EP1931356A2 - Butyric acid ester of carbohydrates and carbohydrate polyols - Google Patents

Abstract

The invention relates to butyric acid ester or butyric ester of carbohydrates and carbohydrate polyols and their use as butyric carrier and butyric source for the gastro-intestinal tract, essentially for the prevention and treatment of diseases of the gastro-intestinal tract, particularly the colon.

Description

 Butyric acid esters of carbohydrates and carbohydrate polyols

The invention relates to butyric esters or butyrate esters of carbohydrates and carbohydrate polyols and their use as butyric-carrier and butyrate source for the gastrointestinal tract, in particular for the prevention and treatment of diseases of the gastrointestinal tract, especially of the colon.

The C ₄ acid butyric acid (butyrate) in the colon of a mammal is generally derived from the fermentation of undigested dietary constituents, especially undigested carbohydrates, by the microbial flora of the colon. Butyrate is the dominant source of energy for epithelial cells, particularly epithelial cells of the posterior colon. In addition to its role as an energy substrate for the colonocytes, butyrate also affects physiological functions such as cellular proliferation, differentiation and apoptosis, plays a central role as a growth factor for a healthy intestinal epithelium and in the maintenance of the mucosal barrier in the colon. Butyrate contributes to the detoxification of possible mutagenic metabolites in the colon and counteracts oxidative stress, for example by inducing gene expression of protective proteins such as intestinal glutathione-S-transferase or the inhibition of ornithine decarboxylase. Furthermore, butyrate acts to control the induction of specific genes of cell cycle regulation, antibacterial peptides and signaling cascades.

Shortage of short chain fatty acids such as butyrate is associated with various inflammatory, infectious and malignant diseases of the intestine. A lack of butyrate can lead to Colon exudates, such as colonic diversion or pseudomembranous colitis (Rombeau, et al., 1995). In pseudomembranous colitis, which occurs at 1-2% of all antibiotics, it comes to a serious clinical picture, which is mainly caused by an infection with the bacterium Clostridium difficile. Butyrate is also important in preventing infection in antibiotic-associated diarrhea, which occurs at 10 to 20% of all antibiotic intakes, and in traveler's diarrhea, which affects 25% of Mediterranean travelers and 50% of tropical or subtropical travelers. Butyrate also plays a role in the pathogenesis of other inflammatory diseases of the colon, such as ulcerative colitis (ulcerative colitis). The diminished iuminal availability of butyrate is considered a factor in such diseases (Cummings, 1995).

The prevalence of inflammatory bowel disease such as

Ulcerative colitis is estimated to be about 0.1%, as is the prevalence of Crohn's disease. The prevalence of irritable bowel syndrome is much higher at 1, 1%. The provision of butyrate in the colon is considered in these diseases as a suitable measure for remission maintenance as well as to improve wound healing, for example after intestinal surgery (Wächtershäuser et al., 2000). Also for colorectal carcinoma, the incidence of which is estimated at about 0.1%, as well as for carcinogenesis, butyrate is considered to be a significant protective factor.

High butyrate concentrations in the colon, especially in the back

Large intestinal areas where inflammatory, infectious and malignant intestinal diseases are essentially localized support a healthy intestinal environment and a healthy intestinal epithelium, improve symptoms of ulcerative inflammation of the colon, prevent infection and are a major protective factor for colorectal cancer, that is, reduce it the risk To get colon cancer. Due to the high incidences infectious, inflammatory and malignant diseases of the intestine cause significant health costs. Measures to support intestinal health by providing sufficiently high levels of butyrate in the colon, especially in the bowel, therefore, have great economic potential to reduce the health costs of these diseases.

In addition to the general provision of butyrate for the colon, so far availability has been the most important over the entire length of the colon, especially in specific regions such as the hindquarters

Intestinal areas critical (Scheppach et al., 1992). Known remedies for providing butyric acid to the colon are the oral administration or consumption of indigestible carbohydrates. Indigestible carbohydrates of food such as the resistant starch or pectin used in foods could

Starting materials for the formation of butyrate after fermentation through the microflora of the colon. Cummings et al. (1996), however, report considerable individual differences in the fermentative production of butyrate; Some people are unable to make indigestible carbohydrates by microbial fermentation in the colon butyrate.

The proportion of butyrate formed in the fermentation can vary widely. It depends on the particular fermented carbohydrate. From various indigestible carbohydrates such as inulin, polydextrose, pectin or arabinogalactan little butyrate is formed but predominantly acetate, propionate and gases such as hydrogen, carbon dioxide and methane (Cummings et al., 2001).

The concentration of butyrate formed in the fermentation of indigestible carbohydrates is high in the anterior colon, but decreases towards the posterior colon (Cummings et al., 1995). to

Support the intestinal health and as a protective factor high butyrate concentrations are beneficial over the entire colon, especially in the posterior areas.

Up to about 5 g / day of butyrate are considered to be preventative or therapeutically effective butyrate (Scheppach et al., 1992). According to Vernia et al. (2000) 4 g / day butyrate support the therapeutic effect of mesalazine (2.4 g / day) in the treatment of ulcerative colitis. This is an amount that can not be achieved by the fermen- tative breakdown of carbohydrates in the colon. For example, it is known that degradation of 30g / day fermentable substrate (dietary fiber, resistant starch, etc.) results in the formation of an average of 2.2g of butyrate (Wolin, 1981). Accordingly, only about 0.07 g of butyrate are formed per 1 g of known fermentable substrates.

It would be advantageous to provide larger amounts of butyrate through the diet in the colon. Free, that is unbound

Butyrate, which is absorbed through the diet, is rapidly and completely absorbed in the small intestine and thus does not enter the large intestine (Schmitt et al., 1976). In the field of food technology, the possibilities of using pure or free butyric acid are limited. Another disadvantage is that free butyric acid is a generally sensory, taste or organoleptically unattractive substance and can not be used directly in foods or drinks. Tributyrin (triglyceride with 3 molecules of butyrate) is known to be rapidly cleaved and formed in the anterior small intestine after oral administration

Butyrate is already absorbed in the small intestine (Gaschott et al., 2001). Oral tributyrin does not enter the colon and is found to be ineffective in the prevention of colon cancer (Newmark et al., 1994).

Alternatively, intravenous administration of butyric acid and of butyric acid esters based on xylitol and other monosacchar rids and derivatives as (pro) -harmaives (Desmet et al., 1991, Pouillart et al., 1992, Santini et al., 1998). The release of butyrate in the colon is not described in this work. On the other hand, intestinal rinses (enema) with short-chain fatty acids such as butyric acid are known (Scheppach et al., 1992).

The technical problem underlying the present invention is thus, above all, to provide means and measures in order to supply the large intestine therapeutically or preventively with sufficient butyrate quantities, especially by simple oral or enteral administration.

The technical problem is solved by the use of at least one Buttersäureesters or a mixture of at least two different Buttersäureestern (Buttersäureester mixture) as Butyratquelle in the digestive tract of the human or animal see body, especially for the treatment and / or prevention of or against diseases of the stomach Intestinal tract, especially the anterior and / or posterior sections of the intestine, especially the large intestine, but especially the colon. According to the invention, the butyric esters are esters of at least one carbohydrate, esters of at least one carbohydrate polyol and / or esters of mixtures of carbohydrate and carbohydrate polyol. The butyric acid ester (s) used according to the invention are preferably administered orally or enterally, especially in micro- and / or macroencapsulated form.

It has surprisingly been found that esters of butyric acid (n-

Butane acid) with carbohydrates and / or with carbohydrate polyols, ie saccharides or saccharide alcohols, can be used as a small intestinal-stable carrier for butyrate. Certain butyric esters of carbohydrates and polyols are surprisingly stable in passage through the stomach and small intestine. They are caused by enzymes present in the small intestine, such as pasen and esterases are not degraded, and there is no butyrate released from it. The bound butyrate thus escapes the digestion and absorption in the small intestine. Advantageously, the butyric acid esters used according to the invention are unchanged in the large intestine. There, the esterified butyric acid is then released from the butyric acid esters by the microbial activity of colon-based bacteria.

This shows above all that,

a) with increasing degree of substitution (DS) of the butyric acid esters, the metabolism and release of butyric acid becomes lower; voiiständig esterified derivatives surprisingly cause a lower release of butyric acid in the colon as partially esterified derivatives;

b) the butyric acid release in the large intestine is surprisingly higher in pure butyric acid derivatives than in the mixed acid derivatives of acetate and butyrate;

c) the release of butyric acid in the large intestine surprisingly depends on the type of carbohydrate or carbohydrate polyol used and also on the degree of esterification;

d) the butyric esters of C ₅ polyols such as xylitol, the C6 polyols such as sorbitol and the disaccharide polyols such as isomalt, each with a DS of 3 to 4, surprisingly lead to a particularly high butyric acid release in the colon.

As also explained in the examples below, for example, the fermentation of sorbitol per 1 g of substrate produces only about 0.3 g of butyrate, and the fermentation of the unesterified carbohydrate polyols isomalt and xylitol results in about 0.2 g and about 0.3 g, respectively butyrate. When degrading other fermentable carbohydrates rate of resistant starch is about 0.2 g of butyrate per 1 g of substrate. In contrast, in tributyrylsorbitol or tetrabutyrylsorbitol according to the invention, surprisingly, about 0.7 g of butyrate are liberated per 1 g of substrate. Likewise, up to 0.7 g of butyrate per 1 g of substrate are also formed from tributyrylxylitol or tetrahydrobyxylitol which is preferred according to the invention. With butyric acid esters according to the invention, surprisingly and advantageously about 3 times more butyrate is formed in comparison with non-esterified substrates. When used according to the invention, the butyric esters according to the invention "deliver", a) due to

Release of the esterified butyrate residues and preferably b) due to the fermentative degradation of the carbohydrate or Kohlenhydratpolyolrests, much more butyrate can be formed in the colon than by the purely fermentative degradation of known non-esterified substrates.

The butyric acid esters of carbohydrate polyols used in accordance with the invention are particularly suitable for supplying the large intestine with the butyrate amounts of about 0.5 to 5 g / day required therapeutically or preventively. These butyrate amounts could already be achieved at a take up of from 0.7 to 7 g / day of butyric acid esters such as tri- and tetrabutyrylsorbitol as well as tri- and tetrabutylaryl. For the same amount of butyrate, it would be necessary to supply unesterified substrates by way of fermentative degradation of carbohydrates, such as resistant starch, in amounts of up to 70 g, that is, almost 10 times more substance.

The results of incubation experiments with colon bacteria in humans show that the butyric esters used according to the invention are surprisingly metabolized only slowly. That is, butyrate is released and formed over a long period of time, especially over more than 72 hours. The butyric acid esters used according to the invention thus provide a continuous and a long-lasting source of butyrate in the colon. The slow release ensures that butyric acid esters used according to the invention are present throughout the large intestine passage and thus also reach the rear colon regions. As a result, sufficiently large amounts of butyrate are advantageously still available in the posterior regions of the colon, and can thereby develop prophylactic or therapeutic effects in those areas of the intestine where the inflammatory, infectious or malignant diseases occur most frequently.

The butyric acid ester used according to the invention preferably has a degree of substitution (DS) of 3 to 4. Also preferred are - depending on the field of application and starting compound - DS of 1, 2, 3, 4, 5, 6, 7, 8 and 9. Preferably, the butyric acid ester is partially esterified and preferably has a degree of esterification of 10 to 90%, 30 to 90 %, 40 to 80% and especially from 50 to 80%. Also preferred are - depending on the field of application and esterified starting compound - degrees of esterification of at least 10, 20, 30, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90 or 95% and / or at most 10, 20, 30, 40, 45, 50, 55, 60, 65, 70, 75,

80, 85, 90 or 95%.

In a preferred variant, the carbohydrate or the carbohydrate polyol is a monosaccharide, disaccharide, oligosaccharide, polysaccharide. Preference is also given to mixtures of at least one carbohydrate and at least one

Carbohydrate polyol, mannitol, sorbitol, xylitol, lactitol, maltitol, erythritol, isomalt, 1, 6-GPS, 1, 1-GPS, 1, 1-GPM, hydrogenated starch hydrolyzate, hydrogenated glucose syrup and / or a mixture thereof. Preferably, the carbohydrate polyol is a C ₅ -PoIyOl and / or a C ₆ polyol. In a further preferred variant, the carbohydrate polyol is a

Disaccharidpolyol. In a preferred embodiment, the butyric acid ester used according to the invention is tributyrylsorbitol, tetrabutyrylsorbitol, tributyrylxylitol, tetrabutyrylxylitol, pentabutyrylisomalt or a mixture thereof and / or a mixture with other butyric acid esters. Butyric acid isomalt esters are also distinguished by their less unpleasant taste, in comparison to other butyric esters used according to the invention, for example butyric acid sorbitol esters.

The invention also provides the use of mixed esters with butyrate and other short-chain alkanoic acids, preferably acetate.

Hergesteiit the alkanoic acid esters, ie butyric acid esters and others, in a conventional manner, preferably by reaction with alkanoic acid or acid anhydride. Depending on the DS to be obtained, the molar ratio of carbohydrate and / or carbohydrate polyol to acid or acid anhydride is generally from 1: 1 to 1:10, in particular from 1: 3 to 1: 6. The esterification can be carried out in the presence of an acidic catalyst, such as tin oxalate respectively. Excess acid is then removed in a conventional manner.

A preferred object of the invention is the use of the above-characterized butyric acid ester for the prophylactic and / or therapeutic support of a healthy intestinal milieu and a healthy intestinal epithelium as well as for the treatment or prevention of diseases of the gastrointestinal tract of the human or animal body.

Such diseases are diseases associated with butyrate administration in the

Colon can be treated or prevented. These include, but are not limited to, diseases associated with butyrate deficiency in the gastrointestinal tract, diseases and conditions wherein butyrate contributes to the detoxification of potential mutagenic metabolites in the colon, diseases and conditions wherein butyrate oxidati- It counteracts stress, for example via the induction of gene expression of protective proteins such as intestinal glutathione-S-transferase or the inhibition of ornithine decarboxylase, diseases with a pathological, toxic or drug-related impairment or damage to the epithelial cells and colons of the posterior colon or the mucosal barrier in the large intestine, inflammation of the colon such as colitis or pseudomembranous colitis, chronic inflammatory bowel disease such as ulcerative colitis and Crohn's disease and irritable bowel syndrome, infections with clostridia, antibiotic-associated diarrhea, traveler's diarrhea, colorectal carcinoma. The use according to the invention also provides remission maintenance and improvement of wound healing, for example after intestinal surgery.

Accordingly, the invention provides for the use of at least one of the butyric acid esters or a butyric acid ester mixture as an active ingredient, in particular as a therapeutic agent. These are preferably used in pharmaceuticals, pharmaceutical compositions, drug-like preparations. When used as an active ingredient, the butyric acid esters are preferably used together with other pharmacologically suitable vehicles, additives and auxiliaries, such as lubricants, release agents, thickeners, emulsifiers, stabilizers, preservatives, lecithin, intensive sweeteners, sweeteners, colorants, flavorings, flavorings, coating materials and or

Fillers used.

According to the invention, the use preferably takes place in solid and / or liquid, in particular in suspended or dissolved form. As suspension and solvent are preferably food-compatible solvents and emulsifiers in

Consider, including water, alcohols and mixtures thereof intended. The administration is preferably carried out - depending on the field of application - in the form of suspension, solution, emulsion, drops, juices, tablets, pills, capsules, troches, dragees, jellies, granules, powders, solution for injection or infusion, or in combinations thereof. The use can also take place in a further, similarly suitable dosage form.

Especially preferred according to the invention is the administration of butyric acid esters in microencapsulated or macroencapsulated form into the human or animal body.

As a result, butyric acid esters can be administered in an organoleptically neutral form. Above all, a taste-neutral transport through the digestive tract is made possible. Preferably, at least one butyric acid ester is present in micro- and / or macroencapsulated form. The encapsulation allows an improved, especially delayed or uniformed and continuous release of Buttersäureester at the target site in the gastrointestinal tract or large intestine. Next can be extended by the encapsulation of the application area; It is possible to prepare dry blends as well as well metered systems containing the butyric acid esters or mixtures according to the invention. Sensory negative effects of the butyric acid esters according to the invention, which are partly present, can be largely concealed by the encapsulation.

In the present case, "encapsulation" of the butyric acid ester is understood to mean an encapsulation which is based primarily on the binding of the

Butyric acid ester to a carrier, for example by adsorption, covalent or ionic bond or linkage with bi- or multi-functional reagents based. Furthermore, the encapsulation is preferably also based on the inclusion of butyric acid esters in a matrix or membrane, for example by ionotropic gelation, polyelectrolyte complexes, symplexes, Cold gelation, formation of hydrocolloids, polymerization and / or solvent precipitation.

Preferably, at least one butyric acid ester is encapsulated by inclusion process in at least one shell material.

As materials for encapsulation of the invention

Butyric acid ester is preferably at least one agent selected from alginates, agar-agar, agarose, pectins and pectinates, guar gum, chitosan, cellulose derivatives, starch derivatives, gum arabic, waxes, mono-, di- and triglycerides and other organic and inorganic substances used , In a particularly preferred embodiment, polysaccharides, in particular pectinate and alginate, are used for the encapsulation. The forms of micro- and macroencapsulation of the butyric acid esters are preferably selected from spheres, cylinders, fibers or films, tablets, granules, powders, pills, lozenges, dragees and

Jellies.

After the addition of the butyric acid ester, at least one further protective layer of pure carrier material is preferably applied to complete the microencapsulation toward the outside. Alternatively, a conventional coating material used in pharmacy, for example hydroxypropylmethylcellulose (HPMC), is coated in a manner known per se. Particular preference is given to using a fluidized-bed agglomerator for fluidized-bed drying.

The production of microencapsulated butyric acid esters is preferably carried out by means of atomizers, for example via the blow-off, electrostatic or vibratory method, by means of rotating disks and / or nozzles and jet cutters. Particular preference is given to polysaccharides, preferably pectinate, alginate, together with butyric acid ester or butyric acid ester mixture in prepared a solution and the solution obtained by means of atomizer, preferably by means of jet cutter dripped into a precipitation solution. The precipitation solution used is preferably calcium chloride solution or magnesium chloride solution. The resulting beads (spheres) have a diameter of less than 50 microns.

Preferably, the beads are then dried in a fluidized bed dryer.

As a manufacturing method for a microencapsulation are further essentially known in the food industry methods such as spray drying, freeze-drying,

Fluidized bed drying, fluidized bed agglomeration or extrusion.

In spray drying, in a preferably continuous process, a syrup of a wall material, for example, sugars, polyols and maltodextrin or other well crystallizing starch products, dried in conjunction with Buttersäureester or Buttersäureester mixture by spraying the syrup, so that a solid, powdery or granular product wherein the butyric acid esters are encapsulated in the selected wall material.

In the freeze-drying, wall material, for example, a

Sugar, polyol or a maltodextrin, with butyric acid ester or butyric acid ester mixture brought together in solution or suspension. After flash freezing and removal of the water in a conventional manner, a powder is obtained in which the Buttersäureester are embedded.

In microencapsulation by means of fluidized bed drying, wall material is introduced as a finely ground powder, for example sugar, polyol or maltodextrin, and then sprayed with an aqueous solution or suspension of the butyric acid ester or butyric acid ester mixture. In a preferred embodiment are the nozzles for spraying the solution or suspension above the fluidized bed (topspray method). In an alternative embodiment, the nozzles are integrated in the bottom of the fluidized bed system (bottom spray method). By the fluidized bed drying particles according to the invention are constructed, which contain up to 20% of Buttersäureesters or Buttersäureester mixture.

Preferably, at least one of the above-characterized butyric acid esters is used as the sole source of butyrate, as the sole therapeutic or prophylactic active ingredient. In a further preferred variant, butyric acid ester is used together with at least one further butyrate source and / or at least one further active ingredient for the treatment or prevention of these diseases.

The use is preferably according to a treatment plan wherein a therapeutically and / or prophylactically effective dose is administered as a single dose or multiple doses, for example throughout the day, and preferably repeatedly administered over a given period of time. Preference is given to a dose of 0.7 to

7 g / day given in a single dose or in divided doses 2 to 5 times a day. Due to the found slow release of butyrate, the correspondingly multiplied daily dose may also be administered every 2, 3 or 4 days, preferably every 72 hours. The dose is mainly from an adult human with 75 kg body weight, for children and for use in animals, the doses must be adjusted accordingly.

In a preferred variant, the use in combination with at least one further active ingredient, in particular in the sense of a

Combination therapy, for example, for the treatment of Diseases such as a manifest colon carcinoma by means of chemotherapy (for example, with 5-Fluorouracιl) provided

The invention also provides a process for the treatment or prevention of the diseases, in particular of the gastrointestinal tract, comprising the, preferably oral or enteral,

Administration of the butyric acid ester into the human or animal body, preferably in a therapeutically or prophylactically effective dose

The invention also provides a pharmaceutical composition comprising at least one of the above-characterizing butyric acid esters as at least one active ingredient as a medicament in the treatment or prevention of the diseases, in particular of the gastrointestinal tract, of the human or animal body

The invention also relates to the use of the above-characterized butyric acid ester as an active ingredient in food, food, semi-luxury foods and animal feeds and preferably for the manufacture of a medicament for the treatment or prevention of the diseases, in particular those of the gastrointestinal tract, of the human or animal body

In the context of the invention, "foodstuffs" are understood to mean, in particular, foods and semi-luxury foods as well as animal feeds, which in particular have a nutritional value and can serve the partial or complete nutrition of the human or animal body

Special foods such as baby foods, dietary foods, tube feeds for enteral nutrition and the like are understood to include animal feed, that is, all types of food for animals both in small animals and livestock, such as farm animals, sport horses, but also domestic, zoo and luxury animals, understood. According to this invention, the food is present as a concentrate, as a raw material or as a semi-finished product. In the present case, foods also include drinks such as soft drinks, soft drinks, effervescent drinks, fruit juice drinks, lemonade, energy drinks, fruit juices, sweet must,

Fruit nectars, coffee, cocoa, milk, mineral drinks, tea and infused drinks and alcoholic beverages such as beer, Nährbier, mixed beer drinks, sour milk drinks (Kefir, Kumys u.a.), wine, fruit wine (cider, etc.) understood.

The invention also relates to a composition, in particular a food, feed or medicament containing at least one butyric acid ester or a butyric acid ester mixture used in accordance with the invention. In preferred embodiments, the composition contains at least one further constituent; this one is selected from:

Carbohydrate polyols, preferably mannitol, sorbitol, xylitol, lactitol, maltitol, erythritol, isomalt, 1, 6-GPS, 1, 1-GPS, 1, 1-GPM, hydrogenated starch hydrolysates, hydrogenated glucose syrups and mixtures thereof;

Carbohydrates, preferably monosaccharides, disaccharides, oligosaccharides, polysaccharides and mixtures thereof;

soluble and / or insoluble fiber, preferably prebiotic and / or butyrogenic fiber, in particular resistant starch, modified starch, polydextrose,

Fructo-oligosaccharides, galactooligosaccharides, transgalactosylated oligosaccharides such as 6'-galactosyllactose or 4'-galactosyllactose lactulose, lactobionic acid, maltobionic acid, xylo-oligosaccharides, lacto-sucrose, malto-oligosaccharides, isomalto-oligosaccharides, gentio-oligosaccharides riden, glucosylsucrose, soybean oligosaccharides, chito-oligosaccharides, chitosan oligosaccharides, pectin, pectin oligosaccharides, condensed oligosaccharides, caramel products, galactomannan oligosaccharides, fucose-containing oligosaccharides, fucosederivative oligosaccharides, pyrodextrin, partially hydrolyzed guar gum, a by partial hydrolysis, hydrogenation, oxidation, enzymatic, chemical modification of saccharides obtained variant thereof, and fiber materials, in particular from oats, wheat, vegetables such as tomato or pea, fruits such

Apples and fruit berries, sugar beets, carob fruits or cellulose;

short-chain fatty acids, preferably butyric acid, propionic acid, acetic acid, lactic acid;

Butyric acid glycerol esters, preferably glycerol tributyrate,

Glycerol dibutyrate, glycerol monobutyrate; and

acylated starch, preferably butyrylated starch.

In a further variant, the composition contains a mixture of at least two of the abovementioned components, in particular of at least one carbohydrate and at least one carbohydrate polyol.

The invention also relates to such a foodstuff selected from:

Dairy products and dairy products such as cheese, butter, yoghurt, kefir, quark, sour milk, buttermilk, cream,

Condensed milk, dried milk, whey, milk sugar, milk protein, milk mix, milk half fat, whey mixed or milk fat products or preparations; Milk fat products, mixed fat products, edible fats and edible oils;

Pudding, cream, mousse and other desserts;

Baked goods such as bread including biscuits and pastries, long-life baked goods, biscuit products and waffles;

Spreads, greasy spreads, margarine products and shortenings;

Instant products and brewery products;

Fruit products or preparations such as jams, marmalades, jellies, fruit preserves, fruit pulp, fruit pulp, fruit juices,

Fruit juice concentrates, fruit nectar and fruit powder;

Cereals, muesli and cereal mixes, and prepared cereal-containing products such as cereal bars and breakfast products;

non-alcoholic drinks, beverage bases and

Powdered drinks; and

Confectionery such as chocolates, hard caramels, soft caramels, chewing gum, dragees, fondant products, jelly products, licorice, marshmallows, flakes, dragées, comestibles, candied fruit, brittle, nougat

Products, ice cream, marzipan, ice cream.

The invention also relates to a dietary special diet derived therefrom and enteral nutrition.

Finally, the invention also relates to a composition comprising at least one of the above-characterized butyric esters as animal feed such as pet food, Premixes for pet food, high-starch feed, concentrate and concentrated feed. Precisely in the animal breeding and meat industry, prophylaxis and therapy of intestinal diseases can thus be made possible or supported in a way that is harmless to humans and animals.

The invention preferably provides the use of the butyric acid esters or mixtures thereof in enteral nutrition products and as a nutritional supplement or nutritional supplement.

The invention will be explained in more detail with reference to the following examples and figures; These are not meant to be limiting.

The figures show:

FIG. 1 shows a diagram of the digestibility of various butyric acid xylitol,

Sorbitol or isomalt ester.

FIG. 2 is a graph of butyrate formation during in vitro fermentation with intestinal bacteria as a function of intestinal bacteria

Time when using different substrates.

Example 1: Butyric acid ester based on sorbitol (DS 3)

In a stirred tank, 100 g of sorbitol (0.55 mol) were suspended in 260.6 g of butyric anhydride (1.65 mol). After heating the suspension to 160 ⁰ C, the mixture was further stirred for 2 hours.

After completion of the reaction, the excess acid was removed under vacuum. The product obtained was a clear light yellow syrup.

Example 2: Butyric Acid Ester Based on Sorbitol (DS 4)

In a stirred tank, 100 g of sorbitol (0.55 mol) were suspended in 347.4 g of butyric anhydride (2.2 mol). After heating the suspension At 160 ^° C., the mixture was stirred for a further 2 hours. After completion of the reaction, the excess acid was removed under vacuum. The product obtained was a clear light yellow syrup.

Example 3 Butyric Acid Ester Based on Sorbitol (DS 6)

In a stirred tank, 100 g of sorbitol (0.55 mol) were suspended in 521.1 g of butyric anhydride (3.3 mol). After heating the suspension to 160 ⁰ C, the mixture was further stirred for 4 hours. After completion of the reaction, the excess acid was removed under vacuum. The product obtained was a clear light yellow syrup.

Example 4 Butyric Acid Ester Based on Sorbitol (DS 4)

In a stirred tank, 100 g of sorbitol (0.55 mol) were suspended in 290.2 g of butyric acid (3.3 mol) and heated to 160 ⁰ C. At this temperature, the mixture was treated with 0.6 g of tin oxalate and stirred under reflux for a further 6 hours. After completion of the reaction and removal of the catalyst, the excess acid was removed under vacuum. The product obtained was a clear light yellow syrup.

Example 5 Essig Butyric Acid Ester Based on Sorbitol (DS 6)

In a stirred vessel was added 100 g of sorbitol (0.55 mol) in 290.2 g of butyric acid was suspended (3.3 mol) and heated to 160 ⁰ C. At this

Temperature was added to the mixture with 0.6 g of tin oxalate and stirred for a further 6 hours under reflux. Thereafter, the batch was mixed with 112.1 g of acetic anhydride (1, 1 mol) and held under reflux for a further hour. After completion of the reaction and removal of the catalyst, the excess acid was under

Vacuum removed. The product obtained was a clear light yellow syrup. Example 6 Butyric Acid Ester Based on Isomalt (DS 5)

In a stirred tank, 50 g of isomalt (0.14 mol) were suspended in 131 g of butyric anhydride (0.83 mol). After heating the suspension to 160 ⁰ C, the mixture was further stirred for 2 hours. After completion of the reaction, the excess acid was removed under vacuum. The product obtained was a clear light yellow syrup.

Example 7 Butyl Acid Ester Based on Xylitol (DS 3)

In a stirred vessel, 100 g of xylitol (0.66 mol) in 312.2 g of butyric anhydride (1, 97 mol) are suspended and heated to 160 ⁰ C. After 2 hours of reaction time at 160 ⁰ C, the excess

Removed acid under vacuum and isolated the product as an almost colorless syrup.

Example 8: In Vitro Digestibility of Butyric Acid Esters of Carbohydrates and Carbohydrate Polyols

To study the small bowel stability of butyric acid esters of

Carbohydrate polyols, the following butyric acid esters were incubated with lipases and esterases from the pancreas and small intestine:

a. Tri buty ry I-Xy I it b. Tetrabutyryl xylitol c. Pentabutyryl xylitol d. Tributyryl sorbitol e. Tetrabutyryl sorbitol f. Tetrabutyryl diacetyl sorbitol g. Hexabutyryl sorbitol h. Pentabutyryl isomalt i. Heptabutyryl-diacetyl isomalt j. Octabutyryl isomalt Enzyme preparation from the small intestine mucosa

Small intestine esterases were isolated from porcine small intestine. For this purpose, an 18 m long small intestine of a freshly slaughtered pig was divided into 6 x 3 m sections, the mucosa of the individual

Prepared sections and homogenized in Ultraturrax. After subsequent centrifugation, the esterase was obtained in the soluble supernatant. Esterase activity was detectable throughout the small intestine, with the highest activity being located in section 4 (9-12 m).

Investigation of small bowel stability

20 mg of tributyrin (control substance) or butyric acid ester were emulsified together with 4 mg of taurocholic acid in 1680 μl of 100 mM phosphate buffer, pH 7.5, with 220 μl of a 0.06% pancreatin solution and 100 μl of mucosal supernatant with esterase activity

(so) and incubated for 3 h at 37 ⁰ C with stirring. At the end of the reaction, the released butyrate was determined by GC.

Results

The control tributyrin was maximized under the incubation conditions, i. split to the level of Monobutyrats.

FIG. 1 shows the hydrolysis rates of the individual butyric acid esters, including the standard deviation (n = 2). The fully esterified polyols (hexabutyryl sorbitol, tetrabutyryldiacetyl sorbitol, octabutyryl isomalt and heptabutyryl diacetyl isomalt) were only hydrolyzed to 0-2.1%. In addition, pentabutyryl isomalt and tributyryl sorbitol were found to be resistant to enzymatic degradation. From tetrabutyryl sorbitol or tri-, tetra- and pentabutyryl-xylitol were 10.7-22.4% Butyrate released. Overall, the results show that butyric acid esters of carbohydrate polyols were not or only slightly hydrolyzed during the passage of the small intestine and were therefore stable to the small intestine.

The acid stability in the course of the gastric passage was determined by incubation at pH 2.0 for 3.5 h at 37 ⁰ C.

From a 1% suspension containing taurocholic acid as emulsifier, only 0 to 0.43% of the maximum available butyrate was released. Butyric acid esters are therefore stable in the stomach.

Example 9 In Vitro Fermentation of Butyric Acid esters of xylose, sorbitol or isomalt

In in vitro fermentation experiments with intestinal bacteria of the human colon, it was investigated whether the above listed butyric esters of large intestinal bacteria or their enzymes are hydrolyzed and metabolised and butyrate is released in the large intestine.

medium

For in vitro fermentation experiments, the following medium was used:

Tryptone 1, 5 g / l

Yeast extract 1, 0 g / l

KH2PO4 0.24 g / l

Na2HPO4 0.24 g / l (NH4) 2SO4 1, 24 g / l

NaCl 0.48 g / l

MgSO4 x 7 H2O 0.10 g / l CaCl ₂ × 2 H ₂ O 0.06 g / l

FeSO ₄ x 7 H ₂ O 2 mg / l

Resazurin 1 mg / l

Cysteine / HCl 0.5 g / l

Vitamin solution (according to DSM 141) 0.5 ml / l

Trace element solution (according to DSM 141) 9.0 ml / l

NaHCO3 2.0 g / l pH 7.0

Cultivation of intestinal bacteria with butyric acid esters

To 9 ml of the anaerobic medium described above was added 0.5% (w / v) of the butyric acid ester to be tested and 0.2% (w / v) of taurocholic acid. This medium was then treated with 1 ml of a 10% Fäzessuspension (mixed faeces of three subjects) in anaerobic 50 mmol / l phosphate buffer, pH 7.0, the 0.5 g / l

Cysteine / HCl was added as a reducing agent, inoculated. Hungate tubes were incubated with shaking at 37 ^° C. for 72 h, sampled at different time points and assayed for short-chain fatty acids, lactic acid and pH. The extent of metabolism of the test substances was determined by determining the release of butyrate.

Results

Table 1: Balancing of butyrate formation in the in vitro fermentation test x-fold

Esterification butyrate / g riser

Substance degree substrate

Isomalt - 0.2 -

Pentabutyryl isomalt 55% 0.2 1, 3

Octabutyryl isomalt 88% 0.1 0.5 Heptabutyryl diacetyl isomalt 100% 0.1 0.4

Sorbitol - 0.3 -

Hexabutyryl sorbitol 100% 0.2 0.8

Tetrabutyryl sorbitol 67% 0.7 2.7

Tetrabutyryl diacetyl sorbitol 100% 0.3 1, 0

Tributyryl sorbitol 50% 0.7 2.8

XyNt - 0.3 -

Pentabutyryl xylitol 100% 0.4 1, 5

Tetrabutyryl xylitol 80% 0.7 2.5

Tributyryl xylitol 60% 0.6 2.2 res. Starch from Noverlose 240 0.2 _

^* = Increase in butyrate concentration in the fermentation medium in Comp. to unreacted carbohydrate or carbohydrate polyol

a) Fermentation of the butyric acid esters of isomalt

From Table 1 it is clear that in the fermentation of isomalt about 0.2 g of butyrate / g substrate were formed. In the fermentation of octabutyryl or heptabutyryl-diacetyl isomalt each about 0.1 g of butyrate / g substrate were achieved, d. H. almost no additional butyrate was released from these substances. In the fermentation of pentabutyryl isomalt, 0.2 g of butyrate / g substrate was formed.

b) Fermentation of the butyric acid esters of sorbitol

In the fermentation of the substances tri- or tetrabutyryl-sorbitol, a strong increase of the butyrate in the fermentation broths could already be observed after a short fermentation time.

After 72 hours, values of 0.7 g of butyrate / g substrate were detected, whereas on fermentation of the non-esterified sorbitol only 0.3 g of butyrate / g substrate was formed (Table 1). Butyrate formation From tri- or tetrabutyryl sorbitol was thus more than two times greater than that from fermentation of the unesterified sorbitol.

Hexabutyryl sorbitol was less metabolized by the intestinal bacteria than tri- or tetrabutyryl sorbitol, as evidenced by the low butyrate formation of 0.2 g butyrate / g substrate.

c) fermentation of the butyric acid esters of xylitol

Fermentation of intestinal bacterial tetrabutyryl xylitol resulted in butyrate binding of 0.7 g butyrate / g substrate versus 0.3 g on fermentation of the unesterified xylitol. This value corresponds to a more than two-fold increase in butyrate formation. Also from

Tributyryl xylitol or the fully esterified pentabutyryl xylitol released large amounts of butyrate compared to the non-esterified carbohydrate polyol (Table 1).

The results show that when using butyric acid esters of carbohydrate polyols in in vitro fermentation experiments with human intestinal bacteria, butyrate formation can be increased more than 3-fold over that of butyrate formation which can be achieved by fermentation of unesterified carbohydrates or resistant starch. Butyric acid esters of carbohydrates or carbohydrate polyols are suitable as small intestine-stable butyrate carriers for the large intestine, with tributyryl sorbitol, tetrabutyryl sorbitol and tetrabutyryl xylitol being particularly suitable because of their high butyrate formation.

Example 10: Nathum alginate encapsulation of tributyryl sorbitol

In a stirred tank 3 g of sodium alginate were dissolved in 82 g of deionized water with vigorous stirring. To this solution was added 15 g of tributyrylsorbitol and mixed homogeneously. The sodium alginate-butyric acid ester mixture was blasted by Schneider dripped into a 100 mmol / l CaCl ₂ solution. It created beads with a diameter smaller than 50 microns. The beads were left in the solution for 2 hours for postcrosslinking, then sieved off and washed with water. The beads can be used wet or after drying in a fluid bed dryer.

Example 11: Pectinate encapsulation of tributyryl sorbitol

75 g of a 3% (w / w) sodium pectinate solution was heated to boiling to complete dissolution. The solution was subsequently cooled to 40 ^° C. To the cooled solution was added

Added 15 g of tributyrylsorbitol and mixed homogeneously. This mixture was finely sprayed by means of a spray apparatus into a 2% magnesium chloride-hexahydrate solution. It created balls. The beads were left in the MgCl ₂ solution for 1 hr. The beads were then sieved and washed in water.

Example 12: Sodium alginate encapsulation of tetrabutyryl sorbitol

In a stirred tank 3 g of sodium alginate were dissolved in 82 g of deionized water with vigorous stirring. To this solution was added 15 g of tetrabutyrylsorbitol and mixed homogeneously. The sodium alginate-butyric acid ester mixture was analyzed by means of

Jet cutter dripped into a 100 mmol / l CaCl ₂ solution. It created beads with a diameter smaller than 50 microns. The beads were left in the solution for 2 hours for postcrosslinking, then sieved off and washed with water. The beads may be wet or used after drying in a fluid bed dryer.

Example 13: Pectinate encapsulation of tetrabutyryl sorbitol

75 g of a 3% (w / w) sodium pectinate solution was heated to boiling to complete dissolution. The solution is finally cooled to 40 ^° C. To the cooled solution was added 15 g of tetrabutyrylsorbitol and mixed homogeneously. This mixture was sprayed by means of a spray apparatus finely a 2% magnesium chloride hexahydrate solution. The resulting beads were left in the MgCl ₂ solution for 1 hr. Subsequently, the balls were screened and washed in water.

Example 14: Fluidized bed agglomeration

5 kg of finely ground isomalt ST are initially charged and fluidized in a fluidized-bed agglomerator as wall material (particle size 90% <50 μm), followed by 1200 g of a spray solution consisting of a mixture of di-, tri- and tetrabutyrylsorbitol (800 g of ester and 400 g of water). The spray solution is then changed and 500 g of a 20% isomalt solution are applied as an outer layer structure by spraying The product is after-dried to a water content of 5.4%.

Example 15: Spreads with butyric acid ester

Recipe for margarine

Leave 95 g of margarine in a blender jar for 2 hours at room temperature. Add 5 g of butyrate ester or microencapsulated butyrate ester and mix for 2 minutes with a blender until a homogeneous mass is obtained. The mass is then stored at 6-10 ⁰ C.

Recipe for hazelnut spread

45 g of sugar

10 g hazelnut paste

7.5 g skimmed milk powder

7.5 g of cocoa powder

24 g fat 5 g of butyrate ester or microencapsulated butyrate ester

1 g of lecithin

Mix ingredients up to lecithin and butyrate ester. Roll mass on a 3-roll mill until a fineness of 20 to 25 μm is achieved. Add lecithin and butyrate ester to the mass. Mix until a homogenous spreadable mass is produced.

Example 16: Pudding and creams

Recipe for biscuit cream

50 g of sugar

25 g of hardened vegetable fat

5 g of butyrate ester or microencapsulated butyrate ester

0.47 g of salt

0.03 g vanillin

3 g milk powder

6 g of cocoa

10.1 g maltodextrin (DE10)

Mix the fat and butyrate ester until a smooth paste is obtained. Add the powdered ingredients and mix for about 10-12 minutes until a homogeneous mass is obtained.

Recipe for dessert cream

310 g of sugar

110 g skimmed milk powder

37 g of corn starch

25 g of butyrate ester or microencapsulated butyrate ester

13 g of carrageenan

5 g of vanilla flavor

2500 ml whole milk

Mix all components well except butyrate ester. In one part of the whole milk, stir the powder until smooth and add the butyrate ester. Boil the rest of the milk. Powder mixture into the coo- stir the milk and bring to a boil. Fill up and store in a cool place until consumption.

Example 17: Milk products and products

Recipe for yoghurt cream with raspberries

450 g whole milk yoghurt

300 g of raspberries

10 g of gelatin

50 g of butyrate ester or microencapsulated butyrate ester

50 g of sugar

20 g lemon juice

20 g whole milk

100 g of cream

Soak the gelatin. Stir yogurt, sugar, butyrate ester, lemon juice and whole milk until smooth. Dissolve the gelatine and add. Beat the cream stiff and pull it under the mass. Raspberries in one

Fill the bowl with yoghurt mixture.

Example 18: Sweets

Recipe for milk chocolate

40 g of sugar

12 g of cocoa mass

20 g of cocoa butter

5 g of butyrate ester or microencapsulated butyrate ester

20 g whole milk powder

2 g hazelnut paste

0.9 g of lecithin

0.1 g vanillin

Process sugar with cocoa mass, half of cocoa butter, whole milk powder and hazelnut paste into a homogenous mixture in a chocolate mixer. Roll mixture to desired fineness. In the conche, residual cocoa butter and rolled cocoa cocoa powder at max. 70 ⁰ C conching about 18-24 hrs.. Add lecithin, butyric ester and vanillin one hour before the end of conching. Tempering the mass and Austafeln.

Example 19: Baked goods

Recipe for breakfast croissants

25 g of yeast

250 g cream

50 g of butyrate ester or microencapsulated butyrate ester

50 g of sugar

400 g wheat flour type 550

0.15 g Saiz

200 g of margarine

50 g egg yolk

Mix the yeast, lukewarm cream, a pinch of salt and a pinch of flour. Let the dough go for 10 min. Knead with other ingredients and let it rise for 20 minutes. Knead dough, roll out, cut out 15 triangles and roll up to croissants. Let rise briefly and bake for 10 min at 200 ⁰ C.

Literature:

Bach Knudsen, K.E., Serena, A., Canibe, N., Juntunen, K.S .:

New insight into butyrate metabolism. Proc. Nutr. Soc. (2003) 62: 81-86.

Cummings, J.H., Beatty, E.R., Kingman, S.M., Bingham, S.A. , Englyst, H.N. Digestion and physiological properties of starch in the human large bowel. Br J Nutr (1996) 75: 733-47.

Cummings, JH, Rombeau, JL, Sakata, T. (Ed.): Physiological and clinical aspects of short chain fatty acids. Cambridge University Press, GB ₁ 1995. Cummings, JH, Macfarlane, GT, Englyst, HN: Prebiotic digestion and fermentation. At J Clin Nutr (2001) 73: 415S-20S.

Desmet, G, Brazier, M, Cerutti, J, Chany, C, Arnould-Guerin, ML: Pharmacokinetics of butyric acid derivative with xylitol. Eur J Drug Metab Pharmacokinet (1991) Spec. 3: 348-51.

Newmark, HL, Lupton, JR, Young, CW: Butyrate as a differentiating agent: pharmacokinetics, analogues and current status. Cancer Letters (1994) 78: 1-5.

Pouillart, P., Cerutti, I ₁ Ronco, G, Villa, P, Chany, C: Enhancers by stable butyrate derivatives of antitumor and antiviral actions of interferon. Int. J. Cancer (1992) 51 (4): 596-601.

Cummings, JH, Rombeau, JL, Saketa, T (Ed.). Physiological and clinical aspects of short chain fatty acids. Cambridge University Press, GB (1995): 401-425.

Santini, V., Scappini, B., Gozzini, A., Grossi, A., Villa, P. Ronco, G., Douillet, O., Pouillart, P., Bernabei, PA, Rossi Ferrini, P .: Butyrate -stable monosaccharide derivatives induce maturation and apoptosis in human acute myeloid leukemia cells. Br J Haematol (1998) 101 (3): 529-38.

Scheppach W, Sommer H, Kirchner T, Paganelli GM, Bartram P, Christi S, Richter F, Dusel G, Kasper H .: Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis gastroenterology (1992) June 103 (1 ): 51-6

Schmitt, MG, Soergel, KH, Wood, CM: Absorption of Short chain fatty acids from the human jejunum. Gastroenterology (1976) 70:21 1-5. Vernia, P, Montelone, G, Grandinetti, G, Villotti, G, Di Giulio, E, Frieri, G, Marcheggiano, A, Pallone, F, Caprilli, R, Torsoli, A: Combined oral sodium butyrate and mesalazine treatment com pared to oral mesalazine alone in ulcerative colitis; randomized, double-blind, placebo-controlled pilot study. Dig Dis Sei (2000)

May 45 (5): 976-981.

Guard houses, A., Stein, J: Rationale for the luminal provi- sion of butyrate in intestinal diseases. Eur J Nutr (2000) 39: 164-171.

WoNn MJ. Fermentation in the space and human large intestines. Science. (1981) 25; 213 (4515): 1463-8.

Claims

claims

1. Use of butyric acid esters of carbohydrate, carbohydrate polyol or carbohydrate / carbohydrate-polyol mixture or butyric ester mixtures thereof as butyrate source in the gastrointestinal tract of the human or animal body.

2. Use according to claim 1 for the treatment and / or prevention of diseases of the gastrointestinal tract of the human or animal body.

3. Use according to claim 1 as Butyratquelle in the colon of the human or animal body

4. Use according to claim 1 as Butyratquelle in the rear colon of the human or animal body.

5. Use according to claim 1, wherein at least one butyric acid ester has a degree of substitution (DS) of 3 to 4.

6. Use according to claim 1, wherein at least one

Butyric acid ester is partially esterified.

7. Use according to claim 6, wherein the partially esterified butyric acid ester has a degree of esterification of 50 to 80%.

8. Use according to claim 1, wherein the carbohydrate and / or carbohydrate polyol are selected from: monosaccharides, disaccharides, oligosaccharides, polysaccharides and mixtures thereof.

Use according to claim 1 wherein the carbohydrate polyol is selected from: mannitol, sorbitol, xylitol, lactitol, maltitol, erythritol, isomalt, 1, 6-GPS, 1, 1-GPS, 1, 1-GPM, hydrogenated Starch hydrolysates, hydrogenated glucose syrups and mixtures thereof.

Use according to claim 1, wherein the carbohydrate polyol is selected from: 1, 6-GPS, 1, 1-GPS and 1, 1-GPM and mixtures thereof.

1 1. Use according to claim 1, wherein the butyric acid ester is selected from: tributyryl sorbitol, tetrabutyryl sorbitol, tributyrylxylite and tetra butyrylxylit and Pentabutyrylisomalt.

Use according to any one of the preceding claims wherein the butyric acid ester or the butyric acid ester mixture is administered orally or enterally to the gastrointestinal tract of the human or animal body.

13. Use according to claim 12, wherein the butyric acid ester or the butyric acid ester mixture is administered in microencapsulated form.

14. Use according to claim 13, wherein the microencapsulation process is selected from spray drying, freeze drying, fluidized bed drying, fluidized bed agglomeration, extrusion and atomization.

Use according to claim 12, wherein the butyric acid ester or the butyric acid ester mixture is administered in macroencapsulated form.

16. Use of characterized in claims 1 to 15 butyric acid ester or butyric acid ester mixture, optionally in micro- or macroencapsulated form, for the preparation of a

Medicament for the treatment or prevention of diseases of the gastrointestinal tract of the human or animal body.

17. A method for the treatment or prevention of diseases of the gastrointestinal tract comprising the, preferably oral or enteral, administration of characterized in claims 1 to 15 Buttersäureester or Buttersäureester mixture, optionally in micro- or macroencapsulated form, in the human or animal body.

18. Pharmaceutical composition comprising characterized in claims 1 to 15 butyric acid esters or butyric acid ester mixture, optionally in micro- or macroencapsulated form, as an active ingredient for the treatment or prevention of diseases of the human or animal body.

19. Use of characterized in claims 1 to 15 butyric acid ester or butyric acid ester mixture, optionally in micro- or macroencapsulated form, for the preparation of a food.

20. Composition, in particular food, containing:

a) at least one characterized in claims 1 to 15 butyric acid ester, optionally in micro- or macroencapsulated form, and

b) at least one further constituent selected from:

i. carbohydrate polyols;

ii. carbohydrates;

iii. soluble and / or insoluble fiber;

iv. short-chain fatty acids; v. Buttersäureglycerinestern; and

vi. acylated starch.

21. The composition of claim 20, wherein the further ingredient is selected from:

i. Mannitol, sorbitol, xylitol, lactitol, maltitol, erythritol, isomalt, 1, 6-GPS,

1, 1 -GPS, 1, 1 -GPM, hydrogenated starch hydrolysates, hydrogenated glucose syrups and mixtures thereof;

ii. Monosaccharides, disaccharides, oligosaccharides, polysaccharides and mixtures thereof;

iii. soluble or insoluble fiber, in particular prebiotic and / or butyrogenic fiber, resistant starch, modified starch, polydextrose, fructo-oligosaccharides, galactooligosaccharides, transgalactosylated oligosaccharides such as 6'-galactosyllactose or 4'-galactosyllactose, lactulose,

Lactobionic acid, maltobionic acid, xylo-oligosaccharides, lacto-sucrose, malto-oligosaccharides, isomalto-oligosaccharides, gentio-oligosaccharides, glucosylsucrose, soybean-oligosaccharides, chito- oligosaccharides, chitosan-oligosaccharides, pectin,

Pectin oligosaccharides, condensed oligosaccharides, caramel products, galactomannan oligosaccharides, fucose-containing oligosaccharides, fucosederivative oligosaccharides, pyrodextrin, partially hydrolyzed guar gum, a variant thereof obtained by partial hydrolysis, hydrogenation, oxidation, enzymatic chemical modification of saccharides, and Fibers, in particular from oats, wheat, vegetables such as tomato or pea, Fruits such as apples and fruit berries, sugar beet, carob fruits or cellulose.

iv. Butyric acid, propionic acid, acetic acid, lactic acid;

v. Glycerol tributyrate, glycerol dibutyrate, glycerol monobutyrate; and

vi. butyrylated starch

22. The composition of claim 20 or 21, wherein the composition is a food and is selected from:

Dairy products and dairy products such as cheese, butter, yoghurt, kefir, quark, sour milk, buttermilk, cream,

Condensed milk, dried milk, whey, milk sugar, milk protein, milk mix, milk half fat, whey mixed or milk fat products or preparations;

Pudding, cream, mousse and other desserts;

Milk fat products, mixed fat products, edible fats,

Edible oils;

Baked goods such as bread including biscuits and pastries, long-life baked goods, biscuit products and waffles;

Spreads, in particular fatty spreads, margarine products and shortenings;

Instant products and brewery products;

Fruit products or preparations such as jams, jams, jellies, fruit preserves, fruit pulp, fruit pulp, fruit juices, fruit juice concentrates, fruit nectar and fruit powder; Cereals, muesli and cereal mixes, and prepared cereal-containing products such as cereal bars and breakfast products;

non-alcoholic drinks, beverage bases and powdered drinks; and

Confectionery such as chocolates, hard caramels, soft caramels, chewing gum, dragées, fondant products, jelly products, licorice, marshmallows, flakes, dragées, com pressed, candied fruits, crackers, nougat products, ice confectionery, marzipan, ice cream;

and derived dietary specialty foods and enteral nutrition.

23. A composition according to claim 20 or 21, wherein the composition comprises a feed, in particular selected from: pet food, premix for pet food, starch-rich

Feed, concentrate feed and concentrates.