KR20180064340A - Methods that inhibit matrix metalloproteinases and reduce aging in skin and related synergistic compositions - Google Patents

Abstract

The present invention relates to a method for suppressing the activity of the matrix metalloproteinases (MMPs) in the skin including the topical application of a composition, which has an effective ratio for the synergistic action related to the concentration of a hydroxamic acid, salt of the hydroxamic acid, and/or a complex thereof and the concentration of glycols, to the skin′s surface. According to partial embodiments of the present invention, the ratio of the weight percentage of the hydroxamic acid, salt of the hydroxamic acid, and/or the complex thereof with respect to the weight percentage of the glycols can be selected from a group including 1:1.4, 1:3, and 1:5 with respect to the weight of the total composition in an approximating manner. The present invention also relates to methods for preventing or reducing aging on the skin surface. The methods include the topical application of a composition, which has the effective ratio for the synergistic action related to the concentration of a hydroxamic acid, salt of the hydroxamic acid, and/or a complex thereof and the concentration of glycols, to the surface of a skin. The methods for increasing the enzymatic inhibition potential of the glycols include a step of coupling one or more glycols with the hydroxamic acid, salt of the hydroxamic acid, and/or a complex thereof in the amounts in accordance with the effective ratio for the synergistic action for forming a synergistic mixture. Enzymatic inhibition potential of the synergistic mixture is greater than the enzymatic inhibition potential of glycols or the hydroxamic in a standalone manner. The present invention also relates to anti-aging compositions for suppressing the activities of MMPs in the skin with the effective ratio of the concentration of the hydroxamic acid, salt of the hydroxamic acid, and/or a complex thereof and the concentration of glycols for the synergetic action within the above-described range. In partial embodiments of the present invention, the weight percentage ratio can be selected from a group including 1:1.4, 1:3, and 1:5 with respect to the weight of the total composition.

Description

METHODS THAT INHIBIT MATRIX METALLOPROTEINASES AND REDUCE AGING IN SKIN AND RELATED SYNERGISTIC COMPOSITIONS FIELD OF THE INVENTION [0001] The present invention relates to methods for inhibiting matrix metalloproteinases in the skin and reducing senescence,

The present invention relates to the use of a substrate metalloproteinase in the skin comprising topical application to the skin surface of a composition comprising a ratio effective to the synergistic action of the amount of hydroxamic acid, its salt and / or complex thereof and the amount of glycol Lt; / RTI > activity.

The phenomenon of cutaneous aging is determined by two unique biological processes, intrinsic and extrinsic aging, which can occur simultaneously. Both cases progressively lead to loss of structural integrity and physiological function. Endogenous skin aging is a natural consequence of a physiologically genetically determined change over time that is obviously inevitable, although it can vary from person to person. Clinical features of endogenously aged skin are characterized by fine wrinkles with pale skin and occasionally exaggerated expression lines. Functionally, endogenously aged skin is dry and less elastic than younger skin.

On the other hand, extrinsic skin aging is somewhat controllable, and it can be controlled by a variety of lifestyles, such as sunlight, pollution or repetitive muscle movements such as nicotine and frown, as well as diet, And exposure to the same environmental impacts. Exogenously aged skin is exemplified by deep and healing wrinkles, mottled hyperpigmentation, and marked damage to elastic recoil.

The major factors associated with skin aging are the generation of reactive oxygen species (ROS), pigment changes, reduced collagen synthesis, and the activity of matrix metalloproteinases (MMPs, hereinafter referred to as MMPs) Induction. The latter will promote collagen destruction, which ultimately leads to more powerful collagen damage. Without providing a collagen matrix, the skin becomes sagging and wrinkles appear. In normal conditions, collagen levels are maintained by ensuring a balance between the synthesis of new collagen and the enzymatic degradation of previous collagen. In aged and / or photodamaged skin, the synthesis of procollagen in fibroblast is naturally reduced and expression of collagen-degrading enzymes is increased.

Metalloproteinases, including matrix metalloproteinases (MMPs), are known to play a role in proteolytic cleavage of extracellular matrix and connective tissue in mammals, superfamily. Based on the structural and functional considerations, MMPs can be used as collagenases (MMP-1, -8 and -13), gelatinases (MMP-2 and -9), metalloeles MMPs (MMP-14, -15, -16, -17, -24, and -25), matrilysins (MMP-12) -7 and -26), stromelysins (MMP-3, -10, and -11) and tumor necrosis factor, TNF-converting enzymes (TACE and ACE) In particular, MMP-1 is known to be responsible for the degradation of the most common form of collagen in the skin, I-type collagen.

The basal expression of MMPs in young skin is relatively low. MMPs are activated by proteolytic enzymes naturally occurring in the skin or by thiol modifying agents (4-aminophenylmercuric acetate, mercury, ethylmaleimide) , Oxidized glutathione, chaotropic agents, and active oxygen species. ≪ / RTI > Low pH and heat treatment can also lead to activity. However, lifestyle choices such as smoking and unprotected sunbathing down-regulate the underlying expression of collagen I, III, and VI genes; Heat shock protein 47 (Hsp 47) genes also increase basal expression of matrix metalloproteinases 1 (MMP-1) and 9 (MMP-9). Indeed, damage caused by sunlight promotes the state of chronic inflammation, which results in the subsequent release of proteolytic enzymes and, consequently, the destruction of the skin substrate. This process, known as "photoaging", can lead to an increase in matrix metalloproteinases (MMPs) in the skin through the pathway of mitogen-activated protein kinase (MARK) . Thus, if the activity and / or expression of matrix metalloproteinases in the MARK pathway or cells can be inhibited, the effects of enhancement / management for skin quality can be achieved.

In fact, it has been previously known that some substances can be used to modulate MMPs activity. For example, U.S. Patent No. 8,853,271 has found that tormentic acid has an excellent effect in inhibiting MMPs activity and further improves and restores skin. Chinese Patent No. 105,087,735, in turn, refers to polypeptides obtained from fish skin gelatin that can inhibit an increase in MMPs content after exposure to ultraviolet light. In addition, U.S. Patent No. 7,618,638 provides a method for extracting ganoderma mushrooms that exhibits MMP inhibitory properties that aid skin aging and other disorders.

Nevertheless, there is a need for a different and efficient method of inhibiting the signs of exogenous skin aging and premature skin aging mediated by overexpression of MMPs, particularly MMP-1, which is still responsible for the degradation of one of the most important components of the extracellular matrix There is a need in the industry for methods.

In a search for combinations of molecules and molecules that exhibit superior ability to inhibit MMPs, particularly MMP-1, the inventors of the present invention have found that synergistic hydroxamic acid, salt and / A combination of the amount of the complex and the amount of the glycol. The level of this synergy of inhibition of MMPs is only obtained when these specific molecules are used together, according to the methods described herein.

The present invention relates to a method for the preparation of a medicament comprising a matrix metalloprotein (R) within the skin comprising topical application to the skin surface of a composition comprising a ratio effective to the synergistic action of the amount of hydroxy triacid, its salt and / And methods of inhibiting the activity of anase. In some embodiments, the ratio of the weight percent of hydroxamic acid, its salt and / or complex thereof to the weight percent of glycol is about 1 to 1.4 (based on the weight of the total composition); About 1 to 3; Is selected from a ratio of about 1 to 5.

Also included are related methods, including methods of preventing or reducing the appearance of aging of the skin surface, the method comprising administering to the skin an effective amount of at least one compound effective to increase the amount of hydroxamic acid, its salt and / The topical application of the composition to the skin surface; Methods of increasing the enzymatic inhibition potential of glycols include combining at least one glycol with a synergistically effective amount of hydroxamic acid, a salt thereof and / or a combination thereof to form a synergistic mixture, Enzymatic inhibition potential of the synergistic mixture is greater than the enzymatic inhibition potential of glycol alone or hardroxenic acid alone.

Within the scope of the present invention there is also provided a pharmaceutical composition which inhibits the activity of matrix metalloproteinases (MMPs) in the skin, comprising a ratio effective to the synergistic action of the amount of hydroxamic acid, its salt and / or complex thereof and the amount of glycol Anti-aging compositions are contemplated. In some embodiments, the ratio is about 1 to 1.4; About 1 to 3; (By weight of the total composition) of about 1 to 5 percent by weight of the composition.

The foregoing summary, as well as the following detailed description of preferred embodiments of the invention, will be better understood when read in conjunction with the appended drawings. BRIEF DESCRIPTION OF THE DRAWINGS For the purpose of this description, there are shown currently preferred embodiments in the drawings. It should be understood, however, that the invention is not limited to the precise arrangements and means shown.
Figure 1 shows data obtained from Example 1 as a synergistic index of a test composition such as calculated by the percent of MMP-1 activity and the Kull equation.
Figure 2 shows the data obtained from Example 2 as a synergy of the test composition as calculated by the percent of MMP-1 activity and the curl equation.
Figure 3 shows the data obtained from Example 3 as a synergy of the test composition as calculated by the percent of MMP-1 activity and the curl equation.
Figure 4 shows the data obtained from Example 5 as the percent of MMP-1 activity and the synergistic index of the test composition as calculated by the curl equation.
Figure 5 shows the data obtained from Example 5 as the percent of MMP-1 activity and the synergistic index of the test composition as calculated by the curl equation.

As a result of the adverse environmental factors, degradation of collagen and other fibers of extracellular matrix of eukaryotic cells, preferably cells of connective tissue, and even more preferably cells of connective tissue of mammalian, May result in reduced skin quality, which is accounted for by the unhealthy appearance as well as the significant damage of elastic recoil. The invention described herein provides a solution - the invention described herein relates to the ability to prevent or reduce collagen degradation resulting from dysfunctional matrix metalloproteinases (MMPs) catalysis. In particular, compositions of glycols and organic acids surprisingly exhibit MMP-1 activity with an efficacy of 2, 3, 5, 6, and / or 7 times greater than the individual use of each of the substances, as assessed using the curl equation Lt; RTI ID = 0.0 > activity, < / RTI > This level of synergy has not previously been achieved and is highly promising for industrial applications in many other personal care and pharmaceutical products.

Thus, the invention described in the Background section inhibits skin collagen degradation by the use of such compositions in pharmaceuticals and in personal care, as well as modulation of the activity of collagenase, such as MMNP-1, preferably MMNP-1. Or < / RTI >

The invention described herein can protect the components of the extracellular matrix of mammalian connective tissue following exposure to environmental and lifestyle impairment factors such as sunlight, pollution or nicotine and diet.

As used herein, "collagen degradation" is intended to encompass the use of collagen protein fibers by mechanisms involving proteolytic enzymes, such as MMPs, particularly when such enzymes are activated and / or modulated by exogenous factors and / The destruction of In addition, as described herein, "inhibition of MMPs activity" means the use of a compound, or combination of compounds, to down-regulate MMPs proteolytic activity and, consequently, their ability to destroy collagen fibers.

Inhibition / non-inhibition of MMPs activity can be quantified using analytical techniques known or to be developed in the prior art. Suitable techniques include techniques for measuring MMPs proteolytic kinetics. Suitable techniques are found in the reaction kit, MMP-1 Inhibitor Screening Kit, supplied by Sigma Aldrich (St. Louis, Mo.).

A mixture of two components in an amount that provides synergistic activity is included in the methods of the invention. The glycols and organic acids of the present invention act synergistically when present together in an identified ratio.

In particular, the organic acid is a hydroxamic acid or a mixture of two or more hydroxamic acids. For use in the present invention, hydroxamic acid may comprise an alkylhydroxamic acid. Hydroxamic acids may exist in their free (un-neutralized) or salt (neutralized) forms, as well as salts and / or complexes (or combinations thereof). Also included are materials which are precursors of such compounds, salts and complexes which serve to form such compounds, salts and composites.

As described above, the hydroxamic acid (s) may be alkyl hydroxamic acid (s). Suitable alkyl hydroxamic acid (s) may have linear or branched carbon chains of about 2 to 22 carbon atoms, and preferably about 6 to 12 carbon atoms. Carbon chains can contain double bonds, i.e., unsaturated regions, and can also have functionality (substitution of functional groups for hydrogen atoms along the carbon chain, depending on the desired end use and properties).

For example, hydroxy groups may be side- or terminal-substituted on the chain of selected hydroxamic acids leading to better water compatibility. In personal care and / or pharmaceutical formulations Other similar functional groups that are compatible and / or meet the presumed standard for the use of the invention may be substituted for one or more hydrogen atoms.

Examples of compounds in which such substitutions are made include, but are not limited to, hexanohtydroxamic acid, caplylohydroxamic acid, caprohydroxamic acid, laurohydroxamic acid, .

In some embodiments, substituted or unsubstituted, selected for use in the present invention, hydroxamic acids include, for example, lipase catalysts, as well as hydroxamic synthesis techniques known or to be developed , And can be synthesized from one or more natural oils.

In some embodiments, as long as the synergistic ratio is maintained, the hydroxamic acid, salt or complex thereof, as described above, may be present in an amount of from about 0.001% to about 50%, from about 0.10% to about 45% %, From about 3% to about 30%, or from about 1% to about 20%. If precursors are used as components in accordance with an aspect of the present invention, the final amount of the desired formed compound in the compositions should be stated in percent by weight.

The methods and compositions of the present invention comprise the amount of glycol. Any combination of glycols or glycols suitable for personal care, pharmacy or human or animal consumption can be used. Suitable examples include, but are not limited to, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, heptylene glycol, caprylyl glycol capryl glycol, glycerin, ethylhexylglycerin, 1,2-hexanediol, propanediol, methylpropanediol, sorbitol, resorcinol, Etc., or a mixture of two or more of these.

In some embodiments, the glycol is present in the composition in an amount ranging from about 0.001% to about 50%, from about 5.0% to about 40.0%, from about 15.0% to about 35%, and from about 20.0% It may be desirable to be present in an amount of about 28%.

Notwithstanding the proposed amount for the total weight of the composition described above, the hydroxamic acid, its salt and / or its north complex and glycol are present in the composition in a ratio effective to synergism with each other. As used herein, the term " synergically effective ratio "refers to an amount (ratio (s)) of the remainder to provide inhibition of MMPs activity greater than inhibition of MMPs activity resulting from either alone of the substances ), Respectively.

Such synergistic effects may be measured or evaluated by any means known or to be developed in the prior art. However, some of the effects here considered synergistic were evaluated using curl equations. F.C. Kull et al., Applied Microbiology Vol. 9, pp. 538-541 (1961); David C. Steinberg, Cosmetics & Toiletries Vol. 115 (No. 110), pp. 59-62, November 2000; The synergism between two compounds, or combinations of compounds, is understood as the unique ability of such compounds, or combinations of compounds, to enhance or add to each other endogenous activity when evaluated simultaneously (synergy index < 1.0) . Two different combinations of two different mixtures or mixtures do not cause any progression to activity and no synergism is observed (synergy index = 1.0). On the other hand, when the same mixture causes a decrease or inhibition of endogenous activity, the mixture is characterized as an antagonist (synergy index> 1.0).

The curl equation is:

SI = CxD / A + CxE / B, where

"A" represents the reaction of the substance A, or the substance A, to the composition at time "t ".

"B" represents the response to the composition of material B, or of material B at time "t ".

"C " represents the reaction to mixture A + B at time" t ".

"D" represents the amount of A in C, and

"E" represents the amount of B in C.

In "amount of" it refers to the amount used in the test (the amount used in a or B) when used alone, divided by the amount used in the bond (the amount used in C).

In some embodiments, the effective ratio to the synergistic action of hydroxamic acid on the glycol is about 1 to 1.4; About 1 to 3; The ratio of the weight percent of hydroxamic acid, its salt and / or complex thereof to the weight percent of glycol selected from ratios of about 1 to 5 weight percent (based on the weight of the total composition) For example). In some embodiments, the ratio of hydroxamic acid to glycol is from about 1: 2 to about 1: 10; From about 1: 3 to about 1: 7; About 1: 4 to about 1: 5.

In some embodiments of the present invention, a mixture of hydroxamic acid, a salt thereof and / or a combination thereof and an antioxidant may allow topical application directly to the skin or other surface of the mixture and / For example, a personal care formulation or a pharmaceutical formulation, which allows easy delivery of the amount of the composition. Examples of suitable vehicles include, without limitation, water, distilled or pure water, alcohols, diols, glycols, esters, polyesters, vegetable oils, mineral oils, silicone oils, triglycerides, dimethylisosorbide dimethyl isosorbide, wax, talc, cornstarch, silica, chitosan, cellulose, tapioca, salts, and combinations thereof. In some embodiments, it may be preferred that the vehicle is a mixture of water and a polymer or emulsion.

Depending on the solubility and other physical-chemical properties of the glycol (s) and alkylhydroxanic acid (s) in the compositions of the present invention, solubilizers and / or emulsifiers are required in the compositions described herein . Examples of suitable solubilizing and / or emulsifying agents are glycerin, propylene glycol, butylene glycol, hexylene glycol, caprylyl glycol, ethylhexyl glycerin, methylpropanediol, propanediol, 1,2-hexanediol, But are not limited to, glyceryl caprylate, glyceryl undecylenate, propylene glycol dibenzoate, neopentyl glycol diheptanoate, ethanol, phenoxyethanol, phenethyl Phenol alcohol, benzyl alcohol, 2- (2-ethoxyethoxy) ethanol, polysorbate-20, polysorbate-60, polysorbate-80, alkyl glucoside, But are not limited to, cocamide, and dimethylisosorbide.

Preferably, the solubilizing agent and / or emulsifier is present in an amount of from 001% to 50.000%, or more preferably from 0.01% to 20.00%, by weight of the total composition of the present invention.

The compositions of the present invention may be topically applied (or otherwise introduced directly into the skin), preferably to the skin surface of the mammal, to inhibit or reduce MMPs activity. Alternatively, The compositions may be incorporated with secondary formulations, such as personal care formulations (including cosmetic or sanitary products) and medical and pharmaceutical formulations.

Such formulations include components other than the composition of the present invention. The components that may be present in the formulations will vary depending on the end user of the formulation, but may include colorants, fragrances, active ingredients, rheology modifiers, pigments, surfactants, , Silica, chitosan, alcohol, silicone, plant extract, gum, petrolatum, wax, ester, texturizer, UV filter, UV blocker, preservative, vitamins, starch and glycerin can do.

The formulations may be in the form of any desired product such as, for example, skin toners, skin cleansers, night creams, skin creams, shaving creams, skin care lotions, anti-aging skin products, or cosmetic products; Make-up, such as foundation, liquid and powder based make-up, mascara, lipstick, blush, gloss, eye-liner and the like; Or ointments, gel-creams, lotions, sunscreens, lip balms, perfumes, massage oils, shampoos, conditioners, conditioning shampoos, hair styling gels, hair restorers hair reparative, hair tonic, hair fixatives, hair mousse, bath and shower gel, liquid soap, moisturizing spray, make-up, compressed powder formulations, bath additives, Other household and / or pharmaceutical compositions, such as medicines, foam soaps, and body wash, sunscreen, sanitizing wipe, hand sanitizer, towelette and wipes, .

If the composition of the present invention is combined with a water-based secondary formulation, it may be desirable to prepare the composition as a hydrophilic delution and add it to the water phase of the secondary formulation.

With respect to oil- or silicone-based formulations, it may be preferred to prepare the compositions as hydrophobic dilutions and to add them to the oil-or silicone phase of the formulation. In solid formulations, the compositions may be the same as silica, talc, magnesium carbonate, magnesium aluminum silicate, kaolin, titanium dioxide, zinc oxide, starch, modified starch, But not limited to, a powdery matrix. Alternatively, the compositions may be prepared as an emulsified system, or as a hydrophilic system, or as a hydrophobic system, preferably between 35-45 C, at the end of the manufacturing process. Such formulations may be prepared using conventional or approaches to be developed.

The amount of composition present in any secondary formulation will vary depending on the end user of the formulation. However, in some embodiments it may be desirable to include a composition in an amount from about 0.01% to about 50%, from about 0.50% to about 20%, or from about 0.1% to about 5%, by weight of the total formulation. If the composition of the present invention is added to a formulation, it can be presumed and added to the formulation. Alternatively, each component of the composition may be added separately to the formulation.

The present invention also includes a method for increasing the enzymatic inhibition potential of glycol by binding at least one glycol to an amount effective for the synergistic action of hydroxamic acid, a salt thereof and / or a complex thereof, to form a synergistic mixture , The possibility of inhibition of the synergistic mixture is less than the inhibition potential of glycol alone. The resulting product can be used in pharmaceutical and consumer product applications.

All permutations of the above-described elements, including the presence or absence of an element, are contemplated within embodiments of the compositions, formulations, and / or methods of the present invention.

Example 1 - Inhibition of MMP-1 activity

Test composition 1 was prepared to contain caprylohydroxamic acid (3.5% w / w) diluted in ethanol (qsp 100% w / w). Test composition 2 contained butylene glycol (5.0% w / w) diluted in the same solvent as test composition 1. Finally, Test Composition 3 was prepared containing both diluted caprylohexanoic acid (3.5% w / w) and butylene glycol (5.0% w / w) as test compositions 1 and 2.

The inhibition of MMP-1 activity was assessed for each test composition 1-3 using the method described by Sigma Aldrich (St. Louis, Mo.), as described in the MMP-1 Inhibitor Screening Kit (cat. MAK212) Respectively.

Briefly, test compositions were stored at room temperature and diluted 25 times (in ethanol) to a final concentration of 0.4% (v / v) and analyzed 3 times. Ethanol was used as a negative control. GM6001, a potential metalloproteinase inhibitor (included in the kit), was used as both control at 13 nM. The kinetics of the release of the hydrolyzed FRET-labeled lipids were measured at a sensitivity (gain) of 40 using an Applied BioSystems Cytofluor 400 microplate fluorometer at an excitation / emission wavelength of 485/530 nm for 3 hours at 2 minute intervals Respectively. Subsequently, sub-signals were displayed, linear regression lines were established, and slopes (b) were calculated using the following formula:

Where x and y are the sample and time coordinates, respectively.

The% MMP-1 activity was determined according to the manufacturer's instructions:% MMP-1 activity = {[control (b) -sample b)] / control (b)} 100%.

A significant significance threshold was arbitrarily defined as a minimum of 20% modulation. The statistical significance was calculated by bilateral t-test and the significance level of p-value was set at 0.05 (the difference from the p-values lower than 0.05 was considered statistically significant).

Using the data, the synergy index for test composition 3 was calculated using the curl equation. Figure 1 shows the synergy index results for MMP-1 inhibition.

Example 2 - Inhibition of MMP-1 activity

In this example, Test Composition 4 was prepared to contain caprylohexaic acid (3.5% w / w) diluted in ethanol (qsp 100% w / w). Test composition 5 contained capryllyl glycol (5.0% w / w) diluted in the same solvent as test composition 4. Finally, Test Composition 6 was prepared containing both diluted caprylohexanoic acid (3.5% w / w) and caprylyl glycol (5.0% w / w) diluted as test compositions 4 and 5.

The evaluation of MMP-1 activity was carried out as in Example 1. Using the generated data, the synergy index for test composition 6 was calculated using the curl equation. Figure 2 shows the synergy index results for NNP-I inhibition.

Example 3 - Inhibition of MMP-1 activity

Test composition 7 was prepared to contain diluted caprylohexroic acid (3.5% w / w) in ethanol (qsp 100% w / w). Test composition 8 contained capryllyl glycol (5.0% w / w) diluted in the same solvent as test composition 7. Finally, Test Composition 9 was prepared containing both diluted caprylohexanoic acid (3.5% w / w) and caprylyl glycol (10.0% w / w) diluted as test compositions 7 and 8.

The evaluation of MMP-1 activity was carried out as in Example 1. Using the generated data, the synergy index for test composition 9 was calculated using the curl equation. Figure 3 shows the synergy index results for NNP-1 inhibition.

Example 4 - Inhibition of MMP-1 activity

Test composition 10 was prepared to contain caprylohexroic acid (3.5% w / w) diluted in ethanol (qsp 100% w / w). Test composition 11 was prepared by diluting ethylhexyl glycerin (2.0% w / w), methylpropanediol (2.0% w / w) diluted in the same solvent as test composition 10, propanediol (2.0% w / w) (2.0% w / w) and hexylene glycol (2.0% w / w /). Finally, a test composition 12 was prepared that contained both pools of caprylohexaic acid (3.5% w / w) and glycols (10.0% w / w) diluted as test compositions 10 and 11.

The evaluation of MMP-1 activity was carried out as in Example 1. Using the generated data, the synergy index for test composition 12 was calculated using the curl equation. Figure 4 shows the synergy index results for NNP-I inhibition.

Example 5 - Inhibition of MMP-1 activity

Test composition 13 was prepared to contain diluted caprylohexroic acid (1.5% w / w) in a 1: 2 hydroalcoholic solution (qsp 100% w / w). Test composition 14 contained sorbitol (5.0% w / w) diluted in the same solvent as Test Composition 13. Finally, a test composition 15 comprising both diluted caprylohexanoic acid (1.5% w / w) and sorbitol (5.0% w / w) diluted as test compositions 13 and 14 was prepared.

The evaluation of MMP-1 activity was carried out as in Example 1. Using the generated data, the synergy index for test composition 15 was calculated using the curl equation. Figure 5 shows the synergy index results for NNP-I inhibition.

It will be understood by those of ordinary skill in the art that changes may be made in the embodiments described above without departing from the broad inventive concept thereof. Accordingly, it is to be understood that the invention is not limited to the specific embodiments described, but is intended to cover modifications within the spirit and scope of the invention as defined by the appended claims.

Claims (14)

A composition for preventing skin aging comprising a ratio of hydroxamic acid, a salt thereof and / or a complex thereof and glycol in an effective ratio to synergism.
The composition of claim 1, wherein the ratio of the weight percent of the hydroxamic acid, its salt and / or complex thereof to the weight percent (by total composition) of the glycol is 1 to 1.4; 1 to 3; 1 < / RTI > to 5 < RTI ID = 0.0 >.≪ / RTI >
The composition for preventing skin aging according to claim 1, wherein the hydroxamic acid, a salt thereof and / or a combination thereof is an alkyl hydroxamic acid, a salt thereof and / or a complex thereof.
The skin antiaging composition according to claim 1, wherein the hydroxamic acid, its salt and / or complex thereof has a carbon chain selected from a chain of 2 to 22 carbon atoms and a chain of 6 to 12 carbon atoms .
The composition for preventing skin aging according to claim 1, wherein the hydroxamic acid, its salt and / or complex thereof has a branched carbon chain.
The composition for preventing skin aging according to claim 1, wherein the hydroxamic acid, its salt and / or complex thereof has a linear carbon chain.
The composition for preventing skin aging according to claim 1, wherein the hydroxamic acid, its salt and / or complex thereof has a carbon chain including at least one unsaturated region.
The composition for preventing skin aging according to claim 1, wherein the hydroxamic acid, its salt and / or complex thereof has at least one substitutional region.
9. The composition of claim 8, wherein the hydrogen atoms in the region of substitution are substituted with substituents which provide enhanced water compatibility with the hydroxamic acid, its salts and / or complexes thereof.
The composition for preventing skin aging according to claim 1, wherein the hydroxamic acid, a salt thereof and / or a complex thereof is synthesized from a natural oil.
The composition according to claim 1, wherein the hydroxamic acid, its salt and / or complex thereof is selected from hexanohydroxamic acid, caprylhydroxamic acid, caprohydroxamic acid, laurohydroxamic acid, and combinations thereof Wherein the composition is a composition for preventing aging of the skin.
The method of claim 1, wherein the glycol is selected from the group consisting of propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, heptylene glycol, caprylyl glycol, glycerin, ethylhexyl glycerin, Propanediol, sorbitol, resorcinol, and mixtures thereof. ≪ RTI ID = 0.0 > 11. < / RTI >
The composition for preventing skin aging according to claim 1, which is used for inhibiting collagen destruction, extracellular matrix breakage and wrinkling after MMPs activity in mammalian tissues.
A composition comprising the composition of any one of claims 1 to 13 and comprising at least one of a colorant, a perfume, an active ingredient, a rheological control agent, a colorant, a surfactant, silica, chitosan, alcohol, silicone, plant extract, Water, distilled water or pure water, alcohol, diols, glycols, esters, polyesters, vegetable oils, mineral oils, silicone oils, triglycerides, dimethylpolysiloxanes, Wherein the composition comprises a component selected from the group consisting of isosorbide, wax, talc, corn starch, silica, chitosan, cellulose, tapioca, salts and combinations thereof.

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