WO2009008803A1

WO2009008803A1 - Inhibition of gastroduodenal diseases in humans by common edible plants

Info

Publication number: WO2009008803A1
Application number: PCT/SE2008/000438
Authority: WO
Inventors: Halina Miller-Podraza
Original assignee: Food & Health Concept Centre I Väst Ab
Priority date: 2007-07-11
Filing date: 2008-07-09
Publication date: 2009-01-15

Abstract

The invention discloses a composition comprising at least two or more fruit material selected from the group comprising rosehip, walnut, acorn, lingonberry, rowanberry, fig and date or extracts thereof and a prebiotic substance.

Description

TITLE

INHIBITION OF GASTRODUODENAL DISEASES IN HUMANS BY COMMON EDIBLE PLANTS

DESCRIPTION TECHNICAL FIELD

This invention relates to functional food using edible plants to inhibit Helicobactor pylori, a pathogenic bacterium which lies behind gastroduodenal diseases in humans.

BACKGROUND OF THE INVENTION

Helicobacter pylori gastroduodenal diseases and infection rate

Gastroduodenal diseases in humans cause medical problems on a global scale. The main cause of these diseases is Helicobacter pylori (H, pylori), a pathogenic bacterium which colonizes the human stomach. H. pylori lies behind common gastric diseases like chronic gastritis and duodenal and gastric ulcers, and increases risks of gastric adenocarcinoma. In 1994 this bacterium was classified by the World Health Organization as a class 1 carcinogen.

H. pylori is present in the stomachs of at least half of the world's population. In industrial countries (like Sweden) the infection rate is just under 50% by age 60. Most of the infected individuals develop a chronic mild and asymptomatic inflammation; however between 10 and 20% develop more serious forms of gastric diseases. Older people are most at risk because the infection rate increases with age. It has been estimated that mortality rates for peptic ulcers rise from around one per million at age 20 to 200 per million at age 70.

Binding properties of H pylori

Pathogenic microbes have to adhere to target cells to cause infection and inflammation. The adhesion is often mediated by cell surface receptors and like many other bacteria. H. pylori has the ability to bind to selected carbohydrates. The following sugar sequences have been described as carbohydrate epitopes for the bacterium: Galactosylceramide (GalβiCer) lactosylceramide (Galβ4Glcβ1 Cer) lactotetraosylceramide (Galβ3GlcNAcβ3Galβ4Glcβ1 Cer) Neutral ganglio structures (e.g Galβ3GalNAcβ4Galβ4Glcβ1 Cer) Neutral neolacto structures (R_rGalβ4GlcNAcβ3Galβ4GlcNAcβ-R₂) Some sialylated structures (NeuAc-containing epitopes) Some fucosylated structures, e.g Lewis b epitope, Fucα2Galβ3(Fucα4)GlcNAcβ-R) Some sulphated structures (HSO₃-R)

Where in the above GIc = glucose, GaI = galactose, GIcNAc = N-acetylglucosamine, GaINAc = N-acetylgalactosamine, NeuAc = N-acetylneuraminic acid, Fuc = fucose, Cer = ceramide (lipid part of glycosphingolipids) The complex pattern of binding specificities of H. pylori is not clear. The Lewis b epitope, lacto structures and sulphated structures should be of importance because they are present in the stomach mucosa. Sialylated structures are also considered to be of importance (see below) although in normal mucosa NeuAc occurs in very small amounts.

Binding of H.pylori to sialylated (NeuAc-containing) structures

NeuAc is considered to be of importance for the development of H.pylori diseases because the infections upregulate the amount of NeuAc in the mucosa layer. It has also been shown that some sialylated carbohydrates inhibit the binding of H.pylori to cultured human stomach cells and to gastric mucosa in vivo.

Treatment of /-/.pWo/7-associated diseases

The current treatment of H.pylori diseases is based on the use of antibiotics; however, this therapy is associated with risks of developing antibiotic resistance. New ways of treatment are needed and one possibility is anti-adhesion therapy based on the inhibition of adhesion of H.pylori to cell surface epitopes. Anti-adhesion agents are expected to be chemically related to natural epitopes present on target cells and, in accordance with this, several sialylated structures turned out to inhibit the binding of H.pylori to target cells both in vitro and in vivo (see above).

Conditions for effective inhibition of H. pylori

The fight against H.pylori is not an easy task. The bacterium is highly adaptable and, as mentioned, it displays several different binding activities. A professional therapy aimed at 100% eradication of H.pylori from the stomach is based on the use of a mixture of antibiotics and a proton pump inhibitor. Thus, alternative therapies should be based on a combination of different anti-H.py/or/ activities rather than on the use of one ant\-H. pylori activity. Anti-adhesion activities may thus be combined with anti-growth activities, and possibly with other activities, such as stimulating the growth of probiotic bacteria.

5 Plant kingdom and anϋ-H. pylori agents

A growing volume of information indicates that plants contain a wide range of components with ability to inhibit both growth and adhesion of H. pylori. Many plants have been described as active against this bacterium, however most of them are rare medicinal plants or spice plants (Rachel O'Msahony et al. 2005, World J Gastroenterol 11 (47),

10 7499-7507 and Ankli A. et al. 2002, Journal of Ethnopharmacology 79, 43-52.). Some of these plants are very active and may function as candidates for the development of drugs. Tumecic has been for example reported as a spice plant with strong bactericidal activity against H. pylori (Rachel O'Msahony et al. 2005, World J Gastroenterol 11 (47), 7499- 7507) and some extracts from Yucatec Mayan medicinal plants were shown to be active

15 against this bacterium at concentrations 8-40 μg/ml (Ankli A. et al. 2002, Journal of Ethnopharmacology 79, 43-52). However, their use in functional food is very limited, if any.

Plants with activity against H.pylori which can be consumed on a larger scale also have 0 been reported, but anti-H. pylori activities of whole tissues of these plants generally are not the highest. The following are three examples of plants with previously described activities against H.pylori which may be used in larger amounts in functional food;

Cranberry juice (Burger et al. 2000, FEMS Immunology and Medical Microbiology, 2000,

29, 295-301 ), 5 Blackcurrant (Lensfeld, C. et al. 2004, Planta Medica 70(7), 620-626),

Fresh broccoli sprouts (Galan, M. V. et al. 2004, Digestive Diseases and Sciences,

49(7/8), 1088-1090).

The main idea of the present invention is to use mixtures of common edible plant tissues 0 with different anti-H. pylori activities and thereby suppress H.py/o/v-associated diseases in human populations by cheap and ecological means. The novelty of the invention is therefore the use of compositions of edible plant material highly active in the inhibition of H. pylori, said compositions remaining active under physiological conditions of low pH while not influencing the normal flora of the gastrointestinal tract. 5 SUMMARY OF THE INVENTION

The present invention relates to a composition comprising plant material from at least two different plants, said plants displaying at least three different activities against H. pylori wherein at least one of said activities is an anti-growth activity; and at least two of said activities are two or more different anti-adhesive activities obtained from tissues from said two or more different plants. The invention uses for inhibition a composition comprising common plants that can be consumed without definite limitations and in amounts that are used in food industry. The invention does not use medicinal plants or spice plants or any other plants where safe levels are undefined. Furthermore, the invention does not use subfractions or purified components if amounts of these components cannot be estimated, or if amounts exceed the amounts commonly used in food products.

Thus the invention relates to a composition comprising at least two or more of the fruit materials selected from the group comprising rosehip, walnut, acorn, lingonberry, rowanberry, fig and date or extracts thereof; and a prebioticum for use as a medicament.

In another embodiment of the invention the composition comprises at least one or more of the fruit materials selected from the group comprising rosehip, walnut and acorn; and a prebioticum; and at least one or more of the fruit materials selected from the group of plants comprising lingonberry, rowanberry, fig and date or extracts thereof.

In another embodiment of the invention the composition comprises rosehip or an extract thereof; a prebioticum; and at least one or more of the fruit materials selected from the group of plants comprising walnut, acorn, lingonberry, rowanberry, fig and date or extracts thereof.

In another embodiment of the invention the composition comprises walnut or an extract thereof; a prebioticum; and at least one or more of the fruit materials selected from the group of plants comprising, rosehip, acorn, lingonberry, rowanberry, fig and date or extracts thereof.

In another embodiment of the invention the composition comprises acorn or an extract thereof; a prebioticum; and at least one or more of the fruit materials selected from the group of plants comprising walnut, rosehip, lingonberry, rowanberry, fig and date or extracts thereof. In another embodiment of the invention the composition comprises rosehip and walnut or extracts thereof, and a prebioticum.

In another embodiment of the invention the composition comprises rosehip and acorn or extracts thereof, and a prebioticum.

In another embodiment of the invention the composition comprises acorn and walnut or extracts thereof, and a prebioticum.

In another embodiment of the invention the composition comprises rosehip, acorn and walnut or extracts thereof, and a prebioticum.

In another embodiment of the invention the prebioticum of the composition is selected from the group comprising fructooligosaccharides (FOS), honey oligosaccharides, galacto-oligosaccharides (GOS)₁ chitosan oligosaccharides, raffinose oligosaccharides, agaro-oligosaccharides and inulin.

In another embodiment of the invention the prebioticum is a short chain fructooligosaccharides (FOS) or inulin.

In another embodiment of the invention the dosage amount, calculated on dried weight of fruit material is the following: for walnut between 1-20 g; for rosehip between 1-20 g; for lingonberry between 2-40 g; for rowanberry between 0.5-3 g; for fig between 2-40 g; and for date between 3-15 g.

In another embodiment of the invention the dosage amount of prebioticum is 1-5 g.

In another embodiment of the invention the composition further comprises 1-2 grape kernels (dried and ground).

In another embodiment of the invention the plant material is in the form of a dried and ground material.

In another embodiment of the invention the invention further comprises one or more probiotic bacteria.

Furthermore, the invention relates to a composition for use in treatment of gastric diseases. In a further embodiment of the invention the gastric disease is chronic gastritis, duodenal ulcers or gastric ulcers.

The invention also relates to a composition for use in inhibition, treatment or prevention of Helicobacter pylori.

The invention also relates to a use of a composition for the manufacture of a medicament for inhibition, treatment or prevention of Helicobacter pylori.

Furthermore the invention relates to the use of the composition as an ingredient in a functional food.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 shows the inhibition of binding of H. pylori to model epitopes separated on TLC plates by extract obtained from rosehip.

Fig. 2 Screening of plant extracts for anti-growth activities using H. pylori CCUG 17874. DETAILED DESCRIPTION OF THE INVENTION

This invention uses common food plants and other components commonly used in food industry to inhibit the human gastric pathogen H. pylori. The invention uses mixtures of components with different inhibitory activities. Each mixture comprises tissues from at least two different plants wherein said plants display at least three different activities against H. pylori: one anti-growth activity and at least two different anti-adhesive activities obtained from at least two different plants. Preferably the mixture also comprises at least one prebiotic oligosaccharide. A prebiotic is a non digestible food ingredient that beneficially affects the host by selectively stimulating the growth and/or activity of one or a limited number of bacteria (e.g. Lactobacillus and Bifidobacterium species) in the gastrointestinal tract that can improve the host health. Various dietary carbohydrates are candidate prebiotics but most effective seem to be oligosaccharides. In particular the ingestion of fructooligosaccharides (FOS) has been shown to stimulate bifidobacteria in the lower gut. FOS are chain polymers of the sugar fructose that are found in a variety of foods. The sugar units can be linked in a single straight chain or can be a chain with side branches. In many cases small amounts of glucose are also contained in the chain. Chemically, FOS are difficult to define, because the length of the fructose chains can vary from source to source. Therefore a FOS analysis of a food may report the total of several closely related compounds. lnulin is an example of a longer chained compound that is considered a FOS. The shorter (lower molecular weight) compounds tend to have a sweet taste. Actilight 950 P™ is an example of a short chain FOS that may be used in this invention. Other prebiotic oligosaccharides that can be used are: honey oligosaccharides (shown to increase populations of bifidobacteria and lactobacilli); Galcto-oligosaccharides (GOS). (H. pylori is known to bind to various Gal-containing epitopes and the prebiotic galacto- oligosaccharides have, in addition to common prebiotic effects, anti-adhesion effects on the bacterium); Chitosan oligosaccharides (shown to have prebiotic effects on the Bifidobacterium bifidium and Lactobacillus sp.); raffinose oligosaccharides (used as a prebiotic to stimulate bifidobacteria strains in fermented milk) and agaro-oligosaccharides (promote the growth of beneficial bacteria).

It is important to note that the addition of a prebiotic fructoligosaccharide (e.g. Actilight 950 P™) to mixtures of the edible plants do not interfere with the anti-H. pylori activity. Prebiotic oligosaccharides stimulate the growth of probiotic bacteria. As discussed above, there are indications that probiotic bacteria help to remove Helicobacter pylori from the stomach. Probiotic bacteria improve results of a standard therapy and the effect seems to be mediated by different mechanisms including direct antimicrobial effects Thus, the mixtures of edible plants are suitable to be used together with the prebiotic oligosaccharides to further enhance the anti H. pylori effects of the plants.

Of relevance is that these probiotic bacteria help to maintain lower levels of H. pylori in the stomach and that the extracts of the invention do not inhibit growth of the important symbiotic and probiotic microorganisms of the human gastrointestinal tract. Walnut, rosehip and acorn (the most potent plants of this invention) were tested against Escherichia coli Nissle 1917 (a probiotic strain of E. coli ) and some other strains of E. coli, as well as two probiotic Lactobacillus species, Lactobacillus reuteri protectis and Lacobacillus acidofilus (L johnsonii). Neither of these strains was inhibited by the mentioned plants in amounts used in this work. Of importance is that Lactobacillus species were recently reported to be present in the human stomach. Another important part of the invention is that all plants used represent food plants which may be used without subfractionation and without definite limitations (in amounts that can affect H. pylori in the stomach according to in vitro studies). The high anti-H.py/or/ activities of these plants (see below comparison with some previously published plants and examples of doses) permit a use of the material in form of raw plant tissues, dried plant tissues or as fresh or dried water extracts in amounts corresponding to the amounts which are commonly used in food industries. Further, the invention uses extracts which are stable at low pH. All plants (except for fig and date) were stable at pH 1.8 (0.15 M HCI). Walnut, rosehip and acorn were tested at pH 1 ,0 (0.1 M HCI), 37⁰C for 1 h and no loss of activity was observed.

Mixtures of components can be prepared in a dried form and consumed with sour milk, or yoghurt, or other drinks of choice. Drinks containing probiotic bacteria, for example the commonly used Lactobacillus acidophilus, are highly recommended. Alternatively, the active plants or their extracts may be prepared as mixtures with other basic food products in form of a gel or as a fast food.

In summary, the invention uses mixtures of plants which are (Zn vitro) highly effective against H pylori, safe in use and resistant to the extreme pH conditions of the stomach. Another important aspect of the invention is that different components in the mixtures complete and strengthen each others activities. The invention has a high potential to be a cheap and commonly available means for prevention and treatment of milder forms of gastroduodenal discomforts in human populations. Many plants have been described as active against H. pylori, but, to our knowledge, an efficient functional food against this bacterium has not yet been developed.

Anti-adhesion properties of plants used in this invention

Screening of a larger number of food plants revealed several plant tissues with strong activities against H. pylori. The following plants turned out to be active as anti-adhesive agents against H. pylori:

Rosehip {Rosa canina), Grape kernels (Vitis vinifera),

Acorn (genera Quercus)

Walnut (Juglans regia)

Rowanberry (Sorbus aucuparia),

Cowberry (lingonberry) (Vaccinium vitis idaea) Plum {Prunus domestica)

Fig (Fikus caria)

Date (Phoenix dactylifera)

Flaxseed {Linum usitatissimum) Hemagglutination inhibition assay.

H. pylori cells are known to agglutinate human erythrocytes through interactions with membrane-bound epitopes and this phenomenon is widely used to investigate the sialic acid-dependent adhesion of the bacterium. The H. pylori strain CCUG 17875 (CCUG = Culture Collection, Gδteborg University, Sweden) was used in this work as a standard strain in all experiments. In addition other strains were used in some experiments like CCUG 17874 or H. p. J99. The inhibition of hemagglutination by active components is evaluated using light microscopy. In a typical experiment the plant tissue is ground and extracted with water (1-20 volumes of water in relation to the tissue) at 37°C for 5 hours, with occasional shaking. The material is then filtered through filter paper.

Rosehip, grape, acorn, walnut, rowanberry, cowberry and plum inhibited the binding of H. pylori to NeuAc whereas fig, date and flaxseed were active as inhibitors of binding of this bacterium to neutral epitopes. Relative strengths of inhibition of the binding of H. pylori to NeuAc of selected plants are shown in Table 1.

In table 1 the inhibitory action on the binding of H. pylori to human erythrocytes (anti- adhesion test) by acorn, rosehip and walnut and a comparison with cranberry (Vaccinium oxycoccus) and blackcurrant {Ribes nigrum) are shown. The two latter plants have in earlier reports been described as active against H. pylori. Table 1

The results are related to the same amount of the dry fruit material of each plant. "- " means no agglutination (= total inhibition), "+" weak agglutination, "++" agglutination;

"+++" strong agglutination (=no inhibition). * uncertain result. Inhibitory binding of H. pylori to model epitopes separated on TLC plates An example of how an extract obtained from rosehip inhibits the binding of H. pylori to NeuAc and sulphatide on TLC plates is shown in Fig.1. In this assay model epitope structures were separated and immobilized on silica gel TLC plates (model epitopes are indicated in the picture). The two panels represent autoradiograms after overlay of the plates with ³⁵S-labeled bacteria, (see also "Background"). The control H. pylori bound to different NeuAc-contalning fractions in lanes 4-5 (H. p., left plate). This binding was blocked in the presence of rosehip (lanes 4-5, HpAN, right plate). Binding to sulphatide (lane 3) (and partly to Neolacto, lane 1) was also affected negatively.

Anti-growth properties of selected plants used in this invention

Screening for anti-H-py/or/ activities revealed several edible plants with anti-growth properties. One of the growth tests is shown in Fig. 2, where the bacteria are grown on agar plates (diameter 3.5 cm, 3 ml agar). The right plate in each panel represents the control growth whereas the left plate shows inhibition of growth by a respective extract. Plant extracts (200 μl of each) were applied in the middle of the agar plates and allowed to soak into the gel. The calculations that followed were done on the assumption that active components were evenly distributed in the gel. However, the final concentration of active components in the gel will be in form of a gradient with highest concentrations in the middle of the plates and lowest concentrations at the edges (see PL = plum, L = cowberry (lingonberry) and RV = redcurrant in Fig 2). Thus, the effective concentrations for V = walnut, Z = acorn and SV = blackcurrant (at the edges of the plates) are lower than the numbers given in the table 3. The bacterial cells were allowed to grow for two days, and as can be seen on the control plates, the bacterium grows in form of a white coating. In Fig. 2 the following codes are used: Z = acorn, RC is the same as rosehip, PL = plum, SV = blackcurrant, RB = rowanberry, L = cowberry (lingonberry), V = walnut, RV = redcurrant.

Comparison to plants having a known inhibitory effect on H.pylori

In table 2, the potency of the anti-growth activity of the plants of this invention was compared with anti-growth activities of cranberry and blackcurrant. The experiments were performed as described in example 3 using diluted plant extracts. The strongest anti- growth properties were displayed by acorn and walnut (Table 2). Table 2

The results are related to the same amount of the dry fruit material of each plant. "- " means no growth (total inhibition of growth); "+" weak growth, "++" growth;

"+++" strong growth (no inhibition).

Table 3 summarizes the inhibitory properties of selected plant extracts. Quantitative results are expressed in the table as lowest effective concentrations or lowest effective amounts of the extracted material (whole tissue extracts).

Table 3

* Whole fruit tissue water extracts obtained from the plants are expected to contain a variety of components including complex carbohydrates, proteins, low-molecular organic molecules and inorganic salts, therefore, again, the real effective doses of active components can be expected to be far below the given numbers.

The most active plants of this invention generally had higher activities as compared with activities of the previously published edible plants tested in this work (Table 1 and 2).

Cranberry was less effective in inhibiting the growth of H. pylori than walnut and less effective than rosehip, walnut and grape kernels regarding its inhibition of binding to sialic acid (NeuAc). Regarding inhibition of binding to sialic acid, cranberry was less effective also after subfractionation. According to published data a partial inhibition of binding to sialic acid by H. pylori could be achieved using a purified subfraction of cranberry at cone. 200 μg/ml (Lensfeld, C. et a/. 2004, Planta Medica 70(7), 620-626 ) whereas in the present invention the total inhibition of the binding to sialic acid is achieved using crude water extracts (without fractionation and enrichment of the active substances) at concentrations of 290 μg/ml for walnut and 20-100 μg/ml for grape kernels (as tested against the same strain of H. pylori as in Lensfeld, C. et a/.). It should be noted that cranberry is one of the most known and best described common food plants which have been reported as active against H. pylori.

Also blackcurrant (SV in Fig. 2) turned out to be less effective as an inhibitor of H. pylori than the most potent plants of this invention (see Tables 1 and 2) although the activities were high. Blackcurrant has been described as an inhibitor of the in vitro adhesion of the bacterium. It has been reported that high molecular weight polysaccharides from blackcurrant seeds inhibit adhesion of H. pylori to human gastric mucosa (Galan, M. V. et al. 2004, Digestive Diseases and Sciences, 49(7/8), 1088-1090).

Another plant which could not compete with plants of this invention was broccoli (regarding its use in functional food). It has previously been shown that sulforaphane isolated from broccoli displays activity against H. pylori and fresh broccoli sprouts were proposed as a means for the treatment of H. pylori infections (Mahady-Gail, B., et al. 2001 , Am. J. Gastroenterol. 96 (12), 3454-3455). However, total water extracts prepared from fresh broccoli sprouts did not affect H. pylori growth on agar plates in our experiments (results not shown).

Also garlic and parsley, previously reported as active against H. pylori, (Shoaf, K. et al.

2006 Infection and Immunity 74(12), 6920-6928 and Rachel O'Msahony et al. 2005, World

J Gastroenterol 11 (47), 7499-7507 respectively) turned out to be without effect in growth tests (as tested in form of water extract on agar plates).

Mixtures of walnut and rosehip displayed higher activities than expected from the sum of individual activities thus indicating synergistic effects as can be seen in Table 4 below.

These effects were visible when walnut and rosehip were mixed having the proportions rosehip:walnut of 1 :2 to 2:1.

Table 4. Synergistic effect: Inhibition of growth of H. pylori by a mixture of walnut and rosehip in comparison with inhibition by walnut extract and rosehip extract alone.

"- " no growth (total inhibition of growth) "+" weak signs of growth, "++" weak growth;

"+++" growth, but somewhat weaker than control "++++" strong growth (as in control growth, no inhibition)..

Examples of doses of plant tissues of this invention (according to the in vitro studies) In the following examples the invention will be described in more detail. However, the described embodiments mentioned below are only given as examples and should not be limiting to the present invention. Other solutions, uses, objectives, and functions within the scope of the invention as claimed in the below described patent claims should be apparent for the person skilled in the art. It should furthermore be noted that the word "comprising" does not exclude the presence of other elements or steps than those listed and the words "a" or "an" preceding an element do not exclude the presence of a plurality of such elements. Anti -H. pylori activities of selected fruit material and examples of recommended doses are as shown below. The calculations were done based on the in vitro studies.

Acorn, 1 g (ground, dried fruit) or the corresponding water extract: 100% inhibition of H. pylori growth in the volume of at least 20 ml (and partial inhibition of growth in the volume of at least 40-80 ml), and 100% inhibition of binding to sialic acid in at least 100 ml (and partial inhibition of binding to sialic acid in 200-400 ml). A recommended dose would be in mixtures with other plants between 0.5 and 4 g per portion, more preferably between 1-2 g per portion, 1-2 times daily.

Walnut, 1 g (ground, dried fruit): 100% inhibition of H. pylori growth in the volume of at least 40 ml (and partial inhibition of growth in the volume of at least 80-160 ml), and 100% inhibition of binding to sialic acid in 50 ml (and partial inhibition of binding to sialic acid in 100-200 ml). A recommended dose to assure the desired effect in the stomach would thus be between 1 and 20 g per portion, more preferably between 3-15 g per portion, most preferably between 5-10 g per portion, 1-2 times daily

Rosehip, 1 g (ground, dried fruit): Partial inhibition of growth in 40-80 ml and 100% inhibition of binding to sialic acid in the volume of 200 ml (and partial inhibition of binding to sialic acid in the volume of 400-800 ml). Recommended dose is between 1 and 20 g per portion, more preferably between 3-15 g, most preferably between 4-10 g, 1-2 times daily

Linqonberrv, 1 g (ground dried fruit): Partial inhibition of growth in 10 ml and 100 % inhibition of binding to sialic acid in 25 ml (and partial inhibition of binding to sialic acid in 50 ml). Recommended dose is between 2 and 40 g per portion, more preferably between 3-30 g per portion, most preferably between 4-20 g per portion, 1-2 times daily.

Rowanberry, 1 g (ground dried fruit): Partial inhibition of growth in 10 ml and 100 % inhibition of binding to sialic acid in 25 ml (and partial inhibition of binding to sialic acid in 50-100 ml). Recommended dose is between 0.5-3 g per portion, more preferably between 2-4 g per portion and most preferably 3 g per portion, 1-2 times daily.

Fig, 1 g (dried ground fruit): Binding by H. pylori in the volume of at least 130 ml (as shown by direct binding of H. Pylori to dilution series of the extracted material on TLC plates). According to inhibition studies (see Fig. 2) the binding is to neutral epitopes. The recommended dose is between 2 and 40 g per portion, more preferably between 3-30 g per portion, most preferably between 5-20 g per portion, 1-2 times daily.

Date, 1 g (the effect of Date is similar to the effect of Figs). The recommended dose is between 2 and 20 g per portion, more preferably between 3-15 g per portion and most preferably between 5-10 g per portion, 1-2 times daily.

Prebioticum: 1-5 g per portion, 1-2 times daily.

The following mixtures are examples of different embodiments of the invention. Each mixture comprises fruit material from at least two different plants wherein said plants display at least three different activities against H. pylori: one anti-growth activity and at least two different anti-adhesive activities obtained from at least two different plants. Preferably the mixture also comprises at least one prebiotic oligosaccharide. All mixtures are expressed as recommended dose per one portion and should preferably be consumed 1-2 times daily. The mixtures of the invention can for example be prepared in a dried form and consumed together with sour milk or yoghurt, or other drinks of choice. Alternatively, the active plants or their extracts may be prepared as mixtures with other basic food products in form of a gel or as a fast food.

Mixture 1 Rosehip, 8 g. Activity: anti growth and anti-adhesive (NeuAc and Sulph). Walnut, 5 g. Activity: Anti-growth and anti-adhesive (NeuAc). Prebioticum, 2.5 g. Activity: stimulation of probiotic bacteria.

Mixture 2

Rosehip, 4 g. Activity: anti growth and anti-adhesive (NeuAc and Sulph). Lingonberry, 4 g. Activity: Anti-growth and anti-adhesive (NeuAc). Fig, 5 g. Activity: Anti-adhesive (neutral epitopes). Prebioticum, 2.5 g. Activity: stimulation of probiotic bacteria.

Mixture 3

Rosehip, 4 g. Activity: anti growth and anti-adhesive (NeuAc and Sulph). Lingonberry, 4 g. Activity: Anti-growth and anti-adhesive (NeuAc). Rowanberry, 0.5 g. Activity: anti-growth and anti-adhesion (NeuAc). Fig: 5 g. Activity: anti-adhesive (neutral epitopes) Prebioticum, 2.5 g. Activity: stimulation of probiotic bacteria.

Mixure 4 Rosehip, 4 g. Activity: anti growth and anti-adhesive (NeuAc and Sulph). Lingonberry, 4 g. Activity: Anti-growth and anti-adhesive (NeuAc). Rowanberry, 0,5 g. Activity: anti-growth and anti-adhesion (NeuAc). Date, 5 g. Activity: anti-adhesive (neutral epitopes) Prebioticum, 2.5 g. Activity: stimulation of probiotic bacteria.

Mixture 5

Walnut, 5 g. Activity: Anti-growth and anti-adhesive (NeuAc). Lingonberry, 5 g. Activity. Anti-growth and anti-adhesive (NeuAc). Fig, 5 g. Activity: Anti-adhesive (neutral epitopes). Prebioticum, 2.5 g. Activity, stimulation of probiotic bacteria

Mixture 6 Walnut, 5 g. Activity: Anti-growth and anti-adhesive (NeuAc). Lingonberry, 5 g. Activity: Anti-growth and anti-adhesive (NeuAc). Date, 5 g. Activity: anti-adhesive (neutral epitopes) Prebioticum, 2.5 g. Activity: stimulation of probiotic bacteria

Mixture 7 Walnut, 5 g. Activity: Anti-growth and anti-adhesive (NeuAc).

Rosehip, 5 g. Activity: anti growth and anti-adhesive (NeuAc and Sulph). Fig, 5 g. Activity: Anti-adhesive (neutral epitopes). Prebioticum, 2.5 g. Activity, stimulation of probiotic bacteria

Mixture 8 Walnut, 5 g. Activity: Anti-growth and anti-adhesive (NeuAc).

Rosehip, 5 g. Activity: anti growth and anti-adhesive (NeuAc and Sulph). Date, 5 g. Activity: anti-adhesive (neutral epitopes) Prebioticum, 2.5 g. Activity: stimulation of probiotic bacteria

Mixture 9 Rosehip, 8 g. Activity: anti growth and anti-adhesive (NeuAc and Sulph). Walnut, 5 g. Activity: Anti-growth and anti-adhesive (NeuAc). Acorn 0.5 g. Activity, anti-growth and anti-adhesive (NeuAc and Sulph). Prebioticum, 2.5 g. Activity: stimulation of probiotic bacteria

Mixture 10

Rosehip 6 g. Activity: anti-growth and anti-adhesive (NeuAc and Sulph). Acorn 0.5 g. Activity: anti-growth and anti-adhesive (NeuAc and Sulph). Prebioticum 2.5 g. Activity: stimulation of probiotic bacteria.

Mixture 11

Lingonberry, 5 g. Activity: Anti-growth and anti-adhesive (NeuAc). Acorn 0.5 g. Activity: anti-growth and anti-adhesive (NeuAc and Sulph). Date, 5 g. Activity: anti-adhesive (neutral epitopes). Prebioticum 2.5 g. Activity: stimulation of probiotic bacteria.

Additionally, all mixtures may contain 1- 2 grape kernels (dried and ground) which display very strong anti-adhesive activity (NeuAc) (see Table 3).

Claims

1. A composition comprising:

- at least two or more of the fruit materials selected from the group comprising rosehip, walnut, acorn, lingonberry, rowanberry, fig and date or extracts thereof; and

- a prebioticum for use as a medicament.

2. A composition according to claim 1 , wherein

- at least one or more of the fruit materials is selected from the group comprising rosehip, walnut and acorn; and - a prebioticum; and

- at least one or more of the fruit materials selected from the group of plants comprising lingonberry, rowanberry, fig and date or extracts thereof.

3. A composition according to claim 1 , comprising rosehip or an extract thereof; a prebioticum; and at least one or more of the fruit materials selected from the group of plants comprising walnut, acorn, lingonberry, rowanberry, fig and date or extracts thereof.

4. A composition according to claim 1 , comprising walnut or an extract thereof; a prebioticum; and at least one or more of the fruit materials selected from the group of plants comprising, rosehip, acorn, lingonberry, rowanberry, fig and date or extracts thereof.

5. A composition according to claim 1 , comprising acorn or an extract thereof; a prebioticum; and at least one or more of the fruit materials selected from the group of plants comprising walnut, rosehip, lingonberry, rowanberry, fig and date or extracts thereof.

6. A composition according to claim 1, comprising rosehip and walnut or extracts thereof, and a prebioticum.

7. A composition according to claim 1, comprising rosehip and acorn or extracts thereof, and a prebioticum.

8. A composition according to claim 1 , comprising acorn and walnut or extracts thereof, and a prebioticum.

9. A composition according to claim 1 , comprising rosehip, acorn and walnut or extracts thereof, and a prebioticum.

10. A composition according to claims 1-9, wherein the prebioticum is selected from the group comprising fructooligosaccharides (FOS), honey oligosaccharides, galcto-oligosaccharides (GOS), chitosan oligosaccharides, raffinose oligosaccharides, agaro-oligosaccharides and inulin.

11. A composition according to claim 10, wherein the prebioticum is a short chain fructooligosaccharides (FOS) or inulin.

12. A composition according to one or more of the claims 1-11 , wherein the dosage amount, calculated on dried weight of fruit material is the following: for walnut between 1-20 g; for rosehip between 1-20 g; for acorn between 0.5-4 g; for lingonberry between 2-40 g; for rowanberry between 0.5-3 g; for fig between 2-40 g; and for date between 3-15 g.

13. A composition according to one or more of the claims 1-11 , wherein the dosage amount of prebioticum is 1-5 g.

14. A composition according to one or more of the claims 1-13, further comprising 1-2 grape kernels (dried and ground).

15. A composition according to one or more of the claims 1-14, wherein the plant material is in the form of a dried and ground material.

16. A composition according to one or more of the claims 1-15, further comprising one or more probiotic bacteria.

17. A composition according to one or more of the claims 1-16, for use in treatment of gastric diseases.

18. A composition according to claim 17, when the gastric disease is chronic gastritis, duodenal ulcers or gastric ulcers.

19. A composition according to one or more of the claims 1-16, for use in inhibition, treatment or prevention of Helicobacter pylori.

20. Use of a composition according to one or more of the claims 1-16, for the manufacture of a medicament for inhibition, treatment or prevention of Helicobacter pylori.

21. Use of the composition according to one or more of the claims 1-16, as an ingredient in a functional food.