solid doses, liquids, gels, lotions, creams, hard gel sticks, roll-on formulations, mousses, aerosol sprays, pad formulations, and film-forming formulations.

[0167] The cosmetic composition of the present invention is preferably applied at least once a day, for example, two or three times a day. Typically, it takes at least two weeks for the desired effect to be achieved. However, it may take several weeks or even months for the desired effect to be fully maximized.

[0168] The amount of keratin substance applied to a cosmetic composition depends on the concentration of active ingredients, such as supramolecular aggregates, in the composition and the desired cosmetic or medicinal effect. For example, the application may be such that a cream is applied to the skin. The cream typically contains 2 mg of cream / cm³. 2 It is applied in amounts on the skin. However, the amount of composition applied to the skin is not important, and if the desired effect cannot be achieved with a specific amount of composition applied, a higher concentration of the active ingredient can be used, for example, by applying more of the composition or by applying a composition containing more active ingredients.

[0169] The supramolecular assemblies of this disclosure can also find a wide range of applications in fields such as personal care, food, nutritional supplements, and pharmaceuticals.

[0170] The present invention will be further described in relation to the following examples, which are provided for illustrative purposes and are not intended to be inherently limiting. [Examples]

[0171] Summary: All solvents were purchased from Macklin Inc. and used as received. Nicotinamide and 10-hydroxystearic acid used in the preparation examples were obtained from DSM Nutritional Products Ltd. and used as received.

[0172] [Table 1]

[0173] Preparation of supramolecular assemblies by programmed cooling method Example 1: NAM (0.1224 g, 0.001 mol) and 10-HSA (0.3003 g, 0.001 mol) were added to 2 mL of ethanol in a 1:1 molar ratio to obtain a mixture. The mixture was heated to 40°C and held at that temperature for 30 minutes with stirring to ensure complete dissolution of the starting materials, thus obtaining a clear system. After complete dissolution, stirring was stopped, the system was cooled to 20°C, and left for 5 hours to produce a self-seed crystallization system in which small visible crystal species emerged from the mother liquor. After further cooling to 0-4°C, the system was left for 6 hours. The resulting crystals were collected and vacuum-dried at 50°C for 24 hours to obtain the pure form. Yield: 59.66%.

[0174] Example 2: NAM (0.1222 g, 0.001 mol) and 10-HSA (0.3004 g, 0.001 mol) were added to 2 mL of ethanol in a 1:1 molar ratio to obtain a mixture. The mixture was heated to 40°C and held at that temperature for 30 minutes with stirring to ensure complete dissolution of the starting materials, thus obtaining a clear system. After complete dissolution, stirring was stopped, the system was cooled to 30°C, and left for 2 hours to ensure the solution was at the desired starting temperature. The solution was further cooled to 20°C and left for 3 hours to produce a self-seed crystal-added crystallization system in which small visible crystal species emerged from the mother liquor. After further cooling to 0-4°C, the system was left for 6 hours. The resulting crystals were collected and vacuum-dried at 50°C for 24 hours to obtain the pure form. Yield: 81.11%.

[0175] Example 3: NAM (0.1223 g, 0.001 mol) and 10-HSA (0.3003 g, 0.001 mol) were added to 2 mL of ethanol in a 1:1 molar ratio to obtain a mixture. The mixture was heated to 40°C and held at that temperature for 30 minutes with stirring to ensure complete dissolution of the starting materials, thus obtaining a clear system. After complete dissolution, stirring was stopped, the system was cooled to 30°C, and left for 1 hour to ensure the solution was at the desired starting temperature. The system was further cooled to 20°C and left for 2 hours to produce a self-seed crystal-adding crystallization system in which small visible crystal species appeared from the mother liquor, followed by further cooling to 0-4°C and left for another 2 hours. Then, after cooling to -8°C, the system was left for 6 hours. The resulting crystals were collected and vacuum-dried at 50°C for 24 hours to obtain the pure form. Yield: 85.59%.

[0176] Example 4: This example was carried out using the same procedure as in Example 3, except that the amount of NAM was increased to 0.2446 g and the molar ratio of NAM to 10-HSA was adjusted to 2:1.

[0177] Example 5: This example was carried out using the same procedure as in Example 3, except that the amount of 10-HSA was increased to 0.6006 g and the molar ratio of NAM to 10-HSA was adjusted to 1:2.

[0178] Characterization of supramolecular assemblies Analysis method: Fourier-transform infrared spectroscopy (FT-IR): FT-IR measurements were collected using a Thermo Nicolet 6700 IR spectrometer (Thermo Fisher Scientific, Waltham, MA). The sample was compressed into a disk using KBr at a pressure of 30 MPa for 6 seconds, and then transferred to a 4000 cm² disk. -1 ~400cm -1 Measurements were taken over the wavenumber range.

[0179] Powder X-ray diffraction (XRD): XRD patterns were collected in a 2-theta range of 5–50° with an angular step of 1° / min using a rotating anode X-ray powder diffractometer equipped with a CuKα (λ=1.5418Å) source and operated at 40kV and 40mA.

[0180] Differential scanning calorimetry (DSC): To determine the thermal properties of the supramolecular assemblies, DCS measurements were performed using an HCT-1 thermal analyzer. Samples weighing 3–5 mg were tested under a nitrogen atmosphere at a temperature range of 40–200°C and a heating rate of 5°C / min.

[0181] Elemental analysis: The carbon, hydrogen, and nitrogen content in the supramolecular aggregate was analyzed using a Bano EL cube element. The sample was completely combusted. The masses of the three products (CO2, H2O, N2) after oxidation and combustion were measured using an elemental analyzer, and the content of each of the three elements (C, H, N) in the sample was determined.

[0182] Figure 1 shows the FT-IR spectra of individual NAM and 10-HSA, as well as the supramolecular assemblies of Examples 3, 4, and 5. The FT-IR spectrum of NAM is 3366 / 3158 cm, corresponding to the stretching of -NH2 and C=O, respectively. -1 and 1698 / 1680cm -1It exhibits a characteristic absorption peak. For the FT-IR spectrum of 10-HSA, 3410 / 3348 cm⁻¹ -1 , 1713cm -1 , and 1700cm -1 The characteristic peaks that appear are attributed to the vibrations of -OH and C=O, respectively. In comparison, the FT-IR spectra of the supramolecular assemblies obtained in Examples 3, 4, and 5 show shifted bands, indicating the formation of hydrogen bonds.

[0183] Figure 2 shows the powder XRD patterns of individual NAM and 10-HSA samples, as well as the supramolecular assemblies from Examples 3, 4, and 5. As can be seen from the figure, the XRD patterns of the supramolecular assemblies obtained in Examples 3, 4, and 5 show new characteristic peaks at 2θ angles (labeled with asterisks in Figure 2) that differ from those of NAM and 10-HSA, indicating the formation of supramolecular structures. All supramolecular assemblies show new peaks around 2θ = 9.7° and 10.1°. Furthermore, the peaks at 2θ angles of 33.6°, 34.5°, 36.9°, and 40.1° in the NAM pattern are not observed in the supramolecular assembly patterns.

[0184] Figure 3 shows the DSC profiles of the individual NAM and 10-HSA, as well as the supramolecular assemblies of Examples 3, 4, and 5. According to their thermal behavior, the melting temperatures of NAM and 10-HSA are 129°C and 88°C, respectively. In contrast, all of the supramolecular assemblies showed an endothermic peak at 84°C, which is clearly different from the thermal behavior of NAM and 10-HSA.

[0185] The composition of the supramolecular assemblies was further identified by elemental analysis. As shown in Table 1, the measured C, H, and N content in each supramolecular assembly was close to the theoretical value, indicating the successful preparation of supramolecular assemblies with different molar ratios.

[0186] [Table 2] * Note: Incomplete combustion

[0187] Example 6: Solubility in water Water solubility tests for 10-HSA and the supramolecular aggregate of Example 3 were performed in deionized water using the flask shaking method. An excess amount of sample equivalent to 10 mg of 10-HSA was separately dispersed in glass flasks containing 100 mL of distilled water. The dispersions were incubated in a water bath kettle at room temperature for 24 hours with continuous stirring. The dispersions were then centrifuged at 8000 rpm for 10 minutes. Furthermore, the concentration of 10-HSA in the supernatants of the 10-HSA raw material and the supramolecular aggregate of Example 3 was evaluated by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS).

[0188] The UPLC-MS assay was performed using a Waters UPLC / MS (Waters ACQUITY H-class-SQD2 MS detector) and a C18 reversed-phase column (ACQUITY HSS T3 column; 1.8 μm, 100 × 2.1 mm inner diameter). The mobile phase composition was acetonitrile and ammonium acetate buffer. The mobile phase gradient flow rate was 0.4 mL / min. -1 The settings were as follows: Column temperature, sample injection volume, and detection m / z were set to 40°C, 3 μl, and 299.3 (negative), respectively. The calibration curve for 10-HSA was 50-1000 ng / mL. -1 The reaction was linear within the concentration range (r 2 (=0.9999).

[0189] [Table 3]

[0190] According to the data in Table 3, the supramolecular aggregates of the present invention exhibit significantly improved solubility in water compared to individual 10-HSA molecules.

[0191] Example 7: Solubility in mixed solvent Solubility tests for 10-HSA and the supramolecular aggregates of Example 3 were also performed in 60% EtOH-water. The saturation concentration of 10-HSA was determined by gravimetric analysis. Specifically, an appropriate amount of sample was accurately weighed using an FA2204B electronic balance and dispersed in 10 mL of 60% EtOH-water at room temperature while continuously stirring with an 85-2 magnetic stirrer until saturation occurred (until insoluble matter was observed). Then, the solubility was calculated according to the solute mass and solvent volume.

[0192] [Table 4]

[0193] The data in Table 4 above demonstrates that the formation of supramolecular assemblies further improves the solubility of 10-HSA in mixed solvents.

[0194] Example 8: Antioxidant stress assay Human epidermal keratinocytes (HEK, FC-0007 purchased from Lifeline Cell Technology) were placed in 12-well plates in a 1.4 × 10⁶ arrangement. 5 Cells were seeded at a cell / well density and then treated with various active substances at concentrations listed in Table 5 for 24 hours. Subsequently, H2O2 (250 μM, 23381-25 mL, Sigma, St. Louis, MO, USA) was added to the cells and incubated for 30 minutes. The cells were then incubated with the reactive oxygen species (ROS) probe DCFH-DA (S0033, Beyotime, Nanjing, China) in the dark for 30 minutes, harvested, and measured by flow cytometry (Beckman, CA, USA). Data were analyzed using mean fluorescence intensity (MFI). The protective effect was calculated using the following formula. Protection rate (%)=[(MFI H2O2 -MFI 対照 )-(MFI 活性 -MFI 対照 )] / (MFI H2O2-MFI 対照 ) × 100%.

[0195] All experiments were conducted in sets of three.

[0196] statistical analysis As shown in Table 5 below, the results are expressed as mean ± standard deviation (SD). All statistical analyses were performed using GraphPad Prism version 8.0.1 (GraphPad Software, San Diego, CA). Data were analyzed using one-way ANOVA and Dunnett's post-hoc test. Adjusted p-values ​​less than 0.05 were considered to reflect statistically significant differences.

[0197] [Table 5]

[0198] The antioxidant stress assay data in Table 5 above demonstrate that the supramolecular assemblies exhibit synergistic effects in antioxidant efficacy compared to individual 10-HSA, nicotinamide, and physical mixtures of NAM and 10-HSA.

[0199] Example 9: Formulation of cosmetic composition A cosmetic composition containing a supramolecular aggregate is prepared by thoroughly mixing the ingredients shown in Table 6 below according to a conventional method.

[0200] [Table 6]

[0201] While the present disclosure and its merits have been described in detail, it should be understood that various changes, substitutions, and modifications can be made herein without departing from the spirit and scope of the present disclosure as defined by the appended claims. Furthermore, the scope of this application is not intended to be limited to specific embodiments of the processes, machines, manufactures, compositions, means, methods, and steps described herein. Existing or subsequently developed processes, machines, manufactures, compositions, means, methods, or steps that perform substantially the same function or achieve substantially the same results as the corresponding embodiments described herein can be utilized in accordance with this disclosure, as will be readily apparent to those skilled in the art. Accordingly, the appended claims are intended to include such processes, machines, manufactures, compositions, means, methods, or steps within their scope.

Claims

1. A supramolecular assembly comprising at least one pyridinylformamide compound and at least one hydroxy fatty acid, wherein the pyridinylformamide compound and the hydroxy fatty acid are bound together by non-covalent bonds.

2. The supramolecular assembly according to claim 1, wherein the non-covalent forces include hydrogen bonding forces, non-covalent electrostatic interactions, and van der Waals forces.

3. The supramolecular assembly according to claim 1 or 2, wherein the molar ratio of the pyridinylformamide compound to the hydroxy fatty acid is in the range of about 1:10 to about 10:1, preferably about 1:8 to about 8:1, more preferably about 1:5 to about 5:1, even more preferably about 1:2 to about 2:1, and most preferably about 1:

1.

4. The supramolecular assembly according to any one of claims 1 to 3, wherein the pyridinylformamide compound is selected from the group consisting of picolinamide, nicotinamide, isonicotinamide, and combinations thereof.

5. The supramolecular assembly according to any one of claims 1 to 4, wherein the hydroxy fatty acid is a C6-C24 saturated linear fatty acid having one or two hydroxyl groups, preferably a C12-C18 saturated linear fatty acid having one hydroxyl group.

6. The supramolecular assembly according to any one of claims 1 to 5, wherein the hydroxy fatty acid is selected from the group consisting of hydroxylauric acid, hydroxystearic acid, dihydroxystearic acid, and combinations thereof.

7. A method for preparing a supramolecular assembly, a) A step of mixing starting materials in a solvent to obtain a mixture, heating the mixture to a first temperature and maintaining it until the starting materials are completely dissolved and a transparent system is obtained, wherein the starting materials comprise at least one pyridinylformamide compound and at least one hydroxy fatty acid. b) A step of cooling the system to a second temperature and leaving the system at the second temperature to generate crystals, wherein the second temperature is -20°C or higher and at least 15°C, preferably at least 25°C, and more preferably at least 35°C lower than the first temperature. c) A method comprising the steps of collecting the crystals obtained in step b) and optionally purifying them to obtain the supramolecular aggregate.

8. The method according to claim 7, wherein the solvent is selected from the group consisting of ethanol, n-propanol, isopropanol, methanol, acetone, propanediol, and acetic acid, citric acid, and phosphate buffer, and mixtures thereof with each other or with water.

9. The method according to claim 7 or 8, wherein in step a), the first temperature is in the range of about 30°C to about 70°C, preferably about 35°C to about 60°C, and more preferably about 40°C to about 50°C.

10. The method according to any one of claims 7 to 9, wherein in step b), the system is left for 1 to 10 hours, preferably 2 to 8 hours, more preferably 4 to 6 hours.

11. The method according to any one of claims 7 to 10, wherein the method further includes n intermediate cooling steps between steps a) and b), where the system is cooled to an intermediate temperature and left for 1 to 10 hours, preferably 1 to 6 hours, more preferably 1 to 3 hours, the intermediate temperature being at least 10°C lower than the first temperature or the intermediate temperature of the previous intermediate cooling step, and at least 10°C higher than the second temperature, and n being 1, 2, 3, 4, or 5, preferably 2, 3, or 4, more preferably 2 or 3.

12. The method according to any one of claims 7 to 11, wherein in step c), the purification is carried out by vacuum drying.

13. A composition, particularly a cosmetic composition for topical application, comprising a supramolecular aggregate according to any one of claims 1 to 6, or a supramolecular aggregate prepared by the method according to any one of claims 7 to 12.

14. The composition according to claim 13, wherein the supramolecular aggregate is present in the composition in an amount of about 0.0001% to about 20% by weight, preferably about 0.001% to about 10% by weight, more preferably about 0.01% to about 5% by weight, and most preferably about 0.1% to about 2% by weight, based on the total weight of the composition.

15. A non-therapeutic method for caring for, protecting and / or makeup a keratinous substance, comprising topically applying the composition according to claim 13 or 14 to the keratinous substance.

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