Specific combinations of lipids and related methods and uses

Abstract

The present invention relates to the fields of life science and medicine. In particular, the present invention relates to a composition comprising a specific combination of lipids and, optionally, one or more additives, and to a method for preparing said composition. Furthermore, the present invention relates to the composition of the present invention for use as a medicament, for use in the treatment of dry eye disease and / or meibomian gland dysfunction, and for use in relieving eye discomfort. Furthermore, the present invention relates to a method for treating dry eye disease and / or meibomian gland dysfunction or relieving eye discomfort. Furthermore, the present invention relates to a non-therapeutic or therapeutic method of slowing water evaporation, and to the use of the composition of the present invention to prevent water evaporation.

Description

[Technical field]

[0001] The present invention relates to the fields of life science and medicine. More particularly, the present invention relates to a composition comprising a specific combination of lipids and, optionally, one or more additives, and a method for preparing said composition. Furthermore, the present invention relates to the composition of the present invention for use as a medicament, for use in the treatment of dry eye disease and / or meibomian gland dysfunction, and for use in relieving eye discomfort. Furthermore, the present invention relates to a method for treating dry eye disease and / or meibomian gland dysfunction or relieving eye discomfort. Furthermore, the present invention relates to a non-therapeutic or therapeutic method of slowing water evaporation, and the use of the composition of the present invention to prevent water evaporation. [Background technology]

[0002] Dry eye disease (DED) affects 300-500 million people worldwide and represents a serious economic burden with annual management costs of $55 billion in the United States alone. DED is the most common reason for seeking medical ophthalmic care and constitutes a significant public health concern and a substantial socio-economic burden. The underlying cause of DED is meibomian gland dysfunction, which alters the tear film lipid layer (TFLL) composition and results in tear film instability. Although a significant amount of research has been invested in understanding DED and providing improved treatments, the most commonly used treatments remain ocular lubricants and artificial tears. These treatments focus on reducing DED symptoms and are often accompanied by unsatisfactory results due to their inability to efficiently target tear film instability defects. Other treatment options, such as topical corticosteroids, are used to treat the resulting ocular surface inflammation, which is associated with severe side effects in long-term use, a pitfall considering the chronic nature of some cases of DED. Novel DED treatment strategies aimed at restoring tear film stability are sorely needed.

[0003] In recent years, there has been growing interest in more efficient management of meibomian gland dysfunction (MGD) and DED (Jones, L., et al. 2017, The Ocular Surface, 15, 575-628). The meibomian glands produce the tear film lipid layer (TFLL), which is the outermost layer of the tear film that covers the ocular surface. TFLLs are unique biological membranes composed primarily of very long chain non-polar wax esters (WE) and cholesteryl esters (CE), with scarce amounts of more polar lipids such as O-acyl-ω-hydroxy fatty acids (OAHFAs) (Brown, S., H., et al. 2013, Invest Ophthalmol Vis Sci, 54, 7417-7423; Lam, S., M., et al. 2014, J Lipid Res, 55, 299-306; Rohit, A., et al. 2014, Optometry and Vision Science, 91, 1384-1390). TFLL dysfunction associated with MGD and DED is currently believed to cause a partial loss of evaporative resistance in the TFLL, which leads to excessive evaporation of tears from the aqueous layer of the tear film and destabilization of the tear film, resulting in dry eye and DED (Craig, J., P., et al. 2017, The Ocular Surface, 15, 276-283).

[0004] There is a clear need for new, effective and specific compositions and methods for treating and / or alleviating the symptoms of DED, MGD, and ocular discomfort. In this regard, novel therapeutic strategies aimed at restoring tear film stability are required and are central to future success in this field. Summary of the Invention [Problem to be solved by the invention]

[0005] Shortcomings of the prior art, including but not limited to the lack of simple, safe, effective, low-cost compositions and methods for preventing water loss or treating and / or alleviating the symptoms of DED and / or MGD, may be overcome with the present invention. [Means for solving the problem]

[0006] The objectives of the present invention, i.e., a simple, safe, low-cost, and effective composition and method for preventing or slowing water evaporation, restoring tear film stability, or treating DED and / or MGD, are achieved by utilizing a specific combination of lipids. The composition of the present invention has an excellent inhibitory effect on water evaporation. In fact, the evaporation resistance achieved with the composition is unparalleled. This remarkable property means that the composition can be utilized to prevent or slow water evaporation from any material and any surroundings. Thus, suitable applications of the composition of the present invention include, but are not limited to, human, any animal, and any material that contains water, and also the treatment of disorders or the prevention / slowing of water evaporation in natural environments such as artificial lakes and reservoirs. The latter application presents an increasing challenge due to global climate change.

[0007] The compositions of the present invention can spread well on aqueous surfaces such as the surface of the tear fluid and can form an effective anti-evaporation film by themselves. Furthermore, the compositions of the present invention are highly natural, allowing the use of natural lipids or their structural analogs by themselves in specific combinations.

[0008] The present invention is based on the idea of ​​using a combination comprising a fatty acid ester of a hydroxy fatty acid (FAHFA) (e.g., O-acyl-ω-hydroxy fatty acid) or its structural analogues and a wax ester (or its structural analogues). The combination rapidly self-assembles at the air-tear interface to form an anti-evaporation barrier. The microscale structure and biophysical properties of the conditioned lipid composition of the present invention reveal the advantages of the present invention over the prior art. The biophysical properties are due to the intrinsic properties of such compositions and are not directly related to the surrounding environment.

[0009] Synergistic and significantly enhanced effects may be obtained with the compositions of the present invention when compared to FAHFAs, OAHFAs, or wax esters alone.

[0010] Specifically, the present invention relates to compositions comprising a combination of fatty acid esters of hydroxy fatty acids (FAHFAs) or structural analogs thereof, wax esters or structural analogs thereof, and, optionally, one or more additives.

[0011] The present invention also relates to a composition of the invention for use as a medicament.

[0012] Furthermore, the present invention relates to compositions of the present invention for use in the treatment of dry eye disease and / or meibomian gland dysfunction, or for use in the relief of ocular discomfort.

[0013] Additionally, the present invention relates to a method of preparing a composition of the present invention, the method comprising combining or mixing a FAHFA or a structural analog thereof, a wax ester or a structural analog thereof, and, optionally, one or more additives.

[0014] The present invention further relates to a non-therapeutic or therapeutic method of preventing water evaporation, the method comprising applying the composition of the present invention to a surface to obtain a reduced evaporation rate or to a material to obtain a reduced evaporation rate.

[0015] The present invention relates to the use of the compositions of the present invention to prevent evaporation of water.

[0016] Additionally, the present invention relates to a method of treating dry eye disease and / or meibomian gland dysfunction or relieving ocular discomfort, the method comprising administering a composition of the present invention to the ocular surface of a subject in need thereof.

[0017] The present invention further relates to the use of a FAHFA or a structural analog thereof, and a wax ester or a structural analog thereof, and optionally one or more additives, in the manufacture of a medicament for the treatment of dry eye disease or meibomian gland dysfunction or the relief of ocular discomfort.

[0018] The present invention also relates to novel branched wax esters and methods for their preparation.

[0019] The object of the invention is achieved by compositions, uses and methods which are characterized by what is stated in the independent claims. Preferred embodiments of the invention are disclosed in the dependent claims.

[0020] Other objects, details and advantages of the present invention will become apparent from the following drawings, detailed description and examples. [Brief description of the drawings]

[0021] [Figure 1A] The surface pressure isotherms of the 20-(oleoyloxy)eicosanoic acid (20-OAHFA):arachidyl oleate (AO)-mixture are revealed together with the corresponding Brewster angle microscopy image (Figure 1C). The results are shown as a function of area / molecule (inset). [Figure 1B] The surface potential isotherm of the 20-(oleoyloxy)eicosanoic acid (20-OAHFA):arachidyl oleate (AO)-mixture is revealed together with the corresponding Brewster angle microscopy image (Figure 1C). The results are shown as a function of area / molecule (inset). [Figure 1C] Corresponding Brewster angle microscopy images are revealed. Selected images correspond to the following conditions: (i) a mixed liquid monolayer of 20-OAHFA and AO, (ii) the collapse of AO on the monolayer surface, (iii) the coexistence of gas and liquid monolayer phases, and (iv) the formation of solid monolayer domains by 20-OAHFA with AO on top. [Figure 1D] In addition, a schematic of the molecular organization of the film is shown with 20-OAHFA molecules in orange (dark grey) and AO molecules in yellow (light grey) (oxygen atoms are shown in black). Selected images correspond to the following conditions: (i) a mixed liquid monolayer of 20-OAHFA and AO, (ii) the collapse of AO on the monolayer surface, (iii) the coexistence of gas and liquid monolayer phases, and (iv) the formation of solid monolayer domains by 20-OAHFA with AO on top. [Diagram 2]1 shows the evaporation resistance on a seconds per centimeter (s / cm) scale for 20-OAHFA:AO blends as a function of area / OAHFA. [Figure 3A] The surface pressure isotherm of the 20-OAHFA:behenyl oleate (BO) mixture is shown together with the corresponding Brewster angle microscopy image (Figure 3C). [Figure 3B] The surface potential isotherm of the 20-OAHFA:behenyl oleate (BO) mixture is shown together with the corresponding Brewster angle microscopy image (FIG. 3C). [Figure 3C] Corresponding Brewster angle microscopy images are shown. Selected images correspond to the following conditions: (i, ii) formation of mixed solid monolayer domains of 20-OAHFA:BO, (iii) excess BO remaining as solid aggregates unmixed in the monolayer, and (iv) a solid mixed monolayer with collapsed excess BO aggregates on the monolayer surface. [Figure 3D] A schematic of the molecular organization of a 20-OAHFA:BO blended film during compression shows 20-OAHFA molecules in orange (dark grey) and BO molecules in yellow (light grey) (oxygen atoms are shown in black). Selected images correspond to the following conditions: (i, ii) formation of mixed solid monolayer domains of 20-OAHFA:BO, (iii) excess BO unmixed in the monolayer remaining as solid aggregates, and (iv) a solid mixed monolayer with excess BO aggregates collapsed on the monolayer surface. [Figure 4] Figure 1 shows the evaporation resistance of 20-OAHFA:BO mixtures at different areas per molecule on the scale of s / cm as a function of film composition (fraction of 20-OAHFA). [Diagram 5]Figure 1 shows the evaporation resistance on a seconds / centimeter (s / cm) scale for the following 1:1 mixtures as a function of area / molecule: 18-(oleoyloxy)stearic acid (18:0 / 18:1 OAHFA):behenyl behenoate (BB), (21Z)-29-(oleoyloxy)nonacos-21-enoic acid (29:1 / 18:1 OAHFA):BO, 18:0 / 18:1-OAHFA:BO, and 18:0 / 18:1-OAHFA:arachidyl laurate (AL). Combinations of 18:0 / 18:1-OAHFA and BO, and 18:0 / 18:1-OAHFA and AL showed improved evaporation resistance compared to the individual components at all areas per molecule, but the average molecular area values ​​were less than 10 Å2, which was too high to determine without recalibration of the instrument. The combinations of 18:0 / 18:1 OAHFA and BB, and 29:1 / 18:1 OAHFA:BO showed no improvement in evaporation resistance. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0022] The tear film consists of two distinct layers, the aqueous layer and the TFLL, which is believed to function as a barrier against evaporation of water from the underlying aqueous layer. Loss of this evaporative resistance function leads to dry eyes in the majority of DED cases, which can further lead to inflammation and ocular surface damage.

[0023] In this invention, the inventors developed a synthetic protocol for the synthesis of an extensive library of TFLL FAHFAs and wax esters, as well as their structural analogs. Using this library, the inventors identified a mixture of key lipid species that combines effective diffusion on the aqueous interface with very high evaporation resistance, in line with the functional principles of intact TFLLs. More specifically, the lipids must rapidly diffuse and cover the entire aqueous tear film surface when the eye is open, and the membrane formed by the lipids must have a condensed structure that prevents or retards the passage of water molecules through it. The result of this invention is a composition of FAHFAs and wax esters that forms an evaporation-resistant barrier on the aqueous interface under physiological conditions. The administration of these lipid compositions onto the ocular surface represents a unique and highly promising treatment for DED and / or ocular discomfort. Moreover, since the biophysical properties are derived from the intrinsic properties of the mixture itself and are not directly related to the surrounding environment, these mixtures can be used to prevent water evaporation from materials and other environments, e.g., artificial lakes and water reservoirs, in a similar manner. The latter challenge presents an increasing problem due to global climate change.

[0024] As used herein, "physiological conditions" takes its ordinary meaning in the art, i.e., refers to the conditions that one of ordinary skill in the art would normally expect at the ocular surface of a subject, such as a human or animal (e.g., a human). For the avoidance of doubt, physiological conditions at the ocular surface of a human or animal may be a temperature of about 35° C., a surface pressure of about 27-31 mN / m, and a pH of about 7.0-7.3. Reference to the physical state of lipids (i.e., FAHFAs and / or wax esters) at (or under) physiological conditions may be understood to refer specifically to the physical state (i.e., liquid or solid) of the lipid in question at a temperature of about 35° C. and atmospheric pressure.

[0025] The present invention relates to a composition comprising or consisting of i) two different types of lipids, such as a combination of polar lipids and non-polar lipids, and optionally ii) one or more additives. In one embodiment, the composition comprises or consists of a combination of i) a polar lipid selected from the group consisting of FAHFAs and their structural analogs, and a non-polar lipid selected from the group consisting of wax esters and their structural analogs, and optionally ii) one or more additives. In one embodiment, the only lipids in the composition are one or more FAHFAs or their structural analogs (such as OAHFAs) and one or more wax esters (i.e., esters of fatty acids and fatty alcohols) or their structural analogs.

[0026] The present invention further relates to compositions comprising or consisting of a combination of a FAHFA or structural analogues thereof, a wax ester or structural analogues thereof, and, optionally, one or more additives. In one embodiment, these compositions do not contain any additional FAHFA (including structural analogues thereof) or wax ester (including structural analogues thereof) components.

[0027] In one embodiment, the evaporation resistance of the composition is greater than 1 s / cm, greater than 2 s / cm, or greater than 3 s / cm. In one embodiment, the evaporation resistance value can be as high as possible, such as greater than 5 s / cm, greater than 9 s / cm, greater than 10 s / cm, greater than 13 s / cm, greater than 15 s / cm, greater than 20 s / cm, greater than 25 s / cm, or even greater than 30 s / cm. More specifically, the evaporation resistance of the composition is higher than the evaporation resistance of the natural tear-forming lipid layer, which is reported as 9 to 13 s / cm. Thus, the evaporation resistance of the composition is preferably greater than 15 s / cm (e.g., greater than 20 s / cm (e.g., 15 to 20 s / cm), such as 15 to 30 s / cm). In particular, such evaporation resistance value is from about 2 to about 5 Å. 2 (e.g., 2-3 Å 2 ) etc. 2 to 10 Å 2 This is achieved with an average average molecular area of ​​.

[0028] As used herein, "evaporation resistance" refers to the ability of a composition to prevent water from evaporating, and optionally the composition is on or above the surface of a material or drug that should be prevented from evaporating. Evaporation resistance can be defined as r=Δc / J, where Δc is the water vapor concentration difference that drives evaporation, J is the evaporation flux from the lower aqueous phase defined as J=(dn / dt) / A, n is the amount of water that evaporates, t is time, and A is the area of ​​the surface. The evaporation resistance of a composition is a property of the lipid film that is present on or above an aqueous surface, independent of the measurement method and conditions of measurement, and can be measured by any method known to those skilled in the art, for example, as described in Section 1.2.4 of the Examples section of this disclosure, or as described in Langmuir et al. (Langmuir, I. and Schaefer, V., J.1943, J.Franklin Inst., Vol.235,119-162).

[0029] Specifically, the evaporation resistance of a composition can be determined by: 1. Measure the evaporation flux from an aqueous surface in the absence of the composition (J w ), 2. The composition is applied to an aqueous surface and the evaporation flux from the surface on which the composition is present is measured (J f ), 3. Evaporation resistance of the composition (r m ) into the formula r m = Δc(1 / J f -1 / J w ) where Δc = water vapor concentration difference driving evaporation.

[0030] Δc can be determined by methods known to those skilled in the art, but for water surface temperatures of 30-35°C at atmospheric pressure, it is 3.4±0.7·10 -5 g cm -3 It is also possible to use the following.

[0031] As described herein, the evaporative resistance may be expressed in units of seconds per centimeter (s / cm). This may be related to the rate of reduction of the evaporation rate at the ocular surface using a model developed by Cerretani et al. (Cerretani, CF; Ho, NH; Radke, CJ, Water-Evaporation Reduction by Duplex Films: Application to the Human Tear Film, Adv. Colloid Interface Sci. 2013, 197-198, 33-57). Using this model, an evaporative resistance of 2s / cm reduces the evaporation rate at the ocular surface by 33-50%, and a value such as 5s / cm corresponds to a reduction of 60-80% when a person is stationary or walking.

[0032] In one embodiment, the two lipid composition of FAHFA such as OAHFA and wax ester provides exceptionally high evaporation resistance. The evaporation resistance is the result of the complex interaction between FAHFA and other specific lipids of the composition of the present invention, namely wax ester. The present disclosure can relate the evaporation resistance to a very specific densely packed condensed lipid structure.

[0033] The carbon chain length of the one or more FAHFAs or analogs thereof suitable for the compositions of the present invention may vary. In one embodiment, there is no maximum carbon length. In one embodiment, the carbon chain length of the one or more FAHFAs or structural analogs thereof is C15-C100, C19-C72, C20-C55, C20-C50, C20-C40, C20-C35, C20-C25, C25-C45, C25-C40, C25-C35, or C25-C30. In one embodiment, the carbon chain length of one or more FAHFAs or structural analogs thereof is C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34, C35, C36, C37, C38, C39, C40, C41, C42, C43, C44, C45, C46, ​​C47, C48, C49, C50, C51, C52, C53, C54 or C55.

[0034] In one embodiment, the FAHFAs or structural analogs thereof have the following formula (I): [ka] During the ceremony, R1 is a carbon atom, an oxygen atom, or a nitrogen atom; R2 is a linear or branched C9-C50 alkyl, alkenyl, or alkynyl chain, or structural analogs thereof; R3 is a carboxyl, hydroxyl, amine, phosphate or silyl ether; R4 is a linear or branched C9 to C50 alkyl, alkenyl, or alkynyl chain, or structural analogs thereof.

[0035] In one embodiment, R1 in formula I is an oxygen atom. When R1 in formula I is an oxygen atom, the composition of the present invention remains stable long enough but still decomposes spontaneously. In one embodiment, the one or more FAHFAs are selected from the group comprising or consisting of O-acyl-ω-hydroxy fatty acids (OAHFAs).

[0036] In one embodiment, the one or more FAHFAs or OAHFAs include or are selected from the group consisting of oleic acid fatty acid esters, palmitoleic acid fatty acid esters, myristoleic acid fatty acid esters, lauric acid fatty acid esters, paulinic acid fatty acid esters, gondoic acid fatty acid esters, erucic acid fatty acid esters, nervonic acid fatty acid esters, linoleic acid fatty acid esters, and linolenic acid fatty acids, and / or structural analogs thereof. In one embodiment, the one or more FAHFAs or OAHFAs include or are selected from the group consisting of oleic acid fatty acid esters, palmitoleic acid fatty acid esters, linoleic acid fatty acid esters, and linolenic acid fatty acid esters, and / or structural analogs thereof.

[0037] In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of or comprise oleic acid based fatty acid esters. In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of 12-oleoyloxy-dodecanoic acid, 13-oleoyloxy-tridecanoic acid, 14-oleoyloxy-tetradecanoic acid, 15-oleoyloxy-pentadecanoic acid, 16-oleoyloxy-hexadecanoic acid, 17-oleoyloxy-heptadecanoic acid, 18-oleoyloxy-octadecanoic acid, 19-oleoyloxy-nonadecanoic acid, 20-oleoyloxy-eicosanoic acid, 21-oleoyloxy-heneicosanoic acid, 22-oleoyloxy-docosanoic acid, 23-oleoyloxy-tricosanoic acid, 24-oleoyloxy-tetracosanoic acid, 25-oleoyloxy-pentacosanoic acid, 26-oleoyloxy-hexacosanoic acid, 27-oleoyloxy-hexacosanoic acid, 28-oleoyloxy-hexacosanoic acid, 29-oleoyloxy-hexacosanoic acid, 30-oleoyloxy-hexacosanoic acid, 31-oleoyloxy-hexacosanoic acid, 32-oleoyloxy-hexacosanoic acid, 33-oleoyloxy-hexacosanoic acid, 34-oleoyloxy-hexacosanoic acid, 35-oleoyloxy-hexacosanoic acid, 36-oleoyloxy-hexacosanoic acid, 37-oleoyloxy-hexacosanoic acid, 38-oleoyloxy-hexacosanoic acid, 39-oleoyloxy-hexacosanoic acid, 40-ole In one embodiment, the oleoyloxy-hexatriacontanoic acid is selected from the group consisting of 2-oleoyloxy-heptatriacontanoic acid, 28-oleoyloxy-octacosanoic acid, 29-oleoyloxy-nonacosanoic acid, 30-oleoyloxy-triacontanoic acid, 31-oleoyloxy-hentriacontanoic acid, 32-oleoyloxy-dotriacontanoic acid, 33-oleoyloxy-tritriacontanoic acid, 34-oleoyloxy-tetratriacontanoic acid, 35-oleoyloxy-pentatriacontanoic acid, 36-oleoyloxy-hexatriacontanoic acid, 37-oleoyloxy-heptatriacontanoic acid, 38-oleoyloxy-octatriacontanoic acid, 39-oleoyloxy-nonatriacontanoic acid, and 40-oleoyloxy-tetratriacontanoic acid.

[0038] In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group comprising or consisting of palmitoleic acid based fatty acid esters. In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of 12-palmitoleoyloxy-dodecanoic acid, 13-palmitoleoyloxy-tridecanoic acid, 14-palmitoleoyloxy-tetradecanoic acid, 15-palmitoleoyloxy-pentadecanoic acid, 16-palmitoleoyloxy-hexadecanoic acid, 17-palmitoleoyloxy-heptadecanoic acid, 18-palmitoleoyloxy-octadecanoic acid, 19-palmitoleoyloxy-nonadecanoic acid, 20-palmitoleoyloxy-eicosanoic acid, 21-palmitoleoyloxy-heneicosanoic acid, 22-palmitoleoyloxy-docosanoic acid, 23-palmitoleoyloxy-tricosanoic acid, 24-palmitoleoyloxy-tetracosanoic acid, 25-palmitoleoyloxy-pentacosanoic acid, 26-palmitoleoyloxy-hexacosanoic acid, 27-palmitoleoyloxy-hexacosanoic acid, 28-palmitoleoyloxy-hexacosanoic acid, 29-palmitoleoyloxy-hexacosanoic acid, 30-palmitoleoyloxy-hexacosanoic acid, 31-palmitoleoyloxy-hexacosanoic acid, 32-palmitoleoyloxy-hexacosanoic acid, 33-palmitoleoyloxy-hexacosanoic acid, 34-palmitoleoyloxy-hexacosanoic acid, 35-palmitoleoyloxy-hexacosanoic acid, 36-palmitoleoyloxy-hexacosanoic acid, 37-palmitoleoyloxy-hexacosanoic acid, 38-palmitoleoyloxy-hexacosanoic acid, 39- The hydroxyl group may be selected from the group comprising or consisting of mitoleoyloxy-heptacosanoic acid, 28-palmitoleoyloxy-octacosanoic acid, 29-palmitoleoyloxy-nonacosanoic acid, 30-palmitoleoyloxy-triacontanoic acid, 31-palmitoleoyloxy-hentriacontanoic acid, 32-palmitoleoyloxy-dotriacontanoic acid, 33-palmitoleoyloxy-tritriacontanoic acid, 34-palmitoleoyloxy-tetratriacontanoic acid, 35-palmitoleoyloxy-pentatriacontanoic acid, 36-palmitoleoyloxy-hexatriacontanoic acid, 37-palmitoleoyloxy-heptatriacontanoic acid, 38-palmitoleoyloxy-octatriacontanoic acid, 39-palmitoleoyloxy-nonatriacontanoic acid, and 40-palmitoleoyloxy-tetracontanoic acid.

[0039] In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group comprising or consisting of myristoleic acid based fatty acid esters. In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of 12-myristoleoyloxy-dodecanoic acid, 13-myristoleoyloxy-tridecanoic acid, 14-myristoleoyloxy-tetradecanoic acid, 15-myristoleoyloxy-pentadecanoic acid, 16-myristoleoyloxy-hexadecanoic acid, 17-myristoleoyloxy-heptadecanoic acid, 18-myristoleoyloxy-octadecanoic acid, 19-myristoleoyloxy-nonadecanoic acid, 20-myristoleoyloxy-eicosanoic acid, 21-myristoleoyloxy-heneicosanoic acid, 22-myristoleoyloxy-docosanoic acid, 23-myristoleoyloxy-tricosanoic acid, 24-myristoleoyloxy-tetracosanoic acid, 25-myristoleoyloxy-pentacosanoic acid, 26-myristoleoyloxy-hexacosanoic acid, 27-myristoleoyloxy-hexanoic acid, 28-myristoleoyloxy-hexanoic acid, 29-myristoleoyloxy-hexanoic acid, 30-myristoleoyloxy-hexanoic acid, 31-myristoleoyloxy-hexanoic acid, 32-myristoleoyloxy-hexanoic acid, 33-myristoleoyloxy-hexanoic acid, 34-myristoleoyloxy-hexanoic acid, 35-myristoleoyloxy-hexanoic acid, 36-myristoleoyloxy-hexanoic acid, 37-myristoleoyloxy-hexanoic acid, 38-myristoleoyloxy-hexanoic acid, The compound is selected from the group comprising or consisting of streaeoyloxy-heptacosanoic acid, 28-myristreaeoyloxy-octacosanoic acid, 29-myristreaeoyloxy-nonacosanoic acid, 30-myristreaeoyloxy-triacontanoic acid, 31-myristreaeoyloxy-hentriacontanoic acid, 32-myristreaeoyloxy-dotriacontanoic acid, 33-myristreaeoyloxy-tritriacontanoic acid, 34-myristreaeoyloxy-tetratriacontanoic acid, 35-myristreaeoyloxy-pentatriacontanoic acid, 36-myristreaeoyloxy-hexatriacontanoic acid, 37-myristreaeoyloxy-heptatriacontanoic acid, 38-myristreaeoyloxy-octatriacontanoic acid, 39-myristreaeoyloxy-nonatriacontanoic acid, and 40-myristreaeoyloxy-tetracontanoic acid.

[0040] In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group comprising or consisting of lauric acid based fatty acid esters. In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of 12-dodecanoyloxy-dodecanoic acid, 13-dodecanoyloxy-tridecanoic acid, 14-dodecanoyloxy-tetradecanoic acid, 15-dodecanoyloxy-pentadecanoic acid, 16-dodecanoyloxy-hexadecanoic acid, 17-dodecanoyloxy-heptadecanoic acid, 18-dodecanoyloxy-octadecanoic acid, 19-dodecanoyloxy-nonadecanoic acid, 20-dodecanoyloxy-eicosanoic acid, 21-dodecanoyloxy-heneicosanoic acid, 22-dodecanoyloxy-docosanoic acid, 23-dodecanoyloxy-tricosanoic acid, 24-dodecanoyloxy-tetracosanoic acid, 25-dodecanoyloxy-pentacosanoic acid, 26-dodecanoyloxy-hexacosanoic acid, 27-dodecanoyloxy-hexacosanoic acid, 28-dodecanoyloxy-hexacosanoic acid, 29-dodecanoyloxy-hexacosanoic acid, 30-dodecanoyloxy-hexacosanoic acid, 31-dodecanoyloxy-hexacosanoic acid, 32-dodecanoyloxy-hexacosanoic acid, 33-dodecanoyloxy-hexacosanoic acid, 34-dodecanoyloxy-hexacosanoic acid, 35-dodecanoyloxy-hexacosanoic acid, 36-dodecanoyloxy-hexacosanoic acid, 37-dodecanoyloxy-hexacosanoic acid, 38-dodecanoyloxy-hexacosanoic acid, 39-dodecanoyloxy-hexacosanoic acid, 40-dodecanoyloxy-hexacosano In one embodiment, the compound is selected from the group including or consisting of dodecanoyloxy-heptatriacontanoic acid, 28-dodecanoyloxy-octacosanoic acid, 29-dodecanoyloxy-nonacosanoic acid, 30-dodecanoyloxy-triacontanoic acid, 31-dodecanoyloxy-hentriacontanoic acid, 32-dodecanoyloxy-dotriacontanoic acid, 33-dodecanoyloxy-tritriacontanoic acid, 34-dodecanoyloxy-tetratriacontanoic acid, 35-dodecanoyloxy-pentatriacontanoic acid, 36-dodecanoyloxy-hexatriacontanoic acid, 37-dodecanoyloxy-heptatriacontanoic acid, 38-dodecanoyloxy-octatriacontanoic acid, 39-dodecanoyloxy-nonatriacontanoic acid, and 40-dodecanoyloxy-tetratriacontanoic acid.

[0041] In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of paulinic acid fatty acid esters. In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of 12-(eicos-13-enoyloxy)-dodecanoic acid, 13-(eicos-13-enoyloxy)-tridecanoic acid, 14-(eicos-13-enoyloxy)-tetradecanoic acid, 15-(eicos-13-enoyloxy)-pentadecanoic acid, 16-(eicos-13-enoyloxy)-hexadecanoic acid, 17-(eicos-13-enoyloxy)-heptadecanoic acid, 18-(eicos-13-enoyloxy)-octadecanoic acid, 19-(eicos-13-enoyloxy)-nonadecanoic acid, 20-(eicos-13-enoyloxy)-eicosanoic acid, 21-(eicos-13-enoyloxy)-heneicosanoic acid, 22-(eicos-13-enoyloxy)-docosanoic acid, 23-(eicos-13-enoyloxy)-tricosanoic acid, 24-(eicos-13-enoyloxy)-tetracosanoic acid, 25-(eicos-13-enoyloxy)-pentacosanoic acid, 26-(eicos-13-enoyloxy)-hexacosanoic acid, 27 -(Eicos-13-enoyloxy)-heptacosanoic acid, 28-(Eicos-13-enoyloxy)-octacosanoic acid, 29-(Eicos-13-enoyloxy)-nonacosanoic acid, 30-(Eicos-13-enoyloxy)-triacontanoic acid, 31-(Eicos-13-enoyloxy)-hentriacontanoic acid, 32-(Eicos-13-enoyloxy)-dotriacontanoic acid, 33-(Eicos-13-enoyloxy)-tritriacontanoic acid, 34-(Eicos-13-enoyloxy) -tetratriacontanoic acid, 35-(eicos-13-enoyloxy)-pentatriacontanoic acid, 36-(eicos-13-enoyloxy)-hexatriacontanoic acid, 37-(eicos-13-enoyloxy)-heptatriacontanoic acid, 38-(eicos-13-enoyloxy)-octatriacontanoic acid, 39-(eicos-13-enoyloxy)-nonatriacontanoic acid, and 40-(eicos-13-enoyloxy)-tetracontanoic acid.

[0042] In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of or comprise gondoic acid fatty acid esters. In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of 12-(eicos-11-enoyloxy)-dodecanoic acid, 13-(eicos-11-enoyloxy)-tridecanoic acid, 14-(eicos-11-enoyloxy)-tetradecanoic acid, 15-(eicos-11-enoyloxy)-pentadecanoic acid, 16-(eicos-11-enoyloxy)-hexadecanoic acid, 17-(eicos-11-enoyloxy)-heptadecanoic acid, 18-(eicos-11-enoyloxy)-octadecanoic acid, 19-(eicos-11-enoyloxy)-nonadecanoic acid, 20-(eicos-11-enoyloxy)-eicosanoic acid, 21-(eicos-11-enoyloxy)-heneicosanoic acid, 22-(eicos-11-enoyloxy)-docosanoic acid, 23-(eicos-11-enoyloxy)-tricosanoic acid, 24-(eicos-11-enoyloxy)-tetracosanoic acid, 25-(eicos-11-enoyloxy)-pentacosanoic acid, 26-(eicos-11-enoyloxy)-hexacosanoic acid, 27 -(Eicos-11-enoyloxy)-heptacosanoic acid, 28-(Eicos-11-enoyloxy)-octacosanoic acid, 29-(Eicos-11-enoyloxy)-nonacosanoic acid, 30-(Eicos-11-enoyloxy)-triacontanoic acid, 31-(Eicos-11-enoyloxy)-hentriacontanoic acid, 32-(Eicos-11-enoyloxy)-dotriacontanoic acid, 33-(Eicos-11-enoyloxy)-tritriacontanoic acid, 34-(Eicos-11-enoyloxy) -tetratriacontanoic acid, 35-(eicos-11-enoyloxy)-pentatriacontanoic acid, 36-(eicos-11-enoyloxy)-hexatriacontanoic acid, 37-(eicos-11-enoyloxy)-heptatriacontanoic acid, 38-(eicos-11-enoyloxy)-octatriacontanoic acid, 39-(eicos-11-enoyloxy)-nonatriacontanoic acid, and 40-(eicos-11-enoyloxy)-tetracontanoic acid.

[0043] In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of erucic acid fatty acid esters. In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of 12-(eicos-13-enoyloxy)-dodecanoic acid, 13-(docos-13-enoyloxy)-tridecanoic acid, 14-(docos-13-enoyloxy)-tetradecanoic acid, 15-(docos-13-enoyloxy)-pentadecanoic acid, 16-(docos-13-enoyloxy)-hexadecanoic acid, 17-(docos-13-enoyloxy)-heptadecanoic acid, 18-(docos-13-enoyloxy)-octadecanoic acid. , 19-(docos-13-enoyloxy)-nonadecanoic acid, 20-(docos-13-enoyloxy)-eicosanoic acid, 21-(docos-13-enoyloxy)-heneicosanoic acid, 22-(docos-13-enoyloxy)-docosanoic acid, 23-(docos-13-enoyloxy)-tricosanoic acid, 24-(docos-13-enoyloxy)-tetracosanoic acid, 25-(docos-13-enoyloxy)-pentacosanoic acid, 26-(docos-13-enoyloxy)-hexacosanoic acid, 27-(docos-13-enoyloxy)-hexacosanoic acid, -(docos-13-enoyloxy)-heptacosanoic acid, 28-(docos-13-enoyloxy)-octacosanoic acid, 29-(docos-13-enoyloxy)-nonacosanoic acid, 30-(docos-13-enoyloxy)-triacontanoic acid, 31-(docos-13-enoyloxy)-hentriacontanoic acid, 32-(docos-13-enoyloxy)-dotriacontanoic acid, 33-(docos-13-enoyloxy)-tritriacontanoic acid, 34-(docos-13-enoyloxy)- The compound is selected from the group including or consisting of tetratriacontanoic acid, 35-(docos-13-enoyloxy)-pentatriacontanoic acid, 36-(docos-13-enoyloxy)-hexatriacontanoic acid, 37-(docos-13-enoyloxy)-heptatriacontanoic acid, 38-(docos-13-enoyloxy)-octatriacontanoic acid, 39-(docos-13-enoyloxy)-nonatriacontanoic acid, and 40-(docos-13-enoyloxy)-tetracontanoic acid.

[0044] In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group comprising or consisting of nervonic acid based fatty acid esters.In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of 12-(tetracos-15-enoyloxy)-dodecanoic acid, 13-(tetracos-15-enoyloxy)-tridecanoic acid, 14-(tetracos-15-enoyloxy)-tetradecanoic acid, 15-(tetracos-15-enoyloxy)-pentadecanoic acid, 16-(tetracos-15-enoyloxy)-hexadecanoic acid, 17-(tetracos-15-enoyloxy)-heptadecanoic acid, 18-(tetracos-15-enoyloxy)-octadecanoic acid, 19-(tetracos-15-enoyloxy)-nonadecanoic acid, 20-(tetracos-15-enoyloxy)-eicosanoic acid, 21-(tetracos-15-enoyloxy)-heneicosanoic acid, 22-(tetracos-15-enoyloxy)-docosanoic acid, 23-(tetracos-15-enoyloxy)-tricosanoic acid, 24-(tetracos-15-enoyloxy)-tetracosanoic acid, 25-(tetracos-15-enoyloxy)-pentacosanoic acid, 26-(tetracos-15-enoyloxy)-hexacosanoic acid, 2 7-(tetracos-15-enoyloxy)-heptacosanoic acid, 28-(tetracos-15-enoyloxy)-octacosanoic acid, 29-(tetracos-15-enoyloxy)-nonacosanoic acid, 30-(tetracos-15-enoyloxy)-triacontanoic acid, 31-(tetracos-15-enoyloxy)-hentriacontanoic acid, 32-(tetracos-15-enoyloxy)-dotriacontanoic acid, 33-(tetracos-15-enoyloxy)-tritriacontanoic acid, 34-(tetracos-15-enoyloxy)- )-tetratriacontanoic acid, 35-(tetracos-15-enoyloxy)-pentatriacontanoic acid, 36-(tetracos-15-enoyloxy)-hexatriacontanoic acid, 37-(tetracos-15-enoyloxy)-heptatriacontanoic acid, 38-(tetracos-15-enoyloxy)-octatriacontanoic acid, 39-(tetracos-15-enoyloxy)-nonatriacontanoic acid, and 40-(tetracos-15-enoyloxy)-tetracontanoic acid.

[0045] In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group comprising or consisting of linoleic acid based fatty acid esters. In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of 12-linoleoyloxy-dodecanoic acid, 13-linoleoyloxy-tridecanoic acid, 14-linoleoyloxy-tetradecanoic acid, 15-linoleoyloxy-pentadecanoic acid, 16-linoleoyloxy-hexadecanoic acid, 17-linoleoyloxy-heptadecanoic acid, 18-linoleoyloxy-octadecanoic acid, 19-linoleoyloxy-nonadecanoic acid, 20-linoleoyloxy-eicosanoic acid, 21-linoleoyloxy-heneicosanoic acid, 22-linoleoyloxy-docosanoic acid, 23-linoleoyloxy-tricosanoic acid, 24-linoleoyloxy-tetracosanoic acid, 25-linoleoyloxy-pentacosanoic acid, 26-linoleoyloxy-hexacosanoic acid, 27-linoleoyloxy-hexanoic acid, 28-linoleoyloxy-hexanoic acid, 29-linoleoyloxy-hexanoic acid, 30-linoleoyloxy-hexanoic acid, 31-linoleoyloxy-hexanoic acid, 32-linoleoyloxy-hexanoic acid, 33-linoleoyloxy-hexanoic acid, 34-linoleoyloxy-hexanoic acid, 35-linoleoyloxy-hexanoic acid, 36-linoleoyloxy-hexanoic acid, 37-linoleoyloxy-hexanoic acid, 38-linoleoyloxy-hexanoic acid, 39-linoleoyloxy-hexanoic acid, 40-linoleoyloxy-hexanoic acid, 41-linoleoyloxy-hexanoic acid, 42-linoleoyloxy- In one embodiment, the linoleoyloxy-hexatriacontanoic acid is selected from the group consisting of 28-linoleoyloxy-heptatriacontanoic acid, 29-linoleoyloxy-nonacosanoic acid, 30-linoleoyloxy-triacontanoic acid, 31-linoleoyloxy-hentriacontanoic acid, 32-linoleoyloxy-dotriacontanoic acid, 33-linoleoyloxy-tritriacontanoic acid, 34-linoleoyloxy-tetratriacontanoic acid, 35-linoleoyloxy-pentatriacontanoic acid, 36-linoleoyloxy-hexatriacontanoic acid, 37-linoleoyloxy-heptatriacontanoic acid, 38-linoleoyloxy-octatriacontanoic acid, 39-linoleoyloxy-nonatriacontanoic acid, and 40-linoleoyloxy-tetratriacontanoic acid.

[0046] In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of linolenic acid based fatty acid esters. In one embodiment, the one or more FAHFAs or OAHFAs are selected from the group consisting of 12-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-dodecanoic acid, 13-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-tridecanoic acid, 14-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-tetradecanoic acid, 15-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-pentadecanoic acid. , 16-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-hexadecanoic acid, 17-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-heptadecanoic acid, 18-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-octadecanoic acid, 19-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-nonadecanoic acid, 20-(((9Z,12Z,15Z)-octadeca-9, 12,15-trienoyl)oxy)-eicosanoic acid, 21-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-heneicosanoic acid, 22-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-docosanoic acid, 23-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-tricosanoic acid, 24-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-tetracosanoic acid, 25- (((9Z,12Z,15Z)-Octadeca-9,12,15-trienoyl)oxy)-pentacosanoic acid, 26-(((9Z,12Z,15Z)-Octadeca-9,12,15-trienoyl)oxy)-hexacosanoic acid, 27-(((9Z,12Z,15Z)-Octadeca-9,12,15-trienoyl)oxy)-heptacosanoic acid, 28-(((9Z,12Z,15Z)-Octadeca-9,12,15-trienoyl)oxy)-octacosanoic acid, 29-(((9Z,12Z,15Z)-Octadeca-9,12,15-trienoyl)oxy)-nonacosanoic acid, 30-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-triacontanoic acid, 31-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-hentriacontanoic acid, 32-(((9Z,12Z,15Z)-octadeca-9,12,15- 33-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-dotriacontanoic acid, 34-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-tetratriacontanoic acid, 35-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-tetratriacontanoic acid, 5-trienoyl)oxy)-pentatriacontanoic acid, 36-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-hexatriacontanoic acid, 37-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-heptatriacontanoic acid, 38-(((9Z,12Z,15Z)-octadeca- 9,12,15-trienoyl)oxy)-octatriacontanoic acid, 39-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-nonatriacontanoic acid, and 40-(((9Z,12Z,15Z)-octadeca-9,12,15-trienoyl)oxy)-tetracontanoic acid.

[0047] In one embodiment, the one or more structural analogs of FAHFA or OAHFA are selected from the group consisting of oleic acid alcohols. In one embodiment, the one or more structural analogs of FAHFA or OAHFA are selected from the group consisting of 12-hydroxydodecyl oleate, 13-hydroxytridecyl oleate, 14-hydroxytetradecyl oleate, 15-hydroxypentadecyl oleate, 16-hydroxyhexadecyl oleate, 17-hydroxyheptadecyl oleate, 18-hydroxyoctadecyl oleate, 19-hydroxynonadecyl oleate, 20-hydroxyeicosyl oleate, 21-hydroxyheneicosyl oleate, 22-hydroxydocosyl oleate, 23-hydroxytricosyl oleate, 24-hydroxytetracosyl oleate, 25-hydroxypentacosyl oleate, 26-hydroxyhexacosyl oleate, 27-hydroxyhexacosyl oleate, 28-hydroxyhexacosyl oleate, 29-hydroxyhexacosyl oleate, 30-hydroxyhexacosyl oleate, 31-hydroxyhexacosyl oleate, 32-hydroxyhexacosyl oleate, 33-hydroxyhexacosyl oleate, 34-hydroxyhexacosyl oleate, 35-hydroxyhexacosyl oleate, 36-hydroxyhexacosyl oleate, 37-hydroxyhexacosyl oleate, 38-hydroxyhexacosyl oleate, 39-hydroxyhexacosyl oleate, 40-hydroxyhexacosyl oleate, 41-hydroxyhexacosyl oleate, 42-hydroxyhexacosyl oleate, 43-hydroxyhexacosyl oleate, 44-hydroxyhexacosyl oleate, 45-hydroxyhexacosyl oleate, 46-hydroxyhexacosyl hydroxyheptatriacontyl oleate, 28-hydroxyoctacosyl oleate, 29-hydroxynonacosyl oleate, 30-hydroxytriacontyl oleate, 31-hydroxyhentriacontyl oleate, 32-hydroxydotriacontyl oleate, 33-hydroxytritriacontyl oleate, 34-hydroxytetratriacontyl oleate, 35-hydroxypentatriacontyl oleate, 36-hydroxyhexatriacontyl oleate, 37-hydroxyheptatriacontyl oleate, 38-hydroxyoctatriacontyl oleate, 39-hydroxynonatriacontyl oleate, and 40-hydroxytetracontyl oleate.

[0048] In one embodiment, the structural analog of one or more FAHFA or OAHFA is selected from the group consisting of palmitoleic alcohols. In one embodiment, the structural analog of one or more FAHFA or OAHFA is selected from the group consisting of 12-hydroxydodecyl palmitate, 13-hydroxytridecyl palmitate, 14-hydroxytetradecyl palmitate, 15-hydroxypentadecyl palmitate, 16-hydroxyhexadecyl palmitate, 17-hydroxyheptadecyl palmitate, 18-hydroxyoctadecyl palmitate, 19-hydroxynonadecyl palmitate, 20-hydroxyeicosyl palmitate, 21-hydroxyheneicosyl palmitate, 22-hydroxydocosyl palmitate, 23-hydroxytricosyl palmitate, 24-hydroxytetracosyl palmitate, 25-hydroxypentacosyl palmitate, 26-hydroxyhexacosyl palmitate, 27-hydroxyhexacosyl palmitate, 28-hydroxyhexacosyl palmitate, 29-hydroxyhexacosyl palmitate, 30-hydroxyhexacosyl palmitate, 31-hydroxyhexacosyl palmitate, 32-hydroxyhexacosyl palmitate, 33-hydroxyhexacosyl palmitate, 34-hydroxyhexacosyl palmitate, 35-hydroxyhexacosyl palmitate, 36-hydroxyhexacosyl palmitate, 37-hydroxyhexacosyl palmitate, 38-hydroxyhexacosyl palmitate, 39-hydroxyhexacosyl palmitate, 40-hydroxyhexacosyl palmitate, 41-hydroxyhexacosyl palmitate, 42-hydroxyhexacosyl palmitate, 43-hydroxyhexacosyl palmitate, 44-hydroxyhexacosyl palmitate, 45-hydroxyhexacosyl palmitate, 46-hydroxyhexacosyl palmit hydroxyheptatriacontyl palmitoleate, 28-hydroxyoctacosyl palmitoleate, 29-hydroxynonacosyl palmitoleate, 30-hydroxytriacontyl palmitoleate, 31-hydroxyhentriacontyl palmitoleate, 32-hydroxydotriacontyl palmitoleate, 33-hydroxytritriacontyl palmitoleate, 34-hydroxytetratriacontyl palmitoleate, 35-hydroxypentatriacontyl palmitoleate, 36-hydroxyhexatriacontyl palmitoleate, 37-hydroxyheptatriacontyl palmitoleate, 38-hydroxyoctatriacontyl palmitoleate, 39-hydroxynonatriacontyl palmitoleate, and 40-hydroxytetratriacontyl palmitoleate.

[0049] In one embodiment, the structural analog of one or more FAHFA or OAHFA is selected from the group consisting of myristoleic alcohols. In one embodiment, the structural analog of one or more FAHFA or OAHFA is selected from the group consisting of 12-hydroxydodecyl myristoleate, 13-hydroxytridecyl myristoleate, 14-hydroxytetradecyl myristoleate, 15-hydroxypentadecyl myristoleate, 16-hydroxyhexadecyl myristoleate, 17-hydroxyheptadecyl myristoleate, 18-hydroxyoctadecyl myristoleate, 19-hydroxynonadecyl myristoleate, 20-hydroxyeicosyl myristoleate, 21-hydroxyheneicosyl myristoleate, 22-hydroxydocosyl myristoleate, 23-hydroxytricosyl myristoleate, 24-hydroxytetracosyl myristoleate, 25-hydroxypentacosyl myristoleate, 26-hydroxyhexacosyl myristoleate, 27-hydroxyhexacosyl myristoleate, 28-hydroxyhexacosyl myristoleate, 29-hydroxyhexacosyl myristoleate, 30-hydroxyhexacosyl myristoleate, 31-hydroxyhexacosyl myristoleate, 32-hydroxyhexacosyl myristoleate, 33-hydroxyhexacosyl myristoleate, 34-hydroxyhexacosyl myristoleate, 35-hydroxyhexacosyl myristoleate, 36-hydroxyhexacosyl myristoleate, 37-hydroxyhexacosyl myristoleate, 38-hydroxyhexacosyl myristoleate, 39-hydroxyhexacosyl myristoleate, 40-hydroxyhexacosyl myristoleate, 41-hydroxyhexacosyl myristoleate, 4 hydroxyheptatriacontyl myristrate, 28-hydroxyoctacosyl myristrate, 29-hydroxynonacosyl myristrate, 30-hydroxytriacontyl myristrate, 31-hydroxyhentriacontyl myristrate, 32-hydroxydotriacontyl myristrate, 33-hydroxytritriacontyl myristrate, 34-hydroxytetratriacontyl myristrate, 35-hydroxypentatriacontyl myristrate, 36-hydroxyhexatriacontyl myristrate, 37-hydroxyheptatriacontyl myristrate, 38-hydroxyoctatriacontyl myristrate, 39-hydroxynonatriacontyl myristrate, and 40-hydroxytetracontyl myristrate.

[0050] In one embodiment, the one or more structural analogs of FAHFA or OAHFA are selected from the group consisting of lauric alcohols. In one embodiment, the one or more structural analogs of FAHFA or OAHFA are selected from the group consisting of 12-hydroxydodecyl laurate, 13-hydroxytridecyl laurate, 14-hydroxytetradecyl laurate, 15-hydroxypentadecyl laurate, 16-hydroxyhexadecyl laurate, 17-hydroxyheptadecyl laurate, 18-hydroxyoctadecyl laurate, 19-hydroxynonadecyl laurate, 20-hydroxyeicosyl laurate, 21-hydroxyheneicosyl laurate, 22-hydroxydocosyl laurate, 23-hydroxytricosyl laurate, 24-hydroxytetracosyl laurate, 25-hydroxypentacosyl laurate, 26-hydroxyhexacosyl laurate, 27-hydroxyhexacosyl laurate, 28-hydroxyhexacosyl laurate, 29-hydroxyhexacosyl laurate, 30-hydroxyhexacosyl laurate, 31-hydroxyhexacosyl laurate, 32-hydroxyhexacosyl laurate, 33-hydroxyhexacosyl laurate, 34-hydroxyhexacosyl laurate, 35-hydroxyhexacosyl laurate, 36-hydroxyhexacosyl laurate, 37-hydroxyhexacosyl laurate, 38-hydroxyhexacosyl laurate, 39-hydroxyhexacosyl laurate, 40-hydroxyhexacosyl laurate, 41-hydroxyhexacosyl laurate, 42-hydroxyhexacosyl laurate, 43-hydroxyhexacosyl laurate, 44-hydroxyhexacosyl laurate, 45-hydroxyhexacosyl laurate, 46-hydroxyhexacosyl The hydroxyl group may be selected from the group consisting of hydroxyheptatriacontyl laurate, 28-hydroxyoctacosyl laurate, 29-hydroxynonacosyl laurate, 30-hydroxytriacontyl laurate, 31-hydroxyhentriacontyl laurate, 32-hydroxydotriacontyl laurate, 33-hydroxytritriacontyl laurate, 34-hydroxytetratriacontyl laurate, 35-hydroxypentatriacontyl laurate, 36-hydroxyhexatriacontyl laurate, 37-hydroxyheptatriacontyl laurate, 38-hydroxyoctatriacontyl laurate, 39-hydroxynonatriacontyl laurate, and 40-hydroxytetracontyl laurate.

[0051] In one embodiment, the structural analog of one or more FAHFA or OAHFA comprises or is selected from the group consisting of paulinic alcohols. In one embodiment, the structural analog of one or more FAHFA or OAHFA comprises 12-hydroxydodecyl eicos-13-enoate, 13-hydroxytridecyl eicos-13-enoate, 14-hydroxytetradecyl eicos-13-enoate, 15-hydroxypentadecyl eicos-13-enoate, 16-hydroxyhexadecyl eicos-13-enoate, 17-hydroxyheptadecyl eicos-13-enoate, 18-hydroxyoctadecyl eicos-13-enoate, 19-hydroxyoctadecyl eicos-13-enoate, 20-hydroxyoctadecyl eicos-13-enoate, 21-hydroxyoctadecyl eicos-13-enoate, 22-hydroxyoctadecyl eicos-13-enoate, 23-hydroxyoctadecyl eicos-13-enoate, 24-hydroxyoctadecyl eicos-13-enoate, 25-hydroxyoctadecyl eicos-13-enoate, 26-hydroxyoctadecyl eicos-13-enoate, 27-hydroxyoctadecyl eicos-13-enoate, 28-hydroxyoctadecyl eicos-13-enoate, 29-hydroxyoctadecyl eicos-13-enoate, 30-hydroxyoctadecyl eicos-13-enoate, 31-hydroxyoctadecyl eicos-13-enoate, 32-hydroxyoctadecyl eicos-13-enoate, 33-hydroxyoctadecyl eicos-13-enoate, 34-hydroxyoctadecyl eicos-13-enoate, 35-hydroxyoctadecyl eicos-13-enoate, eicosyl eicos-13-enoate, 19-hydroxynonadecyleicosyl eicos-13-enoate, 20-hydroxyeicosyl eicos-13-enoate, 21-hydroxyheneicosyl eicos-13-enoate, 22-hydroxydocosyl eicos-13-enoate, 23-hydroxytricosyl eicos-13-enoate, 24-hydroxytetracosyl eicos-13-enoate, 25-hydroxypentacosyl eicos-13-enoate, 26-hydroxyhexacosyl eicos-13-enoate , 27-hydroxyheptacosyl eicos-13-enoate, 28-hydroxyoctacosyl eicos-13-enoate, 29-hydroxynonacosyl eicos-13-enoate, 30-hydroxytriacontyl eicos-13-enoate, 31-hydroxyhentriacontyl eicos-13-enoate, 32-hydroxydotriacontyl eicos-13-enoate, 33-hydroxytritriacontyl eicos-13-enoate, 34-hydroxytetratriacontyl eicos-13-enoate, 35-hydroxypentatriacontyl eicos-13-enoate, 36-hydroxyhexatriacontyl eicos-13-enoate, 37-hydroxyheptatriacontyl eicos-13-enoate, 38-hydroxyoctatriacontyl eicos-13-enoate, 39-hydroxynonatriacontyl eicos-13-enoate, and 40-hydroxytetracontyl eicos-13-enoate.

[0052] In one embodiment, the structural analog of one or more FAHFA or OAHFA comprises or is selected from the group consisting of gondoic acid alcohols. In one embodiment, the structural analog of one or more FAHFA or OAHFA comprises 12-hydroxydodecyl eicos-11-enoate, 13-hydroxytridecyl eicos-11-enoate, 14-hydroxytetradecyl eicos-11-enoate, 15-hydroxypentadecyl eicos-11-enoate, 16-hydroxyhexadecyl eicos-11-enoate, 17-hydroxyheptadecyl eicos-11-enoate, 18-hydroxyoctadecyl eicos-11-enoate, 19-hydroxyoctadecyl eicos-11-enoate, 20-hydroxyoctadecyl eicos-11-enoate, 21-hydroxyoctadecyl eicos-11-enoate, 22-hydroxyoctadecyl eicos-11-enoate, 23-hydroxyoctadecyl eicos-11-enoate, 24-hydroxyoctadecyl eicos-11-enoate, 25-hydroxyoctadecyl eicos-11-enoate, 26-hydroxyoctadecyl eicos-11-enoate, 27-hydroxyoctadecyl eicos-11-enoate, 28-hydroxyoctadecyl eicos-11-enoate, 29-hydroxyoctadecyl eicos-11-enoate, 30-hydroxyoctadecyl eicos-11-enoate, 31-hydroxyoctadecyl eicos-11-enoate, 32-hydroxyoctadecyl eicos-11-enoate, 33-hydroxyoctadecyl eicos-11-enoate, 34-hydroxyoctadecyl eicos-11-enoate, 35-hydroxyoctadecyl eicos-11-enoate eicosyl eicos-11-enoate, 19-hydroxynonadecyleicosyl eicos-11-enoate, 20-hydroxyeicosyl eicos-11-enoate, 21-hydroxyheneicosyl eicos-11-enoate, 22-hydroxydocosyl eicos-11-enoate, 23-hydroxytricosyl eicos-11-enoate, 24-hydroxytetracosyl eicos-11-enoate, 25-hydroxypentacosyl eicos-11-enoate, 26-hydroxyhexacosyl eicos-11-enoate , 27-hydroxyheptacosyl eicos-11-enoate, 28-hydroxyoctacosyl eicos-11-enoate, 29-hydroxynonacosyl eicos-11-enoate, 30-hydroxytriacontyl eicos-11-enoate, 31-hydroxyhentriacontyl eicos-11-enoate, 32-hydroxydotriacontyl eicos-11-enoate, 33-hydroxytritriacontyl eicos-11-enoate, 34-hydroxytetratriacontyl eicos-11-enoate, 35-hydroxypentatriacontyl eicos-11-enoate, 36-hydroxyhexatriacontyl eicos-11-enoate, 37-hydroxyheptatriacontyl eicos-11-enoate, 38-hydroxyoctatriacontyl eicos-11-enoate, 39-hydroxynonatriacontyl eicos-11-enoate, and 40-hydroxytetracontyl eicos-11-enoate.

[0053] In one embodiment, the one or more structural analogs of a FAHFA or OAHFA are selected from the group comprising or consisting of erucic acid alcohols, and in one embodiment, the one or more structural analogs of a FAHFA or OAHFA are selected from the group consisting of 12-hydroxydodecyldocos-13-enoate, 13-hydroxytridecyldocos-13-enoate, 14-hydroxytetradecyldocos-13-enoate, 15-hydroxypentadecyldocos-13-enoate, 16-hydroxyhexadecyldocos-13-enoate, 17-Hydroxyheptadecyldokos-13-enoate, 18-Hydroxyoctadecyldokos-13-enoate, 19-Hydroxynonadecyldokos-13-enoate, 20-Hydroxyeicosyldocos-13-enoate, 21-Hydroxyheneicosyldocos-13-enoate, 22-Hydroxydocosyldocos-13-enoate, 23-Hydroxytricosyldocos-13-enoate, 24-Hydroxytetracosyldocos-13-enoate, 25-Hydroxypentacosyldocos-13-enoate enoate, 26-hydroxyhexacosyldocos-13-enoate, 27-hydroxyheptacosyldocos-13-enoate, 28-hydroxyoctacosyldocos-13-enoate, 29-hydroxynonacosyldocos-13-enoate, 30-hydroxytriacontildocos-13-enoate, 31-hydroxyhentriacontildocos-13-enoate, 32-hydroxytriacontildocos-13-enoate, 33-hydroxytritriacontildocos-13-enoate, 34 35-hydroxytetratriacontildocos-13-enoate, 35-hydroxypentatriacontildocos-13-enoate, 36-hydroxyhexatriacontildocos-13-enoate, 37-hydroxyheptatriacontildocos-13-enoate, 38-hydroxyoctatriacontildocos-13-enoate, 39-hydroxynonatriacontildocos-13-enoate, and 40-hydroxytetratriacontildocos-13-enoate.

[0054] In one embodiment, the one or more structural analogs of FAHFA or OAHFA are selected from the group comprising or consisting of nervonic acid alcohols, and in one embodiment, the one or more structural analogs of FAHFA or OAHFA are selected from the group consisting of 12-hydroxydodecyltetracos-15-enoate, 13-hydroxytridecyltetracos-15-enoate, 14-hydroxytetradecyltetracos-15-enoate, 15-hydroxypentadecyltetracos-15-enoate, 16-hydroxyhexadecyltetracos-15-enoate, 17-hydroxypentadecyltetracos-15-enoate, 18-hydroxyhexadecyltetracos-15-enoate, 19-hydroxyhexadecyltetracos-15-enoate, 20-hydroxyhexadecyltetracos-15-enoate, 21-hydroxyhexadecyltetracos-15-enoate, 22-hydroxyhexadecyltetracos-15-enoate, 23-hydroxyhexadecyltetracos-15-enoate, 24-hydroxyhexadecyltetracos-15-enoate, 25-hydroxyhexadecyltetracos-15-enoate, 26-hydroxyhexadecyltetracos-15-enoate, 27-hydroxyhexadecyltetracos-15-enoate, 28-hydroxyhexadecyltetracos-15-enoate, 29-hydroxyhexadecyltetracos-15-enoate, 30-hydroxyhexadecyltetracos-15-enoate, 31-hydroxyhexadecyltetracos-15-enoate, 32-hydroxyhexadecyltetracos-15-enoate, 33-hydroxyhexadecyltetracos-15-enoate, 34-hydroxyhexadecyltetracos-15-enoate, 35-hydroxyhexadecyltetra 15-hydroxyhexadecyl tetracosyl enoate, 18-hydroxyoctadecyl tetracosyl enoate, 19-hydroxynonadecyl tetracosyl enoate, 20-hydroxyeicosyl tetracosyl enoate, 21-hydroxyheneicosyl tetracosyl enoate, 22-hydroxydocosyl tetracosyl enoate, 23-hydroxytricosyl tetracosyl enoate, 24-hydroxytetracosyl tetracosyl enoate, 25-hydroxypentacosyl tetracosyl enoate enoate, 26-hydroxyhexacosyltetracos-15-enoate, 27-hydroxyheptacosyltetracos-15-enoate, 28-hydroxyoctacosyltetracos-15-enoate, 29-hydroxynonacosyltetracos-15-enoate, 30-hydroxytriacontyltetracos-15-enoate, 31-hydroxyhentriacontyltetracos-15-enoate, 32-hydroxydotriacontyltetracos-15-enoate, 33-hydroxytritriacontyltetracos-15-enoate, 3 The hydroxytetracontyl tetracos-15-enoate is selected from the group consisting of 4-hydroxytetratriacontyl tetracos-15-enoate, 35-hydroxypentatriacontyl tetracos-15-enoate, 36-hydroxyhexatriacontyl tetracos-15-enoate, 37-hydroxyheptatriacontyl tetracos-15-enoate, 38-hydroxyoctatriacontyl tetracos-15-enoate, 39-hydroxynonatriacontyl tetracos-15-enoate, and 40-hydroxytetracontyl tetracos-15-enoate.

[0055] In one embodiment, the structural analog of one or more FAHFA or OAHFA comprises or is selected from the group consisting of linoleic acid alcohols. In one embodiment, the structural analog of one or more FAHFA or OAHFA comprises 12-hydroxydodecyl linoleate, 13-hydroxytridecyl linoleate, 14-hydroxytetradecyl linoleate, 15-hydroxypentadecyl linoleate, 16-hydroxyhexadecyl linoleate, 17-hydroxyheptadecyl linoleate, 18-hydroxyoctadecyl linoleate, 19-hydroxynonadecyl linoleate, 20-hydroxyeicosyl linoleate, 21-hydroxyheneicosyl linoleate, 22-hydroxydocosyl linoleate, 23-hydroxytricosyl linoleate, 24-hydroxytetracosyl linoleate, 25-hydroxypentacosyl linoleate, 26-hydroxyhexacosyl linoleate, 27-hydroxyhexacosyl linoleate, 28-hydroxyhexacosyl linoleate, 29-hydroxyhexacosyl linoleate, 30-hydroxyhexacosyl linoleate, 31-hydroxyhexacosyl linoleate, 32-hydroxyhexacosyl linoleate, 33-hydroxyhexacosyl linoleate, 34-hydroxyhexacosyl linoleate, 35-hydroxyhexacosyl linoleate, 36-hydroxyhexacosyl linoleate, 37-hydroxyhexacosyl linoleate, 38-hydroxyhexacosyl linoleate, 39-hydroxyhexacosyl linoleate, 40-hydroxyhexacosyl linoleate, 41-hydroxyhexacosyl linoleate, 42-hydroxyhexacosyl linoleate, 43-hydroxyhexacosyl linoleate, 44-hydroxyhexacos hydroxyheptacosyl linoleate, 28-hydroxyoctacosyl linoleate, 29-hydroxynonacosyl linoleate, 30-hydroxytriacontyl linoleate, 31-hydroxyhentriacontyl linoleate, 32-hydroxydotriacontyl linoleate, 33-hydroxytritriacontyl linoleate, 34-hydroxytetratriacontyl linoleate, 35-hydroxypentatriacontyl linoleate, 36-hydroxyhexatriacontyl linoleate, 37-hydroxyheptatriacontyl linoleate, 38-hydroxyoctatriacontyl linoleate, 39-hydroxynonatriacontyl linoleate, and 40-hydroxytetracontyl linoleate.

[0056] In one embodiment, the one or more structural analogs of FAHFAs or OAHFAs are selected from the group consisting of linolenic alcohols, including 12-hydroxydodecyl linolenate, 13-hydroxytridecyl linolenate, 14-hydroxytetradecyl linolenate, 15-hydroxypentadecyl linolenate, 16-hydroxyhexadecyl linolenate, 17-hydroxyheptadecyl linolenate, 18-hydroxyoctadecyl linolenate, 19-hydroxynonadecyl linolenate, 20-hydroxyeicosyl linolenate, 21-hydroxyheneicosyl linolenate, 22-hydroxydocosyl linolenate, 23-hydroxytricosyl linolenate, 24-hydroxytetracosyl linolenate, 25-hydroxypentacosyl linolenate, 26-hydroxyhexacosyl linolenate, 27-hydroxyheptadecyl linolenate, 28-hydroxyoctadecyl linolenate, 29-hydroxyoctadecyl linolenate, 30-hydroxyoctadecyl linolenate, 31-hydroxyoctadecyl linolenate, 32-hydroxyoctadecyl linolenate, 33-hydroxyoctadecyl linolenate, 34-hydroxyoctadecyl linolenate, 35-hydroxyoctadecyl linolenate, 36-hydroxyoctadecyl linolenate, 37-hydroxyoctadecyl linolenate, 38-hydroxyoctadecyl linolenate, 39-hydroxyoctadecyl linolenate, 40-hydroxyoctadecyl linolenate, 41-hydroxyoctadecyl linolenate, 42-hydroxyoctadecyl linolenate, 43-hydroxyoctadecyl linolenate, 44-hydroxyoctadecyl linolenate, 45-hydroxyoctadecyl linolenate, Tacosyl linolenate, 28-hydroxyoctacosyl linolenate, 29-hydroxynonacosyl linolenate, 30-hydroxytriacontyl linolenate, 31-hydroxyhentriacontyl linolenate, 32-hydroxydotriacontyl linolenate, 33-hydroxytritriacontyl linolenate, 34-hydroxytetratriacontyl linolenate, 35-hydroxypentatriacontyl linolenate, 36-hydroxyhexatriacontyl linolenate, 37-hydroxyheptatriacontyl linolenate, 38-hydroxyoctatriacontyl linolenate, 39-hydroxynonatriacontyl linolenate, and 40-hydroxytetracontyl linolenate.

[0057] In one embodiment, the FAHFAs are 18-(oleoyloxy)stearic acid (18:0 / 18:1-OAHFA, 18-OAHFA), 12-(linoleoyloxy)dodecanoic acid, 20-(linoleoyloxy)eicosanoic acid, 12-(palmitoleoyloxy)dodecanoic acid, 20-(palmitoleoyloxy)eicosanoic acid, 12-(palmitoyloxy)dodecanoic acid, 20-(palmitoyloxy)eicosanoic acid, 12-(stearoyloxy)dodecanoic acid, 20-(stearoyloxy)dodecanoic acid, 20-(stearoyloxy)eicosanoic acid, 12 ... C) Eicosanoic acid, selected from 12-OAHFA (12-(oleoyloxy)dodecanoic acid), 15-OAHFA (15-(oleoyloxy)pentadecanoic acid), 20-OAHFA (20-(oleoyloxy)eicosanoic acid), 22-OAHFA (22-(oleoyloxy)docosanoic acid), 20:1-OAHFA ((12Z)-20-(oleoyloxy)eicos-12-enoic acid), and 29:1-OAHFA ((21Z)-29-(oleoyloxy)nonacos-21-enoic acid).

[0058] In one embodiment, the FAHFA is selected from 18-(oleoyloxy)stearic acid (18:0 / 18:1-OAHFA, 18-OAHFA), 12-OAHFA (12-(oleoyloxy)dodecanoic acid), 15-OAHFA (15-(oleoyloxy)pentadecanoic acid), 20-OAHFA (20-(oleoyloxy)eicosanoic acid), 22-OAHFA (22-(oleoyloxy)docosanoic acid), 20:1-OAHFA ((12Z)-20-(oleoyloxy)eicos-12-enoic acid), and 29:1-OAHFA ((21Z)-29-(oleoyloxy)nonacos-21-enoic acid).

[0059] In one embodiment, the one or more FAHFAs are selected from 12-OAHFA (12-(oleoyloxy)dodecanoic acid), 15-OAHFA (15-(oleoyloxy)pentadecanoic acid), 20-OAHFA (20-(oleoyloxy)eicosanoic acid), 22-OAHFA (22-(oleoyloxy)docosanoic acid), 20:1-OAHFA ((12Z)-20-(oleoyloxy)eicos-12-enoic acid), and 29:1-OAHFA ((21Z)-29-(oleoyloxy)nonacos-21-enoic acid).

[0060] In one embodiment, the one or more FAHFAs are selected from 18-(oleoyloxy)stearic acid (18:0 / 18:1-OAHFA, 18-OAHFA), 12-(linoleoyloxy)dodecanoic acid, 20-(linoleoyloxy)eicosanoic acid, 12-(palmitoleoyloxy)dodecanoic acid, 20-(palmitoleoyloxy)eicosanoic acid, 12-(palmitoyloxy)dodecanoic acid, 20-(palmitoyloxy)eicosanoic acid, 12-(stearoyloxy)dodecanoic acid, 20-(stearoyloxy)eicosanoic acid.

[0061] In further embodiments, the FAHFA is selected from the group consisting of 20-(palmitoleoyloxy)eicosanoic acid, 20-(oleoyloxy)eicosanoic acid, and 18-(oleoyloxy)stearic acid (18:0 / 18:1-OAHFA, 18-OAHFA).

[0062] In certain embodiments, the FAHFA is selected from the group consisting of 20-(oleoyloxy)eicosanoic acid and 18-(oleoyloxy)stearic acid (18:0 / 18:1-OAHFA, 18-OAHFA).

[0063] In one embodiment, the FAHFA is 20-(oleoyloxy)eicosanoic acid.

[0064] In a further embodiment, the FAHFA is 18-(oleoyloxy)stearic acid.

[0065] In a further embodiment, the FAHFA is 20-(palmitoleoyloxy)eicosanoic acid.

[0066] The carbon chain length of the one or more wax esters or analogs thereof suitable for the compositions of the present invention can vary. In one embodiment, there is no maximum carbon chain length. In one embodiment, the carbon chain length of the one or more wax esters or structural analogs thereof is C15-C100, C19-C72, C20-C55, C20-C50, C20-C40, C20-C35, C20-C25, C25-C45, C25-C40, C25-C35, or C25-C30. In one embodiment, the carbon chain length of the one or more wax esters or analogs thereof is C20, C21, C22, C23, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34, C35, C36, C37, C38, C39, C40, C41, C42, C43, C44, C45, C46, ​​C47, C48, C49, C50, C51, C52, C53, C54 or C55.

[0067] In one embodiment, the wax ester or structural analogs thereof have the following formula (II): [ka] During the ceremony, R1 is a carbon atom, an oxygen atom, or a nitrogen atom; R2 is a linear or branched C9-C50 alkyl, alkenyl, or alkynyl chain, or structural analogs thereof; R3 is a linear or branched C9 to C50 alkyl, alkenyl, or alkynyl chain, or structural analogs thereof.

[0068] In one embodiment, the wax ester is a linear wax ester. In one embodiment, the wax ester is a branched wax ester.

[0069] In one embodiment, the acyl chain of the one or more wax esters is selected from the group comprising or consisting of the following fatty acids: oleic acid, palmitoleic acid, myristoleic acid, lauric acid, paulinic acid, gondoic acid, erucic acid, nervonic acid, linoleic acid, and linolenic acid, and the alkoxy chain of the one or more wax esters is selected from the group comprising or consisting of linear fatty alcohols, iso-branched fatty alcohols, and anteiso-branched fatty alcohols, and / or structural analogs thereof.

[0070] In one embodiment, the one or more wax esters are selected from the group consisting of or comprise oleic acid based esters. In one embodiment, the one or more wax esters are selected from the group consisting of lauryl oleate, tridecyl oleate, myristyl oleate, pentadecyl oleate, palmityl oleate, heptadecyl oleate, stearyl oleate, nonadecyl oleate, arachidyl oleate (AO), heneicosyl oleate, behenyl oleate (BO), tricosyl oleate, lignoceryl oleate, pentacosyl oleate, hexacosyl oleate, heptacosyl oleate. oleate, octatriacontyl oleate, nonacosyl oleate, triacontyl oleate, hentriacontyl oleate, dotriacontyl oleate, tritriacontyl oleate, tetratriacontyl oleate, pentatriacontyl oleate, hexatriacontyl oleate, heptatriacontyl oleate, octatriacontyl oleate, nonatriacontyl oleate, and tetratriacontyl oleate.

[0071] In one embodiment, the one or more wax esters are selected from the group consisting of iso-branched alkyl oleates. In one embodiment, the one or more wax esters are selected from the group consisting of 11-methyl lauryl oleate, 12-methyl tridecyl oleate, 13-methyl myristyl oleate, 14-methyl pentadecyl oleate, 15-methyl palmityl oleate, 16-methyl heptadecyl oleate, 17-methyl stearyl oleate, 18-methyl nonadecyl oleate, 19-methyl arachidyl oleate, 20-methyl heneicosyl oleate, 21-methyl behenyl oleate, 22-methyl tricosyl oleate, 23-methyl lignoceryl oleate, 24-methyl pentacosyl oleate, 25-methyl hexacosyl oleate, 26-methyl heptadecyl oleate, 27-methyl heptadecyl oleate, 28-methyl heptadecyl oleate, 29-methyl heptadecyl oleate, 30-methyl heptadecyl oleate, 31-methyl heptadecyl oleate, 32-methyl heptadecyl oleate, 33-methyl heptadecyl oleate, 34-methyl heptadecyl oleate, 35-methyl heptadecyl oleate, 36-methyl heptadecyl oleate, 37-methyl heptadecyl oleate, 38-methyl heptadecyl oleate, 39-methyl heptadecyl oleate, 40-methyl heptadecyl oleate, 41-methyl heptadecyl oleate, 42-methyl heptadecyl oleate, 43-methyl heptadecyl oleate, 44-methyl heptadecyl oleate, cosyl oleate, 27-methyloctacosyl oleate, 28-methylnonacosyl oleate, 29-methyltriacontyl oleate, 30-methylhentriacontyl oleate, 31-methyldotriacontyl oleate, 32-methyltritriacontyl oleate, 33-methyltetratriacontyl oleate, 34-methylpentatriacontyl oleate, 35-methylhexatriacontyl oleate, 36-methylheptatriacontyl oleate, 37-methyloctatriacontyl oleate, 38-methylnonatriacontyl oleate, 39-methyltetracontyl oleate.

[0072] In one embodiment, the one or more wax esters are selected from the group consisting of anteiso branched alkyl oleates. In one embodiment, the one or more wax esters are selected from the group consisting of 10-methyl lauryl oleate, 11-methyl tridecyl oleate, 12-methyl myristyl oleate, 13-methyl pentadecyl oleate, 14-methyl palmityl oleate, 15-methyl heptadecyl oleate, 16-methyl stearyl oleate, 17-methyl nonadecyl oleate, 18-methyl arachidyl oleate, 19-methyl heptadecyl oleate, 20-methyl behenyl oleate, 21-methyl tricosyl oleate, 22-methyl lignoceryl oleate, 23-methyl pentacosyl oleate, 24-methyl hexacosyl oleate, 25-methyl heptadecyl oleate, 26-methyl heptadecyl oleate, 27-methyl heptadecyl oleate, 28-methyl heptadecyl oleate, 29-methyl heptadecyl oleate, 30-methyl heptadecyl oleate, 31-methyl heptadecyl oleate, 32-methyl heptadecyl oleate, 33-methyl heptadecyl oleate, 34-methyl heptadecyl oleate, 35-methyl heptadecyl oleate, 36-methyl heptadecyl oleate, 37-methyl heptadecyl oleate, 38-methyl heptadecyl oleate, 39-methyl heptadecyl oleate, 40-methyl heptadecyl oleate, 41-methyl heptadecyl oleate, 42-methyl heptadecyl oleate, 43-methyl heptadecyl oleate, silyl oleate, 26-methyloctacosyl oleate, 27-methylnonacosyl oleate, 28-methyltriacontyl oleate, 29-methylhentriacontyl oleate, 30-methyldotriacontyl oleate, 31-methyltritriacontyl oleate, 32-methyltetratriacontyl oleate, 33-methylpentatriacontyl oleate, 34-methylhexatriacontyl oleate, 35-methylheptatriacontyl oleate, 36-methyloctatriacontyl oleate, 37-methylnonatriacontyl oleate, and 38-methyltetracontyl oleate.

[0073] In one embodiment, the one or more wax esters are selected from the group consisting of palmitoleic acid esters. In one embodiment, the one or more wax esters are selected from the group consisting of lauryl palmitate, tridecyl palmitate, myristyl palmitate, pentadecyl palmitate, palmityl palmitate, heptadecyl palmitate, stearyl palmitate, nonadecyl palmitate, arachidyl palmitate, heneicosyl palmitate, behenyl palmitate, tricosyl palmitate, lignoceryl palmitate, pentacosyl palmitate, hexacosyl palmitate, heptacosyl palmitate, tetradec ... The palmitate is selected from the group consisting of palmitate, octatriacontyl palmitate, nonacosyl palmitate, triacontyl palmitate, hentriacontyl palmitate, dotriacontyl palmitate, tritriacontyl palmitate, tetratriacontyl palmitate, pentatriacontyl palmitate, hexatriacontyl palmitate, heptatriacontyl palmitate, octatriacontyl palmitate, nonatriacontyl palmitate, and tetracontyl palmitate.

[0074] In one embodiment, the one or more wax esters are selected from the group consisting of iso-branched alkyl palmitrates. In one embodiment, the one or more wax esters are selected from the group consisting of 11-methyl lauryl palmitate, 12-methyl tridecyl palmitate, 13-methyl myristyl palmitate, 14-methyl pentadecyl palmitate, 15-methyl palmityl palmitate, 16-methyl heptadecyl palmitate, 17-methyl stearyl palmitate, 18-methyl nonadecyl palmitate, 19-methyl arachidyl palmitate, 20-methyl heneicosyl palmitate, 21-methyl behenyl palmitate, 22-methyl tricosyl palmitate, 23-methyl lignoceryl palmitate, 24-methyl pentacosyl palmitate, 25-methyl hexacosyl palmitate, 26-methyl heptadecyl palmitate, 27-methyl heptadecyl palmitate, 28-methyl heptadecyl palmitate, 29-methyl heptadecyl palmitate, 30-methyl heptadecyl palmitate, 31-methyl heptadecyl palmitate, 32-methyl heptadecyl palmitate, 33-methyl heptadecyl palmitate, 34-methyl heptadecyl palmitate, 35-methyl heptadecyl palmitate, 36-methyl heptadecyl palmitate, 37-methyl heptadecyl palmitate, 38-methyl heptadecyl palmitate, 39-methyl heptadecyl palmitate, 40-methyl heptadecyl palmitate, 41-methyl heptadecyl palmitate, 42-methyl heptadecyl palmitate, 43-methyl heptadecyl palmitate, 44-methyl heptadecyl palmitate cosyl palmitate, 27-methyloctacosyl palmitate, 28-methylnonacosyl palmitate, 29-methyltriacontyl palmitate, 30-methylhentriacontyl palmitate, 31-methyldotriacontyl palmitate, 32-methyltritriacontyl palmitate, 33-methyltetratriacontyl palmitate, 34-methylpentatriacontyl palmitate, 35-methylhexatriacontyl palmitate, 36-methylheptatriacontyl palmitate, 37-methyloctatriacontyl palmitate, 38-methylnonatriacontyl palmitate, and 39-methyltetracontyl palmitate.

[0075] In one embodiment, the one or more wax esters are selected from the group consisting of anteiso branched alkyl palmitate. In one embodiment, the one or more wax esters are selected from the group consisting of 10-methyl lauryl palmitate, 11-methyl tridecyl palmitate, 12-methyl myristyl palmitate, 13-methyl pentadecyl palmitate, 14-methyl palmityl palmitate, 15-methyl heptadecyl palmitate, 16-methyl stearyl palmitate, 17-methyl nonadecyl palmitate, 18-methyl arachidyl palmitate, 19-methyl heneicosyl palmitate, 20-methyl behenyl palmitate, 21-methyl tricosyl palmitate, 22-methyl lignoceryl palmitate, 23-methyl pentadecyl palmitate, 24-methyl hexacosyl palmitate, 25-methyl heptadecyl palmitate, 26-methyl heptadecyl palmitate, 27-methyl heptadecyl palmitate, 28-methyl heptadecyl palmitate, 29-methyl heptadecyl palmitate, 30-methyl heptadecyl palmitate, 31-methyl heptadecyl palmitate, 32-methyl heptadecyl palmitate, 33-methyl heptadecyl palmitate, 34-methyl heptadecyl palmitate, 35-methyl heptadecyl palmitate, 36-methyl heptadecyl palmitate, 37-methyl heptadecyl palmitate, 38-methyl heptadecyl palmitate, 39-methyl heptadecyl palmitate, 40-methyl heptadecyl palmitate, 41-methyl heptadecyl palmitate, 42-methyl heptadecyl palmitate, 43-methyl heptadecyl palmitate, 4 cosyl palmitate, 26-methyloctacosyl palmitate, 27-methylnonacosyl palmitate, 28-methyltriacontyl palmitate, 29-methylhentriacontyl palmitate, 30-methyldotriacontyl palmitate, 31-methyltritriacontyl palmitate, 32-methyltetratriacontyl palmitate, 33-methylpentatriacontyl palmitate, 34-methylhexatriacontyl palmitate, 35-methylheptatriacontyl palmitate, 36-methyloctatriacontyl palmitate, 37-methylnonatriacontyl palmitate, and 38-methyltetracontyl palmitate.

[0076] In one embodiment, the one or more wax esters are selected from the group consisting of or comprise myristoleic acid based esters. In one embodiment, the one or more wax esters are selected from the group consisting of lauryl myristoleate, tridecyl myristoleate, myristyl myristoleate, pentadecyl myristoleate, palmityl myristoleate, heptadecyl myristoleate, stearyl myristoleate, nonadecyl myristoleate, arachidyl myristoleate, heneicosyl myristoleate, behenyl myristoleate, tricosyl myristoleate, lignoceryl myristoleate, pentacosyl myristoleate, hexacosyl myristoleate, heptacosyl myristoleate, octacosyl myristoleate, nonacosyl myristoleate, triacontyl myristoleate, hentriacontyl myristoleate, dotriacontyl myristoleate, hexacos ... In some embodiments, the glyceryl myristolate is selected from the group consisting of 11-methyl myristolate, 12-methyl tridecyl myristolate, 13-methyl myristyl myristolate, 14-methyl pentadecyl myristolate, 15-methyl palmityl myristolate, 16-methyl heptadecyl myristolate, and 17-methyl stearyl myristolate.

[0077] In one embodiment, the one or more wax esters are selected from the group consisting of iso-branched alkyl myristoleates. In one embodiment, the one or more wax esters are selected from the group consisting of 18-methylnonadecyl myristoleate, 19-methylarachidyl myristoleate, 20-methylheneicosyl myristoleate, 21-methylbehenyl myristoleate, 22-methyltricosyl myristoleate, 23-methyllignoceryl myristoleate, 24-methylpentacosyl myristoleate, 25-methylhexacosyl myristoleate, 26-methylheptacosyl myristoleate, 27-methyloctacosyl myristoleate, 28-methylnonacosyl myristoleate, 29-methyltriacontyl myristoleate, 28-methyltriacontyl myristoleate, 29 ... 30-methylhentriacontyl myristoleate, 31-methyldotriacontyl myristoleate, 32-methyltritriacontyl myristoleate, 33-methyltetratriacontyl myristoleate, 34-methylpentatriacontyl myristoleate, 35-methylhexatriacontyl myristoleate, 36-methylheptatriacontyl myristoleate, 37-methyloctatriacontyl myristoleate, 38-methylnonatriacontyl myristoleate, and 39-methyltetracontyl myristoleate.

[0078] In one embodiment, the one or more wax esters are selected from the group consisting of anteiso branched alkyl myristoleates. In one embodiment, the one or more wax esters are selected from the group consisting of 10-methyl lauryl myristoleate, 11-methyl tridecyl myristoleate, 12-methyl myristyl myristoleate, 13-methyl pentadecyl myristoleate, 14-methyl palmityl myristoleate, 15-methyl heptadecyl myristoleate, 16-methyl stearyl myristoleate, 17-methyl nonadecyl myristoleate, 18-methyl arachidyl myristoleate, 19-methyl heneicosyl myristoleate, 20-methyl behenyl myristoleate, 21-methyl tricosyl myristoleate, 22-methyl lignoceryl myristoleate, 23-methyl pentacosyl myristoleate, 24-methyl hexacosyl myristoleate, 25-methyl heptadecyl myristoleate, 26-methyl heptadecyl myristoleate, 27-methyl heptadecyl myristoleate, 28-methyl heptadecyl myristoleate, 29-methyl heptadecyl myristoleate, 30-methyl heptadecyl myristoleate, 31-methyl heptadecyl myristoleate, 32-methyl heptadecyl myristoleate, 33-methyl heptadecyl myristoleate, 34-methyl heptadecyl myristoleate, 35-methyl heptadecyl myristoleate, 36-methyl heptadecyl myristoleate, 37-methyl heptadecyl myristoleate, 38-methyl heptadecyl myristoleate, 39-methyl heptadecyl my cosyl myristoleate, 26-methyloctacosyl myristoleate, 27-methylnonacosyl myristoleate, 28-methyltriacontyl myristoleate, 29-methylhentriacontyl myristoleate, 30-methyldotriacontyl myristoleate, 31-methyltritriacontyl myristoleate, 32-methyltetratriacontyl myristoleate, 33-methylpentatriacontyl myristoleate, 34-methylhexatriacontyl myristoleate, 35-methylheptatriacontyl myristoleate, 36-methyloctatriacontyl myristoleate, 37-methylnonatriacontyl myristoleate, and 38-methyltetracontyl myristoleate.

[0079] In one embodiment, one or more wax esters comprise or are selected from the group consisting of lauric acid esters.In one embodiment, one or more wax esters comprise or are selected from the group consisting of lauryl laurate, tridecyl laurate, myristyl laurate, pentadecyl laurate, palmityl laurate, heptadecyl laurate, stearyl laurate, nonadecyl laurate, arachidyl laurate, heneicosyl laurate, behenyl laurate, tricosyl laurate, lignoceryl laurate, pentacosyl laurate, hexacosyl laurate, heptacosyl laurate, octacosyl laurate, nonacosyl laurate, triacontyl laurate, hentriacontyl laurate, dotriacontyl laurate, tritriacontyl laurate, tetratriacontyl laurate, pentatriacontyl laurate, hexatriacontyl laurate, heptatriacontyl laurate, octatriacontyl laurate, nonatriacontyl laurate and tetracontyl laurate.

[0080] In one embodiment, the one or more wax esters are selected from the group consisting of iso-branched alkyl laurates. In one embodiment, the one or more wax esters are selected from the group consisting of 11-methyl lauryl laurate, 12-methyl tridecyl laurate, 13-methyl myristyl laurate, 14-methyl pentadecyl laurate, 15-methyl palmityl laurate, 16-methyl heptadecyl laurate, 17-methyl stearyl laurate, 18-methyl nonadecyl laurate, 19-methyl arachidyl laurate, 20-methyl heneicosyl laurate, 21-methyl behenyl laurate, 22-methyl tricosyl laurate, 23-methyl lignoceryl laurate, 24-methyl pentacosyl laurate, 25-methyl hexacosyl laurate, 26-methyl heptadecyl laurate, 27-methyl heptadecyl laurate, 28-methyl heptadecyl laurate, 29-methyl heptadecyl laurate, 30-methyl heptadecyl laurate, 31-methyl heptadecyl laurate, 32-methyl heptadecyl laurate, 33-methyl heptadecyl laurate, 34-methyl heptadecyl laurate, 35-methyl heptadecyl laurate, 36-methyl heptadecyl laurate, 37-methyl heptadecyl laurate, 38-methyl heptadecyl laurate, 39-methyl heptadecyl laurate, 40-methyl heptadecyl laurate, 41-methyl heptadecyl laurate, 42-methyl heptadecyl laurate, 43-methyl heptadecyl laurate, 44-methyl heptadecyl laurate laurate, 27-methyloctacosyl laurate, 28-methylnonacosyl laurate, 29-methyltriacontyl laurate, 30-methylhentriacontyl laurate, 31-methyldotriacontyl laurate, 32-methyltritriacontyl laurate, 33-methyltetratriacontyl laurate, 34-methylpentatriacontyl laurate, 35-methylhexatriacontyl laurate, 36-methylheptatriacontyl laurate, 37-methyloctatriacontyl laurate, 38-methylnonatriacontyl laurate, and 39-methyltetracontyl laurate.

[0081] In one embodiment, the one or more wax esters are selected from the group consisting of anteiso branched alkyl laurates. In one embodiment, the one or more wax esters are selected from the group consisting of 10-methyl lauryl laurate, 11-methyl tridecyl laurate, 12-methyl myristyl laurate, 13-methyl pentadecyl laurate, 14-methyl palmityl laurate, 15-methyl heptadecyl laurate, 16-methyl stearyl laurate, 17-methyl nonadecyl laurate, 18-methyl arachidyl laurate, 19-methyl heptadecyl laurate, 20-methyl behenyl laurate, 21-methyl tricosyl laurate, 22-methyl lignoceryl laurate, 23-methyl pentacosyl laurate, 24-methyl hexacosyl laurate, 25-methyl heptadecyl laurate, 26-methyl heptadecyl laurate, 27-methyl heptadecyl laurate, 28-methyl heptadecyl laurate, 29-methyl heptadecyl laurate, 30-methyl heptadecyl laurate, 31-methyl heptadecyl laurate, 32-methyl heptadecyl laurate, 33-methyl heptadecyl laurate, 34-methyl heptadecyl laurate, 35-methyl heptadecyl laurate, 36-methyl heptadecyl laurate, 37-methyl heptadecyl laurate, 38-methyl heptadecyl laurate, 39-methyl heptadecyl laurate, 40-methyl heptadecyl laurate, 41-methyl heptadecyl laurate, 42-methyl heptadecyl laurate, 43-methyl heptadecyl laurate, laurate, 26-methyloctacosyl laurate, 27-methylnonacosyl laurate, 28-methyltriacontyl laurate, 29-methylhentriacontyl laurate, 30-methyldotriacontyl laurate, 31-methyltritriacontyl laurate, 32-methyltetratriacontyl laurate, 33-methylpentatriacontyl laurate, 34-methylhexatriacontyl laurate, 35-methylheptatriacontyl laurate, 36-methyloctatriacontyl laurate, 37-methylnonatriacontyl laurate, and 38-methyltetracontyl laurate.

[0082] In one embodiment, the one or more wax esters are selected from the group comprising or consisting of paulinic acid based esters. In one embodiment, the one or more wax esters are selected from the group consisting of lauryl eicos-13-enoate, tridecyl eicos-13-enoate, myristyl eicos-13-enoate, pentadecyl eicos-13-enoate, palmityl eicos-13-enoate, heptadecyl eicos-13-enoate, stearyl eicos-13-enoate, nonadecyl eicos-13-enoate, arachidyl eicos-13-enoate, heneicosyl eicos-13-enoate, behenyl eicos-13-enoate, tricosyl eicos-13-enoate, lignoceryl eicos-13-enoate, pentacosyl eicos-13-enoate, hexacosyl eicos-13-enoate, heptadecyl eicos-13-enoate, and the like. eicosyl eicos-13-enoate, octacosyl eicos-13-enoate, nonacosyl eicos-13-enoate, triacontyl eicos-13-enoate, hentriacontyl eicos-13-enoate, dotriacontyl eicos-13-enoate, tritriacontyl eicos-13-enoate, tetratriacontyl eicos-13-enoate, pentatriacontyl eicos-13-enoate, hexatriacontyl eicos-13-enoate, heptatriacontyl eicos-13-enoate, octatriacontyl eicos-13-enoate, nonatriacontyl eicos-13-enoate, and tetratriacontyl eicos-13-enoate.

[0083] In one embodiment, the one or more wax esters are selected from the group consisting of iso-branched alkyl paulinates. In one embodiment, the one or more wax esters are selected from the group consisting of 11-methyl lauryl eicos-13-enoate, 12-methyl tridecyl eicos-13-enoate, 13-methyl myristyl eicos-13-enoate, 14-methyl pentadecyl eicos-13-enoate, 15-methyl palmityl eicos-13-enoate, 16-methyl heptadecyl eicos-13-enoate, 17-methyl stearyl eicos-13-enoate, 18-methyl stearyl eicos-13-enoate, 19-methyl stearyl eicos-13-enoate, 20-methyl stearyl eicos-13-enoate, 21-methyl stearyl eicos-13-enoate, 22-methyl stearyl eicos-13-enoate, 23-methyl stearyl eicos-13-enoate, 24-methyl stearyl eicos-13-enoate, 25-methyl stearyl eicos-13-enoate, 26-methyl stearyl eicos-13-enoate, 27-methyl stearyl eicos-13-enoate, 28-methyl stearyl eicos-13-enoate, 29-methyl stearyl eicos-13-enoate, 30-methyl stearyl eicos-13-enoate, 31-methyl stearyl eicos-13-enoate, 32-methyl stearyl eicos-13-enoate, 33-methyl stearyl eicos-13-enoate, 34-methyl stearyl eicos-13-enoate, 35-methyl stearyl eicos-13-enoate, 36-methyl stearyl Tyrnonadecyl eicos-13-enoate, 19-methyl arachidyl eicos-13-enoate, 20-methyl heneicosyl eicos-13-enoate, 21-methyl behenyl eicos-13-enoate, 22-methyl tricosyl eicos-13-enoate, 23-methyl lignoceryl eicos-13-enoate, 24-methyl pentacosyl eicos-13-enoate, 25-methyl hexacosyl eicos-13-enoate, 26-methyl Heptacosyl eicos-13-enoate, 27-methyloctacosyl eicos-13-enoate, 28-methylnonacosyl eicos-13-enoate, 29-methyltriacontyl eicos-13-enoate, 30-methylhentriacontyl eicos-13-enoate, 31-methyldotriacontyl eicos-13-enoate, 32-methyltritriacontyl eicos-13-enoate, 33-methyltetratriacontyl eicos-1 3-enoate, 34-methylpentatriacontyl eicos-13-enoate, 35-methylhexatriacontyl eicos-13-enoate, 36-methylheptatriacontyl eicos-13-enoate, 37-methyloctatriacontyl eicos-13-enoate, 38-methylnonatriacontyl eicos-13-enoate, and 39-methyltetracontyl eicos-13-enoate.

[0084] In one embodiment, the one or more wax esters are selected from the group consisting of anteiso branched alkyl paulinates. In one embodiment, the one or more wax esters are selected from the group consisting of 10-methyl lauryl eicos-13-enoate, 11-methyl tridecyl eicos-13-enoate, 12-methyl myristyl eicos-13-enoate, 13-methyl pentadecyl eicos-13-enoate, 14-methyl palmityl eicos-13-enoate, 15-methyl heptadecyl eicos-13-enoate, 16-methyl stearyl eicos-13-enoate, 17-methyl stearyl eicos-13-enoate, 18-methyl stearyl eicos-13-enoate, 19-methyl stearyl eicos-13-enoate, 20-methyl stearyl eicos-13-enoate, 21-methyl stearyl eicos-13-enoate, 22-methyl stearyl eicos-13-enoate, 23-methyl stearyl eicos-13-enoate, 24-methyl stearyl eicos-13-enoate, 25-methyl stearyl eicos-13-enoate, 26-methyl stearyl eicos-13-enoate, 27-methyl stearyl eicos-13-enoate, 28-methyl stearyl eicos-13-enoate, 29-methyl stearyl eicos-13-enoate, 30-methyl stearyl eicos-13-enoate, 31-methyl stearyl eicos-13-enoate, 32-methyl stearyl eicos-13-enoate, 33-methyl stearyl eicos-13-enoate, 34-methyl stearyl eicos-13-enoate, 35-methyl stearyl e Tyrnonadecyl eicos-13-enoate, 18-methyl arachidyl eicos-13-enoate, 19-methyl heneicosyl eicos-13-enoate, 20-methyl behenyl eicos-13-enoate, 21-methyl tricosyl eicos-13-enoate, 22-methyl lignoceryl eicos-13-enoate, 23-methyl pentacosyl eicos-13-enoate, 24-methyl hexacosyl eicos-13-enoate, 25-methyl Heptacosyl eicos-13-enoate, 26-methyloctacosyl eicos-13-enoate, 27-methylnonacosyl eicos-13-enoate, 28-methyltriacontyl eicos-13-enoate, 29-methylhentriacontyl eicos-13-enoate, 30-methyldotriacontyl eicos-13-enoate, 31-methyltritriacontyl eicos-13-enoate, 32-methyltetratriacontyl eicos-13-enoate 3-enoate, 33-methylpentatriacontyl eicos-13-enoate, 34-methylhexatriacontyl eicos-13-enoate, 35-methylheptatriacontyl eicos-13-enoate, 36-methyloctatriacontyl eicos-13-enoate, 37-methylnonatriacontyl eicos-13-enoate, and 38-methyltetracontyl eicos-13-enoate.

[0085] In one embodiment, the one or more wax esters are selected from the group comprising or consisting of gondoic acid based esters. In one embodiment, the one or more wax esters are selected from the group consisting of lauryl eicos-11-enoate, tridecyl eicos-11-enoate, myristyl eicos-11-enoate, pentadecyl eicos-11-enoate, palmityl eicos-11-enoate, heptadecyl eicos-11-enoate, stearyl eicos-11-enoate, nonadecyl eicos-11-enoate, arachidyl eicos-11-enoate, heneicosyl eicos-11-enoate, behenyl eicos-11-enoate, tricosyl eicos-11-enoate, lignoceryl eicos-11-enoate, pentacosyl eicos-11-enoate, hexacosyl eicos-11-enoate, heptacosyl eicos-11-enoate, and the like. eicosyl eicos-11-enoate, octacosyl eicos-11-enoate, nonacosyl eicos-11-enoate, triacontyl eicos-11-enoate, hentriacontyl eicos-11-enoate, dotriacontyl eicos-11-enoate, tritriacontyl eicos-11-enoate, tetratriacontyl eicos-11-enoate, pentatriacontyl eicos-11-enoate, hexatriacontyl eicos-11-enoate, heptatriacontyl eicos-11-enoate, octatriacontyl eicos-11-enoate, nonatriacontyl eicos-11-enoate, and tetratriacontyl eicos-11-enoate.

[0086] In one embodiment, the one or more wax esters are selected from the group consisting of iso-branched alkyl gonadoates. In one embodiment, the one or more wax esters are selected from the group consisting of 11-methyl lauryl eicos-11-enoate, 12-methyl tridecyl eicos-11-enoate, 13-methyl myristyl eicos-11-enoate, 14-methyl pentadecyl eicos-11-enoate, 15-methyl palmityl eicos-11-enoate, 16-methyl heptadecyl eicos-11-enoate, 17-methyl stearyl eicos-11-enoate, 18-methyl stearyl eicos-11-enoate, 19-methyl stearyl eicos-11-enoate, 20-methyl stearyl eicos-11-enoate, 21-methyl stearyl eicos-11-enoate, 22-methyl stearyl eicos-11-enoate, 23-methyl stearyl eicos-11-enoate, 24-methyl stearyl eicos-11-enoate, 25-methyl stearyl eicos-11-enoate, 26-methyl stearyl eicos-11-enoate, 27-methyl stearyl eicos-11-enoate, 28-methyl stearyl eicos-11-enoate, 29-methyl stearyl eicos-11-enoate, 30-methyl stearyl eicos-11-enoate, 31-methyl stearyl eicos-11-enoate, 32-methyl stearyl eicos-11-enoate, 33-methyl stearyl eicos-11-enoate, 34-methyl stearyl eicos-11-enoate, 35-methyl stearyl eicos-11-enoate, 36-methyl ste Tyrnonadecyl eicos-11-enoate, 19-methyl arachidyl eicos-11-enoate, 20-methyl heneicosyl eicos-11-enoate, 21-methyl behenyl eicos-11-enoate, 22-methyl tricosyl eicos-11-enoate, 23-methyl lignoceryl eicos-11-enoate, 24-methyl pentacosyl eicos-11-enoate, 25-methyl hexacosyl eicos-11-enoate, 26-methyl Heptacosyl eicos-11-enoate, 27-methyloctacosyl eicos-11-enoate, 28-methylnonacosyl eicos-11-enoate, 29-methyltriacontyl eicos-11-enoate, 30-methylhentriacontyl eicos-11-enoate, 31-methyldotriacontyl eicos-11-enoate, 32-methyltritriacontyl eicos-11-enoate, 33-methyltetratriacontyl eicos-11-enoate 1-enoate, 34-methylpentatriacontyl eicos-11-enoate, 35-methylhexatriacontyl eicos-11-enoate, 36-methylheptatriacontyl eicos-11-enoate, 37-methyloctatriacontyl eicos-11-enoate, 38-methylnonatriacontyl eicos-11-enoate, and 39-methyltetracontyl eicos-11-enoate.

[0087] In one embodiment, the one or more wax esters are selected from the group consisting of anteiso branched alkyl gonadoates. In one embodiment, the one or more wax esters are selected from the group consisting of 10-methyl lauryl eicos-11-enoate, 11-methyl tridecyl eicos-11-enoate, 12-methyl myristyl eicos-11-enoate, 13-methyl pentadecyl eicos-11-enoate, 14-methyl palmityl eicos-11-enoate, 15-methyl heptadecyl eicos-11-enoate, 16-methyl stearyl eicos-11-enoate, 17-methyl stearyl eicos-11-enoate, 18-methyl stearyl eicos-11-enoate, 19-methyl stearyl eicos-11-enoate, 20-methyl stearyl eicos-11-enoate, 21-methyl stearyl eicos-11-enoate, 22-methyl stearyl eicos-11-enoate, 23-methyl stearyl eicos-11-enoate, 24-methyl stearyl eicos-11-enoate, 25-methyl stearyl eicos-11-enoate, 26-methyl stearyl eicos-11-enoate, 27-methyl stearyl eicos-11-enoate, 28-methyl stearyl eicos-11-enoate, 29-methyl stearyl eicos-11-enoate, 30-methyl stearyl eicos-11-enoate, 31-methyl stearyl eicos-11-enoate, 32-methyl stearyl eicos-11-enoate, 33-methyl stearyl eicos-11-enoate, 34-methyl stearyl eicos-11-enoate, 35-methyl stearyl Tyrnonadecyl eicos-11-enoate, 18-methyl arachidyl eicos-11-enoate, 19-methyl heneicosyl eicos-11-enoate, 20-methyl behenyl eicos-11-enoate, 21-methyl tricosyl eicos-11-enoate, 22-methyl lignoceryl eicos-11-enoate, 23-methyl pentacosyl eicos-11-enoate, 24-methyl hexacosyl eicos-11-enoate, 25-methyl Heptacosyl eicos-11-enoate, 26-methyloctacosyl eicos-11-enoate, 27-methylnonacosyl eicos-11-enoate, 28-methyltriacontyl eicos-11-enoate, 29-methylhentriacontyl eicos-11-enoate, 30-methyldotriacontyl eicos-11-enoate, 31-methyltritriacontyl eicos-11-enoate, 32-methyltetratriacontyl eicos-11-enoate 1-enoate, 33-methylpentatriacontyl eicos-11-enoate, 34-methylhexatriacontyl eicos-11-enoate, 35-methylheptatriacontyl eicos-11-enoate, 36-methyloctatriacontyl eicos-11-enoate, 37-methylnonatriacontyl eicos-11-enoate, and 38-methyltetracontyl eicos-11-enoate.

[0088] In one embodiment, the one or more wax esters are selected from the group comprising or consisting of erucic acid based esters. In one embodiment, the one or more wax esters are selected from the group consisting of lauryl docos-13-enoate, tridecyl docos-13-enoate, myristyl docos-13-enoate, pentadecyldocos-13-enoate, palmityldocos-13-enoate, heptadecyldocos-13-enoate, stearyl docos-13-enoate, nonadecyldocos-13-enoate, arachidyldocos-13-enoate, heneicosyl docos-13-enoate, behenyl docos-13-enoate, tricosyl docos-13-enoate, lignoceryl docos-13-enoate, pentacosyl docos-13-enoate, hexacosyl docos-13-enoate, heptacosyl docos-13-enoate, and the like. docos-13-enoate, octacosyl docos-13-enoate, nonacosyl docos-13-enoate, triacontil docos-13-enoate, hentriacontil docos-13-enoate, dotriacontil docos-13-enoate, tritriacontil docos-13-enoate, tetratriacontil docos-13-enoate, pentatriacontil docos-13-enoate, hexatriacontil docos-13-enoate, heptatriacontil docos-13-enoate, octatriacontil docos-13-enoate, nonatriacontil docos-13-enoate, and tetratriacontil docos-13-enoate.

[0089] In one embodiment, the one or more wax esters are selected from the group consisting of iso-branched alkyl erucate. In one embodiment, the one or more wax esters are selected from the group consisting of 11-methyl lauryl docos-13-enoate, 12-methyl tridecyl docos-13-enoate, 13-methyl myristyl docos-13-enoate, 14-methyl pentadecyld docos-13-enoate, 15-methyl palmityl docos-13-enoate, 16-methyl heptadecyld docos-13-enoate, 17-methyl stearyl docos-13-enoate, 18-methyl stearyl docos-13-enoate, 19-methyl stearyl docos-13-enoate, 20-methyl stearyl docos-13-enoate, 21-methyl stearyl docos-13-enoate, 22-methyl stearyl docos-13-enoate, 23-methyl stearyl docos-13-enoate, 24-methyl stearyl docos-13-enoate, 25-methyl stearyl docos-13-enoate, 26-methyl stearyl docos-13-enoate, 27-methyl stearyl docos-13-enoate, 28-methyl stearyl docos-13-enoate, 29-methyl stearyl docos-13-enoate, 30-methyl stearyl docos-13-enoate, 31-methyl stearyl docos-13-enoate, 32-methyl stearyl docos-13-enoate, 33-methyl stearyl docos-13-enoate, 34-methyl stearyl docos-13-enoate, 35-methyl stearyl docos-13-enoate, 36-methyl Tyrnonadecyldokos-13-enoate, 19-methylarachidyldokos-13-enoate, 20-methylheneicosylokos-13-enoate, 21-methylbehenylokos-13-enoate, 22-methyltricosylokos-13-enoate, 23-methyllignocerylokos-13-enoate, 24-methylpentacosylokos-13-enoate, 25-methylhexacosylokos-13-enoate, 26-methylhetero Ptacosyl docos-13-enoate, 27-methyloctacosyl docos-13-enoate, 28-methylnonacosyl docos-13-enoate, 29-methyltriacosyl docos-13-enoate, 30-methylhentriacontildocos-13-enoate, 31-methyldotriacontildocos-13-enoate, 32-methyltriacosyl docos-13-enoate, 33-methyltetratriacontildocos-13 -enoate, 34-methylpentatriacontildocos-13-enoate, 35-methylhexatriacontildocos-13-enoate, 36-methylheptatriacontildocos-13-enoate, 37-methyloctatriacontildocos-13-enoate, 38-methylnonatriacontildocos-13-enoate, and 39-methyltetracontildocos-13-enoate.

[0090] In one embodiment, the one or more wax esters are selected from the group consisting of anteiso branched alkyl erucium esters. In one embodiment, the one or more wax esters are selected from the group consisting of 10-methyl lauryl docos-13-enoate, 11-methyl tridecyl docos-13-enoate, 12-methyl myristyl docos-13-enoate, 13-methyl pentadecyldodocos-13-enoate, 14-methyl palmityl docos-13-enoate, 15-methyl heptadecyldodocos-13-enoate, 16-methyl stearyl docos-13-enoate, 17-methyl stearyl docos-13-enoate, 18-methyl stearyl docos-13-enoate, 19-methyl stearyl docos-13-enoate, 20-methyl stearyl docos-13-enoate, 21-methyl stearyl docos-13-enoate, 22-methyl stearyl docos-13-enoate, 23-methyl stearyl docos-13-enoate, 24-methyl stearyl docos-13-enoate, 25-methyl stearyl docos-13-enoate, 26-methyl stearyl docos-13-enoate, 27-methyl stearyl docos-13-enoate, 28-methyl stearyl docos-13-enoate, 29-methyl stearyl docos-13-enoate, 30-methyl stearyl docos-13-enoate, 31-methyl stearyl docos-13-enoate, 32-methyl stearyl docos-13-enoate, 33-methyl stearyl docos-13-enoate, 34-methyl stearyl docos-13-enoate, 35- Tyrnonadecyldokos-13-enoate, 18-methylarachidyldokos-13-enoate, 19-methylheneicosylokos-13-enoate, 20-methylbehenylokos-13-enoate, 21-methyltricosylokos-13-enoate, 22-methyllignocerylokos-13-enoate, 23-methylpentacosylokos-13-enoate, 24-methylhexacosylokos-13-enoate, 25-methylhetero Ptacosyl docos-13-enoate, 26-methyloctacosyl docos-13-enoate, 27-methylnonacosyl docos-13-enoate, 28-methyltriacontil docos-13-enoate, 29-methylhentriacontil docos-13-enoate, 30-methyldotriacontil docos-13-enoate, 31-methyltritriacontil docos-13-enoate, 32-methyltetratriacontil docos-13 -enoate, 33-methylpentatriacontildocos-13-enoate, 34-methylhexatriacontildocos-13-enoate, 35-methylheptatriacontildocos-13-enoate, 36-methyloctatriacontildocos-13-enoate, 37-methylnonatriacontildocos-13-enoate, and 38-methyltetracontildocos-13-enoate.

[0091] In one embodiment, the one or more wax esters are selected from the group comprising or consisting of nervonic acid based esters. In one embodiment, the one or more wax esters are selected from the group consisting of lauryl tetracos-15-enoate, tridecyl tetracos-15-enoate, myristyl tetracos-15-enoate, pentadecyl tetracos-15-enoate, palmityl tetracos-15-enoate, heptadecyl tetracos-15-enoate, stearyl tetracos-15-enoate, nonadecyl tetracos-15-enoate, arachidyl tetracos-15-enoate, heneicosyl tetracos-15-enoate, behenyl tetracos-15-enoate, tricosyl tetracos-15-enoate, lignoceryl tetracos-15-enoate, pentacosyl tetracos-15-enoate, hexacosyl tetracos-15-enoate, heptacosyl tetracos-15-enoate, and tetracosyl tetracos-15-enoate. cos-15-enoate, octacosyl tetracos-15-enoate, nonacosyl tetracos-15-enoate, triacontyl tetracos-15-enoate, hentriacontyl tetracos-15-enoate, dotriacontyl tetracos-15-enoate, tritriacontyl tetracos-15-enoate, tetratriacontyl tetracos-15-enoate, pentatriacontyl tetracos-15-enoate, hexatriacontyl tetracos-15-enoate, heptatriacontyl tetracos-15-enoate, octatriacontyl tetracos-15-enoate, nonatriacontyl tetracos-15-enoate, and tetracontyl tetracos-15-enoate.

[0092] In one embodiment, the one or more wax esters are selected from the group consisting of iso-branched alkyl nervonates. In one embodiment, the one or more wax esters are selected from the group consisting of 11-methyl lauryl tetracos-15-enoate, 12-methyl tridecyl tetracos-15-enoate, 13-methyl myristyl tetracos-15-enoate, 14-methyl pentadecyl tetracos-15-enoate, 15-methyl palmityl tetracos-15-enoate, 16-methyl heptadecyl tetracos-15-enoate, 17-methyl stearyl tetracos-15-enoate, 18-methyl tetracos-15-enoate, 19-methyl tetracos-15-enoate, 20-methyl tetracos-15-enoate, 21-methyl tetracos-15-enoate, 22-methyl tetracos-15-enoate, 23-methyl tetracos-15-enoate, 24-methyl tetracos-15-enoate, 25-methyl tetracos-15-enoate, 26-methyl tetracos-15-enoate, 27-methyl tetracos-15-enoate, 28-methyl tetracos-15-enoate, 29-methyl tetracos-15-enoate, 30-methyl tetracos-15-enoate, 31-methyl tetracos-15-enoate, 32-methyl tetracos-15-enoate, 33-methyl tetracos-15-enoate, 34-methyl tetracos-15-enoate, 35-methyl tetracos-15-enoate, 36-methyl tetracos-15-enoate, 37-methyl tetracos-15-enoate, 38- 19-methyl arachidyl tetracos-15-enoate, 20-methyl heneicosyl tetracos-15-enoate, 21-methyl behenyl tetracos-15-enoate, 22-methyl tricosyl tetracos-15-enoate, 23-methyl lignoceryl tetracos-15-enoate, 24-methyl pentacosyl tetracos-15-enoate, 25-methyl hexacosyl tetracos-15-enoate, 26-methyl Heptacosyl tetracos-15-enoate, 27-methyloctacosyl tetracos-15-enoate, 28-methylnonacosyl tetracos-15-enoate, 29-methyltriacontyl tetracos-15-enoate, 30-methylhentriacontyl tetracos-15-enoate, 31-methyldotriacontyl tetracos-15-enoate, 32-methyltritriacontyl tetracos-15-enoate, 33-methyltetratriacontyl tetracos- 15-enoate, 34-methylpentatriacontyl tetracos-15-enoate, 35-methylhexatriacontyl tetracos-15-enoate, 36-methylheptatriacontyl tetracos-15-enoate, 37-methyloctatriacontyl tetracos-15-enoate, 38-methylnonatriacontyl tetracos-15-enoate, and 39-methyltetracontyl tetracos-15-enoate.

[0093] In one embodiment, the one or more wax esters are selected from the group consisting of anteiso branched alkyl nervonates. In one embodiment, the one or more wax esters are selected from the group consisting of 10-methyl lauryl tetracos-15-enoate, 11-methyl tridecyl tetracos-15-enoate, 12-methyl myristyl tetracos-15-enoate, 13-methyl pentadecyl tetracos-15-enoate, 14-methyl palmityl tetracos-15-enoate, 15-methyl heptadecyl tetracos-15-enoate, 16-methyl stearyl tetracos-15-enoate, 17-methyl tetracos-15-enoate, 18-methyl tetracos-15-enoate, 19-methyl tetracos-15-enoate, 20-methyl tetracos-15-enoate, 21-methyl tetracos-15-enoate, 22-methyl tetracos-15-enoate, 23-methyl tetracos-15-enoate, 24-methyl tetracos-15-enoate, 25-methyl tetracos-15-enoate, 26-methyl tetracos-15-enoate, 27-methyl tetracos-15-enoate, 28-methyl tetracos-15-enoate, 29-methyl tetracos-15-enoate, 30-methyl tetracos-15-enoate, 31-methyl tetracos-15-enoate, 32-methyl tetracos-15-enoate, 33-methyl tetracos-15-enoate, 34-methyl tetracos-15-enoate, 35-methyl tetracos-15-enoate, 36-methyl tetracos-15-enoate, 37-methyl 18-methyl-15-pyridine, 19-methyl-15-pyridine, 20-methyl-15-pyridine, 21-methyl-15-pyridine, 22-methyl-15-pyridine, 23-methyl-15-pyridine, 24-methyl-15-pyridine, 25-methyl-15-pyridine, 26-methyl-15-pyridine, 27-methyl-15-pyridine, 28-methyl-15-pyridine, 29-methyl-15-pyridine, 30-methyl-15-pyridine, 31-methyl-15-pyridine, 32-methyl-15-pyridine, 33-methyl-15-pyridine, 34-methyl-15-pyridine, 35-methyl-15-pyridine, 36-methyl-15-pyridine, 37-methyl-15-pyridine, 38-methyl-15-pyridine, 39-methyl-15-pyridine, 40-methyl-15-pyridine, 41-methyl-15-pyridine, 42-methyl-15-pyridine, 43-methyl-15-pyridine, 44-methyl-15-pyridine, 45-methyl-15-pyridine, 46-methyl-15-pyridine, 47-methyl-15-pyridine, 48-methyl-15-pyridine, 49-methyl-15-pyridine, 50-methyl-15-pyridine, 51-methyl-15-pyridine, 52-methyl-15-pyridine, 53-methyl-15-pyridine, 54-methyl-15-pyridine, 55-methyl-15-pyridine, 56-methyl-15-pyridine, 57- Heptacosyl tetracos-15-enoate, 26-methyloctacosyl tetracos-15-enoate, 27-methylnonacosyl tetracos-15-enoate, 28-methyltriacontyl tetracos-15-enoate, 29-methylhentriacontyl tetracos-15-enoate, 30-methyldotriacontyl tetracos-15-enoate, 31-methyltritriacontyl tetracos-15-enoate, 32-methyltetratriacontyl tetracos- 15-enoate, 33-methylpentatriacontyl tetracos-15-enoate, 34-methylhexatriacontyl tetracos-15-enoate, 35-methylheptatriacontyl tetracos-15-enoate, 36-methyloctatriacontyl tetracos-15-enoate, 37-methylnonatriacontyl tetracos-15-enoate, and 38-methyltetracontyl tetracos-15-enoate.

[0094] In one embodiment, the one or more wax esters are selected from the group consisting of linoleic acid based esters, in one embodiment, the one or more wax esters are selected from the group consisting of lauryl linoleate, tridecyl linoleate, myristyl linoleate, pentadecyl linoleate, palmityl linoleate, heptadecyl linoleate, stearyl linoleate, nonadecyl linoleate, arachidyl linoleate, heneicosyl linoleate, behenyl linoleate, tricosyl linoleate, lignoceryl linoleate, pentacosyl linoleate, hexacosyl linoleate, heptacosyl linoleate, ole ... The linoleate may be selected from the group including or consisting of octatriacontyl linoleate, nonacosyl linoleate, triacontyl linoleate, hentriacontyl linoleate, dotriacontyl linoleate, tritriacontyl linoleate, tetratriacontyl linoleate, pentatriacontyl linoleate, hexatriacontyl linoleate, heptatriacontyl linoleate, octatriacontyl linoleate, nonatriacontyl linoleate, and tetracontyl linoleate.

[0095] In one embodiment, the one or more wax esters are selected from the group consisting of iso-branched alkyl linoleates. In one embodiment, the one or more wax esters are selected from the group consisting of 11-methyl lauryl linoleate, 12-methyl tridecyl linoleate, 13-methyl myristyl linoleate, 14-methyl pentadecyl linoleate, 15-methyl palmityl linoleate, 16-methyl heptadecyl linoleate, 17-methyl stearyl linoleate, 18-methyl nonadecyl linoleate, 19-methyl arachidyl linoleate, 20-methyl heneicosyl linoleate, 21-methyl behenyl linoleate, 22-methyl tricosyl linoleate, 23-methyl lignoceryl linoleate, 24-methyl pentacosyl linoleate, 25-methyl hexacosyl linoleate, 26-methyl heptadecyl linoleate, 27-methyl heptadecyl linoleate, 28-methyl heptadecyl linoleate, 29-methyl heptadecyl linoleate, 30-methyl heptadecyl linoleate, 31-methyl heptadecyl linoleate, 32-methyl heptadecyl linoleate, 33-methyl heptadecyl linoleate, 34-methyl heptadecyl linoleate, 35-methyl heptadecyl linoleate, 36-methyl heptadecyl linoleate, 37-methyl heptadecyl linoleate, 38-methyl heptadecyl linoleate, 39-methyl heptadecyl linoleate, 40-methyl heptadecyl linoleate, 41-methyl heptadecyl linoleate, 42-methyl heptadecyl silyl linoleate, 27-methyloctacosyl linoleate, 28-methylnonacosyl linoleate, 29-methyltriacontyl linoleate, 30-methylhentriacontyl linoleate, 31-methyldotriacontyl linoleate, 32-methyltritriacontyl linoleate, 33-methyltetratriacontyl linoleate, 34-methylpentatriacontyl linoleate, 35-methylhexatriacontyl linoleate, 36-methylheptatriacontyl linoleate, 37-methyloctatriacontyl linoleate, 38-methylnonatriacontyl linoleate, and 39-methyltetracontyl linoleate.

[0096] In one embodiment, the one or more wax esters are selected from the group consisting of anteiso branched alkyl linoleates. In one embodiment, the one or more wax esters are selected from the group consisting of 10-methyl lauryl linoleate, 11-methyl tridecyl linoleate, 12-methyl myristyl linoleate, 13-methyl pentadecyl linoleate, 14-methyl palmityl linoleate, 15-methyl heptadecyl linoleate, 16-methyl stearyl linoleate, 17-methyl nonadecyl linoleate, 18-methyl arachidyl linoleate, 19-methyl heneicosyl linoleate, 20-methyl behenyl linoleate, 21-methyl tricosyl linoleate, 22-methyl lignoceryl linoleate, 23-methyl pentacosyl linoleate, 24-methyl hexacosyl linoleate, 25-methyl heptadecyl linoleate, 26-methyl heptadecyl linoleate, 27-methyl heptadecyl linoleate, 28-methyl heptadecyl linoleate, 29-methyl heptadecyl linoleate, 30-methyl heptadecyl linoleate, 31-methyl heptadecyl linoleate, 32-methyl heptadecyl linoleate, 33-methyl heptadecyl linoleate, 34-methyl heptadecyl linoleate, 35-methyl heptadecyl linoleate, 36-methyl heptadecyl linoleate, 37-methyl heptadecyl linoleate, 38-methyl heptadecyl linoleate, 39-methyl heptadecyl linoleate, 40-methyl heptadecyl linoleate, 41-methyl heptadecyl silyl linoleate, 26-methyloctacosyl linoleate, 27-methylnonacosyl linoleate, 28-methyltriacontyl linoleate, 29-methylhentriacontyl linoleate, 30-methyldotriacontyl linoleate, 31-methyltritriacontyl linoleate, 32-methyltetratriacontyl linoleate, 33-methylpentatriacontyl linoleate, 34-methylhexatriacontyl linoleate, 35-methylheptatriacontyl linoleate, 36-methyloctatriacontyl linoleate, 37-methylnonatriacontyl linoleate, and 38-methyltetracontyl linoleate.

[0097] In one embodiment, the one or more wax esters are selected from the group consisting of linolenic acid esters, hi one embodiment, the one or more wax esters are selected from the group consisting of lauryl linolenate, tridecyl linolenate, myristyl linolenate, pentadecyl linolenate, palmityl linolenate, heptadecyl linolenate, stearyl linolenate, nonadecyl linolenate, arachidyl linolenate, heneicosyl linolenate, behenyl linolenate, tricosyl linolenate, lignoceryl linolenate, pentacosyl linolenate, hexacosyl linolenate, heptacosyl linolenate, The linolenate may be selected from the group including or consisting of octacosyl linolenate, nonacosyl linolenate, triacontyl linolenate, hentriacontyl linolenate, dotriacontyl linolenate, tritriacontyl linolenate, tetratriacontyl linolenate, pentatriacontyl linolenate, hexatriacontyl linolenate, heptatriacontyl linolenate, octatriacontyl linolenate, nonatriacontyl linolenate, and tetracontyl linolenate.

[0098] In one embodiment, the one or more wax esters are selected from the group comprising or consisting of iso-branched alkyl linolenates. In one embodiment, the one or more wax esters are 11-methyl lauryl linolenate, 12-methyl tridecyl linolenate, 13-methyl myristyl linolenate, 14-methyl pentadecyl linolenate, 15-methyl palmityl linolenate, 16-methyl heptadecyl linolenate, 17-methyl stearyl linolenate, 18-methyl nonadecyl linolenate, 19-methyl arachidyl linolenate, 20-methyl heneicosyl linolenate, 21-methyl behenyl linolenate, 22-methyl tricosyl linolenate, 23-methyl lignoceryl linolenate, 24-methyl pentacosyl linolenate, 25-methyl hexacosyl linolenate, 26-methyl heptadecyl linolenate, 27-methyl heptadecyl linolenate, 28-methyl heptadecyl linolenate, 29-methyl heptadecyl linolenate, 30-methyl heptadecyl linolenate, 31-methyl heptadecyl linolenate, 32-methyl heptadecyl linolenate, 33-methyl heptadecyl linolenate, 34-methyl heptadecyl linolenate, 35-methyl heptadecyl linolenate, 36-methyl heptadecyl linolenate, 37-methyl heptadecyl linolenate, 38-methyl heptadecyl linolenate, 39-methyl heptadecyl linolenate, 40-methyl heptadecyl linolenate, 41-methyl heptadecyl linolenate, 42-methyl heptadecyl linolenate, 43-methyl heptadecyl linolenate, 44-methyl heptadecyl linolenate, 4 silyl linolenate, 27-methyloctacosyl linolenate, 28-methylnonacosyl linolenate, 29-methyltriacontyl linolenate, 30-methylhentriacontyl linolenate, 31-methyldotriacontyl linolenate, 32-methyltritriacontyl linolenate, 33-methyltetratriacontyl linolenate, 34-methylpentatriacontyl linolenate, 35-methylhexatriacontyl linolenate, 36-methylheptatriacontyl linolenate, 37-methyloctatriacontyl linolenate, 38-methylnonatriacontyl linolenate, and 39-methyltetracontyl linolenate.

[0099] In one embodiment, the one or more wax esters are selected from the group comprising or consisting of anteiso branched alkyl linolenates. In one embodiment, the one or more wax esters are 10-methyl lauryl linolenate, 11-methyl tridecyl linolenate, 12-methyl myristyl linolenate, 13-methyl pentadecyl linolenate, 14-methyl palmityl linolenate, 15-methyl heptadecyl linolenate, 16-methyl stearyl linolenate, 17-methyl nonadecyl linolenate, 18-methyl arachidyl linolenate, 19-methyl heneicosyl linolenate, 20-methyl behenyl linolenate, 21-methyl tricosyl linolenate, 22-methyl lignoceryl linolenate, 23-methyl pentacosyl linolenate, 24-methyl hexacosyl linolenate, 25-methyl heptadecyl linolenate, 26-methyl heptadecyl linolenate, 27-methyl heptadecyl linolenate, 28-methyl heptadecyl linolenate, 29-methyl heptadecyl linolenate, 30-methyl heptadecyl linolenate, 31-methyl heptadecyl linolenate, 32-methyl heptadecyl linolenate, 33-methyl heptadecyl linolenate, 34-methyl heptadecyl linolenate, 35-methyl heptadecyl linolenate, 36-methyl heptadecyl linolenate, 37-methyl heptadecyl linolenate, 38-methyl heptadecyl linolenate, 39-methyl heptadecyl linolenate, 40-methyl heptadecyl linolenate, 41-methyl heptadecyl linolenate, 42-methyl heptadecyl linolenate, 43-methyl heptadecyl linolenate, 4 silyl linolenate, 26-methyloctacosyl linolenate, 27-methylnonacosyl linolenate, 28-methyltriacontyl linolenate, 29-methylhentriacontyl linolenate, 30-methyldotriacontyl linolenate, 31-methyltritriacontyl linolenate, 32-methyltetratriacontyl linolenate, 33-methylpentatriacontyl linolenate, 34-methylhexatriacontyl linolenate, 35-methylheptatriacontyl linolenate, 36-methyloctatriacontyl linolenate, 37-methylnonatriacontyl linolenate, and 38-methyltetracontyl linolenate.

[0100] In one embodiment, the one or more wax esters are selected from palmityl oleate, stearyl oleate, arachidyl oleate (AO), behenyl oleate (BO), lignoceryl oleate, hexocosanyl oleate, 24-methylpentacosanyl oleate, palmityl palmitoleate, stearyl palmitoleate, arachidyl palmitoleate, behenyl palmitoleate, lignoceryl palmitoleate, 24-methylpentacosanyl palmitoleate, palmityl linoleate, stearyl linoleate, arachidyl linoleate, behenyl palmitoleate, lignoceryl linoleate, 24-methylpentacosanyl linoleate, palmityl linolenate, stearyl linolenate, arachidyl linolenate, behenyl palmitoleate, lignoceryl linolenate, and 24-methylpentacosanyl linolenate.

[0101] In certain embodiments, the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate.

[0102] More specifically, the wax ester is behenyl oleate.

[0103] In an alternative embodiment, the wax ester is arachidyl laurate.

[0104] As used herein, "alkyl" as a group or part of a group refers to a straight or branched chain aliphatic hydrocarbon group. Exemplary alkyl groups include, but are not limited to, methyl, ethyl, propyl, butyl, pentyl, and hexyl.

[0105] As used herein, "alkenyl" as a group or part of a group refers to an aliphatic hydrocarbon group that may be linear or branched and contains at least one carbon-carbon double bond. Exemplary alkenyl groups include, but are not limited to, ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, and nonenyl.

[0106] As used herein, "alkynyl" as a group or part of a group refers to an aliphatic hydrocarbon group that may be straight or branched and contains a carbon-carbon triple bond. Exemplary alkynyl groups include, but are not limited to, ethynyl and propynyl.

[0107] Isomeric forms, including diastereoisomers, enantiomers, tautomers, and geometric isomers, are included within the scope of the compounds presented in this disclosure, as well as solvated, unsolvated, hydrated, non-hydrated, charged, and neutral forms.

[0108] As used herein, a "structural analog" refers to a compound that has a similar structure to a compound described in this disclosure, but differs with respect to certain components, such as one or more atoms, functional groups, or substructures being replaced with other atoms, groups, or substructures. In one embodiment, a structural analog is an isoelectronic analog and / or a functional analog.

[0109] The biophysical properties of the specific FAHFAs (or structural analogs thereof) or wax esters (or structural analogs thereof) used in the examples of the present disclosure are representative of the lipid classes FAHFAs (including OAHFAs) or wax esters, respectively, as a whole.

[0110] In one embodiment of the present invention, one or more wax esters of the composition (e.g., arachidyl oleate, AO) are in a liquid state at physiological conditions, and / or one or more wax esters of the composition (e.g., behenyl oleate, BO) are in a solid state at physiological conditions. In a very specific embodiment, one or more or all of the wax esters of the composition are in a solid state at physiological conditions. In one embodiment, the melting point of one or more or all of the wax esters of the composition is below, equal to, or above the temperature of the ocular surface. The compositions of the present invention can include any amount of FAHFAs (or structural analogs thereof) and wax esters (or structural analogs thereof).

[0111] In one embodiment, the molar ratio of the one or more FAHFAs and / or structural analogs thereof to the one or more wax esters and / or structural analogs thereof in the composition is less than or equal to 1:1, from about 1:1 to 1:100, or from 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90. In one embodiment, the molar ratio of the one or more FAHFAs and / or structural analogs thereof to the one or more wax esters and / or structural analogs thereof is greater than 1:1, about 100:1 to 1:1, about 3:2 to 5:1, or 90:1, 80:1, 70:1, 60:1, 50:1, 40:1, 30:1, 20:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, or 2:1.

[0112] As described herein, certain combinations of FAHFAs and wax esters have very advantageous properties in terms of their evaporation resistance on aqueous surfaces (including ocular surfaces in particular).In particular, mixtures of FAHFAs (including 20-OAHFA and 18:1 / 18:0-OAHFA) and wax esters (including BO and AL), in which the amount of wax esters is equal to or greater than that of FAHFAs, have been shown to achieve significantly higher evaporation resistance values ​​and tear-forming lipid layers in healthy subjects than each individual component alone ((9-13s / cm) (Iwata, S., et al.1969, Invest Ophthalmol Vis Sci, 8, 613-619; Peng, C., et al.2014, Ind Eng Cham Res, 53, 18130-18139)).

[0113] Thus, in certain embodiments, the amount of wax ester (or structural analog thereof) is equal to or greater than the amount of FAHFA (or structural analog thereof), i.e., the ratio of FAHFA or structural analog thereof (e.g., FAHFA) to wax ester or structural analog thereof (e.g., wax ester) in the composition is 1:1 or less (FAHFA:wax ester) (e.g., 1:1 to 1:9, such as 1:1 to 1:3, e.g., about 1:1).

[0114] In further particular embodiments, the ratio of FAHFAs or structural analogs thereof (eg, FAHFAs) to wax esters or structural analogs thereof (eg, wax esters) is about 1:1.

[0115] In one embodiment, the composition comprises at least 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50% w / v or weight % FAHFAs and / or structural analogs thereof, and / or wax esters and / or structural analogs thereof. In one embodiment, the composition comprises at least 0.001, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, or 50% w / v or weight % lipids. As used herein, % w / v (i.e., % weight per volume) refers to the mass concentration of the solution. As used herein, wt % (ie, % by weight of solute per weight of solution) refers to the weight percent of the solution.

[0116] In one embodiment, the composition comprises one or more FAHFAs selected from 12-OAHFA (12-(oleoyloxy)dodecanoic acid), 15-OAHFA (15-(oleoyloxy)pentadecanoic acid), 20-OAHFA (20-(oleoyloxy)eicosanoic acid), 22-OAHFA (22-(oleoyloxy)docosanoic acid), 20:1-OAHFA ((12Z)-20-(oleoyloxy)eicos-12-enoic acid), and / or 29:1-OAHFA ((21Z)-29-(oleoyloxy)nonacos-21-enoic acid), in combination with palmityl oleate, stearyl oleate, arachidyl oleate (AO), behenyl oleate (BO), lignoceryl oleate, hexahydroxybenzo ... and, or consisting of, one or more wax esters selected from cosanyl oleate, 24-methyl pentacosanyl oleate, palmityl palmitoleate, stearyl palmitoleate, arachidyl palmitoleate, behenyl palmitoleate, lignoceryl palmitoleate, 24-methyl pentacosanyl palmitoleate, palmityl linoleate, stearyl linoleate, arachidyl linoleate, behenyl palmitoleate, lignoceryl linoleate, 24-methyl pentacosanyl linoleate, palmityl linolenate, stearyl linolenate, arachidyl linolenate, behenyl palmitoleate, lignoceryl linolenate, and 24-methyl pentacosanyl linolenate. In one embodiment, the composition comprises or consists of one or more FAHFAs selected from 20-OAHFA (20-(oleoyloxy)eicosanoic acid), 20:1-OAHFA ((12Z)-20-(oleoyloxy)eicosanoic acid), and 29:1-OAHFA ((21Z)-29-(oleoyloxy)nonacos-21-enoic acid), and one or more wax esters selected from arachidyl oleate, behenyl oleate, hexocosanyl oleate, and 24-methylpentacosanyl oleate.

[0117] In certain embodiments, the FAHFA in the composition is selected from the group consisting of 20-(oleoyloxy)eicosanoic acid, 18-(oleoyloxy)stearic acid, and 20-(palmitoleoyloxy)eicosanoic acid, and the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate. In such compositions, the ratio of FAHFA to wax ester is 1:1 or less, preferably 1:1 to 1:9 (FAHFA:wax ester) (e.g., 1:1 to 1:3, e.g., about 1:1). In certain embodiments, such compositions do not include any other FAHFA or wax ester components.

[0118] In further particular embodiments, the FAHFA is selected from the group consisting of 20-(oleoyloxy)eicosanoic acid and 18-(oleoyloxy)stearic acid, and the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate. In such compositions, the ratio of FAHFA to wax ester is 1:1 or less, preferably 1:1 to 1:9 (FAHFA:wax ester) (e.g., 1:1 to 1:3, e.g., about 1:1). In certain embodiments, such compositions do not include any other FAHFA or wax ester components.

[0119] In a more particular embodiment, the FAHFA is 20-(oleoyloxy) eicosanoic acid and the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate. In an even more particular embodiment, the FAHFA is 20-(oleoyloxy) eicosanoic acid and the wax ester is behenyl oleate. In such compositions, the ratio of 20-(oleoyloxy) eicosanoic acid to wax ester is 1:1 or less, preferably 1:1 to 1:9 (FAHFA:wax ester) (e.g., 1:1 to 1:3 (e.g., 1:1)). In a particular embodiment, such compositions are also free of any other FAHFA or wax ester components.

[0120] In further particular embodiments, the FAHFA is 18-(oleoyloxy)stearic acid and the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate. In such compositions, the ratio of 18-(oleoyloxy)stearic acid to wax ester is 1:1 or less, preferably 1:1 to 1:9 (FAHFA:wax ester) (e.g., 1:1 to 1:3 (preferably about 1:1)). In certain embodiments, such compositions also do not include any other FAHFA or wax ester components.

[0121] In further particular embodiments, the FAHFA is 20-(palmitoleoyloxy) eicosanoic acid and the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate. In such compositions, the ratio of 20-(palmitoleoyloxy) eicosanoic acid to wax ester is less than or equal to 1:1 (FAHFA:wax ester), preferably about 1:1. In certain embodiments, such compositions also do not include any other FAHFA or wax ester components.

[0122] In one embodiment of the invention, the FAHFA (or structural analogues thereof) and the wax ester (or structural analogues thereof) can be separate pre-compositions that are applied or administered simultaneously as a combination to or onto the target of interest, or the FAHFA (or structural analogues thereof) and the wax ester (or structural analogues thereof) can be included in a single composition, which can be, for example, a ready-to-use composition or a composition that is supplemented prior to use. For example, a diluent or any other additives can be added to the composition prior to its use.

[0123] The compositions of the present invention may also include any other lipids or biologically or therapeutically effective agents other than FAHFAs (or structural analogs thereof) and wax esters (or structural analogs thereof). However, in one embodiment, the compositions do not include any other lipids or biologically or therapeutically effective agents other than FAHFAs (or structural analogs thereof) and wax esters (or structural analogs thereof). As used herein, "biologically or therapeutically effective agents" refers to any agent that induces a biological or therapeutic effect in a target of interest. Increased evaporation resistance, reduction of microorganisms, and relief of symptoms are just a few examples of such effects.

[0124] The compositions of the present invention optionally include one or more additives and / or any components normally found in the corresponding products, which may be, for example, selected from the group including or consisting of solvents, diluents, carriers, buffers, excipients, adjuvants, carrier media, preservatives, fillers, stabilizers, thickeners, emulsifiers, disintegrants, lubricants, and binders, and any combination thereof, and / or the one or more additives may be, for example, selected from the group including or consisting of pharma- ceutically acceptable solvents, diluents, carriers, buffers, excipients, adjuvants, carrier media, preservatives, fillers, stabilizers, thickeners, emulsifiers, disintegrants, lubricants, and binders, and any combination thereof. In one embodiment, the one or more pharma- ceutically acceptable excipients are ophthalmically acceptable excipients selected from the group consisting of polyethylene glycol, propylene glycol, glycerin, polyvinyl alcohol, povidone, polysorbate 80, hydroxypropyl methylcellulose, carmellose, carbomer 980, sodium hyaluronate, and dextran.

[0125] In one embodiment, the composition comprises one or more of the following: a pH adjusting agent (e.g., NaOH and / or HCl), a buffering agent (e.g., phosphate and / or borate), a tonicity adjusting agent (e.g., NaCl, trehalose), a viscosity enhancing excipient (e.g., hydroxypropylmethylcellulose, carmellose, carbomer, and / or sodium hyaluronate), a preservative (e.g., benzalkonium chloride), a stabilizer (e.g., polysorbate and / or glycerin), an oil phase (e.g., petrolatum, paraffin, castor oil, and / or mineral oil), water.

[0126] In one embodiment, the composition comprises 0.1-5% w / v of one or more FAHFAs and / or structural analogues thereof, 0.1-10% w / v of one or more wax esters and / or structural analogues thereof, 0-2% w / v of Miglyol 812, 1-8% w / v of Tween 20, 0.25-4% w / v of Kolliphor® EL, 0.25-5% w / v of Span 80, 1-3% w / v of glycerin, and 97.3-76% w / v of ultrapure water.

[0127] In certain embodiments of the present invention, there is provided a composition comprising (or consisting essentially of or consisting of) the following combination: i. O-acyl-ω-hydroxy fatty acids selected from the group consisting of 20-(oleoyloxy)eicosanoic acid, 18-(oleoyloxy)stearic acid, and 20-(palmitoleoyloxy)eicosanoic acid, and ii. a wax ester selected from the group consisting of behenyl oleate and arachidyl laurate; Optionally, the ratio of O-acyl-ω-hydroxy fatty acid to wax ester is at least 1:1 (e.g., 1:1 to 1:3 (e.g., 1:1)), such as 1:1 to 1:9 (O-acyl-ω-hydroxy fatty acid to wax ester).

[0128] In a particular embodiment of this aspect of the invention, the O-acyl-ω-hydroxy fatty acid is 20-(oleoyloxy)eicosanoic acid and the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate. More specifically, the wax ester is behenyl oleate.

[0129] In a further embodiment of this aspect of the invention, the O-acyl-ω-hydroxy fatty acid is 18-(oleoyloxy)stearic acid and the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate. In such compositions, the ratio of O-acyl-ω-hydroxy fatty acid:wax ester is preferably about 1:1.

[0130] In a further embodiment of this aspect of the invention, the O-acyl-ω-hydroxy fatty acid is 20-(palmitoleoyloxy)eicosanoic acid and the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate. In such compositions, the ratio of O-acyl-ω-hydroxy fatty acid:wax ester is preferably about 1:1.

[0131] In certain embodiments of this aspect of the invention, the composition does not include any additional O-acyl-ω-hydroxy fatty acid or wax ester components.

[0132] The composition of the present invention may be in any form, such as liquid, semi-solid, or solid form, that is optionally suitable for administration. The formulation may include or be selected from the group consisting of a solution, an emulsion, a suspension, a spray, a powder, a tablet, a pellet, and a capsule. In one embodiment, the composition is an oil-in-water emulsion. When the FAHFA (or its structural analogue) and the wax ester (or its structural analogue) are in separate pre-compositions, the formulation of each composition may be independently selected from the list of formulations above.

[0133] The composition of the present invention may be any type of composition, such as a pharmaceutical composition. In one embodiment, the composition of the present invention is an eye drop, an eye lotion, a liquid, semi-solid or solid eye preparation, or a powder (e.g., an eye drop or lotion, e.g., lyophilized to a powder). The eye drop may be, for example, a sterile aqueous or oily solution, emulsion, or suspension. The sterile eye preparation may be intended for administration onto the eyeball and / or the conjunctiva, or for insertion into the conjunctival sac. The semi-solid eye preparation may be, for example, a sterile ointment, cream, or gel.

[0134] In one embodiment, the composition of the present invention is a homogeneous or heterogeneous amphiphilic composition.

[0135] The present invention also relates to a method of preparing a composition of the present invention, the method comprising combining or mixing a FAHFA or a structural analog thereof, a wax ester or a structural analog thereof, and, optionally, one or more additives.

[0136] Combining can be performed by any method known to those skilled in the art, for example, by combining FAHFAs and wax esters in dry form, and optionally diluting the combination with, for example, one or more additives. Mixing can be performed by any method or tool, including, but not limited to, stirrers, mixers, vortexers, and stirring. For example, the compositions of the present invention can be combined or mixed from the time of manufacture, and optionally do not require any dilution or further processing before use. In one embodiment, the diluent or additive, FAHFAs or structural analogs thereof, and / or wax esters or structural analogs thereof are separated from the time of manufacture and during storage. For example, in one embodiment, lipids are not in fluid contact until immediately prior to use of the composition.

[0137] The compositions of the invention may be produced by any conventional process known in the art.

[0138] In one embodiment, the method of preparing a composition of the invention further comprises preparing or synthesizing a FAHFA or a structural analog thereof, e.g., prior to combining the FAHFA or a structural analog thereof with the wax ester or a structural analog thereof, and / or preparing or synthesizing a wax ester or a structural analog thereof, e.g., prior to combining the wax ester or a structural analog thereof with the FAHFA or a structural analog thereof.

[0139] FAHFAs or structural analogs thereof and / or wax esters or structural analogs thereof may be produced by any conventional process known in the art. In one embodiment, FAHFAs or structural analogs thereof are synthesized or have been synthesized by the methods described in the Examples below, or by methods previously reported in, for example, Bland, H., C. et al. (2019, Langmuir, Vol. 35, 3545-3552), Viitaja, T. et al. (2021, J. Org. Chem., 86, 4965-4976), or Hancock, S., E., (2018, J. Lipid Res., 59, 1510-1518). In one embodiment, wax esters or structural analogs thereof are synthesized or have been synthesized by the methods described in the Examples below, or by typical esterification protocols.

[0140] Therapeutic and Non-Therapeutic Uses of the Compositions The present invention relates to a non-therapeutic method of preventing water evaporation. According to the present invention, the composition can be applied on the surface to be protected from evaporation or on the material to be protected from evaporation. Suitable surfaces to be protected from water evaporation include, but are not limited to, water reservoirs, artificial lakes, reservoirs, aqueducts, canals, and water reservoirs. Suitable materials to be protected from evaporation include, but are not limited to, membranes and filters. The amount of the composition to be applied on the surface or material can be easily determined by those skilled in the art.

[0141] The present invention also relates to the compositions of the present invention for use as a medicament, for use in the treatment of dry eye disease and / or meibomian gland dysfunction, or for use in relieving ocular discomfort. The present invention further relates to therapeutic methods of preventing or slowing water evaporation, and to methods of treating dry eye disease and / or meibomian gland dysfunction or relieving ocular discomfort.

[0142] As used herein, "dry eye disease" refers to a condition having dry eyes. The condition can occur when tears are unable to provide sufficient lubrication to the eye. For example, dry eye can occur when not enough tears are produced or the tears produced are of poor quality. In one embodiment, the dry eye disease can be selected from allergic conjunctivitis, infectious keratoconjunctivitis, or post-infectious keratoconjunctivitis allergic conjunctivitis. As used herein, "meibomian gland dysfunction" refers to a condition in which the meibomian glands do not secrete enough oil into tears or the oil they secrete is of poor quality. As used herein, "ocular discomfort" refers to a lack of ocular comfort, e.g., the presence of one or more of the following in one or both eyes: stinging, irritation, soreness, dryness, itching, scratchiness, tingling, pain, heaviness, tenderness, fatigue, light sensitivity, wind sensitivity, discharge, tearing, watering, discharge, mucus, crusting, heat, warmth, cold, redness, stinging, blinking.

[0143] In accordance with the present invention, the composition may be applied onto a surface to be protected from evaporation or may be administered to a subject in need thereof, such as the ocular surface of a subject.

[0144] The amount and regimen for therapeutic administration of the composition can be readily determined by one of ordinary skill in the clinical art of treating ocular diseases or disorders. In general, the dosage of the composition of the present invention will vary depending on multiple factors, such as age, sex, other possible treatments, the disorder in question, and the severity of the symptoms. The therapeutically effective amount of the composition can be empirically determined using art-recognized dose escalation and dose-response assays. The composition of the present invention can be administered in a dose of, for example, 0.001 to 0.5 ml. For example, the use of eye drops is well known to those of ordinary skill in the art, and various dosage instructions are available. Monitoring the progress of therapy or side effects of the patient can provide additional guidance for optimal dosing regimens.

[0145] In one embodiment of the present invention, the subject is a human, a child, an adolescent, or an adult. Also, any animal or mammal, such as a pet, livestock, or production animal, may be a subject of the present invention. The subject is in need of treatment or prevention of dry eye disease and / or meibomian gland dysfunction, or relief of eye discomfort.

[0146] As used herein, the term "treatment" or "treating" refers to administering a composition to a subject for purposes including complete cure as well as amelioration, delay, or alleviation of the disorder or symptoms associated with the disorder in question. A therapeutically effective amount of a composition refers to an amount that at least ameliorates the adverse effects of a disorder such as dry eye disease, meibomian gland dysfunction, or eye discomfort. The adverse effects may include, but are not limited to, dry eye, eye irritation, eye redness, eye discharge, easily fatigued eyes, and visual impairment such as blurred vision. A therapeutically effective amount may include an amount effective to reduce, delay, or stop at least a portion of the adverse effects. The effects of the compositions of the present invention may be either short-term or long-term effects.

[0147] Before classifying a subject as suitable for the treatment of the present invention, the clinician may, for example, study any symptoms of the subject or assay any disease markers. Based on results that deviate from normal, the clinician may suggest the treatment of the present invention to the subject. In one embodiment, the subject to which the composition of the present invention is to be administered has been diagnosed with dry eye disease and / or meibomian gland dysfunction.

[0148] Any conventional method can be used for administering the composition to a subject. The route of administration depends on the formulation or form of the composition, the disorder, the patient, and other factors. In one embodiment of the present invention, the composition is administered to the ocular surface (on the eye), to the conjunctiva, to the conjunctival sac, or through the eyelid.

[0149] The desired dosage may be administered in one or more doses at suitable intervals to obtain the desired result. Although only one administration of the composition of the present invention may have a therapeutic effect, certain embodiments of the present invention require several administrations during the treatment period. In one embodiment, the composition is administered once or several times during the treatment period. For example, administration may be performed, for example, 1-10 times or 1-5 times (such as 1-2 times) per day during the treatment period. The length of the treatment period may vary, and may last, for example, 1 week to 12 months, 1-10 years, or even longer.

[0150] The composition of the present invention may be used alone or with one or more other compositions or agents, such as therapeutic agents, to treat dry eye disease and / or meibomian gland dysfunction or to relieve eye discomfort. The administration of the composition of the present invention and the other composition(s) or agent(s) may be simultaneous, separate, or sequential. The administration of the composition of the present invention may be combined with other forms of therapy, such as surgery, and may be more effective than either alone. In one embodiment, the composition of the present invention is utilized as the only therapeutically active agent.

[0151] The efficacy of the present invention for treating dry eye disease and / or meibomian gland dysfunction or relieving eye discomfort can be tested in an in vivo dry eye model using rats or rabbits. Dry eye disease state can be first induced, for example, by treatment with benzalkonium chloride, and then the formulation described in the present invention can be administered in single or multiple doses, and the progression of DED can be monitored by analyzing tear break-up time and performing a thorough biological microscopic evaluation of the effect, followed by vital staining. At the end of the experiment, eyes can be harvested and inflammatory markers can be determined by immunohistochemical analysis.

[0152] The effectiveness of the present invention for slowing the evaporation of water from water reservoirs and artificial lakes can be tested using the techniques described in Section 1.2 below or by conducting field experiments with customized water containers equipped with heat, rain, and wind sensors.

[0153] Any method or use of the present invention may be carried out either in vivo, ex vivo or in vitro.

[0154] It is obvious to those skilled in the art that as technology advances, the concept of the present invention can be implemented in various ways. The present invention and its embodiments are not limited to the examples described below, but may vary within the scope of the claims.

[0155] Further specific embodiments of the present invention are defined in the following numbered paragraphs.

[0156] Paragraph 1. A composition comprising a combination of a fatty acid ester of a hydroxy fatty acid (FAHFA) or a structural analog thereof, a wax ester or a structural analog thereof, and, optionally, one or more additives.

[0157] Paragraph 2. The composition described in paragraph 1, comprising a combination of a FAHFA or a structural analog thereof, a wax ester or a structural analog thereof, and, optionally, one or more additives.

[0158] Paragraph 3. A composition according to any one of Paragraphs 1 or 2, wherein the composition is a pharmaceutical composition.

[0159] Paragraph 4. The composition of any one of Paragraphs 1 to 3, wherein the evaporation resistance of the composition is greater than 1 s / cm, greater than 2 s / cm, or greater than 3 s / cm, greater than 5 s / cm, greater than 9 s / cm, greater than 10 s / cm, greater than 13 s / cm, greater than 15 s / cm, greater than 20 s / cm, greater than 25 s / cm, or greater than 30 s / cm.

[0160] Paragraph 5. The carbon chain length of one or more FAHFAs or structural analogues thereof is C15-C100, C19-C72, C20-C55, C20-C50, C20-C40, C20-C35, C20-C25, C25-C45, C25-C40, C25-C35 or C25-C30, and optionally the carbon chain length is C20, C21, C22, C23, 5. The composition of any one of paragraphs 1 to 4, wherein the composition is C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34, C35, C36, C37, C38, C39, C40, C41, C42, C43, C44, C45, C46, ​​C47, C48, C49, C50, C51, C52, C53, C54 or C55.

[0161] Paragraph 6. The FAHFA or structural analogue thereof has the following formula (I): [ka] During the ceremony, R1 is a carbon atom, an oxygen atom, or a nitrogen atom; R2 is a linear or branched C9-C50 alkyl, alkenyl, or alkynyl chain, or structural analogs thereof; R3 is a carboxyl, hydroxyl, amine, phosphate or silyl ether; The composition of any one of paragraphs 1-5, wherein R4 is a linear or branched C9 to C50 alkyl, alkenyl, or alkynyl chain, or structural analogs thereof.

[0162] Paragraph 7. The composition of any one of Paragraphs 1 to 6, wherein the one or more FAHFAs comprises or are selected from the group consisting of O-acyl-ω-hydroxy fatty acids (OAHFAs).

[0163] Paragraph 8. The composition according to any one of paragraphs 1 to 7, wherein the one or more FAHFAs and / or OAHFAs comprise or are selected from the group consisting of oleic acid-based fatty acid esters, palmitoleic acid-based fatty acid esters, myristoleic acid-based fatty acid esters, lauric acid-based fatty acid esters, paulic acid-based fatty acid esters, gondoic acid-based fatty acid esters, erucic acid-based fatty acid esters, nervonic acid-based fatty acid esters, linoleic acid-based fatty acid esters, and linolenic acid-based fatty acid esters, and / or the structural analogues of the one or more FAHFAs comprise or are selected from the group consisting of oleic acid-based alcohols, palmitoleic acid-based alcohols, myristoleic acid-based alcohols, lauric acid-based alcohols, paulic acid-based alcohols, gondoic acid-based alcohols, erucic acid-based alcohols, nervonic acid-based alcohols, linoleic acid-based alcohols, and linolenic acid-based alcohols.

[0164] Paragraph 9. The composition of any one of Paragraphs 1-8, wherein one or more of the FAHFAs comprises or is selected from the group consisting of 12-OAHFA (12-(oleoyloxy)dodecanoic acid), 15-OAHFA (15-(oleoyloxy)pentadecanoic acid), 20-OAHFA (20-(oleoyloxy)eicosanoic acid), 22-OAHFA (22-(oleoyloxy)docosanoic acid), 20:1-OAHFA ((12Z)-20-(oleoyloxy)eicos-12-enoic acid), and 29:1-OAHFA ((21Z)-29-(oleoyloxy)nonacos-21-enoic acid).

[0165] Paragraph 10. The carbon chain length of one or more wax esters or structural analogs thereof is C15-C100, C19-C72, C20-C55, C20-C50, C20-C40, C20-C35, C20-C25, C25-C45, C25-C40, C25-C35 or C25-C30, and optionally the carbon chain length is C20, C21, C22, C23, C24, C25-C26, C26-C28, C27-C29, C30-C31, C32-C33, C34-C35, C36-C37, C38-C39, C39-C40, C39-C41, C39-C42, C39-C43, C39-C44, C39-C45, C39-C40 ... 3, C24, C25, C26, C27, C28, C29, C30, C31, C32, C33, C34, C35, C36, C37, C38, C39, C40, C41, C42, C43, C44, C45, C46, ​​C47, C48, C49, C50, C51, C52, C53, C54 or C55.

[0166] Paragraph 11. The wax ester or structural analog thereof has the following formula (II): [ka] During the ceremony, R1 is a carbon atom, an oxygen atom, or a nitrogen atom; R2 is a linear or branched C9-C50 alkyl, alkenyl, or alkynyl chain, or structural analogs thereof; 11. The composition of any one of paragraphs 1-10, wherein R3 is a linear or branched C9 to C50 alkyl, alkenyl, or alkynyl chain, or structural analogs thereof.

[0167] Paragraph 12. One or more wax esters are selected from the group consisting of n-oleic acid esters, isobranched alkyl oleates, anteisobranched alkyl oleates, palmitoleic acid esters, isobranched alkyl palmitoleates, anteisobranched alkyl palmitoleates, myristoleic acid esters, isobranched alkyl myristoleates, anteisobranched alkyl myristoleates, lauric acid esters, isobranched alkyl laurates, anteisobranched alkyl laurates, paulic acid esters, isobranched alkyl paulinates, anteisobranched alkyl paulinates, gondolaris ... 12. The composition of any one of paragraphs 1-11, comprising or selected from the group consisting of acid-based esters, iso-branched alkyl gondoates, anteiso-based alkyl gondoates, erucic acid-based esters, iso-branched alkyl eruciates, anteiso-branched alkyl eruciates, nervonic acid-based esters, iso-branched alkyl nervonates, anteiso-branched nervonates, linoleic acid-based esters, iso-branched alkyl linoleates, anteiso-branched alkyl linolenates, linolenic acid-based esters, iso-branched alkyl linolenates, and anteiso-branched alkyl linolenates.

[0168] Paragraph 13. One or more wax esters are selected from the group consisting of palmityl oleate, stearyl oleate, arachidyl oleate (AO), behenyl oleate (BO), lignoceryl oleate, hexocosanyl oleate, 24-methylpentacosanyl oleate, palmityl palmitoleate, stearyl palmitoleate, arachidyl palmitoleate, behenyl palmitoleate, lignoceryl palmitoleate, 24-methylpentacosanyl palmitoleate, 13. The composition of any one of paragraphs 1-12, comprising or selected from the group consisting of palmityl linoleate, stearyl linoleate, arachidyl linoleate, behenyl palmitoleate, lignoceryl linoleate, 24-methylpentacosanyl linolenate, palmityl linolenate, stearyl linolenate, arachidyl linolenate, behenyl palmitoleate, lignoceryl linolenate, and 24-methylpentacosanyl linolenate.

[0169] Paragraph 14. The composition according to any one of paragraphs 1 to 13, wherein the one or more wax esters or structural analogues thereof are in a liquid state at physiological conditions and / or the one or more wax esters or structural analogues thereof are in a solid state at physiological conditions.

[0170] Paragraph 15. The composition according to any one of Paragraphs 1 to 14, wherein the molar ratio of the one or more FAHFAs and / or structural analogues thereof to the one or more wax esters and / or structural analogues thereof is less than or equal to 1:1, about 1:1 to 1:100, or 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:90.

[0171] Paragraph 16. The composition of any one of Paragraphs 1 to 15, wherein the molar ratio of the one or more FAHFAs and / or structural analogues thereof to the one or more wax esters or structural analogues thereof is greater than 1:1, about 100:1 to 1:1, about 3:2 to 5:1, or 90:1, 80:1, 70:1, 60:1, 50:1, 40:1, 30:1, 20:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, or 2:1.

[0172] Paragraph 17. The composition according to any one of Paragraphs 1 to 16, wherein the one or more additives are selected from the group consisting of solvents, diluents, carriers, buffers, excipients, adjuvants, carrier vehicles, preservatives, fillers, stabilizers, thickeners, emulsifiers, disintegrants, lubricants, and binders, and any combination thereof.

[0173] Paragraph 18. The composition of Paragraph 17, wherein the one or more pharma- ceutically acceptable excipients are ophthalmically acceptable excipients selected from the group consisting of polyethylene glycol, propylene glycol, glycerin, polyvinyl alcohol, povidone, polysorbate 80, hydroxypropyl methylcellulose, carmellose, carbomer 980, sodium hyaluronate, and dextran.

[0174] Paragraph 19. The composition of any one of Paragraphs 1 to 18, wherein the composition comprises at least 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of FAHFAs, structural analogs thereof, and / or wax esters and / or structural analogs thereof.

[0175] Paragraph 20. The composition according to any one of Paragraphs 1 to 19, wherein the composition is in the form of a liquid, semi-solid, or solid, the composition is in the form of a solution, emulsion, suspension, spray, powder, tablet, pellet, or capsule, or the composition is an oil-in-water emulsion.

[0176] Paragraph 21. A composition according to any one of paragraphs 1 to 20 for use as a medicament.

[0177] Paragraph 22. A composition according to any one of Paragraphs 1 to 20 for use in the treatment of dry eye disease and / or meibomian gland dysfunction or for use in the relief of ocular discomfort.

[0178] Paragraph 23. A method for preparing a composition according to any one of Paragraphs 1 to 20, the method comprising combining or mixing one or more FAHFAs or structural analogues thereof, one or more wax esters or structural analogues thereof, and, optionally, one or more additives.

[0179] Paragraph 24. The method of Paragraph 23, wherein the method further comprises preparing or synthesizing the FAHFA or structural analog thereof prior to mixing the FAHFA or structural analog thereof with the wax ester or structural analog thereof, and / or preparing or synthesizing the wax ester or structural analog thereof prior to mixing the wax ester or structural analog thereof with the FAHFA or structural analog thereof.

[0180] Paragraph 25. A non-therapeutic or therapeutic method of preventing evaporation of water, the method comprising applying a composition according to any one of paragraphs 1 to 20 onto a surface to be protected from evaporation or to a material to be protected from evaporation.

[0181] Paragraph 26. Use of a composition according to any one of paragraphs 1 to 20 for preventing evaporation of water.

[0182] Paragraph 27. A method of treating dry eye disease and / or meibomian gland dysfunction or relieving ocular discomfort, the method comprising administering a composition described in any one of Paragraphs 1-20 to the ocular surface of a subject in need thereof. EXAMPLES

[0183] 1. Materials and Methods 1.1 Lipid synthesis All reagents were purchased from commercial sources. When dry solvents were required, they were purified by VAC vacuum solvent purification system before use. All reactions containing moisture- or air-sensitive reagents were carried out under an argon atmosphere. All reactions requiring heating were carried out using an oil bath. Thin layer chromatography (TLC) was carried out on aluminum sheets precoated with silica gel 60F254 (Merck). Flash chromatography was carried out using silica gel 40. Spots were visualized with UV followed by spraying with a 1:4 H2SO4 / MeOH solution and heating. HRMS was recorded using a Bruker Micro Q-TOF with ESI (electrospray ionization) operating in positive mode. NMR spectra were recorded using a 500.13 MHz ( 1 H) or 499.82MHz ( 1 H), 125.68MHz ( 13 C) and 202.40MHz ( 31 All products were recorded using a Bruker Avance III NMR spectrometer operating at 1D( 1 H, 13 C, and31 P) and 2D techniques (DQF-COSY, TOCSY, Ed-HSQC, and HMBC) in combination with pulse sequences provided by the instrument manufacturer. Probe temperature was kept at 25 °C unless otherwise stated. Chemical shifts are expressed in δ scale (ppm) using TMS (tetramethylsilane) or residual chloroform as internal standard. Melting point analyses were performed, when possible, using a Büchi B-545 melting point analyzer (Büchi Labortechnik AG).

[0184] 1.1.1 Synthesis of FAHFAs Here, the synthesis of FAHFAs is exemplified by the synthesis of the following oleic acid derivatives: 20-OAHFA (20-(oleoyloxy)eicosanoic acid), 20:1-OAHFA ((12Z)-20-(oleoyloxy)eicos-12-enoic acid), and 29:1-OAHFA ((21Z)-29-(oleoyloxy)nonacos-21-enoic acid). A substantial library of structural analogs has been prepared as well.

[0185] Other FAHFAs can be prepared by processes similar to those described herein and / or conventional synthetic procedures, according to standard techniques, from commercially available starting materials or starting materials available by conventional synthetic procedures, using appropriate reagents and reaction conditions. In this regard, the skilled artisan can refer to, inter alia, "Comprehensive Organic Synthesis" by BM Trost and I. Fleming, Pergamon Press, 1991, "Comprehensive Organic Functional Group Transformations" by AR Katrittzky, O. Meth-Cohn and CW Rees, Pergamon Press, 1995, and / or "Comprehensive Organic Transformations" by RC Larock, Wiley-VCH, 1999, and "March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure," by Michael B. Smith, John Wiley and Sons Ltd, Eighth Ed., 2020.

[0186] Example 1. Synthesis of 20-(oleoyloxy)eicosanoic acid. 20-Hydroxyicosyl oleate. Oleic acid (1.2 equiv), NaHSO4·H2O (3.5 mol%), and 1,20-eicosanediol (0.12 g, 3.8 mmol, 1 equiv) were added to a round bottom flask. The stirred mixture was heated to 100 °C in an oil bath under vacuum. After 2.5 h, the reaction was brought to room temperature, diluted with CHCl3 (20 ml), and washed with saturated NaHCO3 (15 ml). The organic layers were combined, washed with brine (15 ml), dried over Na2SO4, filtered, and concentrated. The crude product was purified by column chromatography (EtOAc:Hexane 1:3), concentrated, and dried on a vacuum line to give the title compound as a white solid (0.10 g, 48% yield). Melt point 59 °C. 1H NMR (500.13MHz; CDCl3): δ5.38~5.30(m, 2H), 4.05(t, 2H), 3.66~3.62(m, 2H), 2.29( ppm. 13 C NMR (125.68MHz; CDCl3): δ174.2, 130.2, 129.9, 64.6, 63.3, 34.6, 33.0, 32.1~27.3, 26.1, 25.9, 25.2, 22.8, 22.2, 14.3ppm. HRMS m / z:[M+H] + C 38 H 75 Calculated value for O3: 597.5716, measured value: 597.5713.

[0187] 20-(Oleoyloxy)eicosanoic acid. Under an argon atmosphere, a solution of 20-hydroxyeicosyl oleate (0.4026 g, 1 eq.) in THF (15 ml), acetone (15 ml), and EtOAc (7.5 ml) was cooled to 0° C. and Jones reagent (0.770 ml, 2.2 eq.) was added dropwise. The reaction mixture was stirred for 1 h, quenched with 2-propanol (8 ml), and filtered through a pad of Celite. The Celite was then washed with Et2O (80 ml), and the collected filtrate was washed with brine (2×80 ml), dried over Na2SO4, filtered, and concentrated. The crude product was purified using column chromatography (EtOAc:Hexanes:AcOH 5:95:0.1) and dried on a vacuum line to give the title compound as a white solid (0.345 g, 84% yield), mp 62° C. 1 H NMR (500.13MHz; CDCl3): δ5.38~5.30(m, 2H), 4.06(t, 2H), 2.35(t, 2H), 2.29(t, 2H), 2.03~1.99(m, 4H), 1.67~1.55(m, 6H), 1.30~1.25(m, 49H) and 0.88(t, 3H)ppm. 13C NMR (125.68MHz; CDCl3): δ177.1, 174.2, 130.2, 129.9, 64.6, 34.6, 33.7~27.3, 26.1, 25.2, 24.9, 22.8 and 14.3ppm. HRMS m / z:[M+K] + C 38 H 72 Calculated value for O4K: 631.5068, measured value: 631.5005.

[0188] Example 2. (12Z)-20-(oleoyloxy)eicos-12-enoic acid. 12-Bromo-1-dodecanol. To a solution containing 1,12-dodecanediol (2 g, 1 eq.) in cyclohexane (26 ml), HBr (26 ml, 24 eq., 48% solution in H2O) was added and the biphasic system was refluxed for 18 h. The reaction mixture was then cooled to room temperature and the organic layer was separated. The aqueous phase was extracted with CH2Cl2 (5×25 ml). The combined organic phase was washed with saturated aqueous NaHCO3 (5×25 ml), brine (50 ml), dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (hexane:EtOAc 7:3) and dried on a vacuum line to give the title compound as a white solid (2 g, 77% yield). 1 H NMR (500.13MHz, CDCl3): δ3.64(t, 2H), 3.41(t, 2H), 1.85(tt, 2H), 1.56(tt, 2H), 1.42(tt, 2H) and 1.38~1.22(m, 14H) ppm. 13 C NMR (125.68 MHz, CDCl3): δ 63.2, 34.2, 33.0, 29.7-28.9, 28.3 and 25.9 ppm. HRMS (EI) m / z C 12 H 25 BrONa[M+Na] + The calculated value is 287.0989 and the measured value is 287.1001.

[0189] 12-Bromo-1-tert-butyldimethylsilyloxydodecane. To a solution containing 12-bromo-1-dodecanol (0.500 g, 1.2 eq.) in dry CHCl (3 ml) was added imidazole (0.215 g, 2 eq.). The reaction mixture was stirred under argon atmosphere and after complete dissolution, TBDSMCl (0.238 g, 1 eq.) was added. The reaction mixture was stirred at room temperature for 18 h, then poured into cold saturated aqueous NaHCO (20 ml) and extracted with CHCl (3×20 ml). The combined organic phases were washed with H0 (50 ml), dried over NaSO, filtered and concentrated. The crude oil was purified by column chromatography (hexane:EtOAc 97:3) and dried on a vacuum line to give the title compound as a colorless thick oil (0.564 g, 94% yield). 1 H NMR (500.13MHz, CDCl3): δ3.60(t, 2H), 3.40(t, 2H), 1.85(tt, 2H), 1.50(tt, 2H), 1.42(tt, 2H), 1.35~1.22(m, 14H), 0.89(s, 9H) and 0.04(s, 6H) ppm. 13 C NMR (125.68 MHz, CDCl3): δ 63.5, 34.1, 33.0, 29.8-28.9, 28.3, 26.1, 26.0, 18.5 and -5.1 ppm. HRMS (EI) m / z of C 18 H 39 BrOSiNa[M+Na] + Calculated value: 401.1854, measured value: 401.1852.

[0190] 1-tert-Butyldimethylsilyloxydodecane, triphenylphosphonium bromide. A mixture containing 12-bromo-1-tert-butyldimethylsilyloxydodecane (2.0 g, 1 equiv.) and PPh3 (1.39 g, 1 equiv.) was stirred overnight at 120° C. under an argon atmosphere and cooled to room temperature. 31 P NMR analysis confirmed the formation of the triphenylphosphonium bromide salt, and the thick resinous product was used directly in the subsequent Wittig reaction. 31 P NMR (202.4MHz, CDCl3): δ24.4ppm.

[0191] 8-Bromo-1-octanal. 8-Bromo-1-octanol (1.01 g, 1 equiv.) was dissolved in CH2Cl2 (80 ml) and PCC (1.563 g, 1.5 equiv.) was added. The reaction mixture was stirred at room temperature for 3 h, then Et2O (80 ml) was added, followed by filtration through Celite to remove PCC residues. The flask was washed with Et2O (2 x 80 ml) and the combined filtrate was filtered through Celite before concentration. H2O (50 ml) and Et2O (50 ml) were added to the residue. The light green organic phase was separated and the aqueous phase was extracted with CH2Cl2 (2 x 50 ml). The combined organic phase was washed with H2O (100 ml), dried over Na2SO4, filtered and concentrated to give the title compound as an oil (84% yield). The crude product was used directly in the subsequent Wittig reaction. 1 H NMR (500.13MHz, CDCl3): δ9.74(t, 1H), 3.38(t, 2H), 2.41(dt, 2H), 1.83(tt, 2H), 1.61(tt, 2H), 1.42(tt, 2H) and 1.35~1.29(m, 4H) ppm.

[0192] (12Z)-20-Bromo-1-tert-butyldimethylsilyloxyeicos-12-ene. A solution containing 1-tert-butyldimethylsilyloxydodecane, triphenylphosphonium bromide (3.164 g, 2 eq.) in dry THF (30 ml) and HMPA (8.9 ml) was cooled to −78° C. under an argon atmosphere. After 10 min, NaHMDS (8.2 ml, 0.6 M in toluene, 2 eq.) was added slowly and the resulting mixture was stirred for 1 h. A solution of freshly prepared 8-bromo-1-octanal (0.536 g, 1.05 eq.) dissolved in dry THF (8 ml) was added slowly at −78° C. and the reaction mixture was allowed to warm to room temperature over 24 h before being quenched with aqueous phosphate buffer (freshly prepared, pH=7.2, 80 ml). Extraction with EtO (3×80 ml) was then performed and the combined organic phases were dried over NaSO, filtered and concentrated. The crude product was purified by column chromatography (Hexanes:EtN 100:0.1→Hexanes:EtOAc:EtN 399:1:0.1→98.7:1.3:0.1) and further dried on a vacuum line to give the title compound as a thick yellowish oil (0.427 g, 34% yield). 1 H NMR (499.82MHz, CDCl3): δ5.35(dtt, 1H), 5.34(dtt, 1H), 3.60(t, 2H), 3.40(t, 2H), 2.02(ddt, 2H), 2.01 (ddt, 2H), 1.85 (tt, 2H), 1.50 (tt, 2H), 1.43 (tt, 2H), 1.38~1.22 (m, 22H), 0.89 (s, 9H) and 0.05 (s, 6H) ppm. 13 C NMR (125.68MHz, CDCl3): δ130.3, 129.9, 63.5, 34.2, 33.1, 33.0, 29.9~28.8, 28.3, 27.4~27.3, 26.2, 26.0, 18.6 and -5.1ppm. C of HRMS(EI)m / z 26 H 53 BrOSiNa[M+Na] + Calculated value: 511.2949, measured value: 511.2995.

[0193] (12Z)-20-Acetoxy-1-tert-butyldimethylsilyloxyeicos-12-ene. To a solution containing 2 (0.265 g, 1 eq.) in DMSO (12 ml), KOAc (0.266 g, 5 eq.) was added and the suspension was stirred at room temperature overnight. After 24 h, additional KOAc (0.159 g, 3 eq.) was added and the temperature was raised to 50° C. After 27 h, the reaction mixture was brought to room temperature and H2O (25 ml) was added. Extraction with Et2O (3×25 ml) was performed and the combined organic phase was washed with brine (30 ml), dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (Hexane:EtOAc:Et3N 98:2:0.1→95.5:0.1) and dried on a vacuum line to give the title compound as a yellowish oil (0.169 g, 66% yield). 1 H NMR (500.13MHz, CDCl3): δ5.35(dtt, 1H), 5.34(dtt, 1H), 4.05(t, 2H), 3.59(t, 2H), 2.04(s, 3H), 2.01(d ppm. 13 C NMR (125.68 MHz, CDCl3): δ 171.4, 130.2, 129.9, 64.8, 63.5, 33.1, 29.9-29.3, 28.8, 27.4-27.3, 26.2, 26.0, 21.2, 18.6 and -5.1 ppm. HRMS (EI) m / z of C 28 H 56 O3SiNa[M+Na] + Calculated value: 491.3899, measured value: 491.3879.

[0194] (12Z)-20-Hydroxy-1-tert-butyldimethylsilyloxyeicos-12-ene. To a solution containing (12Z)-20-acetoxy-1-tert-butyldimethylsilyloxyeicos-12-ene (0.022 g, 1 eq.) in MeOH (1 ml) and THF (0.5 ml) under an argon atmosphere was added NaOMe (0.003 g, 1 eq.) and the resulting mixture was stirred at room temperature. After 22 h, the reaction was quenched by the addition of aqueous HCl (10% solution, v / v, 3 drops) and H2O (15 ml). The resulting mixture was extracted with Et2O (3 x 15 ml) and the combined organic phase was dried over Na2SO4, filtered and concentrated. Drying under vacuum gave the title compound as a white solid (0.015 g, 78% yield). 1 H NMR (500.13MHz, CDCl3): δ5.34(dtt, 1H), 5.34(dtt, 1H), 3.64(t, 2H), 3.59(t, 2H), 2.01(ddt, 2H) ), 2.00 (ddt, 2H), 1.57 (tt, 2H), 1.50 (tt, 2H), 1.40~1.22 (m, 24H), 0.89 (s, 9H) and 0.04 (s, 6H) ppm. 13 C NMR (125.68MHz, CDCl3): δ130.2, 129.9, 63.5, 63.3, 33.0, 32.9, 29.9~29.4, 27.4~27.3, 26.1, 26.0~25.9, 18.6 and -5.1ppm. C of HRMS(EI)m / z 26 H 54 O2SiNa[M+Na] + Calculated value: 449.3793, measured value: 449.3832.

[0195] (12Z)-20-Oleoyloxy-1-tert-butyldimethylsilyloxyeicos-12-ene. To a solution of 3 (0.040 g, 1 equiv.) in dry CHCl (2 ml) under argon atmosphere was added DMAP (0.012 g, 1 equiv.) and EDC·HCl (0.046 g, 2.5 equiv.), and the resulting mixture was cooled to 0°C on an ice bath. Oleic acid (0.032 g dissolved in 0.5 ml dry CHCl, 1.2 equiv.) was added, and the reaction mixture was stirred at 0°C for 10 min and then at room temperature overnight. The reaction mixture was quenched after 20 h with H0 (2 ml) and diluted with CHCl (10 ml). The organic phase was separated and the aqueous phase was extracted with CHCl (2×10 ml). The combined organic phase was washed with H2O (2 x 15 ml), dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (Hexane: EtOAc: Et3N 95:5:0.1) and dried under vacuum to give the title compound as a white solid (0.061 g, 93% yield). 1 H NMR (500.13MHz, CDCl3): δ5.35(dtt, 1H), 5.35(dtt, 1H), 5.34(dtt, 1H), 5.34(dtt, 1H), 4.05(t, 2H), 3.60(t, 2H), 2.29(t, 2H), 2.06~1.96(m, 8H), 1.62(tt, 2H), 1.61(tt, 2H), 1.50(tt, 2H,), 1.37~1.23(m, 44H), 0.89(s, 9H), 0.88(t, 3H) and 0.05(s, 6H)ppm. 13 C NMR (125.68 MHz, CDCl3): δ 174.1, 130.2-129.9, 64.5, 63.5, 34.5, 33.0, 32.1, 29.9-29.3, 28.8, 27.4-27.3, 26.1, 26.0, 25.2, 22.8, 18.6, 14.3 and -5.1 ppm. HRMS (EI) m / z of C 83 O3SiNa[M+Na] + Calculated value: 713.6246, measured value: 713.6214.

[0196] (12Z)-20-oleoyloxyeicos-12-enol. Under argon atmosphere, a solution containing (12Z)-20-oleoyloxy-1-tert-butyldimethylsilyloxyeicos-12-ene (0.031 g, 1 eq.) in dry THF (0.5 ml) was cooled to 0° C. in an ice bath and TBAF (0.140 ml, 1M in THF, 3 eq.) was added. After 5 min, the ice bath was removed and the reaction mixture was stirred at room temperature for 1 h, then quenched with H2O (2 ml) and extracted with EtOAc (3 ml). The organic phase was washed with H2O (2×5 ml) and the aqueous phase was re-extracted with EtOAc (2×5 ml). The combined organic phase was dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (Hexane:EtOAc:Et3N 7:3:0.1) and dried under vacuum to give the title compound as a white solid (0.023 g, 92% yield). 1 H NMR (500.13MHz, CDCl3): δ5.35(dtt, 1H), 5.35(dtt, 1H), 5.34(dtt, 1H), 5.34(dtt, 1H), 4.05(t, 2H), 3.64(t, 2H) , 2.29(t, 2H), 2.06~1.96(m, 8H), 1.62(tt, 2H), 1.61(tt, 2H), 1.56(tt, 2H), 1.37~1.23(m, 44H) and 0.88(t, 3H) ppm. 13 C NMR (125.68 MHz, CDCl3): δ 174.2, 130.2-129.9, 64.5, 63.2, 34.5, 33.0, 32.1, 29.9-29.3, 28.8, 27.4-27.3, 26.0-25.9, 25.2, 22.8 and 14.3. HRMS (EI) m / z C 38 H 72 O3Na[M+Na] + Calculated value: 599.5381, measured value: 599.5342.

[0197] (12Z)-20-oleoyloxyeicos-12-enoic acid. A solution containing 4 (0.026 g, 1 eq.) in acetone (2 ml) and EtOAc (2 ml) was cooled to 0° C. on an ice bath and Jones reagent (0.050 ml, 2.2 eq.) was added. The resulting mixture was stirred at 0° C. for 45 min. H2O (5 ml) was added and the reaction mixture was then extracted with Et2O (3×15 ml). The combined organic phase was washed with brine (15 ml), dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (hexane:EtOAc:AcOH 7:3:0.1 as eluent) and dried on a vacuum line to give the title compound as a white solid (0.024 g, 89% yield). 1 H NMR (500.13MHz, CDCl3): δ5.35(dtt, 1H), 5.35(dtt, 1H), 5.34(dtt, 1H,), 5.34(dtt, 1H), 4.05(t, 2H), 2.34(t, 2H) , 2.29(t, 2H), 2.06~1.96(m, 8H), 1.63(tt, 2H), 1.61(tt, 2H), 1.61(tt, 2H), 1.37~1.23(m, 42H) and 0.88(t, 3H) ppm. 13 C NMR (125.68 MHz, CDCl3): δ 179.6, 174.2, 130.1-129.9, 64.6, 34.5, 34.4, 32.0, 29.9-29.3, 28.8, 27.4-27.3, 26.1, 25.2, 24.9, 22.8 and 14.3. HRMS (EI) m / z of C 38 H 70 O4Na[M+Na] + Calculated value: 613.5174, Found value: 613.5175. Melting point: 29.5-30.7°C.

[0198] Example 3. (21Z)-29-(oleoyloxy)nonacos-21-enoic acid. 1,20-Eicosanediol. A solution containing eicosanedioic acid (0.5101 g, 1 eq.) in 150 ml of THF was cooled to 0° C. on an ice bath. LAH (0.3419 g, 6.05 eq.) was added portionwise and the mixture was allowed to reach room temperature. The reaction mixture was heated to 85° C. and stirred for 18 hours. The reaction was cooled to 0° C. in an ice bath and a saturated aqueous solution containing Rochelle's salt (40 ml) was added. The resulting mixture was stirred for 1 hour and filtered through a celite pad. The filtrate was extracted with DCM (8×30 ml). The combined organic layers were dried over Na2SO4, filtered and concentrated to give the title compound as a white solid (0.405 g, 87% yield). 1 H NMR (500.13MHz, CDCl3): δ3.64 (t, 4H, J=6.1Hz), 1.56 (q, 4H) and 1.38~1.15 (m, 32H) ppm. 13 C NMR (125.68 MHz, CDCl3): δ 63.5, 33.2, 30.0-29.8 and 26.1 ppm. HRMS (EI) m / z of C 20 H 42 O2Na[M+Na] + Calculated value: 337.3083, measured value: 337.3152.

[0199] 20-Bromoeicosan-1-ol. A mixture containing 1,20-eicosanediol (0.66 g, 1 eq), cyclohexane (24 ml), and HBr (9 ml, 48% in water) was heated at 82° C. for 5 h. The reaction was quenched with H2O (20 ml) and the layers were separated. The aqueous layer was extracted with CH2Cl2 (4×20 ml). The combined organic layers were washed with a saturated aqueous solution of NaHCO3 (30 ml) and H2O (30 ml). The organic phase was separated, dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography (EtOAc:hexanes) and dried on a vacuum line to give the title compound as a white solid (0.42 g, 52% yield). 1 H NMR (500.13MHz, CDCl3): δ3.64 (t, 2H, J = 6.1Hz), 3.40 (t, 2H, J = 6.9Hz), 1.85 (m, 2H), 1.56 (m, 2H) and 1.38~1.15 (m, 32H) ppm.13 C NMR (125.68 MHz, CDCl3): δ 63.5, 34.4, 33.2, 31.9, 30.0-28.8, 28.5 and 26.1 ppm. HRMS (EI) m / z of C 20 H 41 OBrNa[M+Na] + Calculated value: 399.2233, measured value: 399.2185.

[0200] 20-Bromo-1-(tetrahydro-2H-pyran-2-yloxy)-eicosanol. To a solution containing 20-bromoeicosan-1-ol (0.23 g, 1 eq.) in CHCl (20 ml), PPTS (0.03 g, 0.13 eq.) and DHP (0.1 ml, 2.15 eq.) were added. The resulting mixture was stirred at room temperature for 23 h. After the crude product was concentrated and purified by flash chromatography (hexane:EtOAc 9:1), the title compound was obtained as a white solid (0.27 g, 97% yield). 1 H NMR (500.13MHz, CDCl3): δ4.57(t, 1H), 3.87(m, 1H), 3.72(m, 1H), 3.50(m, 1H), 3.40(t, 2H, J=6. 89Hz), 3.38 (m, 1H), 1.84 (m, 3H), 1.71 (m, 1H), 1.41 (m, 2H), 1.58 (m, 4H) and 1.38~1.15 (m, 32H) ppm. 13 C NMR (125.68 MHz, CDCl3): δ 98.8, 67.7, 62.3, 34.0, 32.8, 30.8, 29.8-28.2, 26.2, 25.5 and 19.7 ppm. HRMS (EI) m / z of C 25 H 49 OBrNa[M+Na] + Calculated value: 483.2814, measured value: 483.2736.

[0201] 1-O-tert-Butyldimethylsilyl-non-8-yne. A solution containing non-8-yn-ol (0.5 g, 1 eq.) and imidazole (0.567 g, 2.25 eq.) in CHCl (20 ml) was cooled to 0° C. in an ice bath, followed by the addition of TBDMSCl (1.0 g, 1.8 eq.). The mixture was allowed to reach room temperature and stirred for 18 h. The reaction was quenched by pouring the reaction mixture into 20 ml of ice-cold saturated aqueous solution of NHCl. The aqueous layer was separated and extracted with CHCl (4×30 ml). The crude product was purified by flash chromatography (EtOAc:Hexane 9:1) and dried on a vacuum line to give the title compound as a colorless liquid (0.70 g, 78% yield). 1 H NMR (500.13MHz, CDCl3): δ3.58(t, 2H, J=6.6Hz), 2.18(dt, 2H), 1.93(t, 1H, J= 2.7Hz), 1.51(m, 4H), 1.40(m, 2H), 1.31(m, 4H), 0.89(s, 9H) and 0.05(s, 6H)ppm. 13 C NMR (125.68 MHz, CDCl3): 84.7, 68.0, 63.2, 32.8, 28.9, 28.7, 28.4, 26.0, 25.7, 18.4 and -5.3 ppm. HRMS (EI) m / z of C 15 H 30 OSi[M+Na] + Calculated value: 277.1866, measured value: 277.1924.

[0202] 29-(Tetrahydro-2H-pyran-2-yloxy)nonacos-8-yn-1-ol. A solution of 1-O-tert-butyldimethylsilyl-non-8-yn-1-ol (0.236 g, 2.53 eq) in THF (3 ml) and HMPA (1 ml) was cooled to -78°C using an EtOAc / N2 bath. To this solution, BuLi (0.25 ml, 2.39 eq, 2.5M in THF) was added dropwise and the temperature was raised to -40°C and maintained for 2 hours. The reaction mixture was then cooled to -78°C and a solution of 20-bromo-1-(tetrahydro-2H-pyran-2-yloxy)-eicosanol (1 eq) in THF (3 ml) was added dropwise. The resulting mixture was brought to room temperature, TBAI (0.013 g, 1 mol%) was added and the temperature was raised to 80°C. The reaction was quenched after 20 h by pouring into a saturated aqueous solution of NH4Cl (20 ml). The aqueous layer was separated and extracted with EtOAc (6 x 20 ml). The combined organic phases were dried over Na2SO4, filtered and concentrated. The crude product was dissolved in THF (10 ml) and the solution was cooled to 0 °C in an ice bath. TBAF (2.5 ml, 6.83 eq, 1M in THF) was added and the reaction mixture was brought to room temperature and stirred for 1 h. The reaction was quenched with H2O (20 ml) and the aqueous layer was extracted with CH2Cl2 (5 x 20 ml). The combined organic phases were dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (hexane:EtOAc 9:1 -> 4:1) and the fractions containing the product were collected, concentrated and dried on a vacuum line to give the title compound as a white solid (0.099 g, 52% yield). 1 H NMR (500.13MHz, CDCl3): δ4.57(m, 1H), 3.87(m, 1H), 3.72(m, 1H), 3.64(m, 1H), 3.50( ppm. 13 C NMR (125.68 MHz, CDCl3): 98.8, 67.7, 63.0, 62.3, 32.8, 30.8-28.8, 26.2, 25.6, 25.5, 19.7, 18.8 and 18.7 ppm. HRMS (EI) m / z of C 34 H64 O3Na[M+Na] + Calculated value: 543.4753, measured value: 543.4648.

[0203] (8Z)-29-(tetrahydro-2H-pyran-2-yloxy)nonacos-8-en-1-ol. 29-(tetrahydro-2H-pyran-2-yloxy)nonacos-8-yn-1-ol (0.049 g, 1.0 eq.) was dissolved in dry benzene (15 ml) and Lindlar's catalyst (0.025 g) and quinoline (0.11 g, 9.0 eq.) were added. The resulting mixture was placed in a reactor and the air was replaced with H2 atmosphere (1 atm). The reaction mixture was stirred at room temperature for 1 h. Hydrogen gas was removed and the reaction mixture was filtered through a pad of Celite and concentrated. The crude product was purified by flash chromatography (hexane: EtOAc 4:1) and dried on a vacuum line to give the title compound as a white solid (0.044 g, 89% yield). 1 H NMR (500.13MHz, CDCl3): δ5.34(m, 2H), 4.57(m, 1H), 4.05(t, 2H), 3.87(m, 1H), 3.72(m, 1H), 3.49(m, 1H) ), 3.38 (m, 1H), 2.28 (t, 2H), 2.01 (m, 8H), 1.83 (m, 1H), 1.71 (m, 1H), 1.62~1.25 (51H) and 0.88 (t, 3H) ppm. C of HRMS(EI)m / z 34 H 66 O3Na[M+Na] + Calculated value: 545.4910, measured value: 545.4994.

[0204] (8Z)-29-(tetrahydro-2H-pyran-2-yloxy)nonacos-8-en-1-yl oleate. (8Z)-29-(tetrahydro-2H-pyran-2-yloxy)nonacos-8-en-1-ol (0.044 g, 1 eq.) was dissolved in CHCl (2 ml) and DMAP (0.012 g, 1.16 eq.) and EDC·HCl (0.037 g, 2.32 eq.) were added to the reaction mixture, which was then cooled on an ice bath. Oleic acid (0.055 g, 2.34 eq.) in CHCl (2 ml) was added dropwise to the reaction mixture, which was then allowed to come to room temperature and stirred for 22 h. The reaction was quenched by the addition of H0 (20 ml) and the aqueous layer was isolated and extracted with DCM (7×10 ml). The combined organic phase was dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (hexane:EtOAc 98:2→1:1) and dried on a vacuum line to give the title compound as a white solid (0.050 g, 76% yield). 1 H NMR (500.13MHz, CDCl3): δ5.34(m, 4H), 4.57(dt, 1H), 4.05(t, 2H, J=6.8Hz), 3.87(m, 1H), 3.78(m, 1H), 3.49(m , 1H), 3.38(m, 1H), 2.28(t, 2H, J=7.5Hz), 2.01(m, 8H), 1.62~1.55(6H), 1.38~1.20(m, 62H) and 0.88(t, 3H)ppm. 13 C NMR (125.68 MHz, CDCl3): δ 174.0, 130.0, 129.7, 98.8, 67.7, 64.4, 62.3, 34.4, 31.9, 30.8-27.2, 26.2, 25.9, 25.5, 25.0, 22.7, 19.7 and 14.1 ppm. HRMS (EI) m / z of C 52 H 98 O4Na[M+Na] + Calculated value: 809.7139, measured value: 809.7246.

[0205] (21Z)-29-(oleoyloxy)nonacos-21-en-1-ol. (8Z)-29-(tetrahydro-2H-pyran-2-yloxy)nonacos-8-en-1-yl oleate (0.050 g, 1 eq.) was dissolved in MeOH:THF 3:1 (4 ml), the resulting mixture was cooled on an ice bath, and CSA (0.003 g, 0.23 eq.) was added. The reaction mixture was allowed to come to room temperature and stirred for 18 h. The reaction was quenched by the addition of H2O (20 ml) and the aqueous layer was extracted with CH2Cl2 (4 x 20 ml). The combined organic phases were dried over Na2SO4, filtered, and concentrated. The crude product was purified by flash chromatography (hexane:EtOAc 9:1) and dried on a vacuum line to give the title compound as a white solid (0.032 g, 72% yield). 1 H NMR (500.13MHz, CDCl3): δ5.34(m, 4H), 4.05(t, 2H), 3.64(q, 2H), 2.28(2H), 2.05~1.96(m, 8H), 1.62~1.55(m, 6H), 1.38~1.20(m, 62H) and 0.88(t, 3H)ppm. 13 C NMR (125.68MHz, CDCl3): δ174.2, 130.2, 130.2, 130.0, 129.9, 64.6, 63.3, 3 4.6, 33.0, 32.1, 30.0~29.3, 28.9, 27.4, 27.4, 26.1, 25.9, 25.2 and 14.3ppm. C of HRMS(EI)m / z 48 H 90 O3Na[M+H] + Calculated value: 703.6968, Found value: 703.7028. Melting point: 48.7-49.7°C.

[0206] (21Z)-29-(oleoyloxy)nonacos-21-enoic acid. To a solution containing (21Z)-29-(oleoyloxy)nonacos-21-en-1-ol in acetone:EtOAc 1:1 (4 ml) was added Jones reagent (0.05 ml, 2M) and the resulting mixture was stirred for 1 h. The reaction was quenched with isopropanol (1 ml) and filtered through Celite. After careful washing with EtOAc, the combined organic layers were washed with brine (2×30 ml), dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (hexane:EtOAc 9:1) and dried on a vacuum line to give the title compound as a white solid (0.02 g, 61% yield). 1 H NMR (500.13MHz, CDCl3): δ5.34(m, 4H), 4.05(t, 2H), 2.35(t, 2H), 2.29(t, 2H) , 2.05~1.96(m, 8H), 1.67~1.57(m, 6H), 1.38~1.20(m, 62H) and 0.88(t, 3H)ppm. 13 C NMR (125.68MHz, CDCl3): δ177.4, 174.4, 130.2, 130.0, 129.9, 60.6, 34.6, 3 3.7, 32.1, 30.0~29.3, 28.8, 27.4, 27.3, 26.1, 25.2, 24.9, 22.9 and 14.3ppm. C of HRMS(EI)m / z 47 H 88 O4Na[M+Na] + Calculated value: 739.6581, Found value: 739.6803. Melting point: 53.0~54.0℃.

[0207] 18-(oleoyloxy)stearic acid (18:0 / 18:1-OAHFA, 18-OAHFA) Oleic acid (1.29 g, 4.6 mmol, 0.93 equiv), NaHSO4·H2O (0.024 g, 3.5 mol%) and 1,18-octadecanediol (1.40 g, 4.9 mmol, 1 equiv) were added to a round-bottom flask (100 ml). The stirred mixture was heated to 100 °C in an oil bath under vacuum. After 2 h, the reaction was brought to room temperature, diluted with CHCl3 (50 ml) and washed with saturated NaHCO3 (2 × 50 ml). The aqueous phase was re-extracted with CHCl3 (2 × 50 ml) and the organic layers were combined, washed with brine (80 ml), dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (hexane:EtOAc 19:1 → 4:1), concentrated and dried on a vacuum line to give 18-hydroxyoctadecyl oleate as a white solid (1.21 g, 45% yield). Melting point: 51.9~53.0℃. 1 H NMR (499.82MHz, CDCl3, 25℃): δ5.39~5.30(m, 2H), 4.05(t, 2H), 3.66~3.60(m, 2H), 2.2 8(t, 2H), 2.04~1.97(m, 4H), 1.66~1.52(m, 6H), 1.38~1.21(m, 48H) and 0.88(t, 3H)ppm. 13 C NMR (125.68MHz; CDCl3): δ174.1, 130.1, 129.9, 64.6, 63.3, 34.6, 33.0, 32.1, 29.9~29.3, 28.8, 27.4, 27.3, 26.1, 25.9, 25.2, 22.8, 14.3ppm.

[0208] A solution of 18-hydroxyoctadecyl oleate (0.7426 g, 1.4 mmol, 1 equiv) in THF (15 ml), acetone (15 ml) and EtOAc (7.5 ml) was cooled to 0° C. under an argon atmosphere and Jones reagent (1.51 ml, 3.0 mmol, 2.3 equiv) was added dropwise. The reaction mixture was stirred for 1.5 h, quenched with 2-propanol (10 ml) and filtered through a pad of Celite. The Celite was then washed with Et2O (100 ml) and the collected filtrate was washed with brine (2×100 ml), dried over Na2SO4, filtered and concentrated. The crude product was purified using column chromatography (Hexanes:EtOAc:AcOH 19:1:0.01→7:3:0.01) and dried on a vacuum line to give the title compound as a white solid (0.582 g, 78% yield). Melting point: 55.8~56.7℃. 1 H NMR (499.82MHz, CDCl3, 25℃): δ5.39~5.29(m, 2H), 4.05(t, 2H), 2.34(t, 2H), 2.29( ppm. 13 C NMR (125.68 MHz; CDCl3): δ 179.5, 174.2, 130.1, 130.0, 64.6, 34.6, 34.1, 32.1, 29.9-29.2, 28.8, 27.4, 27.3, 26.1, 25.2, 24.8, 22.8 and 14.3 ppm. HRMS m / z C 36 H 68 O4Na[M+Na] + Calculated value: 587.5015, measured value: 587.5030.

[0209] More FAHFAs The following FAHFAs were also prepared following a synthetic process similar to that described for 20-(oleoyloxy)eicosanoic acid (Example 1). 12-(linoleoyloxy)dodecanoic acid, 20-(linoleoyloxy)eicosanoic acid, 12-(palmitoleoyloxy)dodecanoic acid, 20-(Palmitoleoyloxy)eicosanoic acid, 12-(palmitoyloxy)dodecanoic acid, 20-(Palmitoyloxy)eicosanoic acid 12-(stearoyloxy)dodecanoic acid, and 20-(Stearoyloxy)eicosanoic acid.

[0210] Characterization data for the above FAHFAs is provided in the table below. [Table 1-1] [Table 1-2]

[0211] 1.1.2 Synthesis of wax esters Numerous wax esters, such as behenyl oleate, arachidyl oleate, etc., are commercially available and may be used in the present invention. The synthesis of non-commercially available wax esters is exemplified herein by the synthesis of the following oleic acid derivatives: hexocosanyl oleate and 24-methylpentacosanyl oleate. A substantial library of structural analogs has been prepared as well.

[0212] Other wax esters may be prepared by processes similar to those described herein and / or conventional synthetic procedures, according to standard techniques, from available starting materials or starting materials obtainable by conventional synthetic procedures, using appropriate reagents and reaction conditions. Specifically, such compounds may be prepared by Fischer esterification of the corresponding carboxylic acids and alcohols, and / or by reaction of the corresponding acid chlorides or acid anhydrides with the corresponding alcohols under standard reaction conditions. Such carboxylic acids, acid chlorides, acid anhydrides, and alcohols may be commercially available or may be prepared according to conventional synthetic procedures known to those skilled in the art. In this regard, the skilled artisan may refer, inter alia, to "Comprehensive Organic Synthesis" by BM Trost and I. Fleming, Pergamon Press, 1991, "Comprehensive Organic Functional Group Transformations" by ARKatritzky, O. Meth-Cohn and CW Rees, Pergamon Press, 1995, and / or "Comprehensive Organic Transformations" by RC Larock, Wiley-VCH, 1999 and "March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure," by Michael B. Smith, John Wiley and Sons Ltd, Eighth Ed., 2020.

[0213] Example 4. Hexacosyl oleate. Hexacosyl oleate. To a solution of commercially available 1-hexacosanol (0.03 g, 1 equiv.) in dry CHCl (2.5 ml) and pyridine (1 ml) under argon atmosphere, DMAP (0.01 g, 1 equiv.) and EDC·HCl (0.0380 g, 2.5 equiv.) were added. Oleic acid (0.027 g, 1.2 equiv. in 0.5 ml dry CHCl) was added dropwise. The resulting mixture was stirred at room temperature overnight. The reaction mixture was quenched after 18.5 h with H0 (5 ml) and diluted with CHCl (10 ml). The organic phase was separated and the aqueous layer was extracted with CHCl (3×10 ml). The combined organic layers were washed with H0 (2×20 ml), dried over NaSO, filtered and concentrated. The crude product was purified by column chromatography (hexanes:EtOAc 95:5) and dried on a vacuum line to give the title compound as a white waxy solid (0.047 g, 93% yield), mp 47.0-49.0 °C. 1 H NMR (500.13MHz, CDCl3): δ5.35(dtt, 1H), 5.33(dtt, 1H), 4.05(t, 2H), 2.29(t, 2H), 2.01(ddt, 2H) ), 2.00(ddt, 2H), 1.62(tt, 2H), 1.60(tt, 2H), 1.38~1.19(m, 66H), 0.88(t, 3H) and 0.88(t, 3H)ppm. 13 C NMR (125.68MHz, CDCl3): δ 13 C NMR (125.68MHz, CDCl3): δ174.1, 130.1, 129.9, 64.5, 39.2, 34.6, 32.1~32.0, 29 .9~29.7, 29.5~29.4, 29.3~29.2, 28.8, 27.4~27.3, 26.1, 25.2, 22.8 and 14.3ppm. C of HRMS(EI)m / z 44 H 86 O2Na[M+Na] + Calculated value: 669.6528, measured value: 669.6693.

[0214] Example 5.24-Methyl pentacosyl oleate. 1-(2-tetrahydropyranyloxy)-24-methylpentacos-20-yne. A solution containing 4-methyl-1-pentyne (0.65 ml, 5 eq.) in dry THF (4 ml) and HMPA (1.5 ml) was cooled to -78°C under argon atmosphere. n-BuLi (2.2 ml, 2.5 M in hexane, 5 eq.) was slowly added and the resulting mixture was stirred at -40°C for 2 hours. The temperature was then lowered again to -78°C and a solution of 20-bromo-1-(2-tetrahydropyranyloxy)eicosane (0.500 g, 1 eq.) dissolved in dry THF (5 ml) was slowly added and the reaction mixture was allowed to warm to room temperature. TBAI (0.040 g, 0.1 eq.) was added and the reaction mixture was stirred at room temperature for 10 minutes and then refluxed at 80°C overnight. The reaction mixture was then quenched with a saturated solution of NH4Cl (20 ml) and extracted with Et2O (5 x 20 ml). The combined organic phase was washed with H2O (2 x 20 ml), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (hexane: EtOAc 98:2 -> 90:10) and dried on a vacuum line to give the title compound as a yellowish solid (0.445 g, 89% yield). 1 H NMR (500.13MHz, CDCl3): δ4.57(t, 1H), 3.92~3.83(m, 1H), 3.77~3.68(m, 1H), 3.55~3.46(m, 1H), 3.42~3.33(m, 1H), 2.19~2.11(m, 2 H), 2.07~2.01(m, 2H), 1.88~1.67(m, 3H), 1.64~1.43(m, 8H), 1.42~1.33(m, 4H), 1.32~1.17(m, 28H), 0.96(d, 3H) and 0.96(d, 3H)ppm. 13 C NMR (125.68 MHz, CDCl3): δ 98.9, 81.3, 79.2, 67.9, 62.5, 30.9, 29.9-29.0, 28.5, 28.2, 26.4, 25.7, 22.1, 19.9 and 18.9 ppm. HRMS (EI) m / z of C 31 H 58 O2Na[M+Na] + Calculated value: 485.4337, measured value: 485.4325.

[0215] 1-Hydroxy-24-methylpentacos-20-yne. To a solution of 1-(2-tetrahydropyranyloxy)-24-methylpentacos-20-yne (0.153 g, 1 eq.) in dry THF / MeOH (6 ml, 1:3 ratio), add CSA (0.008 g, 0.1 eq.) under argon atmosphere, and the resulting reaction mixture is stirred at room temperature overnight, then concentrated under reduced pressure. The crude product is purified by column chromatography (hexane:EtOAc 100:0→4:1) and dried on vacuum line to obtain the title compound as a white solid (0.118 g, 95% yield). 1 H NMR (500.13MHz, CDCl3): δ3.64(t, 2H), 2.17~2.12(m, 2H), 2.06~2.00(m, 2H), 1.81~1.70 (m, 1H), 1.57 (tt, 2H), 1.48 (tt, 2H), 1.41~1.20 (m, 32H), 0.96 (d, 3H) and 0.96 (d, 3H)ppm. 13 C NMR (125.68 MHz, CDCl3): δ 81.3, 79.2, 63.3, 32.9, 29.8-29.0, 28.5, 28.2, 25.9, 22.1 and 18.9 ppm. HRMS (EI) m / z of C 26 H 50 ONa[M+Na] + The calculated value is 401.3762, the actual value is 401.3760.

[0216] 1-Hydroxy-24-methylpentacosane. To a solution of 1-hydroxy-24-methylpentacos-20-yne (0.110 g, 1.0 equiv.) in dry EtOAc (15 ml) was added Pd / C (10% Pd, 0.220 g, 2 mass equiv.). The reaction mixture was stirred in an autoclave under H2 pressure (6 bar) for 4 h and filtered through Celite. The Celite was washed with EtOAc (20 ml) and the filtrate was concentrated under reduced pressure. The crude product was purified (hexane:EtOAc 4:1) and dried on a vacuum line to give the title compound as a white solid (0.093 g, 84% yield). 1H NMR (500.13MHz, CDCl3): δ3.64(t, 2H), 1.56(tt, 2H), 1.53~1.47(m, 1H), 1.39~1.18(m, 40H), 1.15(q, 2H), 0.86(d, 3H) and 0.86(d, 3H) ppm. 13 C NMR (125.68 MHz, CDCl3): δ 63.3, 39.2, 32.9, 30.1, 29.9-29.6, 28.1, 27.6, 25.9 and 22.8 ppm. HRMS (EI) m / z of C 26 H 54 ONa[M+Na] + Calculated value: 405.4075, measured value: 405.4028.

[0217] 24-Methylpentacosyl oleate. To a solution of 1-hydroxy-24-methylpentacosane (0.035 g, 1 equiv.) in dry CHCl (2.5 ml) and dry pyridine (1 ml) under argon atmosphere was added DMAP (0.012 g, 1 equiv.) and EDC·HCl (0.044 g, 2.5 equiv.). Oleic acid (0.031 g, 1.2 equiv. in 0.5 ml dry CHCl) was added dropwise. The resulting mixture was incubated at room temperature overnight. After 18 h, the reaction mixture was quenched with H0 (10 ml) and diluted with CHCl (10 ml). The organic phase was separated and the aqueous layer was extracted with CHCl (4×10 ml). The combined organic layers were washed with H0 (2×15 ml), dried over NaSO, filtered and concentrated. The crude product was purified by column chromatography (hexanes:EtOAc 95:5) and dried on a vacuum line to give the title compound as a white waxy solid (0.057 g, 96% yield), mp 36.0-37.5° C. 1H NMR (500.13 MHz, CDCl3): δ 5.36 (dtt, 1H), 5.34 (dtt, 1H), 4.05 (t, 2H), 2.29 (t, 2H), 2.01 (ddt, 2H), 2.00 (ddt, 2H), 1.62 (tt, 2H), 1.60 (tt, 2H), 1.56–1.47 (m, 1H), 1.38–1.19 (m, 60H), 1.15 (q, 2H), 0.88 (t, 3H, overlap), 0.86 (d, 3H, overlap) and 0.86 (d, 3H, overlap) ppm. 13 C NMR (125.68MHz, CDCl3): δ174.1, 130.1, 129.9, 64.6, 39.2, 34.6, 32.1, 30.1, 29.9~29.3, 28.8, 28.1, 27.6, 27.4~27.3, 26.1, 25.2, 22.8 and 14.3ppm. C of HRMS(EI)m / z 44 H 87 O2[M+H] + Calculated value: 647.6708, observed value: 647.6725.

[0218] 1.2 Characterization of the surface texture and evaporation resistance of lipid compositions containing FAHFAs and wax esters 1.2.1 Materials and preparation of lipid composition Lipid species were synthesized as described above or obtained from commercial sources (e.g., Nu-Check-Prep, Elysian, MN) and initially studied on their own. A range of lipid mixtures were prepared by weighing selected compounds in specific ratios and further diluting in chloroform to obtain selected concentrations. 2 mM concentrations of the corresponding mixtures were used for surface potential and pressure measurements, and 5 mM concentrations were used for evaporation resistance measurements discussed herein.

[0219] Example 6a. Mixtures containing arachidyl oleate (AO) or behenyl oleate (BO) and 20-(oleoyloxy)eicosanoic acid (20-OAHFA). Several mixtures of 20-OAHFA and either AO or BO were prepared by the methods described above, and we focus here on four different 20-OAHFA:AO mixtures with molar ratios of 1:1, 1:3, 1:6, and 1:9, and six different 20-OAHFA:BO mixtures with molar ratios of 3:1, 2:1, 1:1, 1:2 1:3, and 1:9.

[0220] Example 6b. Mixtures of 18-(oleoyloxy)stearic acid (18:0 / 18:1-OAHFA) and behenyl oleate (BO), 18:0 / 18:1-OAHFA and behenyl behenoate (BB), 18:0 / 18:1-OAHFA and arachidyl laurate (AL), and (29:1 / 18:1-OAHFA) and BO 1:1 mixtures of 18-(oleoyloxy)stearic acid (18:0 / 18:1-OAHFA) and behenyl oleate (BO), 18:0 / 18:1-OAHFA and behenyl behenoate (BB), 18:0 / 18:1-OAHFA and arachidyl laurate (AL), and (29:1 / 18:1-OAHFA) and BO were prepared using the methods described above, and 5 mM solutions of each mixture in chloroform were used for the evaporation resistance measurements described herein.

[0221] 1.2.2 Preparation of the formulation The formulations were prepared by mixing the FAHFAs or their structural analogs and the wax esters or their structural analogs with appropriate excipients, such as emulsifiers, to create a stable emulsion.

[0222] Example 7. Formulation containing 20-(oleoyloxy)eicosanoic acid (20-OAHFA) and behenyl oleate (BO). A formulation containing 0.25 wt% 20-OAHFA, 0.75 wt% BO, 0.8% w / v Miglyol 812, 2% w / v Tween 20, 0.5% w / v Kolliphor® EL, 0.7% w / v Span 80, 2.2% w / v glycerin, and 98.2% w / v ultrapure water was prepared by mixing at 76°C.

[0223] 1.2.3 Surface pressure, Brewster angle microscopy, and surface potential Lipid mixtures or formulations dissolved in chloroform were spread onto the air-buffer interface of either a KSV mini trough (Helsinki, Finland) or a KSV large trough filled with PBS buffer. Measurements were started after 3 min of chloroform evaporation. Surface pressure was measured using a Wilhelmy plate, surface potential was measured with a KSV surface potential sensor (Espoo, Finland), and Brewster angle microscopy images were acquired using a KSV NIMA microBAM (Espoo, Finland) instrument. The membrane was compressed at a constant rate of 5 or 10 mm / min, and the subphase temperature was kept at 35±1°C. To prevent undesired oxidation, measurements were performed in an acrylic box under an ozone-free atmosphere. The ozone-free atmosphere was generated by passing dry air through an ODS-3P ozone destruction unit (Ozone solutions, Hull, Iowa) at a rate of 76 l / min in the enclosure.

[0224] 1.2.4 Evaporation resistance Evaporation resistance is a property of a lipid film present on or above an aqueous surface, independent of the measurement method and conditions. It is defined as r = Δc / J, where Δc is the water vapor concentration difference driving evaporation, J is the evaporation flux from the aqueous phase below, defined as J = (dn / dt) / A, n is the amount of water evaporated, t is time, and A is the area of ​​the surface. The evaporation resistance of a lipid film is, for example, the evaporation flux J from an aqueous surface without a lipid layer. w , and the evaporation flux from an aqueous surface on which a lipid film is present, J f The total evaporation resistance without the lipid film, r w is composed of various components such as diffusion and convection in the air layer covering the aqueous surface, which depends on the measurement setup. The total evaporation resistance in the presence of a lipid film, r f is the additional resistance term r caused by the lipid membrane m Containing these same components with: f =r w +r mThe lipid film evaporation resistance is a function of the measured volume, r m = Δc(1 / J f -1 / J w )

[0225] In this embodiment, it was determined according to the method originally developed by Langmuir et al. (Langmuir, I. and Schaefer, V., J. 1943, J. Franklin Inst., Vol. 235, 119-162), but with certain modifications (see Bland et al., Langmuir, 2019, 35, 3545-3552 (Supp. Info.)).

[0226] The measurement was performed by dividing the film by 2 to 40 Å. 2 This was carried out by compressing the desiccant cartridge to a specific (average molecular area) mma in the range of 100 / molecule and placing a prepared desiccant cartridge with a water-permeable membrane of approximately 2 mm above the aqueous surface. A commercially available silica gel-containing desiccant cartridge (SP Industries, Warminster, PA) was modified by replacing the membrane with a Millipore Immobilon-P PVDF membrane (450 nm pore size, Bedford, MA). The desiccant cartridge was fixed in position for 5 min and the mass of absorbed water was determined by gravimetric techniques. A second background measurement was carried out in parallel in an enclosed acrylic box to account for moisture absorbed from the dry air in the enclosure. The results are therefore an accurate representation of moisture evaporation from an aqueous surface.

[0227] 2.Results 2.1 Chemical synthesis Throughout the synthesis, products were purified by chromatographic techniques and characterized by a wide range of NMR spectroscopic techniques (e.g., 1 H, 13 C. 31P, DQF-COSY, Ed-HSQC, TOCSY, and HMBC) and high-resolution mass spectrometry, thereby ensuring their structural identity and purity. Our thorough structural characterization process has recently been highlighted in the Journal of Organic Chemistry (Viitaja, T. et. al. 2021, J. Org. Chem. 86, 4965-4976), and therefore these aspects will not be discussed further in this document.

[0228] Three separate routes for the synthesis of FAHFAs of differing complexity have been developed and / or modified from literature protocols (see, e.g., Bland et.al. Langmuir 2019, 35, 9, 3545-3552; Viitaja et.al. J. Org. Chem. 2021, 86, 4965-4976; Hancock et.al. J. Lipid Res. 2018, 59, 1510-1518, and references therein). Oleic acid derivatives are described throughout this section as they are the most abundant acyl chain in TFLL FAHFAs, but derivatives with different acyl chains, including linoleic acid, palmitoleic acid, palmitic acid, and stearic acid, have been prepared as well.

[0229] The first route is presented in Scheme 1 and has been developed for the synthesis of unconjugated FAHFA analogs. By this route, the synthesis of FAHFA analogs can be completed in as few as two synthetic steps. The chain length and saturation of the starting material can be tailored, and esterification can be performed with a wide range of carboxylic acids. The route is exemplified by the synthesis of 20-(oleoyloxy)eicosanoic acid, although numerous structural analogs have been prepared as well.

[0230] 1,20-Eicosanediol was subjected to Fischer esterification with oleic acid (1.2 equiv.) using catalytic amount of sodium hydrogen sulfate as catalyst. The reaction was carried out under vacuum at high temperature using neat reaction conditions. This strategy eliminates the need for exhaustive protection-deprotection reactions (Marshall, D., L., et.al. 2016, Rapid Commun. Mass Spectrom., 30, 2351-2359) and 20-hydroxyicosyl oleate could be isolated in 48% yield after column chromatography. The yields observed for structural analogs were all in the range of 30-50%. The synthesis of the corresponding FAHFA, i.e. 20-(oleoyloxy)eicosanoic acid, was achieved by using a standard Jones oxidation protocol (Balas, L. et.al., 2016, Org. Biomol. Chem., 14, 9012-9020). The isolated yields obtained after extraction and column purification were excellent (70% quantitative) in this particular reaction as well as all others performed.

[0231] [ka] Scheme 1. Overview of synthetic route 1 to FAHFAs. i) Oleic acid (1.2 equiv), corresponding diol (1 equiv), NaHSO4·H2O (3.5 mol%), 100 °C, 0.3 mbar, 2.5 h, 40–50% yield. ii) Jones reagent (2.2 equiv), acetone or acetone:EtOAc:THF mixture, 0 °C or room temperature, 0.5–2 h, 70–96% yield.

[0232] Oleic acid is shown in Scheme 1 as an example of a suitable fatty acid and is the most abundant acyl chain in TFLL. Any suitable fatty acid may be used in this synthetic route. Alternative fatty acids include linoleic acid, palmitoleic acid, palmitic acid, stearic acid, among others.

[0233] To provide access to a large library of TFLL lipids of increasing complexity, a second synthetic route, shown in Scheme 2, was developed. This strategy is based on the use of a block approach featuring a Z-selective Wittig olefination reaction with two different fragments: a triphenylphosphonium ylide and an aldehyde. This strategy offers the possibility to adjust the site of the alkene, the length of the hydrocarbon chain, and the modification sites / functional groups present, etc. In addition, a variety of carboxylic acids can be used in a Steglich-type esterification reaction, thus providing ample possibilities to vary the structural features of this fragment as well. Here, this synthetic route is exemplified by the synthesis of (12Z)-20-oleoyloxyeicos-12-enoic acid (Viitaja, T., et.al. 2021, J. Org. Chem., 86, 4965-4976).

[0234] [ka] Scheme 2. Overview of synthetic route 2 to FAHFAs. i) 1) 48% HBr aq, cyclohexane, reflux, 18 h, 77%, 2) imidazole, TBDMSCl, CH2Cl2, room temperature, overnight, 94%, ii) 1) PPh3, neat, 120 °C, 17 h, quantitative, 2) NaHMDS, dry THF, HMPA -78 °C, 1 h, 8-bromo-octanal (or other brominated aldehyde), -78 °C, rt, 24 h, 34%, iii) 1) KOAc, DMSO, 50 °C, 27 h, 66%, 2) NaOMe, THF:MeOH (1:2), 22 h, rt, 78%, iv) 1) Oleic acid, DMAP, EDC·HCl, CH2Cl2, rt, overnight, 93%, v) 1) TBAF, THF, 1 h, rt, 92%, 2) Jones reagent, acetone:EtOAc (1:1), 0 °C, 45 min, 89%.

[0235] The reaction started with the successful monobromination of 1,12-dodecanediol in 77% yield (Greaves, J. et. al. 2017, PNAS, 114, E1365-E1374). The free hydroxyl group was protected as the TBDMS-ether in 94% yield following the protocol of Cateni et al. (Cateni, F. et. al. 2007, Helv. Chim. Acta., 90, 282-290). This product was reacted with one equivalent of PPh3 at 120 °C under neat reaction conditions to give the corresponding triphenylphosphonium bromide salt. The second fragment required for the Wittig olefination reaction, i.e. the monobrominated aldehyde, was obtained by selective oxidation of 8-bromo-1-octanol with PCC. Both of these crude products were carefully dried in a vacuum line and used directly in the subsequent Z-selective Wittig reaction following a modified literature procedure (Primdahl, KGet. al., 2015, Org. Biomol. Chem., 13, 5412-5417). This afforded (12Z)-20-bromo-1-tert-butyldimethylsilyloxyeicos-12-ene in 34% yield. Direct replacement of the bromide with a hydroxyl group proved difficult, and a two-step protocol was devised based on a previously reported protocol (Lee, JH, et. al. 2008, Korean Chem. Soc., 29, 2491-2495). The bromide was replaced by acetate anion in 66% yield and the resulting compound was deacetylated under Zemplen conditions to give (12Z)-20-hydroxy-1-tert-butyldimethylsilyloxyeicos-12-ene in 77% yield. A Stäklich-type esterification reaction with oleic acid was found to be a smooth protocol to install the acyl chain. The temporary silyl protecting group was deprotected at this stage with 3 equivalents of TBAF in excellent yield and the primary alcohol was oxidized to give the representative FAHFA (12Z)-20-oleoyloxyeicos-12-enoic acid in 89% yield.

[0236] To provide access to additional structural analogs of TFLL FAHFAs, a third synthetic route, shown in Scheme 3, was developed. This strategy is based on the use of a block approach featuring the coupling of an acetylide anion with a monobrominated starting material, and requires two different fragments, namely a potentially functionalized hydrocarbon chain containing a terminal alkyne, and a potentially functionalized hydrocarbon chain containing an alkyl halide. This synthetic strategy offers the possibility to adjust the access to the alkyne, the selective reduction of the alkyne to either the E or Z-alkene, the site of the alkyne / alkene, the length of the hydrocarbon chain, and the modification site / functional group present, etc. In addition, a variety of carboxylic acids can be used in the Stäklich-type esterification reaction, thus providing ample possibilities to vary the structural features of this fragment as well. Here, this synthetic route is exemplified by the synthesis of (21Z)-29-(oleoyloxy)nonacos-21-enoic acid.

[0237] [ka] Scheme 3. Overview of synthetic route 3 to FAHFAs. i) 1) 48% HBr aq, cyclohexane, 82 °C, 5 h, 52%, 2) DHP, PPTS, CH2Cl2, rt, 23 h, 97%, ii) 1) 1-O-tert-butyldimethylsilyl-non-8-yn-1-ol (or analogue), HMPA, THF, -78 °C, 2) BuLi, 2 h, -40 °C, 3) monobrominated compound, -78 °C, 4) TBAI, rt, 5) 80 °C, 20 h , iii) 1) TBAF, THF, rt, 1 h, 52% (over two steps), 2) Lindlar catalyst, quinoline, benzene, H2 (1 atm), rt, 1 h, 89%, iv) oleic acid, DMAP, EDC·HCl, CHCl, rt, 22 h, 76%, v) 1) CSA, MeOH / THF, rt, 18 h, 72%, 2) Jones reagent, acetone / EtOAc, rt, 1 h, 61%. The monobromination was carried out as above, however, a significant drop in yield was observed (from 77% to 52%) when 1,20-eicosanediol was used as starting material. The free hydroxyl group was then protected as the THP-ether in 97% yield using the standard reaction protocol. This indicated the successful synthesis of one of the fragments required for the envisaged chain extension reaction (coupling between acetylide anion and primary alkyl halide). The appropriate alkyne was synthesized from commercially available non-8-ynol by protecting the hydroxyl group as the TBDMS-ether with TBDMSCl and imidazole in CHCl. ​​The key conjugation step was performed as follows: the terminal alkyne (2.5 equiv.) was first dissolved in THF:HMPA (3:1) and converted to the acetylide anion with BuLi (2.4 equiv.) at −78° C. Then, 20-bromo-1-((tetrahydro-2H-pyran-2-yloxy)-eicosanol (1 equiv.) dissolved in THF was added and the resulting mixture was brought to room temperature. Finally, a catalytic amount of TBAI was added and the mixture was heated at 80° C. overnight. After work-up, direct deprotection of the TBDMS-ether was performed with TBAF in THF, which led to the isolation of 29-(tetrahydro-2H-pyran-2-yloxy)nonacos-8-yn-1-ol in 52% yield over two steps.The alkyne was selectively reduced to the Z-alkene in an autoclave using Lindlar's catalyst and excess quinoline with benzene as the solvent at 1 atm of hydrogen gas pressure. A high yield of 89% was obtained in this reaction step. A notable difference from previous literature reports (Hancock, SE et. al. 2018, J. Lipid Res., 59, 1510-1518) is that the inventors were able to optimize the reaction conditions, which resulted in the isolation of pure Z-alkene (without significant impurities from the E isomer). A Stäklich-type esterification reaction was again used to install the acyl group, this time in 76% yield. The THP-ether was then hydrolyzed with CSA in MeOH:THF (3:1) in 72% yield, and the unmasked hydroxyl group was subjected to the Jones oxidation protocol established by the inventors. Thereby, (21Z)-29-(oleoyloxy)nonacos-21-enoic acid can be isolated in a yield of 61%.

[0238] As mentioned above, multiple wax esters are commercially available and can be used in combination with FAHFAs in the intended application. However, the inventors have also developed a synthesis protocol for TFLL-specific wax esters as well. To the best of the inventors' knowledge, TFLL-specific branched wax esters have not been synthesized before. Here, two synthetic routes for the synthesis of wax esters are developed. The first route is a short and efficient route based on acylation of alcohols, and the second is a longer route that allows the synthesis of branched wax esters with the possibility of further modification. The methods used for the synthesis are similar to those described above for FAHFAs, and similar variations in structural features are possible, for example, adjusting the length of the hydrocarbon chain, shifting the position of the alkyne / alkene, adjusting the stereochemistry of the alkene functional group, further functionalization of the molecular structure, etc. Here, the synthesis is exemplified by the synthesis of one linear wax ester and one branched wax ester, namely, hexocosanyl oleate and 24-methylpentacosanyl oleate (see Scheme 4).

[0239] [ka] Scheme 4. Overview of synthetic routes to non-commercial wax esters. i) Oleic acid, DMAP, EDC . HCl, CH2Cl2, rt, overnight, 93% (R=H), ii) 1) 48% HBr in water, cyclohexane, reflux, 6 h, 50-70%, 2) DHP, PPTS, CH2Cl2, overnight, 97%, iii) 1) corresponding methyl branched alkyne, BuLi, -78°C to -40°C, 2 h, 2) corresponding monobrominated THP-ether, -78°C to rt, 3) TBAI, 10 min, reflux overnight, 89%, iv) 1) CSA, THF:MeOH (1:3), rt, overnight, 95%, 2) Pd / C (10%), EtOAc, H2 (6 bar), 4 h, 83%, v) oleic acid, DMAP, EDC · HCl, CH2Cl2, rt, overnight, 96%.

[0240] The synthesis of hexocosanyl oleate was accomplished in one step by the Steaglich-type esterification protocol described above. More specifically, commercial hexacosanol was acylated with oleic acid in 93% yield.

[0241] The synthesis of the branched ester began with 1,20-eicosanediol and monobromination followed by THP protection in similar yields as above. This fragment was then catalyzed with the acetylide anion of 4-methylpent-1-yne and S N The 4-methylpent-1-yne was coupled in two reactions. More specifically, 4-methylpent-1-yne was deprotonated with BuLi at -78°C and then reacted with 20-bromo-1-(tetrahydro-2H-pyran-2-yloxy)-eicosanol and TBAI at elevated temperature. This gave the hydrocarbon base in 89% yield. Deprotection of the THP ether with CSA in MeOH:THF 3:1, followed by reduction of the triple bond by hydrogenation gave the branched alcohol in 79% overall yield. Acylation of the alcohol with oleic acid gave the acid 24-methylpentacosanyl oleate in 96% yield.

[0242] 2.2 Characterization of Functional Principles background To effectively retard evaporation from the ocular surface, TFLLs must meet two criteria: 1) the lipids must rapidly spread and cover the entire aqueous tear film surface when the eye is open, and 2) the film formed by the lipids must have a condensed structure that prevents or retards the passage of water molecules through it. These same two requirements must be met by lipid compositions developed to retard or prevent water evaporation if the approach is intended to provide a response to important tear film instability defects or to maintain water in artificial lakes and water reservoirs. Thus, the inventors have focused on providing insight into these two factors, namely 1) diffusion behavior and 2) evaporation resistance, as well as characterizing the underlying functional principles and requirements in terms of composition.

[0243] The inventors have previously reported on the properties of pure OAHFAs and wax esters. More specifically, the inventors have shown that at physiological temperatures and low surface pressures, pure OAHFAs (or their structural analogs, such as O-acyl-ω-hydroxy fatty alcohols) form monolayers on aqueous surfaces, with the molecules lying flat. (Bland, H., C., et al. 2019, Langmuir, Vol. 35, 3545-3552; Schuett, B., S. et al. 2013, Exp Eye Res, Vol. 115, 57-64) With increasing surface pressure, the OAHFAs molecules gradually adopt an upright orientation with the polar head groups (the carboxylic acids in the case of OAHFAs) pointing towards the aqueous phase, and the ester groups pointing away from the aqueous phase. (Bland, H., C., et al. 2019, Langmuir, Vol. 35, 3545-3552; Schuett, B., S. et al. 2013, Exp Eye Res, Vol. 115, 57-64) The long-chain OAHFAs further underwent a transition to a condensed monolayer phase with an evaporation resistance of up to 5 s / cm. (Bland, H., C., et al. 2019, Langmuir, Vol. 35, 3545-3552) When the temperature of the aqueous phase was close to or above the melting point of the wax esters, the wax esters also diffused to form a monolayer on the aqueous surface. (Rantamaeki, A., H. et al. 2013, Invest Ophthalmol Vis Sci, 54, 5211-5217; Paananen, R., O. et al. 2014, Langmuir, 30, 5897-5902; 2019, J. Phys. Chem. Lett., 10, 3893-3898). At low temperatures, no diffusion of wax esters is observed. (Rantamaeki, A., H. et al. 2013, Invest Ophthalmol Vis Sci, 54, 5211-5217; Paananen, R., O. et. al. 2014, Langmuir, 30, 5897-5902; 2019, J. Phys. Chem. Lett., 10, 3893-3898) Thus, wax esters can form solid films that resist evaporation, but this is limited to a critical temperature range close to the melting point of the wax ester.(Rantamaeki, A., H. et al. 2013, Invest Ophthalmol Vis Sci, 54, 5211-5217; Paananen, R., O. et. al. 2014, Langmuir, 30, 5897-5902; 2019, J. Phys. Chem. Lett., 10, 3893-3898). In summary, the limiting temperature range in which wax esters can be applied in their intended applications imposes severe constraints on their practical use. Furthermore, the maximum evaporation resistance achieved with wax esters alone is poor (2-3 s / cm) and our studies on pure OAHFAs show that these are only slightly better (about 5 s / cm). Thus, neither OAHFAs nor wax esters exhibit optimal properties by themselves.

[0244] Mixture of OAHFA and wax esters Mixtures of OAHFA and wax esters exhibit more complex surface behavior that has not been widely studied to date. In addition, the surface behavior varies greatly depending on the individual components utilized. For example, the inventors have previously shown that the use of mixtures of OAHFA and cholesteryl esters does not result in improved properties over OAHFA alone (Paananen et.al. Ocul. Surf. 2020). Thus, mixtures of OAHFA / FAHFA and wax esters are unique in this respect, as will be further highlighted in the discussion below. Two examples are presented herein, the first of which involves the use of a mixture of 20-OAHFA and AO (see FIG. 1).

[0245] The tissue behavior of the mixtures of FAHFAs / OAHFAs with wax esters was investigated by measuring the surface pressure and surface potential isotherms and imaging the monolayer structure with a Brewster angle microscope. A phosphate-buffered saline (PBS) solution was used as an in vitro model of the ocular surface and the measurements were carried out at physiological temperature (35°C). With this model system it is possible to accurately simulate the conditions present at the ocular surface and the changes that occur during blinking of the eye, both in terms of surface pressure and the ability of the monolayer to respread over many compression-expansion cycles. The study protocol therefore provides the essential information necessary to evaluate the suitability of the composition in the intended application. Details of the study protocol can be found in the inventors' previous publications on the subject (Paananen, Ekholm et.al. in Langmuir 2019, Ocul.Surf.2020, J.Org.Chem.2021).

[0246] In their pure forms, both 20-OAHFA and AO have a molecular weight of 140 Å, respectively. 2 / molecule and 70 Å 2 When the molecules spread, they form a liquid monolayer accompanied by surface pressure lift-off. The difference in average molecular area reflects the different orientation of the molecules at the surface. 20-OAHFA lies flat on the aqueous surface, while AO adopts an orientation in which only the ester groups are weakly coordinated toward the interface (Bland, H., C., et al. 2019, Langmuir, Vol. 35, 3545-3552, Paananen, R., O. et. al. 2019, J. Phys. Chem. Lett., 10, 3893-3898). 20-OAHFA undergoes a transition to a solid monolayer at a surface pressure of 2 mN / m, accompanied by a conformational change from the surface pressure plateau to an upright molecular orientation (Figure 1D:iv) and a decrease in surface potential as previously reported (Bland, H., C., et al. 2019, Langmuir, Vol. 35, 3545-3552). In contrast, AO membranes collapsed at similar surface pressures.

[0247] In the mixed films, 20-OAHFA and AO were ideally miscible in the liquid monolayer phase, as indicated by the fact that the average molecular area and surface potential at surface pressure lift-off were directly proportional to the ratio of the two components (Figures 1A, 2B). Upon compressing the film, AO collapsed as droplets on the top of the monolayer at low surface pressures (3-5 mN / m), as indicated by the bright droplets in the BAM images (Figure 1C:ii) and the plateaus of the surface pressure and potential isotherms (Figures 1A, 2B). The 20-OAHFA that remained in the monolayer formed a solid monolayer phase (Figure 1C:iii), unaffected by the presence of AO, which could be estimated by analyzing the surface pressure and potential isotherms per molecule of 20-OAHFA (Figures 1A, 1B). The presence of AO did not affect the evaporation resistance of the 20-OAHFA:AO mixture (Figure 2). It was found that the evaporation resistance was entirely dependent on the adaptation of the solid phase by 20-OAHFA, and a maximum evaporation resistance of 3-5 s / cm was observed, which is consistent with the value obtained for pure 20-OAHFA. (Bland, H., C., et al. 2019, Langmuir, Vol. 35, 3545-3552) The evaporation resistance of the 20-OAHFA:AO mixtures is shown as a function of area / OAHFA in Figure 2.

[0248] Thus, a mixture of 20-OAHFA and AO offers no added advantage over using OAHFA or a structural analog alone.

[0249] In the following example, we focus on the properties of 20-OAHFA and BO mixtures. The only structural difference between AO and BO is the increase in the length of the alkyl chain by 2 carbon atoms, and the only deviation in terms of chemical properties is the slightly higher melting / boiling point of BO. From a biophysical point of view, this is considerable, since AO is in a liquid state at physiological conditions and BO is in a solid state. Due to this factor, it was not possible to obtain a reproducible isotherm for pure BO, since it did not diffuse onto the aqueous surface, but instead formed solid aggregates. This confirms that BO is not suitable by itself for the intended application, since it does not meet the important criteria discussed at the beginning of this section.

[0250] Nevertheless, BO and 20-OAHFA mixtures containing up to 50 mol% BO formed stable homogeneous monolayers (Fig. 3C:i), indicating the synergistic action of well-designed FAHFA / OAHFA and wax ester mixtures. In this case, 20-OAHFA induces the diffusion of BO and the formation of a miscible liquid monolayer at low surface pressures. During compression of the 1:1 mixture, a liquid-to-solid phase transition (Fig. 3C;ii) occurred, with the monolayer shrinking to about 20 Å. 2 This was accompanied by a sharp increase in surface pressure up to 40 mN / m / molecule on average molecular area (Fig. 3A). In contrast to the previous examples, BO was found to be integrated into the condensed monolayer phase instead of collapsing on top of the polar lipid layer. At higher BO ratios (>50 mol%), only a certain percentage of BO was incorporated into the homogeneous amphiphilic monolayer, while the rest formed solid aggregates on top of it, as observed from the BAM images (Fig. 3C; iii). The solid aggregates were retained even under compression (Fig. 3C; iv). In mixtures containing more than 50 mol% BO, a second plateau was evident in the surface pressure isotherms at 17-22 mN / m, followed by a plateau at 40 Å. 2 A sharp increase in the average molecular area of ​​20-OAHFA / OAHFA was evident (Figure 3A). This demonstrated that a 1:1 mixture of 20-OAHFA and BO remained at the interface, while the remaining portion of BO formed solid aggregates on top of it during the second plateau. In a similar manner, a sharp drop in the surface potential isotherm was consistent with the value observed for the 1:1 mixture, indicating that the condensed sublayer consisted of a 1:1 mixture of BO and 20-OAHFA (Figure 3B).

[0251] The rapid and integrated self-assembly and cooperative spreading behavior of the mixtures of 20-OAHFA and BO is intriguing and will undoubtedly affect the important evaporation resistance properties of the monolayers, since it is no longer solemnly dependent on the amphiphilic OAHFA / FAHFA molecules present at the aqueous interface. The evaporation resistance of the mixed condensed monolayer phases formed by 20-OAHFA and BO was tested using the method described in section 1.2.4 for various ratios of the two components. The integration of BO into the 20-OAHFA monolayer dramatically improved the evaporation resistance from 3-5 s / cm observed for pure 20-OAHFA to up to 25 s / cm (Figure 4). We screened the evaporation resistance of several 20-OAHFA:BO mixtures (examples 3:1, 2:1, 3:2, 1:1, 1:3, 1:9 included herein). For mixtures containing less than 50 mol% BO, the maximum evaporation resistance achieved was only slightly improved relative to pure 20-OAHFA. In contrast, mixtures containing 50 mol% or more BO had significantly improved evaporation resistance, indicating that the increase in evaporation resistance is caused by the formation of a mixed monolayer of 20-OAHFA and BO mentioned above. The evaporation resistance of the 20-OAHFA:BO mixtures was significantly higher than the estimated values ​​reported for natural TFLL (9-13 s / cm) (Iwata, S., et al. 1969, Invest Ophthalmol Vis Sci, 8, 613-619; Peng, C., et al. 2014, Ind Eng Cham Res, 53, 18130-18139). To the best of our knowledge, the evaporation resistance of these mixtures exceeds all strategies previously reported in the scientific and patent literature (Barnes, GT, 2008, Agric. Water. Manage., 95, 339-353).

[0252] The evaporation resistance of 18-(oleoyloxy)stearic acid (18:0 / 18:1-OAHFA) and behenyl oleate (BO), (18:0 / 18:1-OAHFA:BO 1:1), (21Z)-29-(oleoyloxy)nonacos-21-enoic acid (29:1 / 18:1-OAHFA) and BO (29:1 / 18:1-OAHFA:B:O 1:1), 18:0 / 18:1-OAHFA and behenyl behenoate (BB), and 18:0 / 18:1-OAHFA and arachidyl laurate (AL) 1:1 mixtures were also investigated using the method described in section 1.2.4. Measurements were performed between 5 and 35 Å. 2 The evaporation resistance of each mixture was measured in s / cm. The results of the experiment are shown in Figure 5.

[0253] As can be seen from Figure 5, 1:1 mixtures of 18:0 / 18:1-OAHFA and BO, and 18:0 / 18:1-OAHFA and AL show improved evaporation resistance properties compared to the individual components, and these combinations also form densely packed layers at the aqueous surface, thus indicating that improved evaporation resistance may be achieved by different combinations of OAHFA and wax esters. In particular, for both of these combinations, the 1:1 mixtures of 18:0 / 18:1-OAHFA and BO show improved evaporation resistance properties compared to the individual components, and these combinations also form densely packed layers at the aqueous surface, thus indicating that improved evaporation resistance may be achieved by different combinations of OAHFA and wax esters. 2Very high evaporation resistance was observed at an area per molecule of 18:0 / 18:1. Even higher evaporation resistance was observed at lower areas per molecule, but the exact values ​​were not measurable in the available experimental setup. However, a 1:1 mixture of 18:0 / 18:1 OAHFA and BB, as well as a mixture of 29:1 / 18:1-OAHFA and BO, did not show improved evaporation resistance properties over OAHFA alone. Thus, it is clear that both OAHFA and wax esters, and how they interact in combination, are important for evaporation resistance. Furthermore, 18:0 / 18:1-OAHFA has been shown to form very evaporation resistant mixtures with BO, which is solid under physiological conditions, and AL, which is liquid under these conditions, indicating that the effect cannot be easily predicted from the melting point of the wax esters. Similarly, the difference between the melting points of 18-OAHFA and 29:1-OAHFA is about 3°C ​​(56°C vs. 53°C), but the melting point of OAHFA does not appear to be the primary determining factor in the behavior of the mixture, since combinations of 29:1-OAHFA with BO did not show improved properties.

[0254] Here, we show that properly designed mixtures of FAHFAs / OAHFAs and wax esters spread rapidly on aqueous surfaces under ambient conditions, and the condensed monolayers formed have remarkable resistance to evaporation. These unique biophysical properties result from the inherent properties of properly designed FAHFAs / OAHFAs and wax ester mixtures alone. It is therefore clear that such mixtures can be applied in multiple applications where increased water evaporation rates present a challenge. Application areas range from the treatment of ocular surface diseases to maintaining water in artificial lakes and reservoirs, and beyond.

[0255] 3. Conclusion The tear film consists of two distinct layers: the aqueous layer and the TFLL. It is widely accepted that the TFLL plays a central role in stabilizing the tear film. Over the years, accumulated research by the inventors and others suggests that the TFLL stabilizes the tear film by acting as a barrier against the evaporation of water from the underlying aqueous layer (Paananen, R., O. et.al. 2014, Langmuir, 30, 5897-5902; 2019, J. Phys. Chem. Lett., 10, 3893-3898; 2019, J. Phys. Chem. Lett., 10, 3893-3898; 2019, J. Phys. Chem. Lett., 10, 3893-3898). 20, Ocul.Surf.,18,545-553; Craig,J.,P.et.al.1997,Optom.Vis.Sci.,8,613-619; King-Smith,PE,et.al.2010,Invest.Ophthalmol.Vis.Sci.,51,2418-2423; Dursh,T.,J.et.al.2018,Optom.Vis.Sci.,95:5). This loss of evaporation resistance function leads to ocular dryness in the majority of DED cases, which may further cause inflammation and ocular surface damage. To effectively retard evaporation from the ocular surface, TFLL must meet two criteria: 1) the lipids must spread rapidly when the eye is open and cover the entire aqueous tear film surface, and 2) the membrane formed by the lipids must have a condensed structure that prevents or retards the passage of water molecules through it. These same two criteria need to be met for a DED treatment aimed at replenishing the anti-evaporative properties of TFLL and targeting the key tear film instability defect.

[0256] The inventors have developed synthetic protocols for the synthesis of an extensive library of TFLL FAHFAs and wax esters, as well as their structural analogues. Using this library, the inventors have identified a mixture of key lipid species that combines effective diffusion on aqueous interfaces with very high evaporation resistance, i.e., a composition that meets the two criteria above. Importantly, the inventors' core technology is based on tailored synthetic lipid compositions with few variables, and the synthetic tools necessary to generate the individual building blocks and a wide range of structural analogues have been established. The inventors have focused their efforts on mapping the molecular-level mechanisms of the core technology with experimental biophysical techniques.

[0257] The result of the development process is a core composition of FAHFAs and wax esters that form an evaporation-resistant barrier on aqueous interfaces under physiological conditions. The inventors have shown that the mixture offers properties superior to the pure components themselves. The evaporation resistance described exceeds the highest evaporation resistance values ​​reported in the literature for any other type of compound, mixture, or product (Barnes, GT, 2008, Agric. Water. Manage., 95, 339-353). The administration of this lipid composition onto the ocular surface represents a unique and highly promising treatment option for DED and / or ocular discomfort. Furthermore, since the biophysical properties are derived from the intrinsic properties of the mixture itself and are not directly related to the surrounding environment, these mixtures can be used to prevent water evaporation from materials and other environments, such as artificial lakes and water reservoirs, in a similar manner. The latter challenge presents an increasing challenge due to global climate change.

Claims

1. A composition comprising a combination of a fatty acid ester of a hydroxy fatty acid (FAHFA) or structural analogues thereof, a wax ester or structural analogues thereof, and, optionally, one or more additives.

2. 10. The composition of claim 1, wherein the composition consists of a combination of FAHFA or a structural analog thereof, a wax ester or a structural analog thereof, and, optionally, one or more additives.

3. The composition according to claim 1 or 2, wherein the composition is a pharmaceutical composition.

4. 3. The composition of claim 1 or 2, wherein the evaporation resistance of the composition is greater than 1 s / cm, greater than 2 s / cm, or greater than 3 s / cm, greater than 5 s / cm, greater than 9 s / cm, greater than 10 s / cm, greater than 13 s / cm, greater than 15 s / cm, greater than 20 s / cm, greater than 25 s / cm, or greater than 30 s / cm, preferably the evaporation resistance of the composition is greater than 20 s / cm.

5. The composition of claim 1 or 2, wherein the FAHFA is an O-acyl-ω-hydroxy fatty acid (OAHFA).

6. 3. The composition of claim 1, wherein the FAHFA is selected from the group consisting of 12-OAHFA (12-(oleoyloxy)dodecanoic acid), 15-OAHFA (15-(oleoyloxy)pentadecanoic acid), 20-OAHFA (20-(oleoyloxy)eicosanoic acid), 22-OAHFA (22-(oleoyloxy)docosanoic acid), 20:1-OAHFA ((12Z)-20-(oleoyloxy)eicos-12-enoic acid), 29:1-OAHFA ((21Z)-29-(oleoyloxy)nonacos-21-enoic acid), 18-(oleoyloxy)stearic acid, and 20-(palmitoleoyloxy)eicosanoic acid.

7. 3. The composition of claim 1 or 2, wherein the FAHFA is selected from the group consisting of 20-(oleoyloxy)eicosanoic acid and 18-(oleoyloxy)stearic acid, optionally wherein the FAHFA is 20-(oleoyloxy)eicosanoic acid.

8. 3. The composition of claim 1 or 2, wherein the wax ester is behenyl oleate or arachidyl laurate, optionally wherein the wax ester is behenyl oleate.

9. 3. The composition of claim 1 or 2, wherein the molar ratio of FAHFA or structural analogs thereof to wax esters and / or structural analogs thereof is 1:1 or less, about 1:1 to 1:100, or 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9 or 1:10, 1:20, 1:30, 1:40, 1:50, 1:60, 1:70, 1:80, 1:

90.

10. 3. The composition of claim 1 or 2, wherein the molar ratio of FAHFA or structural analogues thereof to wax ester or structural analogues thereof is greater than 1:1, about 100:1 to 1:1, about 3:2 to 5:1, or 90:1, 80:1, 70:1, 60:1, 50:1, 40:1, 30:1, 20:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, or 2:

1.

11. 3. The composition of claim 1 or 2, wherein the molar ratio of the FAHFA or structural analogues thereof to the wax ester or structural analogues thereof is from 1:1 to 1:9 (FAHFA or structural analogues thereof: wax ester or structural analogues thereof).

12. 3. The composition of claim 1 or 2, wherein the molar ratio of said FAHFA or structural analogues thereof to said wax ester or structural analogues thereof is about 1:1 (FAHFA or structural analogues thereof: wax ester or structural analogues thereof).

13. 3. The composition of claim 1 or 2, wherein the FAHFAs are selected from the group consisting of 20-(oleoyloxy)eicosanoic acid and 18-(oleoyloxy)stearic acid, and the wax esters are selected from the group consisting of behenyl oleate and arachidyl laurate.

14. 3. The composition of claim 1 or 2, wherein the FAHFA is 20-(oleoyloxy) eicosanoic acid and the wax ester is behenyl oleate, optionally with a molar ratio of 20-(oleoyloxy) eicosanoic acid to behenyl oleate of 1:1 or less, such as from 1:1 to 1:

9.

15. 3. The composition of claim 1 or 2, wherein the FAHFA is 18-(oleoyloxy)stearic acid and the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate, optionally with a molar ratio of 18-(oleoyloxy)stearic acid to wax ester of less than or equal to 1:1, such as about 1:

1.

16. the one or more additives are selected from the group consisting of solvents, diluents, carriers, buffers, excipients, adjuvants, carrier media, preservatives, fillers, stabilizers, thickeners, emulsifiers, disintegrants, lubricants, and binders, and any combination thereof; and optionally 3. The composition of claim 1 or 2, wherein the one or more pharma- ceutically acceptable excipients are ophthalmically acceptable excipients selected from the group consisting of polyethylene glycol, propylene glycol, glycerin, polyvinyl alcohol, povidone, polysorbate 80, hydroxypropyl methylcellulose, carmellose, carbomer 980, sodium hyaluronate, and dextran.

17. the composition comprises at least 0.001%, 0.005%, 0.01%, 0.05%, 0.1%, 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, or 50% by weight of the FAHFA or a structural analogue thereof, and a wax ester or a structural analogue thereof; and / or 3. The composition of claim 1 or 2, wherein the composition is in the form of a liquid, semi-solid, or solid; the composition is in the form of a solution, emulsion, suspension, spray, powder, tablet, pellet, or capsule; or the composition is an oil-in-water emulsion.

18. 1. A composition comprising: i. an O-acyl-ω-hydroxy fatty acid selected from the group consisting of 20-(oleoyloxy)eicosanoic acid, 18-(oleoyloxy)stearic acid, and 20-(palmitoleoyloxy)eicosanoic acid; ii. a wax ester selected from the group consisting of behenyl oleate and arachidyl laurate; The composition, wherein the molar ratio of O-acyl-ω-hydroxy fatty acid to wax ester is 1:1 or less, such as 1:1 to 1:9 (O-acyl-ω-hydroxy fatty acid:wax ester).

19. 19. The composition of claim 18, wherein the O-acyl-ω-hydroxy fatty acid is 20-(oleoyloxy)eicosanoic acid and the wax ester is behenyl oleate.

20. 19. The composition of claim 18, wherein the O-acyl-ω-hydroxy fatty acid is 18-(oleoyloxy)stearic acid and the wax ester is selected from the group consisting of behenyl oleate and arachidyl laurate, and optionally the molar ratio of O-acyl-ω-hydroxy fatty acid:wax ester is about 1:

1.

21. A compound which is 18-(oleoyloxy)stearic acid.

22. 3. A composition according to claim 1 or 2 for use as a medicament.

23. A compound according to claim 21 for use as a medicine.

24. 3. A composition as claimed in claim 1 or 2 for use in the treatment of dry eye disease and / or meibomian gland dysfunction or for use in the relief of ocular discomfort.

25. A compound as described in claim 21 for use in the treatment of dry eye disease and / or meibomian gland dysfunction or for use in relieving ocular discomfort.

26. 3. A method for preparing a composition according to claim 1 or 2, said method comprising combining or mixing one or more FAHFAs or structural analogues thereof, one or more wax esters or structural analogues thereof, and optionally one or more additives, optionally comprising: The method further comprises preparing or synthesizing the FAHFA or a structural analog thereof prior to mixing the FAHFA or a structural analog thereof with the wax ester or a structural analog thereof, and / or preparing or synthesizing the wax ester or a structural analog thereof prior to mixing the wax ester or a structural analog thereof with the FAHFA or a structural analog thereof.

27. 13. A non-therapeutic or therapeutic method of preventing evaporation of water, said method comprising applying a composition according to claim 1 or 2 onto a surface to be protected from evaporation or to a material to be protected from evaporation.

28. A non-therapeutic or therapeutic method for preventing evaporation of water, said method comprising applying a compound described in claim 21 onto a surface to be protected from evaporation or to a material to be protected from evaporation.

29. 3. Use of a composition according to claim 1 or 2 for preventing evaporation of water.

30. Use of a compound according to claim 21 to prevent evaporation of water.

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