Modified black soldier fly oil extract and uses thereof

Abstract

A modified, monoglyceride-enriched black soldier fly (BSF) oil extract, compositions, and edible products such as feed and food supplemental products comprising same and uses thereof in treating or preventing inflammation and / or microbial infection and / or biofilm formation, and / or in reducing a mortality, increasing an average body weight and / or improving a feed conversion ratio in a population comprising a plurality of subjects, are provided. A composition comprising a monoglyceride-enriched oil and a plant oil or extract derived from a Lamiaceae plant and uses thereof are also provided. The subjects to treated include, for example, human being, pets, farm animals, fish and crustaceans.

Description

[0001] MODIFIED BLACK SOLDIER FLY OIL EXTRACT AND USES THEREOF

[0002] RELATED APPLICATION

[0003] This application claims the benefit of priority from US Provisional Application No. 63 / 523,421, filed June 27, 2023, the contents of which are incorporated herein by reference in their entirety.

[0004] FIELD AND BACKGROUND OF THE INVENTION

[0005] The present invention, in some embodiments thereof, relates to monoglyceride-enriched oil, such as, but not limited to, monoglyceride-enriched black soldier fly (BSF) oil extract, to processes of preparing same, to compositions and products comprising same and to uses thereof.

[0006] Black soldier fly (BSF; Hermetia illucens) larvae (BSFL) are rich in fat, with levels typically ranging between 15 % and 49 % on dry matter basis. Notably, the fatty acid profile of the prepupae is high in the medium-chain fatty acids (MCFAs), with lauric acid (C12:0) being the major component. Lauric acid is known to have antiviral, antifungal and antibacterial activity, and as particularly active against Gram positive bacteria. The fatty acid profile of the prepupae contains additional MCFAs such as capric acid (C10:0) and caprylic acid (C8:0). Trials showed that black soldier fly prepupal fat (0.58 gram C 12:0 / 100ml) suppressed growth of Lactobacilli, and exhibited substantial antibacterial effects against D-streptococci infections in pigs. In vivo experimentations suggested that these positive effects are most likely seen when farming conditions and / or health status are sub-optimal [Gasco et al., Journal of Insects as Food and Feed (2018), 4(1), 1-4],

[0007] It has also been reported that while some components of virgin coconut oil (VCO), such as medium-chain fatty acids (MCFAs), monoglycerides and free fatty acids (FFA) exhibit antimicrobial activity, other components such as triglycerides and diglycerides have a lesser antimicrobial activity. It has been suggested that VCO may be metabolized to release MCFAs such as caprylic acid (C8:0), capric acid (C10:0), and lauric acid (C12:0) to exert its antimicrobial effects [Shilling et al., Journal of medicinal food (2013), 16(12), 1079-1085],

[0008] Lauric acid in insect larvae is stored mainly as triglycerides [Liland et al., PLoS ONE (2017), 12(8), eO 183188] . There are several ways known in the industry to break triglycerides into monoglycerides and free fatty acids to enhance its antimicrobial properties. For example, WO 2007 / 067028 describes that coconut oil and palm kernel are hydrolyzed using the catalytic activity of 1,3 -positional specific lipases to provide modified oil compositions that comprise free fatty acids (FFAs, 9.40-25.01 %), monoglycerides (MAGs, 1.31-14.28 %), diglycerides (DAGs, 21.66- 39.98 %) and triglycerides (TAGs, 25.08-64.16 %), and that these compositions are able to inhibit the growth of Gram-positive bacteria (i.e., Staphylococcus aurous aureus, Listeria monocytogenes, Streptococcus pyogenes), Gram-negative bacteria (i.e., Vibrio cholerae, Escherichia coli) and yeast (i.e., Candida albicans).

[0009] Fatty acids and monoglycerides achieve their antimicrobial effects by several mechanisms. An early postulated mechanism is the perturbation of the microorganism’s plasma membrane lipid bilayer. For example, the antiviral action attributed to monolaurin involves fluidizing the lipids and phospholipids in the envelope of the virus, and thereby causing the disintegration of the microbial membrane. Some studies indicate that one antimicrobial effect in bacteria is related to monolaurin's interference with signal transduction / toxin formation [Projan, et al., J Bacteriology (1994), 176, 4204-4209], Another antimicrobial effect in viruses relates to lauric acid's interference with virus assembly and viral maturation [Hornung et al., Journal of General Virology (1994), 75(2), 353-361], Another suggested mode of action involves an effect on the immune system itself [Witcher et al., Clinical and Diagnostic Faboratory Immunology (1996), 3, 10-13],

[0010] Hess et al. [Surgical Infections (2015), 16(5), 538-542] teach using the natural surfactant glycerol monolaurate (GML) to inhibit biofilm development.

[0011] WO 2020 / 234884 discloses a method that comprises extracting black soldier fly larvae (BSFL) oil, and modifying the BSFL oil by converting triglycerides in the BSFL oil to medium chain fatty acids (MCFAs) in the form of monoacylglycerides (MAGs, monoglycerides or MGs), up to 7.33 % w / w in BSFL oil; out of which monolaurin is the most abundant - up to 2.39 % w / w in BSFL oil), fatty acid salts and / or free fatty acids (FFAs, up to 3.13 % w / w in oil), by, e.g., saponification and / or hydrolysis.

[0012] WO 2020 / 234884 teaches that the obtained modified BSFL (MBSFL) oil is usable in suppressing biofilm development and / or microorganism growth.

[0013] Additional background art includes U.S. Patent Application Publication No. 2018 / 256483.

[0014] SUMMARY OF THE INVENTION

[0015] According to an aspect of some embodiments of the present invention there is provided a modified, monoglyceride-enriched black soldier fly (BSF) oil extract, comprising one or more monoglycerides in a total amount that is higher by at least 20 % of a total amount of monoglycerides in an unmodified BSF oil extract.

[0016] According to embodiments of the invention, the modified BSF oil extract comprises one or more monoglycerides in a total amount of at least 25 %, at least 30 %, at least 35 %, at least 40 %, at least 45 %, at least 50 %, at least 55 %, at least 60 % or at least 65%, by weight of the total weight of the modified BSF oil extract.

[0017] According to embodiments of the invention, the modified BSF oil extract comprises one or more monoglycerides in a total amount that ranges from 25 to 70 % by weight, of the total weight of the modified BSF oil extract.

[0018] According to an aspect of some embodiments of the present invention there is provided a modified BSF oil extract comprising monoglycerides in a total amount of at least 25 %, at least 30 %, least 35 %, at least 40 %, at least 45 %, at least 50 %, at least 55 %, at least 60 % or at least 65 % by weight of the total weight of the modified BSF oil extract.

[0019] According to embodiments of the invention, the total amount of the monoglycerides ranges from 25 to 70 %, by weight, of the total weight of the modified BSF oil.

[0020] According to embodiments of the invention, the modified BSF oil comprises monolaurin in an amount of at least at least 10 %, or 15 %, or at least 20 %, or at least 25 %, or at least 30% by weight, of the total weight of the modified BSF oil.

[0021] According to embodiments of the invention, the modified BSF oil comprises monolaurin in an amount that ranges from 10 to 40 %, by weight, of the total weight of the modified BSF oil.

[0022] According to embodiments of the invention, the modified BSF oil comprises monolaurin in an amount that ranges from 25 to 75 %, by weight, of the total weight of the one or more monoglycerides in the modified BSF oil.

[0023] According to embodiments of the invention, the modified BSF oil further comprises triglycerides in a total amount of no more than 25%, no more than 20 % or no more than 10% by weight of the total weight of the modified BSF oil.

[0024] According to embodiments of the invention, the modified BSF oil further comprises di glycerides in a total amount of no more than 40 %, no more than 35% or no more than 30 %, by weight of the total weight of the modified BSF oil.

[0025] According to embodiments of the invention, the modified BSF oil further comprises free fatty acids, in a total amount of no more than 10, % by weight of the total weight of the modified BSF oil.

[0026] According to embodiments of the invention, the modified BSF oil further comprises glycerol in an amount of no more than 15 %, no more than 12% or no more than 10 %, by weight of the total weight of the modified BSF oil.

[0027] According to another aspect of the invention, there is provided a process of preparing a modified, monoglycerides-enriched BSF oil, the process comprising contacting a BSF oil extract with glycerol, and an alkaline substance, under conditions that promote transesterification. According to embodiments of the invention, the mol ratio of the BSF oil extract and the glycerol ranges from 2: 1 to 1 : 10, or from 1 : 1 to 1 : 10, or from 1 : 1 to 1 :6, or from 1 : 1 to 1 :4, or from 1 :2 to 1 :3.

[0028] According to embodiments of the invention, the alkaline catalyst is a methoxide or a hydroxide.

[0029] According to embodiments of the invention, the mol ratio of the alkaline substance and said BSF oil extract ranges from 1: 100 to 10: 100.

[0030] According to embodiments of the invention, the conditions comprise heating the mixture, for example, to a temperature of at least 100, or at least 150 °C, under reduced pressure.

[0031] According to embodiments of the invention, the contacting is for a time period that ranges from 1 to 24 hours.

[0032] According to embodiments of the invention, the process further comprises subsequent to the contacting, removing the glycerol from the mixture, to thereby obtain the modified BSF oil.

[0033] According to embodiments of the invention, the removing is such that an amount of the glycerol in the modified BSF oil is less than 20 %, or less than 15%, or less than 10% by weight of the total weight of the modified BSF oil.

[0034] According to another aspect of the invention, there is provided a modified, monoglycerides- enriched BSF oil obtainable by a process described herein.

[0035] According to another aspect of the invention, there is provided a composition comprising a modified BSF oil as described herein.

[0036] According to embodiments of the invention, the composition comprises an edible carrier.

[0037] According to embodiments of the invention, the composition is formulated for oral administration to a subject in need thereof.

[0038] According to embodiments of the invention, the composition is in a form of a liquid, a paste, a powder, a syrup, a particulate material, a gel, and a capsule.

[0039] According to embodiments of the invention, the carrier is a solid carrier, and wherein the modified BSF oil is associated with the carrier.

[0040] According to embodiments of the invention, the carrier is dispersable in a liquid.

[0041] According to embodiments of the invention, the carrier is a solid particulate carrier, the composition being in a form of a powder or a particulate carrier.

[0042] According to embodiments of the invention, the composition is in a form of microcapsules or nanoparticles having the modified BSF oil encapsulated therewithin.

[0043] According to embodiments of the invention, the composition is a liquid emulsion. According to embodiments of the invention, the composition further comprises an additional agent selected from chitin, chitosan, a BSF protein extract, an anti -microbial agent, an anti-inflammatory agent, a plant extract and a plant and / or mineral oil.

[0044] According to embodiments of the invention, the composition further comprises an extract or an oil derived from a plant of the Lamiaceae family.

[0045] According to another aspect, there is provided a composition comprising a monoglyceride- enriched oil and at least one of a plant oil, a plant extract a thymol, a carvacrol, a eugenol, a cinnamaldehyde, a limonene, a myrcene, a germacrene, a pinene, a cymene, an ocimene, a terpinene, a caryophyllene and / or bisabolene.

[0046] According to embodiments of the invention, the plant is a Lamiaceae plant.

[0047] According to embodiments of the invention, the plant oil or extract acts in synergy with the monoglyceride-enriched oil in treating and / or preventing inflammation and / or microbial infection and / or in preventing biofilm formation.

[0048] According to embodiments of the invention, the amount of the monoglyceride-enriched oil and / or an amount of the plant oil or extract in the composition is less than the therapeutically effective amount when used as a single agent.

[0049] According to embodiments of the invention, the monoglyceride-enriched oil is a plant oil, a mineral oil, or an animal oil.

[0050] According to embodiments of the invention, the monoglyceride-enriched oil is a modified BSF oil extract as described herein.

[0051] According to embodiments of the invention, the composition further comprises a carrier, preferably an edible carrier.

[0052] According to embodiments of the invention, the modified BSF or the composition described herein is for use in the manufacture of a feed or food product.

[0053] According to still another aspect there is provided an edible product comprising the modified BSF oil described herein or the composition described herein.

[0054] According to embodiments of the invention, the amount of the modified BSF oil in the product is in a range of from 0.001% to 1 % by weight of the total weight of the product.

[0055] According to embodiments of the invention, the edible product is a food or feed product or a supplemental feed or food product.

[0056] According to embodiments of the invention, the edible product is for treating or preventing inflammation and / or microbial infection and / or biofilm formation in a subject.

[0057] According to embodiments of the invention, the subject is selected from a a human being, a companion animal, a farm animal, a fish and a crustacean. According to another aspect of the invention, there is provided a method of treating or preventing inflammation in a subject in need thereof, the method comprising orally administering to the subject an effective amount of the modified BSF oil described herien, or the composition described herein, or the edible product described herein, thereby treating or preventing the inflammation.

[0058] According to another aspect of the invention there is provided a method of treating or preventing a disease or disorder associated with a pathogenic microorganism in a subject in need thereof, the method comprising orally administering to the subject an effective amount of the modified BSF oil described herien, or the composition described herein, or the edible product described herein, thereby treating or preventing the disease or disorder.

[0059] According to embodiments of the invention, the modified BSF oil or the composition are administered to the subject as a food supplement or a feed supplement.

[0060] According to embodiments of the invention, the subject is selected from a human being, a companion animal, a farm animal, a fish and a crustacean.

[0061] According to embodiments of the invention, the effective amount of the modified BSF oil is in a range of from 0.001% to 1 % by weight of the total weight of a composition or a product comprising same.

[0062] According to embodiments of the invention, the method is for reducing a mortality, increasing an average body weight and / or improving a feed conversion ratio in a population comprising a plurality of subjects.

[0063] According to another aspect there is provided a method of reducing a mortality, increasing an average body weight, reducing antibiotic intake, reducing a number of days to reach target body weight, reducing a number of sick days until marketing, reduction in diarrhea days until weaning and / or improving a feed conversion ratio in a population comprising a plurality of subjects, the method comprising treating the plurality of subjects with the modified BSF oil described herein, or the composition described herein, or the edible product described herein.

[0064] According to embodiments of the invention, the subjects are selected from the group consisting of farm animals, fish and crustaceans.

[0065] According to embodiments of the invention, the modified BSF oil or the composition are administered to the subject as a food supplement or a feed supplement.

[0066] According to embodiments of the invention, the modified BSF oil or the composition are administered to the subject via inhalation.

[0067] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0068] BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0069] Some embodiments of the invention are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of embodiments of the invention. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the invention may be practiced.

[0070] In the drawings:

[0071] FIG. 1 is a graph illustrating that black soldier fly modified oil (BSFMO) inhibits fungal growth of Aspergillus niger. Average values ± SEM (n=3). Significance was determined by oneway ANOVA with Tukey HDS post-hoc analysis. Asterisks indicate significant differences (* < 0.05; ** < 0.01, ***<0.001).

[0072] DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

[0073] The present invention, in some embodiments thereof, relates to monoglyceride-enriched oil, such as, but not limited to, monoglyceride-enriched black soldier fly (BSF) oil extract, to processes of preparing same, to compositions and products comprising same and to uses thereof.

[0074] Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.

[0075] In a search for monoglyceride-enriched oils, and while considering the low conversion of triglycerides to monoglycerides in the modification of black soldier fly (BSF) oil extract as taught in WO 2020 / 234884, the present inventors have turned to other modification methodologies. In excessive studies conducted to this effect, the present invention have succeeded to come up with processes that provide monoglyceride-enriched black soldier fly (BSF) oil extract, have demonstrated its anti -microbial and anti-inflammatory efficacy and have utilized this efficacy for treating a variety of animal subjects. Embodiments of the present invention therefore relate to modified, monoglyceride- enriched, black soldier fly (BSF) oil extract, to processes of preparing same, to compositions and edible products comprising same and to uses thereof.

[0076] The black soldier fly oil extract described herein, typically, but not obligatory, refers to an oil extract derived from the black soldier fly larvae which are harvested between 6 and 30 days after hatching, preferably between 6 and 20 days after hatching, more preferably 6-14 days after hatching, more preferably between 8-12 days after hatching, e.g. 10 days after hatching. In exemplary' embodiments, the extract is derived from larvae which are harvested between 12 hours and 3 days before the larvae transform into prepupae, such as 1-2 days before transformation.

[0077] The oil extract can be obtained by separating a fat fraction from a protein fraction, such that the fat fraction is preferably devoid or mostly devoid of proteins. Optionally, prior to generation of the extract, the BSFs or the larvae thereof may be rinsed. The BSFs or the larvae thereof may also be subjected to a steaming process.

[0078] In one embodiment, the separation of the fat fraction and the protein fraction is carried out under dry conditions. The BSFs or the larvae thereof are typically reduced in size by mechanical treatment e.g. crushed, homogenized or minced under conditions whereby crude fat (i.e. lipids) can be extracted therefrom (squeezed or pressed therefrom).

[0079] In one embodiment, the separation of the fat fraction and the protein fraction is carried out under wet conditions. Following optional rinsing and steaming, wet pulp comprising larvae may be centrifuged so as to separate the fat layer from the water soluble layer.

[0080] BSF oil extract can also be obtained from commercial vendors including for example Protix, Innovafeed, eNorm, Agronutris, Nutrition Technologies, Ento-System, and EntoBell.

[0081] Herein, “modified black soldier fly oil extract”, which is also referred to herein interchangeably as “ black soldier fly modified oil (BSFMO)” or simply as “modified BSF oil” describes a BSF oil extract as defined herein, which has been subject to ex-situ modification, typically chemical modification, for example, by subjecting the oil extract to one or more chemical reactions to thereby modify the composition of the fatty substances in the oil extract.

[0082] The phrase “fatty substance” generally encompasses water-immiscible non-aqueous substances which can be solid or liquid at room temperature (25 °C) and atmospheric pressure (760 mmHg). In the context of an oil derived from an animal source, as is the case of a BSF oil extract, the fatty substances generally comprise naturally occurring lipids, which can be in a form of free fatty acids (FFAs), and / or, mostly, as glycerolipids. As used herein, the term "lipid" describes a hydrocarbon residue having 3-30 carbon atoms. In naturally-occurring compounds, the lipids in the glycerolipids are derived from fatty acids and are therefore attached to the glycerolic backbone via an O-acyl (ester) bond.

[0083] Glycerolipids can be "mono-esterified", "di-esterified" or “tri-esterified”, in which one or two or three of the lipid moieties, respectively, are attached to the glycerol backbone via an ester (e.g., O-fatty acyl) bond.

[0084] Mono-esterified glycerolipids are also referred to herein as monoacylglycerides, or as monoglycerides or are abbreviated as MAG.

[0085] Di-esterified glycerolipids are also referred to herein as diacylglycerides, or as diglycerides, or are abbreviated as DAG.

[0086] Tri-esterified glycerolipids are also referred to herein as triacylglycerdies, or as triglycerides, or are abbreviated as TAG.

[0087] Glycerolipids can be collectively represented by the following formula: in which each of Ri, R2 and R3 is independently selected from hydrogen and a saturated or unsaturated alkylene chain of at least 6 carbon atoms (e.g., of from 7 to 40, or from 7 to 30, carbon atoms), whereby at least of one of Ri, R2 and R3 is other than hydrogen.

[0088] Typically, when Ri, R2 and / or R3 is an alkylene chain as defined herein, this alkylene chain is a residue of a fatty acid, that is it is the “R” component of “R-C(=O)=OH) that represents a free fatty acid.

[0089] In TAGs, each of Ri, R2 and R3 is an alkylene chain as defined, e.g., a residue of a fatty acid as described herein. The alkylene chains can be the same or different.

[0090] In DAGs, two of Ri, R2 and R3 is an alkylene chain as defined, e.g., a residue of a fatty acid as described herein, and the third is hydrogen. The alkylene chains can be the same or different. In MAGs, one of Ri, R2 and R3 is an alkylene chain as defined, e.g., a residue of a fatty acid as described herein, and the other two are each hydrogen.

[0091] Typically, in BSF oil extract (and also in other animal-derived oil extracts), most of the fatty substances (e.g., more than 50 %, typically more than 70 %, or more than 80 %, typically more than 90 %) are in a form of triglycerides.

[0092] The lipid moiety or moieties in glycerolipid compounds (MAG, DAG or TAG) is typically a residue of a fatty acid, as described herein for Ri, R2 and / or R3. Representative examples of fatty acids include, without limitation, saturated or unsaturated fatty acids that have 8 or more carbon atoms, preferably 10 or more carbon atoms, for example, 12-14 carbon atoms, such as, but not limited to, lauric acid, sebacic acid, myristic acid, , palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, arachidonic acid, palmitoleic acid, erucic acid, etc.

[0093] In some embodiments, a BSF oil extract typically includes a substantial portion (e.g., more than 30 % or more than 40 % or more) of fatty substances (e.g., FFA, MAG, DAG and / or TAG) that include lauric acid or a residue thereof (a lauric acid portion that if bound to the glycerolic backbone).

[0094] According to an aspect of some embodiments of the present invention, there is provided a modified, monoglyceride-enriched, black soldier fly (BSF) oil extract, which also referred to herein for simplicity as black soldier fly modified oil (BSFMO).

[0095] According to the present embodiments, a monoglyceride-enriched oil extract (e.g., modified BSF oil extract) comprises one or more monoglycerides in a total amount that is higher by at least 20 % (by weight) of a total amount of monoglycerides in the unmodified oil extract (e.g., an unmodified BSF oil extract).

[0096] A monoglyceride-enriched oil extract according to embodiments of the present invention therefore includes a relative portion of monoglycerides that is higher (by 20 % or more, by weight) than the relative portion of the monoglycerides in the unmodified oil extract, which has been processed without subjecting the oil extract to a chemical reaction that modifies the composition of the fatty substances therein.

[0097] For example, while a BSF oil extract typically includes mostly (more than 90 %) TAGs, and less than 5 % MAGs, a modified, monoglyceride-enriched BSF oil extract according to embodiments of the present invention includes at least 25 % mol of MAGs.

[0098] According to an aspect of some embodiments of the present invention, there is provided a modified, monoglyceride-enriched BSF oil extract, which comprises one or more monoglycerides in a total amount of at least 25 %, at least 30 %, at least 35 %, at least 40 %, at least 45 %, at least 50 %, at least 55 %, at least 60 %, at least 65 % or at least 70 %, by weight of the total weight of the modified BSF oil extract.

[0099] According to an aspect of some embodiments of the present invention, there is provided a modified, monoglyceride-enriched BSF oil extract, which comprises one or more monoglycerides in a total amount that ranges from about 25 to about 70 % by weight, of the total weight of the modified BSF oil extract, including any intermediate values and subranges therebetween.

[0100] The modified BSF oil extract can comprise one, two or more monoglycerides, which differ from one another by the type of the fatty acid residue that is attached to the glycerol backbone.

[0101] According to some of any of the embodiments described herein, a substantial portion of the monoglycerides in the modified BSF oil comprises a monolaurin, that is, a monoglyceride according to the formula above, in which on Ri or R2 is a residue of laurin and the other two are each hydrogen, and as shown below.

[0102] 1-mnonolaurin 2-monolaurin

[0103] The two possible structures of monolaurin

[0104] According to some of any of the embodiments described herein, at least 10 %, or at least 20 %, or at least 30 %, or at least 40 %, or at least 50 %, or at least 60 %, or at least 70 %, or more, by weight, of the total amount of monoglycerides in the modified BSF oil extract, is a monolaurin.

[0105] According to some of any of the embodiments described herein, the modified BSF oil extract comprises monolaurin in an amount that ranges from about 25 to about 75 %, by weight, of the total weight of the one or more monoglycerides in the modified BSF oil extract.

[0106] According to some of any of the embodiments described herein, the modified BSF oil extract comprises monolaurin in an amount that ranges from about 10 to about 40 %, by weight, of the total weight of the modified BSF oil, including any intermediate values and subranges therebetween.

[0107] According to some of any of the embodiments described herein, the modified BSF oil further comprises other fatty substances that were either present in the BSF oil extract prior to modification and / or formed during the modification. According to some of any of the embodiments described herein, a total amount of triglycerides in the modified BSF oil is no more than 30 %, or no more than 25 %, no more than 20 % or no more than 10 % by weight of the total weight of the modified BSF oil, and can range, for example, from about 5 to about 30 % by weight, including any intermediate values and subranges therebetween.

[0108] According to some of any of the embodiments described herein, a total amount of diglycerides in the modified BSF oil is no more than 40 %, no more than 35 % or no more than 30 % by weight of the total weight of the modified BSF oil, and can range, for example, from about 10 to about 40 % by weight, including any intermediate values and subranges therebetween.

[0109] According to some of any of the embodiments described herein, the modified BSF oil can further comprises free fatty acids (FFAs), in a total amount of no more than 10 (e.g. from 0.1-10), or no more than 5, or no more than 3, or no more than 2, % by weight of the total weight of the modified BSF oil. In some embodiments, a total amount of the FFAs in the modified BSF oil is from 0 to about 10, or from 0 to about 5, or from 0 to about 3 % by weight, including any intermediate values and subranges therebetween.

[0110] The modified BSF oil according to some of the embodiments described herein can further comprise other fatty substances that originate from the unmodified BSF oil extract or result from the modification process. In exemplary embodiments, the modified BSF oil further comprises glycerol, and in some of these embodiments, the modified BSF comprises glycerol in an amount of no more than 15 % (e.g. from 0.1 to 15 %), no more than 12% or no more than 10 %, by weight of the total weight of the modified BSF oil. In some of these embodiments, the modified BSF oil comprises glycerol in an amount of from 0 to about 15, or from 0 to about 10, or from 0 to about 5, %, by weight, including any intermediate values and subranges therebetween.

[0111] According to some of any of the embodiments described herein, the fatty acid residues in the fatty substances of the modified BSF oil (that is, the fatty acid residues in the MAGs, DAGs, TAGs and FFAs in the modified BSF oil) are mostly derived from saturated fatty acids, and are further mostly of medium-chain residues of from 10 to 16 carbon atoms in length. In some embodiments, at least 50 % or at least 60 %, for example, from about 50 to about 85, or from about 50 to about 80, or from about 60 to about 80, %, of the fatty acid residues in the fatty substances as a whole are saturated fatty acid residues. In some embodiments, at least 60 % or at least 70 %, for example, from about 60 to about 80, %, of the fatty acid residues in the fatty substances as a whole are medium-chain fatty acid residues of from 10 to 16 carbon atoms in length. In some embodiments, from about 30 to about 50, or from about 40 to about 50, % of the fatty acid residues in the fatty substances as a whole are residues of lauric acid. A modified, monoglyceride-enriched, BSF oil extract as described herein can be efficiently obtained by a newly designed process, which is described in detail in the Examples section that follows. The process is based a transesterification reaction between the fatty substances in the BSF oil extract, which include mainly TAGs, and glycerol, in the presence of an alkaline substance, typically in a catalytic amount, as shown in the Examples section that follows.

[0112] According to an aspect of some embodiments of the present invention there is provided a process of preparing a modified, monoglycerides-enriched BSF oil such as described herein in any of the respective embodiments and any combination. The process, according to the embodiments of this aspect of the present invention, comprises a BSF oil extract, such as described herein in any of the respective embodiments and any combination thereof, and glycerol, under conditions that promote transesterification.

[0113] The conditions that promote transesterification include any reaction conditions, such as, for example, temperature, reaction time (duration), other reagents, amounts and ratios of the reagents, etc.

[0114] According to some of any of the embodiments of this aspect of the present invention, contacting the BSF oil extract and the glycerol is effect in the presence of a catalyst suitable for transesterification. Any such a catalyst or any combination of two or more such catalysts is contemplated. Exemplary catalysts include sodium hydroxide, potassium hydroxide, lithium hydroxide, and other hydroxides of alkali metals, sodium alkoxide (e.g., methoxide), potassium alkoxide (e.g., methoxide), lithium alkoxide (e.g., methoxide), and other alkoxides (e.g., methoxides) of alkali metals, as well as calcium dihydroxide, calcium oxide, and more. According to some embodiments, the catalyst is an alkaline substance, such as, but not limited to, a hydroxide or alkoxides, preferably methoxide, of an alkali metal, preferably sodium. In exemplary embodiments, the catalyst is sodium methoxide. In exemplary embodiments, the catalyst is sodium hydroxide.

[0115] The catalyst or alkaline substance can be added to a reaction mixture that comprises the BSF oil extract and the glycerol, either per se, or in a solution (for example, an aqueous solution, an alcoholic solution or an aqueous alcoholic solution).

[0116] According to some of any of the embodiments of the present invention, an amount of the alkaline substance or the catalyst, relative to the BSF oil extract, ranges from 1 to 10 % mol, such that a mol ratio therebetween ranges from 1 : 100 to 10: 100, including any intermediate value and subranges therebetween. In exemplary embodiments, this ratio is 4: 100 (4% mol of the alkaline substance relative to the initial amount of the BSF oil extract in the reaction). According to some of any of the embodiments described herein, a mol ratio of the BSF oil extract and the glycerol ranges from 2: 1 to 1 : 10, or from 1 : 1 to 1 : 10, or from 1 : 1 to 1 :6, or from 1 : 1 to 1 :4, or from 1 : 1 to 1 :3 or from 1 : 1 to 1 :2, or from 1 :2 to 1 :3, including any intermediate values and subranges therebetween. As demonstrated in the Examples section that follows, it has been shown that the reaction can proceed efficiently at suboptimal ratios of, for example, 1 :2 and 1 :3.

[0117] According to some any of the embodiments of this aspect of the present invention, the reaction conditions involve heating the reaction mixture (comprising the BSF oil extract, the glycerol and optionally and preferably the alkaline substance or catalyst). According to some embodiments, heating is to a temperature of at least 100, or at least 150 (e.g., 150-200) °C, under reduced pressure (e.g., of about 100 mbar or lower), or any other equivalent temperature, when a different reduced pressure is applied. Preferably, the reduced pressure is such that the reaction temperature does not exceed the boiling temperature of glycerol.

[0118] According to some of any of the embodiments described herein, the contacting (reaction time or duration), is for a time period that ranges from 1 to 24 hours, including any intermediate values and subranges therebetween. Typically, shorter reaction times, of, for example, from 1 to 10 or from 1 to 8, hours, are contemplated.

[0119] According to some of any of the embodiments described herein, the BSF oil extract used as the starting material has an acid number lower than 1. Optionally, when a BSF oil extract has a higher fatty acid number, the process further comprises, prior to the contacting, pre-treating the BSF oil extract so as to remove acidic components (e.g., FFAs), and thereby reduce the acid number. This can be done, for example, by distillation (e.g., short-path distillation) and / or washings.

[0120] The acid value of the raw BSF oil can be determined according to NF EN ISO 660 and is also referred to in the art an acid index (Ai or IA).

[0121] According to some of any of the embodiments of this aspect of the present invention, subsequent to the contacting, the glycerol, or a part thereof is removed from the obtained reaction mixture.

[0122] Preferably, removing the glycerol is such that an amount of the glycerol in the modified BSF oil product is less than 20 %, or less than 15 %, or less than 10 % by weight of the total weight of the modified BSF oil, for example, from 0 to 15, or from 1 to 10, or from 1 to 5, % by weight.

[0123] Removing the glycerol can be done by any method known in the art, including, for example, distillation, washings and / or absorption. An exemplary efficient methodology for removing glycerol is described in the Examples section that follows. According to some of any of the embodiments described herein, the process further comprises loading the obtained BSF oil product onto a particulate matter (e.g., a powder). An exemplary procedure and particulate matters are described in the Examples section that follows.

[0124] According to an aspect of some embodiments of the present invention there is provided a modified, monoglycerides-enriched BSF oil obtainable by a process as described herein in any of the respective embodiments and any combination thereof.

[0125] According to some of these embodiments, the modified BSF oil obtained by the process features a chemical composition (e.g., of the fatty substances therein) and other properties as described herein in any of the respective embodiments for a modified, monoglycerides-enriched BSF oil extract.

[0126] By being enriched with monoglycerides such as monolaurin, and other monoglycerides which exhibit advantageous therapeutic properties, the modified BSF oil as described herein can be included in various compositions and products and beneficially used in various applications, as follows.

[0127] According to an aspect of some embodiments of the present invention, there is provided a composition comprising a modified BSF oil as described herein in any of the respective embodiments and any combination thereof.

[0128] According to some of any of the embodiments of this aspect of the present invention, the composition further comprises a carrier.

[0129] According to some of any of the embodiments described herein, the composition is formulated for oral administration to a subject as described herein, e.g., a subject in need thereof. The composition may be formulated as a drink or a food.

[0130] According to some of any of the embodiments described herein, the composition further comprises an edible carrier. Such a composition is also referred to herein as an edible composition.

[0131] As used herein “edible” refers to a composition which is safe for human or animal consumption (e.g. by eating or drinking). For example, this includes, but is not limited to a food product or a drink that is generally recognized as safe per a government or regulatory body (such as the United States Food and Drug Administration). In certain embodiments, the food product or drink is considered safe to consume by a person of skill. Any edible food product suitable for a human consumption should also be suitable for consumption by another animal and such an embodiment is intended to be within the scope herein.

[0132] As used herein “food grade” refers to a substance (food or drink) which is either safe for human consumption or confirmed to come into direct contact with food products. According to some embodiments of the invention, the substances included in a composition as described herein (e.g., substances that compose the carrier) are of “food grade” classification.

[0133] Such substance are also referred to herein and in the art as “food contact substances” or “food contact materials”.

[0134] The phrase "food contact substance" or FCS, is used herein to describe substances that are generally safe for human consumption by virtue of being generally recognized as safe (GRAS) or by passing standard safety tests, and thus qualify for use as a component of materials used in manufacturing, packing, packaging, transporting, or holding food, in the same manner it is meant in the guideline and regulation of worldwide food administration authorities, such as, for example, the U.S. Food and Drug Administration (FDA), Center for Food Safety and Applied Nutrition (CFSAN), the Office of food Additive Safety.

[0135] The phrase "generally recognized as safe" or GRAS, as used herein, is meant in the same manner which is defined, for example, under sections 201(s) and 409 of the U.S. FD&C Act. The U.S. law states that any substance that intentionally contacts food or added to food is a food additive, that is subject to premarket review and approval by FDA, unless the substance is generally recognized, among qualified experts, as having been adequately shown to be safe under the conditions of its intended use, or unless the use of the substance is otherwise excluded from the definition of a food additive. GRAS substances are distinguished from food additives by the type of information that supports the GRAS determination, that it is publicly available and generally accepted by the scientific community, but should be the same quantity and quality of information that would support the safety of a food additive.

[0136] Since the qualification to an FCS or GRAS category can be obtained through a process of applying, testing and qualifying to the requirements of the various official food and drug authorities, the present embodiments are meant to encompass all relevant substances and their derivatives which are to become FCSs and GRAS in the future, as well as those which already qualify as FCSs and GRAS.

[0137] The edible carrier can be a liquid carrier and / or a solid carrier, and can determine the form of the composition.

[0138] A composition as described herein (e.g., an edible composition) can be in a form of a liquid, a paste, a powder, a syrup, a particulate material (e,g., microcapsules, nanoparticles, granules), a liquid emulsion, a gel, a capsule, or any other suitable form as described herein or known in the art. According to some of any of the embodiments described herein, the carrier is or comprises a solid carrier. For example, the carrier can be a solid particulate carrier, for example, in a form of a powder, with particles featuring an average size in the nanoscale, microscale or milliscale.

[0139] When the carrier is a solid carrier, the modified BSF oil is associated with the carrier. For example, the carrier can comprise solid particulate matter (e.g., powder, pellets, etc.) and the modified BSF oil can be associated with the carrier by being absorbed to the surface of the particulate matter. Alternatively, the solid carrier can provide a composition that comprises a plurality of capsules (e.g., microcapsules or nanocapsules), and the BSF oil is encapsulated within the capsules. Further alternatively, the solid carrier can be a solid matrix (e.g., a solid polymeric matrix) and the modified BSF oil can be dispersed in and / or the solid matrix.

[0140] Accordingly, the modified BSF oil may be provided to a subject per se (i.e. not encapsulated or carried), loaded on a powder, micro-encapsulated in a matrix powder, non-encapsulated in a matrix powder, micro-encapsulated in a core-shell powder, nano-encapsulated in a core-shell powder, as a liquid micro-emulsion or as a liquid nano-emulsion.

[0141] In one embodiment, the modified BSF oil is associated with the carrier and dispersed in a liquid forming a drinkable product. The carrier ensures that the BSF oil remains stably dispersed in the liquid for a duration required for the liquid consumption.

[0142] In some embodiments, the carrier can comprise both solid and liquid substances, such that, for example, the composition comprises a plurality of particulate matter to which the modified BSF is absorbed, and the particulate matter is dispersed in a liquid carrier. For example, the composition can comprise a plurality of capsules encapsulating the modified BSF oil, and the capsules are dispersed in a liquid carrier.

[0143] Solid carriers suitable for use in the context of any of the respective embodiments include, for example, natural polymers such as, but are not limited to, sodium alginate, gum Arabic, chitosan, cellulose and carboxymethylcellulose, pectin, Shellac, xanthan gum, gum Arabic, zein, pullulan, maltodextrin, whey protein, galactomannan, modified starch, polycaprolactone, and sodium caseinate.

[0144] Exemplary methods for encapsulation include freeze-drying, spray-drying, spray-chilling, fluidized bed, extrusion, coacervation, complexation, and supercritical anti-solvent drying. The encapsulation may result in monolayer capsules, multilayer capsules, multinuclear capsules, regular shaped capsules, matrices or irregular shaped capsules.

[0145] Exemplary methods for providing particulate matter having the modified BSF oil loaded thereon are described in the Examples section that follows. According to exemplary embodiments, the carrier is a solid, powdered carrier, for example, comprising a plurality of particles having an average size (in diameter) in a range of between 1 micron to 2,500 microns, or from 100 microns and 2,500 microns.

[0146] The weight % of the modified BSF oil out of the total weight of the oil-loaded powdered carrier can range between 1% and 60%, preferably between 20% and 50% oil loading, e.g., from 35% oil and 65% carrier to 50 / 50 % weight oil / carrier.

[0147] Examples of powdered carrier usable for preparing oil-loaded powder include, but are not limited to, mineral carriers such as, but not limited to Attapulgite, Palygorskite, Ditomaceous Earth, Calcium Carbonate, Silica; plant based powders such as, but not limited to, Wheat powder / flower, Maize powder / flower, Pea powder / flower; sugar-based powders such as, but not limited to, Sucrose, Glucose, Fructose, Maltodextrin, Cyclodextrin.

[0148] Exemplary modes of delivering the compositions described herein to animals (e.g. companion animals, aquaculture, ruminants and monogastrics) are provided herein below:

[0149] (a) via solid feed: Liquefied (warmed) oil, powdered oil, liquid oil emulsion:

[0150] (b) via solid food: Liquefied (warmed) oil, powdered oil, liquid oil emulsion;

[0151] (c) via liquid feed: Water-dispersible powdered oil, liquid oil emulsion;

[0152] (d) via liquid food: Water-dispersible powdered oil, liquid oil emulsion;

[0153] (e) via drinking liquid: Water-dispersible powdered oil, liquid oil emulsion; or

[0154] (f) via drinking water: Water-dispersible powdered oil, liquid oil emulsion.

[0155] A composition as described herein in any of the respective embodiments can further comprise additional agents that can contribute to its therapeutic and / or performance-enhancing effect. Such agents include, for example, additional components that can be derived from BSF, such as, for example, chitosan and / or a BSF protein extract, which can be used per se or as a modified form. Alternatively, or in addition, such agents can include, additional naturally- occurring substances, derived or extracted from plants and / or animals, such as, for example, chitin, chitosan (e.g. extracted from BSF chitin), protein extracts from other sources (optionally modified), plant extracts, plant oils, mineral oils and any combination thereof. Further alternatively or in addition, such agents include agents that provide a therapeutic effect, for example, anti-microbial agents and / or anti-inflammatory agents, as described herein.

[0156] The phrase “antimicrobial” as used herein, refers to a property of a substance (e.g., a compound or a composition) that can effect a parameter of microorganism (e.g., a pathogenic microorganism), as defined herein, including death, eradication, elimination, reduction in number, reduction of growth rate, inhibition of growth, change in population distribution of one or more species of microbial life forms. This term encompasses antibacterial agents, which are also referred to herein as antibiotics, as well as, for example, anti -mycobacterial agent, antiviral agents, antifungal agents, anti -protozoal agents, and anti-parasitic agents, as well as anti-biofilm agents (also known as anti-biofouling agents).

[0157] Non-limiting examples of conventional antifungal agents include polyene-based antifungal agents such as amphotericin, amphotericin B, nystatin and pimaricin, azole-based antifungal agents such as fluconazole, itraconazole and ketoconazole, allylamine- or morpholine-based antifungal agents such as allylamines (naftifine, terbinafine), and antimetabolite-based antifungal agents such as 5 -fluorocytosine, and fungal cell wall inhibitor such as echinocandins like caspofungin, micafungin and anidulafungin.

[0158] Exemplary antibacterial agents, or antibiotics, include, without limitations, aminoglycosides (e.g., gentamicin, tobramycin, amikacin, streptomycin), fluoroquinolones (e.g., ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin), carbapenems (e.g., imipenem, meropenem, ertapenem), polymyxins (e.g., colistin, polymyxin B, polymyxin E), tetracyclinea (e.g., tetracycline, doxycycline), macrolides (e.g., azithromycin, clarithromycin, erythromycin), beta-lactams (e.g., ampicillin, amoxicillin, ticarcillin, piperacillin, imipenem, oxacillin, cephalosporins), sulfonamides (e.g., sulfamethoxazole, sulfadiazine, sulfisoxazole, sulfacetamide, sulfamethazine, sulfasalazine), rifamycins (e.g., rifampin, rifabutin), nitroimidazoles (e.g., metronidazole, tinidazole), phosphonic acid antibiotics (e.g., fosfomycin), chloramphenicol, glycopeptides (e.g., vancomycin), oxazolidinones (e.g., linezolid), cephalosporins (e.g., cefazolin, ceftriaxone, cephalothin, ceftazidime, cefepime), monobactams (e.g., aztreonam), nitrofurans (e.g., nitrofurantoin), polyphenols (e.g., ellagic acid and derivative thereof) [see, e.g., M. Daglia, Current Opinion in Biotechnology, 23(2), 2012, 174-181] and lipopeptides (e.g., daptomycin).

[0159] Non-limiting examples of conventional antibacterial agents (antibiotics) include, but are not limited to, gentamicin, ampicillin, amikacin (AK), cefazolin, ceftriaxone, clindamycin, cephalothin, ciprofloxacin, chloramphenicol, ceftazidime (CAZ), cefepime (CPE), erythromycin, trimethoprim / sulfamethoxazole (T / S), gatifloxacin, piperacillin / tazobactam (P / T), aztreonam (AZT), imipenem, levofloxacin, penicillin, oxacillin, nitrofurantoin, linezolid, moxifloxacin, meropenem (MER), tobramycin (TO), ciprofloxacin (CP), tetracycline, vancomycin, rifampin, synercid, streptomycin, colistin (CT) and chloramphenicol (C).

[0160] Exemplary compounds useable as anti-biofilm agents include, but are not limited to, antibiotics as described herein, dispersants (i.e., compounds that can penetrate or break down the extracellular matrix of biofilms, optionally making the biofilm more susceptible to antimicrobial agents) (e.g., dispersin B, D-amino acids, DNase, proteases), quorum sensing inhibitors (QSIs as known in the art; e.g., N-acyl homoserine lactone inhibitors), EDTA and N-acetylcysteine. Non-limiting examples of anti-inflammatory agents include, but are not limited to, steroids (e.g., corticosteroids such as cortisone, prednisone), non-steroidal anti-inflammatory drugs (NSAIDs, e.g., ibuprofen, aspirin, naproxen), COX-2 inhibitors (e.g., celecoxib), biologies (e.g., TNF inhibitors), and antihistamines.

[0161] Exemplary mineral oils include, without limitation, silicon oil, white oil, white mineral oil, liquid petrolatum, liquid paraffin or white paraffin oil. The mineral oil may optionally comprise a mineral oil replacement. Mineral oil replacements include alkanes having at least 10 carbon atoms (e.g., isohexadecane), benzoate esters, aliphatic esters, noncomodogenic esters, volatile silicone compounds (e.g., cyclomethicone), and volatile silicone substitutes. Examples of benzoate esters include C12C15 alkyl benzoate, isostearyl benzoate, 2-ethyl hexyl benzoate, dipropylene glycol benzoate, octyldodecyl benzoate, stearyl benzoate, and behenyl benzoate. Examples of aliphatic esters include C12C15 alkyl octonoate and dioctyl maleate. Examples of noncomodogenic esters include isononyl isononanoate, isodecyl isononanoate, diisostearyl dimer dilinoleate, arachidyl propionate, and isotridecyl isononanoate. Examples of volatile silicone substitutes include isohexyl decanoate, octyl isononanoate, isononyl octanoate, and diethylene glycol di octanoate.

[0162] Exemplary plant (vegetable) oils include, but are not limited to, olive oil, canola oil, coconut oil, rapeseed oil, corn oil, cottonseed oil, peanut oil, saffron oil, safflower oil, sesame oil, soybean oil, palm oil, sunflower oil and any combination thereof.

[0163] Additional exemplary plant (vegetable) oils include nut oils, including, but not limited to, Almond oil, Beech nut oil, Brazil nut oil, Cashew oil, Hazelnut oil, Macadamia oil, Mongongo nut oil (or manketti oil), Pecan oil, Pine nut oil, Pistachio oil, Walnut oil, and Pumpkin seed oil.

[0164] Additional exemplary plant (vegetable) oils include citrus oils, including, but not limited to, grapefruit seed oil, lemon oil and orange oil.

[0165] Additional exemplary plant (vegetable) oils are derived from melon and gourd seeds and include, but are not limited to, Bitter gourd oil, from the seeds of Momordica charantia, Bottle gourd oil, extracted from the seeds of the Lagenaria siceraria, Buffalo gourd oil, from the seeds of the Cucurbita foetidissima, Butternut squash seed oil, from the seeds of Cucurbita moschata, Egusi seed oil, from the seeds of Cucumeropsis mannii naudin, Pumpkin seed oil, and Watermelon seed oil, pressed from the seeds of Citrullus vulgaris.

[0166] Additional exemplary plant (vegetable) oils include, but are not limited to, Agai oil, Black seed oil, Blackcurrant seed oil, Borage seed oil, Evening primrose oil, Flaxseed oil (called also linseed oil), Amaranth oil, Apricot oil, Apple seed oil, Argan oil, Avocado oil, Babassu oil, Ben oil, Borneo tallow nut oil, Cape chestnut oil, Carob pod oil (Algaroba oil), Cocoa butter, Cocklebur oil, Cohune oil, Coriander seed oil, Date seed oil, Dika oil, False flax oil, Grape seed oil, Hemp oil, Kapok seed oil, Kenaf seed oil, Lallemantia oil, Mafura oil, Manila oil, Meadowfoam seed oil, Mustard oil Niger seed oil, Nutmeg butter, Okra seed oil, Papaya seed oil, Perilla seed oil, Persimmon seed oil, Pequi oil, Pili nut oil, Pomegranate seed oil, Poppyseed oil, Pracaxi oil, Prune kernel oil, Quinoa oil, Ramtil oil, Rice bran oil, Royle oil, Sacha inchi oil, Sapote oil, Seje oil, Shea butter, Taramira oil, Tea seed oil (Camellia oil), Thistle oil, Tigemut oil (or nut-sedge oil), Tobacco seed oil, Tomato seed oil, and Wheat germ oil.

[0167] Any of the mineral and / or plant oils can be used per se or as a modified form thereof.

[0168] According to exemplary embodiments, the composition further comprises an extract or an oil derived from a plant of the Lamiaceae family (e.g. mint, rosemary, sage, oregano or basil).

[0169] In further embodiments, the composition further comprises at least one of thymol, carvacrol, eugenol, cinnamaldehyde, limonene, myrcene, germacrene, pinene, cymene, ocimene, terpinene, caryophyllene and / or bisabolene.

[0170] In some of any of the embodiments described herein, a combination of two or more agents are included in the composition, in addition to the modified BSF oil.

[0171] In some of any of the embodiments described herein, the agent that is included in the composition together with the modified BSF oil, provides an additive effect.

[0172] As used herein, the term “additive effect” refers to a combined effect of two or more agents which is equal to the sum of the individual effects of each agent.

[0173] In some of any of the embodiments described herein, the agent that is included in the composition together with the modified BSF oil, provides a synergistic effect.

[0174] As used herein, the term “synergistic effect” refers to a combined effect of two or more agents which is greater than the sum of the individual effects of each agent. Synergy can be determined by methods well-known in the art, for example, using isobolograms.

[0175] The present inventors have conceived that an extract or an oil derived from a plant of the Lamiaceae family (e.g. mint, rosemary, sage, oregano or basil), when combined with monoglycerides, for example, in a form of a monoglyceride-enriched oil (which can be a plant oil and / or an animal oil and / or a mineral oil, and which can be unmodified or modified, e.g., a BSF oil extract as described herein and / or a modified BSF oil as described herein, and / or any other monoglyceride-enriched oil or extract), provide at least additive and possibly synergistic effect.

[0176] According to an aspect of some embodiments of the present invention there is provided a composition that comprises a monoglyceride-enriched oil, as described herein, and a plant oil or extract derived from a Lamiaceae plant, as described herein. In some embodiments of this aspect of the present invention the plant oil or extract acts in synergy with the monoglyceride-enriched oil in treating and / or preventing inflammation and / or microbial infection and / or in preventing biofilm formation and / or in any of the other methods and uses as described herein.

[0177] A synergistic effect between two agents allows using one or both agents in a sub- therapeutically effective amount, compared to each agent when used alone.

[0178] According to some of any of the embodiments of this aspect of the invention, an amount of the monoglyceride-enriched oil and / or an amount of the plant oil or extract in the composition is no more than 75 % by weight of its therapeutically effective amount when used as a single agent.

[0179] The composition according to this aspect of the present invention can further comprise a carrier, which can be a pharmaceutically acceptable carrier and / or an edible carrier, as described herein in any of the respective embodiments and any combination thereof, rendering the composition a pharmaceutical composition and / or an edible composition.

[0180] Any of the modified BSF oil extract and / or the edible compositions as described herein can be beneficially form a part of an edible product, and can be used in the manufacturing of an edible product.

[0181] Herein, an edible product encompasses any product that can be orally consumed by a subject, and / or which may serve as a food, a drink or feed product (whether consumed orally or otherwise).

[0182] As used herein, the phrase “food or feed product” describes an edible product consisting essentially of protein, carbohydrate and / or fat, which is used in the body of an organism to sustain growth, repair vital processes and to furnish energy. Food products may also contain supplementary substances such as minerals, vitamins and condiments. See Merriam-Webster's Collegiate Dictionary, 10th Edition, 1993. The phrase “food product” as used herein further includes a beverage adapted for human or animal consumption.

[0183] A food product can also include additional additives such as, for example, antioxidants, sweeteners, flavorings, colors, preservatives, enzymes, nutritive additives such as vitamins and minerals, emulsifiers, pH control agents such as acidulants, hydrocolloids, antifoams and release agents, flour improving or strengthening agents, raising or leavening agents, gases and chelating agents, the utility and effects of which are well-known in the art.

[0184] An edible product can also be a supplemental food or feed product, which provides a beneficial effect other than sustaining growth, repairing vital processes and furnishing energy, for example, an antimicrobial activity, an anti-inflammatory activity, an anti-biofilm (antifouling) activity and / or performance-enhancing activity, as described in further detail hereinafter. According to an aspect of some embodiments of the present invention there is provided an edible product comprising the modified BSF oil extract as described herein in any of the respective embodiments, or a composition (e.g., an edible composition) as described herein in any of the respective embodiments. The edible product can be a food, a drink or feed product or a supplemental food or feed product, as described herein, for animal subjects as described herein.

[0185] The animal feeds or feed supplement may comprise additional edible materials including for example crude protein, crude fat, carbohydrates, polysaccharides, starch, crude fibers, ash, minerals, trace elements, vitamins, fatty acids, proteins, peptides (other than those specifically described herein), amino acids, herbs, lipids, antioxidants, carotenoids, tocopherols, tocotrienols, phytosterols, polyphenols, bioflavonoids and / or dietary fiber.

[0186] Animal feeds, as well as most foods, may further include one or more components selected from a carbohydrate-containing substance, a protein-containing substance, and a lipid-containing substance, so the feeds of the invention may contain one or more of these components, preferably a combination of all of these components.

[0187] Suitable starch-bearing feed / food components may for example be derived from grains, e.g. selected from the group consisting of corn, soybean, wheat, sorghum, barley, oat, and mixtures thereof. Examples of suitable starch-bearing substances include, but are not limited to, corn flour, ground corn, soybean flour, wheat flour, ground oat flour, wheat middlings, soybean meal, corn grit, and mixtures thereof.

[0188] Crude protein-bearing substances include, but are not limited to, a BSF protein extract (modified and / or unmodified), a fish meal, dried whey, a soybean meal, and mixture thereof can be used. Other suitable protein-bearing substances include, but are not limited to, soybean protein concentrate, soy flour, blood meal, plasma protein, dried skim milk, whey protein concentrate, canola meal, corn gluten meal, wheat gluten meal, yeast, sunflower meal, and mixtures thereof.

[0189] Suitable fat-containing substances (not including the modified BSF oil extracts described herein) include, but are not limited to, lard, tallow, soybean oil, lecithin, coconut oil, whey-fat blend, and mixtures thereof.

[0190] The animal feeds or feed supplement may comprise one or more of a palatability enhancer and a humectant, including any combination thereof.

[0191] Examples of palatability enhancers include, but are not limited to metal pyrophosphate, 2- methyl furan, 2-methyl 10 pyrrole, dimethyl disulfide. Exemplary humectants include, but are not limited to propylene glycol, glycerin, corn syrup and a mineral salt.

[0192] The animal feed or feed supplement may be suitable for any animal including for example for a companion animal, including a cat, dog, rabbit or bird, hi another embodiment, the feed is a fish food including, shrimp such as white leg shrimp, tuna, cod, a farmed marine organism, a farmed fresh water organism, turbot, salmon and carp.

[0193] According to another embodiment, the animal is a livestock food and further comprises plant biomass (e.g. vegetable biomass).

[0194] Non-limiting examples of suitable livestock animals may include chicken, pigs, cows, horses, goats, sheep, llamas and alpacas.

[0195] According to some of any of the embodiments described herein, an amount of the modified BSF oil extract of the present embodiments, when present in the edible product as described herein is in a range of from 0.001% to 1 % by weight of the total weight of the product, or from 0.01 to 1 %, or from 0.001 to 0.1 %, or from 0.01 to 0.1 %, or from 0.1 to 1 %, by weight of the total weight of the product, including any intermediate values and subranges therebetween.

[0196] According to some of any of the embodiments described herein, an amount of the modified BSF oil extract of the present embodiments, when present in the edible product as described herein is lower by at least 25 %, or by at least 50 %, or by at least 75 %, or by at least 100 %, or by at least 200 %, of an amount of unmodified BSF oil extract, when added to the edible product for providing a beneficial effect as described herein.

[0197] According to additional embodiments of the present inventions, the modified BSF oil extract as described herein, any of the compositions as described herein or any of the edible products as described herein are usable, or are for use, in treating or preventing inflammation (an inflammatory disease or disorder) and / or microbial infection and / or biofilm formation in a subject.

[0198] The subject is an animal subject and include, for example, a human being, companion animals (e.g., pets and equine), farm animals (e.g., broilers, layers, turkeys, swine), fish and crustaceans, and any other subject as described herein.

[0199] According to an aspect of some embodiments of the present invention there is provided a method of treating or preventing inflammation (an inflammatory disease or disorder) in a subject in need thereof, which is effected by orally administering to the subject an effective amount of the modified BSF oil, or the composition, or the edible product, as these are described herein.

[0200] Examples of inflammatory diseases and disorders include inflammatory bowel diseases (IBDs), which are severe gastrointestinal disorders characterized by intestinal inflammation and tissue remodeling, that increase in frequency and may prove disabling for patients. The major forms of IBD, ulcerative colitis (UC) and Crohn's disease are chronic, relapsing conditions that are clinically characterized by abdominal pain, diarrhea, rectal bleeding, and fever

[0201] Thus, according to another aspect of the present invention, there is provided a method of treating or preventing an inflammatory disease in a subject comprising providing a therapeutically effective amount of the animal feed described herein, the BSF oil extract described herein or the modified BSF oil extract described herein to the subject, thereby treating or preventing the inflammatory disease of the subject.

[0202] As used herein, the term “subject” includes mammals, including human beings, companion animals, livestock animals, at any age which suffer from the pathology. Those in need of treatment may include individuals already having IBD, as well as those at risk of having, or who may ultimately acquire the disease. The need for treatment is assessed, e.g., by the presence of one or more risk factors associated with the development of IBD, the presence or progression of IBD, or likely receptiveness to treatment of a subject having IBD. For example, “treating” IBD may encompass reducing or eliminating associated symptoms, and does not necessarily encompass the elimination of the underlying disease etiology, e.g., a genetic instability locus.

[0203] According to an aspect of some embodiments of the present invention there is provided a method of treating or preventing a disease or disorder associated with a pathogenic microorganism in a subject in need thereof, which is effected by orally administering to the subject an effective amount of an effective amount of the modified BSF oil, or the composition, or the edible product, as these are described herein.

[0204] Herein, the phrase “pathogenic microorganism” is used to describe any microorganism which can cause a disease or disorder in a higher organism, such as the animated subjects as described herein. The pathogenic microorganism may belong to any family of organisms such as, but not limited to prokaryotic organisms, eubacterium, archaebacterium, eukaryotic organisms, virus, yeast, fungi, algae, protozoan, and other parasites.

[0205] According to a particular embodiment, the disease is associated with a gram positive bacteria (e.g. Streptococcus agalactiae infection).

[0206] According to a particular embodiment, the disease is associated with Escherichia coli infection.

[0207] According to a particular embodiment, the disease is associated with a Aspergillus, niger fungal infection or toxins produced by A. niger.Non-limiting examples of pathogenic microorganism include Plasmodium falciparum and related malaria-causing protozoan parasites, Acanthamoeba and other free-living amoebae, Aeromonas hydrophila, Anisakis and related worms, and further include, but not limited to Acinetobacter baumanii, Ascaris lumbricoides, Bacillus cereus, Brevundimonas diminuta, Campylobacter jejuni, Clostridium botulinum, Clostridium perfringens, Cryptosporidium parvum, Cyclospora cayetanensis, Diphyllobothrium, Entamoeba histolytica, certain strains of Escherichia coli, Eustrongylides, Giardia lamblia, Klebsiella pneumoniae, Listeria monocytogenes, Nanophyetus, Plesiomonas shigelloides, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella, Serratia odorifera, Shigella, Staphylococcus aureus, Stenotrophomonas maltophilia, Streptococcus, Trichuris trichiura, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus and other vibrios, Yersinia enterocolitica, Yersinia pseudotuberculosis and Yersinia kristensenii.

[0208] Other pathogens include Strep, pyogenes (Group A), Strep, pneumoniae, Strep. GpB, Strep, viridans, Strep. GpD (Enterococcus), Strep. GpC and GpG, Staph, aureus, Staph, epidermidis, Bacillus subtilis, Bacillus anthracis, Listeria monocytogenes, Anaerobic cocci, Clostridium spp., Actinomyces spp, Escherichia coli, Enterobacter aerogenes, Kiebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia stuartii, Serratia marcescens, Citrobacter freundii, Salmonella typhi, Salmonella paratyphi, Salmonella typhi murium, Salmonella virchow, Shigella spp., Yersinia enterocolitica, Acinetobacter calcoaceticus, Flavobacterium spp., Haemophilus influenzae, Pseudomonas aeruginosa, Campylobacter jejuni, Vibrio parahaemolyticus, Brucella spp., Neisseria meningitidis, Neisseria gonorrhoea, Bacteroides fragilis, Fusobacterium spp., Mycobacterium tuberculosis (including MDR and XDR strains from hospital origins isolated from patients) and Mycobaterium smegmatis.

[0209] Accordingly, a condition (a disease or disorder) associated with a pathogenic microorganism describes an infectious condition that results from the presence of the microorganism in a subject. The infectious condition can be, for example, a bacterial infection, a fungal infection, a protozoal infection, a viral infection, and the like, collectively referred to herein as “microbial infection”.

[0210] Some higher forms of microorganisms are pathogenic per-se, and other harbor lower forms of pathogenic bacteria, thus present a medical threat expressed in many medical conditions, such as, without limitation, actinomycosis, anthrax, aspergillosis, bacteremia, bacterial skin diseases, bartonella infections, botulism, brucellosis, burkholderia infections, Campylobacter infections, candidiasis, cat-scratch disease, chlamydia infections, cholera, Clostridium infections, coccidioidomycosis, cryptococcosis, dermatomycoses, dermatomycoses, diphtheria, ehrlichiosis, epidemic louse borne typhus, Escherichia coli infections, fusobacterium infections, gangrene, general infections, general mycoses, gram-negative bacterial infections, Gram-positive bacterial infections, histoplasmosis, impetigo, kiebsiella infections, legionellosis, leprosy, leptospirosis, listeria infections, Lyme disease, maduromycosis, melioidosis, mycobacterium infections, mycoplasma infections, necrotizing fasciitis, nocardia infections, onychomycosis, ornithosis, pneumococcal infections, pneumonia, pseudomonas infections, Q fever, rat-bite fever, relapsing fever, rheumatic fever, rickettsia infections, Rocky-mountain spotted fever, salmonella infections, scarlet fever, scrub typhus, sepsis, sexually transmitted bacterial diseases, staphylococcal infections, streptococcal infections, surgical site infection, tetanus, tick-borne diseases, tuberculosis, tularemia, typhoid fever, urinary tract infection, vibrio infections, yaws, yersinia infections, Yersinia pestis plague, zoonoses and zygomycosis.

[0211] Additional microbial infections include those caused by bacterial strains that include Gram-positive bacteria such as Strep, pyogenes (Group A), Strep, pneumoniae, Strep. GpB, Strep, viridans, Strep. GpD -(Enterococcus), Strep. GpC and GpG, Staph, aureus, Staph, epidermidis, Bacillus subtilis, Bacillus anthraxis, Listeria monocytogenes, Anaerobic cocci, Clostridium spp., and Actinomyces spp,' and Gram-negative bacteria such as Escherichia coli, Enterobacter aerogenes, Kiebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia stuartii, Serratia marcescens, Citrobacter freundii, Salmonella typhi, Salmonella paratyphi, Salmonella typhi murium, Salmonella virchow, Shigella spp., Yersinia enterocolitica, Acinetobacter calcoaceticus, Flavobacterium spp., Haemophilus influenzae, Pseudomonas aueroginosa, Campylobacter jejuni, Vibrio parahaemolyticus, Brucella spp., Neisseria meningitidis, Neisseria gonorrhoea, Bacteroides fragilis, and Fusobacterium spp.

[0212] Representative examples of pathogenic parasites and protozoa include, but are not limited to, various types of amoeba, Leishmania spp, Plasmodium falciparum Trypanosoma cruzi (causing Chagas' disease), Trypanosoma bucei (causing "sleeping sickness"), Plasmodium vivax (causing malaria), Cryptosporidium parvum (causing cryptosporidiosis), Cyclospora cayetanensis, Giardia lamblia (causing giardiasis) and many others.

[0213] Representative examples of pathogenic fungi include, without limitation, fungi of the genus Absidia: Absidia corymbifera,' genus Ajellomyces: Ajellomyces capsulatus, Ajellomyces dermatitidis,' genus Arthroderma: Arthroderma benhamiae, Arthroderma fulvum, Arthroderma gypseum, Arthroderma incurvatum, Arthroderma otae, Arthroderma vanbreuseghemii,' genus Aspergillus: Aspergillus flavus, Aspergillus fumigatus, Aspergillus niger, genus Blastomyces: Blastomyces dermatitidis,' genus Candida: Candida albicans, Candida glabrata, Candida guilliermondii, Candida krusei, Candida parapsilosis, Candida tropicalis, Candida pelliculosa,' genus Cladophialophora: Cladophialophora carrionii,' genus Coccidioides: Coccidioides immitis,' genus Cryptococcus: Cryptococcus neoformans,' genus Cunninghamella: Cunninghamella sp.,' genus Epidermophyton: Epidermophyton floccosunv, genus Exophiala: Exophiala dermatitidis,' genus Filobasidiella: Filobasidiella neoformans,' genus Fonsecaea: Fonsecaea pedrosoi,' genus Fusarium: Fusarium solani,' genus Geotrichum: Geotrichum candidum,' genus Histoplasma: Histoplasma capsulatunr, genus Hortaea: Hortaea werneckii,' genus Issatschenkia: Issatschenkia orientalis,' genus Madurella: Madurella grisae,' genus Malassezia: Malassezia furfur, Malassezia globosa, Malassezia obtusa, Malassezia pachydermatis, Malassezia restricta, Malassezia slooffiae, Malassez.ia sympodialis: genus Microsporum'. Microsporum canis, Microsporum fulvum, Microsporum gypseum,' genus Mucor. Mucor circinelloides,' genus Nectria'. Nectria haematococca,' genus Paecilomyces'. Paecilomyces variolii,' genus Paracoccidioides'. Paracoccidioides brasiliensis,' genus Penicillium'. Penicillium marneffei,' genus Pichia, Pichia anomala, Pichia guilliermondii,' genus Pneumocystis'. Pneumocystis carinii: genus Pseudallescheria'. Pseudallescheria boydii,' genus Rhizopus'. Rhizopus oryz.ae: genus Rhodotorula'. Rhodotorula rubra,' genus Scedosporium'. Scedosporium apiospermum,' genus Schizophyllum'. Schizophyllum commune,' genus Sporothrix'. Sporothrix schenckii,' genus Trichophyton'. Trichophyton mentagrophytes, Trichophyton rubrum, Trichophyton verrucosum, Trichophyton violaceum,' and of the genus Trichosporon'. Trichosporon asahii, Trichosporon cutaneum, Trichosporon inkin, Trichosporon mucoides.

[0214] According to some embodiments, a condition associated with a pathogenic microorganism includes biofilm formation, and the method or use as described herein is for preventing, retarding or inhibiting biofilm formation and / or disrupting or reducing a load of a formed biofilm.

[0215] In some of any of the embodiments, the biofilm is a bacterial biofilm formed by a pathogenic bacterium such as, but are not limited to, Pseudomonas, Escherichia, Klebsiella, Enterobacter, Acinetobacter, Serratia, Haemophilus, Chlamydia, Salmonella, Arsenophonus , Cosenzaea, Moraxella, Brucella, Bordetella, Vibrio, Campylobacter, Legionella, Francisella, Photorhabdus, Neisseria, Proteus, Shigella, Edwardsiella, Plesiomonas, Aeromonas, Alcaligenes, Providencia, Yersinia, Staphylococcus, Bacillus, Listeria, Streptococcus, Gardnerella, Cronobacter, Enterococcus, Clostridium, Corynebacterium, Mycobacterium, Micrococcus, Hafnia, Morganella, Pasteurella, Mycoplasma, Ureaplasma, Coxiella, Borrelia, Aerococcus, Lactococcus, Actinomyces, Rhodococcus, Propionibacterium, Bartonella, Lactobacillus, Bifidobacterium, Rothia, Porphyromonas, Prevotella, Bacteroides, Fusobacterium, Megasphaera, Acidaminococcus, Deinococcus, Helicobacter, Burkholderia, Campylobacter, Veilonella, Norcardia, Treponema, Leptospira, Micropolyspora and Thermoactinomyces .

[0216] In some embodiments, the Gram-negative biofilm-forming bacteria may be selected from the group of pathogenic Gram-negative biofilm-forming bacteria such as, but not limited to, at least one of Pseudomonas, Escherichia, Klebsiella, Enterobacter, Acinetobacter, Serratia, Haemophilus, Chlamydia, Salmonella, Arsenophonus, Veilonella, Cosenzaea, Moraxella, Brucella, Bordetella, Vibrio, Campylobacter, Legionella, Francisella, Prevotella, Acidaminococcus, Megasphaera, Fusobacterium, Photorhabdus, Neisseria, Proteus, Shigella, Bacteroides, Porphyromonas, Edwardsiella, Plesiomonas, Aeromonas, Alcaligenes, Providencia, Pasteurella, Hafnia, Morganella, Mycoplasma, Ureaplasma, Coxiella, Leptospira, Treponema, Borrelia, Aerococcus, Lactococcus, Bartonella, Yersinia, Deinococcus, Helicobacter, Burkholderia, Campylobacter, Micropolyspora and Thermoactinomyces .

[0217] In some embodiments, the Gram-positive biofilm-forming bacteria may be selected from the group of pathogenic Gram-positive biofilm-forming bacteria such as, but not limited to, at least one of Staphylococcus, Bacillus, Listeria, Streptococcus, Gardnerella, Cronobacter, Enterococcus, Rothia, Lactobacillus, Clostridium, Corynebacterium, Mycobacterium, Norcardia, Rhodococcus, Propionibacterium, Bifidobacterium, Actinomyces, and Micrococcus .

[0218] In some embodiment, the biofilm is a fungal biofilm formed of a pathogenic fungus such as, but not limited to, Candida, Aspergillus, Fusarium, Cryptococcus, Rhizopus, Trichophyton, Malassezia and Pneumocystis.

[0219] In some embodiments, inhibiting, reducing and / or retarding biofilm formation as described herein is reflected by reducing biofilm load in a subject in need thereof by at least 20 %, at least 30 %, at least 40 %, at least 50 %, at least 60 %, at least 70 %, at least 80 %, at least 90 %, including any value therebetween, compared to the same subject in need thereof prior to administration of the modified BSF oil extract, the composition or the edible product.

[0220] In some of any of these embodiments, the modified BSF oil extract or the composition is administered to the subject as a part of a food supplement or a feed supplement, as described herein.

[0221] According to additional embodiments of the present inventions, the modified BSF oil extract as described herein, any of the compositions as described herein or any of the edible products as described herein are usable, or are for use as production performance enhancers, for reducing a mortality, increasing an average body weight and / or improving a feed conversion ratio in a population comprising a plurality of subjects, as described herein. In addition, the modified BSF oil extract may be useful for reducing antibiotic intake, reducing a number of days to reach target body weight, reducing a number of sick days until marketing, reduction in diarrhea days until weaning.

[0222] According to an aspect of some embodiments of the present invention there is provided a method of reducing a mortality, increasing an average body weight and / or improving a feed conversion ratio in a population comprising a plurality of subjects, the method comprising treating the plurality of subjects, e.g., by orally administering to the subjects, with the modified BSF oil extract, or the composition or the edible product as described herein in any of the respective embodiments.

[0223] In some of these embodiments, the modified BSF oil extract is administered to the subjects as a feed or food supplement. Exemplary subjects include, but are not limited to, broilers, turkeys, swine, shrimps and prawns, although any other subjects such as described herein are contemplated.

[0224] By “reducing a mortality” it is meant that an average mortality in the population of subjects is reduced by at least 1.5 %, preferably by at least 2 %, or by at least 2.5 %, or by at least 3 %, or by at least 3.5 %, compared to untreated population of the same subjects.

[0225] By “improving feed conversion ratio” or “improving PCR” it is meant improving the average ratio of the feed weight to the body mass gained by the animal subject by at least 1.5 %, preferably by at least 2 %, or by at least 2.5 %, or by at least 3 %, or by at least 3.5 %, compared to the average ratio in untreated population of the same subjects.

[0226] By “increasing body weight” it is meant that an average raw body weight or an average carcass weight per production day is increased by at least 1.5 %, preferably by at least 2 %, or by at least 2.5 %, or by at least 3 %, or by at least 3.5 %, compared to an untreated population of the same subjects.

[0227] By “reducing antibiotic intake” it is meant that an average intake in the population of subjects is reduced by at least 1.5 %, preferably by at least 2 %, or by at least 2.5 %, or by at least 3 %, or by at least 3.5 %, compared to untreated population of the same subjects.

[0228] By “reducing a number of days to reach target body weight” it is meant that an average intake number of days to reach target body weight is reduced by at least 1.5 %, preferably by at least 2 %, or by at least 2.5 %, or by at least 3 %, or by at least 3.5 %, compared to untreated population of the same subjects.

[0229] By “reducing a number of sick days until marketing” it is meant that an average number of sick days until marketing is reduced by at least 1.5 %, preferably by at least 2 %, or by at least 2.5 %, or by at least 3 %, or by at least 3.5 %, compared to untreated population of the same subjects.

[0230] By “reduction in diarrhea days until weaning” it is meant that an average number of diarrhea days until weaning is reduced by at least 1.5 %, preferably by at least 2 %, or by at least 2.5 %, or by at least 3 %, or by at least 3.5 %, compared to untreated population of the same subjects.

[0231] In any of the methods and uses described herein, the modified BSF oil extract can be provided to the subject per se, or in a composition comprising same. The composition can be an edible composition, which further comprises an edible carrier, or a pharmaceutical composition where it is mixed with suitable carriers or excipients.

[0232] As used herein a "pharmaceutical composition" refers to a preparation of one or more of the active ingredients described herein (e.g., the modified BSF oil as described herein, and optionally as additional active agent as described herein) with other chemical components such as physiologically suitable carriers and excipients. The purpose of a pharmaceutical composition is to facilitate administration of a compound to an organism.

[0233] Herein, the phrases "physiologically acceptable carrier" and "pharmaceutically acceptable carrier" which may be interchangeably used refer to a carrier or a diluent that does not cause significant irritation to an organism and does not abrogate the biological activity and properties of the administered compound. An adjuvant is included under these phrases.

[0234] Herein the term "excipient" refers to an inert substance added to a pharmaceutical composition to further facilitate administration of an active ingredient. Examples, without limitation, of excipients include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils and polyethylene glycols.

[0235] Techniques for formulation and administration of drugs may be found in “Remington’s Pharmaceutical Sciences,” Mack Publishing Co., Easton, PA, latest edition, which is incorporated herein by reference.

[0236] Suitable routes of administration may, for example, include oral, rectal, transmucosal, especially transnasal, intestinal or parenteral delivery, including intramuscular, subcutaneous and intramedullary injections as well as intrathecal, direct intraventricular, intracardiac, e.g., into the right or left ventricular cavity, into the common coronary artery, intravenous, intraperitoneal, intranasal, or intraocular injections.

[0237] Pharmaceutical compositions of some embodiments of the invention may be manufactured by processes well known in the art, e.g., by means of conventional mixing, dissolving, granulating, dragee-making, levigating, emulsifying, encapsulating, entrapping or lyophilizing processes.

[0238] Pharmaceutical compositions for use in accordance with some embodiments of the invention thus may be formulated in conventional manner using one or more physiologically acceptable carriers comprising excipients and auxiliaries, which facilitate processing of the active ingredients into preparations which, can be used pharmaceutically. Proper formulation is dependent upon the route of administration chosen.

[0239] For injection, the active ingredients of the pharmaceutical composition may be formulated in aqueous solutions, preferably in physiologically compatible buffers such as Hank’s solution, Ringer’s solution, or physiological salt buffer. For transmucosal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art.

[0240] For oral administration, the pharmaceutical composition can be formulated readily by combining the active compounds with pharmaceutically acceptable carriers well known in the art. Such carriers enable the pharmaceutical composition to be formulated as tablets, pills, dragees, capsules, liquids, gels, syrups, slurries, suspensions, and the like, for oral ingestion by a patient. Pharmacological preparations for oral use can be made using a solid excipient, optionally grinding the resulting mixture, and processing the mixture of granules, after adding suitable auxiliaries if desired, to obtain tablets or dragee cores. Suitable excipients are, in particular, fillers such as sugars, including lactose, sucrose, mannitol, or sorbitol; cellulose preparations such as, for example, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, sodium carbomethylcellulose; and / or physiologically acceptable polymers such as polyvinylpyrrolidone (PVP). If desired, disintegrating agents may be added, such as cross-linked polyvinyl pyrrolidone, agar, or alginic acid or a salt thereof such as sodium alginate.

[0241] Dragee cores are provided with suitable coatings. For this purpose, concentrated sugar solutions may be used which may optionally contain gum arabic, talc, polyvinyl pyrrolidone, carbopol gel, polyethylene glycol, titanium dioxide, lacquer solutions and suitable organic solvents or solvent mixtures. Dyestuffs or pigments may be added to the tablets or dragee coatings for identification or to characterize different combinations of active compound doses.

[0242] Pharmaceutical compositions which can be used orally, include push-fit capsules made of gelatin as well as soft, sealed capsules made of gelatin and a plasticizer, such as glycerol or sorbitol. The push-fit capsules may contain the active ingredients in admixture with filler such as lactose, binders such as starches, lubricants such as talc or magnesium stearate and, optionally, stabilizers. In soft capsules, the active ingredients may be dissolved or suspended in suitable liquids, such as fatty oils, liquid paraffin, or liquid polyethylene glycols. In addition, stabilizers may be added. All formulations for oral administration should be in dosages suitable for the chosen route of administration.

[0243] For buccal administration, the compositions may take the form of tablets or lozenges formulated in conventional manner.

[0244] Pharmaceutical compositions suitable for use in context of some embodiments of the invention include compositions wherein the active ingredients are contained in an amount effective to achieve the intended purpose. More specifically, a therapeutically effective amount means an amount of active ingredients effective to prevent, alleviate or ameliorate symptoms of a disorder (e.g., inflammatory disease) or prolong the survival of the subject being treated.

[0245] Determination of a therapeutically effective amount is well within the capability of those skilled in the art, especially in light of the detailed disclosure provided herein.

[0246] For any preparation used in the methods of the invention, the therapeutically effective amount or dose can be estimated initially from in vitro and cell culture assays. For example, a dose can be formulated in animal models to achieve a desired concentration or titer. Such information can be used to more accurately determine useful doses in humans.

[0247] Toxicity and therapeutic efficacy of the active ingredients described herein can be determined by standard pharmaceutical procedures in vitro, in cell cultures or experimental animals. The data obtained from these in vitro and cell culture assays and animal studies can be used in formulating a range of dosage for use in human. The dosage may vary depending upon the dosage form employed and the route of administration utilized. The exact formulation, route of administration and dosage can be chosen by the individual physician in view of the patient's condition. (See e.g., Fingl, et al., 1975, in "The Pharmacological Basis of Therapeutics", Ch. 1 p.1).

[0248] Dosage amount and interval may be adjusted individually to provide tissue levels of the active ingredient are sufficient to induce or suppress the biological effect (minimal effective concentration, MEC). The MEC will vary for each preparation, but can be estimated from in vitro data. Dosages necessary to achieve the MEC will depend on individual characteristics and route of administration. Detection assays can be used to determine plasma concentrations.

[0249] Depending on the severity and responsiveness of the condition to be treated, dosing can be of a single or a plurality of administrations, with course of treatment lasting from several days to several weeks or until cure is effected or diminution of the disease state is achieved.

[0250] The amount of a composition to be administered will, of course, be dependent on the subject being treated, the severity of the affliction, the manner of administration, the judgment of the prescribing physician, etc.

[0251] According to exemplary embodiments, the pharmaceutical composition is formulated for oral administration.

[0252] Compositions of some embodiments of the invention may, if desired, be presented in a pack or dispenser device, such as an FDA approved kit, which may contain one or more unit dosage forms containing the active ingredient. The pack may, for example, comprise metal or plastic foil, such as a blister pack. The pack or dispenser device may be accompanied by instructions for administration. The pack or dispenser may also be accommodated by a notice associated with the container in a form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals, which notice is reflective of approval by the agency of the form of the compositions or human or veterinary administration. Such notice, for example, may be of labeling approved by the U.S. Food and Drug Administration for prescription drugs or of an approved product insert. Compositions comprising a preparation of the invention formulated in a compatible pharmaceutical carrier may also be prepared, placed in an appropriate container, and labeled for treatment of an indicated condition, as is further detailed above. As used herein the term “about” refers to ± 10 % or ± 5 %.

[0253] The terms “comprises”, “comprising”, “includes”, “including”, “having” and their conjugates mean “including but not limited to”.

[0254] The term “consisting of’ means “including and limited to”.

[0255] The term “consisting essentially of’ means that the composition, method or structure may include additional ingredients, steps and / or parts, but only if the additional ingredients, steps and / or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

[0256] As used herein, the singular form “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a compound” or “at least one compound” may include a plurality of compounds, including mixtures thereof.

[0257] Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0258] Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. The phrases “ranging / ranges between” a first indicate number and a second indicate number and “ranging / ranges from” a first indicate number “to” a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.

[0259] As used herein the term “method” refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

[0260] The term “treating” refers to inhibiting, preventing or arresting the development of a pathology (disease, disorder or condition) and / or causing the reduction, remission, or regression of a pathology. Those of skill in the art will understand that various methodologies and assays can be used to assess the development of a pathology, and similarly, various methodologies and assays may be used to assess the reduction, remission or regression of a pathology.

[0261] As used herein, the term “preventing” refers to keeping a disease, disorder or condition from occurring in a subject who may be at risk for the disease, but has not yet been diagnosed as having the disease.

[0262] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

[0263] Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.

[0264] EXAMPLES

[0265] Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments of the invention in a non-limiting fashion.

[0266] EXAMPLE 1

[0267] General Design

[0268] The present inventors have conceived of producing a Black Soldier Fly Monoglyceride enriched oil (BSFMO), which can be advantageous utilized in various applications, as detailed herein, have studied various methodologies for obtaining such a modified BSF oil and envision several applications for said modified oil.

[0269] To this end, the present inventors have studied the chemical composition of BSF larvae oil extract.

[0270] Herein throughout, the BSF oil extract refers to an extract derived from the black soldier fly (or larvae thereof) which is composed mainly of lipids (oily or fatty substances such as free fatty acids (FFAs), monoacylglycerides (monoglycerids; MAGs), diacylglycerides (diglycerids; DAGs), triacylglycerides (triglycerids; TAGs)) and is the naturally occurring amount of lipids present in the fly or larvae. The BSF oil extract is also referred to herein simply as BSF oil.

[0271] The raw BSF oil was characterized by determining the division of the lipids between monoglycerides, diglycerides, triglycerides, and free fatty acids and the glycerol content and its acid value (see, Table 1). The composition of the fatty acids that make up the mono, di and triglycerides was also determined (see, Table 2).

[0272] The glycerol content, determined according to NF EN 14105, was less than 0.0005 gram / 100 gram.

[0273] The acid value of the raw BSF oil, determined according to NF EN ISO 660 and presented also as acid index denoted as Ai or IA, was 7.99 mgKOH / gram for supplier 1 and 0.44 mgKOH / gram for supplier 2. The BSF oil of supplier 1 required short path distillation before all experimental procedures. After short path distillation the acid value determined was 0.4 mgKOH / gram.

[0274] Fatty substances’ composition was determined using gas chromatography (GC) coupled with a flame ionization detector (FID, GC-FID). FFA, MAG, DAG and TAG contents were determined. Furthermore, MAGs, DAGs and TAGs were hydrolyzed to obtain the fatty acids that are contained in them, and the identity of these fatty acids was determined. All the methods used for hydrolysis and analysis are in common use and are known to someone skilled in the art.

[0275] Table 1 below presents the composition of the raw, unprocessed, BSF oil.

[0276] Table 1

[0277] As can be seen, the raw BSF oil is composed mainly of TAGs, which consists of more than 93% lipids.

[0278] Table 2 below present the fatty acid composition of raw, unprocessed, BSF oil Table 2

[0279] Most of the fatty acids in the unprocessed BSF oil are saturated (69.2% and 69.03% in the oils of suppliers 1 and 2 respectively). The majority of the fatty acids are of medium length, CIO to C16 (70% and 69.01% in the oils of suppliers 1 and 2 respectively). In both oils the most abundant fatty acid is lauric acid, C12:0 (41.3% and 42.94% in the oils of suppliers 1 and 2 respectively).

[0280] MAG-enriched BSF oil can be obtained from raw BSF oil by transesterification of the TAGs, which represent a major portion of the raw oil, and of DAGs, in the presence of glycerol, in accordance with the general synthetic procedure depicted in scheme 1 below. Scheme 1

[0281] Wherein x is an integer of at least 7, or at least 9, and y represents the number of hydrogen atoms on each carbon and depends on the saturation degree of each fatty acid residue in the triglyceride.

[0282] Typically, transesterifications are driven in the presence of a large excess of alcohol (e.g., glycerol, methanol, ethanol) to ensure the full and rapid conversion of the ester, in this case triglycerides. Following transesterification, one or two consecutive purification process(es) can be performed to remove the residual alcohol (e.g., glycerol) and isolate the fatty substances. Glycerol is the preferred alcohol in the transesterification of TAGs and DAGs, as the end results are MAGs.

[0283] The following examples describe optimization process parameters for the transesterification reaction which results in a modified BSF oil enriched by MAGs as described, e.g., in Scheme 1.

[0284] EXAMPLE 2

[0285] The proposed approach involves mixing the BSF oil with glycerol at various molar ratios to determine the optimum ratios that enable maximum MAG content with minimum glycerol content.

[0286] Transesterification was performed in the presence of different oil-to-glycerol (oil: glycerol) molar ratios (mol / mol) and using different catalysts (e.g., sodium methoxide, MeONa, 2.1-3 % molar ratio; or calcium oxide, CaO, 2.9 % molar ratio), while heating the reaction mixture for a specified duration. The composition of the modified oil was determined by GC-FID, as described hereinabove. For all experiments, 500 grams of raw BSF oil were used, and glycerol and catalyst amounts were calculated according to the desired ratio.

[0287] Trial #1 - a ratio of 1 :2 (oil: glycerol) was tested. Transesterification was performed on BSF oil (500 grams) in the presence of glycerol (124 grams), catalyzed by sodium methoxide (MeONa; 3 % molar ratio), at a temperature range of 160-205 °C under reduced pressure (<100 mb ar). The conversion was completed after 6 hours but the reaction was extended to 24 hours. The obtained product was a black solid with a foul odor. GC-FID of the resulting oil (535 grams) (see, Table 3 hereinbelow) indicates a MAG content of 45 %, glycerol content of 18%, DAGs 25% and TAGs 10% in the product.

[0288] Trial #2 - a ratio of 1 : 1.8 (oil: glycerol) was tested to evaluate the effect of a lower amount of residual glycerol, a constant temperature and a shorter reaction time on the resulting MAG content. Transesterification was performed on BSF oil (500 grams) in the presence of glycerol (111 grams) catalyzed by sodium methoxide MeONa (3% mol ratio), at a temperature of 180 °C for 5 hours under reduced pressure (<100 mbar), to provide a black solid with a foul odor.

[0289] GC-FID of the resulting sample (see, Table 3 hereinbelow) indicated that while the amount of glycerol slightly decreased and the % MAG remained a constant 45 %, and the DAG and TAG contents were higher compared to trial #1 and FFA % were lower.

[0290] Trial #3 - a ratio of 1 :3 (oil: glycerol) was tested. Transesterification was performed on BSF oil (500 grams) in the presence of glycerol (185 grams) catalyzed by MeONa (2.1 % molar ratio), at a temperature of 180 °C for 12.5 hours under reduced pressure (≤100 mbar), to provide a black solid with a foul odor. The conversion was completed after 4 hours but reaction was continued for 8 more hours. This progress did not significantly affect the results.

[0291] GC-FID of the resulting sample (575 grams, Table 3 hereinbelow) indicated that the amount of glycerol increased, while the MAG content was similar (44 % MAGs) compared with Trials #1, and #2. If purification steps can remove the glycerol from the reaction media, a mixture comprising 61 % MAGs can be obtained under these conditions (see, “Results [%] oil only” Table 3).

[0292] Trial #4 was performed to examine the effect of an equimolar oil:glycerol ratio on the composition of the sample following transesterification, and to test if another catalyst (calcium oxide, CaO) might prove more effective. Transesterification was performed on BSF oil (500 grams) in the presence of glycerol (62 grams) catalyzed by calcium oxide (CaO, 2.9 % mol ratio), at a temperature of 180 °C for 12 hours under reduced pressure (<100 mbar), to provide a black solid with a foul odor.

[0293] GC-FID of the resulting sample (475 grams) (see, Table 3 hereinbelow) indicated that because the initial amount of glycerol was lower, the MAG content in the resulting oil decreased as well.

[0294] Table 3 below presents the results obtained from GC-FID analyses of the products obtained in Trials #1-4, while presenting also the oil content (FFA, MAG, DAG, TAG and glycerol) when glycerol was integrated in the GC-FID chromatogram (“Results [%]”) and when it was not integrated (“Results [%] oil only”), and the final raw oil to product weight ratio (w / w).

[0295] As can be seen in Table 3, a 3: 1 glycero1:BSF oil molar ratio results with the best TAG transesterification outcome, yielding the highest % of MAG. However, it does result in the highest proportion of glycerol in the product. This glycerol should be eliminated or at least reduced in quantity in the post-transesterification product.

[0296] Table 3

[0297] EXAMPLE 3

[0298] Several trials were conducted to establish a method for removing glycerol from the modified BSF oil and improving the economic feasibility of the transesterification process. Shortening the duration of the reaction, as well as reducing reaction temperatures were tested. Trial #1 was performed to examine distillation. Transesterification of BSF oil was performed with 3: 1 mol ratio of glycerol:BSF oil, with MeONa as the catalyst (1.6 % mol ratio) at 140 °C under reduced pressure (<100 mbar). The resulting product was composed of 32 % glycerol and 38 % MAGs, that made up 55.2 % of the oils (glycerol excluded, see table 4).

[0299] Short path distillation'. This product was distilled twice in a short path distillation: distillation #1 : was performed at 130 °C under reduced pressure of 0.4 mbar. Distillation #2 was performed at 13° C under a reduced pressure of 0.2 mbar. Both distillation steps reduced glycerol content (see, Table 4 below) to 25.7 % and 4.5 % for distillation #1 and #2 respectively. However, MAGs were also removed from the distillate, leaving MAGs at only 35.5 % and 40.4 % of the total oil compounds for the two distillations, respectively. DAGs and FFAs were enriched in the oil compounds: from 31.3 % DAGs and 1.5 % FFA in the reaction product to 26.5 % DAGs and 26.4 % FFAs in distillate #1 and 37.5 % DAGs and 5.6 % FFAs in distillate #2 (see, Table 4). The loss of MAGs in the distillation required a different method to remove the glycerol.

[0300] Trisyl treatment. The reaction product was mixed with 1% (w / w) trisyl and 0.3 % (w / w) distilled water. The mixture was mixed at 180 °C for 1 hour and then filtered on Clarcel. The resulting product was almost entirely clear of glycerol (only 0.6 %) and was composed of 50.3 % MAGs, 34.5 % DAGs, 14.5 % TAGs and 0.8% FFA, a mixture similar to the reaction product (see, Table 4). Trial #2: This trial was carried out to test whether water could be used to remove the glycerol and whether the catalysis MeONa could be exchanged with NaOH. Transesterification was performed using glycerol :BSF oil at a 3: 1 ratio, with NaOH as the catalyst (4 % mol ratio) at 185 °C under reduced pressure (< 100 mbar). The resulting product was composed of 11 % glycerol, a significant improvement compared with all previous trials. MAG content was 27.7 %, making its % of all oil compounds 42.9 % (glycerol excluded, see, Table 4). This makes the reaction with NaOH under these conditions comparable to reactions with MeONa in terms of MAG production yields, while improving on glycerol leftover amounts.

[0301] Wash #1 : The reaction product was washed with 10 % (w / w) double distilled water at 80 °C for 8 hours. Then, the two phases (oil and water) were allowed to separate and the oily phase was collected. Glycerol content was slightly reduced to 10.3 %. MAGs were enriched to 47.9 % of all oily substances (see, Table 4 below). Interestingly, TAG content was significantly reduced by the wash, from 25.6 % of all oily compounds in the reaction product to 13.4 % of all oily compounds in the oily phase after the wash.

[0302] Wash #2: The oily phase of wash #1 was washed with 10 % (w / w) double distilled water at 80 °C for 8 hours. Then, the two phases (oil and water) were allowed to separate, and the oily phase was collected. Glycerol content were reduced to 8 %. MAG content was enriched to 51.5 % of all oily compounds (see, Table 4 below).

[0303] The reaction condition in trial #2, including the two washes, make an efficient method for BSF oil transesterification using a non-methanol production catalyst coupled with a cost effective method for glycerol removal, yielding a cost effective method for highly MAG enrichment of BSF oil.

[0304] Table 4

[0305] EXAMPLE 4

[0306] BSFMO was loaded on a powdered solid carrier (Attapulgite (Sunfed Ultra®, GeoHellas) to 35% w / w). The powder-loaded BSFMO is referred to herein as BSFPMO. A machine incorporating a rotating cylindrical chamber filled with a carrier powder in the chamber was used to load BSFMO on the carrier powder.

[0307] The BSFMO was sprayed on the powder via an injector placed inside the rotating chamber

[0308] In order to prevent temperature drop and solidification of the oil within the delivery and injection piping, both the oil and the apparatus was heated to at least 35 °C.

[0309] To improve flowability and prevent stickiness and caking of the oil-loaded powder, silica powder was added to the powdered carrier powder in an amount of up to 15 % of the weight of the powdered carrier.

[0310] EXAMPLE 5

[0311] Materials and Methods:

[0312] Anti-bacterial activity was tested in accordance with (Schumacher et al. 2018 Eur J Clin Microbiol Infect Dis.), with modifications.

[0313] Preparation ofMBSFL oil: 600gr of BSF oil were heated to 70°C and mixed with distilled water at a ratio of 1 :3 and an excess of KOH (5% more than indicated according to the saponification number of 19.9%). This mixture was blended and mixed until a viscous mixture was obtained. Excess water was evaporated by heating.

[0314] 20% w / w stock solutions of BSFMO and MBSFL oil of application were prepared in water. Serial 1 :2 dilutions were prepared to bring the samples to 5%. 205%, 1.25% and 0.63% w / w. The samples were heated and homogenized before testing. Bacteria were grown and an inoculation solution was prepared with IxlO8~1.5xl08CFU / ml. These bacteria were sown uniformly on Muller Hinton agar (supplied by a commercial supplier (HyLabs.co.il)). Using a sterile tip, lOpl of the solution to be tested were placed on the plate. The plates were incubated for 24 hours at 37°C. The diameter of inhibition surrounding each testing spot was measured and recorded.

[0315] Results and conclusions:

[0316] Table 5: diameters of inhibition by BSFMO on several pathogens

[0317] Table 6: diameters of inhibition by MBSFL oil

[0318] It can be observed that BSFMO shows anti-bacterial activity against Gram positive bacteria, especially a potent activity against Streptococcus agalactiae. BSFMO is a potent inhibitor of

[0319] Escherichia coli, while having less effect on other Gram negative bacteria tested, such as Salmonella and Vibrio. MBSFL oil possessed a less specific activity as compared to BSFMO (e.g. inhibited Salmonella and Vibrio to a greater extent) and did not inhibit S. agalactiae growth at all. These results indicate these two different modified BSF oils function differently.

[0320] EXAMPLE 6

[0321] Materials and Methods:

[0322] Serial dilutions were prepared as described in Example 5. 80pl of inoculum suspension with a load of 5X103and 20pl 0.02% resazurin solution were complemented by 100 pl of the treatment solution in a 96 well plate. The plates were incubated at 37 °C. Fungal growth was determined by the OD at 570 nm with a microplate reader.

[0323] Results and conclusions:

[0324] As illustrated in Figure 1, BSFMO shows anti-fungal activity against A. niger.

[0325] EXAMPLE 7

[0326] Swine piglet study: BSFPMO vs. positive control (Oregano oil)

[0327] Background: The study included 120 piglets aged 23 days since birth at the study start date, 60 in the study treatment and 60 in the control treatment. The study treatment incorporated a standard feed formulation without any growth promoters, and was supplemented by 1,500 grams per ton of BSFPMO (525 grams of BSFMO). The control formulation incorporated a standard feed formulation without any growth promoters, and was supplemented by 25 grams per ton of Oregano oil loaded at 5% on Attapulgite powder. The study was carried out between days 23 to day 44 days from birth of the 2 piglets treatments, who were placed in pens of 12 piglets per pen throughout the study period. At the beginning of the study, the weight of the piglets in each treatment was measured. At the end of the 21 days of the study (day 44 of age for all piglets), the weight and the feed consumption of each treatment was measured.

[0328] Results:

[0329] Table 7:

[0330] The treatment group, incorporating BSFMO alone, was superior in both parameters comparing to the positive control group which incorporated a high 25 grams / ton dose of antibacterial Oregano oil. The ADWG (Average Daily Weight Gain) of the BSFMO treatment group was superior by 1.7% to the control group, and ADFI (Average Daily Feed Intake) was decreased by 6.2% compared with the control group.

[0331] EXAMPLE 8

[0332] Swine piglet study; BSFPMO & Oresano oil vs. commercial feed

[0333] The study included 144 piglets aged 28 days at the beginning of the study, 72 in the study treatment and 72 in the control treatment. The study treatment incorporated a standard feed formulation without any growth promoters, and was supplemented with 2,142 grams of BSFPMO (750 grams of BSFMO) per ton; and 25 grams per ton of Oregano oil. The control formulation incorporated a standard feed formulation without any growth promoters. The study was carried out between days 28 to 42 days from birth of the 2 piglets treatments, who were placed in pens of 6 piglets per pen throughout the study period. At the beginning of the study, the weight of the piglets in each treatment was measured. At the end of the 14 days of the study (day 42 of age for all piglets), the weight and the feed consumption of each treatment was measured. Results

[0334] Table 8

[0335] Pen data analysis. Values are LSmeans of 12 pens of 6 pigs / pen per treatment. SEM=Standard Error of the Mean. BW= Body Weight. ADG= average daily weight gain. FCR= feed conversion rate. n.s. = non-significant between treatments.

[0336] The treatment group, incorporating BSFPMO and Oregano oil, was superior in both ADWG and ADFI parameters compared with the negative control group which incorporated a standard pre-starter feed formulation. The ADWG (Average Daily Weight Gain) of the treatment group was superior by 10.9% (p<0.05) to the control group, and ADFI (Average Daily Feed Intake) was superior by 5.9% (p<0.05) comparing with the control group.

[0337] EXAMPLE 9

[0338] Broiler field experiment; BSFPMO + BMP antibiotics + Monensin coccidiostat vs. positive control commercial feed (BMP antibiotics + Monensin coccidiostat) As a safety field trial, BSFPMO was in combination with the broilers’ farm best performing commercial feed formulation, which incorporated, in the positive control house, a combination of the anti-bacterial BMD antibiotics and the anti-coccidiosis Monensin. The treatment group house, received feed formulations which incorporated identical dosing of BSD and Monensin, augmented by 3,000 grams of BSFPMO (1,050 grams per ton of BSFMO per ton of feed). Results:

[0339] Table 9

[0340] ADG= average daily weight gain. FCR= feed conversion rate. PEF= performance efficiency factor = (livability (%) X body weight (kg) X 100) / FCR

[0341] Surprisingly, the treatment group performed better than the positive control group on all key parameters. Marketing body weight in the treatment group of 3.6% superior to the positive control group, and FCR (Feed Conversion Ratio) of the treatment group was 0.7% superior to the positive control group. The PEF parameter, which measures overall economic profitability was 2.7% superior in the treatment group compared to the positive control group.

[0342] EXAMPLE 10

[0343] Broiler field experiment; BSFPMO + Oregano oil vs. best performing commercial feed (Presan™ + Monolaurin + Monobutyrin)

[0344] The control house was fed the best performing commercial feed formulation (starter, grower and finisher) which incorporated a combination of natural growth promoters: Presan™ (Trouw Nutrition, The Netherland), Monobutyrin and Monolaurin. The treatment group feed formulations incorporated a combination of BSFMO and Oregano oil. In the starter formulation, BSFMO were supplemented at 700 grams per ton of feed and Oregano oil was supplemented at a rate of 9 grams per ton. In the following Grower and Finisher feed formulations, the rate of BSFMO supplementation was 560 grams per ton, and the Oregano oil rate was supplemented at 9 grams per ton. Results:

[0345] Table 10

[0346] In this field experiment, the treatment group performed better than the positive control group on all key parameters. Marketing body weight in the treatment group of 9.73% superior to the positive control group, and FCR (Feed Conversion Ratio) of the treatment group was 2.31% superior to the positive control group. The PEF parameter, which measures overall economical profitability was 9.65% superior in the treatment group comparing to the positive control group. EXAMPLE 11

[0347] Layers field experiment; BSFPMO vs. commercial feed

[0348] In this study, the negative control battery received standard layers’ commercial feed (Rafael Feeds, Emek Hefer, Israel). The study battery received the standard layers commercial feed supplemented by 1,500 grams per ton of BSFPMO (525 grams per ton of BSFMO).

[0349] Results:

[0350] Table 11

[0351] The treatment group aggregately laid 30,046 eggs during the tested month, +143 eggs compared to the negative control group. Average age weight during February 2024 was 65.70 grams, 1.10 grams higher or 1.70% higher than in the control group.

[0352] Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. It is the intent of the applicant(s) that all publications, patents and patent applications referred to in this specification are to be incorporated in their entirety by reference into the specification, as if each individual publication, patent or patent application was specifically and individually noted when referenced that it is to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting. In addition, any priority document(s) of this application is / are hereby incorporated herein by reference in its / their entirety.

Claims

WHAT IS CLAIMED IS:

1. A modified, monoglyceride-enriched black soldier fly (BSF) oil extract, comprising one or more monoglycerides in a total amount that is higher by at least 20 % of a total amount of monoglycerides in an unmodified BSF oil extract.

2. The modified BSF oil extract of claim 1, comprising one or more monoglycerides in a total amount of at least 25 %, at least 30 %, at least 35 %, at least 40 %, at least 45 %, at least 50 %, at least 55 %, at least 60 % or at least 65%, by weight of the total weight of the modified BSF oil extract.

3. The modified BSF oil extract of claim 1, comprising one or more monoglycerides in a total amount that ranges from 25 to 70 % by weight, of the total weight of the modified BSF oil extract.

4. A modified BSF oil extract comprising monoglycerides in a total amount of at least 25 %, at least 30 %, least 35 %, at least 40 %, at least 45 %, at least 50 %, at least 55 %, at least 60 % or at least 65 % by weight of the total weight of the modified BSF oil extract.

5. The modified BSF oil extract of claim 4, wherein a total amount of the monoglycerides ranges from 25 to 70 %, by weight, of the total weight of the modified BSF oil.

6. The modified BSF oil of any one of claims 1 to 5, comprising monolaurin in an amount of at least at least 10 %, or 15 %, or at least 20 %, or at least 25 %, or at least 30% by weight, of the total weight of the modified BSF oil.

7. The modified BSF oil of any one of claims 1 to 5, comprising monolaurin in an amount that ranges from 10 to 40 %, by weight, of the total weight of the modified BSF oil.

8. The modified BSF oil of any one of claims 1 to 7, comprising monolaurin in an amount that ranges from 25 to 75 %, by weight, of the total weight of the one or more monoglycerides in the modified BSF oil.

9. The modified BSF oil of any one of claims 1 to 8, further comprising triglycerides in a total amount of no more than 25%, no more than 20 % or no more than 10% by weight of the total weight of the modified BSF oil.

10. The modified BSF oil of any one of claims 1 to 9, further comprising diglycerides in a total amount of no more than 40 %, no more than 35% or no more than 30 %, by weight of the total weight of the modified BSF oil.

11. The modified BSF oil of any one of claims 1 to 10, further comprising free fatty acids, in a total amount of no more than 10, % by weight of the total weight of the modified BSF oil.

12. The modified BSF oil of any one of claims 1 to 11, further comprising glycerol in an amount of no more than 15 %, no more than 12% or no more than 10 %, by weight of the total weight of the modified BSF oil.

13. A process of preparing a modified, monoglycerides-enriched BSF oil, the process comprising contacting a BSF oil extract with glycerol, and an alkaline substance, under conditions that promote transesterification.

14. The process of claim 13, wherein a mol ratio of said BSF oil extract and said glycerol ranges from 2: 1 to 1 : 10, or from 1 : 1 to 1 : 10, or from 1 : 1 to 1 :6, or from 1 : 1 to 1 :4, or from 1 :2 to 1 :3.

15. The process of claim 13 or 14, wherein said alkaline catalyst is a methoxide or a hydroxide.

16. The process of any one of claims 13 to 15, wherein a mol ratio of said alkaline substance and said BSF oil extract ranges from 1 : 100 to 10: 100 .

17. The process of any one of claims 13 to 16, wherein said conditions comprise heating said mixture, for example, to a temperature of at least 100, or at least 150 °C, under reduced pressure .

18. The process of any one of claims 13 to 17, wherein said contacting is for a time period that ranges from 1 to 24 hours.

19. The process of any one of claims 13 to 18, further comprising, subsequent to said contacting, removing the glycerol from said mixture, to thereby obtain the modified BSF oil.

20. The process of claim 19, wherein said removing is such that an amount of the glycerol in the modified BSF oil is less than 20 %, or less than 15%, or less than 10% by weight of the total weight of the modified BSF oil.

21. A modified, monoglycerides-enriched BSF oil obtainable by a process according to any one of claims 13 to 20.

22. The modified BSF oil of claim 21, being as described in any one of claims 1 to 12.

23. A composition comprising a modified BSF oil according to any one of claims 1 to12, 21 and 22.

24. The composition of claim 23, further comprising an edible carrier.

25. The composition of claim 23 or 24, being formulated for oral administration to a subject in need thereof.

26. The composition of any one of claims 23 to 25, being in a form of a liquid, a paste, a powder, a syrup, a particulate material, a gel, and a capsule.

27. The composition of any one of claims 23 to 25, wherein said carrier is a solid carrier, and wherein the modified BSF oil is associated with the carrier.

28. The composition of claim 27, wherein said carrier is dispersable in a liquid.

29. The composition of claim 27, wherein the carrier is a solid particulate carrier, the composition being in a form of a powder or a particulate carrier.

30. The composition of any one of claims 23 to 25, being in a form of microcapsules or nanoparticles having the modified BSF oil encapsulated therewithin.

31. The composition of any one of claims 23 to 25, being a liquid emulsion.

32. The composition of any one of claims 23 to 31, further comprising an additional agent selected from chitin, chitosan, a BSF protein extract, an anti-microbial agent, an antiinflammatory agent, a plant extract and a plant and / or mineral oil.

33. The composition of any one of claims 23 to 32, further comprising an extract or an oil derived from a plant of the Lamiaceae family.

34. A composition comprising a monoglyceride-enriched oil and at least one of a plant oil, a plant extract a thymol, a carvacrol, a eugenol, a cinnamaldehyde, a limonene, a myrcene, a germacrene, a pinene, a cymene, an ocimene, a terpinene, a caryophyllene and / or bisabolene.

35. The composition of claim 34, wherein said plant is a Lamiaceae plant.

36. The composition of claim 34, wherein said plant oil or extract acts in synergy with the monoglyceride-enriched oil in treating and / or preventing inflammation and / or microbial infection and / or in preventing biofilm formation.

37. The composition of claim 34 or 35, wherein an amount of the monoglyceride- enriched oil and / or an amount of the plant oil or extract in the composition is less than the therapeutically effective amount when used as a single agent.

38. The composition of any one of claims 34 to 37, wherein said monoglyceride- enriched oil is a plant oil, a mineral oil, or an animal oil.

39. The composition of any one of claims 34 to 37, wherein said monoglyceride- enriched oil is a modified BSF oil extract according to any one of claims 1 to 12, 21 and 22.

40. The composition of any one of claims 34 to 39, further comprising a carrier, preferably an edible carrier.

41. The modified BSF oil of any one of claims 1 to 12, 21 and 22 or the composition of any one of claims 23 to 40, for use in the manufacture of a feed or food product.

42. An edible product comprising the modified BSF oil of any one of claims 1 to 12, 21 and 22 or the composition of any one of claims 23 to 40.

43. The edible product of claim 42, wherein an amount of the modified BSF oil in the product is in a range of from 0.001% to 1 % by weight of the total weight of the product.

44. The edible product of any one of claims 42 to 43, being a food or feed product or a supplemental feed or food product.

45. The edible product of any one of claims 42 to 44, being for treating or preventing inflammation and / or microbial infection and / or biofilm formation in a subject.

46. The edible product of claim 45, wherein the subject is selected from a a human being, a companion animal, a farm animal, a fish and a crustacean.

47. A method of treating or preventing inflammation in a subject in need thereof, the method comprising orally administering to the subject an effective amount of the modified BSF oil of any one of claims 1 to 12, 21 and 22, or the composition of any one of claims 23 to 40, or the edible product of any one of claims 42 to 43, thereby treating or preventing the inflammation.

48. A method of treating or preventing a disease or disorder associated with a pathogenic microorganism in a subject in need thereof, the method comprising orally administering to the subject an effective amount of the modified BSF oil of any one of claims 1 to 12, 21 and 22, or the composition of any one of claims 23 to 40, or the edible product of any one of claims 42 to 46, thereby treating or preventing the disease or disorder.

49. The method of claims 47 or 48, wherein the modified BSF oil or the composition are administered to the subject as a food supplement or a feed supplement.

50. The method of any one of claims 47 to 49, wherein the subject is selected from a human being, a companion animal, a farm animal, a fish and a crustacean.

51. The method of any one of claims 47 to 50, wherein an effective amount of the modified BSF oil is in a range of from 0.001% to 1 % by weight of the total weight of a composition or a product comprising same.

52. The method of any one of claims 47 to 51, being for reducing a mortality, increasing an average body weight and / or improving a feed conversion ratio in a population comprising a plurality of subjects.

53. A method of reducing a mortality, increasing an average body weight, reducing antibiotic intake, reducing a number of days to reach target body weight, reducing a number of sick days until marketing, reduction in diarrhea days until weaning and / or improving a feed conversion ratio in a population comprising a plurality of subj ects, the method comprising treating the plurality of subjects with the modified BSF oil of any one of claims 1 to 12, 21 and 22, or the composition of any one of claims 23 to 40, or the edible product of any one of claims 42 to 46.

54. The method of claim 52 or 53, wherein the subjects are selected from the group consisting of farm animals, fish and crustaceans.

55. The method of claim 54, wherein the modified BSF oil or the composition are administered to the subject as a food supplement or a feed supplement.

56. The method of claim 53, wherein the modified BSF oil or the composition are administered to the subject via inhalation.

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