Palmitoyl lysylvalyl lysine mandelate

Abstract

The present invention relates to a mandelic acid addition salt of palmitoyl lysylvalyl-lysine and to cosmetic formulations containing said salt. Furthermore, the present invention relates to the use of mandelic acid for preparing a mandelic acid addition salt of palmitoyl lysylvalyl-lysine, which increases the storage stability of palmitoyl lysylvalyl-lysine.

Description

Detailed Description of the Invention

[0001] The present invention relates to a mandelic acid addition salt of palmitoyl lysylvalyl-lysine and to cosmetic formulations containing said salt. Furthermore, the present invention relates to the use of mandelic acid for preparing a mandelic acid addition salt of palmitoyl lysylvalyl-lysine, which increases the storage stability of palmitoyl lysylvalyl-lysine.

[0002] The excellent essential role of peptides makes them valuable cosmetic ingredients: they are involved in many physiological processes (e.g., increasing collagen production) and have various benefits (e.g., anti-wrinkle, reduced pigmentation, firming).

[0003] Palmitoyl-lysylvalyl-lysine bistrifluoroacetate, commercially available as SYN®-COLL from DSM Nutritional Products Ltd, is the bistrifluoroacetic acid addition salt of the synthetic tripeptide Pal-KVK and is widely used in cosmetic applications.

[0004] Trifluoroacetic acid (TFA) is usually used in peptide synthesis in the process of cleaving peptides from their respective resins, and also as an ion-pairing agent in HPLC purification.Therefore, synthetic peptides are generally in the form of TFA salts (TFA content up to 45%).In addition, TFA salts generally exhibit good solubility, which is a prerequisite for cosmetic applications.

[0005] However, cosmetic compositions containing TFAs and their salts are no longer fully appreciated by all consumers.

[0006] Therefore, there is a continuing need for alternative peptide salts that are TFA-free yet exhibit sufficient solubility and also provide good storage stability.

[0007] It has now surprisingly been found that the mandelic acid addition salt of palmitoyllysylvalyl-lysine overcomes the drawbacks of the prior art.

[0008] Thus, in a first embodiment, the present invention relates to the mandelic acid addition salt of palmitoyllysylvalyl-lysine (Pal-KVK).

[0009] The term "palmitoyllysylvalyl-lysine" includes all possible isomeric forms as well as mixtures thereof, including racemic mixtures and mixtures of rotamers.

[0010] In all embodiments of the present invention, palmitoyl lysylvalyl-lysine is preferably palmitoyl L-lysyl-L-valyl-L-lysine (CAS number 623172-55-4:N 2 -(1-oxohexadecyl)-L-lysyl-L-valyl-L-lysine).

[0011] It is well understood that in all embodiments of the present invention, mandelic acid can be used as D-(-)-mandelic acid (CAS No. 611-71-2), L-(+)-mandelic acid (CAS No. 17199-29-0) or D,L-mandelic acid (CAS No. 611-72-3), with D,L-mandelic acid being preferred for use in all embodiments of the present invention.

[0012] The molar equivalent of mandelic acid to palmitoyllysylvalyl-lysine is preferably selected within the range of 0.5 to 3 molar equivalents, preferably 0.75 to 2.5 molar equivalents, most preferably 0.8 to 2.25 molar equivalents, for example, 1.75 to 2.25 molar equivalents, based on palmitoyllysylvalyl-lysine, and more preferably 0.75 to 1.5 molar equivalents or 1 to 1.25 molar equivalents.

[0013] Preferably, in all embodiments of the present invention, the mandelic acid addition salt of palmitoyl lysylvalyl-lysine is N 2-(1-oxohexadecyl)-lysyl-valyl-lysine mandelic acid (peptide / acid molar equivalents of about 1:2), most preferably N 2 -(1-oxohexadecyl)-L-lysyl-L-valyl-L-lysine D,L-mandelic acid (molecular equivalent of peptide / acid is approximately 1:2).

[0014] In all embodiments of the present invention, the mandelate salts of palmitoyl lysylvalyl-lysine are preferably prepared by dissolving the respective acetate salt of palmitoyl lysylvalyl-lysine (e.g., prepared as outlined in Example 6 of U.S. Patent Application Publication No. 2007 / 0099842) in a suitable solvent to form a peptide acetate solution, combining the peptide acetate solution with a mandelic acid solution dissolved in a solvent (either by adding the peptide solution to the mandelic acid solution or vice versa), and then removing the solvent by suitable means such as evaporation and / or lyophilization.

[0015] Suitable solvents include C 10 solvents such as methanol, ethanol, propanol, and isopropanol. 1~6 Alkyl alcohols and acetic acid, and mixtures thereof with methanol and acetic acid, are included, and any mixtures thereof are particularly preferred.

[0016] The amount of solvent is preferably selected so that palmitoyl lysylvalyl-lysine acetate and mandelic acid are completely dissolved.

[0017] Thus, in a particularly preferred embodiment, the mandelate salt of palmitoyl lysylvalyl-lysine, with all of the definitions and preferences described herein, is (i) dissolving each palmitoyl lysylvalyl-lysine acetate in a solvent having all of the definitions and preferences described herein to form a peptide acetate solution; (ii) combining the respective mandelic acid and peptide acetate solutions dissolved in solvents having all of the definitions and preferences described herein; (iii) removing the solvent by evaporation, optionally and preferably followed by freeze-drying It is prepared by

[0018] In a preferred embodiment, the mandelic acid addition salt of palmitoyllysylvalyl-lysine, having all of the definitions and preferences described herein, is contained in a composition (also referred to herein as a peptide composition) further comprising at least one water-soluble polyol containing 2 to 10 carbon atoms and 2 to 7 hydroxyl groups, and optionally water.

[0019] In a particularly advantageous embodiment, the peptide composition according to the invention comprises: (i) 0.001 to 12.5% ​​by weight, in particular 0.01 to 2% by weight, and most in particular 0.1 to 0.5% by weight of the mandelic acid addition salt of palmitoyl lysylvalyl-lysine with all the definitions and preferences described herein; (ii) up to 99.999% by weight, in particular 40 to 80% by weight, and most in particular 60 to 75% by weight, of at least one water-soluble polyol containing 2 to 10 carbon atoms and 2 to 7 hydroxyl groups, and optionally (iii) up to 90% by weight, especially up to 50% by weight, most especially 0-35% by weight of water Includes:

[0020] Even more preferably, the peptide composition according to the invention comprises: (i) about 1000 to about 2000 ppm of the mandelic acid addition salt of palmitoyl lysylvalyl-lysine, with all of the definitions and preferences described herein; (ii) about 60 to about 75% by weight of glycerin and / or 1,3-propanediol, and (iii) about 24.9 to about 39.9 wt. % water Includes:

[0021] In a particularly advantageous embodiment, the sum of components (i) to (iii) in the peptide composition amounts to 100% by weight.

[0022] The peptide composition according to the present invention may further contain a surfactant and / or a thickener. Surfactants suitable for use in the peptide composition are those suitable for cosmetic applications. Such surfactants are well known to those skilled in the art, and include, for example, nonionic surfactants such as polysorbate 20. Thickeners suitable for use in the peptide composition are also those suitable for cosmetic applications, such as polyacrylic acid (carbomer).

[0023] In another embodiment, the present invention relates to the use of mandelic acid to increase the storage stability of palmitoyl lysylvalyl-lysine, preferably in a peptide composition comprising at least one water-soluble polyol containing 2 to 10 carbon atoms and 2 to 7 hydroxyl groups, with all of the definitions and preferences described herein, and optionally water, and / or in a topical formulation as defined herein.

[0024] Increased storage stability as defined herein refers to, for example, increased stability after 3 months of storage at 4°C, 22°C (room temperature) and 40°C compared to the respective methanesulfonyl sulfonate salt (preferably in glycerin) or 2-methoxy-2-phenylacetic acid addition salt (preferably in propanediol).

[0025] Preferably, the increase in storage stability at room temperature after 3 months is at least 10%, more preferably at least 15%, and most preferably at least 20%, compared to, for example, the respective methanesulfonyl sulfonate dissolved in glycerin or 2-methoxy-2-phenylacetic acid dissolved in propanediol.

[0026] The water-soluble polyol containing 2 to 10 carbon atoms and 2 to 7 hydroxyl groups is specifically selected from ethylene glycol, 1,2-propylene glycol, 1,3-propanediol (also referred to herein as propanediol), 1,4-butylene glycol, glycerin, erythritol (meso-1,2,3,4-butanetetrol), sorbitol, mannitol, methyl glucoside, diglycerin, triglycerin, and / or pentaerythritol. In particular, the polyol is glycerin or 1,3-propanediol, and most preferably glycerin.

[0027] In certain embodiments, the addition salt is (a) 0.05 to 1% by weight, preferably 0.1 to 1% by weight, and most preferably 0.2 to 0.5% by weight of the addition salt according to the present invention, (b) 15 to 50% by weight, preferably 20 to 40% by weight, and most preferably 25 to 35% by weight of panthenol; (c) 0.1 to 1% by weight, preferably 0.2 to 0.8% by weight, and most preferably 0.25 to 0.7% by weight of sodium hyaluronate; (d) 0.25 to 7% by weight, preferably 0.3 to 5% by weight, and most preferably 0.5 to 3% by weight of at least one algal extract; (e) 0.25 to 7 wt. %, preferably 0.3 to 5 wt. %, and most preferably 0.5 to 3 wt. % of pentylene glycol; (f) up to 1% by weight, preferably 0.001 to 1% by weight, of citric acid, and (g) more than 50% water It is used in the form of a blend consisting essentially of

[0028] The use of water to adjust the blend to 100% by weight is well understood by those skilled in the art.

[0029] The term "blend essentially consisting of," as used in accordance with the present invention, means that the total amounts of the listed components ideally add up to 100% by weight, but it is not excluded that small amounts of impurities or additives may be present, provided that the total amount of such impurities or additives is preferably less than 3% by weight, more preferably less than 2% by weight, and most preferably less than 1% by weight, introduced via the respective raw materials.

[0030] It is further appreciated that the (total) amount of water in the blend is the sum of the water added via each ingredient, e.g., via the aqueous algae extract, and the "free" water.

[0031] The blend is preferably a colorless to yellowish liquid, exhibiting a pH value of about 4.0 to 6.0, preferably 4.5 to 5.5, and a viscosity in the range of less than 3000 mPas, preferably less than 2000 mPas, most preferably less than 1500 mPas (measured on a Brookfield RVDV-II+ at 25°C, spindle 3, shear rate of 10 rpm for 30 seconds).

[0032] The algae extract in the blend according to the invention is preferably an extract of the biotechnologically produced microalgae Dunaliella Salina.

[0033] Such extracts can be obtained by culturing the respective algae and subsequently harvesting the cells. The harvested cells are then rehydrated and extracted with hot water. The crude extract is then centrifuged and ultrafiltered. In preparing the blend, the algal extract can be used in a dry form or in the form of a concentrated aqueous algal extract with a known solids content. Preferably, the algal extract is added to the blend in the form of a concentrated aqueous algal extract with a known algal extract content (solids). Aqueous algal extracts with an algal extract content selected in the range of 0.5-10% by weight, preferably 1-5% by weight, based on the total aqueous algal extract, are preferably used in preparing the blends according to the present invention. A suitable algal extract for use in preparing the blends according to the present invention is PEPHA®-CTIVE CB, which consists of 1-5% Dunaliella Salina extract, 1-5% pentylene glycol, 0.01-0.1% citric acid, and a total amount of water up to 100%.

[0034] Panthenol [CAS 81-13-0] is commercially available, for example, as D-Panthenol or D-Panthenol 75L from DSM Nutritional Products Ltd.

[0035] As used herein, the term sodium hyaluronate [CAS 9067-32-7] refers to the sodium salt of hyaluronic acid. Low molecular weight sodium hyaluronate, such as sodium hyaluronate having a molecular weight (MW) in the range of 10-800 kDa, preferably 200-600 kDa, and most preferably 200-400 kDa, is preferably used in the blends according to the present invention. Such sodium hyaluronate is available, for example, from DSM Nutritional Products Ltd under the trade name HYA-ACT™ S, and from Soliance under the trade name BasHyal (MW 100-300 kDa) or Renovhyal (MW 15-50 kDa). The use of HYA-ACT™ S, a low molecular weight hyaluronic acid of 200-400 kDa, is most preferred in all embodiments.

[0036] The addition salts, respective peptide compositions, and blends as defined herein can be incorporated into cosmetic formulations useful for improving skin appearance and physiology, such as reducing fine lines, wrinkles, and other symptoms associated with aging or photodamaged skin, treating stretch marks, or tightening, firming, and / or moisturizing the skin.

[0037] Thus, the present invention also relates to cosmetic formulations comprising the addition salts, the respective peptide compositions as defined herein, and a cosmetically acceptable carrier.

[0038] The term cosmetic preparation as defined herein specifically refers to a cosmetic preparation that can be applied topically to mammalian keratinous tissue, such as, for example, human skin or hair (including eyelashes, eyebrows) or nails, especially human skin.

[0039] The term "cosmetic preparation" as used in this application refers to cosmetic compositions as defined in the "Kosmetika" section of Römpp Lexikon Chemie, 10th edition 1997, Georg Thieme Verlag Stuttgart, New York, as well as in A. Domsch, "Cosmetic Compositions", Verlag für chemische Industrie (ed. H. Ziolkowsky), 4 th The present invention refers to the cosmetic compositions disclosed in the 1992 edition.

[0040] The term cosmetically acceptable carrier refers to all carriers and / or excipients and / or diluents conventionally used in cosmetic formulations.

[0041] In one advantageous embodiment, the cosmetic preparation according to the invention comprises from 50% to 99%, preferably from 60% to 98%, more preferably from 70% to 98%, for example in particular from 80% to 95%, of carrier, based on the total weight of the composition.

[0042] In particularly advantageous embodiments, the carrier in all embodiments of the present invention further comprises at least 30% by weight, preferably at least 40% by weight, more preferably at least 45% by weight, and most preferably at least 50% by weight of water, for example specifically 50 to 95% by weight, 50 to 80% by weight, 50 to 70% by weight, or 50 to 60% by weight of water.

[0043] The cosmetic formulations are in the form of suspensions or dispersions suspended or dispersed in solvents or fatty substances, or in the form of emulsions (including micro-, PIT, Pickering and multiple emulsions), in particular in the form of gels such as O / W or W / O types, hydrogels, alcoholic gels, lipogels, single- or multiphase solutions or vesicular dispersions, or other conventional forms, which are preferably also applicable by pen, mask or spray. If the cosmetic formulation is or comprises an emulsion, it can also contain one or more anionic, nonionic, cationic or amphoteric surfactants.

[0044] Preferred cosmetic formulations are skin care compositions and functional compositions.

[0045] The cosmetic formulation according to the invention can be in the form of a solution, lotion, thickened lotion, gel, cream, emulsion, ointment, paste, powder, make-up or solid tube stick, and can optionally be packaged as an aerosol and provided in the form of an aerosol mousse, a mousse such as a foam or spray foam, a spray, a stick, a bandage, a wash, a soap, a wipe or a lyophilisate.

[0046] The cosmetic preparations according to the invention are preferably formulated as oil-in-water or water-in-oil emulsions, water-in-silicone or silicone-in-water emulsions, or as aqueous serums or gels, in particular as oil-in-water emulsions (O / W emulsions).

[0047] In another preferred embodiment, the cosmetic preparation according to the invention is in the form of an aqueous gel and / or a transparent gel.

[0048] The cosmetic preparation according to the invention has a pH in the range of 3-10, preferably in the range of 4-8, most preferably in the range of 4-6.

[0049] According to the present invention, topical formulations may be used for skin whitening; sun protection; treatment of pigmentation disorders; prevention or reduction of acne, wrinkles, fine lines, atrophy and / or inflammation, and may optionally comprise further ingredients such as local anesthetics, antibacterial and / or antifungal agents, chelating and / or sequestrants, anti-cellulite and slimming agents (e.g., phytanic acid), firming agents, moisturizing and revitalizing agents, self-tanning agents, soothing agents, and agents for improving elasticity and skin barrier properties, and / or UV filter substances. The topical cosmetic formulations of the present invention may also contain conventional cosmetic adjuvants and additives, such as preservatives / antioxidants, fatty substances / oils, water, organic solvents, silicones, thickeners, emollients, emulsifiers, antifoaming agents, moisturizers, aesthetic ingredients such as fragrances, surfactants, fillers, sequestering agents, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorants / coloring agents, abrasives, absorbents, essential oils, skin sensates, astringents, antifoaming agents, pigments or nanopigments, e.g., those suitable for physically filtering ultraviolet light and thereby providing photoprotection, or any other ingredient typically incorporated into cosmetic formulations. Such cosmetic ingredients commonly used in the skin care industry and suitable for use in the cosmetic formulations of the present invention are described, for example, but not limited to, in the CTFA Cosmetic Ingredient Handbook, Second Edition (1992).

[0050] Conventional cosmetic adjuvants and additives, such as emulsifiers, thickeners, surface-active ingredients and film-formers, can exhibit synergistic effects, which can be determined by experts in routine testing or using the usual considerations for formulating cosmetic formulations.

[0051] The amount required can be readily determined by one of ordinary skill in the art based on the desired product. Cosmetic actives useful herein may in some cases provide more than one benefit or function by more than one mechanism of action.

[0052] Unless otherwise specified, the carriers, excipients, additives, diluents, adjuvants, and additives mentioned below are particularly suitable for cosmetic preparations according to the invention.

[0053] The following examples are provided to further illustrate the present invention. These examples are illustrative only and are not intended to limit the scope of the invention in any way.

[0054] [Example] Abbreviations: MA = mandelic acid (hydroxyphenylacetic acid) MSA = methanesulfonic acid MPAA = 2-methoxy-2-phenylacetic acid DAB: 1,4-diaminobutyric acid (building block in tripeptides)

[0055] Example 1: Preparation of various Palm-Lys-Val-Lys-OH addition salts 1.1 Palm-Lys-Val-Lys-OH * 2MA 2 g (2.73 mmol) Palm-Lys-Val-Lys-OH * To a solution of 2AcOH in 90% aqueous MeOH was added 0.852 g (5.60 mmol, 2.05 equiv.) of mandelic acid dissolved in 20 ml of MeOH. The mixture was stirred until a homogeneous solution was obtained. The MeOH was then first removed under reduced pressure, followed by lyophilization.

[0056] 1.2 Palm-Lys-Val-Lys-OH * 2MPAA (control) 500 mg (0.68 mmol) Palm-Lys-Val-Lys-OH *To a solution of 2AcOH in 90% aqueous MeOH was added 233 g (1.40 mmol, 2.05 equiv.) of methoxyphenylacetic acid. The mixture was stirred until a homogeneous solution was obtained. Then, MeOH was first removed under reduced pressure, followed by lyophilization.

[0057] 1.3 Palm-Lys-Val-Lys-OH * 2MSA (control) 200 mg (0.273 mmol) Palm-Lys-Val-Lys-OH * To a solution of 2AcOH in 90% aqueous MeOH was added 53.8 g (0.56 mmol, 2.05 equiv.) of methanesulfonic acid (MSA). The mixture was stirred until a homogeneous solution was obtained. The MeOH was then first removed under reduced pressure, followed by lyophilization.

[0058] Example 2: Preparation of peptide composition 2.1 Palm-Lys-Val-Lys-OH * 2MA-glycerin / water composition (MA-Gly) 100 mg of Palm-Lys-Val-Lys-OH prepared as outlined above * 2MA was placed in a 100 ml round-bottom flask. 21.0 g of water (from a total of 24.9 g) was added, and the peptide was dissolved briefly (approximately 5-15 seconds) in an ultrasonic bath at 85 °C. 58.1 g of glycerin (99.9%) was then added (pH adjusted to approximately 4.5 with aqueous NaOH (approximately 0.05 M)), followed by 3.36 g of water.

[0059] 2.2 Palm-Lys-Val-Lys-OH*2MA-1,3-propanediol (PDO) / water composition (MA-PDO) 100mg Palm-Lys-Val-Lys-OH *The 2-mandelate was placed in a 100 ml round-bottom flask. 21.4 g (from a total of 24.9 g) of water was added and the peptide was dissolved briefly (approximately 5-15 seconds) at 85 °C using an ultrasonic bath. 58.1 g of PDO (99.9%) was added (pH approximately 4.5), followed by 3.5 g of water.

[0060] 2.3 Palm-Lys-Val-Lys-OH * 2MSA-glycerin / water composition (MSA-Gly) 200mg Palm-Lys-Val-Lys-OH * 2MSA is placed in a 250 ml round-bottom flask. 33.2 g of water is added and the peptide is dissolved at approximately 80° C. Next, 132.3 g of glycerin (86.5%) is added (adjust the pH to approximately 4.5 with aqueous NaOH (approximately 0.05 M)).

[0061] 2.4 Palm-Lys-Val-Lys-OH * 2MPAA-1,3-propanediol (PDO) / water composition (MPAA-PDO) 100mg Palm-Lys-Val-Lys-OH * Place 2MPPA in a 100 ml round-bottom flask. Add 21.7 g of water and briefly (approximately 5-15 seconds) sonicate at 85 °C to dissolve the peptide. Add 58.1 g of PDO (99.9%) (pH approximately 4.5) followed by 3.2 g of water.

[0062] Example 3: Storage stability Colorless solutions of various salts of the tripeptide palmitoyl lysylvalyl-lysine (target initial peptide content: approximately 1200 ppm) dissolved in glycerin and 1,3-propanediol, respectively, prepared as outlined above, were stored at 4°C, 22°C (room temperature), and 40°C. After 3 months of storage, samples were analyzed for their peptide content using analytical HPLC. In addition, the color was assessed, i.e., whether it remained colorless or turned yellow (yellowish). The results are shown in Table 1.

[0063] [Table 1]

[0064] As can be seen from Table 1-a, the MA salts according to the invention show good stability on storage, whereas the MSA or MPAA salts, respectively, show a significant loss of activity on storage.

[0065] For comparison, the mandelate salt of tetradecyl Dab-Val-Dab-OH (also known as tetradecylaminobutyroylvalylaminobutyric acid urea mandelate) and the respective peptide compositions dissolved in glycerin and propanediol were prepared as outlined above (designated TDVD-MA-Gly and TDVD-MA-PDO). After storage at 40°C for 2 weeks, samples were analyzed for their peptide content using analytical HPLC. The results are listed in Table 1-b.

[0066] [Table 2]

[0067] As can be seen from Tables 1-a and 1-b, the MA salts according to the invention show good storage stability, whereas tetradecyl Dab-Val-Dab-OH mandelate shows a significant loss of activity already after 2 weeks.

[0068] [Example 4] Stability in cosmetic preparations

[0069] [Table 3]

[0070] [Table 4]

[0071] As can be seen from Table 3, the use of the glycerin composition results in improved stability in the final drug product compared to the use of the 1,3-propanediol composition.

[0072] [Table 5]

[0073] As can be seen from Tables 3 and 4, the MA salts according to the invention show significantly better stability on storage compared to the respective MPAA salts, the MPAA salts showing a loss of 52% of activity (at 40°C) already after one month, while the corresponding MA salts show only a loss of 19% after 3 months of storage at 40°C.

[0074] Example 5: Blend A blend consisting essentially of 1.25 g of palmitoyl lysylvalyl-lysine mandelate (D / L form), 150 g of D-panthenol (DSM Nutritional Products Ltd), 2.5 g of hyaluronic acid (HYA-ACT S, DSM Nutritional Products Ltd), 288 g of PEPHA-CTV (DSM Nutritional Products Ltd), 25 g of pentylene glycol (Hydrolite 5 green), and 55 g of ultrapure water was prepared. This blend showed excellent storage stability and recovery of the peptide after storage (2256 ppm after 3 months at 40°C).

[0075] Example 5: Exemplary Cosmetic Formulations Table 5 outlines exemplary O / W emulsions containing peptide compositions according to the present invention.

[0076] [Table 6]

[0077] [Table 7]

Claims

1. Mandelic acid addition salt of palmitoyl lysylvalyl-lysine.

2. The palmitoyl lysylvalyl-lysine is N ２ 2. The mandelic acid addition salt of claim 1, which is -(1-oxohexadecyl)-L-lysyl-L-valyl-L-lysine.

3. 3. The mandelic acid addition salt according to claim 1, wherein the mandelic acid is D-(-)-mandelic acid, L-(+)-mandelic acid, or D,L-mandelic acid, preferably D,L-mandelic acid.

4. 4. The mandelic acid addition salt according to claim 1, wherein the molar equivalent of mandelic acid in the mandelic acid addition salt is selected in the range of 0.5 to 3 molar equivalents based on palmitoyllysylvalyl-lysine.

5. The salt is prepared by reacting palmitoyl lysylvalyl-lysine acetate with C １～６ alkyl alcohol and / or acetic acid to form a peptide acetate solution, and １～６ and a solution of mandelic acid dissolved in alkyl alcohol and / or acetic acid, followed by evaporation and / or freeze-drying to obtain the C １～６ 5. The mandelic acid addition salt according to any one of claims 1 to 4, prepared by removing alkyl alcohol and / or acetic acid.

6. Said C １～６ 6. The mandelic acid addition salt of claim 5, wherein the alkyl alcohol is methanol.

7. 7. The mandelic acid addition salt of any one of claims 1 to 6, wherein the addition salt is contained in a composition further comprising at least one water-soluble polyol containing from 2 to 10 carbon atoms and from 2 to 7 hydroxyl groups.

8. The composition comprises: (i) 0.001 to 12.5% ​​by weight, in particular 0.01 to 2% by weight, and most in particular 0.1 to 0.5% by weight of said mandelic acid addition salt of palmitoyllysylvalyl-lysine; (ii) up to 99.999% by weight, particularly 40 to 80% by weight, most particularly 60 to 75% by weight, of at least one water-soluble polyol containing 2 to 10 carbon atoms and 2 to 7 hydroxyl groups; and (iv) up to 90% by weight, especially up to 50% by weight, most especially 0 to 35% by weight of water 8. The mandelic acid addition salt of claim 7, comprising:

9. 9. The mandelic acid addition salt of claim 8, wherein the total of components (i) to (iii) of the composition totals 100% by weight.

10. 10. Mandelic acid addition salt according to any one of claims 7 to 9, wherein the at least one water-soluble polyol containing from 2 to 10 carbon atoms and from 2 to 7 hydroxyl groups is selected from glycerin, 1,2-propylene glycol, 1,3-propanediol and / or 1,4-butylene glycol, preferably glycerin, 1,3-propanediol, most preferably glycerin.

11. The addition salt is (a) 0.05 to 1% by weight, preferably 0.1 to 1% by weight, and most preferably 0.2 to 0.5% by weight of said mandelic acid addition salt; (b) 15 to 50% by weight, preferably 20 to 40% by weight, and most preferably 25 to 35% by weight of panthenol; (c) 0.1 to 1% by weight, preferably 0.2 to 0.8% by weight, and most preferably 0.25 to 0.7% by weight, of sodium hyaluronate; (d) 0.25-7% by weight, preferably 0.3-5% by weight, and most preferably 0.5-3% by weight of at least one algae extract, preferably Dunaliella Salina extract; (e) 0.25 to 7 wt. %, preferably 0.3 to 5 wt. %, and most preferably 0.5 to 3 wt. % pentylene glycol; (f) up to 1% by weight, preferably 0.001 to 1% by weight, and most preferably 0.001 to 0.1% by weight, of citric acid; and (g) at least 50% by weight of water 11. The mandelic acid addition salt of any one of claims 1 to 10, contained in a blend consisting essentially of

12. A cosmetic preparation comprising the mandelic acid addition salt of palmitoyl lysylvalyl-lysine according to any one of claims 1 to 11 and a cosmetically acceptable carrier.

13. 13. The cosmetic composition of claim 12, wherein said carrier consists of at least 50% by weight of water.

14. 14. The cosmetic composition according to claim 12 or 13, wherein the composition is in the form of a gel or emulsion.

15. Use of mandelic acid to enhance the storage stability of palmitoyl lysylvalyl-lysine, preferably in a cosmetic formulation comprising a composition comprising at least one water-soluble polyol containing 2 to 10 carbon atoms and 2 to 7 hydroxyl groups, and / or a cosmetically acceptable carrier.

16. The use according to claim 15, wherein the at least one water-soluble polyol is glycerin or 1,3-propanediol.

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