Mixed triglycerides

Abstract

The present invention relates to mixed triglycerides, in particular, the present invention provides a composition comprising a compound having the formula (1), (2), (3), (4) or a combination thereof wherein n1, n2, n3, n4, n5, and n6 are independently 4 to 10. # imgabs0 #

Description

[0001] This application is a divisional application of the international application with application number PCT / EP2019 / 085525 and invention name “Mixed triglycerides” filed on December 17, 2019. The international application entered the Chinese national phase on June 16, 2021 with application number 201980083345.9. Technical Field

[0002] The present invention relates to dietary sources of triglycerides comprising butyric acid having improved organoleptic properties. The present invention also provides triglycerides comprising butyric acid which provide a rich source of ketones. Background Art

[0003] Salts and esters of butyric acid are called butyrates or butanoates. Butyric acid in ester form is present in many foods, such as milk, especially milk of goats, sheep, cattle, camels and buffaloes, and dairy products such as butter and cheeses such as Parmesan cheese. Butyric acid is also a product of anaerobic fermentation, for example, as a product of fermentation produced by intestinal microflora. Tributyrin is a triglyceride composed of three ester functional groups, with three butyrate moieties and a glycerol backbone. Under hydrolysis conditions, such as those occurring during digestion, tributyrin may be the source of three moles of butyric acid per mole of tributyrin.

[0004] The multiple beneficial effects of butyrate are well documented in mammals and livestock. At the intestinal level, butyrate modulates transepithelial fluid transport, improves mucosal inflammation and oxidative status, enhances intestinal barrier function, and influences visceral sensitivity and intestinal motility.

[0005] It has been shown that butyrate can improve the intestinal structure of piglets with short bowel syndrome (Bartholome et al., J of Parenter Enteral Nutr., 2004, Vol. 28, No. 4, pp. 210-222) and reduce the proliferation of colon cancer cells in human cell lines (Lupton, J Nutr., 2004, Vol. 134, No. 2, pp. 479-482). The production of volatile fatty acids such as butyrate from fermentable fiber can contribute to the role of dietary fiber in colon cancer (Lupton, J Nutr., 2004, Vol. 134, No. 2, pp. 479-482). Short-chain fatty acids including but not limited to acetate, propionate and butyrate are produced by colon bacteria that ingest or ferment non-digestible fiber and / or prebiotics. Butyrate also benefits colon cells by increasing energy production. In addition, butyrate has been shown to reduce the incidence of diarrhea (Berni Canani et al., Gastroenterol., 2004, Vol. 127, No. 2, pp. 630-634), improve inflammatory bowel disease (Scarpellini et al., Dig Liver Dis., 2007, Vol. 1, No. 1, pp. 19-22) and small intestinal health (Kotunia et al., J Physiol Pharmacol., 1994, Vol. 55, No. 2, pp. 59-68).

[0006] It is also known that when ingested, butyrate stimulates the production of large amounts of ketones (Saint-Pierre et al., 2016, Vol. 32, Journal of Functional Foods, Vol. 32, pp. 170-175). Ketones are alternative energy sources (except carbohydrates, proteins, and fats) that can effectively reach peripheral organs such as the brain. Ketones can directly produce acetyl-CoA in mitochondria, thereby supporting the production of ATP, and can be used by neural tissue instead of glucose (Tetrick et al., 2010, Comparative Medicine, Vol. 60, pp. 486-490). Ketones can also exert a protective effect on neurons from free radical damage (Vanltallie TB et al., 2003, Ketones: metabolism's ugly duckling. Nutr. Rev, Vol. 61: pp. 327-341).

[0007] Studies have shown that ketone administration after ischemic injury reduces the effects on the ischemic brain. In fact, ketone supplementation has been considered a treatment option for traumatic brain injury (White and Venkatesh, 2011, Critical Care, Vol. 15: p. 219). In addition, studies have shown that neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease will benefit from ketone administration. By way of example, Reger et al. (2004, Neurobiol Aging, Vol. 25, pp. 311-4.14) found that increased serum ketone levels in patients with Alzheimer's disease improved cognitive scores.

[0008] Butyric acid and tributyrin are generally regarded as safe (GRAS) (21 CFR582.60 and 21 CFR184.1903, respectively) food additives and are natural components of many dairy products. However, butyric acid is associated with negative organoleptic qualities, such as vomit-like, fecal-like, and cheese-like aroma attributes. Tributyrin also has negative organoleptic qualities, particularly high bitterness. These unpleasant taste and odor attributes can make oral administration of compositions containing these compounds particularly difficult, especially in the pediatric population.

[0009] Medium chain triglycerides (MCT) and medium chain fatty acids (MCFA) are also sources of ketones. Caprylic acid (C8) is the most effective MCFA in producing blood ketones in the human body (Vanderberghe et al., 2017, Curr. Dev. Nutr. Vol. 1 No. 4). However, adverse consequences of gastrointestinal intolerance (such as diarrhea and stomach cramps) are associated with high dose intake (> 10g), which limits the amount that can be ingested at one time, and therefore limits the amount of blood ketones produced.

[0010] It would be beneficial to provide a food-grade butyric acid source having improved organoleptic properties compared to available products. Summary of the invention

[0011] The present invention provides compounds as a source of butyrate, which have improved organoleptic properties and may produce large amounts of ketones after oral or enteral ingestion in humans and other mammals. Specifically, the present invention provides novel triglycerides (TGs) composed of a mixture of butyrate and medium-chain fatty acids (MCFAs). The compounds have improved odor and / or taste relative to butyric acid, butyrate and / or tributyrin. The compounds can be used as a dietary source of butyric acid. The compounds can be used, for example, in nutritional compositions and dietary supplements, and as a source of ketones. The compounds can also simultaneously lead to an increase in blood levels of butyrate and ketones.

[0012] The fatty acids are liberated from the triglycerides by lipases naturally present in the gastrointestinal tract. Relative to butyrate, these compounds do not add additional mineral salts to the final formulation.

[0013] According to a first aspect of the present invention, there is provided a composition comprising a compound having the formula

[0014]

[0015] or a combination thereof, wherein n1, n2, n3, n4, n5 and n6 are independently 4 to 10.

[0016] In one embodiment, n1 = n2 and / or n5 = n6. In another embodiment, n1 = n2 = n3 = n4 = n5 = n6.

[0017] The composition may comprise a compound having formula (1) and a compound having formula (2).

[0018] The composition may comprise a compound having formula (1) and a compound having formula (3).

[0019] The composition may comprise a compound having formula (1) and a compound having formula (4).

[0020] The composition may comprise a compound having formula (2) and a compound having formula (3).

[0021] The composition may comprise a compound having formula (2) and a compound having formula (4).

[0022] The composition may comprise a compound having formula (3) and a compound having formula (4).

[0023] The composition may comprise a compound having formula (1), a compound having formula (2), and a compound having formula (3).

[0024] The composition may comprise a compound having formula (1), a compound having formula (2), and a compound having formula (4).

[0025] The composition may comprise a compound having formula (1), a compound having formula (3), and a compound having formula (4).

[0026] The composition may comprise a compound having formula (2), a compound having formula (3), and a compound having formula (4).

[0027] The composition may include a compound having formula (1), a compound having formula (2), a compound having formula (3), and a compound having formula (4).

[0028] In one embodiment, the compound of formula (1) comprises at least 2%, 5%, 10%, or 15% by weight of the total triglycerides in the composition. In one embodiment, the compound of formula (1) comprises 2% to 35%, 5% to 30%, or 10% to 25% by weight of the total triglycerides in the composition.

[0029] In one embodiment, the compound of formula (2) comprises at least 2%, 5%, 10%, or 15% by weight of the total triglycerides in the composition. In one embodiment, the compound of formula (2) comprises 2% to 35%, 5% to 30%, or 10% to 25% by weight of the total triglycerides in the composition.

[0030] In one embodiment, the compound of formula (3) comprises at least 2%, 5%, 10%, or 15% by weight of the total triglycerides in the composition. In one embodiment, the compound of formula (3) comprises 2% to 35%, 5% to 30%, or 10% to 25% by weight of the total triglycerides in the composition.

[0031] In one embodiment, the compound of formula (4) comprises at least 2%, 5%, 10%, or 15% by weight of the total triglycerides in the composition. In one embodiment, the compound of formula (4) comprises 2% to 35%, 5% to 30%, or 10% to 25% by weight of the total triglycerides in the composition.

[0032] The compound of formula (1), (2), (3) and (4) may comprise at least 50%, 60%, 70%, 80%, 90%, 95% or 99% by weight of the total triglycerides in the composition.

[0033] In one embodiment, the compound of formula (1) comprises at least 2%, 5%, 10% or 15% by weight of the total butyrate-containing triglycerides in the composition, and / or the compound of formula (2) comprises at least 2%, 5%, 10% or 15% by weight of the total butyrate-containing triglycerides in the composition, and / or the compound of formula (3) comprises at least 2%, 5%, 10% or 15% by weight of the total butyrate-containing triglycerides in the composition, and / or the compound of formula (4) comprises at least 2%, 5%, 10% or 15% by weight of the total butyrate-containing triglycerides in the composition.

[0034] The compound of formula (1), (2), (3) and (4) may comprise at least 50%, 60%, 70%, 80%, 90%, 95% or 99% by weight of the total triglycerides containing butyrate moieties in the composition and / or at least 50%, 60%, 70%, 80%, 90%, 95% or 99% by weight of the total triglycerides containing medium-chain fatty acid moieties in the composition.

[0035] According to one embodiment of the present invention, there is provided a composition comprising a compound having the formula

[0036]

[0037] or a combination thereof.

[0038] The composition may comprise a compound having formula (5) and a compound having formula (6).

[0039] The composition may comprise a compound having formula (5) and a compound having formula (7).

[0040] The composition may comprise a compound having formula (5) and a compound having formula (8).

[0041] The composition may comprise a compound having formula (6) and a compound having formula (7).

[0042] The composition may comprise a compound having formula (6) and a compound having formula (8).

[0043] The composition may comprise a compound having formula (7) and a compound having formula (8).

[0044] The composition may comprise a compound having formula (5), a compound having formula (6), and a compound having formula (7).

[0045] The composition may comprise a compound having formula (5), a compound having formula (6), and a compound having formula (8).

[0046] The composition may comprise a compound having formula (5), a compound having formula (7), and a compound having formula (8).

[0047] The composition may comprise a compound having formula (6), a compound having formula (7), and a compound having formula (8).

[0048] The composition may include a compound having formula (5), a compound having formula (6), a compound having formula (7), and a compound having formula (8).

[0049] In one embodiment, the compound of formula (5) comprises at least 2%, 5%, 10%, 15%, 20%, or 25% by weight of the total triglycerides in the composition. In one embodiment, the compound of formula (5) comprises 5% to 35%, 10% to 30%, or 20% to 30% by weight of the total triglycerides in the composition.

[0050] In one embodiment, the compound of formula (6) comprises at least 2%, 5%, 10%, 15%, 20%, or 25% by weight of the total triglycerides in the composition. In one embodiment, the compound of formula (6) comprises 5% to 35%, 10% to 30%, or 15% to 25% by weight of the total triglycerides in the composition.

[0051] In one embodiment, the compound of formula (7) comprises at least 2%, 5%, 10%, 15%, 20%, or 25% by weight of the total triglycerides in the composition. In one embodiment, the compound of formula (7) comprises 5% to 35%, 10% to 30%, or 10% to 20% by weight of the total triglycerides in the composition.

[0052] In one embodiment, the compound of formula (8) comprises at least 2%, 5%, 10%, 15%, 20%, or 25% by weight of the total triglycerides in the composition. In one embodiment, the compound of formula (8) comprises 5% to 35%, 5% to 20%, or 5% to 15% by weight of the total triglycerides in the composition.

[0053] In one embodiment, the compound having formula (5) accounts for at least 5 weight percent of the total triglycerides in the composition, the compound having formula (6) accounts for at least 5 weight percent of the total triglycerides in the composition, the compound having formula (7) accounts for at least 5 weight percent of the total triglycerides in the composition, and the compound having formula (8) accounts for at least 5 weight percent of the total triglycerides in the composition.

[0054] In one embodiment, the compound of formula (5) accounts for at least 25 weight percent of the total triglycerides in the composition, the compound of formula (6) accounts for at least 15 weight percent of the total triglycerides in the composition, the compound of formula (7) accounts for at least 10 weight percent of the total triglycerides in the composition, and the compound of formula (8) accounts for at least 5 weight percent of the total triglycerides in the composition.

[0055] In one embodiment, the compound of formula (5) comprises 20% to 30% by weight of the total triglycerides in the composition, the compound of formula (6) comprises 15% to 25% by weight of the total triglycerides in the composition, the compound of formula (7) comprises 10% to 20% by weight of the total triglycerides in the composition, and the compound of formula (8) comprises 5% to 15% by weight of the total triglycerides in the composition.

[0056] Compounds of formula (5), (6), (7) and (8) may comprise at least 50%, 60%, 70%, 80%, 90%, 95% or 99% by weight of the total triglycerides in the composition.

[0057] In one embodiment, the compound of formula (5) comprises at least 5% by weight of the total butyrate-containing triglycerides in the composition. In one embodiment, the compound of formula (5) comprises at least 10%, 20%, or 30% by weight of the total butyrate-containing triglycerides in the composition.

[0058] In one embodiment, the compound of formula (6) comprises at least 5% by weight of the total butyrate-containing triglycerides in the composition. In one embodiment, the compound of formula (6) comprises at least 10%, 15%, or 20% by weight of the total butyrate-containing triglycerides in the composition.

[0059] In one embodiment, the compound of formula (7) comprises at least 5%, 10% or 15% by weight of the total butyrate-containing triglycerides in the composition.

[0060] In one embodiment, the compound of formula (8) comprises at least 5% or 10% by weight of the total butyrate-containing triglycerides in the composition.

[0061] The compounds of formula (5), (6), (7) and (8) may comprise at least 50%, 60%, 70%, 80%, 90%, 95% or 99% by weight of the total butyrate-containing triglycerides in the composition and / or at least 50%, 60%, 70%, 80%, 90%, 95% or 99% by weight of the total caprylate-containing triglycerides in the composition.

[0062] In a preferred embodiment, tributyrin comprises less than 10 wt % of the total triglycerides in the composition, preferably less than 8 wt % of the total triglycerides in the composition, more preferably less than 5 wt % of the total triglycerides in the composition.

[0063] The composition of the present invention may be a nutritional composition.

[0064] The composition may be a dietary supplement. The dietary supplement may be in the form of capsules, tablets, sachets, powders or liquid pellets.

[0065] According to another aspect, there is provided a composition of the invention for providing a butyric acid source having improved organoleptic properties.

[0066] According to another aspect, there is provided a composition of the present invention for improving or maintaining gastrointestinal health.

[0067] According to another aspect, there is provided a composition of the invention for increasing ketone levels, preferably blood ketone levels.

[0068] According to another aspect, there is provided a composition of the invention for use in treating a disease treatable by ketone levels, preferably blood ketone levels.

[0069] According to another aspect, a composition of the invention for use in treating a disease associated with low ketone levels, preferably low blood ketone levels is provided. In one embodiment, a composition of the invention for use in treating or preventing a neurological disease, a metabolic disease, cancer and / or myocardial ischemia is provided.

[0070] In one embodiment, a composition of the invention is provided for use in the treatment or prevention of one or more diseases selected from the list consisting of brain energy deficiency, migraine, memory impairment, age-related memory impairment, brain injury, stroke, amyloid lateral sclerosis, multiple sclerosis, cognitive impairment, post-intensive care cognitive impairment, age-induced cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, inherited metabolic disorders (such as type 1 glucose transporter deficiency syndrome and pyruvate dehydrogenase complex deficiency), depression, schizophrenia, epilepsy, narcolepsy, diabetes, obesity, non-alcoholic fatty liver disease and polycystic ovary syndrome.

[0071] In one embodiment, a composition of the invention is provided for use in the treatment or prevention of epilepsy.

[0072] According to another aspect, a compound of formula (1) is provided. In one embodiment, n1 = n2 = 6. In this embodiment, the compound of formula (1) corresponds to the compound of formula (5).

[0073] According to another aspect, a compound of formula (2) is provided. In one embodiment, n3=6. In this embodiment, the compound of formula (2) corresponds to the compound of formula (6).

[0074] According to another aspect, a compound of formula (3) is provided. In one embodiment, n4=6. In this embodiment, the compound of formula (3) corresponds to the compound of formula (7).

[0075] According to another aspect, a compound of formula (4) is provided. In one embodiment, n5=n6=6. In this embodiment, the compound of formula (4) corresponds to the compound of formula (8).

[0076] According to another aspect, there is provided the use of a compound of formula (1), (2), (3) and / or (4), preferably of formula (5), (6), (7) and / or (8) as defined herein, for providing a source of butyric acid with improved organoleptic properties.

[0077] According to another aspect, a compound of formula (1), (2), (3) or (4) or a combination thereof, preferably a compound of formula (5), (6), (7) or (8) or a combination thereof, is provided for use in increasing blood ketone levels, preferably blood ketone levels.

[0078] According to another aspect, a compound of formula (1), (2), (3) or (4) or a combination thereof, preferably a compound of formula (5), (6), (7) or (8) or a combination thereof, is provided for use in improving or maintaining gastrointestinal (GI) health and / or for increasing blood ketone levels.

[0079] According to another aspect, a compound of formula (1), (2), (3) or (4) or a combination thereof, preferably a compound of formula (5), (6), (7) or (8) or a combination thereof, is provided for use as a medicament.

[0080] According to another aspect, a compound of formula (1), (2), (3) or (4) or a combination thereof, preferably a compound of formula (5), (6), (7) or (8) or a combination thereof, is provided for use in treating a disease treatable by increasing blood ketone levels.

[0081] According to another aspect, a composition of the invention for use in treating a disease associated with low ketone levels, preferably low blood ketone levels is provided. In one embodiment, a compound of formula (1), (2), (3) or (4) or a combination thereof, preferably a compound of formula (5), (6), (7) or (8) or a combination thereof, is provided for use in preventing or treating a neurological disease, a metabolic disease, a cancer and / or myocardial ischemia.

[0082] In one embodiment, compounds of formula (1), (2), (3) and / or (4), preferably compounds of formula (5), (6), (7) and / or (8), are provided for use in the treatment or prevention of one or more diseases selected from the list consisting of brain energy deficiency, migraine, memory impairment, age-related memory impairment, brain injury, stroke, amyloid lateral sclerosis, multiple sclerosis, cognitive impairment, post-intensive care cognitive impairment, age-induced cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, inherited metabolic disorders (such as type 1 glucose transporter deficiency syndrome and pyruvate dehydrogenase complex deficiency), depression, schizophrenia, epilepsy, narcolepsy, diabetes, obesity, non-alcoholic fatty liver disease and polycystic ovary syndrome.

[0083] In one embodiment, a compound of formula (1), (2), (3) or (4) or a combination thereof, preferably a compound of formula (5), (6), (7) or (8) or a combination thereof, is provided for use in treating epilepsy.

[0084] According to another aspect, there is provided a method of increasing ketone levels, preferably blood ketone levels, which method comprises administering a compound or composition as defined herein to a subject in need thereof.

[0085] According to another aspect, there is provided a method of treating a disease treatable by increasing ketone levels, preferably blood ketone levels, which method comprises administering a compound or composition as defined herein to a subject in need thereof.

[0086] According to another aspect, there is provided a method of treating or preventing a disease associated with low ketone levels, preferably low blood ketone levels, which method comprises administering a compound or composition as defined herein to a subject in need thereof.

[0087] According to another aspect, there is provided a method of treating or preventing a neurological disease, a metabolic disease, cancer and / or myocardial ischemia, the method comprising administering a compound or composition as defined herein to a subject in need thereof.

[0088] In one embodiment, a method of treating or preventing one or more diseases selected from the list consisting of brain energy deficiency, migraine, memory impairment, age-related memory impairment, brain injury, stroke, amyloid lateral sclerosis, multiple sclerosis, cognitive impairment, post-intensive care cognitive impairment, age-induced cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, inherited metabolic disorders (such as type 1 glucose transporter deficiency syndrome and pyruvate dehydrogenase complex deficiency), depression, schizophrenia, epilepsy, narcolepsy, diabetes, obesity, non-alcoholic fatty liver disease and polycystic ovary syndrome is provided, the method comprising administering a compound or composition as defined herein to a subject in need thereof.

[0089] According to another aspect, there is provided a process for preparing a composition of the invention or a compound of formula (1), (2), (3) or (4) as defined herein, the process comprising the transesterification of tributyrin with one or more triglycerides selected from the list consisting of tricaproin, triheptanoin, tricaprylin, tripelargonylglycerol, tricaprin, triundecanoin, and tridodecanoin.

[0090] According to one embodiment, there is provided a process for preparing a composition of the invention or a compound of formula (5), (6), (7) or (8) as defined herein, the process comprising the transesterification of tributyrin and tricaprylin. BRIEF DESCRIPTION OF THE DRAWINGS

[0091] Figure 1 Shown are mean total plasma ketone (BHB and AcAc) levels within 4 hours after consumption of C4C8 butyrated triglycerides "MCT C4 / C8" or MCT according to the present invention.

[0092] Figure 2 Plasma BHB, AcAc and total ketone levels within 4 hours after consumption of C4C8 butyrated triglycerides "MCT C4 / C8" according to the present invention are shown.

[0093] Figure 3 Plasma propionate, butyrate and caproate levels within 4 hours after consumption of C4C8 butyrated triglycerides "MCT C4 / C8" according to the present invention are shown. DETAILED DESCRIPTION

[0094] Triglycerides

[0095] Triglycerides (also called triacylglycerols) are triesters derived from glycerol and three fatty acids.

[0096] Fatty acids can be unsaturated or saturated. Fatty acids that are not attached to other molecules are called free fatty acids (FFA).

[0097] The term "fatty acid moiety" refers to the portion of a triglyceride produced from a fatty acid in an esterification reaction with glycerol. The triglycerides used in the present invention contain at least one butyric acid (C4) moiety and at least one medium-chain fatty acid moiety (C6, C7, C8, C9, C10, C11 or C12).

[0098] The medium chain fatty acid moiety may contain between 6 and 12 carbon atoms. Thus, the medium chain fatty acid moiety may be hexanoate (caproic acid), heptanoate (heptanoic acid), octanoate (octanoic acid), nonanoate (nonanoic acid), decanoate (decanoic acid), undecanoate (undecanoic acid), or dodecanoate (lauric acid).

[0099] When one or more medium chain fatty acid moieties are present in a triglyceride, the medium chain fatty acid moieties may contain the same or different numbers of carbon atoms.

[0100] In some embodiments, the one or more medium chain fatty acid moieties contain between 6 and 10 carbon atoms. In a preferred embodiment, the one or more medium chain fatty acid moieties contain 8 carbon atoms (the medium chain fatty acid moiety is caprylate).

[0101] The triglyceride of the present invention can be synthesized by esterification of, for example, medium-chain FFA (e.g., caproic acid, heptanoic acid, caprylic acid, nonanoic acid, capric acid, undecanoic acid and / or dodecanoic acid) and butyric acid with glycerol. When the medium-chain fatty acid moiety is caprylic acid ester, the triglyceride can be synthesized by esterification of, for example, caprylic acid and butyric acid with glycerol.

[0102] Alternatively, the triglyceride of the present invention can be synthesized by, for example, transesterification between tributyrin and tricaproic acid glyceryl, triheptanoin, tricaprylic acid glyceryl, trinonanoic acid glyceryl, tricapric acid glyceryl, triundecanoic acid glyceryl and / or tridodecanoic acid glyceryl. When the medium-chain fatty acid moiety is caprylic acid ester, the triglyceride can be synthesized by, for example, transesterification between tributyrin and tricaprylic acid glyceryl (tricaprylin).

[0103] By way of example, methods of obtaining compounds of formula (5), (6), (7) and (8) are as follows:

[0104]

[0105] Triglycerides containing a single butyrate moiety may be used herein. Alternatively, mixtures of triglycerides containing different butyrate moieties may be used.

[0106] Composition

[0107] The present invention provides a composition comprising a triglyceride containing a butyrate moiety as mentioned herein. The composition may be, for example, a nutritional composition or a dietary supplement.

[0108] The expression "nutritional composition" refers to a composition that provides nutrition to an individual.

[0109] In some embodiments, the nutritional composition according to the invention is an "enteral nutritional composition", i.e., a food material that is administered in the gastrointestinal tract. Gastric introduction may involve the use of a nasogastric or orogastric tube that leads directly to the stomach. This may be used in particular in a hospital or clinic.

[0110] A "dietary supplement" can be used to supplement an individual's nutrition (it is usually used as such, but it can also be added to any kind of composition intended for ingestion). A supplement can be in tablet, capsule, lozenge or liquid form, for example. A supplement can also contain protective hydrophilic colloids (such as gums, proteins, modified starches), binders, film formers, encapsulating agents / materials, wall / shell materials, matrix compounds, coatings, emulsifiers, surfactants, solubilizers (oils, fats, waxes, lecithins, etc.), adsorbents, carriers, fillers, co-compounds, dispersants, wetting agents, processing aids (solvents), flow agents, taste masking agents, weighting agents, gelling agents and gel forming agents. Dietary supplements may also contain conventional pharmaceutical additives and adjuvants, excipients and diluents, including but not limited to: water, gelatin from any source, vegetable gums, lignin sulfonates, talc, sugars, starches, gum arabic, vegetable oils, polyalkylene glycols, flavors, preservatives, stabilizers, emulsifiers, buffers, lubricants, colorants, wetting agents, fillers, etc. When the composition is a supplement, it can be provided in unit dosage form.

[0111] The nutritional composition of the present invention may comprise a protein source, a carbohydrate source and / or a lipid source. However, in some embodiments, particularly if the nutritional composition of the present invention is a supplement or fortifier, only lipids (or a lipid source) may be present.

[0112] Protein sources based on, for example, whey, casein and mixtures thereof may be used, as well as soy-based protein sources. As far as whey protein is concerned, the protein source may be based on acid whey or sweet whey or mixtures thereof, and may contain alpha-lactalbumin and beta-lactoglobulin in any desired ratio.

[0113] The protein may be fully hydrolyzed or partially hydrolyzed. If hydrolyzed protein is desired, a hydrolysis process may be performed as desired and as known in the art. For example, a whey protein hydrolyzate may be prepared by enzymatic hydrolysis of the whey fraction in one or more steps.

[0114] In one embodiment, the protein of the composition is a plant-based protein.

[0115] The nutritional composition according to the present invention may include a carbohydrate source. Any carbohydrate source may be used, such as lactose, sucrose, cane sugar, maltodextrin, starch and mixtures thereof. The nutritional composition of the present invention may also contain the necessary vitamins and minerals that are considered to be necessary for daily diet and in significant amounts of nutrition. The minimum requirements of certain vitamins and minerals have been determined. Examples of minerals, vitamins and other nutrients optionally present in the composition of the present invention include vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorus, iodine, iron, magnesium, copper, zinc, manganese, chlorine, potassium, sodium, selenium, chromium, molybdenum, taurine and L-carnitine. Minerals are usually added in the form of salts. The presence and amount of specific minerals and other vitamins will vary depending on the target group. If necessary, the nutritional composition of the present invention may contain emulsifiers and stabilizers, such as soybeans, lecithin, citric acid monoglycerides and citric acid diglycerides, etc. The nutritional composition of the present invention may also contain other substances that may have a beneficial effect, such as lactoferrin, osteopontin, TGFbeta, slgA, glutamine, nucleotides, nucleosides, etc.

[0116] The composition of the present invention may further comprise at least one non-digestible oligosaccharide (eg, prebiotic).

[0117] Prebiotics are generally non-digestible in the sense that they are not broken down and absorbed in the stomach or small intestine, and thus they can remain intact as they pass through the stomach and small intestine to the colon, where they are selectively fermented by beneficial bacteria. Examples of prebiotics include certain oligosaccharides, such as fructooligosaccharides (FOS), inulin, xylooligosaccharides (XOS), polydextrose, or any mixture thereof. In a specific embodiment, the prebiotic may be fructooligosaccharides and / or inulin. In a specific embodiment, the prebiotic is a combination of FOS and inulin, such as that produced by BENEO-Orafti under the trademark Fructo-oligosaccharides (formerly ) or sold by BENEO-Orafti under the trademark Inulin (formerly ). Another example is the combination of 70% short chain oligofructose and 30% inulin, which is registered by Nestle under the trademark "Prebio 1". The nutritional composition of the present invention may also comprise at least one milk oligosaccharide, which may be a BMO (bovine milk oligosaccharide) and / or an HMO (human milk oligosaccharide). The composition of the present invention may also comprise at least one probiotic (or probiotic strain), such as a probiotic bacterial strain.

[0118] The most commonly used probiotic microorganisms are mainly most bacteria and yeasts of the following genera: Lactobacillus spp., Streptococcus spp., Enterococcus spp., Bifidobacterium spp., Clostridium spp. and Saccharomyces spp.

[0119] In some embodiments, the probiotic is a probiotic bacterial strain. In some embodiments, it is a bifidobacterium and / or a lactobacillus.

[0120] In some embodiments, the microorganisms are derived from fecal matter.The compositions of the invention may be in solid (eg, powder), liquid, or gel form, for example.

[0121] The composition of the invention may be in the form of, for example, tablets, dragees, capsules, gel caps, powders, granules, solutions, emulsions, suspensions, coated granules, spray-dried granules, pills, or in the form of pellets, e.g., small amounts of liquid that can be consumed quickly in one or more mouthfuls.

[0122] The composition may be in the form of a pharmaceutical composition and may contain one or more suitable pharmaceutically acceptable carriers, diluents and / or excipients.

[0123] Examples of such suitable excipients for the compositions described herein may be found in "Handbook of Pharmaceutical Excipients," 2nd edition, 1994, edited by A Wade and PJ Weller.

[0124] Acceptable carriers or diluents for therapeutic use are well known in the pharmaceutical art and are described, for example, in Remington's Pharmaceutical Sciences, Mack Publishing Co. (AR Gennaro, ed., 1985).

[0125] The pharmaceutical composition may contain the following substances as carriers, excipients or diluents or in addition to carriers, excipients or diluents: any suitable binder, lubricant, suspending agent, coating agent and / or solubilizer. Examples of suitable binders include starch, gelatin, natural sugars such as glucose, anhydrous lactose, free-flowing lactose, beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, tragacanth or sodium alginate, carboxymethylcellulose and polyethylene glycol.

[0126] Examples of suitable lubricants include sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride, and the like.

[0127] Preservatives, stabilizers, dyes and even flavoring agents may be provided in the composition. Examples of preservatives include sodium benzoate, sorbic acid and esters of p-hydroxybenzoic acid. Antioxidants and suspending agents may also be used.

[0128] treat

[0129] It should be appreciated that all references to treatment herein include curative, palliative and prophylactic treatment. Treatment may also include arresting the progression of disease severity.

[0130] Both human and veterinary treatments are within the scope of the present invention.

[0131] Gastrointestinal (GI) health

[0132] The compounds and compositions defined herein are sources of butyrate / butyric acid and are therefore useful for improving or maintaining gastrointestinal (GI) health.

[0133] The multiple beneficial effects of butyrate on GI health are well documented. At the intestinal level, butyrate modulates transepithelial fluid transport, improves mucosal inflammation and oxidative status, enhances epithelial defense barriers, and modulates visceral sensitivity and intestinal motility.

[0134] Fatty acids, including butyrate, are the main energy source for colonic mucosal cells (Reodriger, Gut., 1980, Vol. 21, pp. 793-798), and are most important for colonic epithelial cells in the distal region of the colon. A strong nutritional effect of butyrate on the small intestinal mucosa has been observed in experimental animals (Guilloteau et al., 2 J Anim Feed Sci., 2004, Vol. 13, Supplement 1, pp. 393-396). A reduction in intestinal butyrate concentrations leads to atrophy of the colonic mucosa, which is generally explained by a reduced utilization of substrates by colonocytes. On the other hand, the administration of butyrate into the colonic lumen leads to weight gain, increased DNA synthesis, and increased intestinal crypt depth (Kripke et al., J Parenter Enter Nutr., 1989, Vol. 13, pp. 109-116).

[0135] High concentrations of butyrate obtained by fermentation of insoluble dietary fiber or after anal administration of butyrate can inhibit early and late stages of colon carcinogenesis by regulating the transcription, expression and activation of key proteins of the apoptotic cascade (Aviv-Green et al., J Nutr., 2002, Vol. 132, No. 7, pp. 1812-1818).

[0136] Chapman et al. (Gut, 1994, Vol. 35, No. 1, pp. 73-76) showed that inflamed colonic mucosa captures much more butyrate than glutamine or glucose. Experiments have shown that butyrate infusion leads to a significant reduction in inflammation and a reduction in the extent of ulceration in the colon wall of rats (Andoh et al., J Parenter Enter Nutr., 1999, Vol. 23, No. 5, pp. 70-73).

[0137] The effectiveness of butyrate enemas has been demonstrated by clinical observations in patients with ulcerative colitis (Han et al., Gastroenterol Clin North Am., 1999, Vol. 28, pp. 423-443; Scheppach et al., Gastroenterol Suppl., 1997, Vol. 222, pp. 53-57).

[0138] The direct anti-inflammatory activity of butyrate may be related to the inhibition of the migration of nuclear factor KappaB (NFKB) and its binding to DNA, and for the same reason, it may also inhibit the transcription and production of pro-inflammatory cytokines (Segain et al., Gut., 2000, Vol. 47, pp. 397-403).

[0139] In one embodiment, the compounds and compositions defined herein may be used to treat inflammatory bowel disease, such as Crohn's disease or ulcerative colitis.

[0140] ketone

[0141] As discussed above, compounds and compositions of the invention comprising C4 and medium chain fatty acids are rich sources of ketones.

[0142] In vivo, ketones are produced from fatty acids primarily by the liver via ketogenesis. In ketogenesis, medium-chain fatty acids are enzymatically broken down via β-oxidation to form acetyl-CoA and "ketone bodies" (water-soluble molecules containing ketone groups). Octanoate is the most effective medium-chain fatty acid in the preparation of ketone bodies via C4 ketogenesis. The three main ketone bodies are acetoacetate, β-hydroxybutyrate, and acetone. Therefore, in some embodiments, the compounds and compositions of the present invention are sources of acetoacetate, β-hydroxybutyrate, and / or acetone.

[0143] Ketogenesis can occur in response to ineffectiveness of blood glucose, such as during fasting, starvation, low carbohydrate diets, prolonged exercise, and untreated type 1 diabetes. In particular, ketogenesis is promoted by a low carbohydrate diet or "ketogenic diet". In one embodiment, the composition according to the invention is used as part of a low carbohydrate or ketogenic diet.

[0144] In addition to providing a fatty acid source for ketogenesis, butyrate can also stimulate the oxidation of fatty acids and the production of ketones (Cavaleri, F. and Bashar, E., 2018, Journal of Nutrition and Metabolism).

[0145] In one embodiment, a compound or composition according to the invention is used to provide ketones to a bodily fluid of a subject.

[0146] In one embodiment, the compounds or compositions according to the invention are used to increase blood ketone levels and / or to treat a disease that can be treated by increasing blood ketone levels.

[0147] Ketone bodies are transported from the liver to other tissues, particularly the brain. Ketones can be transported to the brain, for example, by monocarboxylate transporter 1 (MCT1), where they are primarily metabolized by neurons. Ketone bodies can provide an energy source by being reconverted into acetyl-CoA. When glucose is not as available as normal, the brain obtains part of its fuel needs from ketone bodies. The heart can also use ketone bodies effectively.

[0148] The free fatty acids and ketones produced from the triglycerides described herein can provide an alternative energy source to glucose to supplement or replace energy in cells, such as myocytes, cardiomyocytes, or neuronal cells. Thus, in metabolic disorders such as cancer, trauma, and ischemia, ketone bodies can be beneficial by providing an additional energy source to tissues at risk for cell death ( KW and Hartman, AL, 2008, Current treatment options in neurology, vol. 10, no. 6, p. 410). For example, the ketogenic diet (a way to promote ketone body production) is a treatment for drug-resistant epilepsy and may have therapeutic effects on a range of neurological disorders (Gano, L., Patel, M. and Rho, JM, 2014, Journal of lipid research, p. jlr-R048975).

[0149] Brain tissue consumes a large amount of energy in proportion to its volume. In average healthy subjects, the brain obtains most of its energy from the oxygen-dependent metabolism of glucose. Normally, most of the brain's energy is used to help neurons, or nerve cells, send signals, and the rest is used to keep cells healthy. A lack of brain energy (for example, caused by impaired glucose utilization) can lead to neuronal hyperactivity, seizures, and cognitive impairment.

[0150] Thus, the compounds and compositions of the present invention are useful for treating deficiencies in neurological disorders or diseases.The compounds and compositions of the present invention are useful for treating brain energy deficiencies and / or disorders associated with such deficiencies.

[0151] Examples of brain energy deficiency disorders or diseases include: migraine, memory impairment, age-related memory impairment, brain injury, neurorehabilitation, stroke and stroke sequelae, amyloid lateral sclerosis, multiple sclerosis, cognitive impairment, post-intensive care cognitive impairment, age-induced cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, inherited metabolic disorders (such as type 1 glucose transporter deficiency syndrome and pyruvate dehydrogenase complex deficiency), bipolar disorder, schizophrenia and / or epilepsy.

[0152] "Neurological disorder" refers to a disorder of the nervous system. A neurological disorder may be damage to the brain, spine, or nerves due to disease or injury. Examples of symptoms of a neurological disorder include paralysis, muscle weakness, poor coordination, loss of sensation, seizures, confusion, pain, and altered levels of consciousness. Responses to touch, pressure, vibration, limb position, heat, cold, and pain, as well as reflexes, may be assessed to determine if the subject's nervous system is damaged.

[0153] In one embodiment, the neurological disorder is the result of traumatic injury to the brain.

[0154] The terms "cognitive impairment" and "cognitive impairment" refer to disorders that cause impaired cognition, particularly disorders that primarily affect learning, memory, perception, and / or problem solving. Subjects may develop cognitive impairment following intensive care. Cognitive impairment may occur as part of the aging process.

[0155] The term “cognitive ability” refers to the collection of all mental abilities and processes, including knowledge, attention, memory and working memory, judgment and evaluation, reasoning and “calculation,” problem solving and decision making, comprehension, and the production of language.

[0156] Those skilled in the art can easily assess the level and improvement of cognitive ability using any suitable neurological and cognitive tests known in the art, including cognitive tests designed to assess information processing speed, executive function and memory. Suitable exemplary tests include Mini-Mental State Examination (MMSE), Cambridge Neuropsychological Test Automated Battery (CANTAB), Alzheimer's Disease Assessment Scale-Cognitive Test (ADAScog), Wisconsin Card Sorting Test, Verbal and Figural Fluency Test and Trail Making Test, Wisconsin Memory Scale (Wechsler Memoryscale) (WMS), Immediate and Delayed Visual Reproduction Test (Trahan et al., Neuropsychology, 1988, Vol. 19, No. 3, pp. 173-189), Rey Auditory Verbal Learning Test (RAVLT) (Ivnik, RJ. et al., "Psychological Assessment: A Journal of Consulting and Clinical Psychology, 1990, Vol. 2, pp. 304-312), electroencephalography (EEG), magnetoencephalography (MEG), positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), computed tomography, and long-term potentiation.

[0157] The ketogenic diet may also have therapeutic effects on metabolic diseases such as type 1 glucose transporter (GLUT-1) deficiency, pyruvate dehydrogenase (PDH) deficiency, phosphofructokinase (PFK) deficiency, and glycogen storage diseases including McArdle's disease (in addition to cancer (astrocytoma, prostate cancer, and gastric cancer) and myocardial ischemia. KW and Hartman, AL, 2008, Current treatment options in neurology, Vol. 10, No. 6, p. 410). The ketogenic diet has also been shown to be an effective strategy for the management of type 2 diabetes (Azar, ST, Beydoun, HM and Albadri, MR, 2016, J Obes Eat Disord, Vol. 2, No. 2).

[0158] Therefore, the compounds and compositions of the present invention can be used to treat type 1 glucose transporter (GLUT-1) deficiency, pyruvate dehydrogenase (PDH) deficiency, phosphofructokinase (PFK) deficiency; and glycogen storage diseases including McArdle disease and diabetes. The compounds and compositions of the present invention can also be used to treat cancer and myocardial ischemia.

[0159] Application

[0160] Preferably, the compounds and compositions described herein are administered enterally.

[0161] Enteral administration may be oral, gastric and / or rectal administration.

[0162] Generally, administration of the combinations or compositions described herein may be, for example, by the oral route or another route into the gastrointestinal tract, such as by tube feeding.

[0163] In a preferred embodiment, the administration is oral administration.

[0164] The subject may be a mammal, such as a human, canine, feline, equine, caprine, bovine, ovine, porcine, cervidae, and primate. Preferably, the subject is a human.

[0165] Further preferred features and embodiments of the invention will now be described by way of non-limiting examples.

[0166] Example

[0167] Unless otherwise indicated, the practice of the present invention will employ conventional techniques of chemistry, molecular biology, microbiology, recombinant DNA and immunology, which are within the capabilities of one of ordinary skill in the art and are described in the literature. See, e.g., J. Sambrook, E. F. Fritsch, and T. Maniatis, 1989, "Molecular Cloning: A Laboratory Manual", 2nd edition, Books 1-3, Cold Spring Harbor Laboratory Press; Ausubel, FM et al., (1995 and regular supplements; "Current Protocols in Molecular Biology", Chapters 9, 13, and 16, John Wiley & Sons, New York, NY); B. Roe, J. Crabtree, and A. Kahn, 1996, "DNA Isolation and Sequencing: Essential Techniques", John Wiley & Sons; J. M. Polk and James O'D. McGee, 1990, "In Situ Hybridization: Principles and Practice"; Oxford University Press; M. J. Gait (ed.), 1984, "Oligonucleotide Synthesis: A Practical Approach", Irl Press; DMJ Lilley and JE Dahlberg, 1992, "Methods of Enzymology: DNA Structure Part A: Synthesis and Physical Analysis of DNA Methods in Enzymology", Academic Press; and EM Shevach and W. Strober, 1992 and regular supplements, "Current Protocols in Immunology", John Wiley & Sons, New York, NY. Each of these general texts is incorporated herein by reference.

[0168] Example 1—Preparation of butyrated triglycerides (TAG)

[0169] The composition comprising butylated TAG is generated by chemical transesterification between tributyrin and tricaprylin in the presence of sodium methoxide catalyst.

[0170] Use the following steps:

[0171] reaction

[0172] · Glyceryl tricaprylate (Neobee 895 from Stepan) and glyceryl tributyrate were mixed at room temperature.

[0173] The esters were added sequentially to the multifunctional reactor L2600. 1 liter of glyceryl tricaprylate was set aside to facilitate the addition of sodium methoxide.

[0174] Degas with nitrogen while stirring.

[0175] • Heat the reactor to 60°C.

[0176] - Add sodium methoxide suspended in 1 liter of tricaprylin (stir before addition).

[0177] Heat the mixture to 80°C under an inert atmosphere (nitrogen) for 3 h (starting from 60°C).

[0178] Start counting.

[0179] Post-processing

[0180] - Cool the mixture to below 60°C.

[0181] The mixture was washed in deionized water (approximately 8 L) until a neutral pH was obtained (elimination of formazan).

[0182] Sodium alcoholate).

[0183] After the first wash, empty the reactor and if part of the sodium methoxide is glued to the wall,

[0184] - Wash in hot water.

[0185] After the final wash and removal of the aqueous layer, the crude oil was dried under vacuum (60 mbar and 60

[0186] ℃ until no water remains).

[0187] refined

[0188] · Add 3% of Tonsil Supreme 110FF to the suspension.

[0189] - Stir and heat at 70°C under vacuum (60 mbar) for 40 min.

[0190] Nitrogen compensation.

[0191] • Filter the bleaching lands on a büchner (Filtrox 8-20 micron).

[0192] 16.48 kg crude product.

[0193] Deodorization

[0194] Add 8 kg of decolorized product to 6 L of L800 deodorant.

[0195] Heating at 142°C and 0.8 mbar with steam injection (Vwater / h = 30 mL / h) for 3 h (145

[0196] ℃ to 1 mbar, 149℃ to 1.2 mbar, 154℃ to 1.5 mbar).

[0197] · Samples were collected at 1 hour, 2 hours and at the end of deodorization.

[0198] Cool to 60°C (1h15).

[0199] Nitrogen compensation.

[0200] ·filter.

[0201] Gained 6.07 kg.

[0202] The composition of the triglycerides is shown in Table 1 below. These triglycerides are represented by the three fatty acids they contain. These fatty acids are represented by their lipid numbers: butyrate is 4:0; octanoic acid is 8:0.

[0203] The middle fatty acid is located at the sn-2 position in the triglyceride. For example, 8:0-4:0-8:0 is a triglyceride that has both butyrate at the sn-2 position and caprylate at the sn-1 and sn-3 positions.

[0204] TAG distribution and regioisomers were analyzed by liquid chromatography coupled to a high-resolution mass spectrometer. The proportions of lipid classes were assessed by liquid chromatography coupled to an evaporative light scattering detector (ELSD).

[0205] The C4C8 triglyceride composition has good organoleptic properties (neutral taste, no odor).

[0206] Table 1: TAG regioisomer distribution [g / 100g]

[0207] C4 / C8 crude product C4 / C8 after deodorization TAG g / 100g TAG g / 100g TAG 8:0-8:0-4:0 26.5 26.6 4:0-4:0-8:0 18.51 18.6 8:0-8:0-8:0 16.04 20.1 4:0-8:0-4:0 14.25 13.2 4:0-4:0-4:0 10.98 4.4 8:0-4:0-8:0 8.89 11.8 4:0-10:0-8:0 0.78 1 4:0-8:0-10:0 0.54 0.6 8:0-4:0-10:0 0.52 0.6 4:0-4:0-10:0 0.49 0.5 8:0-8:0-10:0 0.41 0.5 4:0-10:0-4:0 0.4 sum 97.9 98.4

[0208]

[0209] Example 2— (In vivo) Administration of Butyrated Triglycerides (TAG)

[0210] After an overnight fast, at time 0, 15 healthy volunteers orally took 15 g of C4C8 butyrylated triglyceride "MCT C4 / C8" of Example 1 emulsified in 70 mL of a 5% aqueous solution of milk protein, and 15 healthy volunteers orally took 15 g of medium chain triglycerides, wherein a mixture of "MCT" with a C8:C10 ratio of about 58:42 was emulsified in 70 mL of a 5% aqueous solution of milk protein. At time 30 min, a standard breakfast was provided and consumed within 15 min. Blood samples were collected at regular intervals within 4 h via an intravenous catheter, and C3, C4, C8, 3-hydroxybutyric acid (BHB) and acetoacetate (AcAc) in plasma were analyzed by UPLC-MSMS.

[0211] The mean total plasma ketone (BHB and AcAc) levels of 15 patients in each treatment group: C4C8 butyrated triglycerides "MCT C4 / C8" group and MCT group over 4 hours are shown in Figure 1 In. Figure 1 As can be seen in Figure 3, higher maximum concentrations of plasma ketones were observed for the C4C8 butyrated triglyceride treatment group.

[0212] Plasma C3, C4, C8, BHB, AcAc, and total ketone levels over 4 hours for one individual from the C4C8 butyrated triglyceride "MCT C4 / C8" treatment group are shown in Figure 2 and Figure 3 Total ketone levels were the sum of 3-hydroxybutyrate and acetoacetate measured by UPLC-MSMS.

Claims

1. A composition comprising a compound having the formula or a combination thereof, wherein n1, n2, n3, n4, n5 and n6 are independently 4 to 10.

2. The composition according to claim 1, wherein the composition comprises a compound having formula (1), a compound having formula (2), a compound having formula (3) and a compound having formula (4).

3. A composition according to claim 1 or 2, wherein the compound of formula (1), (2), (3) and (4) accounts for at least 50%, 60%, 70%, 80%, 90%, 95% or 99% by weight of the total triglycerides in the composition.

4. The composition according to claim 1, comprising a compound having the formula or a combination thereof.

5. The composition according to claim 4, wherein the composition comprises a compound having formula (5), a compound having formula (6), a compound having formula (7) and a compound having formula (8).

6. A composition according to claim 4 or 5, wherein the compound of formula (5) accounts for 20% to 30% by weight of the total triglycerides in the composition, the compound of formula (6) accounts for 15% to 25% by weight of the total triglycerides in the composition, the compound of formula (7) accounts for 10% to 20% by weight of the total triglycerides in the composition, and the compound of formula (8) accounts for 5% to 15% by weight of the total triglycerides in the composition.

7. A composition according to any one of claims 4 to 6, wherein the compound of formula (5), (6), (7) and (8) comprises at least 50%, 60%, 70%, 80%, 90%, 95% or 99% by weight of the total triglycerides in the composition and / or comprises at least 50%, 60%, 70%, 80%, 90%, 95% or 99% by weight of the total butyrate-containing triglycerides in the composition and / or comprises at least 50%, 60%, 70%, 80%, 90%, 95% or 99% by weight of the total caprylate-containing triglycerides in the composition.

8. The composition according to any one of claims 1 to 7, wherein tributyrin represents less than 10 wt. % of the total triglycerides in the composition, preferably less than 8 wt. % of the total triglycerides in the composition, more preferably less than 5 wt. % of the total triglycerides in the composition.

9. The composition according to any one of claims 1 to 8, wherein the composition is a nutritional composition, preferably wherein the composition is a dietary supplement, optionally wherein the dietary supplement is in the form of a capsule, tablet, sachet, powder or liquid pellet.

10. Use of a composition according to any one of claims 1 to 9 for providing a butyric acid source with improved organoleptic properties.

11. A composition according to any one of claims 1 to 9 for use in increasing blood ketone levels and / or treating a disease treatable by increasing blood ketone levels, preferably wherein the disease is selected from the list consisting of brain energy deficiency, neurological disorders, migraine, memory impairment, age-related memory impairment, brain injury, stroke, amyloid lateral sclerosis, multiple sclerosis, cognitive impairment, post-intensive care cognitive impairment, age-induced cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, inherited metabolic disorders (such as type 1 glucose transporter deficiency syndrome and pyruvate dehydrogenase complex deficiency), depression, schizophrenia, epilepsy, narcolepsy, diabetes, obesity, non-alcoholic fatty liver disease and polycystic ovary syndrome.

12. The composition according to any one of claims 1 to 9, for use in treating or preventing neurological diseases, metabolic diseases, cancer and / or myocardial ischemia.

13. Compounds having the formula or a combination thereof, the compound is used for increasing blood ketone levels, wherein n1, n2, n3, n4, n5 and n6 are independently 4 to 10, preferably wherein n1=6, n2=6, n3=6, n4=6, n5=6 and n6=6.

14. Compounds having the formula or a combination thereof, the compound is used as a drug, preferably for preventing or treating neurological diseases, metabolic diseases, cancer or myocardial ischemia, wherein n1, n2, n3, n4, n5 and n6 are independently 4 to 10, preferably wherein n1=6, n2=6, n3=6, n4=6, n5=6 and n6=6.

15. A process for preparing a composition according to any one of claims 1 to 9 or a compound of formula (1), (2), (3), (4), (5), (6), (7) or (8) as defined therein, said process comprising the transesterification of tributyrin with one or more triglycerides selected from the list consisting of tricaproic acid glyceryl, triheptanoic acid glyceryl, tricaprylic acid glyceryl, trinonanoic acid glyceryl, tricapric acid glyceryl, triundecanoic acid glyceryl and tridodecanoic acid glyceryl, preferably wherein the triglyceride is tricaprylic acid glyceryl.

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