Fatty acid esters of hydroxy fatty acid

Abstract

Disclosed herein are compositions comprising fatty acid esters of hydroxy fatty acid (FAHFA), and their uses. The preferred embodiment for FAHFA is palmitic acid esters of hydroxystearic acid, stearic acid esters of hydroxystearic acid, lauric acid esters of hydroxystearic acid and oleic acid esters of hydroxystearic acid. The uses of the FAHFA include treating dry and / or scaly skin, or preventing trans-epidermal water loss (TEWL).

Description

FATTY ACID ESTERS OF HYDROXY FATTY ACIDFIELD OF THE INVENTION

[0001] The present invention relates generally to the field of organic chemistry. In particular, the present invention relates to the preparation and use of fatty acid esters of hydroxy fatty acid (FAHFA) and their use.BACKGROUND OF THE INVENTION

[0002] Ceramides are a structurally heterogeneous and complex group of sphingolipids that account for 50% of skin lipids. It is well known that ceramides play an essential role in structuring and maintaining the water permeability barrier function of the skin. Ceramides enhance the skin’s capacity for moisture retention, rejuvenates the skin’s surface, restores skin tone and helps maintain overall dermal wellness. The secretion of ceramides decreases with age, leading to dry skin, dermal infections and sensitive epidermis.

[0003] Thus, there is an unmet need for cosmetic ingredients which can mimic the role of ceramides in skin.SUMMARY

[0004] In one aspect, provided herein is a composition comprising at least one fatty acid ester of hydroxy fatty acid (FAHFA), wherein the at least one fatty acid ester of hydroxy fatty acid is of the formula (I):wherein n1is a C12-alkyl, a C14-alkyl, a C16-alkyl, C18-alkyl, C20-alkyl, C22-alkyl, or C24- alkyl; wherein n2is a C1- to C15-alkyl; wherein n is a C1- to C15alky, wherein the sum of carbon atoms of n2and n3is 15; and wherein the fatty acid ester of hydroxy fatty acid (FAHFA) is a free fatty acid.

[0005] In another aspect, provided herein is a method of treating dry and / or scaly skin, wherein the method comprises applying the composition of any one of the preceding claims to the dermal surface of a subject in need thereof.

[0006] In another aspect, provided herein is a method of preventing trans-cpidcrmal water loss (TEWL), wherein the method comprises applying the composition of any one of the preceding claims to the dermal surface of a subject in need thereof.

[0007] In another aspect, provided herein is a method of preparing a fatty acid ester of hydroxy fatty acid of Formula (I):the method comprising the steps of: contacting a hydroxy fatty acid with a fatty acid; wherein said contact results in production of a fatty acid ester of hydroxy fatty acid of Formula (I) as defined in claim 1.BRIEF DESCRIPTION OF THE DRAWINGS

[0008] The invention will be better understood with reference to the detailed description when considered in conjunction with the non-limiting examples and the accompanying drawings, in which:

[0009] Figure 1 is a diagram showing the similarities in the molecular structures of ceramide and fatty acid esters of hydroxy fatty acid (FAHFA). Figure 1A shows the molecular structure of ceramide. Figure IB shows the molecular structure of palmitic acid esters of 3 -hydroxy stearic acid (3-PAHSA). Figure 1C shows the molecular- structure of palmitic acid esters of 5 -hydroxy stearic acid (5-PAHSA). Figure ID shows the molecular structure of palmitic acid esters of 12-hydroxystearic acid (12-PAHSA). Highlighted in pink arc polar atoms that form hydration centres and bind to water by hydrogen bonds.

[0010] Figure 2 is a diagram showing the general enzymatic synthesis reaction of palmitic acid esters of hydroxy stearic acid (PAHSA) and stearic acid esters of hydroxystearic acid (SAHSA) by immobilised Candida antarctica lipase A (IM-CalA). Palmitic acid (PA) in an amount of 0.8 grams and 1 gram of 12-hydroxystearic acid (12- HSA) were added to a 20 mL glass vial. Immobilised Candida antarctica lipase A (IM- CalA) in an amount of 150 mg was then added. The synthesis reaction was performed with an Eppcndorf thermomixer, open capped, at 70°C and at 1000 rpm. After 8 hours, a small amount of crude mixture was aliquoted, derivatized with BSTFA+TMCS and analysed withgas chromatography with flame ionization detection (GC-FID). Recrystallization was performed by melting the crude mixture at 60°C and incubating in a 30°C oven. The crystal was removed by centrifugation at 6000 g for 20 minutes).

[0011] Figure 3 is a diagram showing the general synthesis scheme of fatty acid esters of hydroxy fatty acid (FAHFA). A hydroxy stearic acid in dry dichloromethane, and dry pyridine or triethylamine is contacted with fatty acid chloride at 0°C and stirred for 24 hours at room temperature in a nitrogen atmosphere. The reaction mixture was extracted with dichloromcthanc by successive washing with 0.5 M HC1, saturated NaHCCh and NaCl, and dried over sodium sulfate. The crude extract was concentrated under reduced pressure and the resulting mixture was purified with flash column chromatography with a yield of about 65-70%.

[0012] Figure 4 is a diagram showing the general synthesis scheme of fatty acid esters of 12-hydroxy fatty acid (12-FAHFA) via trans-esterification. 12-hydroxystearic acid was melted and contacted with the desired fatty acids. An acid catalyst (0.3%) was added to the reaction mixture and heated at about 100°C for 10 hours. The reaction mixture was next washed with the required amount of aqueous alkali solution. The product was dried and can be stored for further use.

[0013] Figure 5 is a radar chart showing the results of the sensory evaluation with palmitic acid esters of 12-hydroxystearic acid (12-PAHSA) and stearic acid esters of 12- hydroxystearic acid (12-SAHSA). The variables assessed in the sensory evaluation are: good slip, good spreading, no soaping, fast absorption, non-greasy, good smoothness, no tacky feel, and overall skin comfort.

[0014] Figure 6 is a bar chart showing the changes in trans epidermal water loss (TEWL) and moisture of skin applied with test substances after five days, compared to before test substances were applied. Measurements were taken using the Delfin Moisture Meter SC (moisturisation test) and Delfin Vapometer (trans epidermal water loss (TEWL) test). The results show that skin applied with palmitic acid esters of 12-hydroxystearic acid (12-PAHSA) or stearic acid esters of 12-hydroxystearic acid (12-SAHSA) had decreased trans epidermal water loss (TEWL) and increased moisture after five days compared to skin applied with petrolatum.DETAILED DESCRIPTION OF THE PRESENT INVENTION

[0015] The skin is the largest organ of the body which provides a protective barrier against mechanical, thermal, chemical, or physical injuries, and pathogenic infections. Theskin’s outermost layer, the epidermis, is covered with a film of water and lipids which has a role in preventing moisture loss.

[0016] Epidermal sphingolipids arc a class of lipids found in the outermost layer of the skin where differences in, for example, chain length, type and extent of hydroxylation, and saturation result in heterogeneity of the lipids. Ceramides are a group of sphingolipids that account for 50% of skin lipids. Ceramides are crucial for maintaining the water permeability barrier function of the skin. Thus, ceramides are important for maintaining the skin’s capacity for moisture retention, and overall dermal wellness.

[0017] However, the secretion of ceramides decreases with age, leading to, for example, dry skin or dermal infections. Thus, there is a need for compositions which can mimic the role of ceramides to maintain the water permeability barrier function of the skin.

[0018] Fatty acid esters of hydroxy fatty acid (FAHFA) are lipids with antiinflammatory and anti-diabetic properties. Analysis of their molecular structures show that fatty acid esters of hydroxy fatty acid (FAHFA) and ceramides share some structural similarities. Both fatty acid esters of hydroxy fatty acid (FAHFA) and ceramides contain four polar atoms that can form hydrogen bonds with water, and two long acyl chains that facilitate the interaction with skin lipids (scc Figure 1).

[0019] Thus, without being bound by theory, it is hypothesised that due to the structural similarity with ceramides, fatty acid esters of hydroxy fatty acid (FAHFA) can be used in compositions to mimic the role of ceramides in the skin.

[0020] As used herein, the term “fatty acid ester of hydroxy fatty acid (FAHFA)” refers to lipids which arc characterized by an cstolidc bond that links a hydroxy fatty acid backbone and a fatty acid. As used herein, the term “monoestolides” can also be used synonymously to refer to fatty acid ester of hydroxy fatty acids.

[0021] Fatty acid esters of hydroxy fatty acid (FAHFA) can be formed by, for example, but not limited to, transesterification of a hydroxy fatty acid with a fatty acid. As used herein, the term “transesterification” is a reaction of a chemical reaction in which the organic functional group R’ ’ of an ester is exchanged with the organic group R' of an alcohol.

[0022] Faty acid esters of hydroxy faty acid (FAHFA) can also be formed by, for example, a condensation reaction that occurs between a hydroxy fatty acid with a fatty acid. As used herein, the term “condensation” refers to a chemical reaction in which two molecules are combined to form a single molecule, with the loss of water. In one example, the condensation reaction is an esterification reaction. As used herein, the term “esterification” refers to a chemical reaction in which the carboxyl group of a first molecule reacts with the hydroxyl group of a second molecule to form an ester, with the loss of water.

[0023] As used herein, the term “hydroxy fatty acid” refers to a fatty acid with a hydroxyl functional group attached to the principal chain. Thus, in one example, the hydroxy fatty acid is a hydroxystcaric acid.

[0024] As used herein, the term “fatty acid” refers to a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Thus, in one example, the faty acid is a palmitic acid. Tn another example, the faty acid is a stearic acid. In another example, the fatty acid is a lauric acid. In another example, the fatty acid is an oleic acid.

[0025] Fatty acids involved in transesterification with a hydroxy fatty acid can be a free fatty acid. As used herein, the term “free fatty acid” refers to a fatty acid that circulates in the plasma of blood in a non-esterified form, while bound to a transport protein.

[0026] Accordingly, depending on the length and saturation of the acyl chain and the position of the branching carbon, the resulting faty acid ester of hydroxy faty acid (FAHFA) from a transesterification reaction can be further differentiated. Thus, disclosed herein is a fatty acid ester of hydroxy fatty acid (FAHFA) is of the formula (I):wherein n1is 12, 14, or 16;wherein n2is a 5, 12, or 14; wherein n3is a 1, 3, or 10; and wherein the fatty acid ester of hydroxy fatty acid (FAHFA) is a free fatty acid.

[0027] In one example, the fatty acid ester of hydroxy fatty acid (FAHFA) of the formula (I) comprises a double bond.

[0028] In one example, the fatty acid ester of hydroxy fatty acid (FAHFA) is selected from the group consisting of palmitic acid ester of hydroxy stearic acid (PAHS A), steric acid ester of hydroxy stearic acid (SAHSA), and lauric acid ester of hydroxystcaric acid (LAHSA). In yet another example, the fatty acid ester of hydroxy fatty acid (FAHFA) is oleic acid ester of hydroxy stearic acid (OAHSA).

[0029] In another example, the fatty acid ester of hydroxy fatty acid (FAHFA) is a palmitic acid ester of hydroxy stearic acid (PAHS A) and is defined by the molecular formula C34H66O4. In another example, the fatty acid ester of hydroxy fatty acid (FAHFA) is a stearic acid ester of hydroxy stearic acid (SAHSA) and is defined by the molecular formula C36H70O4. In another example, the fatty acid ester of hydroxy fatty acid (FAHFA) is a lauric acid ester of hydroxy stearic acid (LAHSA) and is defined by the molecular formula C36H66O4. In another example, the fatty acid ester of hydroxy fatty acid (FAHFA) is an oleic acid ester of hydroxy stearic acid (OAHSA) and is defined by the molecular formula C 6H68O4.

[0030] As appreciated by a person skilled in the art, the location of the hydroxyl group within a hydroxy fatty acid would have an effect on the structure of the resulting fatty acid ester of hydroxy fatty acid. Accordingly, in one example, when fatty acid ester of hydroxy fatty acid (FAHFA) is a palmitic acid ester of hydroxystearic acid (PAHSA), n1is 14, and n2is 5, n3is 10; or n2is 12, n3is 3; or n2is 14, n3is 1. Examples of palmitic acid ester of hydroxystearic acid (PAHSA) can be, but are not limited to, the following:3 -Hexadecanoyloxy octadecanoic acid (3 -PAHS A);5-hexadecanoyloxyoctadecanoic acid (5-PAHSA); or12-hexadecanoyloxyoctadecanoic acid (12-PAHSA), as shown in Figure 1.

[0031] Accordingly, in one example, provided herein is a composition comprising at least one fatty acid ester of hydroxy fatty acid (FAHFA), wherein the at least one fatty acid ester of hydroxy fatty acid is of the formula (I):

[0036] In recent years, there is an increase in demand for compositions that are based on natural materials. Therefore, one major objective of the present application is to provide compositions based on natural starting materials.

[0037] Thus, disclosed herein is a method of preparing a fatty acid ester of hydroxy fatty acid (FAHFA), wherein the method comprises a first step of contacting a hydroxy group of a hydroxy fatty acid with a fatty acid ester.

[0038] As will be appreciated by a person skilled in the art, the contacting of a hydroxy group of a hydroxy fatty acid with a carboxyl group of a fatty acid can result in a condensation reaction. In one example, the contacting of a hydroxy group of a hydroxy fattyacid with a carboxyl group of a fatty acid can result in the production of a fatty acid ester of hydroxy fatty acid. In yet another example, the fatty acid ester of hydroxy fatty acid is a fatty acid ester of hydroxy fatty acid of Formula (I):Accordingly, disclosed herein is a method of preparing a fatty acid ester of hydroxy fatty acid of Formula (I):the method comprising the steps of: contacting a hydroxy fatty acid with a fatty acid; wherein said contact results in production of a fatty acid ester of hydroxy fatty acid of Formula (I).

[0039] In one example, the hydroxy fatty acid is a hydroxystearic acid. In another example, the fatty acid is selected from the group consisting of palmitic acid, stearic acid, lauric acid, and oleic acid. Accordingly, in one example, the fatty acid ester of hydroxy fatty acid is a palmitic acid ester of hydroxy stearic acid (PAHS A). In another example, the fatty acid ester of hydroxy fatty acid is a stearic acid ester of hydroxystearic acid (SAHSA). another example, the fatty acid ester of hydroxy fatty acid is a lauric acid ester of hydroxy stearic acid (LAHSA). In another example, the fatty acid ester of hydroxy fatty acid is an oleic acid ester of hydroxystearic acid (OAHSA).

[0040] In one example, the condensation reaction is a transesterification.

[0041] As will also be appreciated by a person skilled in the art, condensation reactions can be catalysed by the presence of a catalyst in the reaction solution. In one example, the method as disclosed herein can be chemical or enzymatic. Suitable catalysts can be, but are not limited to, a biological catalyst. In one example, the biological catalyst is an enzyme capable of catalysing a condensation reaction.

[0042] Thus, the contacting step of the method as disclosed herein can be performed in the presence of an enzyme. In one example, the enzyme is a lipase. In another example, the enzyme is Candida antarctica lipase A (CalA). In yet another example, the enzyme is immobilised Candida antarctica lipase A (IM-CalA). Thus, in one example, the method as disclosed herein can be performed enzymatically using a lipase.

[0043] Suitable temperature ranges for enzymatic reactions are well known by a person skilled in the ail. Thus, in one example, the reaction condition can be performed at a temperature range of between 65 °C to 70°C, or between 70°C to 75°C. In another example, the incubation step is carried out at a temperature of about 65°C, about 66°C, about 67°C, about 68°C, about 69°C, about 70°C, about 71°C, about 72°C, about 73°C, about 74°C, or about 75°C. In another example, the first incubation step is carried out at 70°C.

[0044] Suitable pH ranges for performing enzymatic reactions are also well known by a person skilled in the art. Thus, in one example, the contacting step is carried out at a pH of between about 6.5 to 7.0, or about 7.0 to 7.5. In another example, the pH of the incubation step is about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, or about 7.5. In another example, the first contacting step is carried out at a pH of about 7.0.

[0045] Enzymatic reactions can be facilitated by improving the probability of an enzyme contacting a substrate, such as, but not limited to, by agitating the solution containing the enzyme. Thus, in one example, the contacting step can be carried out under agitated conditions or under agitation. Methods of agitation include, but are not limited to, shaking, or stirring, using, for example, magnetic stirrer, shaking cabinet, vortexer, shaker machine, or a thermomixer, and that are capable of inducing a state of agitation in a reaction mixture. In one example, the method of agitation is performed with a thermomixer.

[0046] When agitating a solution containing the enzyme using any methods of agitation as disclosed herein, the speed of mixing would be well known by a person skilled in the art. In one example, the contacting step is carried out at a mixing speed of about 500 rpm to 600 rpm, about 600 rpm to 700 rpm, about 700 rpm to 800 rpm, about 800 rpm to 900 rpm, or about 900 rpm to 1000 rpm. In another example, the contacting step is carried out at a mixing speed of about 500 rpm, about 510 rpm, about 520 rpm, about 530 rpm, about 540 rpm, about 550 rpm, about 560 rpm, about 570 rpm, about 580 rpm, about 590 rpm, about 600 rpm, about 610 rpm, about 620 rpm, about 630 rpm, about 640 rpm, about 650 rpm, about 660 rpm, about 670 rpm, about 680 rpm, about 690 rpm, 700 rpm, about 710 rpm, about 720 rpm, about 730 rpm, about 740 rpm, about 750 rpm, about 760 rpm, about 770 rpm, about780 rpm, about 790 rpm, about 800 rpm, about 810 rpm, about 820 rpm, about 830 rpm, about 840 rpm, about 850 rpm, about 860 rpm, about 870 rpm, about 880 rpm, about 890 rpm, about 900 rpm, about 910 rpm, about 920 rpm, about 930 rpm, about 940 rpm, about 950 rpm, about 960 rpm, about 970 rpm, about 980 rpm, about 990 rpm, about 1000 rpm. In one example, the contacting step is carried out at a mixing speed of about 1000 rpm.

[0047] As will be appreciated by a person skilled in the art, the success of an enzymatic reaction can be dependent on how long the reactants remain in contact. Thus, in one example, the contacting step is carried out for between 4 to 12 hours. In another example, the contacting step is carried out for at least 4 hours, at least 8 hours, or at least 12 hours. In yet another example, the contacting step is carried out for about 4 hours, about 5 hours, about 6 hours, about 7 hours, about 8 hours, about 9 hours, about 10 hours, about 1 1 hours, or about 12 hours. In one example, the first contacting step is carried out for 8 hours.

[0048] As will be appreciated by a person skilled in the art, the contacting of a hydroxy group of a hydroxy fatty acid with a fatty acid ester can result in a transesterification reaction. As will also be appreciated by a person skilled in the art, transesterification reactions can be catalysed by the presence of a catalyst in the reaction solution. Suitable catalysts can be, but arc not limited to, chemical catalysts. In one example, a catalyst for catalysing a transesterification reaction can be a chemical catalyst. In one example, the chemical catalyst can be an acid, or a base capable of catalysing a transesterification reaction. Thus, the contacting step of the method as disclosed herein can be performed in the presence of a chemical catalyst. In one example, the chemical catalyst is an acid.

[0049] Suitable reaction conditions for performing the method disclosed herein with a chemical catalyst are well known by a person skilled in the art. Reaction conditions for performing the method disclosed herein with a chemical catalyst can be, but are not limited to, temperature, atmosphere, reagents, or combinations thereof.

[0050] Thus, in one example, the reaction condition for carrying out the method as disclosed herein with a chemical catalyst can be performed at a temperature range of 0°C to 20°C. In another example, the incubation step is carried out at a temperature of about 0°C, 1°C, about 2°C, about 3°C, about 4°C, about 5°C, about 6°C, about 7°C, about 8°C, about 9°C, about 10°C, about 11°C, about 12°C, about 13°C, about 14°C, about 15°C, about 16°C, about 17°C, about 18°C, about 19°C, or about 20°C. In another example, the first incubation step is carried out at 0°C.

[0051] Suitable atmospheres for carrying out the method as disclosed herein with a chemical catalyst can be, but are not limited to, a nitrogen atmosphere, a pressurisedatmosphere, or in the absence of oxygen. Other suitable atmospheres arc well-known by a person skilled in the art.

[0052] Solvents suitable for conducting transesterification reaction arc well-known by a person skilled in the art. Suitable solvents can be but are not limited to, dry pyridine, or triethylamine.

[0053] As will be appreciated by a person skilled in the art, to ensure the success of a chemical reaction, a skilled person can, for example, increase the duration in which the reactants remain in contact with a chemical catalyst. Thus, in one example, the contacting step is carried out for between 18 to 30 hours. In another example, the contacting step is carried out for at least 18 hours, at least 24 hours, or at least 30 hours. In yet another example, the contacting step is carried out for about 12 hours, about 13 hours, about 14 hours, about 15 hours, about 16 hours, about 17 hours, about 18 hours, about 19 hours, about 20 hours, about 21 hours, 22 hours, about 23 hours, about 24 hours, about 25 hours, about 26 hours, about 27 hours, about 28 hours, about 29 hours, or about 30 hours. In one example, the contacting step is carried out for 24 hours.

[0054] The success of a chemical reaction can be determined by the detection of the products of the reaction. Thus, the method disclosed herein comprises a second step of analysis.

[0055] Analysis can be performed on the products of a reaction to identify or quantify the products. Suitable types of analysis can be but are not limited to, chromatography, electrophoresis, or field flow fractionation. In one example, the device for analysis is a device for gas chromatography. In another example, the device for analysis is a gas chromatography with flame ionization detection (GC-FID).

[0056] Methods of preparing substances for analysis would be known by a skilled person of the art. Suitable types of analysi can be but are not limited to, derivatization, or washing of the products with suitable washing reagents.

[0057] Subsequent chemical reactions can be performed after analysis. Thus, the resulting products of a chemical reaction can be combined with other ingredients to form a composition. In one example, the composition described herein is formulated for dermal application. Suitable ingredients can be, but are not limited to, water, a humectant, a water thickener, a pH adjuster, an emulsifier, a co-cmulsificr, an emollient, a preservative, and any combinations thereof.

[0058] As used herein, the term “humectant” refers to a substance which attracts and retains moisture from the air. In one example, the humectant can be, but is not limited to,proline and arginine aspartate, 1,3-butylcnc glycol, codium tomentosum extract, collagen amino acids, creatinine, diglycerol, biosaccharide gum-1, glucamine salts, glucuronic acid salts, glutamic acid salts, polyethylene glycol ethers of glycerine, glycerine, glycerol monopropoxylate, glycogen, hexylene glycol, honey, hydrolyzed mucopolysaccharides, inositol, keratin amino acids, glycosaminoglycans, methoxy PEG 10, methyl glucose, 3- methyl-l,3-butanediol, N-acetyl glucosamine salts, pentaerythitol, 1,2 pentanediol, PPG-1 glyceryl ether, sericin, silk amino acids, sodium acetylhyaluronate, sodium hyaluronate, sodium poly-aspartate, sodium polyglutamatc, sorbeth 20, sorbeth 6, glucose, mannose, polyglycerol sorbitol, trehalose, triglycerol, trimethyolpropane, tris (hydroxymethyl) amino methane salts, glycerine, diglycerin, glycerol, erythritol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, maltitol, mannose, inositol, triethyleneglycol, sodium pyrrolidone carboxylic acid (PCA), and any combinations thereof. In another example, the humectant is glycerine.

[0059] As used herein, the term “water thickener” refers to a substance which can increase the viscosity of a liquid without substantially changing its other properties. In one example, a water thickener can be, but is not limited to, a water-soluble polymer, carbomer, agar, agarose, alicaligcncs polysaccharides, algin, alginic acid, acacia gum, amylopectin, chitin, dextran, cassia gum, cellulose gum, gelatin, gellan gum, hydroxyethyl cellulose, methyl cellulose, ethyl cellulose, pectin, sclerotium gum, xanthan gum, pectin, trehelose, gelatin, ammonium alginate, calcium alginate, calcium carrageenan, carnitine, carrageenan, guar gum, guar hydroxypropyltrimonium chloride, hydroxypropyl chitosan, hydroxypropyl guar, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, potassium carrageenan, propylene glycol alginate, sodium carboyxmethyl dextran, sodium carrageenan, tragacanth gum, and any combinations thereof. In one example, the water thickener is carbomer.

[0060] As used herein, the term “pH adjuster” refers to a substance which can alter the pH to a desired pH level. In one example, the pH adjuster can be, but is not limited to, sodium hydroxide, triethanolamine, malonic acid, succinic acid, sodium succinate, disodium succinate, glutaric acid, adipic acid, azclaic acid, dipotassium azelate, disodium azelate, sebacic acid, disodium sebacate, dodecanedioic acid, diethyl malonate, decyl succinate, dimethyl succinate, diethyl succinate, dicapryl succinate, dicctcaryl succinate, diisobutyl succinate, diethylhexyl succinate, dimethyl glutarate, diisobutyl glutarate, diisostearyl glutarate, dimethyl adipate, diethyl adipate, dipropyl adipate, dibutyl adipate, dihexyl adipate, dicapryl adipate, di-C12-15 alkyl adipate, ditridecyl adipate, dicetyl adipate,diisopropyl adipate, diisobutyl adipate, dicthylhcxyl adipate, diisooctyl adipate, diisononyl adipate, diisodecyl adipate, diliexyldecyl adipate, dilieptylundecyl adipate, dioctyldodecyl adipate, diisocctyl adipate, diisostcaryl adipate, isostcaryl sebacate, diethyl sebacate, dibutyl sebacate, dicaprylyl sebacate, capryl sebacate, diisopropyl sebacate, diethylhexyl sebacate, dibutyloctyl sebacate, diisooctyl sebacate, dihexyldecyl sebacate, dioctyldodecyl sebacate, diisostearyl sebacate, dioctyldodecyl dodecanedioate, diisocetyl dodecanedioate, and any combinations thereof. In one example, the pH adjuster is sodium hydroxide. In another example, the pH adjuster is triethanolamine.

[0061] As used herein, the term “emulsifier” refers to a substance that aids in the mixture of two immiscible liquids. In one example, the emulsifier can be, but is not limited to, an anionic emulsifier, a non-ionic emulsifier, glyceryl stearate, PEG-100 stearate, ethers of polyglycols and of fatty alcohols, esters of polyglycols and of fatty acids, ethers of poly glycols and of fatty alcohols which are glycosylated, esters of poly glycols and of fatty acids which are glycosylated, ethers of C12 -30 alcohols and of glycerol or of polyglycerol, esters of C12-30 fatty acids and of glycerol or of polyglyccrol, ethers of oxyalkylcnc-modificd C12-30 alcohols and of glycerol or poly glycerol, esters of sucrose and of C 12-30 fatty acids, esters of pcntacrythritol and of C12-30 fatty acids, esters of sorbitol and / or of sorbitan and of C12-30 fatty acids, ethers of sorbitol and / or of sorbitan and of alkoxylated sorbitan, ethers of polyglycols and of cholesterol, esters of C 12-30 fatty acids and of alkoxylated ethers of sorbitol and / or sorbitan, and any combinations thereof. In one example, the emulsifier is glyceryl stearate. In another example, the emulsifier is PEG-100 stearate. In yet another example, the emulsifier is glyceryl stearate and PEG- 100 stearate.

[0062] As used herein, the term “co-emulsifier” refers to a substance that aids an emulsifier in the mixture of two immiscible liquids. In one example, the co-emulsifier can be, but is not limited to, a fatty alcohol, cetearyl alcohol, polyol alkyl esters, glycerol and / or sorbitan esters, polyglyceryl-4 isostearate, sorbitan isostearate, sorbitan glyceryl isostearate, and any combinations thereof. In one example, the co-emulsifier is cetearyl alcohol.

[0063] As used herein, the term “emollient” refers to a substance that aids in protecting, moisturizing, and lubricating the skin. In one example, the emollient can be, but is not limited to, an ester oil, isopropyl myristate, isostearic acid derivatives, isopropyl palmitate, lanolin oil, diisopropyl dimcratc, diisopropyl adipate, dimethyl isosorbidc, malcatcd soybean oil, octyl palmitate, isopropyl isostearate, cetyl lactate, cetyl ricinoleate, tocopheryl acetate, acetylated lanolin alcohol, cetyl acetate, phenyl trimethicone, glyceryl oleate, tocopheryl linoleate, wheat germ glycerides, arachidyl propionate, myristyl lactate, decyloleate, propylene glycol ricinoleate, isopropyl lanolatc, pcntacrythrityl tctrastcaratc, neopentylglycol dicaprylate / dicaprate, hydrogenated coco-glycerides, isononyl isononanoatc, isotridccyl isononanoatc, myristyl myristate, triisocctyl citrate, octyl dodecanol, octyl hydroxystearate, and any combinations thereof. In one example, the ester oil is isopropyl myristate.

[0064] As used herein, the term “preservative” refers to a substance that aids to prevent decomposition by microbial growth or by undesirable chemical changes. In one example, the preservative can be, but is not limited to, phenoxyethanol, decylene glycol, 1,2- hexanediol, phenoxyethanol, formaldehyde solution, parabens, pentanediol, sorbic acid, and any combinations thereof. In one example, the preservative is phenoxyethanol. In another example, the preservative is decylene glycol. In yet another example, the preservative is 1 ,2- hexanediol. In yet another example, the preservative is selected from the group consisting of phenoxyethanol, decylene glycol, 1,2-hexanediol, and any combinations thereof.

[0065] Suitable ingredients for a composition would be well known by a person skilled in the art. Thus, in one example, the concentration of the humectant is at least 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, or 10.0%, of the total weight. In another example, the concentration of the humectant is between 3.0% to 4.0%, 4.0% to 5.0%, 5.0% to 6.0%, 6.0% to 7.0%, 7.0% to 8.0%, 8.0% to 9.0%, or 9.0% to 10.0%. In yet another example, the concentration of the humectant is between 1.0% to 2.0%, or 2.0% to 3.0%. In another example, the concentration of the humectant is about 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, or 10.0%.

[0066] In another example, the concentration of the water thickener is at least 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1.0%,, of the total weight. In another example, the concentration of the water thickener is between 0.3% to 0.4%, 0.4% to 0.5%, 0.5% to 0.6%, 0.6% to 0.7%, 0.7% to 0.8%, 0.8% to 0.9%, or 0.9% to 1 .0%. In yet another example, the concentration of the water thickener is between 0.1% to 0.2%, or 0.2% to 0.3%. In another example, the concentration of the water thickener is about 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1.0%.

[0067] In another example, the concentration of the pH adjuster is provided in an amount sufficient to obtain a pH of about 6.0. In another example, the concentration of the emulsifier is at least 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, or 10.0%, of the total weight. In another example, the concentration of the pH adjuster is between 3.0% to 4.0%, 4.0% to 5.0%, 5.0% to 6.0%, 6.0% to 7.0%, 7.0% to 8.0%, 8.0% to 9.0%, or 9.0% to 10.0%. In yet another example, the concentration of the pH adjuster is between 1.0% to 2.0%, or2.0% to 3.0%. In another example, the concentration of the pH adjuster is about 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, or 10.0%.

[0068] In another example, the concentration of the co-cmulsificr is at least 1.0%, 2.0%, 3.0%;, 4.0%;, 5.0%), 6.0%;, 7.0%), 8.0%), 9.0%), or 10.0%), of the total weight. In another example, the concentration of the co-emulsifier is between 1.0% to 2.0%, 2.0% to 3.0%, 3.0% to 4.0%, 4.0% to 5.0%, 5.0%) to 6.0%, 6.0% to 7.0%, 7.0% to 8.0%, 8.0% to 9.0%, or 9.0% to 10.0%. In yet another example, the concentration of the co-emulsifier is between 0.1% to 1.0%. In another example, the concentration of the co-cmulsificr is about 1.0%, 2.0%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, or 10.0%.

[0069] In another example, the concentration of the emollient is at least 6.0%, 7.0%, 8.0%, 9.0%>, or 10.0%, of the total weight. In another example, the concentration of the emollient is between 6.0% to 7.0%, 7.0% to 8.0%, 8.0% to 9.0%, or 9.0% to 10.0%. In yet another example, the concentration of the emollient is between 1.0% to 2.0%, 2.0% to 3.0%, 3.0% to 4.0%, 4.0% to 5.0%, or 5.0% to 6.0%. In another example, the concentration of the emollient is about 6.0%, 7.0%, 8.0%, 9.0%, or 10.0%.

[0070] In another example, the concentration of the preservative is at least 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0% of the total weight. In another example, the concentration of the preservative is between 0.5% to 0.6%, 0.6% to 0.7%, 0.7%) to 0.8%), 0.8%> to 0.9%), or 0.9%) to 1.0%. In yet another example, the concentration of the preservative is between 0.1% to 0.2%, 0.2% to 0.3%, or 0.3% to 0.4%. In another example, the concentration of the preservative is about 00.5%, 0.6%, 0.7%, 0.8%, 0.9%, or 1.0%.

[0071] Thus, disclosed herein is a composition comprising water, a humectant, a water thickener, a pH adjuster, an emulsifier, a co-emulsifier, an emollient, a preservative, and a fatty acid ester. Also disclosed herein is a composition comprising water, a humectant, a water thickener, a pH adjuster, an emulsifier, a co-emulsifier, an emollient, and a preservative.

[0072] In one example, disclosed herein is a composition comprising water, a humectant, a water-soluble polymer, a fatty alcohol, an ester oil, a pH adjuster selected from the group consisting of sodium hydroxide or triethanolamine, an emulsifier selected from the group consisting of glyceryl stearate or PEG- 100 stearate, a humectant which is glycerine, and a preservative selected from the group consisting of a phenoxyethanol, decylene glycol, or 1 ,2-hexanediol. In a specific example, disclosed herein is a composition comprising water, glycerine, carbomer, sodium hydroxide or triethanolamine, glyceryl stearate and / or PEG- 100 stearate, cetearyl alcohol, isopropyl myristate, phenoxyethanoland / or dccylcnc glycol and / or 1,2-Hcxancdiol, and a fatty acid ester. In one example, the composition comprises a palmitic acid ester of hydroxy stearic acid (PAHSA). In another example, the composition comprises a stearic acid ester of hydroxystcaric acid (SAHSA). In another example, the composition comprises a lauric acid ester of hydroxystearic acid (LAHSA). In another example, the composition comprises an oleic acid ester of hydroxystearic acid (OAHSA).

[0073] Accordingly, in one example, the composition comprises palmitic acid ester of hydroxystcaric acid (PAHSA), water, a humectant, a water thickener, a pH adjuster, an emulsifier, a co-emulsifier, an emollient, and a preservative. In one example, disclosed herein is a composition comprising palmitic acid ester of hydroxystearic acid (PAHSA), a humectant, a water-soluble polymer, a fatty alcohol, an ester oil, a pH adjuster selected from the group consisting of sodium hydroxide or triethanolamine, an emulsifier selected from the group consisting of glyceryl stearate or PEG- 100 stearate, a humectant which is glycerine, and a preservative selected from the group consisting of a phenoxyethanol, dccylcnc glycol, or 1,2-hcxancdiol. In a specific example, disclosed herein is a composition comprising palmitic acid ester of hydroxy stearic acid (PAHSA), water, glycerine, carbomer, sodium hydroxide or triethanolamine, glyceryl stearate and / or PEG- 100 stearate, cctcaryl alcohol, isopropyl myristate, phenoxyethanol and / or decylene glycol and / or 1,2-Hexanediol, and a fatty acid ester. In another example, the concentration of palmitic acid ester of hydroxystearic acid (PAHSA) is at least 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% of the total weight. In another example, the concentration of palmitic acid ester of hydroxy stearic acid (PAHSA) is between 3.0% to 4.0%, 4.0% to 5.0%, 5.0% to 6.0%, 6.0% to 7.0%, 7.0% to 8.0%, 8.0% to 9.0%, or 9.0% to 10.0%. In yet another example, the concentration of palmitic acid ester of hydroxystearic acid (PAHSA) is between 1.0% to 2.0%, or 2.0% to 3.0%. In another example, the concentration of palmitic acid ester of hydroxystearic acid (PAHSA) is about 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, or 10.0%.

[0074] In another example, the composition as disclosed herein comprises steric acid ester of hydroxy stearic acid (SAHSA), water, a humectant, a water thickener, a pH adjuster, an emulsifier, a co-cmulsificr, an emollient, and a preservative. In one example, disclosed herein is a composition comprising steric acid ester of hydroxy stearic acid (SAHSA), a humectant, a water-soluble polymer, a fatty alcohol, an ester oil, a pH adjuster selected from the group consisting of sodium hydroxide or triethanolamine, an emulsifier selected from the group consisting of glyceryl stearate or PEG- 100 stearate, a humectant which is glycerine, and a preservative selected from the group consisting of a phenoxyethanol,dccylcnc glycol, or 1,2-hcxancdiol. In a specific example, disclosed herein is a composition comprising steric acid ester of hydroxystearic acid (SAHSA), water, glycerine, carbomer, sodium hydroxide or triethanolamine, glyceryl stearate and / or PEG- 100 stearate, cctcaryl alcohol, isopropyl myristate, phenoxyethanol and / or decylene glycol and / or 1,2-Hexanediol, and a fatty acid ester. In another example, the concentration of steric acid ester of hydroxystearic acid (SAHSA) is at least 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, of the total weight. In another example, the concentration of steric acid ester of hydroxystearic acid (SAHSA) is between 3.0% to 4.0%, 4.0% to 5.0%, 5.0% to 6.0%, 6.0% to 7.0%, 7.0% to 8.0%, 8.0% to 9.0%, or 9.0% to 10.0%. In yet another example, the concentration of steric acid ester of hydroxystearic acid (SAHSA) is between 1.0% to 2.0%, or 2.0% to 3.0%. In another example, the concentration of steric acid ester of hydroxystearic acid (SAHSA) is about 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0%, 9.0%, or 10.0%.

[0075] The composition as disclosed herein can be formulated for dermal application. As used herein, the term “dermal application” refers to the application of a substance on the external surface of a subject’s body. The external surface of a subject’s body can be but are not limited to, skin on the limbs, on the torso, on the extremities, on the head, or on the face.

[0076] Suitable formulations for dermal application can be but arc not limited to, a cream, a lotion, a balm, a masque, a paste, a foam, a moisturiser, or an ointment.

[0077] Other suitable formulations for dermal application can be, but are not limited to, a gel, a serum, an oil, a hydrator, an emulsion, an emulsion chassis, or an oil-in-water emulsion.

[0078] As shown by the non-limiting examples disclosed herein, dermal application of the compositions disclosed herein are shown to decrease trans-epidermal water loss (TEWL). As used herein, the term “trans epidermal water loss (TEWL)” refers to the amount of water that passively evaporates through skin to the external environment due to water vapor pressure gradient on both sides of the skin barrier.

[0079] Dermal application of the composition as disclosed herein can be used for cosmetic purposes. In one example, the decrease in trans epidermal water loss (TEWL) can, in one example, decrease the appearance of wrinkles, fine lines, dark spots, age spots, mottled pigmentation, skin pigmentation, melasma, darkened skin, skin elasticity, dark circles under the eyes, or changes associated with skin aging. In another example, the decrease in trans epidermal water loss (TEWL) can provide skin lightening, colour reduction, skin pigmentation reduction, skin redness reduction, skin flushing reduction, inflammation reduction, fine line reduction, wrinkle reduction, wrinkle depth reduction, skin drynessreduction, skin roughness reduction, enhanced skin radiance, enhanced skin tone, enhanced skin clarity, enhanced skin firmness, enhanced skin tightness, enhanced skin elasticity, and / or enhanced overall skin appearance. Accordingly, disclosed herein is a method of preventing trans-epidermal water loss (TEWL), wherein the method comprises applying the composition of the disclosure to the dermal surface of a subject in need thereof.

[0080] The decrease in trans epidermal water loss (TEWL) can also contribute to the reduction in skin dryness or scaliness. Accordingly, dermal application of the composition as disclosed herein can also be used for medical purposes. In one aspect, provided herein is a method of treating dry and / or scaly skin, wherein the method comprises applying the composition as disclosed herein to the dermal surface of a subject in need thereof. In another aspect, provided herein is a composition for use in treating dry and / or scaly skin, wherein the method comprises applying the composition as disclosed herein to the dermal surface of a subject in need thereof. In yet another aspect, provided herein is a use of the composition as disclosed herein in the manufacture of a medicament for treating dry and / or scaly skin. In yet another aspect, provided herein is a composition for use in therapy.

[0081] In one example, the method of treating dry and / or scaly skin as disclosed herein can reduce dry and / or scaly skin associated with skin diseases which can be, but arc not limited to, topic dermatitis, ichthyosis, perioral dermatitis, eczema, rosacea, psoriasis, or seborrheic dermatitis.

[0082] In yet another example, provided herein is a method of preventing trans- epidermal water loss (TEWL) or treating dry and / or scaly skin, wherein the method decreases trans-epidermal water loss (TEWL) on a subject’s skin compared to when the composition is not applied.

[0083] The invention illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms "comprising", "including", "containing", etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the inventions embodied therein herein disclosedmay be resorted to by those skilled in the art, and that such modifications and variations arc considered to be within the scope of this invention.

[0084] As used in this application, the singular form “a,” “an,” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a fatty acid ester of hydroxy fatty acid (FAHFA)” includes a plurality of fatty acid esters of hydroxy fatty acid (FAHFA), including mixtures and combinations thereof.

[0085] As used herein, the term “about”, in the context of concentrations of components of the formulations, typically means + / - 5% of the stated value, more typically + / - 4% of the stated value, more typically + / - 3% of the stated value, more typically, + / - 2% of the stated value, even more typically + / - 1% of the stated value, and even more typically + / - 0.5% of the stated value.

[0086] Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0087] Certain embodiments may also be described broadly and generically herein. Each of the narrower species and sub-generic groupings falling within the generic disclosure also form part of the disclosure. This includes the generic description of the embodiments with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

[0088] The invention has been described broadly and generically herein. Each of the narrower species and sub-generic groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

[0089] Other embodiments arc within the following claims and non- limiting examples. Tn addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.EXAMPLES

[0090] In the following text, the present invention is illustrated in further details by the following non-limiting examples.Materials and methods

[0091] Lauric acid (LA, min. 98%), palmitic acid (PA, min. 98%), stearic acid (SA, min. 92%) and oleic acid (OA, min. 75%) used in the examples below were from PGEO Edible Oils SDN BHD, Malaysia. 12-hydroxystcaric acid was purchased from Tokyo Chemical Industry Co., Ltd (TCI, Tokyo, Japan). Liquid Candida antarctica lipase A (CalA) lipase was a generous gift from Novozymes (Novozymes, Malaysia). ECR8806M resin was purchased from Purolite (Purolite, PA, USA). N,O-Bis (trimethylsilyl)trifluoroacetamide with trimethylchloro silane (BSTFA+TMCS) was purchased from Sigma-aldrich, Singapore. Candida antarctica lipase A (CalA) lipase immobilization

[0092] ECR8806M resin in an amount of 10 grams was added to lOmL of distilled deionized water. Liquid Candida antarctica lipase A (CalA) in an amount of 12mL was next added to the resin suspension. The mixture was mixed with orbital shaker for 2 hours at room temperature. The resin was then filtered, and the liquid was removed under vacuum. The resin was washed with lOmL 40% (w / w) sucrose three times. After removal of excessive sucrose solution, the resin was dried in 40°C for 4 hours. Dried immobilized Candida antarctica lipase A (IM-CalA) lipase in an amount of 6.4g was obtained.Enzymatic synthesis of fatty acid esters of hydroxy fatty acid (FAHFA)Example 1: Enzymatic synthesis of palmitic acid ester of 12-hydroxy stearic acid (12- PAHSA).

[0093] Palmitic acid (PA) in an amount of 0.8 grams and 1 gram of 12-hydroxystearic acid (12-HSA) were added to a 20mL glass vial. L50mg of immobilized Candida antartica lipase A (IM-CalA) was added. The synthesis reaction was performed with an Eppendorf thermomixer, open capped, at 70°C and at 1000 rpm. After 8 hours, a small amount of crude mixture was aliquoted, derivatized with BSTFA+TMCS and analyzed with gas chromatography with flame ionization detection (GC-FID).

[0094] A diagram showing the enzymatic synthesis of palmitic acid ester of 12- hydroxystcaric acid (12-PAHSA) is shown in Figure 2.

[0095] Recrystallization was performed by melting the crude mixture at 60°C and incubating in 30°C. The crystal was removed by centrifugation at 6000 g for 20 min. After purification by recrystallization, the amount of palmitic acid ester of 12-hydroxystearic acid(12-PAHSA) is 81.9%. The amount of palmitic acid ester of 12-hydroxystearic acid (12- PAHSA) and stearic acid ester of 12-hydroxystearic acid (12-SAHSA) together is 89.8%. The remaining 10.1% arc palmitic acid (PA), stearic acid (SA) and 12-hydroxy stearic acid (12-HSA).Example 2. Enzymatic synthesis of stearic acid ester of 12-hydroxy stearic acid (12-SAHSA).

[0096] Stearic acid (SA) in an amount of 0.8 grams and 1 gram of 12-hydroxystearic acid (12-HSA) were added in a 20 mL glass vial. 150mg of immobilized Candida antartica lipase A (IM-CalA) was added. The synthesis reaction was performed with an Eppcndorf thermomixer, open capped, at 70°C and at 1000 rpm. After 8 hours, a small amount of crude mixture was aliquoted, derivatized with BSTFA+TMCS and analyzed with GC-FID.

[0097] Recrystallization was performed by melting the crude mixture at 60°C and incubating in 30°C. The crystal was removed by centrifugation at 6000 g for 20 min. After purification by recrystallization the amount of stearic acid ester of 12-hydroxystearic acid (12-SAHSA) is 90.0%. The remaining 9.9% are palmitic acid (PA), stearic acid (SA) and 12-hydroxystearic acid (12-HSA).Example 3. Enzymatic synthesis of lauric acid ester of 12-hydroxystearic acid. (12-LAHSAf

[0098] Lauric acid (LA) in an amount of 0.8 grams and 1 gram of 12-hydroxystearic acid (12-HSA) were added in a 20 mL glass vial. 150 mg of immobilized Candida antartica. lipase A (IM-CalA) was added. The synthesis reaction was performed with an Eppendorf thermomixer, open capped, at 70°C and at 1000 rpm. After 8 hours, a small amount of crude mixture was aliquoted, derivatized with BSTFA+TMCS and analyzed with GC-FID.The crude mixture consists of 72.1%, 8.4% and 1.2% of lauric acid ester of 12- hydroxystearic acid (12-LAHSA), stearic acid ester of 12-hydroxystearic acid (12-SAHSA) and palmitic acid ester of 12-hydroxystearic acid (12-PAHSA), respectively. The remains are 14.5% lauric acid (LA), 1.9% stearic acid (SA), and 1.5% 12-hydroxystearic acid (12- HA).Example 4. Enzymatic synthesis of oleic acid ester of 12-hydroxystearic acid (12-OAHSA).

[0099] Oleic acid (OA) in an amount of 0.8 grams and 1 gram of 12-HSA were added in a 20 mL glass vial. 150mg of immobilized Candida antartica lipase A (IM-CalA) lipase was added. The synthesis reaction was performed with an Eppendorf thermomixer, open capped, at 70°C and at 1000 rpm. After 8 hours, a small amount of crude mixture was aliquoted, derivatized with BSTFA+TMCS and analyzed with GC-FID.

[0100] The crude mixture consisted of 42.8% oleic acid ester of 12-hydroxystearic acid (12-OAHSA).Chemical synthesis of fatty acid esters of hydroxy fatty acid (FAHFA)Example 5. General synthesis scheme.

[0101] To a solution of 12-hydroxystcaric acid in dry dichloromclhanc and dry pyridine or triethylamine at 0°C, fatty acid chloride was added slowly and stirred for 24 hours at room temperature under nitrogen atmosphere. Reaction mixture was extracted with dichloromethane by successive washing with 0.5 M HC1, saturated NaHCOj and NaCl, and dried over sodium sulfate. The crude extract was concentrated under reduced pressure and the resulting mixture was purified with flash column chromatography with a yield of about 65- -70%.

[0102] A diagram sho wing the general synthesis scheme of fatty acid esters of hydroxy fatty acid (FAHFA) is shown in Figure 3.Example 6. General Procedure for synthesis of fatly acid ester of 12-hydroxy fatly acid (12 FAHFA) using trans-esterification.

[0103] 12-hydroxystearic acid (12-HSA) was melted and intended fatty acids were added. Acid catalyst (0.3%) was added to the reaction mixture and the reaction mixture was heated at about 100°C for 10 hours.

[0104] The reaction mixture was next washed with the required amount of aqueous alkali solution. Tire end product was then dried and stored for further use.

[0105] A diagram sho wing the general synthesis scheme of fatty acid esters of hydroxy fatty acid (FAHFA) using trans-esterification is shown in Figure 4.Sensory Evaluation

[0106] On evaluation day, test subjects were reminded to wash their forearms about an hour before the start of evaluation session. Test sites on forearm were marked with circles. Test samples were coded with three digits and presented to test subjects in a randomised manner. All test subjects were instructed to mark their answers on ballot forms which were collected immediately after each test.

[0107] Using a syringe, 0.2ml of sample was dispensed on the test subject’s forearm. Test subjects are required to apply the sample in circular motion around the tested area and evaluate on the following attributes: good slip, good spreading, no soaping, fast absorption, non-greasy, good smoothness, no tacky feel and overall skin comfort.

[0108] A radar chart showing the results of the sensory evaluation with palmitic acid esters of 12-hydroxystearic acid (12-PAHSA) and stearic acid esters of hydroxystearic acid (12-SAHSA) is shown in Figure 5, where the trans epidermal water loss (TEWL) is measured relative to before the formulation was applied.Moisture and trans-epidermal water loss evaluation

[0109] Four test subjects were used for the test. The test area is the volar forearm. Four test sites measuring 3x3 cm, each separated by 2.5 cm, were allocated symmetrically on both inner forearms of each participant. The study period spanned 5 days.

[0110] Three non-invasive measurements were taken using the Delfin Moisture Meter SC (moisturisation test) and Delfin Vapomctcr (TEWL test). All measurements were carried out in accordance with the relevant published guidelines. Baseline measurements were obtained.

[0111] Test subjects were instructed to apply the test products twice daily by light massaging on the site until the product was completely absorbed.

[0112] After five days, measurements were conducted using the Delfin Moisture Meter SC (moisturisation test) and Delfin Vapometer (TEWL test).

[0113] A bar chart showing the changes in trans epidermal water loss (TEWL) and moisture of skin applied with test substances after five days, compared to before test substances were applied, is shown in Figure 6.

[0114] The results show that trans epidermal water loss of skin applied with either palmitic acid ester of 12-hydroxystearic acid (12-PAHSA) and stearic acid ester of 12- hydroxystearic acid (12-SAHSA) was decreased compared to skin applied with petrolatum.

[0115] Further, the results also show that skin applied with either palmitic acid ester of 12-hydroxystearic acid (12-PAHSA) and stearic acid ester of 12-hydroxystearic acid (12- SAHSA) had increased moisture compared to skin applied with petrolatum.Conclusion

[0116] Fatty acid esters of hydroxy fatty acid (FAHFA), in particular, palmitic acid esters of hydroxystearic acid (PAHSA) and stearic acid esters of hydroxystearic acid (SAHSA) show protective effects against trans epidermal water loss and increase in skin moisture compared to petrolatum.

[0117] These compounds also show improvement of non-soaping properties, where the amount of foam and / or a film on the surface of the skin upon application of the composition is decreased.

Claims

CLAIMS1. A composition comprising at least one fatty acid ester of hydroxy fatty acid (FAHFA), wherein the at least one fatty acid ester of hydroxy fatty acid is of the formula (I):wherein n1is a C12-alkyl, a C14-alkyl, a C16-alkyl, C18-alkyl, C20-alkyl, C22-alkyl, or C24-alkyl; wherein n2is a C1- to C15-alkyl; wherein n3is a C1- to C15-alky,l wherein the sum of carbon atoms of n2and n3is 15; and wherein the fatty acid ester of hydroxy fatty acid (FAHFA) is a free fatty acid.

2. The composition of claim 1, wherein n1is a C12-alkyl, a Ci4-alkyl, a Ci6-alkyl, C18- alkyl, a C20-alkyl, a C22-alkyl, a C24-alkyl; wherein n2is a C5-alkyl, a C12-alkyl, or a Ci4-alkyl; and / or, wherein n3is a C1-alkyl, a C3-alkyl, or a C10-alkyl.

3. The composition of claim 1 , wherein n1is C14-alkyl, n2is C5-alkyl, and n3is C10- alkyl.

4. The composition of claim 1, wherein n1is C14-alkyl, n2is C12-alkyl, and n3is C3- alkyl.

5. The composition of claim 1, wherein n1is C14-alkyl, n2is Ci4-alkyl, and n3is C1- alkyl.

6. The composition of claim 1, wherein n1is C12-alkyl, n2is C5-alkyl, and n3is C3- alkyl.

7. The composition of claim 1, wherein n1is C12-alkyl, n2is Cw-alkyl, and n3is C3- alkyl.

8. The composition of claim 1, wherein n1is C12-alkyl, n2is Ci4-alkyl, and n3is C1- alkyl.

9. The composition of claim 1, wherein n1is C16-alkyl, n2is C5-alkyl, and n3is C10- alkyl.

10. The composition of claim 1, wherein n1is C16-alkyl, n2is Cw-alkyl, and n3is C3- alkyl.

11. The composition of claim 1, wherein n1is C16-alkyl, n2is C14-alkyl, and n3is C1- alkyl.

12. The composition of claim 1, wherein n1is C18-alkyl, n2is C5-alkyl, and n3is C10- alkyl.

13. The composition of claim 1 , wherein n1is C18-alkyl, n2is C12-alkyl, and n3is C3- alkyl.

14. The composition of claim 1, wherein n1is C18-alkyl, n2is Cu-alkyl, and n3is C1- alkyl.

15. The composition of claim 1, wherein n1is C20-alkyl, n2is C5-alkyl, and n3is C10- alkyl.

16. The composition of claim 1, wherein n1is C20-alkyl, n2is C12-alkyl, and n3is C3- alkyl.

17. The composition of claim 1 , wherein n1is C20-alkyl, n2is C14-alkyl, and n3is C1- alkyl.

18. The composition of claim 1, wherein n1is C22-alkyl, n2is C5-alkyl, and n3is C10- alkyl.

19. The composition of claim 1, wherein n1is C22-alkyl, n2is C12-alkyl, and n3is C3- alkyl.

20. The composition of claim 1, wherein n1is C22-alkyl, n2is C14-alkyl, and n3is C1- alkyl.

21. The composition of claim 1, wherein n1is C24-alkyl, n2is C5-alkyl, and n3is C10- alkyl.

22. The composition of claim 1 , wherein n1is C24-alkyl, n2is C12-alkyl, and n3is C3- alkyl.

23. The composition of claim 1, wherein n1is C24-alkyl, n2is Cu-alkyl, and n3is C1- alkyl.

24. The composition of any one of the preceding claims, wherein the fatty acid ester of hydroxy fatty acid (FAHFA) is selected from the group consisting of palmitic acid ester of hydroxystearic acid (PAHSA), steric acid ester of hydroxy stearic acid (SAHSA), and lauric acid ester of hydroxy stearic acid (LAHSA).

25. The composition of claim 1, wherein n1comprises a double bond.

26. The composition of claim 1, wherein n1is27. The composition of claim 1, wherein n1is (CH2)7HC=CH(CH2)9, n2is C12-alkyl, and n3is C3-alkyl.

28. The composition of claim 1, wherein n1is (CH2)7HC=CH(CH2)9, n2is C14-alkyl, and n3is C1-alkyl.

29. The composition of claims 26 to 28, wherein the fatty acid ester of hydroxy fatty acid (FAHFA) is oleic acid ester of hydroxy stearic acid (OAHSA).

30. The composition of any one of the preceding claims, further comprising water, a humectant, a water thickener, a pH adjuster, an emulsifier, a co-emulsifier, an emollient, and a preservative.

31. The composition of claim 30, wherein the humectant is selected from the group consisting of honey, silk amino acids, trehalose, glycerine, erythritol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, maltitol, inositol, and combinations thereof.

32. The composition of any one of claim 30 to 31 , wherein the humectant is glycerine.

33. The composition of claim 30, wherein the water thickener is a water-soluble polymer.

34. The composition of claim 33, wherein the water thickener is selected from the group consisting of carbomcr, agar, agarose, acacia gum, amylopectin, chitin, dextran, cassia gum, cellulose gum, gelatin, hydroxycthyl cellulose, methyl cellulose, ethyl cellulose, pectin, xanthan gum, pectin, trchclosc, gelatin, ammonium alginate, guar gum, karaya gum, kelp, locust bean gum, natto gum, potassium alginate, sodium carboyxmethyl dextran, and combinations thereof.

35. The composition of any one of claims 33 to 34, wherein the water thickener is carbomer.

36. The composition of claim 30, wherein the pH adjuster is selected from the group consisting of sodium hydroxide, triethanolamine, malonic acid, succinic acid, sodium succinate, dodecanedioic acid, diethyl malonate, decyl succinate, dimethyl succinate, diethyl succinate, dicapryl succinate, dicetearyl succinate, diisobutyl succinate, diethylhexyl succinate, diisostearyl glutarate, dimethyl adipate, diethyl adipate, dipropyl adipate, dibutyl adipate, dihexyl adipate, dicapryl adipate, di-Cl 2- 15 alkyl adipate, ditridecyl adipate, dicetyl adipate, diisopropyl adipate, diisobutyl adipate, diethylhexyl adipate, diisooctyl adipate, diisononyl adipate, diisodecyl adipate, dihexyldecyl adipate, diheptylundecyl adipate, dioctyldodecyl adipate, diisocetyl adipate, diisostearyl adipate, and combinations thereof.

37. The composition of claim 36, wherein the pH adjuster is sodium hydroxide, or triethanolamine.

38. The composition of claim 30, wherein the emulsifier is an anionic, a non-ionic emulsifier, and combinations thereof.

39. The composition of claim 38, wherein the emulsifier is selected from the group consisting of glyceryl stearate, PEG- 100 stearate, ethers of polyglycols and of fatty alcohols, esters of polyglycols and of fatty acids, and combinations thereof.

40. The composition of any one of claims 38 to 39, wherein the emulsifier is glyceryl stearate and / or PEG- 100 stearate.

41. The composition of claim 40, wherein the co-emulsifier is fatty alcohol.

42. The composition of claim 41, wDraftherein the co-emulsifier is selected from the group consisting of cetearyl alcohol, polyol alkyl esters, glycerol and / or sorbitan esters, polyglyceryl-4 isostearate, sorbitan isostearate, sorbitan glyceryl isostearate, and combinations thereof.

43. The composition of any one of claims 41 to 42, wherein the co-emulsifier is cetearyl alcohol.

44. The composition of claim 30, wherein the emollient is an ester oil.

45. The composition of claim 44, wherein the emollient is selected from the group consisting of isopropyl myristate, isopropyl palmitate, isopropyl isostearate, cetyl acetate, wheat germ glycerides, isopropyl lanolate, hydrogenated coco-glycerides, and combinations thereof .

46. The composition of any one of claims 44 to 45, wherein the emollient is isopropyl myristate.

47. The composition of claim 30, wherein the preservative is selected from the group consisting of phenoxyethanol, decylene glycol, 1,2-hexanediol, phenoxyethanol, formaldehyde solution, parabens, pentanediol, sorbic acid, and combinations thereof.

48. The composition of claim 47, wherein the preservative is selected from the group consisting of phenoxyethanol, decylene glycol, 1,2-hcxancdiol, and combinations thereof.

49. The composition of claim 30, wherein the composition comprises water, a humectant, a water-soluble polymer, fatty alcohol, ester oil; wherein the pH adjuster is selected from the group consisting of sodium hydroxide or triethanolamine; wherein the emulsifier is selected from the group consisting of glyceryl stearate or PEG- 100 stearate; wherein the humectant is glycerine; and wherein the preservative is selected from the group consisting of a phenoxyethanol, decylene glycol, or 1,2-hcxancdiol.

50. The composition of claim 49, wherein the composition comprises palmitic acid ester of hydroxystearic acid (PAHSA), water, a humectant, a water-soluble polymer, fatty alcohol, ester oil;wherein the pH adjuster is selected from the group consisting of sodium hydroxide or triethanolamine; wherein the emulsifier is selected from the group consisting of glyceryl stearate orPEG- 100 stearate; wherein the humectant is glycerine; and wherein the preservative is selected from the group consisting of a phenoxyethanol, decylene glycol, or 1,2-hexanediol.

51. The composition of claim 50, wherein the concentration of palmitic acid ester of hydroxystearic acid (PAHSA) is at least 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, of the total weight.

52. The composition of claim 49, wherein the composition comprises steric acid ester of hydroxy stearic acid (SAHSA), water, a humectant, a water-soluble polymer, fatty alcohol, ester oil; wherein the pH adjuster is selected from the group consisting of sodium hydroxide or triethanolamine; wherein the emulsifier is selected from the group consisting of glyceryl stearate orPEG- 100 stearate; wherein the humectant is glycerine; and wherein the preservative is selected from the group consisting of a phenoxyethanol, decylene glycol, or 1,2-hexanediol.

53. The composition of claim 52, wherein the concentration of steric acid ester of hydroxy stearic acid (SAHSA) is at least 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, of the total weight.

54. The composition of any one of the preceding claims, wherein the composition is formulated for dermal application.

55. A method of treating dry and / or scaly skin, wherein the method comprises applying the composition of any one of the preceding claims to the dermal surface of a subject in need thereof.

56. A method of preventing trans-epidermal water loss (TEWL), wherein the method comprises applying the composition of any one of the preceding claims to the dermal surface of a subject in need thereof.

57. The method of claims 55 or 56, wherein the method decreases trans-epidermal water loss (TEWL) on a subject’s skin compared to when the composition is not applied.

58. A method of preparing a fatty acid ester of hydroxy fatty acid of Formula (1):the method comprising the steps of: contacting a hydroxy fatty acid with a fatty acid; wherein said contact results in production of a fatty acid ester of hydroxy fatty acid of Formula (I) as defined in claim 1.

59. The method of claim 58, wherein the hydroxy fatty acid is a hydroxy stearic acid.

60. The method of claim 58, wherein the fatty acid is selected from the group consisting of palmitic acid, stearic acid, lauric acid, and oleic acid.

61. The method of claim 58, wherein the fatty acid ester of hydroxy fatty acid is a palmitic acid ester of hydroxystearic acid (PAHS A).

62. The method of claim 58, wherein the fatty acid ester of hydroxy fatty acid is a stearic acid ester of hydroxy stearic acid (SAHSA).

63. The method of claim 58, wherein the fatty acid ester of hydroxy fatty acid is a lauric acid ester of hydroxystearic acid (LAHSA).

64. The method of claim 58, wherein the fatty acid ester of hydroxy fatty acid is an oleic acid ester of hydroxy stearic acid (OAHSA).

65. The method of any one of claims 58 to 64, wherein the method is a transesterification.

66. The method of any one of claims 58 to 65, wherein the method is chemical or enzymatic.

67. The method of claim 66, wherein the method is performed enzymatically using a lipase.

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