Patent Application
20080193406
The present invention is related to the area of alimentation and concerns oral and/or topical compositions comprising defined fatty acids or their esters and prebiotics, dietary supplements and food compositions comprising said fatty acids or their esters and prebiotics, and the use of mixtures comprising physiologically active fatty acids or their esters and prebiotics for improving the stimulation of the growth of healthy bacteria.
Probiotics contain live bacteria and represent an important part of the complex world of foods that are good for health. Its the bacteria and the metabolites which they produce that give these products their health promoting properties. The best known example of a probiotic is yoghurt. The experimental data for yoghurt is still not as conclusive as one would like, however, human studies related to the consumption of dietary milk products show increased milk digestibility, quicker recovery from certain types of diarrhoea, enhanced immune function, relation in certain cancers, and possible lowering of blood cholesterol levels.
Bacteria found in products like yoghurt, kefir or fermented vegetables usually aren't found in the human intestine. In fact, the intestinal environment is often a hostile one for these foreign bacteria. Because of this, bacteria eaten in probiotic products don't colonise the intestine but are flushed through and eliminated from the body.
The bacteria living in the intestine make up a very large and very diverse population. The numbers of each kind of bacteria change depending on age, diet, health status, and use of drugs and supplements. The effects are linked to the ability of the bacteria to adhere to the intestinal wall and use the semi-digested food that it passing through the intestines. It is not surprising to found that the bacterial population in the intestines of vegetarians is much different compared to that of meat eaters. Because some bacteria have specific nutrient requirements it has been proposed that adding these particular foods or nutrients to the diet could be a way of increasing the numbers of specific bacteria. Such additives are called “prebiotics”. Thus, to be effective, prebiotics must escape digestion in the upper gastrointestinal tract and be used by a limited number of the micro-organisms comprising the colonic microflora. In the large intestine prebiotics are converted into short-chain fatty acids like capronic or caprylic acid. Said acids are used by the human body as an energy source. Beside this, the short-chain acids are known to inhibit inflammatories of the intestine, which represents a kind of cancer prophylaxis. In addition, prebiotics increase the resorption time in the intestine which leads to an improve uptake of minerals. Typical examples for well-known prebiotics are oligosaccharides, e.g. in 1995 Gibson et al found that oligofructose and inulin, when fed to humans, selectively stimulated the growth of bifidobacteria without influencing the numbers of lactobacillus. Since prebiotics mainly stimulate the growth of bifidobacteria, for which reason the also are referred to as bifidogenetic factors.
Although various types of prebiotics are known from the literature and can be found in the market there is still an increasing need for more active alternatives or additives which support the various activities of existing products in synergistic manner. Therefore, the object of the present invention has been to provide a new system of prebiotic compounds which shows a synergistic stimulation of the growth of healthy bacteria, preferably bifido and lactic bacteria both and improves the health status of the human body.
The present invention refers to oral and/or topical compositions, comprising
Surprisingly it has been observed that mixtures of said physiologically active fatty acids and prebiotics show a synergistic behaviour with respect to stimulation of growth of bacteria selected from the group consisting of Bifidobacterium breve, Bifidobacterium infantis, Bifidobacterium longum and Bifidobacterium adolescentis on one hand, and Lactobacillus bulgaricus, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Streptococcus faecium, and Streptococcus thermophilus on the other. In addition, prebiotics were found to increase the conversion of vaccinic and linoleic acid to CLA in the intestine.
Prebiotics
Prebiotics are defined as non-digestible food ingredients that may beneficially affect the host be selectively stimulating the growth and/or the activity of a limited number of bacteria in the colon. The following describes the various oligosaccharides which can be taken into account as suitable prebiotics (component a):
Fructooligosaccharides
Inulins
Isomaltooligosaccharides
Lactilol
Lactosucrose
Lactulose
Pyrodextrins
Soy Oligosaccharides
Transgalactooligosaccharides
Xylooligosaccharides
Biopolymers
A common criteria for fatty acids with physiological activity, which represent component (b), is a fat chain having a sufficient number of carbon atoms providing a lipophilic behaviour that allows the molecule pass through the gastrointestinal tract of the body and a sufficient number of double bonds. Therefore, said fatty acids usually comprise 18 to 26 carbon atoms and 2 to 6 double bonds.
In a first embodiment of the present invention conjugated linoleic acid (CLA) or its alkaline or alkaline earth salts and esters, preferably esters with lower aliphatic alcohols having 1 to 4 carbon atoms—or their glycerides, specially their triglycerides come into account. Conjugated linoleic acid (CLA) represents a commercially available product which usually is obtained by base-catalysed isomerisation of sunflower oil or their respective alkyl esters and subsequent isomerisation in the presence of enzymes. CLA is an acronym used for positional and geometric isomers deriving from the essential fatty acid linoleic acid (LA, cis-9,cis-12-octadecadienoic acid, 18:2n-6). From a physiological point of view the use of the cis-9,trans-11 isomer according to the present invention is of special importance having at least 30, preferably at least 50 and most preferably at least 80 % b.w. of said cis-9,trans-11 isomer—calculated on the total CLA content of the crude mixture. In addition, it has been found advantageous if the content of the trans-10,cis-12 isomer is at most 45, preferably at most 10 % b.w. and most preferably is less than 1% b.w., and the sum of 8,10-, 11,13- and trans,trans-isomers in total is less than 1% b.w.—again calculated on the total CLA content. Such products can be found in the market for example under the trademark Tonalin® CLA-80 (Cognis).
In a second embodiment also so-called omega-3 fatty acids can come into account, which typically comprise 18 to 26, preferably 20 to 22 carbon atoms and at least 4 and up to 6 double bonds, Also these molecules are very well known from the art and can be obtained by standard methods of organic chemistry, for example via transesterification of fish oils, followed by urea precipitation of the alkyl esters thus obtained and a final extraction using non-polar solvents as described in the German patent DE 3926658 C2 (Norsk Hydro). Fatty acids thus obtained are rich in omega-3 (all-Z)-5,8,11,14,17-eicosapentanoic acid (EPA) C 20:5 and (all-Z)-4,7,10,13,16,19-docosahexanoic acid (DHA) C 22:6. Such products can be found in the market under the trademark Omacor® (Pronova).
In a third embodiment also linoleic acid, vaccinic acid (trans 11-octadecenoic acid) or cis-hexadecenoic acid (obtained for example from the plant Thunbergia alata) can be used.
In addition said physiologically active fatty acid esters can not only be used in form of their lower alkyl esters or glycerides, an additional well preferred embodiment of the present invention relates to compositions comprising esters of said fatty acids with sterols. Like glycerides sterol esters are easily resorbed and splitted by the human body, however, a significant advantage comes from the fact that the cleavage of the ester bond releases a second molecule with health promoting properties. To avoid unclearities, the phrases “sterol”, “stanol” and “sterin” shall be used as synonyms defining steroids showing a single hydroxyl group linked to the C-3. In addition sterols, which consist of 27 to 30 carbon atoms, may show a double bond, preferably in ⅚ position. According to the present invention esters of CLA or omega-3 fatty acids with β-sitosterol or its hydrogenation product β-sitostanol are preferred.
Oral and/or Topical Compositions
The oral and/or topical compositions according to the present invention may comprise the prebiotics and the fatty acids in a weight ratio of 99 to 1 to 50:50 and more particularly 95:10 to 75:25. The highest synergistic effects, however, are observed at ratios of 92:8 to 80:20. In general, the compositions can be used in a concentration of up to about 10, particularly 0.5 to 8 and more particularly 1 to 2% b.w.—calculated on the probiotic micro-organisms being present in the final food composition. One percent, however, has been found to be particularly suitable.
In a special embodiment of the present invention said compositions are macro- or micro-encapsulated. “Microcapsules” are understood to be spherical aggregates with a diameter of about 0.1 to about 5 mm which contain at least one solid or liquid core surrounded by at least one continuous membrane. More precisely, they are finely dispersed liquid or solid phases coated with film-forming polymers, in the production of which the polymers are deposited onto the material to be encapsulated after emulsification and coacervation or interfacial polymerization. In another process, liquid active principles are absorbed in a matrix (“micro-sponge”) and, as microparticles, may be additionally coated with film-forming polymers. The microscopically small capsules, also known as nanocapsules, can be dried in the same way as powders. Besides single-core microcapsules, there are also multiple-core aggregates, also known as microspheres, which contain two or more cores distributed in the continuous membrane material. In addition, single-core or multiple-core microcapsules may be surrounded by an additional second, third etc. membrane. The membrane may consist of natural, semisynthetic or synthetic materials. Natural membrane materials are, for example, gum arabic, agar agar, agarose, maltodextrins, alginic acid and salts thereof, for example sodium or calcium alginate, fats and fatty acids, cetyl alcohol, collagen, chitosan, lecithins, gelatin, albumin, shellac, polysaccharides, such as starch or dextran, polypeptides, protein hydrolyzates, sucrose and waxes. Semisynthetic membrane materials are inter alia chemically modified celluloses, more particularly cellulose esters and ethers, for example cellulose acetate, ethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose and carboxymethyl cellulose, and starch derivatives, more particularly starch ethers and esters. Synthetic membrane materials are, for example, polymers, such as polyacrylates, polyamides, polyvinyl alcohol or polyvinyl pyrrolidone. Examples of known microcapsules are the following commercial products (the membrane material is shown in brackets) Hallcrest Microcapsules (gelatin, gum arabic), Coletica Thalaspheres (maritime collagen), Lipotec Millicapseln (alginic acid, agar agar), Induchem Unispheres (lactose, microcrystalline cellulose, hydroxypropylmethyl cellulose), Unicerin C30 (lactose, microcrystalline cellulose, hydroxypropylmethyl cellulose), Kobo Glycospheres (modified starch, fatty acid esters, phospholipids), Softspheres (modified agar agar), Kuhs Probiol Nanospheres (phospholipids) and Primaspheres or Primasponges (chitosan, anionic polymers). The encapsulation of the compositions according to the present invention is preferred in case the active should be liberated at the same part of the intestine. Therefore, one skilled in the art can easily select the adequate encapsulation system by comparing the stability of the capsules under the pH-conditions of the respective part of the intestine.
A further object of the present invention relates to food compositions, comprising
The compositions may further comprise certain plant extracts, like extracts of Camellia sinensis (Green tea) or Olea europensis (Olive tree) which are rich in actives like polyphenols, oleuropein and hydroxtyrosol.
A final object of the present invention is related to the use of mixtures, comprising
The stimulation of growth of micro-organisms has been studied by enumerating bifidobacterium and lactobacilli in vitro in the presence of various test substances. More specifically, aliquots (1 mL) of human faecal homogenates (10 g per 100 mL diluent) were added to diluted WC broth (diluted 50:50 with 0.05M phosphate buffer) to which were added the test mixtures and a lactobacillus or bifidobacterium strain. For each of the combinations, parallel tubes were prepared with one set being inoculated with Bifidobacterium spp or Lactobacillus spp. All mixtures were then incubated for up to 24 hours and bacterial numbers enumerated. The results are presented in Tables 1 and 2:
Starting from a control of 1.0 106 CFU/ml (0) the addition of 1% b.w. of various prebiotics (Comparative Examples C1-C4) increases the CFU by a factor of 10, while the addition of the fatty acids does only have a weak effect on the stimulation of cell growth (Comparative Examples C5-C8). Adding however mixture of prebiotics and fatty acids to the samples, the CFU numbers were multiplied by a factor of about 40 (Inventive Examples 1 to 5). The highest synergistic effect can be seen at a relation prebiotic:fatty acid of about 90:10.
Starting from a control of 2.8 105 CFU/ml (0) the addition of 1% b.w. of various prebiotics (Comparative Examples C9-C12) increases the CFU by a factor of 4, while the addition of the fatty acids does only have a weak effect on the stimulation of cell growth (Comparative Examples C13-C16). Adding however, mixture of prebiotics and fatty acids to the samples, the CFU numbers were multiplied by a factor of about 15 (Inventive Examples 6 to 10). The highest synergistic effect can be seen again at a relation prebiotic:fatty acid of about 90:10.
Soy milk is added to 15-75 parts by volume of cow milk to make 100 parts of the mixture. The mixture is then pasteurised at about 90° C. for 15 seconds and then cooled. The cooled, pasteurised mixtures are then inoculated with 3 to 5 percent by volume of a yoghurt culture having 1:1 ratio of Lactobacillus bulgaricus and Bifidobacterium adolescentis. The incubation is carried out at about 42° C. In about 2 hours thickening will occur. The fermentation is carried out for about 5.5 hours. The yoghurt compositions thus obtained is treated with 1%—calculated on the amount of micro-organisms being present—of a 9:1 mixture of inulin and CLA. The products firm consistency and have a flavour like or substantially indistinguishable from that of a corresponding yoghurt composition using 100 percent of fresh cow milk. A small amount of citric acid can be added to the fermentation mixture to enhance the flavour of the final yoghurt composition. A suitable amount of citric acid is 0.5 percent based on the weight of the composition.
| Number | Date | Country | Kind |
|---|---|---|---|
| 04012287.1 | May 2004 | EP | regional |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP2005/005318 | 5/14/2005 | WO | 00 | 3/7/2008 |
