WO2025059904A1

WO2025059904A1 - Supramolecular assemblies and compositions comprising the same

Info

Publication number: WO2025059904A1
Application number: PCT/CN2023/119993
Authority: WO
Inventors: Zhen Li; Yan Wu; Yulan QU; Feng Cao; Jizong YAO; Yufeng Li; Xiaoyong Wang; Huanjun ZHOU
Original assignee: Estee Lauder Cos Innovation R & D China Co Ltd; ELC Management LLC
Current assignee: Estee Lauder Cos Innovation R & D China Co Ltd; ELC Management LLC
Priority date: 2023-09-20
Filing date: 2023-09-20
Publication date: 2025-03-27
Anticipated expiration: 2026-03-20
Also published as: CN120021420A; TW202513039A

Abstract

A supramolecular assembly comprises at least one hydroxycinnamic acid derivative and at least one betaine compound, wherein the betaine compound and the hydroxycinnamic acid derivative are assembled by non-covalent bonding forces. A cosmetic composition comprises the supramolecular assembly. Also provided a method for preparing the supramolecular assembly.

Description

SUPRAMOLECULAR ASSEMBLIES AND COMPOSITIONS COMPRISING THE SAME

FIELD OF THE DISCLOSURE

The present disclosure generally relates to supramolecular assemblies and applications thereof in cosmetics and personal care products. More particularly, the present disclosure relates to a supramolecular assembly comprising at least one hydroxycinnamic acid derivative and at least one betaine compound, a composition comprising the same, and a method for producing the same.

BACKGROUND ART

Some active ingredients commonly used in cosmetic products, such as whitening agents, conditioners, antioxidants, sunscreen agents, antibacterial agents, or the like, often suffer from shortcomings such as low solubility, poor transdermal permeability, slow onset of action, instability, and/or unsatisfactory functions. It is desirable to develop new derivatives or modified products based on the raw actives that may overcome one or more of these shortcomings to meet the requirements of the market and consumers.

With such an expectation, supramolecular chemistry is applied to the upstream development of cosmetic raw materials. Supramolecular chemistry has expanded the scope of Chemistry, allowing for the design and development of smart and functional materials. While traditional synthetic molecules are covalently linked molecules or macromolecules, supramolecular complexes contain non-covalent binding on the association of two or more building blocks which are held together by intermolecular bonds, such as hydrogen bonding, dipole-dipole interactions, van der Waals forces, cation-π interactions, π-π bonds, CH/π interactions, or hydrophobic effects, and etc., showing inclusion, selectivity and other functionality. The application of supramolecular chemistry has greatly increased the diversity of ingredients for cosmetic raw materials, and provided new routes to improve the properties, such as solubility, bioavailability, stability, and efficacy, of these materials.

Accordingly, there is a need for a novel active material modified by supramolecular chemistry that may exhibit improved properties, such as solubility and functionalities, and thus increase the efficacy of products comprising the actives.

SUMMARY

Therefore, one of the objects of the present disclosure is to provide a supramolecular assembly with improved properties relative to the individual components contained therein.

Another object of the present disclosure is to provide a method for preparing the supramolecular assembly according to the present disclosure.

Yet another object of the present disclosure is to provide a composition, especially a cosmetic and/or personal care composition for topical application, comprising the supramolecular assembly according to the present disclosure.

Still another object of the present disclosure is to provide a non-therapeutic method for caring for, protecting, and/or making up keratin materials, such as skin.

The inventors have now discovered that the one or more of these objects can be achieved by the following aspects.

In one aspect, the present disclosure provides a supramolecular assembly comprising at least one hydroxycinnamic acid derivative and at least one betaine compound, wherein the betaine compound and the hydroxycinnamic acid derivative are assembled by non-covalent bonding forces.

According to an embodiment, the non-covalent bonding forces may include hydrogen bonding forces, non-covalent electrostatic interactions, and van der Waals forces.

According to a preferable embodiment, the supramolecular assembly according to present disclosure is a cocrystal.

According to an embodiment, the supramolecular assembly may have a ratio between the betaine compound and the hydroxycinnamic acid derivative of from about 10: 1 to about 1: 10, preferably from about 3: 1 to about 1: 3, more preferably from about 2: 1 to about 2: 1, and particularly preferably, the supramolecular assembly has a ratio between the betaine compound and the hydroxycinnamic acid derivative selected from the group consisting of about 2: 1, about 1: 1 and about 1: 2.

According to an embodiment, the betaine compound may be selected from the group consisting of histidine betaine, glycine betaine, proline betaine, phenylalanine betaine, tyrosine betaine, tryptophan betaine, leucine betaine, isoleucine betaine, valine betaine, betaine glutamate, alanine betaine, betaine aspartate, lysine betaine, arginine betaine, and combinations thereof.

According to a preferable embodiment, the betaine compound is glycine betaine.

According to an embodiment, the hydroxycinnamic acid derivative may be selected from the group consisting of caffeic acid (CaA) , chlorogenic acid (ChA) , sinapic acid (SA) , ferulic acid (FA) , p-coumaric acid (CoA) , and combinations thereof.

According to a preferable embodiment, the hydroxycinnamic acid derivative is ferulic acid (FA) .

In another aspect, the present disclosure provides a supramolecular assembly A comprising glycine betaine and ferulic acid, wherein the supramolecular assembly A has a Powder X-ray Diffraction (XRD) pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 7.2°, 14.5°, 19.9°, 21.6°, 22.0°, 24.2° ± 0.2°.

According to an embodiment, the supramolecular assembly A has a Differentia Scanning Calorimetry (DSC) curve exhibiting an endotherm peak at 153.2℃.

In another aspect, the present disclosure provides a supramolecular assembly B comprising glycine betaine and ferulic acid, wherein the supramolecular assembly B has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 10.5°, 12.5°, 14.3°, 20.8°, 21.9°, 25.1° ± 0.2°.

According to an embodiment, the supramolecular assembly B has a DSC curve exhibiting an endotherm peak at 154.0℃.

In another aspect, the present disclosure provides a supramolecular assembly C comprising glycine betaine and ferulic acid, wherein the supramolecular assembly C has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 9.0°, 12.5°, 14.4°, 17.3°, 20.8°, 22.0°, 25.1°, 39° ± 0.2°.

According to an embodiment, the supramolecular assembly C has a DSC curve exhibiting an endotherm peak at 154.8℃.

In another aspect, the present disclosure provides a method for preparing the supramolecular assembly according to the present disclosure, comprising steps of:

a) mixing starting materials in a solvent to obtain a mixture, heating the mixture to a first temperature which is maintained until the starting materials are completely dissolved to obtain a clear system, wherein the starting materials comprise at least one hydroxycinnamic acid derivative and at least one betaine compound;

b) cooling the system from step a) to a second temperature, at which the system is left to dwell to produce crystals, wherein the second temperature is equal to or greater than -20℃ and is at least 15℃, preferably at least 25℃, and more preferably at least 35℃ lower than the first temperature; and

c) collecting and optionally purifying the crystals from step b) to obtain the supramolecular assembly.

In a further aspect, the present disclosure provides a composition, especially a cosmetic composition for topical application, comprising the supramolecular assembly according to the present disclosure.

According to an embodiment, the supramolecular assembly is present in the composition in an amount of from about 0.0001 wt%to about 50 wt%, preferably from about 0.001 wt%to about 20 wt%, more preferably from about 0.01 wt%to about 10 wt%, and most preferably from about 0.1 wt% to about 2 wt%, relative to the total weight of the composition.

In a further aspect, the present disclosure provides a non-therapeutic method for caring for, protecting and/or making up keratin materials, comprising topically applying the composition according to the present disclosure to the keratin materials, such as skin.

In a further aspect, the present disclosure provides use of the supramolecular assembly according to the present disclosure or the cosmetic composition according to the present disclosure for improving the state of keratin materials, such as skin.

These solutions are based on the surprising finding that the supramolecular assembly prepared from at least one betaine compound and at least one hydroxycinnamic acid derivative exhibits improved solubility in water compared to the individual component and a synergistic effect in terms of the functionalities such as the anti-oxidative property.

Other advantages of the present disclosure will emerge more clearly on reading the description and the examples that follow.

BRIEF DESCRIPTION OF THE DRAWINGS

For a more complete understanding of this disclosure, reference is now made to the following description, taken in conjunction with the accompanying drawing, in which:

FIGURE 1 shows the FT-IR spectra of supramolecular assemblies obtained in Examples 1-3 and the corresponding raw materials;

FIGURE 2 shows the XRD patterns of supramolecular assemblies obtained in Examples 1-3 and the corresponding raw materials;

FIGURE 3 shows the DSC profiles of supramolecular assemblies obtained in Examples 1-3 and the corresponding raw materials.

DETAILED DESCRIPTION

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art the present disclosure belongs to. When the definition of a term in the present description conflicts with the meaning as commonly understood by those skilled in the art the present disclosure belongs to, the definition described herein shall apply.

Unless otherwise indicated, all numbers expressing quantities of ingredients, properties such as molecular weight, reaction conditions, and so forth used in the specification and claims are to be understood as being modified in all instances by the term "about" , with conventionally known meaning in the art, e.g., within 10%of the indicated number (e.g. "about 10%" means 9%-11 %and "about 2%" means 1.8%-2.2%) . Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained by the present disclosure. At the very least, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Further, the ranges stated in this disclosure and the claims are intended to include the entire range specifically and not just the endpoint (s) . For example, a range stated to be 0 to 10 is intended to disclose all whole numbers between 0 and 10 such as, for example 1, 2, 3, 4 and any sub-ranges formed by any two values thereof, etc., all fractional numbers between 0 and 10, for example 1.5, 2.3, 4.57, 6.1113 and any sub-ranges formed by any two values thereof, etc., and the endpoints 0 and 10.

Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the invention are approximations, the numerical values set forth in the specific examples are intended to be reported precisely in view of methods of measurement. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements.

It is to be understood that the mention of one or more process steps does not preclude the presence of additional process steps before or after the combined recited steps or intervening process steps between those steps expressly identified. Moreover, the denomination of process steps, ingredients, or other aspects of the information disclosed or claimed in the application with letters, numbers, or the like is a convenient means for identifying discrete activities or ingredients and the recited lettering can be arranged in any sequence, unless otherwise indicated.

As used herein, the singular forms "a" , "an" , and "the" include plural referents unless the context clearly dictates otherwise. For example, reference to a Cn alcohol equivalent is intended to include multiple types of Cn alcohol equivalents. Thus, even use of language such as "at least one" in one location is not intended to imply that other uses of "a" , "an" , and "the" excludes plural referents unless the context clearly dictates otherwise.

As used herein, the term "comprising" is to be interpreted as encompassing all specifically mentioned features as well optional, additional, unspecified ones. As used herein, the use of the term "comprising" also discloses the embodiment wherein no features other than the specifically mentioned features are present (i.e. "consisting of" ) .

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 can be employed by itself, or any combination of two or more of the listed items can be employed. For example, if a composition is described as containing components A, B, and/or C, the composition can contain A alone; B alone; C alone; A and B in combination; A and C in combination; B and C in combination; or A, B, and C in combination.

As used herein, the phrase "supramolecular assembly" or "supramolecular complex" , which can be used interchangeably, refers to a molecular self-assembly where two or more compounds interact with each other via various weak intermolecular interactions, such as, for example, hydrogen bonding, dipole-dipole interactions, van der Waals forces, cation-π interactions, π-π bonds, CH/π interactions, or hydrophobic effects.

As used herein, the phrase "topical application" means that the composition is applied or spread onto the surface of the keratin materials, such as at least one zone of the skin.

As used herein, the term "keratin materials" is intended to cover skin, hair, mucous membranes such as the lips.

As used herein, "room temperature" means a temperature of about 25℃.

All percentages in the present disclosure refer to weight percentage, unless otherwise specified.

Supramolecular Assemblies

The supramolecular assembly of the present disclosure comprises at least one hydroxycinnamic acid derivative and at least one betaine compound, wherein the betaine compound and the hydroxycinnamic acid derivative are assembled by non-covalent bonding forces.

While not wishing to be bound by any particular theory, it is proposed herein that the inter-molecular interactions, such as hydrogen bonding interaction, between the building blocks of betaine compound and hydroxycinnamic acid derivative, result in the formation of the supramolecular assemblies, which are responsible for the observation of enhanced functionalities of the supramolecular assemblies and improved solubility of water insoluble or sparely soluble active ingredients.

In one embodiment, the supramolecular assembly according to present disclosure is a cocrystal.

Betaine Compound

The supramolecular assembly of the present disclosure may comprise at least one betaine compound selected from the group consisting of betaines and analogs thereof.

The term "betaines" used herein represents the general name for the intramolecular salt formed of a quaternary ammonium as a cation and an anion of an acid, particularly a carboxylic acid, in one molecule.

The betaine compound suitable for use in the composition of the present disclosure includes those known to be useful in cosmetic or dermatological compositions.

In one embodiment, the betaine compound used herein is a betaine derivative formed with an amino acid. In a preferable embodiment, the betaine compound used herein may be selected from the group consisting of histidine betaine, glycine betaine, proline betaine, phenylalanine betaine, tyrosine betaine, tryptophan betaine, leucine betaine, isoleucine betaine, valine betaine, betaine glutamate, alanine betaine, betaine aspartate, lysine betaine, and arginine betaine, depending on the amino acid involved.

In another embodiment, the betaine compound used herein may be selected from the group consisting of alkyl betaines, alkyl amidobetaines, alkyl sulfobetaines, and imidazolinium betaines, in particular, alkyl N-betaines, alkyl N-sulfobetaines, acyl N-betaines, alkyl N-substituted aminopropionic acid, alkyl imidazolinium betaines, etc.

Further, the betaine compound suitable for use in the composition of the present disclosure includes the analog of the betaine as listed above.

In a preferred embodiment, the betaine compound used herein may be glycine betaine. In a specific embodiment, the betaine compound herein is commercially available as CAS No. 107-43-7.

Glycine betaine is also called as trimethylglycine or abbreviated as betaine having the following structure.

Moreover, the term "analog of the betaine" used herein represents any compound having similar structures and/or properties with betaine, in particular, trimethylglycine.

Hydroxycinnamic Acid Derivative

The supramolecular assembly of the present disclosure may comprise at least one hydroxycinnamic acid derivative.

The hydroxycinnamic acid derivative is a class of phenolic acid compounds originated from the Mavolanate-Shikimate biosynthesis pathways in plants. The hydroxycinnamic acid derivative comprises a large group of simple phenolic acids, found mainly in cereals, fruits and vegetables. Several simple phenolic compounds such as caffeic acid, chlorgenic acid, sinapic acid, ferulic acid, and p-coumaric acid belong to this class. These phenolic compounds possess potent antioxidant and anti-inflammatory properties.

Structures of some hydroxycinnamic acid derivatives

In one embodiment, the hydroxycinnamic acid derivative used herein may be selected from the group consisting of caffeic acid, chlorgenic acid, sinapic acid, ferulic acid, p-coumaric acid, and combinations thereof, preferably ferulic acid.

In another embodiment, the hydroxycinnamic acid derivative used herein may be selected from the group consisting of oligomers of caffeic acid, chlorgenic acid, sinapic acid, ferulic acid, p-coumaric acid, and combinations thereof, such as oligomers of ferulic acid oligomer, preferably diferulic acid.

In a preferred embodiment, the hydroxycinnamic acid derivative used herein may be ferulic acid (4-hydroxy-3-methoxycinnamic acid, with a structure formula as shown above) . In a specific embodiment, the hydroxycinnamic acid derivative herein is commercially available as CAS No. 1135-24-6.

Ferulic acid is a potent antioxidant present in cell walls of grains, fruits, and vegetables where it is conjugated with mono-, di-, and polysaccharides and other compounds. Ferulic acid is a promising and attracting raw material used in cosmetics. It's believed to neutralize free radicals, unstable molecules that damage and age cells. Moreover, ferulic acid is used as sunscreen as it aids in the protection of human skin by absorbing certain UV radiation. It is also utilized as a whitening agent owing to its ability to hinder pigmentation due to its inhibitory effect on the production of melanin.

Characteristics of supramolecular assemblies

Ratios between the betaine compound and the hydroxycinnamic acid derivative

In one particular embodiment, the supramolecular assembly may have a ratio between the betaine compound and the hydroxycinnamic acid derivative of from about 10: 1 to about 1: 10. In a preferable embodiment, the supramolecular assembly may have a ratio between the betaine compound and the hydroxycinnamic acid derivative of from about 3: 1 to about 1: 3. In a more preferable embodiment, the supramolecular assembly may have a ratio between the betaine compound and the hydroxycinnamic acid derivative of from about 2: 1 to about 2: 1.

In a particularly preferable embodiment, the supramolecular assembly may have a ratio between the betaine compound and the hydroxycinnamic acid derivative selected from the group consisting of about 10: 1, about 9: 1, about 8: 1, about 7: 1, about 6: 1, about 5: 1, about 4: 1, about 3: 1, about 2: 1, about 1: 1, about 1: 2, about 1: 3, about 1: 4, about 1: 5, about 1: 6, about 1: 7, about 1: 8, about 1: 9 and about 1: 10. In a specific preferable embodiment, the supramolecular assembly may have a ratio between the betaine compound and the hydroxycinnamic acid derivative selected from the group consisting of about 2: 1, about 1: 1 and about 1: 2.

Composition of supramolecular assemblies

In one particular embodiment, the supramolecular assembly of the present disclosure comprises, substantially consists of, or consists of at least one hydroxycinnamic acid derivative and at least one betaine compound. In one particular embodiment, the supramolecular assembly of the present disclosure comprises, substantially consists of, or consists of ferulic acid and glycine betaine.

In one specific embodiment, the present disclosure comprises, substantially consists of, or consists of at least one hydroxycinnamic acid derivative and at least one betaine compound, which interact with each other via intermolecular interactions, for example, hydrogen bonding forces, non-covalent electrostatic interactions, and van der Waals forces.

In another specific embodiment, the present disclosure comprises, substantially consists of, or consists of ferulic acid and glycine betaine, which interact with each other via intermolecular interactions, for example, hydrogen bonding forces, non-covalent electrostatic interactions, and van der Waals forces.

Supramolecular assembly A

In one aspect, provided is a supramolecular assembly A, wherein the supramolecular assembly A of the present disclosure is formed from glycine betaine and ferulic acid.

In one embodiment, the supramolecular assembly A is formed from glycine betaine and ferulic acid in a molar ratio of 1: 1.

In one embodiment, the supramolecular assembly A has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 7.2°, 14.5°, 19.9°, 21.6°, 22.0°, 24.2° ± 0.2°. In a preferable embodiment, the supramolecular assembly A has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 7.2°, 10.5°, 14.5°, 15.7°, 17.0°, 18.9°, 19.9°, 21.6°, 22.0°, 23.4°, 24.2°, 26.6°, 29.4° ± 0.2°.

In one embodiment, the supramolecular assembly A has a Differentia Scanning Calorimetry (DSC) curve exhibiting an endotherm peak at about 153.2℃.

Supramolecular assembly B

In one aspect, provided is a supramolecular assembly B, wherein the supramolecular assembly B of the present disclosure is formed from glycine betaine and ferulic acid.

In one embodiment, the supramolecular assembly B is formed from glycine betaine and ferulic acid in a molar ratio of 2: 1.

In one embodiment, the supramolecular assembly B has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 10.5°, 12.5°, 14.3°, 20.8°, 21.9°, 25.1° ± 0.2°. In a preferable embodiment, the supramolecular assembly B has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 10.5°, 12.5°, 14.3°, 17.3°, 19.5°, 20.4°, 20.8°, 21.9°, 22.6°, 25.1°, 27.1°, 29.3°, 32° ± 0.2°.

In one embodiment, the supramolecular assembly B has a DSC curve exhibiting an endotherm peak at about 154.0℃.

Supramolecular assembly C

In one aspect, provided is a supramolecular assembly C, wherein the supramolecular assembly of the present disclosure is formed from glycine betaine and ferulic acid.

In one embodiment, the supramolecular assembly C is formed from glycine betaine and ferulic acid in a molar ratio of 1: 2.

In one embodiment, the supramolecular assembly has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 9.0°, 12.5°, 14.4°, 17.3°, 20.8°, 22.0°, 25.1°, 39° ± 0.2°. In a preferable embodiment, the supramolecular assembly C has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 9.0°, 10.6°, 12.5°, 12.8°, 14.4°, 15.6°, 17.3°, 19.5°, 20.4°, 20.8°, 22.0°, 22.4°, 24.6°, 25.1°, 39° ± 0.2°.

In one embodiment, the supramolecular assembly C has a DSC curve exhibiting an endotherm peak at about 154.8℃.

Advantageous technical effects

The supramolecular self-assembly where the betaine compound and the hydroxycinnamic acid derivative interact with each other via various non-covalent intermolecular interactions, such as hydrogen bonding forces, non-covalent electrostatic interactions, and van der Waals forces, results in the formation of intermolecular assemblies with enhanced or different functionalities relative to each individual molecules, including e.g. solubility, anti-oxidative property, stability, transdermal permeability, and the like.

Preparation Method

The methods for preparing the supramolecular assemblies may include, but not limited to, hot melt method, cooling method, solvent evaporation method, ball milling method, or the like.

In a preferable embodiment, the supramolecular assembly of the present disclosure is prepared by a method including the steps of:

a) mixing starting materials in a solvent to obtain a mixture, heating the mixture to a first temperature which is maintained until the starting materials are completely dissolved to obtain a clear system;

b) cooling the system from step a) to a second temperature, at which the system is left to dwell to produce crystals, wherein the second temperature is at least 15℃, preferably at least 25℃, and more preferably at least 35℃ lower than the first temperature; and

The method may further comprise n intermediate cooling step (s) between step a) and b) , in which the system is cooled to an intermediate temperature and left to dwell for 1-10 hrs, preferably 1-6 hrs, and more preferably 1-3 hrs, wherein the intermediate temperature is at least 10℃lower than the first temperature or the intermediate temperature of previous intermediate cooling step and is at least 10℃ higher than the second temperature, wherein n is 1, 2, 3, 4 or 5.

In step a) of the programmed cooling method, the first temperature may be in a range of from about 30℃ to about 70℃, preferably from about 35℃ to about 60℃, and more preferably from about 45℃ to about 55℃. In step b) of the programmed cooling method, the system may be left to dwell for 1-10 hrs, preferably 1-6 hrs, and more preferably 1-3 hrs. The collection in step c) may be accomplished by any suitable solid-liquid separation process, such as filtration. The purification in step c) may be conducted by any suitable purification process, such as vacuum-drying, for example, at a temperature of from about 20℃ to about 70℃, preferably from about 40℃ to about 50℃, for a period of 5-48 hrs, preferably 10-24 hrs.

In one embodiment, solvents suitable for use in the process of the present disclosure include any suitable polar or non-polar solvents that are liquid under the method conditions and capable of dissolving the starting materials, such as various hydrocarbons, alcohols, carboxylic acids, esters, ketones, acetals, ethers and water.

The polar solvents, as used therein, include those with water solubility up to 100%and polarity index greater than about 5.0, such as water, acetic acid, methanol, ethanol, n-propanol, iso-propanol, propanediol, glycerol, dimethyl sulfoxide, dimethyl formamide, acetonitrile, acetone, dioxane, tetrahydrofuran, etc., or acetic, citric, phosphate acid buffer solutions, or mixtures thereof in different ratios. This list is not intended to limit the solvent used, however considering safety for cosmetic or pharmaceutical applications, water, ethanol, n-propanol, iso-propanol, methanol, acetone, propanediol, and acetic, citric and phosphate acid buffer solutions, are preferred.

The non-polar organic solvents, as used therein, include those with less than about 30%of water solubility and a polarity index from 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, trichloroefhylene, cyclohexane, pentane, and heptane, or mixtures thereof in different ratios. This list is not intended to limit solvent used, however considering safety for cosmetic or pharmaceutical applications, ethyl acetate, butyl acetate, and n-butanol are preferred.

Ethanol and a mixed solvent thereof with water are particularly preferred.

In one embodiment, the method for preparing supramolecular assemblies of the present disclosure may be a seeded process with or without the addition of exogenous seed crystals. In a conventional seeded process, exogenous seed crystals derived from other sources, such as solvent evaporation, are added into the system to initiate the crystallization. Preferably, the method of the present disclosure is a self-seeded process without the addition of exogenous seed crystals.

Cosmetic Compositions

The cosmetic composition of the present disclosure comprises the supramolecular assembly with the definitions and preferences as defined above.

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

The cosmetic composition may be skin care products such as facial, hand and foot care products; acne treatment products, shaving products, cleansing products; powders, antiperspirants; hair remover products, tooth whitening products, color makeup products such as makeup base, foundation, eye shadow, eyeliner, blush; sun screen products; insect repellants, and the like.

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

Provided that the beneficial effect of the supramolecular assemblies of the present disclosure is not affected, the compositions of the present disclosure may further comprise at least one cosmetically acceptable medium, such as additives, excipients, diluents, and/or other active ingredients, as detailed below.

A. Humectants

The composition of the present disclosure may contain one or more humectants. If present, they may range from about 0.1 to 75%, preferably from about 0.5 to 70%, more preferably from about 0.5 to 40%. Examples of suitable humectants include glycols, sugars, and the like. Suitable glycols are in monomeric or polymeric form and include polyethylene and polypropylene glycols such as PEG 4-10, which are polyethylene glycols having from 4 to 10 repeating ethylene oxide units; as well as C_1-6 alkylene glycols such as propylene glycol, butylene glycol, pentylene glycol, and the like. Suitable sugars, some of which are also polyhydric alcohols, are also suitable humectants. Examples of such sugars include glucose, fructose, honey, hydrogenated honey, inositol, maltose, mannitol, maltitol, sorbitol, sucrose, xylitol, xylose, and so on. Also suitable is urea. Preferably, the humectants used in the composition of the present disclosure are C_1-6, preferably C_2-4 alkylene glycols, most particularly butylene glycol.

B. Botanical Extracts

The composition of the present disclosure may contain one or more additional botanical extracts. If present, suggested ranges are from about 0.0001 to 20%, preferably from about 0.0005 to 15%, more preferably from about 0.001 to 10%. Suitable botanical extracts include extracts from plants (herbs, roots, flowers, fruits, seeds) such as flowers, fruits, vegetables, and so on, including yeast ferment extract, Padina pavonica extract, Thermus thermophilis ferment extract, Camelina sativa seed oil, Boswellia serrata extract, olive extract, Acacia dealbata extract, Acer saccharinum (sugar maple) , Acidopholus, Acorus, Aesculus, Agaricus, Agave, Agrimonia, algae, aloe, citrus, Brassica, cinnamon, orange, apple, blueberry, cranberry, peach, pear, lemon, lime, pea, seaweed, caffeine, green tea, chamomile, willowbark, mulberry, poppy, and those set forth on pages 1646 through 1660 of the CTFA Cosmetic Ingredient Handbook, Eighth Edition, Volume 2. Further specific 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 longa, Menyanthes trifoliata, Helianthus annuus, Hordeum vulgare, Cucumis sativus, Evernia prunastri, Evernia furfuracea, Kola acuminata, and mixtures thereof.

C.Surfactants

The composition of the present disclosure may contain one or more surfactants, especially if in the emulsion form. However, such surfactants may be used if the compositions are solutions, suspensions, or anhydrous also. If present, the surfactant may range from about 0.001 to 30%, preferably from about 0.005 to 25%, more preferably from about 0.1 to 20%by weight of the total composition. Suitable surfactants may be silicone or organic, nonionic, anionic, amphoteric or zwitterionic.

1. Organic Nonionic Surfactants

The composition of the present 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 or propylene oxide. Suitable alcohols include mono-, di-, or polyhydric short chain (C_1-6) alcohols; aromatic or aliphatic saturated or unsaturated fatty (C_12-40) alcohols, of cholesterol; and so on.

Cholesterol is suitable, or an aromatic or aliphatic saturated or unsaturated fatty alcohol which may have from 6 to 40, preferably from about 10 to 30, more preferably from about 12 to 22 carbon atoms. Examples include oleyl alcohol, cetearyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, and the like. Examples of such ingredients include Oleth 2-100; Steareth 2-100; Beheneth 5-30; Ceteareth 2-100; Ceteth 2-100; Choleth 2-100 wherein the number range means the number of repeating ethylene oxide units, e.g. Ceteth 2-100 means Ceteth where the number of repeating ethylene oxide units ranges from 2 to 100. Derivatives of alkoxylated alcohols are also suitable, such as phosphoric acid esters thereof.

Some preferred organic nonionic surfactants include Oleth-3, Oleth-5, Oleth-3 phosphate, Choleth-24; Ceteth-24; and so on.

Also suitable are alkoxylated alcohols formed with mono-, di-, or polyhydric short chain alcohols, for example those having from about 1 to 6 carbon atoms. Examples include glucose, glycerin, or alkylated derivatives thereof. Examples include glycereth 2-100; gluceth 2-100; methyl gluceth 2-100 and so on. More preferred are methyl gluceth-20; glycereth-26 and the like.

Other types of alkoxylated alcohols are suitable surfactants, including ethylene oxide polymers having varying numbers of repeating EO groups, generally referred to as PEG 12 to 200. More preferred are PEG-75, which is may be purchased from Dow Chemical under the trade name Carbowax PEG-3350.

Other suitable nonionic surfactants include alkoxylated sorbitan and alkoxylated sorbitan derivatives. For example, alkoxylation, in particular ethoxylation of sorbitan provides polyalkoxylated sorbitan derivatives. Esterification of polyalkoxylated sorbitan provides sorbitan esters such as the polysorbates. For example, the polyalkyoxylated sorbitan can be esterified with C_6-30, preferably C_12-22 fatty acids. Examples of such ingredients include Polysorbates 20-85, sorbitan oleate, sorbitan sesquioleate, sorbitan palmitate, sorbitan sesquiisostearate, sorbitan stearate, and so on.

2. Silicone or Silane Surfactants

Also suitable are various types of silicone or silane-based surfactants. Examples include organosiloxanes substituted with ethylene oxide or propylene oxide groups such as PEG dimethicones which are dimethicones substituted with polyethylene glycols including those having the INCI names PEG-1 dimethicone; PEG-4 dimethicone; PEG-8 dimethicone; PEG-12 dimethicone; PEG-20 dimethicone; and so on.

Also suitable are silanes substituted with ethoxy groups or propoxy groups or both, such as various types of PEG methyl ether silanes such as bis-PEG-18 methyl ether dimethyl silane; and so on.

Further examples of silicone based surfactants include those having the generic names dimethicone copolyol; cetyl dimethicone copolyol; and so on.

D. Biological Materials

The composition of the present disclosure may contain various types of biological materials such as those derived from cells, fermented materials, and so on. If present such materials may range from about 0.001 to 30%, preferably from about 0.005 to 25%, more preferably from about 0.01 to 20%. Examples include fragments of cellular RNA or DNA, or probiotic microorganisms. Particularly preferred are RNA fragments.

E. Thickeners

Suitable thickeners may be incorporated into the composition of the present disclosure. If present, suggested ranges are from about 0.01 to 30%, preferably from about 0.1 to 20%, more preferably from about 0.5 to 15%by weight of the total composition.

Examples of thickeners include animal, vegetable, mineral, silicone, or synthetic waxes which may have melting points ranging from about 30 to 150℃ including but not limited to Examples of such waxes include waxes made by Fischer-Tropsch synthesis, such as polyethylene or synthetic wax; or various vegetable waxes such as bayberry, candelilla, ozokerite, acacia, beeswax, ceresin, cetyl esters, flower wax, citrus wax, carnauba wax, jojoba wax, japan wax, polyethylene, microcrystalline, rice bran, lanolin wax, mink, montan, bayberry, ouricury, ozokerite, palm kernel wax, paraffin, avocado wax, apple wax, shellac wax, clary wax, spent grain wax, grape wax, and polyalkylene glycol derivatives thereof such as PEG6-20 beeswax, or PEG-12 carnauba wax; or fatty acids or fatty alcohols, including esters thereof, such as hydroxystearic acids (for example 12-hydroxy stearic acid) , tristearin, tribehenin, and so on.

Also suitable as thickening agents are silicas, silicates, silica silylate, and alkali metal or alkaline earth metal derivatives thereof. These silicas and silicates are generally found in the particulate form and include silica, silica silylate, magnesium aluminum silicate, and the like.

Silicone elastomers may also be used as thickening agents. Such elastomers include those that are formed by addition reaction-curing, by reacting an SiH-containing diorganosiloxane and an organopolysiloxane having terminal olefinic unsaturation, or an alpha-omega diene hydrocarbon, in the presence of a platinum metal catalyst. Such elastomers may also be formed by other reaction methods such as condensation-curing organopolysiloxane compositions in the presence of an organotin compound via a dehydrogenation reaction between hydroxyl-terminated diorganopolysiloxane and SiH-containing diorganopolysiloxane or alpha omega diene; or by condensation-curing organopolysiloxane compositions in the presence of an organotin compound or a titanate ester using a condensation reaction between an hydroxyl-terminated diorganopolysiloxane and a hydrolysable organosiloxane; peroxide-curing organopolysiloxane compositions which thermally cure in the presence of an organoperoxide catalyst.

One type of elastomer that may be suitable is prepared by addition reaction-curing an organopolysiloxane having at least 2 lower alkenyl groups in each molecule or an alpha-omega diene; and an organopolysiloxane having at least 2 silicon-bonded hydrogen atoms in each molecule; and a platinum-type catalyst. While the lower alkenyl groups such as vinyl, can be present at any position in the molecule, terminal olefinic unsaturation on one or both molecular terminals is preferred. The molecular structure of this component may be straight chain, branched straight chain, cyclic, or a network. These organopolysiloxanes are exemplified by methylvinylsiloxanes, methylvinylsiloxane-dimethylsiloxane copolymers, dimethylvinylsiloxy-terminated dimethylpolysiloxanes, dimethylvinylsiloxy-terminated dimethylsiloxane-methylphenylsiloxane copolymers, dimethylvinylsiloxy-terminated dimethylsiloxane-diphenylsiloxane-methylvinylsiloxane copolymers, trimethylsiloxy-terminated dimethylsiloxane-methylvinylsiloxane copolymers, trimethylsiloxy-terminated dimethylsiloxane-methylphenylsiloxane-methylvinylsiloxane copolymers, dimethylvinylsiloxy-terminated methyl (3, 3, 3-trifluoropropyl) polysiloxanes, and dimethylvinylsiloxy-terminated dimethylsiloxane-methyl (3, 3, -trifluoropropyl) siloxane copolymers, decadiene, octadiene, heptadiene, hexadiene, pentadiene, or tetradiene, or tridiene.

Curing proceeds by the addition reaction of the silicon-bonded hydrogen atoms in the dimethyl methylhydrogen siloxane, with the siloxane or alpha-omega diene under catalysis using the catalyst mentioned herein. To form a highly crosslinked structure, the methyl hydrogen siloxane must contain at least 2 silicon-bonded hydrogen atoms in each molecule in order to optimize function as a crosslinker.

The catalyst used in the addition reaction of silicon-bonded hydrogen atoms and alkenyl groups, and is concretely exemplified by 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 carrier-supported platinum.

Examples of suitable silicone elastomers for use in the compositions of the present disclosure may be in the powder form, or dispersed or solubilized in solvents such as volatile or non-volatile silicones, or silicone compatible vehicles such as paraffinic hydrocarbons or esters. Examples of silicone elastomer powders include vinyl dimethicone/methicone silesquioxane crosspolymers like Shin-Etsu's KSP-100, KSP-101, KSP-102, KSP-103, KSP-104, KSP-105, hybrid silicone powders that contain a fluoroalkyl group like Shin-Etsu's KSP-200 which is a fluoro-silicone elastomer, and hybrid silicone powders that contain a phenyl group such as Shin-Etsu's KSP-300, which is a phenyl substituted silicone elastomer; and Dow Coming's DC 9506. Examples of silicone elastomer powders dispersed in a silicone compatible vehicle include dimethicone/vinyl dimethicone crosspolymers supplied by a variety of suppliers including Dow Corning Corporation under the tradenames 9040 or 9041, GE Silicones under the tradename SFE 839, or Shin-Etsu Silicones under the tradenames KSG-15, 16, 18. KSG-15 has the CTFA name cyclopentasiloxane/dimethicone/vinyl dimethicone crosspolymer. KSG-18 has the INCI name phenyl trimethicone/dimethicone/phenyl vinyl dimethicone crossoplymer. Silicone elastomers may also be purchased from Grant Industries under the Gransil trademark. Also suitable are silicone elastomers having long chain alkyl substitutions such as lauryl dimethicone/vinyl dimethicone crosspolymers supplied by Shin Etsu under the tradenames KSG-31, KSG-32, KSG-41, KSG-42, KSG-43, and KSG-44. Cross-linked organopolysiloxane elastomers useful in the present disclosure and processes for making them are further described in U.S. Pat. No. 4,970,252 to Sakuta et al., issued Nov. 13, 1990; U.S. Pat. No. 5,760,116 to Kilgour et al., issued Jun. 2, 1998; U.S. Pat. No. 5,654,362 to Schulz, Jr. et al. issued Aug. 5, 1997; and Japanese Patent Application JP 61-18708, assigned to Pola Kasei Kogyo KK, each of which are herein incorporated by reference in its entirety.

Polysaccharides may be suitable aqueous phase thickening agents. Examples of such polysaccharides include naturally derived materials such as agar, agarose, alicaligenes polysaccharides, algin, alginic acid, acacia gum, amylopectin, chitin, dextran, cassia gum, cellulose gum, gelatin, gellan gum, hyaluronic acid, hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, pectin, sclerotium gum, xanthan gum, pectin, trehelose, gelatin, and so on.

Also suitable are different types of synthetic polymeric thickeners. One type includes acrylic polymeric thickeners comprised of monomers A and B, wherein A is selected from the group consisting of acrylic acid, methacrylic acid, and mixtures thereof; and B is selected from the group consisting of a C1-22 alkyl acrylate, a C1-22 alky methacrylate, and mixtures thereof are suitable. Acrylic polymer solutions include those sold by Seppic, Inc., under the tradenameor those sold under the tradename

Also suitable are acrylic polymeric thickeners that are copolymer of A, B, and C monomers wherein A and B are as defined above, and C has the general formula:

wherein Z is - (CH₂) _m; wherein m is 1-10, n is 2-3, o is 2-200, and R is a C_10-30 straight or branched chain alkyl. Examples of the secondary thickening agent above, are copolymers where A and B are defined as above, and C is CO, and wherein n, o, and R are as above defined. Examples of such secondary thickening agents include acrylates/steareth-20 methacrylate copolymer, which is sold by Rohm &Haas under the tradename Acrysol ICS-1.

Also suitable are acrylate based anionic amphiphilic polymers containing at least one hydrophilic unit and at least one allyl ether unit containing a fatty chain. Preferred are those where the hydrophilic unit contains an ethylenically unsaturated anionic monomer, more specificially a vinyl carboxylic acid such as acrylic acid, methacrylic acid or mixtures thereof, and where the allyl ether unit containing a fatty chain corresponds to the monomer of formula:

CH₂ = CR’CH₂OB_nR

wherein R'denotes H or CH₃, B denotes the ethylenoxy radical, n is zero or an integer ranging from 1 to 100, R denotes a hydrocarbon radical selected from alkyl, arylalkyl, aryl, alkylaryl and cycloalkyl radicals which contain from 8 to 30 carbon atoms, preferably from 10 to 24, and even more particularly from 12 to 18 carbon atoms. More preferred in this case is where R'denotes H, n is equal to 10 and R denotes a stearyl (C₁₈) radical. Anionic amphiphilic polymers of this type are described and prepared in U.S. Patent Nos. 4,677,152 and 4,702,844, both of which are hereby incorporated by reference in their entirety. Among these anionic amphiphilic polymers, polymers formed of 20 to 60%by weight acrylic acid and/or methacrylic acid, of 5 to 60%by weight lower alkyl methacrylates, of 2 to 50%by weight allyl ether containing a fatty chain as mentioned above, and of 0 to 1%by weight of a crosslinking agent which is a well-known copolymerizable polyethylenic unsaturated monomer, for instance diallyl phthalate, allyl (meth) acrylate, divinylbenzene, (poly) ethylene glycol dimethacrylate and methylenebisacrylamide. One commercial example of such polymers are crosslinked terpolymers of methacrylic acid, of ethyl acrylate, of polyethylene glycol (having 10 EO units) ether of stearyl alcohol or steareth-10, in particular those sold by the company Allied Colloids under the names SALCARE SC80 and SALCARE SC90, which are aqueous emulsions containing 30%of a crosslinked terpolymer of methacrylic acid, of ethyl acrylate and of steareth-10 allyl ether (40/50/10) .

Also suitable are acrylate copolymers such as Polyacrylate-3 which is a copolymer of methacrylic acid, methylmethacrylate, methylstyrene isopropylisocyanate, and PEG-40 behenate monomers; Polyacrylate-10 which is a copolymer of sodium acryloyldimethyltaurate, sodium acrylate, acrylamide and vinyl pyrrolidone monomers; or Polyacrylate-11, which is a copolymer of sodium acryloyldimethylacryloyldimethyl taurate, sodium acrylate, hydroxyethyl acrylate, lauryl acrylate, butyl acrylate, and acrylamide monomers.

Also suitable are crosslinked acrylate based polymers where one or more of the acrylic groups may have substituted long chain alkyl (such as 6-40, 10-30, and the like) groups, for example acrylates/C10-30 alkyl acrylate crosspolymer which is a copolymer of C10-30 alkyl acrylate and one or more monomers of acrylic acid, methacrylic acid, or one of their simple esters crosslinked with the allyl ether of sucrose or the allyl ether of pentaerythritol. Such polymers are commonly sold under the Carbopol or Pemulen tradenames and have the CTFA name carbomer.

One particularly suitable type of aqueous phase thickening agent are acrylate based polymeric thickeners sold by Clariant under the Aristoflex trademark such as Aristoflex AVC, which is ammonium acryloyldimethyltaurate/VP copolymer; Aristoflex AVL which is the same polymer has found in AVC dispersed in mixture containing caprylic/capric triglyceride, trilaureth-4, and polyglyceryl-2 sesquiisostearate; or Aristoflex HMB which is ammonium acryloyldimethyltaurate/beheneth-25 methacrylate crosspolymer, and the like.

Also suitable as thickening agents are various polyethylene glycols (PEG) derivatives where the degree of polymerization ranges from 1,000 to 200,000. Such ingredients are indicated by the designation "PEG" followed by the degree of polymerization in thousands, such as 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, 180M, and the like.

Also suitable are polyglycerins which are repeating glycerin moieties where the number of repeating moieties ranges from 15 to 200, preferably from about 20-100. Examples of suitable polyglycerins include those having the CTFA names polyglycerin-20, polyglycerin-40, and the like.

F. Oils

In the case that the compositions of the present disclosure are in emulsion form, the composition will contain an oil phase. Oily ingredients are desirable for the skin moisturizing and protective properties. Suitable oils include silicones, esters, vegetable oils, synthetic oils, including but not limited to those set forth herein. The oils may be volatile or nonvolatile, and are preferably in the form of a pourable liquid at room temperature. The term "volatile" means that the oil has a measurable vapor pressure, or a vapor pressure of at least about 2 mm. of mercury at 20℃. The term "nonvolatile" means that the oil has a vapor pressure of less than about 2 mm.of mercury at 20℃.

1. Volatile Oils

Suitable volatile oils generally have a viscosity ranging from about 0.5 to 5 centistokes 25℃ and include linear silicones, cyclic silicones, paraffinic hydrocarbons, or mixtures thereof.

(a) . Volatile Silicones

Cyclic silicones are one type of volatile silicone that may be used in the composition. Such silicones have the general formula:

wherein n=3-6, preferably 4, 5, or 6.

Also suitable are linear volatile silicones, for example, those having the general formula:

(CH₃) ₃Si─O─ [Si (CH₃) ₂─O] _n─Si (CH₃) ₃

wherein n=0, 1, 2, 3, 4, or 5, preferably 0, 1, 2, 3, or 4.

Cyclic and linear volatile silicones are available from various commercial sources including Dow Corning Corporation and General Electric. The Dow Corning linear volatile silicones are sold under the tradenames Dow Corning 244, 245, 344, and 200 fluids. These fluids include hexamethyldisiloxane (viscosity 0.65 centistokes (abbreviated cst) ) , octamethyltrisiloxane (1.0 cst) , decamethyltetrasiloxane (1.5 cst) , dodecamethylpentasiloxane (2 cst) and mixtures thereof, with all viscosity measurements being at 25℃.

Suitable branched volatile silicones include alkyl trimethicones such as methyl trimethicone, a branched volatile silicone having the general formula:

Methyl trimethicone may be purchased from Shin-Etsu Silicones under the tradename TMF-1.5, having a viscosity of 1.5 centistokes at 25℃.

(b) . Volatile Paraffinic Hydrocarbons

Also suitable as the volatile oils are various straight or branched chain 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. Suitable hydrocarbons include pentane, hexane, heptane, decane, dodecane, tetradecane, tridecane, and C_8-20 isoparaffins as disclosed in U.S. Pat. Nos. 3,439,088 and 3,818,105, both of which are hereby incorporated by reference.

Preferred volatile paraffinic hydrocarbons have a molecular weight of 70-225, preferably 160 to 190 and a boiling point range of 30 to 320, preferably 60 to 260℃, and a viscosity of less than about 10 cst. at 25℃. Such paraffinic hydrocarbons are available from EXXON under the ISOPARS trademark, and from the Permethyl Corporation. Suitable C₁₂ isoparaffins are manufactured by Permethyl Corporation under the tradename Permethyl 99A. Various C₁₆ isoparaffins commercially available, such as isohexadecane (having the tradename Permethyl R) , are also suitable.

2. Non-Volatile Oils

A variety of nonvolatile oils are also suitable for use in the compositions of the present disclosure. The nonvolatile oils generally have a viscosity of greater than about 5 to 10 centistokes at 25℃, and may range in viscosity up to about 1,000,000 centipoise at 25℃. Examples of nonvolatile oils include, but are not limited to:

(a) . Esters

Suitable esters are mono-, di-, and triesters. The composition may comprise one or more esters selected from the group, or mixtures thereof.

(i) Monoesters

Monoesters are defined as esters formed by the reaction of a monocarboxylic acid having the formula R-COOH, wherein R is a straight or branched chain saturated or unsaturated alkyl having 2 to 45 carbon atoms, or phenyl; and an alcohol having the formula R-OH wherein R is a straight or branched chain saturated or unsaturated alkyl having 2-30 carbon atoms, or phenyl. Both the alcohol and the acid may be substituted with one or more hydroxyl groups. Either one or both of the acid or alcohol may be a "fatty" acid or alcohol, and may have from about 6 to 30 carbon atoms, more preferably 12, 14, 16, 18, or 22 carbon atoms in straight or branched chain, saturated or unsaturated form. Examples of monoester oils that may be used in the compositions of the present disclosure include hexyl laurate, butyl isostearate, hexadecyl isostearate, cetyl palmitate, isostearyl neopentanoate, stearyl heptanoate, isostearyl isononanoate, steary lactate, stearyl octanoate, stearyl stearate, isononyl isononanoate, and so on.

(ii) . Diesters

Suitable diesters are the reaction product of a dicarboxylic acid and an aliphatic or aromatic alcohol or an aliphatic or aromatic alcohol having at least two substituted hydroxyl groups and a monocarboxylic acid. The dicarboxylic acid may contain from 2 to 30 carbon atoms, and may be in the straight or branched chain, saturated or unsaturated form. 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 in the straight or branched chain, saturated, or unsaturated form. Preferably, one or more of the acid or alcohol is a fatty acid or alcohol, i.e. contains 12-22 carbon atoms. The dicarboxylic acid may also be an alpha hydroxy acid. The ester may be in the dimer or trimer form. Examples of diester oils that may be used in the compositions of the present disclosure include diisotearyl malate, neopentyl glycol dioctanoate, dibutyl sebacate, dicetearyl dimer dilinoleate, dicetyl adipate, diisocetyl adipate, diisononyl adipate, diisostearyl dimer dilinoleate, diisostearyl fumarate, diisostearyl malate, dioctyl malate, and so on.

(iii) . Triesters

Suitable triesters comprise the reaction product of a tricarboxylic acid and an aliphatic or aromatic alcohol or alternatively the reaction product of an aliphatic or aromatic alcohol having three or more substituted hydroxyl groups with a monocarboxylic acid. As with the mono-and diesters mentioned above, the acid and alcohol contain 2 to 30 carbon atoms, and may be saturated or unsaturated, straight or branched chain, and may be substituted with one or more hydroxyl groups. Preferably, one or more of the acid or alcohol is a fatty acid or alcohol containing 12 to 22 carbon atoms. Examples of triesters include esters of arachidonic, citric, or behenic acids, such as triarachidin, tributyl citrate, triisostearyl citrate, tri C_12-13 alkyl citrate, tricaprylin, tricaprylyl citrate, tridecyl behenate, trioctyldodecyl citrate, tridecyl behenate; or tridecyl cocoate, tridecyl isononanoate, and so on.

Esters suitable for use in the composition of the present disclosure are further described in the C.T.F.A. Cosmetic Ingredient Dictionary and Handbook, Eleventh Edition, 2006, under the classification of "Esters" , the text of which is hereby incorporated by reference in its entirety.

(b) . Hydrocarbon Oils

It may be desirable to incorporate one or more nonvolatile hydrocarbon oils into the composition of the present disclosure. Suitable nonvolatile hydrocarbon oils include paraffinic hydrocarbons and olefins, preferably those having greater than about 20 carbon atoms. Examples of such hydrocarbon oils include C_24-28 olefins, C_30-45 olefins, C_20-40 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 ranging from about 300 to 1000 Daltons.

(c) . Glyceryl Esters of Fatty Acids

Synthetic or naturally occurring glyceryl esters of fatty acids, or triglycerides, are also suitable for use in the compositions. Both vegetable and animal sources may be used. Examples of such oils include castor oil, lanolin oil, C_10-18 triglycerides, caprylic/capric/triglycerides, sweet almond oil, apricot kernel oil, sesame oil, camelina sativa oil, tamanu seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, ink oil, olive oil, palm oil, illipe butter, rapeseed oil, soybean oil, grapeseed oil, sunflower seed oil, walnut oil, and the like.

Also suitable are synthetic or semi-synthetic glyceryl esters, such as fatty acid mono-, di-, and triglycerides which are natural fats or oils that have been modified, for example, mono-, di-or triesters of polyols such as glycerin. In an example, a fatty (C_12-22) carboxylic acid is reacted with one or more repeating glyceryl groups. glyceryl stearate, diglyceryl diiosostearate, 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 oils, PEG glyceryl oleates, PEG glyceryl stearates, PEG glyceryl tallowates, and so on.

(d) . Nonvolatile Silicones

Nonvolatile silicone oils, both water soluble and water insoluble, are also suitable for use in the composition. Such silicones preferably have a viscosity ranging from about greater than 5 to 800,000 cst, preferably 20 to 200,000 cst at 25℃. Suitable water insoluble silicones include amine functional silicones such as amodimethicone.

For example, such nonvolatile silicones may have the following general formula:

wherein R and R' are each independently C_1-30 straight or branched chain, saturated or unsaturated alkyl, phenyl or aryl, trialkylsiloxy, and x and y are each independently 1-1,000,000; with the proviso that there is at least one of either x or y, and A is alkyl siloxy endcap unit. Preferred is where A is a methyl siloxy endcap unit; in particular trimethylsiloxy, and R and R' are each independently a C_1-30 straight or branched chain alkyl, phenyl, or trimethylsiloxy, more preferably a C_1-22 alkyl, phenyl, or trimethylsiloxy, most preferably methyl, phenyl, or trimethylsiloxy, and resulting silicone is dimethicone, phenyl dimethicone, diphenyl dimethicone, phenyl trimethicone, or trimethylsiloxyphenyl dimethicone. Other examples include alkyl dimethicones such as cetyl dimethicone, and the like wherein at least one R is a fatty alkyl (C₁₂, C₁₄, C₁₆, C₁₈, C₂₀, or C₂₂) , and the other R is methyl, and A is a trimethylsiloxy endcap unit, provided such alkyl dimethicone is a pourable liquid at room temperature. Phenyl trimethicone can be purchased from Dow Corning Corporation under the tradename 556 Fluid. Trimethylsiloxyphenyl dimethicone can be purchased from Wacker-Chemie under the tradename PDM-1000. Cetyl dimethicone, also referred to as a liquid silicone wax, may be purchased from Dow Corning as Fluid 2502, or from DeGussa Care &Surface Specialties under the trade names Abil Wax 9801, or 9814.

G. Sunscreens

It may also be desirable to include one or more sunscreens in the compositions of the present disclosure. Such sunscreens include chemical UVA or UVB sunscreens or physical sunscreens in the particulate form. Inclusion of sunscreens in the compositions containing the whitening active ingredient will provide additional protection to skin during daylight hrs and promote the effectiveness of the whitening active ingredient on the skin. If present, the sunscreens may range from about 0.1 to 50%, preferably from about 0.5 to 40%, more preferably from about 1 to 35%.

1. UVA Chemical Sunscreens

If desired, the composition may comprise one or more UVA sunscreens. The term "UVA sunscreen" means a chemical compound that blocks UV radiation in the wavelength range of about 320 to 400 nm. Preferred UVA sunscreens are dibenzoylmethane compounds of the formula:

wherein R₁ is H, OR and NRR wherein each R is independently H, C_1- ₂₀ straight or branched chain alkyl; R₂ is H or OH; and R₃ is H, C_1-20 straight or branched chain alkyl.

Preferred is where R₁ is OR where R is a C_1-20 straight or branched alkyl, preferably methyl; R₂ is H; and R₃ is a C_1-20 straight or branched chain alkyl, more preferably, butyl.

Examples of suitable UVA sunscreen compounds of 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'-methoxydibenzoymethane, 2-methyl-5-tert-butyl-4'-methoxydibenzoylmethane, and so on. Particularly preferred is 4-tert-butyl-4'-methoxydibenzoylmethane, also referred to as Avobenzone. Avobenzone is commercially available from Givaudan-Roure under the trademark1789, and Merck &Co. under the tradename9020.

Other types of UVA sunscreens include dicamphor sulfonic acid derivatives, such as ecamsule, a sunscreen sold under the trade name which is terephthalylidene dicamphor sulfonic acid, having the formula:

The composition may contain from about 0.001-20%, preferably 0.005-5%, more preferably about 0.005-3%by weight of the composition of UVA sunscreen. In the preferred embodiment of the present disclosure the UVA sunscreen is Avobenzone, and it is present at not greater than about 3%by weight of the total composition.

2. UVB Chemical Sunscreens

The term "UVB sunscreen" means a compound that blocks UV radiation in the wavelength range of from about 290 to 320 nm. A variety of UVB chemical sunscreens exist including alpha-cyano-beta, beta-diphenyl acrylic acid esters as set forth in U.S. Pat. No. 3,215,724, which is hereby incorporated by reference in its entirety. One particular example of an alpha-cyano-beta, beta-diphenyl acrylic acid ester is Octocrylene, which is 2-ethylhexyl 2-cyano-3, 3-diphenylacrylate. In certain cases, the composition may contain no more than about 10%by weight of the total composition of octocrylene. Suitable amounts range from about 0.001-10%by weight. Octocrylene may be purchased from BASF under the tradenameN-539.

Other suitable sunscreens include benzylidene camphor derivatives as set forth in U.S. Pat. No. 3,781,417, which is hereby incorporated by reference in its entirety. Such benzylidene camphor derivatives have the general formula:

wherein R is p-tolyl or styryl, preferably styryl. Particularly preferred is 4-methylbenzylidene camphor, which is a lipid soluble UVB sunscreen compound sold under the tradename Eusolex 6300 by Merck.

Also suitable are cinnamate derivatives having the general formula:

wherein R and R₁ are each independently a C_1-20 straight or branched chain alkyl. Preferred is where R is methyl and R₁ is a branched chain C_1- ₁₀, preferably C₈ alkyl. The preferred compound is ethylhexyl methoxycinnamate, also referred to as Octoxinate or octyl methoxycinnamate. The compound may be purchased from Givaudan Corporation under the tradenameMCX, or BASF under the tradenameMC 80.

Also suitable are mono-, di-, and triethanolamine derivatives of such methoxy cinnamates including diethanolamine methoxycinnamate. Cinoxate, the aromatic ether derivative of the above compound is also acceptable. If present, the Cinoxate should be found at no more than about 3%by weight of the total composition.

Also suitable as UVB screening agents are various benzophenone derivatives having the general formula:

wherein R through R₉ are each independently H, OH, NaO₃S, SO₃H, SO₃Na, Cl, R”, OR” where R” is C_1-20 straight or branched chain alkyl Examples of such compounds include Benzophenone 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. Particularly preferred is where the benzophenone derivative is Benzophenone 3 (also referred to as Oxybenzone) , Benzophenone 4 (also referred to as Sulisobenzone) , Benzophenone 5 (Sulisobenzone Sodium) , and the like. Most preferred is Benzophenone 3.

Also suitable are certain menthyl salicylate derivatives having the general formula:

wherein R₁, R₂, R₃, and R₄ are each independently H, OH, NH₂, or C_1- ₂₀ straight or branched chain alkyl. Particularly preferred is where R₁, R₂, and R₃ are methyl and R₄ is hydroxyl or NH₂, the compound having the name homomenthyl salicylate (also known as Homosalate) or menthyl anthranilate. Homosalate is available commercially from Merck under the trademarkHMS and menthyl anthranilate is commercially available from Haarmann &Reimer under the trademarkIf present, the Homosalate should be found at no more than about 15%by weight of the total composition.

Various amino benzoic acid derivatives are suitable UVB absorbers including those having the general formula:

wherein R₁, R₂, and R₃ are each independently H, C_1-20 straight or branched chain alkyl which may be substituted with one or more hydroxy groups. Particularly preferred is wherein R₁ is H or C_1-8 straight or branched alkyl, and R₂ and R₃ are H, or C_1-8 straight or branched chain alkyl. Particularly preferred are PABA, ethyl hexyl dimethyl PABA (Padimate O) , ethyldihydroxypropyl PABA, and the like. If present Padimate O should be found at no more than about 8%by weight of the total composition.

Salicylate derivatives are also acceptable UVB absorbers. Such compounds have the general formula: wherein R is a straight or branched chain alkyl, including derivatives of the above compound formed from mono-, di-, or triethanolamines. Particular preferred are octyl salicylate, TEA-salicylate, DEA-salicylate, and mixtures thereof.

Generally, the amount of the UVB chemical sunscreen present may range from about 0.001-45%, preferably 0.005-40%, more preferably about 0.01-35%by weight of the total composition.

If desired, the compositions of the present disclosure may be formulated to have certain SPF (sun protective factor) values ranging from about 1-50, preferably about 2-45, most preferably about 5-30. Calculation of SPF values is well known in the art.

H. Vitamins and Antioxidants

It may be desirable to incorporate one or more vitamins or antioxidants in the composition of the present disclosure. If present, suggested ranges are from about 0.001 to 20%, preferably from about 0.005 to 15%, more preferably from about 0.010 to 10%. Preferably such vitamins, vitamin derivatives and/or antioxidants are operable to scavenge free radicals in the form of singlet oxygen. Such vitamins may include tocopherol or its derivatives such as tocopherol acetate, tocopherol ferulate; ascorbic acid or its derivatives such as ascorbyl palmitate, magnesium ascorbyl phosphate; Vitamin A or its derivatives such as retinyl palmitate; or vitamins D, K, B, or derivatives thereof.

As those skilled in the art will appreciate, the compositions containing the supramolecular assemblies according to the present disclosure may further comprise about 0.001-99%, preferably about 0.01-90%, more preferably about 0.1-70%, and most preferably about 1-50%by weight of the total composition of one or more additional cosmetically acceptable medium.

Preparation of the above-named cosmetic compositions and others may be accomplished with reference to any of the cosmetic formulation guidebooks and Industry journals which are available in the cosmetic industry. These references supply standard formulations which may be modified by the addition or substitution of the supramolecular complexes of the present disclosure into the formulation. Suitable guidebooks include Cosmetics and Toiletries Magazine, Vol. 111 (March, 1996) ; Formulary: Ideas for Personal Care; Croda, Inc, Parsippany, N. J. (1993) ; and Cosmeticon: Cosmetic Formulary, BASF, which are hereby incorporated in their entirety by reference. The cosmetic composition may be in any form. Suitable forms include but are not limited to solid doses, liquids, gels, lotions, creams, hard gel sticks, roll-ons formulations, mousses, aerosol sprays, pad-applied formulations, and film-forming formulations.

The cosmetic composition of the present disclosure is preferably applied at least once per day, e.g. twice or three times a day. Usually, it takes at least two weeks until the desired effect is achieved. However, it can take several weeks or even months until the desired effect is fully maximized.

The amount of the cosmetic composition, which is to be applied to the keratin materials, depends on the concentration of the active ingredients, such as the supramolecular assemblies, in the compositions and the desired cosmetic or pharmaceutical effect. For example, application can be such that a cream is applied to the skin. A cream is usually applied in an amount of 2 mg cream/cm² skin. The amount of the composition which is applied to the skin is, however, not critical, and if with a certain amount of applied composition, the desired effect cannot be achieved, a higher concentration of the active ingredients can be used e.g. by applying more of the composition or by applying compositions which contain more active ingredients.

The supramolecular assembly of the present disclosure may also find a broad range of applications in fields such as personal care, food, dietary supplements, and pharmaceutics.

The invention will be further described in connection with the following example which is set forth for purposes of illustration without being limiting in nature.

Examples

Main raw materials used, trade names and supplier thereof are listed in Table 1 below. Materials without specification here were each commercially available.

Table 1. Raw materials information

Preparation of Supramolecular Assemblies

Example 1. Supramolecular assembly A (BTN-FA (1: 1) )

BTN (0.1171 g, 0.001 mol) and FA (0.1941 g, 0.001 mol) were added into 9 mL ethanol at a molar ratio of 1: 1 to obtain a mixture. The mixture was heated to 50℃ and held at that temperature for 20 min under stirring to ensure complete dissolution of the starting materials. Upon complete dissolution, the stirring was stopped, and the system was cooled to room temperature. After further cooling to 5℃, the seeded crystallization medium was left to dwell for 2 h. The produced crystals were collected and vacuum-dried at 50℃ for 24 h to get pure form. Yield: 51.98%.

Example 2. Supramolecular assembly B (BTN-FA (2: 1) )

BTN (0.2343 g, 0.002 mol) and FA (0.1941 g, 0.001 mol) were added into 11 mL ethanol at a molar ratio of 1: 1 to obtain a mixture. The mixture was heated to 50℃ and held at that temperature for 20 min under stirring to ensure the complete dissolution of the starting materials. Upon complete dissolution, the stirring was stopped, and the system was cooled to room temperature. After further cooling to 5℃, the seeded crystallization medium was left to dwell for 2 h. The produced crystals were collected and vacuum-dried at 50℃ for 24 h to get pure form. Yield: 58.65%.

Example 3. Supramolecular assembly C (BTN-FA (1: 2) )

BTN (0.1171 g, 0.001 mol) and FA (0.3883 g, 0.002 mol) were added into 11 mL ethanol at a molar ratio of 1: 2 to obtain a mixture. The mixture was heated to 50℃ and held at that temperature for 20 min under stirring to ensure the complete dissolution of the starting materials. Upon complete dissolution, the stirring was stopped, and the system was cooled to room temperature. After further cooling to 5℃, the seeded crystallization medium was left to dwell for 2 h. The produced crystals were collected and vacuum-dried at 50℃ for 24 h to get pure form. Yield: 67.84%.

Characterization of Supramolecular Assemblies

FT-IR

Fourier-transform infrared spectroscopy (FT-IR) : FT-IR measurements were collected on a Thermo Nicolet 6700 IR spectrometer (Thermo Fisher Scientific, Waltham, MA) . Samples were compressed into disks with KBr at a pressure of 30 MPa for 6 s and then measured over the wavenumber range of from 4000 cm^-1 to 400 cm^-1.

The FT-IR spectra of individual components BTN and FA, as well as the supramolecular assemblies A-C of Examples 1-3, were recorded and shown in Figure 1. In the FT-IR spectrum of BTN, one of the characteristic absorption peaks was observed at 1622 cm^-1, corresponding to the C=O stretching. In the FT-IR spectrum of FA, one of the characteristic peaks was observed at 3436 cm^-1, corresponding to the vibrations of -OH. As for the FTIR spectra of supramolecular assemblies with different mole ratios, the band corresponding to O-H stretching was observed at 3434, 3389, and 3431 cm^-1 (BTN: FA = 1: 1, 2: 1, 1: 2) , respectively, differing from the raw components and representing a change in chemical environment of phenolic O-H groups. Furthermore, compared with BTN and FA, the band corresponding to C=O stretching in FT-IR spectrum was changed to 1687, 1689, and 1691 cm^-1, respectively, for the supramolecular assemblies A-C. The bands shift showed in the FTIR confirmed the formation of hydrogen bonds in the supramolecular assemblies.

Powder XRD

Powder X-ray diffraction (XRD) : Powder X-ray diffraction was recorded on Rotating Anode X-ray Powder Diffractometer equipped with Cu Kαsource and operated at 40 kV and 40 mA. XRD patterns were collected in the 2θ range of 5-50° with angular step of 1°/min.

Powder XRD patterns of individual components BTN and FA, as well as the supramolecular assemblies A-C of Examples 1-3, were measured and shown in Figure 2. The FA presented characteristic peaks at 2θ of 9.0°, 10.5°, 12.8°, 15.6° 17.4°, 18.1°, 21.1°, 22.4°, 24.6°, 25.9°, 26.5° and 29.5° and BTN at 2θ of 12.1°, 13.5°, 15.4°, 16.4°, 16.8°, 18.1°, 19.3°, 20.2°, 22.6°, 24.4°, 25.2°, 25.5° and 27.7°. As shown in Figure 2 of the XRD patterns, the supramolecular assemblies A-C showed new characteristic peaks at 2θangles (labeled with pentacles in Figure 2) , which were different from those of BTN and FA, indicating the cocrystals formation. All supramolecular assemblies A-C showed new peaks at 2θ angle of around 14.4°. Moreover, a new peak at 2θ angle of 7.2° appeared in the pattern of the supramolecular assembly A (BTN: FA=1: 1) .

DSC

Differential scanning calorimetry (DSC) : DCS measurements were conducted in a HCT-1 thermal analyzer. Samples weighing 3-5 mg were tested under a nitrogen atmosphere by heating in the temperature range between 40 and 200℃ with a heating rate of 5℃ min^-1.

The Calorimetric profiles of individual components BTN and FA, as well as the supramolecular assemblies A-C of Examples 1-3 were measured and shown in Figure 3. In the DSC profiles, the melting temperatures of BTN and FA were observed at 304℃ and 171℃, respectively. On the other hand, an endotherm peak at 153.2℃, 154.0℃, or 154.8℃ was observed respectively for the supramolecular assemblies A-C, obviously differing from that of BTN or FA.

Evaluation on Properties of Supramolecular Assemblies

Example 4. Solubility Test

The solubility tests for FA and the supramolecular assembly A of Example 1 were performed in deionized water by shake-flask method. An excess amount of the samples equivalent to 100 mg FA were dispersed separately in glass flasks with 100 ml of distilled water. The suspension dispersions were incubated in water bath kettle with continuous stirring at room temperature for 24 h. After this period, the suspension dispersions were centrifuged at 5000 rpm for 15 min. Further, the supernatants were then filtered (0.45 μm nylon filter) and concentration of the FA in the supernatants for the raw material compound FA as well as for the supramolecular assembly A of Example 1 was evaluated by Shimadzu UV-1800 spectrophotometer. As show in Table 2, FA solubility in distilled water increased approximately 1.29 times, from 0.439 mg mL^-1 for raw FA to 0.565 mg mL^-1 for the supramolecular assembly A of Example 1.

Table 2. Solubility in water

Example 5. Anti-Oxidative Stress Assay

Human Epidermal Keratinocytes (HEKs, FC-0007, purchased from Lifeline Cell Technology) were seeded on 12-well plates at a density of 1.4 × 10⁵ cells/well and then treated with various actives at a concentration as listed in Table 5 for 24 h. Then, H₂O₂ (250 μM, 23381-25mL, Sigma, St. Louis, MO, USA) was added to the cells followed by incubation for 30 min. The cells were then incubated with the reactive oxygen species (ROS) probe DCFH-DA (S0033, Beyotime, Nanjing, China) in the dark for 30 min, harvested, and measured by flow cytometry (Beckman, CA, USA) . The data were analyzed using the mean fluorescence intensity (MFI) . The protective effect was calculated using the following equation:

Protection (%) = [ (MFI_H2O2 -MFI_control) - (MFI_active -MFI_control) ] / (MFI_H2O2 -MFI_control) × 100%.

All experiments were performed in triplicate.

Statistical Analysis

As shown in Table 3 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 by one-way ANOVA and Dunnett's post hoc tests. An adjusted P value lower than 0.05 was considered to reflect a statistically significant difference.

Table 3. Anti-oxidative performances

The data of anti-oxidative stress assay in Table 3 above demonstrate that the supramolecular assembly exhibits the synergic effect in anti-oxidative efficacy compared to individual FA and BTA as well as the physical mixture of BTN and FA.

Example 6: Formulation of Cosmetic Composition

The ingredient amounts/concentrations in the compositions/formulas described below were expressed in %by weight, relative to the total weight of each composition/formula.

The cosmetic composition containing the supramolecular assembly is prepared by thoroughly mixing the ingredients as shown in Table 4 below in accordance with a conventional method.

Table 4. Formulation of cosmetic composition

Every document cited herein, including any cross referenced or related patent or application, is hereby incorporated herein by reference in its entirety unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is prior art with respect to any invention disclosed or claimed herein or that it alone, or in any combination with any other reference or references, teaches, suggests or discloses any such invention. Further, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern.

Claims

A supramolecular assembly comprising at least one hydroxycinnamic acid derivative and at least one betaine compound, wherein the betaine compound and the hydroxycinnamic acid derivative are assembled by non-covalent bonding forces.
The supramolecular assembly according to claim 1, wherein the non-covalent bonding forces include hydrogen bonding forces, non-covalent electrostatic interactions, and van der Waals forces.
The supramolecular assembly according to claim 1 or 2, wherein the supramolecular assembly has a ratio between the betaine compound and the hydroxycinnamic acid derivative of from about 10: 1 to about 1: 10, preferably from about 3: 1 to about 1: 3, more preferably from about 2: 1 to about 2: 1, and particularly preferably, the supramolecular assembly has a ratio between the betaine compound and the hydroxycinnamic acid derivative selected from the group consisting of about 2: 1, about 1: 1 and about 1: 2.
The supramolecular assembly according to any one of claims 1 to 3, wherein the betaine compound is selected from the group consisting of histidine betaine, glycine betaine, proline betaine, phenylalanine betaine, tyrosine betaine, tryptophan betaine, leucine betaine, isoleucine betaine, valine betaine, betaine glutamate, alanine betaine, betaine aspartate, lysine betaine, arginine betaine, and combinations thereof;

preferably, the betaine compound is glycine betaine.
The supramolecular assembly according to any one of claims 1 to 4, wherein the hydroxycinnamic acid derivative is selected from the group consisting of caffeic acid (CaA) , chlorogenic acid (ChA) , sinapic acid (SA) , ferulic acid (FA) , p-coumaric acid (CoA) , and combinations thereof;

preferably, the hydroxycinnamic acid derivative is ferulic acid (FA) .
A supramolecular assembly A comprising glycine betaine and ferulic acid, wherein the supramolecular assembly A has a Powder X-ray Diffraction (XRD) pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 7.2°, 14.5°, 19.9°, 21.6°, 22.0°, 24.2° ± 0.2°;

preferably, the supramolecular assembly A has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 7.2°, 10.5°, 14.5°, 15.7°, 17.0°, 18.9°, 19.9°, 21.6°, 22.0°, 23.4°, 24.2°, 26.6°, 29.4° ± 0.2°.
A supramolecular assembly B comprising glycine betaine and ferulic acid, wherein the supramolecular assembly B has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 10.5°, 12.5°, 14.3°, 20.8°, 21.9°, 25.1° ± 0.2°;

preferably, the supramolecular assembly B has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 10.5°, 12.5°, 14.3°, 17.3°, 19.5°, 20.4°, 20.8°, 21.9°, 22.6°, 25.1°, 27.1°, 29.3°, 32° ± 0.2°.
A supramolecular assembly C comprising glycine betaine and ferulic acid, wherein the supramolecular assembly C has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 9.0°, 12.5°, 14.4°, 17.3°, 20.8°, 22.0°, 25.1°, 39° ± 0.2°;

preferably, the supramolecular assembly C has a Powder XRD pattern exhibiting characteristic diffraction peaks at the following 2θ angles: 9.0°, 10.6°, 12.5°, 12.8°, 14.4°, 15.6°, 17.3°, 19.5°, 20.4°, 20.8°, 22.0°, 22.4°, 24.6°, 25.1°, 39° ± 0.2°.
A method for preparing the supramolecular assembly according to any one of claims 1 to 8, comprising steps of:

a) mixing starting materials in a solvent to obtain a mixture, heating the mixture to a first temperature which is maintained until the starting materials are completely dissolved to obtain a clear system, wherein the starting materials comprise at least one hydroxycinnamic acid derivative and at least one betaine compound;

b) cooling the system from step a) to a second temperature, at which the system is left to dwell to produce crystals, wherein the second temperature is equal to or greater than -20℃ and is at least 15℃, preferably at least 25℃, and more preferably at least 35℃ lower than the first temperature; and

c) collecting and optionally purifying the crystals from step b) to obtain the supramolecular assembly.
A composition, especially a cosmetic composition for topical application, comprising the supramolecular assembly according to any one of claims 1 to 8 or prepared by the method according to claim 9.
The composition according to claim 10, wherein the supramolecular assembly is present in the composition in an amount of from about 0.0001 wt%to about 20 wt%, preferably from about 0.001 wt%to about 10 wt%, more preferably from about 0.01 wt%to about 5 wt%, and most preferably from about 0.1 wt%to about 2 wt%, relative to the total weight of the composition.
A non-therapeutic method for caring for, protecting and/or making up keratin materials, comprising topically applying the composition according to claim 10 or 11 to the keratin materials.
Use of the supramolecular assembly according to any one of claims 1-8 or the composition according to claim 10 or 11 in caring for, protecting and/or making up keratin materials.