Dietary supplement compositions |
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| 申请号 | EP12185153.9 | 申请日 | 2012-09-20 | 公开(公告)号 | EP2710901A1 | 公开(公告)日 | 2014-03-26 |
| 申请人 | Symrise AG; | 发明人 | Krammer, Gerhard; Widder, Sabine; | ||||
| 摘要 | Suggested is a dietary supplement composition, comprising (a) at least one probiotic micro-organism and (b) at least one anthocyanin or a plant extract or a fruit juice comprising anthocyanins, and optionally (c) at least one prebiotic on condition that the compositions are free of milk fermentation products. |
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| 权利要求 | |||||||
| 说明书全文 | The present invention relates to the area of food additives and is directed to dietary supplements comprising probiotics and a defined group of flavonoids for improving the health status of the body and in particular the health of the intestine. Probiotics contain live bacteria and represent an important part of the complex world of foods that are good for health. It is 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. In this context reference is made to Italian patent From Bacteria found in products like yoghurt, kefir or fermented vegetables often 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. There are a lot of different health benefits linked to the administration of probiotics to the human body which are reported in the literature, such as
However, probiotics also show some disadvantages. For example, in case of inflammatory diseases of the intestine the mucosa epidermis becomes permeable for probiotic bacteria, so that they can enter into the serum. The same is true for elderly people. Also in case of a medicamentation with antibiotics the administration of probiotics is not suggested in order to allow the intestine flora de regenerate without being mixed up with probiotic bacteria which cannot settle in the intestine. Therefore, the object of the present invention has been to provide a suitable additive for the administration of probiotics to the human body providing the same health benefits without being linked with the disadvantages as described above. Object of the present invention are dietary supplement compositions comprising
on condition that the compositions are free of milk fermentation products. Surprisingly it has been observed that probiotics and anthocyanes showing synergistic behaviour in terms of health benefits. In Particular, adding anthocyanins, which show a strong anti-oxidative effect, improve the performance of probiotic bacteriae. In particular it was found that by adding anthocyanins the concentration of toxic metabolism products was significantly reduced. Probiotic organisms, also called "probiotics" forming component (a) represent live micro-organisms which are considered to be beneficial to the host organism. According to the currently adopted definition by FAO/WHO, probiotics are: "Live microorganisms which when administered in adequate amounts confer a health benefit on the host". Lactic acid bacteria (LAB) and bifidobacteria are the most common types of microbes used as probiotics; but certain yeasts and bacilli may also be used. Probiotics are commonly consumed as part of fermented foods with specially added active live cultures; such as in yogurt, soy yogurt, or as dietary supplements. Live probiotic cultures are available in fermented dairy products and probiotic fortified foods. However, tablets, capsules, powders and sachets containing the bacteria in freeze dried form are also available. Table 1 provides an overview of common probiotics and their respective health claims that can be used as component (a) of the present invention: Some additional forms of lactic acid bacteria, representing also suitable probiotics include:
Some fermented products containing similar lactic acid bacteria include:
Anthocyanins, also called anthocyans, forming component (b) represent water-soluble vacuolar pigments that may appear red, purple, or blue according to the pH. They belong to the class of flavonoids synthesized via the phenylpropanoid pathway following general formula (I) Anthocyanins are odourless and nearly flavourless, contributing to taste as a moderately astringent sensation. Anthocyanins occur in all tissuesof higher plants, including leaves, stems, roots, flowers, and fruits. Anthoxanthins are their clear, white to yellow counterparts occurring in plants. Anthocyanins are derivatives of anthocyanidins, which include pendant sugars. Most frequent in nature are the glycosides of cyanidin, delphinidin, malvidin, pelargonidin, peonidin, and petunidin. Roughly 2% of all hydrocarbons fixated in photosynthesis are converted into flavonoids and their derivatives such as the anthocyanins. Table 2 provides an overview of the most common anthocyanin species. The anthocyanins, anthocyanidins with sugar group(s), are mostly 3-glucosides of the anthocyanidins. The anthocyanins are subdivided into the sugar-free anthocyanidin aglycones and the anthocyanin glycosides. As of 2003 more than 400 anthocyanins had been reported while more recent literature (early 2006), puts the number at more than 550 different anthocyanins. The difference in chemical structure that occurs in response to changes in pH is the reason why anthocyanins are often used as pH indicator, as they change from red in acids to blue in bases. Anthocyanins are thought to be subject to physiochemical degradation in vivo and in vitro. It is generally known that structure, pH, temperature, light, oxygen, metal ions, intramolecular association, and intermolecular association with other compounds (co-pigments, sugars, proteins, degradation products, etc.) are known to affect the colour and stability of anthocyanins. It has been demonstrated that B-ring hydroxylation status and pH mediate the degradation of anthocyanins to their phenolic acid and aldehyde constituents. Indeed, significant portions of ingested anthocyanins are likely to degrade to phenolic acids and aldehyde in vivo, following oral consumption. This characteristic confounds scientific isolation of specific anthocyanin mechanisms in vivo. Cancer research on anthocyanins is the most advanced, where black raspberry (Rubus occidentalis L.) preparations were first used to inhibit chemically induced cancer of the rat esophagus by 30-60% and of the colon by up to 80%. Effective at both the initiation and promotion/progression stages of tumour development, black raspberries are a practical research tool and a promising therapeutic source, as they contain the richest contents of anthocyanins among native North American Rubus berries. Work on laboratory cancer models has shown that black raspberry anthocyanins inhibit promotion and progression of tumour cells by
On a molecular level, berry anthocyanins were shown to turn off genes involved with tumour proliferation, inflammation and angiogenesis, while switching on apoptosis. In 2007, black raspberry studies entered the next pivotal level of research - the human clinical trial - for which several approved studies are underway to examine anti-cancer effects of black raspberries and cranberries on tumours in the esophagus, prostate and colon. For these reasons, the preferred source for anthocyanins forming component (b) is an extract or fruit juice obtained from
or their mixtures. Particular preferred are extracts or juices from bilberries, black raspberries or cranberries or their mixtures. In another embodiment of the present invention the dietary supplement compositions may include 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. Adding prebiotics to the compositions leads to another inprovement of the stability of the anthocyanins against degradation within the intestine. The following describes in particular various oligosaccharides which can be taken into account as suitable prebiotics (component c):
The compositions according to the present invention are typically administered orally, however, it also possible to prepare compositions for topical applications, for example a cream, a lotion or an ointment. The compositions may comprise the probiotics and the anthocyanines in a weight ratio of about 99:1 to about 50:50 and more particularly about 95:15 to about 75:25. The highest synergistic effects, however, are observed at ratios of about 92:8 to about 80:20. In general, the compositions can be used in a concentration of up to about 90, particularly about 10 to about 75 and more particularly about 25 to about 50 % b.w. - calculated on the final food composition. In case probiotics are incorporated into the compositions, the mixture may comprise them in amounts of about 5 to about 20, more particularly about 10 to about 15 % b.w. - all these amounts calculated on the total composition and on condition that they add to 100 % b.w. 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 in amounts of typically 1 to 10 and particularly about 2 to 5 % b.w. In a special embodiment of the present invention said dietary supplements 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 ("microsponge") 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) Hall-crest 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. Another object of the present invention is related to the use of a composition, comprising
Another object of the present invention relates to a non-therapeutic method for improving the health status of the human body, in particular of the human intestine by oral or topical administration of a composition comprising
Finally, the invention is also directed to a method for making a medicament for improving the health status of the human body, in particular of the human intestine, for example with respect to
Soy milk was added to 15-75 parts by volume of cow milk to make 100 parts of the mixture. The mixture was then pasteurised at about 90 °C for 15 seconds and then cooled and separated into four samples. The cooled, pasteurised mixtures are then inoculated with 3 to 5 percent by volume of
The incubation was carried out at about 42 °C. After two hours thickening occurred. The fermentation was carried out for about 5.5 hours. The average faecal excretion of lithocholic and deoxycholic acid (secondary bile acids which represent important metabolic products for the formation of colon cancer of the human body) related to 100 g fat intake per day has been studied over a period of two weeks. Table 1 reflects the results after consummation of the four yoghurt compositions according to Preparation Example 1. Examples 1 and 2 are according to the invention, examples C1 and C2 serve for comparison. The results indicate that adding anthocyanins to the probiotic micro-organisms leads to a significant decrease of secondary bile acids compared to the results taking the probiotics alone. Adding prebiotics to the composition even improves the results. |
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