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WO2024246759A1 - Mélanges lipidiques - Google Patents

Mélanges lipidiques Download PDF

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Publication number
WO2024246759A1
WO2024246759A1 PCT/IB2024/055198 IB2024055198W WO2024246759A1 WO 2024246759 A1 WO2024246759 A1 WO 2024246759A1 IB 2024055198 W IB2024055198 W IB 2024055198W WO 2024246759 A1 WO2024246759 A1 WO 2024246759A1
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Prior art keywords
formula
blend
alkyl
lipids
hydrogen
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English (en)
Inventor
Cornelia PYKO
Bogdan KURPI
Ricardo Figueiredo
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Cataya Bio Shanghai Co Ltd
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Cataya Bio Shanghai Co Ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41—Amines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/22—Separation; Purification; Stabilisation; Use of additives
    • C07C231/24—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
    • C07C29/09—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis
    • C07C29/095—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrolysis of esters of organic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11C—FATTY ACIDS FROM FATS, OILS OR WAXES; CANDLES; FATS, OILS OR FATTY ACIDS BY CHEMICAL MODIFICATION OF FATS, OILS, OR FATTY ACIDS OBTAINED THEREFROM
    • C11C1/00—Preparation of fatty acids from fats, fatty oils, or waxes; Refining the fatty acids
    • C11C1/007—Preparation of fatty acids from fats, fatty oils, or waxes; Refining the fatty acids using organic solvents
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11C—FATTY ACIDS FROM FATS, OILS OR WAXES; CANDLES; FATS, OILS OR FATTY ACIDS BY CHEMICAL MODIFICATION OF FATS, OILS, OR FATTY ACIDS OBTAINED THEREFROM
    • C11C3/00—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom
    • C11C3/003—Fats, oils, or fatty acids by chemical modification of fats, oils, or fatty acids obtained therefrom by esterification of fatty acids with alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/10—General cosmetic use

Definitions

  • the present invention relates to blends of lipids comprising fatty acids and/or ceramides, and to a method for the production thereof.
  • Sphingolipids are an important class of polar lipids mainly found on the surface of eukaryotic cells. Sphingolipids are structurally characterized by a sphingoid base backbone and by M-acyl moiety deriving from a fatty acid. Sphingolipids can be divided into different classes such as, ceramides, and glycosphingolipids.
  • Sphingolipids are involved in diverse biological processes and play important structural and functional roles such as cell-cell recognition, communication, and intercellular adhesion. Particularly, glycosphingolipids, such as gangliosides are found in the brain and play roles in neurological diseases, whereas ceramides are the main constituent of the stratum corneum lipid layer and have a major role in the water-retaining properties of the epidermis, as well as in the barrier function of the skin.
  • sphingolipids hold great potential as therapeutics and cosmetics.
  • Ceramides are /V-acylated sphingoid bases lacking additional head groups at the 1-position of the sphingoid base backbone, and wherein the A/-acyl group of ceramides typically derives from a fatty acid.
  • the high diversity of ceramides arises from their molecular structure, which may be composed by various combinations of a sphingoid bases and acyl moieties.
  • the diversity and complexity of ceramide molecules create a challenge for their low-cost industrial production, which typically comprises separate procedures to synthesize each of the components of the ceramide molecule, and wherein, each procedure, often comprising multiple steps.
  • ceramides like phytosphingosine, its derivatives, and its ceramides thereof, are now commercially available, (e.g. Skinmimics® by Evonik). However, most of the commercially available ceramides comprise the acyl moiety of palmitic or stearic acid (Cis or Cis acyl, respectively), whereas natural occurring ceramides typically contain longer acyl moieties.
  • Ceramides containing longer acyl moieties i.e. > C 20 acyl
  • longer fatty acids i.e. > C 20
  • Ceramides containing longer acyl moieties i.e. > C 20 acyl
  • longer fatty acids i.e. > C 20
  • it has been reported that skin enriched with blends comprising ceramides carrying long acyl moieties (i.e. > C 20 acyl) and/or long chain fatty acids (i.e. > C 2 o) has an improved barrier function as described in Smeden et al., J. Invest. Dermatol 2014, 134:1238-1245.
  • Natural sources of fatty acids are plant oils and waxes. Fatty acids may also be produced via biotechnology, however biotech production is still limited to medium-chain length fatty acids, like Ci 6 - Cig fatty acids.
  • Plant waxes in particular Rice Bran Wax (RBW) have a unique composition of very long chain esters, and therefore could be utilized as a source of long chain fatty acids, such as C 22 -C3s fatty acids.
  • RBW Rice Bran Wax
  • This reference does not describe a method of synthesis of ceramides using the obtained fatty acids.
  • Production of ceramides from spingoid bases can be done chemically or enzymatically.
  • ceramides are typically based on the M-acylation of sphingoid bases, which may comprise the use of acylating agents such as acyl chloride (W00172701 Al), activating agents such as l-ethyl-3-(3'-dimethylaminopropyl)carbodiimide hydrochloride (EDC) (Skolova et al, Biochim Biophys Acta Biomembr. 2017, 1859, 824-834, W00172701 Al), or enzymes such as lipases (WO1994026919A1, US2011077302A1).
  • esters of acids have been utilized for the A/-acylation of phytosphingosine and dihydrosphingosine (EP2757090A1, EP2796444A1).
  • Figure 1 Schematic diagram of the method for the production of a blend of lipids.
  • the present invention relates to a method for the production of a blend of lipids from defatted and saponified rice bran wax (dsRBW), wherein said dsRBW comprising 50 wt% of fatty alcohols, said blend comprising:
  • R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl,
  • R 2 is selected from -OH, and/or -NHR 3 , wherein R 3 is a moiety of formula (2): wherein
  • W is hydrogen or a glycosyl moiety
  • R 4 is hydrogen, aryl, or a substitute or unsubstituted C1-C50 alkyl, preferably a substituted or unsubstituted C1-C17 alkyl, more preferably a substituted or unsubstituted C13-C17 alkyl,
  • R 5 is hydrogen or -OR 7 , wherein R 7 is selected from hydrogen, a substituted or unsubstituted Ci-Ce alkyl, or a substituted or unsubstituted C 2 -C 6 acyl, the bond - may be a double or a single bond when R 5 is hydrogen, or is a single bond when
  • R 5 is -OR 7 ,
  • R s is hydrogen, a substituted or unsubstituted Ci-Cg alkyl, or a substituted or unsubstituted Ci- C s acyl, preferably hydrogen, and
  • the present invention relates to a blend of lipids comprising lipids of formula (1): wherein
  • R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl,
  • R 2 is selected from -OH, and/or -NHR 3 , wherein R 3 is a moiety of formula (2): wherein
  • W is hydrogen or a glycosyl moiety
  • R 4 is hydrogen, aryl, or a substituted or unsubstituted C1-C50 alkyl, preferably a substituted or unsubstituted C1-C17 alkyl, more preferably a substituted or unsubstituted C13-C17 alkyl
  • R 5 is hydrogen or -OR 7 , wherein R 7 is selected from hydrogen, a substituted or unsubstituted Ci-C 6 alkyl, or a substituted or unsubstituted C 2 -C 3 acyl, the bond - may be a double or a single bond when R 5 is hydrogen, or is a single bond when R 5 is -OR 7 ,
  • R s is hydrogen, a substituted or unsubstituted Ci-Cg alkyl, or a substituted or unsubstituted Ci-C 6 acyl, preferably hydrogen, wherein said blend of lipids comprising about 0.5-30 wt% of a C22-C38 fatty alcohol.
  • the present invention relates to a cosmetic or therapeutic composition comprising the lipid blends of the second aspect.
  • the present invention relates to use of a lipid blend or composition comprising thereof for maintaining physiologically normal skin barrier function or improving a deteriorated skin barrier function in an individual.
  • the present invention relates to a blend comprising lipids such as fatty acids and/or sphingolipids, wherein a majority of said lipids either represented or comprising long-chain fatty acids, such as C 22 and C 2 4 fatty acids (behenic and lignoceric acids, respectively).
  • the blend comprises at least 50 wt% of lipids that are either representing or comprising long-chain fatty acids, such as C22 and C 24 fatty acids.
  • the lipid blends also comprise between about 0.5- 30 wt% of C 22 -C 3 s fatty alcohols.
  • the present invention also provides a method for the large-scale production of said blend of lipids, wherein rice bran wax (RBW) is utilized as the source of fatty acids.
  • RBW rice bran wax
  • the term "at least” means an unlimited range of values starting from the indicated value or, in case of wt% range, a range starting from the indicated value and up to 100 wt%.
  • blend or “composition” or “mixture” or “mix” mean a combination of different elements, e.g. molecules, in which the component elements are individually distinct; in some embodiments the component elements could be identical, in other embodiments they could be different by one or more structural features.
  • derivative or “derivate” may be used interchangeably and mean a compound that is synthesised from a structurally similar compound by a chemical reaction with the replacement of one atom or group of atoms.
  • - ester is a derivative of carboxylic acid.
  • the term "population” means several (two or more) identical or structurally different entities present simultaneously in one and the same place , e.g. one or more molecules in a composition.
  • cosmetic relates to improving in appearance, in particular, in appearance of keratinous tissue, i.e. human skin and hair.
  • terapéutica relates to healing of disease or pathologic condition.
  • treat means in different embodiments either to cosmetically address deterioration in appearance of keratinous tissue, or to therapeutically address a pathologic condition or disease with the objective of improving or stabilising an outcome in the person being treated, or addressing an underlying need, or prophylactically preventing development a pathologic condition or disease by maintaining normal/healthy condition.
  • Treating includes Preferably, both cosmetic and therapeutic treating are topical.
  • topical treatment means treatment applied to body surfaces such as the skin.
  • wt% is meant the weight of the named substance contained in the 100 g of the named composition e.g., blend comprising at least about 50 wt% of C22 and C24 fatty acids means that 100 g of the blend typically contains at least about 50 g of C22 and C24 fatty acids.
  • juuv TM means a point of attachment to another group or atom.
  • the various functional groups or substituents represented will be understood to have a point of attachment at the functional group or atom having the dash (-).
  • the point of attachment is the oxygen atom. If a group is listed without a dash, then the attachment point is indicated by the plain and ordinary meaning of the recited group.
  • Positions C-l, C-2, C-3, C-4, C-5 may also be referred to as 1-position, 2-position, 3-position, 4-position, and 5-position respectively.
  • alkyl refers to an acyclic straight or branched hydrocarbyl group having 1-50 carbon atoms which may be saturated or contain one or more double and/or triple bonds (so, forming for example an alkenyl or an alkynyl), and/or which may be substituted or unsubstituted, as herein further described.
  • alkyl refers to a straight acyclic hydrocarbyl group having 1-50 carbons, which may be substituted or unsubstituted.
  • aryl refers to an aromatic cyclic hydrocarbyl group having 5-14 ring carbon atoms, which may be mono- or polycyclic, which may contain fused rings, preferably 1 to 3 fused or unfused rings, and which may contain one or more heteroatoms, and/or which may be substituted or unsubstituted, as herein further described.
  • aryl examples include, but are not limited to, phenyl, naphtyl, anthracyl, phenantryl, pyrrolyl, imidazolyl, thiophenyl, furanyl, oxazolyl, thiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, triazinyl, and benzofuranyl, each of which may be substitute or unsubstituted.
  • aryl refers to a substituted or unsubstituted phenyl.
  • acyl refers to a group derived by the removal of one or more hydroxyl group from an oxoacid, preferably from a carboxylic acid.
  • the acyl group according to the present invention is typically a saturated or unsaturated C2-C34 acyl, which may be substitute or unsubstituted.
  • substituted means that the group in question is substituted with a group which typically modifies the general chemical characteristics of the group in question.
  • the substituents can be used to modify characteristics of the molecule, such as molecule stability, molecule solubility and the ability of the molecule to form crystals.
  • suitable substituents of a similar size and charge characteristics which could be used as alternatives in a given situation.
  • alkyl In connection with the terms “alkyl”, “aryl”, and “acyl the term substituted means that the group in question is substituted one or several times, preferably 1 to 3 times, with group(s) selected from hydroxy (which when bound to an unsaturated carbon atom may be present in the tautomeric keto form), oxo, Ci-C 6 -alkoxy (i.e.
  • Ci-C 3 -alkyl-oxy C 2 -C 6 -alkenyloxy, carboxy, oxo, Ci-C 6 -alkoxycarbonyl, Ci-C 3 - alkylcarbonyl, formyl, aryl, aryloxycarbonyl, aryloxy, arylamino, arylcarbonyl, heteroaryl, heteroarylamino, heteroaryloxycarbonyl, heteroaryloxy, heteroarylcarbonyl, amino, mono- and di-(Ci- C 6 -alkyl)amino, carbamoyl, mono- and di-(Ci-C 6 -alkyl)aminocarbonyl, amino-Ci-C 6 -alkyl-aminocarbonyl, mono- and di-(Ci-C 6 -alkyl)amino-Ci-C 6 -alkyl-aminocarbonyl, Ci-C 6 -alkylcarbonylamino, cyano,
  • alkyl the term “substituted” preferably means that the group in question is substituted one or several times, preferably 1 to 3 times, with group(s) selected from a hydroxyl group, an alkoxy group, an acyloxy group, an acylamido group, a thiol, a thioether or a phosphorus- containing functional group.
  • glycosyl moiety when used herein is defined to encompass a moiety derived from a monosaccharide or from an oligosaccharide (more than one monosaccharide units), wherein the anomeric carbon of the monosaccharide or the anomeric carbon at the reducing end of the oligosaccharide is engaged in a glycosidic bond with another chemical entity, and the bond, if not further specified, may be an alpha or a beta glycosidic bond.
  • a glycosyl moiety having more than one monosaccharide unit may represent a linear or a branched structure.
  • the monosaccharide unit can be any 5-9 carbon atom sugar, comprising aldoses (e.g. D-glucose, D- galactose, D-mannose, D-ribose, D-arabinose, L-arabinose, D-xylose, etc.), ketoses (e.g. D-fructose, D- sorbose, D-tagatose, etc.), deoxysugars (e.g. L-rhamnose, L-fucose, etc.), deoxy-aminosugars (e.g.
  • aldoses e.g. D-glucose, D- galactose, D-mannose, D-ribose, D-arabinose, L-arabinose, D-xylose, etc.
  • ketoses e.g. D-fructose, D- sorbose, D-tagatose, etc.
  • deoxysugars e.
  • the monosaccharide unit can form different cyclic structures such as pyranose (sixmembered) cyclic structures or furanose (five-membered) cyclic structures.
  • glycosyl moieties according to the present invention may be illustrated in the following style: Ga I pi-4G Icl-, wherein the dash (-) represents the point of attachment of the glycosyl moiety and wherein the glycosyl moiety may be linked via an alpha or a beta glycosidic bond, preferably a beta glycosidic bond.
  • fatty alcohol refers to a C 4 -C 3 8 acyclic aliphatic primary alcohol, preferably to a C22-C38 acyclic aliphatic primary alcohol.
  • the fatty alcohol may be linear or branched, saturated or unsaturated.
  • lipid refers to hydrophobic or amphiphilic molecules such as for example fatty acids, sphingolipids, glycosphingolipids, phospholipids etc.
  • Lipids according to the present invention are typically represented by a lipid of formula (1): wherein
  • R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl,
  • R 2 is selected from -OH, and/or -NHR 3 , wherein R 3 is a moiety of formula (2):
  • W is hydrogen or a glycosyl moiety
  • R 4 is hydrogen, aryl, or a substituted or unsubstituted C1-C50 alkyl, preferably a substituted or unsubstituted C1-C17 alkyl, more preferably a substituted or unsubstituted C13-C17 alkyl,
  • R 5 is hydrogen or -OR 7 , wherein R 7 is selected from hydrogen, a substituted or unsubstituted Ci-Cs alkyl, or a substituted or unsubstituted C 2 -C 6 acyl, the bond - may be a double or a single bond when R 5 is hydrogen, or is a single bond when R 5 is -OR 7 , R s is hydrogen, a substituted or unsubstituted Ci-C 3 alkyl, or a substituted or unsubstituted Ci-Cg acyl, preferably hydrogen.
  • R 2 of the lipid of formula (1) is -OH. Accordingly, in some embodiments, the lipid of formula (1) is a fatty acid of formula (3): wherein R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl,
  • the present invention describes a method for the production of a blend comprising a C 8 -C 3 4 non-hydroxy fatty acid ( N), preferably C14-C30 non hydroxy fatty acid (N).
  • R 2 of the lipid of formula (1) is -NHR 3 , wherein R 3 is a moiety of formula (2). Accordingly in some embodiments, the lipid of formula (1) is a lipid of formula (6):
  • R 1 is a C7-C33 alkyl, preferably a C14-C30 alkyl,
  • W is hydrogen or a glycosyl moiety
  • R 4 is hydrogen, aryl, or a substituted or unsubstituted C1-C50 alkyl, preferably a substituted or unsubstituted C1-C17 alkyl, more preferably a substituted or unsubstituted C13-C17 alkyl,
  • R 5 is hydrogen or -OR 7 , wherein R 7 is selected from hydrogen, a substituted or unsubstituted Ci-Cs alkyl, or a substituted or unsubstituted C 2 -C 6 acyl, the bond - may be a double or a single bond when R 5 is hydrogen, or is a single bond when R 5 is -OR 7 ,
  • R s is hydrogen, a substituted or unsubstituted Ci-C 3 alkyl, or a substituted or unsubstituted Ci-C 6 acyl, preferably hydrogen.
  • R 4 is a saturated unsubstituted Cu-Ci? alkyl
  • R 5 is -OH
  • R 6 is hydrogen
  • the bond - is a single bond.
  • R 4 is a saturated unsubstituted C13-C17 alkyl
  • R 5 and R 6 are hydrogen
  • the bond - is a single bond.
  • R 4 is a saturated unsubstituted C13-C17 alkyl
  • R 5 and R 6 are hydrogen
  • the bond - is a double bond.
  • the lipid of formula (1) is a lipid of formula (6), wherein the lipid of formula (6) is a ceramide.
  • the lipid of formula (6) is a ceramide selected from the group consisting of CER[NP], CER[NDS], CER[NS],or CER[NH],
  • the present invention describes a method for the production of a blend comprising a ceramide carrying the acyl moiety of a C 8 -C 3 4 non hydroxy fatty acids (N), preferably of a Cu-Cao non hydroxy fatty acids (N).
  • the present invention describes a method for the production of a blend comprising a C 8 -C 3 4 non hydroxy fatty acids (N), and a ceramide carrying the acyl moiety of a C 8 -C 3 4 non hydroxy fatty acid (N).
  • the present invention describes a method for the production of a blend comprising a C14-C30 non hydroxy fatty acids (N), and a ceramide carrying the acyl moiety of a C14-C30 non hydroxy fatty acid (N).
  • the present invention describes a method for the production of a blend comprising CER[N (8-34:0) P(18)].
  • the present invention describes a method for the production of a blend comprising CER[N (14-30:0) P(18)].
  • the present invention describes a method for the production of a blend comprising CER[N (8-34:0) DS(18)].
  • the present invention describes a method for the production of a blend comprising CER[N (14-30:0) DS(18)]. In some embodiments, the present invention describes a method for the production of a blend comprising CER[N (8-34:0) S(18)].
  • the present invention describes a method for the production of a blend comprising CER[N (14-30:0) S(18)].
  • the present invention describes a method for the production of a blend comprising CER[N (8-34:0) H(18)].
  • the present invention describes a method for the production of a blend comprising CER[N (14-30:0) H(18)].
  • the present invention describes a method for the production of a blend comprising CER[N (8-34:0) P(18)] and CER[N (8-34:0) DS( 18)].
  • the present invention describes a method for the production of a blend comprising CER[N (14-30:0) P(18)] and CER[N (14-30:0) DS(18)].
  • the present invention describes a method for the production of a blend comprising a C 8 -C 3 4 non hydroxy fatty acid and CER[N (8-34:0) P( 18)] .
  • the present invention describes a method for the production of a blend comprising a C14-C30 non hydroxy fatty acid and CER[N (14-30:0) P( 18)].
  • the present invention describes a method for the production of a blend comprising a Cg-C 3 4 non hydroxy fatty acid and CER[N (8-34:0) DS(18)].
  • the present invention describes a method for the production of a blend comprising C14-C30 non hydroxy fatty acids, CER[N (14-30:0) P(18)] and CER[N (14-30:0) DS(18)].
  • Ceramides denote, in the context of the present invention, naturally occurring ceramides, analogues thereof or derivatives thereof. Preferred ceramides are those naturally occurring in humans.
  • Naturally occurring human ceramides include, but are not limited to, CER[NS], CER[AS], CER[EOS], CER[NH], CER[AH], or CER[EOH], CER[NP], CER[AP], or CER[EOP], CER[NDS], CER[ADS], or CER[EODS], wherein letters in brackets refer to the shorthand nomenclature developed by Motta et al., Biochim Biophys Acta., 1993, 1182:147-151 and expanded by Rabionet et al., Biochim Biophys Acta, 2014, 1841:422-434, and by Masukawa et al., Journal of Lipid Research, 2008, 49, 1466-1476.
  • N, A, and EO represent non-hydroxy fatty acids (N), alpha-hydroxy fatty acids (A), and omega-linoleoyloxy fatty acids (EO), respectively, wherein the number of fatty acid carbons and unsaturations may be expressed in parentheses following the letters of N, A, E, and O.
  • S, H, P, and DS represent o-erythro- sphingosine (S), 6-hydroxy-D-eryt ro-sphingosine (H), D-r/bo-phytosphingosine (P), D-erythro- dihydrosphingosine (DS), respectively, wherein the number of sphingoid carbons may be expressed in parenthesis following the letters S, H, P, and DS.
  • Ceramides, CER[NDS], CER[ADS], or CER[EODS] may also be referred to as CER[NG], CER[AG], or CER[EOG], respectively, wherein the letter G represents the INCI name for D-erythro-dihydrosphingosine.
  • the lipid of formula (1) is a lipid of formula (6), wherein the lipid of formula (6) is a glycosphingolipid.
  • W is a glycosyl moiety selected from the group consisting of Glcl-, Gall-, Gaipi-4Glcl-.
  • the present invention describes a method for the production of a blend comprising a glycosphingolipid carrying the acyl moiety of C8-C34 non hydroxy fatty acids [N(8-34:0)].
  • W is Glcl-.
  • the lipid of formula (6) is a glycosphingolipid selected from the group consisting of GIcCE R[N(8-34:0) P(18)], GlcCER[N(8-34:0) DS(18)], GlcCER[N(8-34:0) S(18)],or GlcCER[N (8-34:0) H(18)].
  • the lipid of formula (6) is a glycosphingolipid selected from the group consisting of GlcCER[N(14-30:0) P(18)], GlcCER[N(14-30:0) DS(18)], GlcCER[N(14-30:0) S(18)],or GlcCER[N (14-30:0) H(18)].
  • W is Gall-.
  • the lipid of formula (6) is a glycosphingolipid selected from the group consisting of GalCER[N(8-34:0) P(18)], GalCER[N(8-34:0) DS(18)], GalCER[N(8-34:0) S(18)],or GalCER[N(8-34:0) H(18)].
  • the lipid of formula (6) is a glycosphingolipid selected from the group consisting of GalCER[N(14-30:0) P(18)], GalCER[N(14-30:0) DS(18)], GalCER[N(14-30:0) S( 18)], or GalCER[N(14-30:0) H(18)].
  • W is Gaipi-4Glcl-.
  • the lipid of formula (6) is a glycosphingolipid selected from the group consisting of LacCER[N(8-34:0) P(18)], LacCER[N(8-34:0) DS(18)], LacCER[N(8-34:0) S(18)],or LacCER[N(8-34:0) H(18)].
  • the lipid of formula (6) is a glycosphingolipid selected from the group consisting of LacCER[N(14-30:0) P(18)], LacCER[N(14-30:0) DS(18)], LacCER[N(14-30:0) S(18)], or LacCER[N(14-30:0) H(18)].
  • the present invention describes a method for the production of a blend comprising a C 8 -C 3 4 non hydroxy fatty acid (N), and a glycosphingolipid carrying the acyl moiety of a C 8 - C34 non hydroxy fatty acids (N).
  • the present invention describes a method for the production of a blend comprising a C14-C30 non hydroxy fatty acid (N), and a glycosphingolipid carrying the acyl moiety of a C M - C30 non hydroxy fatty acids (N).
  • lysosphingol ipid when used herein refers to a sphingolipid which lacks the amide-linked fatty acid at the C-2 position of the sphingoid base backbone.
  • Suitable lysosphingolipids for use in the context of the present invention are sphingoid bases, glycosylated sphingoid bases, and analogs thereof and are preferably represented by a lysosphingolipid of formula (5): wherein
  • W is H or a glycosyl moiety
  • R 4 is hydrogen, aryl, or a substituted or unsubstituted C1-C50 alkyl, preferably a substituted or unsubstituted C1-C17 alkyl, more preferably a substituted or unsubstituted C13-C17 alkyl,
  • R 5 is hydrogen or -OR 7 , wherein R 7 is selected from hydrogen, a substituted or unsubstituted Ci-Cg alkyl, or a substituted or unsubstituted C 2 -C 6 acyl, the bond - may be a double or a single bond when R 5 is hydrogen, or is a single bond when R 5 is -OR 7 ,
  • R s is hydrogen, a substituted or unsubstituted Ci-C 5 alkyl, or a substituted or unsubstituted Ci-C 6 acyl, preferably hydrogen.
  • R 4 is a saturated unsubstituted C13-C17 alkyl
  • R 5 is -OH
  • R 6 is hydrogen
  • the bond - is a single bond.
  • R 4 is a saturated unsubstituted C13-C17 alkyl
  • R 5 and R s are hydrogen
  • the bond - is a single bond.
  • R 4 is a saturated unsubstituted C13-C17 alkyl
  • R 5 and R s are hydrogen
  • the bond - is a double bond.
  • W is H. Accordingly, in some embodiments the lysosphingolipid of formula (5) is a sphingoid base.
  • the lysosphingolipid of formula (5) is a sphingoid base selected from the group consisting of D-erytbro-sphingosine [S(18)], 6-hydroxy-D-erytbro-sphingosine [H(18J], D-ribo- phytosphingosine [P(18)], D-erytbro-dihydrosphingosine [DS(18)].
  • the lysosphingolipid of formula (5) is D-r/bo-phytosphingosine [P(18)].
  • the lysosphingolipid of formula (5) is D-erytbro-dihydrosphingosine [DS(18)].
  • the lysosphingolipid of formula (5) is a mixture of D-r/bo-phytosphingosine [P(18)] and D-erytbro-dihydrosphingosine [DS(18)].
  • W is a glycosyl moiety. Accordingly, in some embodiments the lysosphingolipid of formula (5) is a glycosylated sphingoid base.
  • W is a glycosyl moiety selected from the group consisting of Glcl-, Gall-, Gaipi-4Glcl-.
  • W is Glcl-.
  • the lysosphingolipid of formula (5) is a glycosylated sphingoid base selected from the group consisting of Glc[P(18)], Glc[DS( 18)], Glc[S(18)],or Glc[H(18)].
  • W is Gall-.
  • the lysosphingolipid of formula (5) is a glycosylated sphingoid base selected from the group consisting of Gal[P(18)], Gal[DS(18)], Gal[S(18)],or Gal[H(18)].
  • W is Gaipi-4Glcl-.
  • the lysosphingolipid of formula (5) is a glycosylated sphingoid base selected from the group consisting of Lac [P(18)], Lac[DS(18)], Lac[S(18)],or Lac[H(18)].
  • Lysosphingolipids for use in the context of the present invention are preferably obtained via synthetic and/or biotechnological approaches such as those described in WO 2021170624 A2, or in WO2019238970 Al, WO2022158993 Al, or by Sarmientos et al., Eur. J. Biochem. 1986, 160,527-535.
  • the lysosphingolipid of formula (5) may be produced or utilized in the form of a salt, preferably in the form of pharmaceutical acceptable salts.
  • the salt of lysosphingolipids of formula (5) may be formed from the following acids: hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, acetic acid, camphor sulfonic acid, p-toluene sulfonic acid, methane sulfonic acid, trifluoromethanesulfonic acid, perchloric acid.
  • the acid is selected from hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, perchloric acid.
  • the acid is hydrochloric acid.
  • C8-C34 triazine-based acylating agent(s) refers to an activated derivate of a carboxylic acid, wherein the acidic hydroxyl group of the carboxylic acid is converted into a good leaving group via the replacement of the hydrogen atom with a 1,3,5-triazynyl group.
  • Suitable triazine-based acylating agents for use in the context of the present invention are for example those represented by formula (7), or a combination thereof: wherein represents a conjugated system of bonds such that either two or three double bonds are present in the ring;
  • X b is selected from N, or NR 8 ;
  • R 1 is C7-C33 alkyl, preferably a C13-C29 alkyl
  • R 8 is selected from methyl, ethyl, 2,2,2-trifluoroethyl, and substituted or unsubstituted benzyl, preferably methyl.
  • Suitable triazine-based acylating agents for use in the context of the present invention carry one acyl group, such as a C 8 -C 3 4 acyl group, preferably such as a C14-C30 acyl group.
  • Triazine-based acylating agents carrying one acyl group can form several isomeric structures resulting from the migration of substituents on different positions of the 1,3,5-triazine ring. Depending on conditions such as temperature, solvent, and/or the use of a certain reagent such as a certain base, these isomeric structures can be isolated in a pure form or obtained as an isomeric mixture.
  • the term "combination of triazine-based acylating agents” refers to a mixture comprising triazine isomeric structures which differ only in the position of the substituents on the triazine ring and can all serve as acylating agents.
  • the triazine-based acylating agent of formula (7) is a triazine-based acylating agent of formula (8), (9), (10), or (11): wherein
  • R 1 and R 8 are as defined as for the triazine-based acylating agent of formula (7).
  • the triazine-based acylating agent of formula (7) is a combination comprising triazine-based acylating agents of formulas (8), (9), (10) and (11), and wherein each of said triazinebased acylating agent is present, in said combination, in the amount from about 1% to about 99%.
  • the triazine-based acylating agent of formula (7) is a combination comprising triazine-based acylating agents of formulas (8) and (10), and wherein each of said triazines is present, in said combination, in the amount from about 1% to about 99%.
  • the triazine-based acylating agent of formula (7) is a combination comprising triazine-based acylating agents of formulas (8) and (10), and wherein the triazine-based acylating agents of formulas (8) is present, in said combination, in the amount from about 5% to about 75%.
  • the triazine-based acylating agent of formula (7) is a combination comprising triazine-based acylating agents of formulas (8) and (10), and wherein the triazine-based acylating agents of formulas (9) is present, in said combination, in the amount from about 5% to about 75%.
  • the triazine-based acylating agent of formula (7) is a combination comprising triazine-based acylating agents of formulas (9) and (11), and wherein each of said triazines is present, in said combination, in the amount from about 1% to about 99%.
  • the triazine-based acylating agent of formula (7) is a combination comprising triazine-based acylating agents of formulas (9) and (11), and wherein the triazine-based acylating agents of formulas (8) is present, in said combination, in the amount from about 5% to about 50%.
  • the triazine-based acylating agent of formula (7) is a combination comprising triazine-based acylating agents of formulas (9) and (11), and wherein the triazine-based acylating agents of formulas (10) is present, in said combination, in the amount from about 5% to about 50%.
  • the amount of the triazine-based acylating agents comprised in the combination is typically determined via 1 H NMR spectroscopy.
  • characteristic signals deriving from each of the triazine-based acylating agents of the combination are identified, ii. the signals are integrated, iii. the ratio of the integrals is calculated and utilized to the define the amount of the different triazine-based acylating agents of the combination.
  • the amount of the triazine-based acylating agents of the combination may represent a molar ratio or mol %, or a weight ratio or wt% .
  • the person skilled in the art will also understand that the molar ratio or mol %, or the weight ratio or wt% of the triazinebased acylating agents of the combination, may vary over time due interconversion between the different isomeric structures of the triazine-based acylating agent.
  • R 8 of the compound of formula (4) and of triazine-based acylating agents of formulas (8)-( 11) is methyl.
  • the triazine-based acylating agents according to the present invention may be utilized or produced in different polymorphic forms.
  • Polymorphic forms as referred to herein can include crystalline and amorphous forms as well as solvate and hydrate forms, which can be further characterized as follows: i. Crystalline forms have different arrangements and/or conformations of the molecules in the crystal lattice. ii. Amorphous forms consist of disordered arrangements of molecules that do not possess a distinguishable crystal lattice. iii. Solvates are crystal forms containing either stoichiometric or non-stoichiometric amounts of a solvent. If the incorporated solvent is water, the solvate is commonly known as a hydrate.
  • the present invention provides a method for the production of a blend of lipids comprising lipids of formula (1), from defatted and saponified rice bran wax (dsRBW), wherein said dsRBW comprising 50 wt% of fatty alcohols, and wherein the method comprising a step of reducing the fatty alcohol content of the dsRBW, or a derivative thereof, to a content of around 0.5-30 wt%.
  • dsRBW may be obtained by methods known to the skilled person such as that described by Vali et al., JAOCS 2005, 82, 57-64, or such as that described below in Examples 1 and 2.
  • the step of reducing the fatty alcohol content is typically performed via solvent extraction, wherein the solvent extraction may be conducted in in a continuous mode (e.g. Soxhlet extraction), or in a batch mode, and by using one or more extraction solvent(s).
  • solvent extraction may be conducted in in a continuous mode (e.g. Soxhlet extraction), or in a batch mode, and by using one or more extraction solvent(s).
  • Solvents suitable for use in the context of the present invention may be polar or apolar solvents, in particular one can mention Ci-Cio alkyl esters (e.g. ethyl or butyl acetate), Ci-Cio aliphatic nitriles (e.g. acetonitrile), Cs-Cio hydrocarbons (e.g. n-heptane or cyclohexane), or supercritical fluids (e.g. supercritical CO 2 ).
  • the one or more extraction solvent(s) are selected from ethyl acetate, n-heptane, cyclohexane, acetonitrile, or supercritical CO 2 .
  • the extraction solvent is ethyl acetate.
  • the extraction solvent is supercritical CO 2 .
  • the extraction is conducted in a continuous mode, wherein dsRBW, or a derivative thereof, is contacted with an extraction solvent in a Soxhlet extractor at reflux temperature.
  • the extraction is continued for a period of time sufficient to extract most of the fatty alcohols from the dsRBW, or the derivative thereof.
  • the extraction is continued for about 1-6 hours, preferably the extraction is continued for about 4-6 hours. Accordingly in some preferred embodiments, the extraction is continued for about 4, 4.5, 5, 5.5, or 6 hours.
  • the solid residue enriched with fatty acid salts, or derivatives thereof, is collected for further processing (e.g. solvent washes, drying, and/or further synthetic steps).
  • the extraction is conducted in a batch mode, wherein the dsRBW, or a derivative thereof, is contacted with an extraction solvent at a temperature ranging from room temperature to reflux temperature, for a period of time sufficient to extract most of the fatty alcohols from the dsRBW, or the derivative thereof.
  • the extraction is continued for about 1-4 hours, preferably between about 1-2 hours. Accordingly, in some preferred embodiments, the extraction is continued for about 1, 1.5, or 2 hours.
  • the solvent extract, containing the fatty alcohols is separated from the extraction slurry by filtration or centrifugation.
  • the residue enriched with fatty acid salts, or the derivatives thereof is collected for further processing (e.g. solvent washes, drying and/or further synthetic steps).
  • the dsRBW, or the derivative thereof may be subjected to several extraction cycle(s), as described above.
  • the solvent extract obtained after the continuous extraction, or the batch extraction is enriched with fatty alcohols.
  • Fatty alcohols hold potential as therapeutics, cosmetics, and functional food. Therefore, it is of interest to recover the fatty alcohols after extraction.
  • Fatty alcohols can be easily recovered from the solvent extract by subjecting the solvent extract to further processing.
  • the solvent extract comprising the fatty alcohols and their O-acetylated derivatives is subjected to an acid treatment.
  • the acid treatment of the solvent extract is typically performed via the use of an inorganic acid or an organic acid, preferably with an inorganic acid.
  • Acids suitable for use in the context of the present invention include but are not limited to hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, camphor sulfonic acid, p-toluene sulfonic acid, methane sulfonic acid, trifluoromethanesulfonic acid, perchloric acid.
  • the acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, perchloric acid.
  • the acid is hydrochloric acid.
  • the acid may be utilized in the form of an aqueous solution.
  • amount of acid used in the reaction is dependent upon a variety of factors such as the identity of the reactants (including the identity of the acid), and the reaction conditions that are employed. It is therefore understood that amount of acid may be optimally and independently chosen for each reaction.
  • the acid treatment is performed in a solvent, preferably a polar solvent.
  • the solvent is methanol.
  • the acid treatment is typically performed at a temperature between about 60° C and about 65° C. Accordingly, in some embodiments, the acid treatment is performed at a temperature of about 60° C, 51° C, 62° C, 63° C, 64° C, or 65° C.
  • the components of the acid treatment may be combined in any order, and it will be appreciated that the order of combining the reactants may be adjusted as needed.
  • the acid may be added to the solvent extract.
  • the solvent extract may be added to a solution of the acid.
  • the acid, the solvent extract, as well as any other reagent used during the acid treatment may be added to the reaction either as a solid, a liquid, or dissolved in a solvent, and in any quantities and manner effective for the intended result of the reaction.
  • the fatty alcohols are precipitated from the reaction of mixture of the acid treatment.
  • the precipitation of the fatty alcohols may be achieved for example via partial removal of the reaction solvent by evaporation, i.e. concentrating the reaction mixture, or via the addition of another solvent to the reaction mixture, or via changes of temperature or pressure, or via addition of other solutes, or combinations of these.
  • the precipitation of the fatty alcohols is achieved via cooling the reaction mixture of the acid treatment to a temperature from about 0° C to about 30° C, preferably from about 10° C to about 25° C.
  • the precipitation of the salt is achieved via cooling the reaction mixture to a temperature of about 10° C, 11° C, 12° C, 13° C, 14° C, 15° C, 16° C, 17° C, 18° C, 19° C, 20° C, 21° C, 22° C, 23° C, 24° C, or 25° C.
  • the extraction of dsRBW, or a derivative thereof is performed via super critical liquid CO 2 (scrCO 2 ) extraction.
  • the scrCO 2 extraction is a known technique for extraction of oily, waxy, and fatty material from rice bran, as described by Garcia A., et al. JAOCS 1996, 73, 1127-1131, by Moreira et al., The Journal of Supercritical Fluids 2023, 192, 105786, and in CN102994215A. These references, however, do not describe the scrCO 2 extraction of blends deriving from the saponification of defatted rice bran wax (dsRBW).
  • the dsRBW, or the derivative thereof could be extracted in a supercritical fluid equipment using carbonic anhydride at high pressures (250-500 bar) and at a temperature ranging from about 40 to about 120°C.
  • the extraction process typically takes 1-4 h.
  • the dsRBW, or the derivative thereof, enriched with the fatty acid salts, or derivatives thereof is collected for further processing (e.g. further synthetic steps)
  • the scrCO 2 extraction is performed in the presence of a co-solvent.
  • the solvent extraction typically results in the reduction of the C22-C38 fatty alcohol content from about 50 wt% to a content of about 0.5-30 wt%. Accordingly, in some embodiments, the fatty alcohol content may be reduced to a content of about 0.5-5 wt% , or to a content of about 5-10 wt% , or to a content of about 10-20 wt% , or to a content of about 20-30 wt% .
  • the step of reducing the alcohol content is performed on a derivative of dsRBW. Accordingly, in some embodiments, the method comprising the steps of:
  • dsRBW defatted and saponified rice bran wax
  • fatty acid esters comprising about 70-99.5 wt% of C 8 -C 34 fatty acid esters, preferably Ci4-C 30 fatty acid esters, and about 0.5-30 wt% of fatty alcohols.
  • Derivative of dsRBW according to the present invention are typically obtained via reacting dsRBW with an alcohol in the presence of an acid, thereby obtaining a dsRBW derivative comprising C 8 -C 34 , preferably Ci 4 -C 3 o fatty acid esters and between about 0.5-30 wt% of fatty alcohols.
  • dsRBW and the alcohol are reacted in the presence of an inorganic acid or an organic acid, preferably with an inorganic acid.
  • Acids suitable for use in the context of the present invention include but are not limited to hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, camphor sulfonic acid, p-toluene sulfonic acid, methane sulfonic acid, trifluoromethanesulfonic acid, perchloric acid.
  • the acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, perchloric acid.
  • the acid is hydrochloric acid.
  • the acid may be utilized in the form of an aqueous solution.
  • the acid may be utilized in the form of an alcoholic solution.
  • amount of acid used in the reaction is dependent upon a variety of factors such as the identity of the reactants (including the identity of the acid), and the reaction conditions that are employed. It is therefore understood that amount of acid may be optimally and independently chosen for each reaction.
  • Alcohols suitable for use in the context of the present invention include but are not limited to C1-C7 alcohols, or mixtures of C1-C7 alcohols.
  • the alcohol is selected from methanol, ethanol, 1-propanol, isopropanol, 1- butanol, or isobutanol.
  • the alcohol is methanol.
  • the dsRBW, the alcohol, and the acid are typically reacted at a temperature from about 50° C to about 60° C. Preferably at a temperature from about 60°C to about 65° C. Accordingly, in some preferred embodiments, the reaction is performed at a temperature of about 60° C, 61° C, 62° C, 63° C, 64° C, or 65°C.
  • dsRBW The reaction between the dsRBW and the alcohol results in the formation of a dsRBW derivative, wherein said derivative comprises C 8 -C 3 4 fatty acid esters, preferably C14-C30 fatty acid esters, and about 50 wt% of fatty alcohols.
  • the extraction is performed on dsRBW, thereby obtaining a blend comprising C 8 - C3 fatty acid salts, preferably C14-C30 fatty acid salts, and wherein said blend may further comprise between about 0.5-30 wt% of fatty alcohol.
  • the method comprising the steps of:
  • dsRBW defatted and saponified rice bran wax
  • the fatty alcohol content of the blend comprising the fatty acid salts is about 0.5- 5 wt% .
  • the fatty alcohol content of the blend comprising the fatty acid salts is about 5- 10 wt% .
  • the fatty alcohol content of the blend comprising the fatty acid salts is about 10- 20 wt% .
  • the fatty alcohol content of the blend comprising the fatty acid salts is about 20- 30 wt% .
  • the blend comprising fatty acid salts has a content of at least 50 wt% of C22 and C2 fatty acid salts.
  • the ratio between said fatty acid salts is from about 1:10 to about 10:1.
  • the blend comprising the fatty acid salts has a content of at least 50 wt% of C22 and C24 fatty acid salts, and wherein the ratio between said fatty acid salts is from about 1:2.5.
  • the method further comprising a step of treating with an acid the blend comprising the fatty acid salts, thereby obtaining a blend comprising fatty acids of formula (3): wherein R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl, and between about 0.5-30 wt% of fatty alcohols.
  • the present invention describes a method for the production of a blend of lipids comprising a lipid of formula (1), the method comprising the steps of:
  • dsRBW defatted and saponified rice bran wax
  • the acid treatment, of the blend comprising the fatty acid salts is typically performed via reacting the blend comprising the fatty acid salts, with an inorganic acid or an organic acid, preferably with an inorganic acid.
  • Acids suitable for use in the context of the present invention include but are not limited to hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, camphor sulfonic acid, p-toluene sulfonic acid, methane sulfonic acid, trifluoromethanesulfonic acid, perchloric acid.
  • the acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, perchloric acid.
  • the acid is hydrochloric acid.
  • the acid may be utilized in the form of an aqueous solution.
  • amount of acid used in the reaction is dependent upon a variety of factors such as the identity of the reactants (including the identity of the acid), and the reaction conditions that are employed. It is therefore understood that amount of acid may be optimally and independently chosen for each reaction.
  • the acid treatment is performed in a solvent, preferably a polar solvent.
  • the solvent is water.
  • the acid treatment is typically performed at a temperature between about 50 °C and about 60 °C.
  • the acid treatment is performed at a temperature of about 50 °C, 51 °C, 52 °C, 53 °C, 54 °C, 55 °C, 56 °C, 57 °C, 58 °C, 59 °C, or 60 °C.
  • the components of the acid treatment may be combined in any order, and it will be appreciated that the order of combining the reactants may be adjusted as needed.
  • the acid may be added to a solution of the blend comprising the fatty acid salts.
  • the blend comprising the fatty acid salts may be added to a solution of the acid.
  • the acid, the blend comprising the fatty acid salts, as well as any other reagent used during the acid treatment may be added to the reaction either as a solid, a liquid, or dissolved in a solvent, and in any quantities and manner effective for the intended result of the reaction.
  • the acid treatment of the blend comprising the fatty acid salts results in the formation of a blend comprising fatty acids of formula (3).
  • the blend comprising the fatty acids of formula (3) is precipitated from the reaction of mixture of the acid treatment.
  • the precipitation may be achieved for example via partial removal of the reaction solvent by evaporation, i.e. concentrating the reaction mixture, or via the addition of another solvent to the reaction mixture, or via changes of temperature or pressure, or via addition of other solutes, or combinations of these.
  • the precipitation of the blend comprising the fatty acids of formula (3) is achieved via cooling the reaction mixture of the acid treatment to a temperature from about 0° C to about 30° C, preferably from about 10 °C to about 25 °C. Accordingly, in some preferred embodiments, the precipitation is achieved via cooling the reaction mixture to a temperature of about 10° C, 11° C, 12° C, 13° C, 14° C, 15° C, 16° C, 17° C, 18° C, 19° C, 20° C, 21° C, 22° C, 23° C, 24° C, or 25° C.
  • the acid treatment of the blend comprising the fatty acid salts results in the formation of a blend comprising 70-99.5 wt% of fatty acids of formula (3), and about 0.5-30 wt% , of fatty alcohol.
  • the fatty alcohol content of the blend comprising the fatty acids of formula (3) is about 0.5-5 wt% .
  • the fatty alcohol content of the blend comprising the fatty acids of formula (3) is about 5-10 wt% .
  • the fatty alcohol content of the blend comprising the fatty acids of formula (3) is about 10-20 wt% .
  • the fatty alcohol content of the blend comprising the fatty acids of formula (3) is about 20-30 wt% .
  • the blend comprising the fatty acids of formula (3) has a content of at least about 50 wt% , of fatty acids of formula (3) wherein R 1 is a C 2i alkyl and of fatty acids of formula (3) wherein R 1 is a C 23 alkyl, and wherein the ratio between said fatty acids is from about 1:10 to about 10:1.
  • the blend comprising the fatty acids of formula (3) has a content of at least about 50 wt% , of fatty acids of formula (3) wherein R 1 is a C 2i alkyl and of fatty acids of formula (3) wherein R 1 is a C 23 alkyl.
  • the ratio between said fatty acids is about 1:2.5.
  • the method further comprising a step of reacting the blend comprising the fatty acids of formula (3) with an alcohol in the presence of an acid, thereby obtaining a blend comprising a C8-C34 fatty acid ester, preferably C14-C30 fatty acid ester.
  • the present invention describes a method for the production of a blend of lipids comprising lipids of formula (1), the method comprising the steps of:
  • dsRBW defatted and saponified rice bran wax
  • the blend comprising the fatty acids of formula (3) and the alcohol are reacted in the presence of an inorganic acid or an organic acid, preferably with an inorganic acid.
  • Acids suitable for use in the context of the present invention include but are not limited to hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, camphor sulfonic acid, p-toluene sulfonic acid, methane sulfonic acid, trifluoromethanesulfonic acid, perchloric acid.
  • the acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, polyphosphoric acid, perchloric acid.
  • the acid is hydrochloric acid.
  • the acid may be utilized in the form of an aqueous solution.
  • the acid may be utilized in the form of an alcoholic solution.
  • amount of acid used in the reaction is dependent upon a variety of factors such as the identity of the reactants (including the identity of the acid), and the reaction conditions that are employed. It is therefore understood that amount of acid may be optimally and independently chosen for each reaction.
  • Alcohols suitable for use in the context of the present invention include but are not limited to C1-C7 alcohols, or mixtures of C1-C7 alcohols.
  • the alcohol is selected from methanol, ethanol, 1-propanol, isopropanol, 1- butanol, or isobutanol. In some preferred embodiments, the alcohol is methanol.
  • the blend comprising the fatty acids of formula (3), the alcohol, and the acid are typically reacted at a temperature from about 50° C to about 60° C. Preferably at a temperature from about 60° C to about 65° C. Accordingly, in some preferred embodiments, the reaction is performed at a temperature of about 60° C, 61° C, 62° C, 63° C, 64° C, or 65° C.
  • the blend comprising fatty acid esters is precipitated from the reaction mixture.
  • the precipitation may be achieved for example via partial removal of the reaction solvent by evaporation, i.e. concentrating the reaction mixture, or via the addition of another solvent to the reaction mixture, or via changes of temperature or pressure, or via addition of other solutes, or combinations of these.
  • the precipitation of the blend of fatty acid esters is achieved via cooling the reaction mixture of the acid treatment to a temperature from about 0° C to about 30° C, preferably from about 10 °C to about 25 °C. Accordingly, in some preferred embodiments, the precipitation is achieved via cooling the reaction mixture to a temperature of about 10° C, 11° C, 12° C, 13° C, 14° C, 15° C, 16° C, 17° C, 18° C, 19° C, 20° C, 21° C, 22° C, 23° C, 24° C, or 25° C.
  • the reaction between the alcohol and the blend comprising fatty acids of formula (3) results in the formation of a blend comprising about 70-99.5 wt% of C8-C34 fatty acid ester, preferably a C14-C30 fatty acid ester, and about 0.5-30 wt% , of fatty alcohol.
  • the fatty alcohol content of the blend comprising the fatty acid esters is about 0.5-5 wt% .
  • the fatty alcohol content of the blend comprising the fatty acid esters is about 5- 10 wt% .
  • the fatty alcohol content of the blend comprising the fatty acid esters is about 10-20 wt% .
  • the fatty alcohol content of the blend comprising the fatty acid esters is about 20-30 wt% .
  • the blend comprising the fatty acid esters has a content of at least about 50 wt% , of C22 and a of C24 fatty acid esters, and wherein the ratio between said fatty acid esters is from about 1:10 to about 10:1.
  • the blend comprising the fatty acid esters has a content of at least about 50 wt% , of C22 and a of C 2 4 fatty acid esters, and wherein the ratio between said fatty acid esters is about 1:2.5.
  • the method further comprising a step of reacting the blend comprising the fatty acids of formula (3) with a triazine of formula (4): wherein
  • R 8 is selected from methyl, ethyl, 2,2,2-trifluoroethyl, and substituted or unsubstituted benzyl, preferably methyl, in the presence of an organic base, thereby obtaining a blend comprising triazine-based acylating agents of formula (7), and about 0.5-30 wt% of fatty alcohols.
  • the present invention describes a method for the production of a blend comprising a lipid of formula (1), the method comprising the steps of:
  • dsRBW defatted and saponified rice bran wax
  • the step of reacting the blend comprising the fatty acids of formula (3) with the triazine of formula (4) is performed in the presence of an organic base.
  • the organic base is selected from 4-methylmorpholine, 1,4- diazabicyclo[2.2.2]octane, preferably 4-methylmorpholine.
  • the steps of reacting the blend comprising the fatty acids of formula (3) with the compound of formula (4) is performed in a non-halogenated solvent.
  • the non-halogenated solvent is preferably selected from a ketone, an alcohol, or an aliphatic hydrocarbon.
  • the non-halogenated solvent is a ketone selected from acetone, diethyl ketone, methyl isobutyl ketone, or butan-2-one, preferably acetone.
  • water may be added to the reaction mixture.
  • the non-halogenated solvent is an alcohol selected from methanol, ethanol, propanol, isopropanol, butanol, isobutanol, preferably methanol, or a mixture thereof.
  • the non-halogenated solvent is an aliphatic hydrocarbon selected from petroleum ether, hexane, or an isomeric mixture thereof, n-heptane, or an isomeric mixture thereof, octane, or an isomeric mixture thereof.
  • the non-halogenated solvent is a mixture of two alcohols, and wherein the mixture of two alcohols is preferably selected from a mixture of methanol and ethanol, methanol and propanol, methanol and isopropanol, methanol and butanol, or methanol and isobutanol, preferably a mixture of methanol and ethanol.
  • the step of reacting the blend comprising the fatty acids of formula (3) with the triazine of formula (4) is performed at a temperature between about 30° C and about 100° C, preferably between about 30° C and about 55° C.
  • the step of reacting the blend comprising the fatty acids of formula (3) with the triazine of formula (4) results in the formation of a blend comprising C 8 -C 3 4 triazine-based acylating agents, preferably C14-C30 triazine-based acylating agents.
  • the blend comprising the triazine-based acylating agent is precipitated from the reaction.
  • the precipitation may be achieved for example via partial removal of the reaction solvent by evaporation, i.e. concentrating the reaction mixture, or via the addition of another solvent to the reaction mixture, or via changes of temperature or pressure, or via addition of other solutes, or combinations of these.
  • the precipitation is performed at a temperature between about -20 °C and about 25 °C, preferably at a temperature between about -10 °C and about 25 °C, even more preferably at a temperature between about 5 °C and about 25 °C.
  • the reaction between the blend of fatty acids of formula (3) with and triazine of formula (4) results in the formation of a blend comprising C8-C34 triazine-based acylating agents, preferably C1 -C30 triazinebased acylating, and wherein said blend further comprising about 20-30 wt% , of fatty alcohols.
  • the fatty alcohol content of the blend comprising the triazine-based acylating agents is about 0.5-5 wt% .
  • the fatty alcohol content of the blend comprising the triazine-based acylating agents is about 5-10 wt% . In some embodiments, the fatty alcohol content of the blend comprising the triazine-based acylating agents is about 10-20 wt% .
  • the fatty alcohol content of the blend comprising the triazine-based acylating agents is about 20-30 wt% .
  • C 8 -C 34 triazine-based acylating agents may be represented by a triazine-based acylating agent of formula (7).
  • the blend comprising the triazine-based acylating agent has a content of at least about 50 wt% of a triazine-based acylating agent of formula (7) wherin R 1 is a C 2i alkyl and of a triazinebased acylating agent of formula (7) wherein R 1 is a C 23 alkyl, and wherein the ratio between said triazine-based acylating agents is from about 1:10 to about 10:1.
  • the blend comprising the triazine-based acylating agent has a content of at least about 50 wt% of a triazine-based acylating agent of formula (7) wherein R 1 is a C 2i alkyl and of a triazine-based acylating agent of formula (7) wherein R 1 is a C 23 alkyl, and wherein the ratio between said triazine-based acylating agents is about 1:2.5.
  • the method further comprising a step of reacting a lysosphingolipid of formula (5) with the blend comprising the fatty acid esters in the presence of a base, thereby obtaining a blend of lipids of formula (6), and 0.5-30 wt% of fatty alcohols.
  • the present invention describes a method for the production of a blend comprising lipids of formula (5), the method comprising the steps of:
  • dsRBW defatted and saponified rice bran wax
  • W is hydrogen or a glycosyl moiety
  • R 4 is hydrogen, aryl, or a substituted or unsubstituted Ci-Csoalkyl, preferably a substituted or unsubstituted C1-C17 alkyl, more preferably a substituted or unsubstituted C13-C17 alkyl,
  • R 5 is hydrogen or -OR 7 , wherein R 7 is selected from hydrogen, a substituted or unsubstituted Ci-
  • the bond - may be a double or a single bond when R 5 is hydrogen, or is a single bond when R 5 is -OR 7 ,
  • R 6 is hydrogen, a substituted or unsubstituted Ci-C 3 alkyl, or a substituted or unsubstituted Ci-C 3 acyl, preferably hydrogen, with the blend comprising the fatty acid esters in the presence of a base, thereby obtaining a blend comprising lipids of formula (6): wherein
  • R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl,
  • W, R 4 , R 5 and R s are as defined as for the lysosphingolipid of formula (5).
  • the lysosphingolipid of formula (5) and the blend comprising the fatty acid esters are reacted in the presence of a base such as an alkoxide, an amine, a carbonate, or a bicarbonate.
  • a base such as an alkoxide, an amine, a carbonate, or a bicarbonate.
  • the lysosphingolipid of formula (5) and the blend comprising the fatty acid esters are reacted in the presence of an amine, wherein the amine is preferably selected from triethylamine, /V,/V-diisopropylethylamine, and pyridine.
  • the lysosph ingo li pid of formula (5) and the blend comprising the fatty acid esters are reacted in the presence of a carbonate, wherein the carbonate is preferably selected from Na 2 CO 3 , K 2 CO 3 , CaCO 3 , Li 2 CO 3 , (NH 4 ) 2 CO 3 .
  • the lysosphingolipid of formula (5) and the blend comprising the fatty acid esters are reacted in the presence of a bicarbonate, wherein the bicarbonate is preferably selected from NaHCO 3 , KHCO3, Ca(HCO 3 ) 2 , LiHCO 3 , NH 4 HCO 3 .
  • the lysosphingolipid of formula (5) and the blend comprising the fatty acid esters are reacted in the presence of an alkoxide, and wherein the alkoxide is an alkoxide of formula (12):
  • R 9 is a Ci-C 4 alkyl, preferably selected from methyl, ethyl, propyl, isopropyl, butyl, or isobutyl, more preferably selected from methyl, or ethyl;
  • X + is a cation selected from Na + , K + , Li + or NH 4+ , preferably Na + .
  • the lysosphingolipid of formula (5) and the blend comprising the fatty acid esters are reacted in the presence of sodium methoxide.
  • the base may be used in catalytic amounts, equimolar amounts or in excess.
  • the lysosphingolipid of formula (5) is in the free-base form and the base is used in a catalytic amount from about 0.1 to about 0.5 molar equivalents based on the amount of the lysosphingolipid.
  • the lysosphingolipid of formula (5) is in a salt form and the base is used in an amount from about 1.0 to about 1.7 molar equivalents based on the amount of the lysosphingolipid.
  • the lysosphingolipid of formula (5) is in a salt form and the base is used in an amount from about 1.2 to 1.3 molar equivalents based on the amount of the lysosphingolipid.
  • the lysosphingolipid, the blend comprising the fatty acid esters, and the base are reacted in a polar solvent such as methanol, ethanol, propanol, isopropanol, butanol, or isobutanol.
  • a polar solvent such as methanol, ethanol, propanol, isopropanol, butanol, or isobutanol.
  • the reaction is performed in methanol. In some embodiments the reaction is performed in a mixture of one or more polar solvents, such as a mixture of methanol and ethanol, methanol and propanol, methanol and isopropanol, methanol and butanol, methanol and isobutanol, or the mixture of water and an aliphatic alcohol. In some embodiments, the reaction is performed in acetonitrile.
  • the lysosphingolipid, the blend comprising the fatty acid esters, and the base are reacted in C 5 -Cio hydrocarbon solvent, preferably wherein the hydrocarbon solvent is heptane.
  • the reaction is performed solvent-free.
  • the lysosphingolipid, the blend comprising the fatty acid esters, and the base are typically reacted at a temperature from about 50° C to about 125° C. Preferably at a temperature from about 60° C to about 65° C. Accordingly, in some preferred embodiments, the reaction is performed at a temperature of about 50° C, 51° C, 62° C, 63° C, 64° C, or 65° C.
  • the components of the reaction may be combined in any order, and it will be appreciated that the order of combining the reactants may be adjusted as needed.
  • the base may be added to a solution of the lysosphingolipid and the blend comprising the fatty acid esters.
  • a solvent may be added to a flask containing the lysosphingolipid and the blend comprising the fatty acid esters, followed by the base.
  • the lysosphingolipid, the blend comprising the fatty acid esters, and the base, as well as any other reagent used during the reaction may be added to the reaction either as a solid or dissolved in a solvent, and in any quantities and manner effective for the intended result of the reaction.
  • the method further comprising a step of reacting a lysosphingolipid of formula (5) with the blend comprising the triazine-based acylating agents in the presence of a base, thereby obtaining a blend comprising lipids of formula (5), and 0.5-30 wt% of fatty alcohols.
  • the present invention describes a method for the production of a blend comprising lipids of formula (5), the method comprising the steps of:
  • dsRBW defatted and saponified rice bran wax
  • W is hydrogen or a glycosyl moiety
  • R 4 is hydrogen, aryl, or a substituted or unsubstituted Ci-C 5 oalkyl, preferably a substituted or unsubstituted C1-C17 alkyl, more preferably a substituted or unsubstituted C13-C17 alkyl,
  • R 5 is hydrogen or -OR 7 , wherein R 7 is selected from hydrogen, a substituted or unsubstituted Ci-
  • the bond ⁇ ⁇ ⁇ may be a double or a single bond when R 5 is hydrogen, or is a single bond when R 5 is -OR 7 ,
  • R 6 is hydrogen, a substituted or unsubstituted Ci-C 6 alkyl, or a substituted or unsubstituted Ci-C 3 acyl, preferably hydrogen, with the blend comprising the triazine-based acylating agents, thereby obtaining a blend comprising lipids of formula (6): wherein
  • R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl,
  • W, R 4 , R 5 and R s are as defined as for the lysosphingolipid of formula (5).
  • the lysosphingolipid and the blend comprising the triazine-based acylating agents are reacted in a polar solvent such as methanol, ethanol, propanol, isopropanol, butanol, or isobutanol.
  • a polar solvent such as methanol, ethanol, propanol, isopropanol, butanol, or isobutanol.
  • the reaction is performed in methanol.
  • the reaction is performed in a mixture of one or more polar solvents, such as a mixture of methanol and ethanol, methanol and propanol, methanol and isopropanol, methanol and butanol, methanol and isobutanol, or methanol and water.
  • the lysosphingolipid and the blend comprising the triazine-based acylating agents are reacted in the presence of a base such as NaOH, KOH, LiOH, Ca(OH) 2 , triethylamine, N,N- diisopropylethylamine, and pyridine.
  • a base such as NaOH, KOH, LiOH, Ca(OH) 2 , triethylamine, N,N- diisopropylethylamine, and pyridine.
  • the base is selected from NaOH, or KOH.
  • the reaction between the lysosphingolipid and the blend comprising the triazine-based acylating agents is typically performed at a temperature from about 25° C to about 65° C. Accordingly, in some embodiments, the reaction is performed at a temperature of about 25° C, 26° C , 27° C, 28° C, 29° C, 30° C, 31° C, 32° C, 33° C, 34° C, 35° C, 36° C, 37° C, 38° C, 39° C, 40° C, 41° C, 42° C, 43° C, 44° C, 45° C, 46° C, 47° C, 48° C, 49° C, 50° C, 51° C, 52° C, 53° C, 54° C, 55° C, 56° C, 57° C, 58° C, 59° C, 60° C, 61° C, 62° C, 63° C, 64° C, or 65° C.
  • the reaction is performed at temperature from about 45° C to about 55
  • the reaction is performed at a temperature of 45° C, 46° C, 47° C, 48° C, 49° C, 50° C, 51° C, 52° C, 53° C, 54° C, or 55° C.
  • the components of the reaction may be combined in any order, and it will be appreciated that the order of combining the reactants may be adjusted as needed.
  • the lysosphingolipid may be added to a solution of the blend comprising the triazine-based acylating agents.
  • the blend comprising the triazine-based acylating agents may be added to a solution of the lysosphingolipid.
  • a solvent may be added to a flask containing the lysosphingolipid and the blend comprising the triazine-based acylating agents.
  • the lysosphingolipid and the blend comprising the triazine-based acylating agents, as well as any other reagent used during the reaction may be added to the reaction either as a solid or dissolved in a solvent, and in any quantities and manner effective for the intended result of the reaction.
  • the reaction between the blend comprising the fatty acid esters and the lysosphingolipid of formula (5), or the reaction between the blend comprising the triazine-based acylating agents and the lysosphingolipid of formula (5) results in the selective /V-acylation of the amino group at the C-2 carbon atom of the lysosphingolipid of formula (5), thereby producing a blend comprising lipids of formula (6), and wherein said blend may further comprise between about 0.5-30 wt% of fatty alcohols.
  • the fatty alcohol content of the blend comprising the lipids of formula (6) is about 0.5-5 wt% .
  • the fatty alcohol content of the blend comprising the lipids of formula (6) is about 5-10 wt% . In some embodiments, the fatty alcohol content of the blend comprising the lipids of formula (6) is about 10-20 wt% .
  • the fatty alcohol content of the blend comprising the lipids of formula (6) is about 20-30 wt% .
  • the blend comprising the lipids of formula (6) has a content of at least about 50 wt% of a lipid of formula (6) wherein R 1 is a C21 alkyl and of a lipid of formula (6) wherein R 1 is a C23 alkyl, and wherein the ration between said lipids is from about 1:10 to about 10:1.
  • the ratio between the lipid of formula (6) wherein R 1 is a C 2i alkyl and of the lipid of formula (5) wherein R 1 is a C23 alkyl in about 1:2.5.
  • the present invention relates to a blend of lipids comprising lipids of formula (1): wherein
  • R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl,
  • R 2 is selected from -OH, and/or -NHR 3 , wherein R 3 is a moiety of formula (2):
  • W is hydrogen or a glycosyl moiety
  • R 4 is hydrogen, aryl, or a substituted or unsubstituted C1-C50 alkyl, preferably a substituted or unsubstituted C1-C17 alkyl, more preferably a substituted or unsubstituted C13-C17 alkyl,
  • R 5 is hydrogen or -OR 7 , wherein R 7 is selected from hydrogen, a substituted or unsubstituted Ci-Cs alkyl, or a substituted or unsubstituted C 2 -C 6 acyl, the bond - may be a double or a single bond when R 5 is hydrogen, or is a single bond when R 5 is -OR 7 ,
  • R s is hydrogen, a substituted or unsubstituted Ci-C 3 alkyl, or a substituted or unsubstituted Ci-C 6 acyl, preferably hydrogen, wherein said blend may further comprise between about 0.5-30 wt% of fatty alcohols.
  • R 2 of the lipid formula (1) is -OH. Accordingly, in some embodiments, the lipid of formula (1) is a fatty acid of formula (3):
  • R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl.
  • the present invention relates to a blend comprising a fatty acid of formula (3), wherein said blend comprising at least about 50 wt% of a fatty acid of formula (3) wherein R 1 is a C 2i alkyl and of a fatty acid of formula (3) wherein R 1 is a C 23 alkyl, and wherein the ratio between the fatty acid of formula (3) wherein R 1 is a C21 alkyl and the fatty acid of formula (3) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5-30 wt% of fatty alcohols.
  • the present invention relates to a blend comprising lipids of formula (3), wherein said blend comprising at least about 50 wt% of a fatty acid of formula (3) wherein R 1 is a C21 alkyl and of a fatty acid of formula (3) wherein R 1 is a C 23 alkyl, and wherein the ratio between the fatty acid of formula (3) wherein R 1 is a C 2i alkyl and the fatty acid of formula (3) wherein R 1 is a C 23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5-5 wt% of fatty alcohols.
  • the present invention relates to a blend comprising lipids of formula (3), wherein said blend comprising at least about 50 wt% of a fatty acid of formula (3) wherein R 1 is a C 2i alkyl and of a fatty acid of formula (3) wherein R 1 is a C 23 alkyl, and wherein the ratio between the fatty acid of formula (3) wherein R 1 is a C 2i alkyl and the fatty acid of formula (3) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 20-30 wt% of fatty alcohols.
  • the ratio between the fatty acid of formula (3) wherein R 1 is a C 2i alkyl and the fatty acid of formula (3) wherein R 1 is a C 2 3 alkyl is about 1:2.5.
  • the lipids of formula (3) are C 8 -C 3 4 non-hydroxy fatty acid.
  • C 8 -C 3 4 Non-hydroxy fatty acids may also be referred to as N(8-34:0).
  • the fatty acids of formula (3) are C14-C30 non-hydroxy fatty acid.
  • C14-C30 Non- hydroxy fatty acid may also be referred to as N(14-30:0).
  • R 2 of the lipids of formula (1) is -NHR 3 , wherein R 3 is a moiety of formula (2). Accordingly in some embodiments, the lipids of formula (1) are lipids of formula (6):
  • R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl,
  • W is hydrogen or a glycosyl moiety
  • R 4 is hydrogen, aryl, or a substituted or unsubstituted C1-C50 alkyl, preferably a substituted or unsubstituted C1-C17 alkyl, more preferably a substituted or unsubstituted C13-C17 alkyl,
  • R 5 is hydrogen or -OR 7 , wherein R 7 is selected from hydrogen, a substituted or unsubstituted Ci-C 6 alkyl, or a substituted or unsubstituted C2-C6 acyl, the bond - may be a double or a single bond when R 5 is hydrogen, or is a single bond when R 5 is -OR 7 ,
  • R s is hydrogen, a substituted or unsubstituted Ci-C 3 alkyl, or a substituted or unsubstituted Ci-C 6 acyl, preferably hydrogen.
  • R 4 is a saturated unsubstituted C13-C17 alkyl
  • R 5 is -OH
  • R 6 is hydrogen
  • the bond - is a single bond.
  • R 4 is a saturated unsubstituted C13-C17 alkyl
  • R 5 and R 6 are hydrogen
  • the bond - is a single bond.
  • R 4 is a saturated unsubstituted C13-C17 alkyl
  • R 5 and R s are hydrogen
  • the bond - is a double bond.
  • the present invention relates to a blend comprising lipids of formula (6), wherein said blend comprising at least about 50 wt% of a lipid of formula (6) wherein R 1 is a C21 alkyl and of a lipid of formula (6) wherein R 1 is a C23 alkyl, and wherein the ratio between the lipid of formula (6) wherein R 1 is a C 2i alkyl and the lipid of formula (6) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5-30 wt% of fatty alcohols.
  • the present invention relates to a blend comprising lipids of formula (6), wherein said blend comprising at least about 50 wt% of a lipid of formula (6) wherein R 1 is a C21 alkyl and of a lipid of formula (6) wherein R 1 is a C23 alkyl, and wherein the ratio between the lipid of formula (6) wherein R 1 is a C21 alkyl and the lipid of formula (6) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5-5 wt% of fatty alcohols.
  • the present invention relates to a blend comprising lipids of formula (6), wherein said blend comprising at least about 50 wt% of a lipid of formula (6) wherein R 1 is a C21 alkyl and of a lipid of formula (6) wherein R 1 is a C23 alkyl, and wherein the ratio between the lipid of formula (6) wherein R 1 is a C21 alkyl and the lipid of formula (6) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 20-30 wt% of fatty alcohols.
  • the ratio between the lipid of formula (6) wherein R 1 is a C21 alkyl and the lipid of formula (6) wherein R 1 is a C23 alkyl is from about 1:2.5.
  • W is H. Accordingly, in some embodiments, the lipids of formula (6) are ceramides.
  • the lipid of formula (6) is a ceramide selected from the group consisting of ceramides of formula (13), (14), (15), or (16), or a mixture thereof: wherein
  • R 1 is a C7-C33 alkyl, preferably a C13-C30 alkyl.
  • the present invention relates to a blend comprising ceramides of formula (13), wherein said blend comprising at least about 50 wt% of a ceramide of formula (13) wherein R 1 is a C 2i alkyl and of a ceramide of formula (13) wherein R 1 is a C 23 alkyl, and wherein the ratio between the ceramide of formula (13) wherein R 1 is a C 2i alkyl and the ceramide of formula (13) wherein R 1 is a C 23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5- 30 wt% of a C 22 -C 38 fatty alcohol.
  • the present invention relates to a blend comprising ceramides of formula (13), wherein said blend comprising at least about 50 wt% of a ceramide of formula (13) wherein R 1 is a C 2i alkyl and of a ceramide of formula (13) wherein R 1 is a C 23 alkyl, and wherein the ratio between the ceramide of formula (13) wherein R 1 is a C 2i alkyl and the ceramide of formula (13) wherein R 1 is a C 23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5- 5 wt% of a C 22 -C 3 s fatty alcohol.
  • the present invention relates to a blend comprising ceramides of formula (13), wherein said blend comprising at least about 50 wt% of a ceramide of formula (13) wherein R 1 is a C 2i alkyl and of a ceramide of formula (13) wherein R 1 is a C 23 alkyl, and wherein the ratio between the ceramide of formula (13) wherein R 1 is a C 2i alkyl and the ceramide of formula (13) wherein R 1 is a C 23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 20- 30 wt% of a C 22 -C 38 fatty alcohol.
  • the ratio between the ceramide of formula (13) wherein R 1 is a C 2i alkyl and the ceramide of formula (13) wherein R 1 is a C 23 alkyl is about 1:2.5.
  • the present invention relates to a blend comprising ceramides of formula (14), wherein said blend comprising at least about 50 wt% of a ceramide of formula (14) wherein R 1 is a C 23 alkyl and of a ceramide of formula (14) wherein R 1 is a C 23 alkyl, and wherein the ratio between the ceramide of formula (14) wherein R 1 is a C 2i alkyl and the ceramide of formula (14) wherein R 1 is a C 23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5- 30 wt% of a C 22 -C 3 8 fatty alcohol.
  • the present invention relates to a blend comprising ceramides of formula (14), wherein said blend comprising at least about 50 wt% of a ceramide of formula (14) wherein R 1 is a C 2i alkyl and of a ceramide of formula (14) wherein R 1 is a C 23 alkyl, and wherein the ratio between the ceramide of formula (14) wherein R 1 is a C 2i alkyl and the ceramide of formula (14) wherein R 1 is a C 23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5- 5 wt% of a C 22 -C 3 s fatty alcohol.
  • the present invention relates to a blend comprising ceramides of formula (14), wherein said blend comprising at least about 50 wt% of a ceramide of formula (14) wherein R 1 is a C 23 alkyl and of a ceramide of formula (14) wherein R 1 is a C23 alkyl, and wherein the ratio between the ceramide of formula (14) wherein R 1 is a C 2i alkyl and the ceramide of formula (14) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 20- 30 wt% of a C22-C38 fatty alcohol.
  • the ratio between the ceramide of formula (14) wherein R 1 is a C21 alkyl and the ceramide of formula (14) wherein R 1 is a C23 alkyl is about 1:2.5.
  • the present invention relates to a blend comprising ceramides of formula (15), wherein said blend comprising at least about 50 wt% of a ceramide of formula (15) wherein R 1 is a C21 alkyl and of a ceramide of formula (15) wherein R 1 is a C23 alkyl, and wherein the ratio between the ceramide of formula (15) wherein R 1 is a C 2i alkyl and the ceramide of formula (15) wherein R 1 is a C 23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5- 30 wt% of a C22-C38 fatty alcohol.
  • the present invention relates to a blend comprising ceramides of formula (16), wherein said blend comprising at least about 50 wt% of a ceramide of formula (16) wherein R 1 is a C 2i alkyl and of a ceramide of formula (16) wherein R 1 is a C23 alkyl, and wherein the ratio between the ceramide of formula (16) wherein R 1 is a C21 alkyl and the ceramide of formula (16) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5- 30 wt% of a C22-C38 fatty alcohol.
  • R 1 of the ceramides of formula (13)-(16) is a C7-C33 non-hydroxy alkyl. Accordingly, in some embodiments, ceramides of formula (13), (14), (15), and (16) can be referred to as CER[N (8-34:0) P(18)], CER[N (8-34:0) DS(18)], CER[N (8-34:0) 5(18)], and CER[N (8-34:0) H(18)], respectively.
  • R 1 of the ceramides of formula (13)-(16) is a C13-C29 non-hydroxy alkyl. Accordingly, in some embodiments, ceramides of formula (13), (14), (15), and (16) can be referred to as CER[N (14-30:0) P(18)], CER[N (14-30:0) DS(18)], CER[N (14-30:0) 5(18)], and CER[N (14-30:0) H(18)], respectively.
  • W is a glycosyl moiety. Accordingly, in some preferred embodiments, the lipids of formula (6) are glycosphingolipids.
  • the lipid of formula (6) is a glycosphingolipid selected from the group consisting of glycosphingolipids of formula (17), (18), (19), or (20), or a mixture thereof: wherein
  • W is a glycosyl moiety selected from the group consisting of Glcl-, Gall-, Gaipi-4Glcl-,
  • R 1 is a C7-C33 alkyl, preferably a C13-C29 alkyl.
  • the present invention relates to a blend comprising glycosphingolipids of formula (17), wherein said blend comprising at least about 50 wt% of a glycosphingolipid of formula (17) wherein R 1 is a C21 alkyl and of a glycosphingolipid of formula (17) wherein R 1 is a C23 alkyl, and wherein the ratio between the glycosphingolipid of formula (17) wherein R 1 is a C21 alkyl and the glycosphingolipid of formula (17) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5-30 wt% of a C22-C38 fatty alcohol.
  • the present invention relates to a blend comprising glycosphingolipids of formula (17), wherein said blend comprising at least about 50 wt% of a glycosphingolipid of formula (17) wherein R 1 is a C21 alkyl and of a glycosphingolipid of formula (17) wherein R 1 is a C23 alkyl, and wherein the ratio between the glycosphingolipid of formula (17) wherein R 1 is a C21 alkyl and the glycosphingolipid of formula (17) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5-5 wt% of a C22-C38 fatty alcohol.
  • the present invention relates to a blend comprising glycosphingolipids of formula (17), wherein said blend comprising at least about 50 wt% of a glycosphingolipid of formula (17) wherein R 1 is a C21 alkyl and of a glycosphingolipid of formula (17) wherein R 1 is a C23 alkyl, and wherein the ratio between the glycosphingolipid of formula (17) wherein R 1 is a C21 alkyl and the glycosphingolipid of formula (17) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 20-30 wt% of a C22-C38 fatty alcohol.
  • the ratio between the glycosphingolipid of formula (17) wherein R 1 is a C 2i alkyl and the glycosphingolipid of formula (17) wherein R 1 is a C23 alkyl is about 1:2.5.
  • the present invention relates to a blend comprising glycosphingolipids of formula (18), wherein said blend comprising at least about 50 wt% of a glycosphingolipid of formula
  • R 1 is a C21 alkyl and of a glycosphingolipid of formula (18) wherein R 1 is a C23 alkyl
  • the ratio between the glycosphingolipid of formula (18) wherein R 1 is a C 2i alkyl and the glycosphingolipid of formula (18) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5-30 wt% of a C22-C38 fatty alcohol.
  • the present invention relates to a blend comprising glycosphingolipids of formula (18), wherein said blend comprising at least about 50 wt% of a glycosphingolipid of formula (18) wherein R 1 is a C21 alkyl and of a glycosphingolipid of formula (18) wherein R 1 is a C23 alkyl, and wherein the ratio between the glycosphingolipid of formula (18) wherein R 1 is a C21 alkyl and the glycosphingolipid of formula (18) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5-5 wt% of a C22-C38 fatty alcohol.
  • the present invention relates to a blend comprising glycosphingolipids of formula (18), wherein said blend comprising at least about 50 wt% of a glycosphingolipid of formula
  • R 1 is a C21 alkyl and of a glycosphingolipid of formula (18) wherein R 1 is a C23 alkyl, and wherein the ratio between the glycosphingolipid of formula (18) wherein R 1 is a C 2i alkyl and the glycosphingolipid of formula (18) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 20-30 wt% of a C22-C38 fatty alcohol.
  • the ratio between the glycosphingolipid of formula (18) wherein R 1 is a C21 alkyl and the glycosphingolipid of formula (18) wherein R 1 is a C23 alkyl is about 1:2.5.
  • the present invention relates to a blend comprising glycosphingolipids of formula (19), wherein said blend comprising at least about 50 wt% of a glycosphingolipid of formula
  • R 1 is a C21 alkyl and of a glycosphingolipid of formula (19) wherein R 1 is a C23 alkyl
  • the ratio between the glycosphingolipid of formula (19) wherein R 1 is a C21 alkyl and the glycosphingolipid of formula (19) wherein R 1 is a C23 alkyl is from about 1:10 to about 10:1, and wherein said blend may further comprise between about 0.5-30 wt% of a C22-C38 fatty alcohol.
  • the present invention relates to a blend comprising glycosphingolipids of formula (20), wherein said blend comprising at least about 50 wt% of a glycosphingolipid of formula
  • R 1 is a C7-C33 non-hydroxy alkyl
  • W is Glcl-.
  • the glycosphingolipids of formula (17), (18), (19), and (20) can be referred to as GlcCER[N (8-34:0) P(18)], GlcCER[N (8-34:0) DS(18)], GlcCER[N (8-34:0) 5(18)], and GlcCER[N (8-34:0) H(18)], respectively.
  • R 1 is a C13-C29 non-hydroxy alkyl
  • W is Glcl-.
  • the glycosphingolipids of formula (17), (18), (19), and (20) can be referred to as GlcCER[N (14-30:0) P(18)], GlcCER[N (14-30:0) DS(18)], GlcCER[N (14-30:0) S(18)], and GlcCER[N (14-30:0) H(18)], respectively.
  • R 1 is a C7-C33 non-hydroxy alkyl, and W is Gall-.
  • the glycosphingolipids of formula (17), (18), (19), and (20) can be referred to as GalCER[N (8-34:0) P(18)], GalCER[N (8-34:0) DS(18)], GalCER[N (8-34:0) S(18)], and GalCER[N (8-34:0) H(18)], respectively.
  • R 1 is a C13-C29 non-hydroxy alkyl, and W is Gall-.
  • the glycosphingolipids of formula (17), (18), (19), and (20) can be referred to as GalCER[N (14-30:0) P(18)], GalCER[N (14-30:0) DS(18)], GalCER[N (14-30:0) 5(18)], and GalCER[N (14-30:0) H(18)], respectively.
  • R 1 is a C7-C33 non-hydroxy alkyl
  • W is Gaipi-4Glcl-.
  • the glycosphingolipids of formula (17), (18), (19), and (20) can be referred to as LacCER[N (8-34:0) P(18)], LacCER[N (8-34:0) DS(18)], LacCER[N (8-34:0) 8(18)], and LacCER[N (8-34:0) H(18)], respectively.
  • R 1 is a C13-C29 non-hydroxy alkyl
  • W is Gaipi-4Glcl-.
  • the glycosphingolipids of formula (17), (18), (19), and (20) can be referred to as LacCER[N (14-30:0) P(18)], LacCER[N (14-30:0) DS(18)], LacCER[N (14-30:0) S(18)], and LacCER[N (14-30:0) H(18)], respectively.
  • the of fatty alcohol content of the blends of the present invention may be quantified via techniques known to the skilled person such as HPLC analysis or 1 H NMR spectroscopy.
  • the present invention relates to a cosmetic composition comprising the blend according to the present invention.
  • a cosmetic composition comprising the blend of lipids any one defined in the above embodiments and in the claims, or a combination thereof.
  • blend of lipids provided by the invention are biologically active compounds and may be beneficial for use in cosmetic compositions aimed for
  • Cosmetic use according to the invention includes reducing and/or ameliorating signs of skin aging such as reducing or ameliorating one or more of the following signs on the skin: wrinkles, thinning, decrease of elasticity,
  • treatment of skin of mammals, especially, human skin, with the lipids comprised in blends of the invention has been associated with activation of biological pathways in skin cells relating to
  • the lipid blends described herein could also be beneficially used for cosmetic improvement of hair.
  • Cosmetic compositions comprising a lipid blend of the invention may comprise any further active compounds that could enhance or support any of the above mentioned beneficial effects, e.g. such compounds as vitamins, anti-oxidants, oils, etc.
  • the cosmetic compositions can be formulated as liquid, semi-liquid (e.g. emulsions) or solid compositions following guidelines of the art.
  • the cosmetic compositions are topical compositions.
  • the invention relates to therapeutic composition comprising a lipid blend of the invention.
  • the blend of lipids comprised in a therapeutic composition according to the invention is not a therapeutically active compound, but a compound used for a cosmetic support of therapeutic treatment, e.g. for a cosmetic recovery of skin following the therapeutic treatment.
  • HPLC analyses was performed on a Dionex Ultimate 3000 HPLC system coupled with a Corona Veo Charged Aerosol Detector using an Accucore aQ (150 mm x 4.6 mm, 2.6 pm) column.
  • Defatted RBW was suspended in isopropanol (6 vol.) and potassium hydroxide was added. The mixture was refluxed until the full saponification of RBW was obtained (reaction monitored by TLC or ⁇ -NMR). The mixture was cooled down to a temperature of about 60° C, and acetonitrile (5-6 vol.) was added. The mixture was cooled down to room temperature to form a suspension. The suspension was filtered and the collected solid washed with acetonitrile and dried under vacuum. Following the procedure described above a blend comprising a 1:1 mixture of potassium salts of fatty acids and of fatty alcohols was obtained.
  • dsRBW Defatted and saponified RBW
  • ethyl acetate 3-5 vol.
  • the extraction was continued until most of the fatty alcohols were removed (about 4-6 hours, monitored by TLC).
  • the remaining solid residue, enriched with fatty acid salts, was suspended in ethyl acetate or acetonitrile (3-4 vol) and stirred at room temperature for about 15-30 minutes.
  • the suspension was filtered and, the collected solid was washed with ethyl acetate or acetonitrile and dried in vacuum.
  • the blend obtained in example 3 was added to a 1:10 mixture of HCI (37% aq.) and water.
  • the resulting suspension was stirred at a temperature of about 50-60° C for 1-2 hours, then cooled down to room temperature and stirred for additional 1-2 hours.
  • the suspension was filtered, the solid collected, washed with water (3-4 vol.) and dried.
  • the identity and content of the fatty acids comprised in the blend obtained in example 4 were determined via LCMS and HPLC analysis.
  • the LCMS eluent profile consisted of solvent A: 1 L water + 2 mL formic acid + 2 mmol ammonium formate, and solvent B: 1 L MeOH + 1 L acetonitrile + 4 mL formic acid + 4 mmol ammonium formate.
  • a gradient of 80-100% B in A was applied over 50 min, followed by an isocratic of 80% B in A for 55 min.
  • the HPLC eluent profile consisted of solvent A: 1 L water + 2 mL formic acid + 2 mmol ammonium formate, and solvent B: 1 L MeOH + 1 L acetonitrile + 4 mL formic acid + 4 mmol ammonium formate.
  • Example 6 Production of a fatty acid esters blend from the blend of fatty acids
  • the fatty acid blend obtained in Example 4 was suspended in methanol (5 vol.), and HCI (37% aq. 0.3-0.6 vol.) was added.
  • the reaction mixture was refluxed until the fatty acids were fully converted into their corresponding methyl esters (monitored by TLC).
  • the reaction mixture was cooled down to room temperature and water (5 mL) was added.
  • the obtained suspension was filtered, the solid collected, washed with a 1:1 mixture of Methanol and water (3-4 vol.) and dried in vacuum. Following the procedure described above, a blend comprising between about 75-85 wt% of C14-C30 fatty acid methyl esters was obtained.
  • the fatty acid methyl ester blend obtained in Example 6 was characterized via GC analysis.
  • the GC conditions were as follow: The initial oven temperature was 60° C for 1 min, then programmed to 180° C at a rate of 40° C/min. and a hold time of 5 minutes, then programmed to 320° C at a rate of 10°C/min. and a hold time of 17 min.
  • the FID detector temperature was 280° C.
  • a constant flow of Helium was applied with a rate of 2 mL/min.
  • the fatty acid methyl ester content of the blend was quantified via peak area analysis using external standards. The results of the GC analysis are summarized in Table 2.
  • the fatty acid blend obtained in Example 4 was suspended in acetone (8 vol.). 4-Methylmorpholine (1.1 eq.) was added and obtained mixture was stirred at 35-40 °C for 15 min. Then, 2-chloro-4,6-dimethoxy- l,3,5-triazine(1.05 eq.) was added and the mixture was stirred at 35-40° C. After 2 h. The reaction mixture was cooled down to room temperature, water (12 vol.) was added, and the obtained suspension was filtered. The collected solid was washed with a 1:1 mixture of acetone and water (5-6 vol.) and dried in vacuum.
  • a hydrochloride salt of a sphingoid base (1 eq.) was dissolved in MeOH (10 vol.), sodium methoxide (25% in MeOH, 1.4 eq.) was added followed by the fatty acid methyl ester blend obtained in Example 6 (1.1 eq.).
  • the reaction mixture was stirred at 60 °C until full conversion of the starting materials (monitored by TLC). Subsequently, the reaction mixture was cool down to room temperature to form a suspension. The suspension was filtered, and the obtained solid was first washed with methanol (10 vol.), then resuspended in methanol and refluxed for about 0.5-1 h. Subsequently, water was added to the suspension, and the mixture was first cooled down to room temperature and then filtered. The collected solid was washed with a 10:1 mixture of methanol and water (2 times, 2-3 vol.) and dried in vacuum.
  • D-erythro-Dihydrosphingosine hydrochloride (1 eq.) and the blend of fatty acid methyl esters were reacted under the conditions of Example 9 to produce a blend comprising ceramides DS(18) carrying non-hydroxy C16-C30 acyl groups.
  • the CER[N (14-30:0) DS( 18)] blend was characterized by LCMS analysis.
  • the LCMS eluent profile consisted of solvent A: 2 mL formic acid, 2mM ammonium formate in IL of water, and solvent B: 2ml formic acid, 2mM ammonium formate in 500ml Acetonitrile+500ml Methanol.
  • a gradient of 80-100% B in A was applied over 10 min., followed by an isocratic of 100% B in A for 50 min., followed by an isocratic of 80% B in A for 40 min.
  • Example 3 The solvent extract obtained in Example 3, comprising fatty alcohols and O-acetylated fatty alcohols, was concentrated, MeOH (10 vol.) was added, followed by HCI (37% aq., 0.5-1.2 vol.). The resulting mixture was stirred at reflux until all the O-acetylated fatty alcohol derivatives were converted into the corresponding fatty alcohols (reaction monitored by TLC). Then, the reaction mixture was cooled down to RT and stirred for about 0.5-1 hour. The obtained suspension was filtered, the solid collected, washed with MeOH (3-4 vol.) and dried in vacuum.
  • the fatty alcohol blend obtained in Example 11 was characterized via HPLC analysis.
  • the HPLC eluent profile consisted of solvent A: methanol, and solvent B: acetonitrile. A gradient of 50- 93% A in B was applied over 20 min, followed by an isocratic of 50% A in B for 45 min. The fatty alcohol content of the blend was quantified via peak area analysis using external standards. The results of the HPLC analysis are summarized in Table 2.
  • dsRBW Defatted and saponified RBW
  • methanol 10 vol.
  • Hydrochloric acid was added to the suspension (37% aq.), and the suspension was stirred under reflux until full conversion (monitored by TLC).
  • the reaction mixture was cooled down to room temperature and the resulting suspension was filtered.
  • the obtained solid was washed with methanol (3-4 vol.), dried in vacuum, and then suspended in ethyl acetate (10 vol.).
  • the suspension was refluxed for 1-2 hours, then cooled down to room temperature and filtered.
  • the obtained solid was washed with ethyl acetate (3-4 vl.) and dried in vacuum.
  • dsRBW Defatted and saponified RBW

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Abstract

La présente invention concerne des mélanges comprenant des lipides tels que des acides gras et/ou des sphingolipides, lesdits mélanges comprenant entre environ 0,5 à 30 % en poids d'alcools gras en C22-C38, et des compositions comprenant les mélanges lipidiques. La présente invention concerne également un procédé de production à grande échelle desdits mélanges lipidiques, la cire de son de riz (RBW) étant utilisée en tant que source d'acides gras.
PCT/IB2024/055198 2023-05-29 2024-05-29 Mélanges lipidiques Pending WO2024246759A1 (fr)

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