Compositions comprising acylated tetrapeptides for dermatological and cosmetic applications

Abstract

The present invention provides a formula (II) R 1 ‑X 1 ‑X 2 ‑X 3 ‑X 4 (II), its dermatologically acceptable salt, solvate and / or enantiomer, wherein R 1 represents a fatty acid residue having a chain length suitable for assisting the compound of formula (II) to penetrate the skin, and wherein X 1 represents a basic amino acid or a hydrophobic aromatic amino acid, X 2 represents basic amino acids, X 3 represents acidic amino acids, and X 4 represents a hydrophobic aliphatic amino acid or a polar neutral amino acid; a composition comprising: (a) formula (I) R-X 1 ‑X 2 ‑X 3 ‑X 4 (I), its dermatologically acceptable salts, solvates and / or enantiomers, wherein R represents a fatty acid residue having a chain length suitable for helping the compound of formula (I) penetrate the skin; and (b) a dermatologically acceptable carrier; an optionally acylated peptide of formula (I) for use in inhibiting or preventing the development of skin conditions; and a method for inhibiting or preventing the development of skin conditions, the method comprising the step of administering a peptide of formula (I) to a human or animal in need of such protection.

Description

Technical Field

[0001] The present invention relates to an improved skin care composition comprising an optionally acylated peptide of formula (I), an acylated peptide and a method of protecting the skin from damage. Background Art

[0002] It has been known for many years that lipid peroxides (also called lipid hydroperoxides or lipid peroxides) are produced in the skin when the skin is exposed to sunlight. This is not only due to the UVB wavelengths once thought, but also to UVA, infrared and visible wavelengths. Recent studies have found that several atmospheric pollutants (ozone, nitrogen dioxide, particulate matter and polycyclic hydrocarbons) and cigarette smoke also produce lipid peroxides in the skin.

[0003] Lipid peroxides are thought to be an important cause of changes that occur in the skin during aging, both for cosmetic effects such as wrinkles, roughness, thinning and brown spots, and for all three major types of skin cancer, which are increasing in incidence worldwide and are collectively the most common forms of cancer.

[0004] Lipid peroxide is produced by oxidation of lipid by reactive oxygen species (ROS). Solar radiation (e.g. sunlight), atmospheric pollutants and cigarette smoke induce the formation of lipid peroxide by producing ROS in the skin. Lipid peroxide and some molecules derived therefrom (e.g. MDA, 4-HNE) are toxic to cell membranes, destroy structural proteins (e.g. collagen and elastin) between cells, inhibit some antioxidant enzymes (e.g. superoxide dismutase), increase the secretion of matrix metalloproteinases (which digest collagen) of cells and damage DNA. All these effects are considered to contribute to the cosmetic changes of skin in the aging process, while damage to DNA is the cause of all types of cancer. After severe exposure to sunlight, lipid peroxide also contributes to the redness, soreness and pain (sunburn) of the skin. Lipid peroxide has acute effects (e.g. inflammation, pain and sunburn) and chronic effects (e.g. damage to cells, proteins, DNA; changes in enzyme activity; skin aging; and cancer).

[0005] Sunscreens and lotions attempt to reduce the damaging effects of sunlight by reflecting it, absorbing it or inhibiting the oxidative process (e.g. alpha-tocopherol). However, even in combination, they are only partially effective and then usually only last for a few hours. Some skin care products attempt to protect against atmospheric pollution by forming a barrier on the surface, but there is little evidence that this is effective.

[0006] No skin care product attempts to prevent the harmful effects of lipid peroxides once they form in the skin.

[0007] A method of alleviating these problems has been sought. Summary of the invention

[0008] According to the present invention, a composition is provided, which comprises (a) an acylated peptide of formula (I)

[0009] RX 1 -X 2 -X 3 -X 4 (I)

[0010] Its dermatologically acceptable salts, solvates and / or enantiomers, wherein R represents a fatty acid residue having a chain length suitable for helping the compound of formula (I) to penetrate the skin, X 1 represents a basic amino acid or a hydrophobic aromatic amino acid, X 2 represents basic amino acids, X 3 represents acidic amino acids, and X 4 represents a hydrophobic aliphatic amino acid or a polar neutral amino acid; and (b) a dermatologically acceptable carrier.

[0011] According to the present invention, there is also provided an acylated peptide of formula (II)

[0012] R 1 -X 1 -X 2 -X 3 -X 4 (II)

[0013] Its dermatologically acceptable salts, solvates and / or enantiomers, wherein R 1 represents a fatty acid residue having a chain length suitable for assisting the compound of formula (II) to penetrate the skin, and wherein X 1 , X 2 , X 3 and X 4 is as defined above for the peptide of formula (I).

[0014] According to the present invention there is provided an acylated peptide of formula (I) as defined above for use in inhibiting or preventing the development of a skin condition.

[0015] According to the present invention there is further provided a method of inhibiting or preventing the development of a skin condition, the method comprising the step of administering a peptide of formula (I) to a human or animal in need of such protection.

[0016] Advantages of the invention include the use of peptides, compositions and / or methods according to the invention, by using the peptides to sequester lipid peroxides, the damaging effects that lipid peroxides can cause in the skin can be partially or completely prevented; the peptides are small enough to penetrate the epidermis and dermis; and fatty acylation of the peptides will aid penetration into the skin by making the peptides more lipophilic. Further advantages include improved membrane integrity and function of cells in the epidermis and dermis; increased activity of antioxidant enzymes; reduced secretion of matrix metalloproteinases by fibroblasts (reduced collagen breakdown); reduced damage to proteins by MDA and 4-HNE and other reactive aldehydes derived from lipid peroxides; and reduced damage to DNA by MDA and 4-HNE and other reactive aldehydes. Penetration of the skin will reduce wash-off from sweating and swimming. The peptides will not reduce tanning or the production of vitamin D (the skin is an important source of the vitamin). In addition, protection will be against all wavelengths of sunlight known to damage the skin.

[0017] Several peptides are used in skin care products for their cosmetic effects, although for most of them, little or no efficacy data is available from clinical studies. One peptide with proven efficacy is Matrixyl Pentapeptide-4. TM ), Pal-Lys-Thr-Thr-Lys-Ser (pal-KTTKS), which stimulates the production of collagen, elastin, fibronectin, and glucosaminoglycans in the skin. Its effectiveness in reducing skin wrinkles has been demonstrated in double-blind placebo-controlled clinical studies. Another is palmitoyl tripeptide-3 / 5, Pal-Lys-Val-Lys (pal-KVK), which mimics the effects of the extracellular matrix protein thrombospondin-1, leading to increased collagen synthesis and has been shown to reduce wrinkles and increase skin smoothness. Tetrapeptide-21, Gly-Glu-Lys-Gly (GEKG), increases collagen and other matrix proteins and has been shown to improve skin elasticity to a similar degree to that achieved with palmitoyl pentapeptide-4. Acetyl hexapeptide-3, Acetyl-Glu-Glu-Met-Gln-Arg-Arg (Acetyl-EEMQRR), Argireline TM , inhibiting the release of neurotransmitters in the skin, thereby producing a transient "botulinum-like" effect (relaxation of the subcutaneous muscles).

[0018] Neither the above peptides nor any other peptides used in skin care products are known to chelate lipid peroxides.

[0019] The pro-inflammatory properties of lipid peroxides have been discussed as potential contributions to the pathogenesis of diseases, especially those of the cardiovascular system (Navab M. Circ Res 2005; 97: 524-32). However, their role in age-related changes in the skin and their cosmetic effects, which are not a result of inflammation but rather a result of changes in DNA integrity, collagen breakdown, elastin synthesis and enzyme activity, has not been considered. Aging of tissues, including that of the skin, is not a disease but an inevitable transition (Rattan SIS. Aging and Disease 2014; 5: 196-202), although its rate may be influenced by environmental factors.

[0020] In principle, the accumulation of lipid peroxides can be prevented by one or more of the following three mechanisms to prevent their long-term effects on the composition and structure of the skin: reducing their production, increasing their decomposition, or chelating them in a way that eliminates their biological activity. Sunscreens and antioxidants (such as vitamin E) can partially reduce production (Rinnerthaler M. Biomolecules 2015; 5, 545-589). In theory, decomposition can be enhanced by applying appropriate enzymes, although several enzymes are still required given the variable nature of lipid peroxides. In addition, they are unlikely to enter the skin when applied topically, and the role of the resulting end product is unclear. On the other hand, molecular chelation has several attractions.

[0021] The essential properties of an effective chelator of lipid peroxides in the skin are that the chelator (a) has a high binding affinity for them, and (b) can enter the epidermis and superficial dermis. The two main determinants of penetration into the skin are molecular size and lipophilicity. The smaller the size of the molecule and the greater the lipophilicity, the greater the permeability. Acylated tetrapeptides that irreversibly bind lipid peroxides are ideally suited for this purpose. In addition, such a molecule would have the additional property of binding to the surface membranes of cells (Resh MD. Current Biology 2013; 23: R431-5), thereby preventing its entry into the blood and ensuring that the peptide-peroxide complex is eventually shed during the normal desquamation process of keratinocytes. This mechanism also avoids the subsequent production of metabolites whose acute and chronic effects are unknown. Ideally, such an agent should also be biodegradable, unlikely to cause allergies during long-term use, and not cause a reduction in vitamin D production in the skin.

[0022] The sequential process of entry into the skin, sequestration of lipid peroxides, binding to cell surfaces, and eventual loss through desquamation provides a mechanism by which such molecules physically "cleanse" the skin without producing deleterious local or systemic biochemical effects.

[0023] Apolipoprotein mimetic peptides (AMPs) are short chains of amino acids that mimic some of the properties of apolipoproteins, the protein components of plasma lipoproteins (particles that carry fat in the blood). They first attracted the interest of cardiovascular disease researchers due to their ability to bind cholesterol and lipid peroxides, whose localized accumulation in arterial walls contributes to the development of atherosclerosis, the cause of coronary artery disease. When cholesterol and lipid peroxides are sequestered by AMPs, they are rendered harmless.

[0024] AMP has a binding affinity for lipid peroxides in vitro that is thousands of times greater than that for apolipoproteins (VanLenten et al., J Lipid Res 2008;49:2302). AMP binding to non-oxidized lipids does not interfere with the binding of lipid peroxides. AMP does not occur naturally and has not been commercially developed.

[0025] Most academic research on AMPs has been done using peptides that mimic the activity of a specific apolipoprotein, called apo A1, which is the main protein component of high-density lipoprotein, the carrier of so-called "good" cholesterol. Because apo A1 appears to remove cholesterol from artery walls and carry it to the liver, the hope is that intravenous infusions of AMPs that mimic its effects will reverse atherosclerosis. However, no AMPs have been successfully developed for this or any other use.

[0026] The AMP that initially generated the greatest interest among cardiovascular researchers was an 18 amino acid chain with the following amino acid sequence, which was designated 18A: DWLKAFYDKVAEKLKEAF (Anantharamaiah et al., J Biol Chem 1985;260:10248).

[0027] Subsequent work by the academic community produced successively smaller AMPs of only a few amino acids with similar biological activity, including two peptides with four amino acids: Lys-Arg-Glu-Ser (KRES) and Phe-Arg-Glu-Leu (FREL) (Navab et al., Circ Res 2005;97:524).

[0028] At a time when the pharmaceutical industry was interested in the potential of AMPs to reverse coronary artery disease, an 18-amino acid AMP that closely resembled the 18A peptide was infused intravenously into humans in a Phase 1 clinical study, but no further studies were conducted. Interest declined when it was found that it was quickly cleared from the blood (probably through the kidneys, the physiological pathway by which most natural peptides are eliminated). No adverse effects were reported.

[0029] Although AMPs share some of the physicochemical and biological properties of apolipoprotein, they do not share any part of its amino acid sequence (ie, they are not equivalent to small fragments of apolipoprotein). They are artificial molecules with no structural similarity to the proteins corresponding to their shared properties.

[0030] In some embodiments, R or R 1 Can represent the fatty acid residue of formula RC(O)-, wherein R represents saturated or unsaturated straight or branched chain alkyl having 12 to 24 carbon atoms. In some embodiments, R can represent palmitoyl or myristoyl.

[0031] In some embodiments, X 1 May represent phenylalanine, tyrosine, tryptophan, histidine, lysine or arginine.

[0032] In some embodiments, X 2 Can represent histidine, lysine or arginine.

[0033] In some embodiments, X 3 May represent aspartic acid or glutamic acid.

[0034] In some embodiments, X 4 It may represent alanine, valine, methionine, leucine, isoleucine, threonine, glutamine, cysteine, asparagine or serine.

[0035] In some embodiments, at position X 4 The amino acid at position X may depend on 1 In some embodiments, when X 1 When having a hydrophobic aromatic side chain (e.g., phenylalanine (F), tryptophan (W), or tyrosine (Y)), X 4 X may have a hydrophobic aliphatic side chain (e.g., leucine (L), alanine (A), isoleucine (I), methionine (M), or valine (V)). 1 When it is a basic amino acid (such as lysine (K), histidine (H) or arginine (R)), X 4 It may have a polar neutral side chain (eg, asparagine (N), cysteine ​​(C), glutamine (Q), threonine (T), or serine (S)).

[0036] In some embodiments, the optionally acylated peptide of formula (I) may be an optionally acylated peptide of formula (IA) or (IB)

[0037] KRES(IA)

[0038] FREL(IB)

[0039] wherein one or more amino acids are subjected to conservative substitutions, and wherein the optional acyl substituent is a fatty acid residue having a chain length suitable for facilitating the peptide of formula (IA) or (IB) to enter the epidermis and dermis of the skin. In some embodiments, the acylated peptide of formula (II) may be an acylated peptide of formula (IIA) or (IIB)

[0040] KRES(IIA)

[0041] FREL(IIB)

[0042] wherein one or more amino acids are subjected to conservative substitution, and wherein the acyl substituent is a fatty acid residue of a chain length suitable to assist the acylated peptide of formula (IIA) or (IIB) to penetrate the skin. Those skilled in the art will know what would constitute a conservative substitution of amino acids in the optionally acylated peptide of formula (IA) or (IB) or the acylated peptide of formula (IIA) or (IIB).

[0043] In some embodiments, the peptide of formula (I) may have the following formula:

[0044] KRES (SEQ ID NO: 1) (IC)

[0045] Palmitoyl-KRES (SEQ ID NO: 3) (ID)

[0046] Myristoyl-KRES (SEQ ID NO: 5) (IID)

[0047] FREL (SEQ ID NO: 2) (IE)

[0048] Palmitoyl-FREL (SEQ ID NO: 4) (IF)

[0049] Myristoyl-FREL (SEQ ID NO: 6) (IG).

[0050] In some embodiments, the peptide of formula (II) may have the following formula:

[0051] Palmitoyl-KRES (SEQ ID NO: 3) (IIC)

[0052] Myristoyl-KRES (SEQ ID NO: 5) (IID)

[0053] Palmitoyl-FREL (SEQ ID NO: 4) (IIE)

[0054] Myristoyl-FREL (SEQ ID NO: 6) (IIF)

[0055] In some embodiments, the method for inhibiting or preventing the development of skin conditions comprises the following steps: applying a safe and effective amount of a peptide of formula (I) disclosed herein topically to a treatment surface of the body in need of such treatment. The peptides as defined above include dermatologically acceptable salts, solvates and enantiomers thereof.

[0056] The peptides and compositions according to the present invention are effective in preventing a variety of skin conditions in which lipid peroxides play a role, including but not limited to sunburn, UV sensitivity, and the cosmetic effects associated with aging.

[0057] In some embodiments, a safe and effective amount of the peptides described herein are delivered topically to the skin of a human or animal (particularly a mammal). When applied topically, the peptides disclosed herein that are small in molecular size and lipophilic are able to effectively penetrate the upper layers of the skin.

[0058] In addition, it will be appreciated that the benefits of the present invention can be achieved by combining application with one or more additional skin care agents. In some embodiments, the composition according to the present invention may comprise additional skin care agents. In some embodiments, the method according to the present invention may additionally include application by additional skin care agents. In some embodiments, the additional skin care agents may be one or more of the following: desquamation agents, anti-acne agents, wrinkle repair agents, antioxidants, free radical scavengers, chelating agents, anti-inflammatory agents, local anesthetics, anti-cellulite agents, flavonoids, antimicrobial agents, antifungal agents, sunscreens and / or conditioning agents.

[0059] In some embodiments, additional skin care agents include sunscreens. As used herein, "sunscreens" refer to agents applied to the skin to physically (reflect) or chemically (absorb) protect against the acute and / or chronic harmful effects of solar radiation. Many sunscreens are known in the art and include one or more of the following: titanium dioxide, zinc oxide, PABA esters (e.g., glyceryl, padimate A and / or padimate O), salicylates (e.g., homosalate or octisalate), cinnamates (e.g., cinoxate, octyl methoxycinnamate or octocrylene), benzophenones, and / or ecamsule.

[0060] In some embodiments, the methods according to the invention comprise substantially simultaneous administration of a peptide of formula (I) and an additional skin care agent. In some embodiments, treatment with a peptide of formula (I) disclosed herein may be separated by a few minutes to a few weeks before or after administration of the additional skin care agent.

[0061] In some embodiments, the composition according to the present invention may be a skin care composition comprising (a) a safe and effective amount of a peptide of formula (I), and (b) one or more dermatologically acceptable carriers.

[0062] "Dermatologically acceptable carrier" herein refers to a carrier that is suitable for topical application to the skin, has good aesthetic properties, is compatible with the actives and any other components disclosed herein, and does not cause any safety or toxicity issues. In some embodiments, a safe and effective amount of the carrier is from about 50%, particularly from about 60%, more particularly from about 70% to about 99.99%, particularly to about 99.9%, and more particularly to about 98% by weight of the composition.

[0063] The dermatologically acceptable carrier used in the present invention can be one of various types. For example, suitable types include emulsion carriers, including but not limited to oil-in-water, water-in-oil, water-in-oil-in-water or oil-in-water-in-oil emulsions. In some embodiments, silicone can also be used as oil, so that potential emulsion carriers include silicone-in-water, water-in-silicone, water-in-water-in-silicone and water-in-water-in-silicone emulsions. Dermatologically acceptable carriers can also take one of various forms, and its non-limiting examples include liquid, milk, serum, paint, cream, spray, aerosol, mousse, foam, stick, gel and pen-shaped object. It may also include liposomes or nanoparticles.

[0064] In some embodiments, emulsions used as dermatologically acceptable carriers may include aqueous solutions and lipids and / or oils. Suitable lipids and / or oils may be derived from animals, plants, or petroleum, and may be natural or synthetic (i.e., artificial, such as silicones).

[0065] In some embodiments, the emulsion may also include a humectant, such as glycerol. In some embodiments, the emulsion may also include an emulsifier, such as from about 0.05%, more particularly from about 0.1% to about 10%, more particularly to about 5% emulsifier based on the weight of the composition. Suitable emulsifiers may be nonionic, anionic or cationic. Suitable emulsifiers are disclosed in, for example, McCutcheon's 2013 Emulsifiers and Detergents, North American Edition (2013). Suitable emulsions may have a wide range of viscosities, depending on the desired product form.

[0066] In some embodiments, the peptides of this patent can be used alone or in combination with each other in the composition or method according to the present invention at a concentration of about 0.1 to about 1000 ppm, preferably 1 to 100 ppm.

[0067] In some embodiments, the composition according to the present invention can be a topical composition comprising from about 20% to about 50% by weight of the carrier of propylene glycol and from about 50% to about 80% by weight of the carrier of water as a dermatologically acceptable carrier, the pH adjusted to 4.0 with 10 mM citric acid.

[0068] In some embodiments, skin conditions prevented by the present invention include cosmetic skin conditions such as wrinkles, roughness, freckles (brown spots), and sun damage.

[0069] The peptides of formula (I) and (II) disclosed herein can be synthesized from their constituent amino acids or their derivatives by conventional chemical synthesis in solution or solid phase procedures based on the Fmoc / tBu method and now widely used in the cosmetics and skin care industry (Amblard et al., Mol Biotechnol 2006; 33: 239), and purified by reverse phase HPLC. Alternatively, enzymatic synthesis can be used. Fatty acid acylation of the peptide enhances penetration into the outer layers of the skin by making it more lipophilic. Covalent attachment of fatty acids (e.g. palmitic acid or myristic acid) to the N-terminal amino acid of small peptides is readily achieved by established chemical procedures (Lumbierres et al., Chemistry-A European Journal. 2005; 11: 7405).

[0070] The efficacy of the peptides was evaluated first in vitro and then in healthy humans.The invention will now be illustrated with reference to the following examples which are not intended to limit the scope of the claimed invention. Example

[0071] Example 1

[0072] In vitro testing of the efficacy of the peptides of formula (I) according to the present invention will utilize monolayer cultures of normal human skin keratinocytes and fibroblasts. A validated procedure for quantifying the effects of metabolic changes induced by UVA (320-400nm), UVB (280-320nm) and infrared A (near IR) (700-1400nm) irradiation will be employed. Measurements will include ROS production; messenger RNA abundance of matrix metalloproteinase-1, collagen, and elastin; secretion of matrix metalloproteinase-1 into the culture medium; secretion of interleukin-1 and interleukin-6 (proinflammatory cytokines) into the culture medium; and two or more of the established indicators of DNA damage. In addition, a commercially reconstructed full-thickness human skin model (T-Skin) that has been independently validated (Alépée et al. (Toxicol in vitro 2015; 29: 1779) may be used. TM ) (Episkin, Lyon, France) measures one or more of the effects on cell viability, interleukin-1 production, and DNA damage (pyrimidine dimer production).

[0073] Example 2

[0074] The clinical effect of the peptide will be evaluated by four randomized, double-blind, placebo-controlled trials in a group of healthy women aged 30-65 years (each serving as her own control). First, the test peptide in a suitable carrier is applied to the skin wrinkles at the outer corner of one eye (the so-called crow's feet), and a placebo consisting of the same amount of carrier without the peptide is applied to the corresponding area of ​​the skin on the other side. The application will be carried out morning and evening for 42 days, and the measurement of wrinkle depth will be carried out at the beginning and end of this time by video computer analysis of silicone "fingerprints" of the skin surface, as described by Corcuff et al. (Int. J. Cosm. Sci. 1985; 17: 126). The study will be conducted in 40-50 healthy subjects.

[0075] The in vivo effects on the skin will also be evaluated in a second double-blind trial in different groups of 40-50 healthy women, where the test peptide and placebo will be applied morning and evening on different sides of the face for 42 days. At the beginning and end of the treatment period, skin roughness will be measured by rapid optical in vivo topography (3-D imaging) as described by Kaczvinsky JR et al. (J Cosmet Dermatol 2009; 8: 228).

[0076] In a third trial, the test formulation and placebo were applied to the left and right forearms of 10 healthy women aged 30-65 years twice daily for 42 days. At the beginning and end of the study, biopsies of the corresponding areas of skin on each side were obtained and pyrimidine dimers and 8-oxo-7,8-dihydro-2-deoxyguanosine (an indicator of DNA damage) were measured as described by Emanuele et al. (J Drugs Dermatol 2014; 13: 309). Sequence Listing <110> Norman E. Miller Irina Miller <120> Compositions comprising acylated tetrapeptides for dermatological and cosmetic applications <130> JH / MB / 11652 <160> 6 <170> PatentIn version 3.5 <210> 1 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Apolipoprotein mimetic peptide <400> 1 Lys Arg Glu Ser 1 <210> 2 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Apolipoprotein mimetic peptide <400> 2 Phe Arg Glu Leu 1 <210> 3 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Apolipoprotein mimetic peptide <220> <221> LIPID <222> (1)..(4) <223> PALMITATE <400> 3 Lys Arg Glu Ser 1 <210> 4 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Apolipoprotein mimetic peptide <220> <221> LIPID <222> (1)..(4) <223> PALMITATE <400> 4 Phe Arg Glu Leu 1 <210> 5 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Apolipoprotein mimetic peptide <220> <221> LIPID <222> (1)..(4) <223> MYRISTATE <400> 5 Lys Arg Glu Ser 1 <210> 6 <211> 4 <212> PRT <213> Artificial sequence <220> <223> Apolipoprotein mimetic peptide <220> <221> LIPID <222> (1)..(4) <223> MYRISTATE <400> 6 Phe Arg Glu Leu 1

Claims

1. A composition comprising: (a) Acylated peptide of formula (I) R-X 1 -X 2 -X 3 -X 4 (I), or a dermatologically acceptable salt thereof, wherein R represents a fatty acid residue having a chain length suitable for assisting the compound of formula (I) to penetrate the skin, and wherein R is of the formula R 2 C(O)-, where R 2 represents a saturated or unsaturated straight or branched chain alkyl group having 12 to 24 carbon atoms, X 1 represents a basic amino acid or a hydrophobic aromatic amino acid, X 2 represents basic amino acids, X 3 represents acidic amino acids, and X 4 represents a hydrophobic aliphatic amino acid or a polar neutral amino acid, wherein the acylated peptide of formula (I) is as follows: palmitoyl-KRES (SEQ ID NO: 3); and (b) a dermatologically acceptable carrier.

2. The composition of claim 1 comprising an additional skin care agent.

3. The composition of claim 2, wherein the additional skin care agent is one or more of the following: a desquamative agent, an anti-acne agent, a wrinkle repair agent, an antioxidant, a free radical scavenger, a chelating agent, an anti-inflammatory agent, a local anesthetic, an anti-cellulite agent, a flavonoid, an antimicrobial agent, a sunscreen agent and / or a conditioning agent.

4. The composition of claim 2, wherein the additional skin care agent is an antifungal agent.

5. The composition of claim 2, wherein the additional skin care agent comprises a sunscreen.

6. The composition of claim 1 or claim 2, which is a skin care composition comprising (a) a safe and effective amount of an acylated peptide of formula (I), and (b) one or more dermatologically acceptable carriers.

7. The composition of claim 1 or claim 2 comprising the acylated peptide of formula (I) at a concentration of 0.1 ppm to 1000 ppm.

8. Acylated peptide of formula (I) R 1 -X 1 -X 2 -X 3 -X 4 (I), or a dermatologically acceptable salt thereof, wherein R 1 represents a fatty acid residue having a chain length suitable for assisting the compound of formula (I) to penetrate the skin, and wherein R 1 Formula R 2 C(O)-, where R 2 represents a saturated or unsaturated straight or branched chain alkyl group having 12 to 24 carbon atoms, and wherein X 1 , X 2 , X 3 and X 4 is as defined in claim 1 or claim 2 with respect to an acylated peptide of formula (I), The acylated peptide is an acylated peptide represented by the following formula: palmitoyl-KRES (SEQ ID NO: 3).

9. Use of an acylated peptide of formula (I) as claimed in claim 1 or claim 2 for the preparation of a medicament for use in a method for inhibiting or preventing the development of UV-induced skin damage.