KR20200117951A - Methods that inhibit matrix metalloproteinases and reduce aging in skin and related synergistic compositions - Google Patents

Abstract

The present invention comprises methods for inhibiting the activity of matrix metalloproteinases (MMPs) in the skin including topical application, to the skin surface, of a composition including an effective ratio for the synergistic action of the amount of a hydroxamic acid, a salt thereof, and/or a complex thereof and the amount of glycol. In some embodiments, the ratio of the weight percent of a hydroxamic acid, a salt thereof, and/or a complex thereof to the weight percent of glycol is selected from the ratio of approximately 1 to 1.4; approximately 1 to 3; and approximately 1 to 5 (with respect to the weight of the total composition). In addition, the present invention comprises related methods including methods for preventing or reducing the appearance of aging on the skin surface, wherein the method comprises topical application, to the skin surface, of the composition comprising the effective ratio for the synergistic action of the amount of a hydroxamic acid, a salt thereof, and/or a complex thereof and the amount of glycol. Methods for increasing the enzymatic inhibition potential of glycol comprise a step of combining at least one glycol with a hydroxamic acid, a salt thereof, and/or a complex thereof in the amounts in accordance with the effective ratio for the synergistic action to form a synergistic mixture, wherein the enzymatic inhibition potential of the synergistic mixture is greater than that of the glycol alone or the hydroxamic acid alone. The present invention also relates to anti-aging compositions which inhibit the activity of MMPs in the skin, including the effective ratio of the amount of a hydroxamic acid, a salt thereof, and/or a complex thereof and the amount of glycol for the synergistic action within the range of the present invention. In some embodiments, the ratio is selected from the weight percent of approximately 1 to 1.4; approximately 1 to 3; and approximately 1 to 5 (with respect to the weight of the total composition).

Description

BACKGROUND OF THE INVENTION Methods and related synergistic compositions for inhibiting matrix metalloproteinase and reducing aging in the skin TECHNICAL FIELD TECHNICAL FIELD

The present invention relates to the use of a matrix metalloproteinase in the skin comprising topical application to the skin surface of a composition comprising a proportion effective for synergistic effect of the amount of hydroxamic acid, its salts and/or their complexes and the amount of glycol. It relates to a method of inhibiting the activity.

The phenomenon of skin aging is determined by two unique biological processes that can occur simultaneously: endogenous and exogenous aging. Both cases progressively lead to loss of structural integrity and physiological function. Endogenous skin aging can vary from person to person, but is obviously a natural result of physiologically genetically determined changes over time that are inevitable. The clinical feature of endogenously aged skin is characterized by fine wrinkles with pale skin surfaces and sometimes exaggerated expressive lines. Functionally, endogenously aged skin is dry and less elastic than younger skin.

On the other hand, exogenous skin aging is to some extent controllable, which means that the environment, such as sunlight, pollution or nicotine, repetitive muscle movements such as frowning, as well as various lifestyles such as diet, sleeping position and overall health. Includes exposure to influences. Exogenously aged skin is exemplified by deep, healed wrinkles, mottled hyperpigmentation, and significant damage of elastic recoil.

The main factors associated with skin aging include the generation of reactive oxygen species (ROS), pigment alteration, reduced collagen synthesis, and induction of the activity of matrix metalloproteinases (MMPs, hereinafter referred to as MMPs). . The latter will promote collagen breakdown, ultimately leading to more powerful collagen damage. Without the provision of a collagen matrix, the skin sags and wrinkles appear. Under normal conditions, collagen levels are maintained by ensuring a balance between synthesis of new collagen and enzymatic degradation of previous collagen. In aged and/or photodamaged skin, the synthesis of procollagen in fibroblasts is naturally reduced and the expression of collagen-lowering enzymes is increased.

Metalloproteinases, including matrix metalloproteinases (MMPs), are a superfamily of proteolytic enzymes known to have a role in proteolytic destruction of almost all components of the extracellular matrix and connective tissue in mammals. superfamily). Based on structural and functional considerations, MMPs were identified as collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), and metalloella. Starases (mettaloelastases, MMP-12), MT (membrane type)-MMPs (MMP-14, -15, -16, -17, -24, and -25), matrilysins (MMP) -7 and -26), stromelysins (MMP-3, -10, and -11) and tumor necrosis factor, such as sheddases, such as TNF-converting enzymes (TACE and ACE). They have been classified into different families and subfamily. In particular, MMP-1 is known to be responsible for the lowering of I-type collagen, the most common form of collagen in the skin.

The basal expression of MMPs in young skin is relatively low. MMPs are activated by proteolytic enzymes naturally present in the skin, or thiol modifying agents (4-aminophenylmercuric acetate, mercury, N-ethylmaleimide), glutathione oxide It is activated in vitro by certain chemical agents such as (oxidized glutathione), chaotropic agents, and free radicals. Low pH and heat treatment can also lead to activity. However, lifestyle choices such as smoking and unprotected sunbathing downregulate basal expression of collagen I, III, and VI genes; Heat shock protein 47 (Hsp 47) genes also increase basal expression of substrate metalloproteinases 1 (MMP-1) and 9 (MMP-9). In fact, damage caused by sunlight promotes a state of chronic inflammation, which continues to release proteolytic enzymes and, as a result, destroy the skin matrix. This process, known as "photoaging", can lead to an increase in the matrix metalloproteinase (MMP) in the skin through the mitogen activated protein kinase (MARK, hereinafter referred to as MARK) pathway. . Thus, if the activity and/or expression of matrix metalloproteinases in the MARK pathway or cells can be inhibited, the effects of improvement/management for skin quality can be achieved.

Indeed, it has been previously known that some substances can be used to modulate MMPs activity. For example, U.S. Patent No. 8,853,271 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 a polypeptide obtained from fish skin gelatin, which can inhibit the increase in MMPs content after exposure to ultraviolet light. Additionally, US Pat. No. 7,618,638 provides a method for extracting ganoderma mushrooms, which exhibit MMP inhibitory properties that aid in skin aging and other disorders.

Nevertheless, a different and effective suppression of the signs of exogenous skin aging and premature skin aging mediated by overexpression of MMPs, especially MMP-1, still responsible for the deterioration of one of the most important components of the extracellular matrix in the skin. There is a need in the industry for the method.

In the search for molecules and combinations of molecules that exhibit excellent ability to inhibit MMPs, in particular MMP-1, the inventors of the present invention have found that hydroxamic acids, salts thereof and/or complexes thereof are effective for synergistic action. A combination of amount and amount of glycol was found. The level of this synergy of inhibition of MMPs is obtained only when these specific molecules are used together, according to the method described herein.

The present invention is a matrix metalloprotein in the skin comprising topical application to the skin surface of a composition comprising an amount effective for synergistic effect of the amount of hydroxamic acid, its salts and/or their complexes and the amount of glycol. Including methods of inhibiting the activity of Inase. In some embodiments the ratio of the weight percent of the hydroxamic acid, its salt and/or its complexes to the weight percent of glycol (to the weight of the total composition) is about 1 to 1.4; About 1 to 3; It is selected from a ratio of about 1 to 5.

Also included are related methods, including methods for preventing or reducing the appearance of aging on the skin surface, the method being effective for synergistic action of the amount of hydroxamic acid, its salts and/or its complexes and the amount of glycols. Topical application of the composition comprising the proportion to the skin surface; Methods of increasing the likelihood of enzymatic inhibition of glycols include the step of combining at least one glycol with an amount of hydroxamic acid, a salt thereof, and/or a complex thereof in a synergistically effective proportion to form a synergistic mixture, The likelihood of enzymatic inhibition of the synergistic mixture is greater than that of glycol alone or hardroxamic acid alone.

It is also within the scope of the present invention that inhibits the activity of matrix metalloproteinases (MMPs) in the skin, including a ratio effective for synergistic action of the amount of hydroxamic acid, its salts and/or its complexes 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; It is selected from a ratio of about 1 to 5, by weight percent (to weight of the total composition).

In addition to the previous summary, the detailed description of the preferred embodiments of the present invention below will be better understood when read in conjunction with the accompanying drawings. For purposes of explanation of the invention, presently preferred embodiments are shown in the drawings. However, it should be understood that the invention is not limited to the precise arrangements and means shown.
1 shows the data obtained from Example 1 as the percent of MMP-1 activity and the synergy index of the test composition as calculated by the Kull equation.
Figure 2 shows the data obtained from Example 2 as the percent of MMP-1 activity and the synergy index of the test composition as calculated by the curl equation.
Figure 3 shows the data obtained from Example 3 as the percent of MMP-1 activity and the synergy index of the test composition as calculated by the curl equation.
Figure 4 shows the data obtained from Example 5 as the percent of MMP-1 activity and the synergy 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 synergy index of the test composition as calculated by the curl equation.

As a result of harmful environmental factors, the deterioration of collagen and other fibers of the extracellular matrix of eukaryotic cells, preferably cells of connective tissue, even more preferably cells of mammalian connective tissue, leads to deep, coarse wrinkles and It can lead to marked impairment of elastic recoil as well as reduced skin quality, which is explained by an unhealthy appearance. The invention described herein provides a solution-the invention described herein relates to the ability to prevent or reduce collagen degradation resulting from catalysis of dysfunctional matrix metalloproteinases (MMPs). In particular, compositions of glycols and organic acids surprisingly inhibit MMP-1 activity with 2, 3, 5, 6, and/or 7 times greater effectiveness than the individual use of each substance, as assessed using the Curl equation. So, it has been proven to act synergistically. This level of synergy has not been achieved before and it is very promising for industrial applications in many other personal care and pharmaceutical products.

Accordingly, the present invention described herein inhibits skin collagen degradation by the use of such compositions in pharmaceutical and personal care as well as modulating the activity of collagenase, such as MMPs, preferably MMNP-1. And compositions that can be reduced or reduced.

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

As used herein, "collagen lowering" refers to collagen protein fibers by mechanisms including proteolytic enzymes, such as MMPs, particularly when such enzymes are activated and/or regulated by exogenous factors and/or factors. Means the destruction of people. Moreover, as described herein, "inhibition of MMPs activity" refers to 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 in the art or to be developed. Suitable techniques include techniques to measure the proteolytic kinetics of MMPs. A suitable technique is found in the reaction kit, MMP-1 Inhibitor Screening Kit, provided by Sigma Aldrich (St. Louis, Mo.).

Mixtures of the two components in amounts that provide synergistic activity are included in the methods of the present invention. The glycols and organic acids of the present invention act synergistically when present together in a confirmed 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 acids may include alkyl hydroxamic acids. Hydroxamic acids may exist in their free (non-neutralized) or salt (neutralized) form, as well as salts and/or complexes (or combinations thereof). Also additionally included are substances that are precursors of such compounds, salts and complexes, which act to form such compounds, salts and complexes.

As described above, the hydroxamic acid(s) can be an alkylhydroxamic acid(s). Suitable alkylhydroxamic 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 may contain double bonds, i.e. regions of unsaturation, and may also have functionality (substitution of functional groups for hydrogen atoms along the carbon chain, depending on the desired end use and properties).

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

Examples of compounds for which such substitutions have been made include, without limitation, hexanohydroxamic acid, caprylohydroxamic acid, caprohydroxamic acid, laurohydroxamic acid.

In some embodiments, the substituted or unsubstituted, hydroxamic acid selected for use in the present invention uses, for example, a lipase catalyst, as well as previously known or intended to be developed hydroxamic synthesis techniques. Thus, it 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, is from about 0.001% to about 50%, from about 0.10% to about 45, respectively, by weight of the total composition. %, from about 3% to about 30%, or from about 1% to about 20%. If precursors are used as components according to one aspect of the invention, the weight percent should be stated as the final amount of the desired formed compound in the compositions.

The methods and compositions of the invention comprise an amount of glycol. Any glycol or combination of glycols suitable for personal care, pharmaceutical or human or animal consumption may be used. Suitable examples include, without limitation, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, heptylene glycol, caprylyl glycol, glycerin, ethylhexylglycerin, 1,2-hexanediol, propanediol, methylpropanediol, Sorbitol, resorcinol, and the like, or mixtures of two or more thereof.

In some embodiments, the glycol is 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% to all total weight of the composition, as long as the synergy ratio is maintained. It may be desirable to be present in an amount of about 28%.

Notwithstanding the suggested amounts by weight of the total composition described above, the hydroxamic acids, their salts and/or their mixtures and glycols are present in the composition in a synergistically effective ratio with respect to each other. As used herein, the term "synergically effective ratio" refers to the amount of the remainder to provide for inhibition of MMPs activity greater than inhibition of MMPs activity resulting from either of the substances alone (ratio ) Means the presence of each substance.

Such synergistic effects can be measured or evaluated by any means known or intended to be developed. However, some effects considered synergistic here were evaluated using the curl equation. F.C. Kull et al., Applied Microbiology Vol. 9, pp. 538-541 (1961); By David C. Steinberg, Cosmetics & Toiletries Vol. 115 (No. 110), pp. 59-62, November 2000; see. The synergy between two compounds, or a combination 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 mixtures or two different combinations of mixtures do not cause any progress in the activity and no synergy 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 antogonist (synergy index> 1.0).

The curl equation is as follows:

SI = CxD/A + CxE/B, where

"A" denotes a reaction to substance A, or a composition of substance A, at time "t".

"B" denotes a reaction to substance B, or a composition of substance 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" this means the amount used in the test (amount used in a or B) when used alone divided by the amount used in the bond (amount used in C).

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

In some embodiments of the present invention, a mixture of hydroxamic acids, salts thereof and/or combinations thereof and antioxidants allows topical application of the mixture directly to the skin or other surface and/or as a secondary formulation, e.g. It is transported into a delivery vehicle that allows easy delivery of the amount of the composition, for example in a personal care formulation or pharmaceutical formulation. Examples of suitable vehicles include, without limitation, water, distilled or pure water, alcohols, diols, glycols, esters, polyesters, vegetable oils, mineral oils, silicone oils, triglycerides, dimethyl isosorbide, waxes. , Talc, cornstarch, silica, chitosan, cellulose, tapioca, salts and combinations thereof. In some embodiments, it may be desirable for the vehicle to be a water and polymer or emulsion mixture.

Depending on the solubility and other physico-chemical properties of the glycol(s) and alkylhydroxamic acid(s) in the compositions of the present invention, solubilizing and/or emulsifying agents may be required in the compositions described herein. . Examples of suitable solubilizing and/or emulsifying agents are glycerin, propylene glycol, butylene glycol, hexylene glycol, caprylyl glycol, ethylhexylglycerin, methylpropanediol, propanediol, 1,2-hexanediol, glyceryl capryl Rate, glyceryl undecylenate, propylene glycol dibenzoate, neopentyl glycol diheptanoate, ethanol, phenoxyethanol, phenethyl alcohol, benzyl alcohol, 2-(2-ethoxyethoxy)ethanol, polysorbate- 20, polysorbate-60, polysorbate-80, alkyl glucoside, cocamide, and dimethyl isosorbide.

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

The compositions of the present invention can be applied topically (or otherwise introduced directly into the skin) to the skin surface, preferably of a mammal, to inhibit or reduce the activity of MMPs. As an alternative, of the present invention The compositions can be integrated with personal care (including cosmetic or hygiene) formulations and secondary formulations, such as medical, pharmaceutical formulations.

Such formulations contain ingredients other than the composition of the present invention. The ingredients that may be present in the formulations will vary depending on the end user of the formulation, but dyes, fragrances, active ingredients, rheology modifiers, colorants, surfactants, silica, chitosan, alcohols, silicones, plant extracts, gums. (gum), petrolatum, wax, ester, texturizer, UV filter, UV blocker, preservative, vitamin, starch, and glycerin.

The formulations may be any desired product, such as, for example, skin toner, skin cleanser, night cream, skin cream, shaving cream, skin care lotion, anti-aging skin products, or cosmetic products; Make-ups, such as foundations, liquid and powder based make-ups, mascara, lipsticks, blush, gloss, eye-liners, and the like; Or ointment, gel-cream, lotion, sunscreen, lip balm, perfume, massage oil, shampoo, conditioner, conditioning shampoo, hair styling gel, hair reparative, hair tonic, hair fixatives, hair mousse , Bath and shower gels, liquid soaps, moisturizing sprays, makeup, compressed powder formulations, bath additives, ophthalmic agents, foam soaps, and body wash, sunscreens, sanitizing wipes, hand sanitizers, napkins And other household products and/or pharmaceutical compositions, such as wipes, etc.; can be prepared to be.

If the composition of the present invention is incorporated 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 a hydrophobic dilution and add them to the oil- or silicone phase of the formulation. In solid formulations, the compositions may be absorbed onto a powder substrate, such as, but not limited to, silica, talc, magnesium carbonate, magnesium aluminum silicate, kaolin, titanium dioxide, zinc oxide, starch, modified starch, and the like. As an alternative, the compositions may be prepared as an emulsified system, or as a hydrophilic system, or as a hydrophobic system, preferably between 35-45° C. and added at the final stage of the manufacturing process. Such formulations can be prepared using conventional or intended to be developed operations.

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 the composition in an amount of about 0.01% to about 50%, about 0.50% to about 20%, or about 0.1% to about 5% by weight of the total formulation. If the composition of the present invention is added to the formulation, it can be premised and added to the formulation. Alternatively, each component of the composition can be added individually to the formulation.

The present invention also includes a method of increasing the likelihood of enzymatic inhibition of glycols by binding at least one glycol to a synergistically effective amount of hydroxamic acid, a salt thereof and/or a complex thereof to form a synergistic mixture, However, the inhibitory potential of the synergistic mixture is more than that of glycol alone. The resulting product can be used in pharmaceutical and consumer product operations.

All permutations of the elements described above, 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 containing both diluted caprylohydroxamic acid (3.5% w/w) and butylene glycol (5.0% w/w) as Test Compositions 1 and 2 was prepared.

Inhibition of MMP-1 activity was evaluated for each test composition 1-3 using the method described in the MMP-1 Inhibitor Screening Kit (cat. MAK212) provided by Sigma Aldrich (St. Louis, Mo.). I did.

Briefly, test compositions were stored at room temperature, 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 (contained in the kit), was used as a positive control at 13 nM. The kinetics of the release of hydrolyzed FRET-labeled lipids were determined at a sensitivity (gain) of 40 with an Applied BioSystems Cytofluor 400 microplate fluorometer using excitation/emission wavelengths of 485/530 nm at 2 minute intervals for 3 hours. Was measured. After that the ruler signals were displayed, the linear regression lines were established and the slopes (b) were calculated using the following formula:

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

% MMP-1 activity was identified according to the kit manufacturer's instructions:% MMP-1 activity = {[control(b)-sampleb)]/control(b)}x100%.

Significance threshold was arbitrarily defined as at least 20% modulation. Statistical significance was calculated with a two-sided t-test, and the p-value significant threshold was set at 0.05 (differences from p values lower than 0.05 were considered statistically significant).

Using the data, the synergy index for Test Composition 3 was calculated using the Curl equation. 1 shows synergy index results for MMP-1 inhibition.

Example 2-Inhibition of MMP-1 activity

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

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. 2 shows the results of synergy index for NNP-1 inhibition.

Example 3-Inhibition of MMP-1 activity

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

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. 3 shows synergy index results for NNP-1 inhibition.

Example 4-Inhibition of MMP-1 activity

Test composition 10 was prepared to contain caprylohydroxamic acid (3.5% w/w) diluted in ethanol (qsp 100% w/w). Test composition 11 is ethylhexyl glycerin (2.0% w/w), methylpropanediol (2.0% w/w), propanediol (2.0% w/w), 1,2-hexane diluted in the same solvent as Test Composition 10 Prepared to contain a pool of glycols, including diol (2.0% w/w) and hexylene glycol (2.0% w/w/). Finally, as test compositions 10 and 11, test composition 12 containing both a pool of diluted caprylohydroxamic acid (3.5% w/w) and glycols (10.0% w/w) was prepared.

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. 4 shows synergy index results for NNP-1 inhibition.

Example 5-Inhibition of MMP-1 activity

Test composition 13 was prepared to contain caprylohydroxamic acid (1.5% w/w) diluted 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, as test compositions 13 and 14, a test composition 15 containing both diluted caprylohydroxamic acid (1.5% w/w) and sorbitol (5.0% w/w) was prepared.

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. 5 shows synergy index results for NNP-1 inhibition.

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

Claims (14)

A composition for preventing skin aging comprising a synergistically effective ratio of hydroxamic acid, a salt thereof and/or a combination thereof and a glycol.
The method of claim 1, wherein the ratio of the weight percent of the hydroxamic acid, its salt and/or its complexes to the weight percent of the glycol (to the total composition) is 1 to 1.4; 1 to 3; Composition for anti-aging skin, characterized in that selected from 1 to 5.
The composition for preventing skin aging according to claim 1, wherein the hydroxamic acid, a salt thereof, and/or a complex thereof is an alkylhydroxamic acid, a salt thereof, and/or a combination thereof.
The composition for preventing skin aging according to claim 1, wherein the hydroxamic acid, a salt thereof, and/or a 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 its complex has a branched carbon chain.
The composition for anti-aging skin according to claim 1, wherein the hydroxamic acid, its salt and/or its complex has a linear carbon chain.
The composition for anti-aging skin according to claim 1, wherein the hydroxamic acid, its salt and/or its complex has a carbon chain containing at least one unsaturated region.
The composition for anti-aging skin according to claim 1, wherein the hydroxamic acid, its salt, and/or a combination thereof has at least one area of substitution.
9. The composition for anti-aging skin according to claim 8, wherein the hydrogen atom in the region of substitution is substituted with a substituent that provides improved water compatibility for the hydroxamic acid, its salt and/or a combination thereof.
The composition for preventing skin aging according to claim 1, wherein the hydroxamic acid, its salt and/or its complex is synthesized from natural oil.
The method of claim 1, wherein the hydroxamic acid, its salt and/or a complex thereof is selected from hexanohydroxamic acid, caprylohydroxamic acid, caprohydroxamic acid, laurohydroxamic acid, and combinations thereof. Composition for preventing skin aging, characterized in that.
The method of claim 1, wherein the glycol is propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, heptylene glycol, caprylyl glycol, glycerin, ethylhexyl glycerin, 1,2-hexanediol, propanediol, methyl A composition for preventing skin aging, characterized in that it is selected from propanediol, sorbitol, resorcinol, and mixtures thereof.
The composition for preventing skin aging according to claim 1, which is used not only for MMPs activity in mammalian tissues, but also for subsequent destruction of collagen, destruction of extracellular matrix, and inhibition of wrinkle formation.
Containing the composition of any one of claims 1 to 13, and comprising a colorant, perfume, active ingredient, rheology modifier, colorant, surfactant, silica, chitosan, alcohol, silicone, plant extract, gum, petrolatum, wax , Ester, texturizer, UV filter, UV blocker, preservative, vitamin, starch, glycerin, water, distilled water or pure water, alcohol, diol, glycol, ester, polyester, vegetable oil, mineral oil, silicone oil, triglyceride, dimethyl A personal care formulation comprising an ingredient selected from isosorbide, wax, talc, cornstarch, silica, chitosan, cellulose, tapioca, salts and combinations thereof.

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