The invention is related to preparation of a food supplement comprising microorganism mixtures, which is developed scientifically and technologically in order to prevent chronic constipation problems in humans, especially elderly and children, and to usage of probiotics and prebiotics as food supplement in human consumption. State of the art

It is known that the probiotics subject to the invention are at least as old as human history. The first usage of probiotics is closely related to the usage of historic fermented foods. With contemporary sophisticated techniques in molecular archeology, evidences showing the existence of probiotic products has been traced back to approximately 10,000 years ago. Results arising from the analysis of the findings show that microorganisms were used in the production of fermented beverages even in the B.C. 7000s. Most probiotics are non- pathogenic microorganisms and are naturally found in human digestive system such as Lactobacilli, Bifidobacteria and Enterococci. Probiotics have a variety of effect mechanism although it has not been explained exactly how they realize their effects. Probiotics modulate immune system of a host, directly affect other microorganisms, or are effective on microbial products, host products or food components.

Constipation, having a probability of occurrence in humans up to 30%, also means that intestinal movements are less than normal. In other words, constipation is defined as excretion of stool (feces) as being dry, hard, less than normal and late. Bifidobacteria, Bacteroides and Clostridia have decreased in the fecal flora of the individuals having a complaint of constipation. Treatment for signs (symptomatic treatment) is firstly administered in eliminating constipation due to colorectal cancer, irritable intestine syndrome and many other diseases related to the digestive tract, or malnutrition. So, it is preferred to use a product that increases intestinal movements. For this purpose, many natural or synthetic products are sold under the name of cato -cathartic (such as Magnesium sulphate, Sodium sulphate, Bisacodyl, Dantron, Lactulose, Castor oil, Senna). Nevertheless, most of such products are pharmaceutical products and studies have shown that they have some serious side effects such as cardiac arrhythmia, abdominal cramps, coronary artery contractions and even myocardial infarction due to the active substance itself or the excipients it comprises. It is stated that Senna plant which is shown as a natural product and sold in herbalists should not be used in people with abdominal pain, intestinal obstruction, Crohn's disease, ulcerative colitis, appendicitis, gastroenteritis, anal prolapsus or hemorrhoids due to the glycosides it comprises. Although synbiotic products, comprised of prebiotics, probiotics or a mixture of both, are brought in the market to eliminate constipation, it is known from scientific studies that some bacteria contained in these products treat diarrhea rather than constipation and these are randomly recommended. In order to prove definitively that a product eliminates constipation, the effectiveness of that product should be proven by means of a controlled study. Therefore, excessive side effects of the products used to eliminate constipation in the market, of which efficiency is proven, and the lack of information about the efficacy of prebiotic and probiotic products with no side effects or fewer side effects necessitate to develop a product of which efficiency is fully proven by a controlled study and will not have side effects. For example, studies carried out with individual probiotic bacteria have shown that Bifidobacterium animalis, Lactobacillus casei Shirota, Lactobacillus paracasei and Propionibacterium freudenreichii bacteria increase the frequency of defecation and can reduce intestine transition time. Unlike these bacteria, studies carried out with some probiotic microorganisms show that not all types of microorganisms provide a beneficial effect in constipation. For example, Lactobacillus rhamnosus GG does not eliminate constipation.

The product developed in this invention is a synbiotic consisting of a combination of bacteria of which efficiency is proven in scientific studies and inulin, which is a dietary fiber (prebiotic). Inulin is a substance that increases growth of Bifidobacterium and Lactobacillus- type bacteria in intestines when taken with a diet in low amounts, and has a stronger laxative effect compared to other prebiotics, and also attracts attention with its cheapness. Today, each capsule of the product named as Probicn ^: available on the market contains 11 bacterial strains (total 5 billion cfu-colony forming units) and 600 mg inulin. These are Lactobacillus acidophilus (1 Billion cfu), Bifidobacterium longum (1 Billion cfu), Bifidobacterium bifidum (500 Million cfu), Lactobacillus plantarum (500 Million cfu), Lactobacillus rhamnosus (500 Million cfu), Lactobacillus bulgaricus (250 Million cfu), Lactobacillus paracasei (250 Million cfu), Lactobacillus breve (250 Million cfu), Lactobacillus reuteri (250 Million cfu), Streptococcus thermophilus (250 Million cfu), Bifidobacterium infantis (250 Million cfu), inulin (600 mg), and the product is administered as 2 capsules a day, in the morning and evening. Each capsule of another product on the market (Mastervit ^® ) contains 12 different bacterial strains (10 billion cfu) and 272 mg inulin and 100 mg glutamine. These are Lactobacillus acidophilus (1,25 Billion cfu), Lactobacillus plantarum (1,25 Billion cfu), Lactobacillus rhamnosus (1,25 Billion cfu), Bacillus subtilis (1 Billion cfu), Bifidobacterium lactis (1 Billion cfu), Bifidobacterium longum (750 Million cfu), Bifidobacterium infantis (750 Million cfu), Streptococcus thermophilus (750 Million cfu), Lactobacillus bulgaricus (500 Million cfu), Bifidobacterium bifidum (500 Million cfu), Lactobacillus paracasei (500 Million cfu), Lactobacillus breve (500 Million cfu), Inulin (272 mg), Glutamine (100 mg), and the product is administered as 2 capsules a day, in the morning and evening.

There is no similar study with the product subject to the invention. This is the same when looking at patent applications. The patent application No. US4476121A is related to a product used against constipation and comprises senna, glycerin and fruit in its content. The patent application No. US5232699A is related to a product used against constipation and comprises psyllium in its content.

The product developed in this invention is a synbiotic consisting of a combination of bacteria of which efficiency is proven in scientific studies and inulin, which is a dietary fiber (prebiotic). Inulin is a substance that increases growth of Bifidobacterium and Lactobacillus- type bacteria in intestines when taken with a diet in low amounts, and has a stronger laxative effect compared to other prebiotics, and also attracts attention with its cheapness.

As a result, the product subject to the invention has been supported with inulin in which it is known that probiotic microorganisms, which have been shown to be effective when used in constipation and aimed to be more effective by combining them, show cheaper and stronger laxative effect compared to other prebiotics and thus a new synbiotic product has been obtained.

Technical problems to be solved by the invention

As a technical feature, there are 11 bacterial strains and 5 billion cfu in the Probien ^® ; 12 bacterial strains and 10 billion cfu in the Mastervit ^® . There are 5 bacterial strains and 5 billion cfu in the product subject to the invention. According to the findings of the World Health Organization, it is reported that 25 thousand people die annually just in Europe due to antibiotic resistance. Furthermore, as long as the wrong and unconscious usage of antibiotics continues, it is claimed that in 20-30 years, more than 10 million people in the world will die due to resistant bacterial infections since there will be no antibiotics to cure them. Until recent years, it was believed that probiotic bacteria would not carry antibiotic - resistance genes. Nevertheless, in the recent reports of the European Medicines Agency (EM A) and the American Food and Drug Administration (FDA), it has been understood that probiotic bacteria now carry antibiotics-resistance genes and serve to spread the resistance. Therefore, in such products, the fewer bacterial strains are used, the less antibiotic -resistance genes will be spread. Thus, the product subject to the invention seems more advantageous in terms of preventing the spread of antibiotic -resistance genes.

In a study on Lactobacillus rhamnosus found in known products, it has been stated that this probiotic bacterium is not effective in treating constipation in children. Another bacterium, Lactobacillus acidophilus, is used in the treatment of traveler’s diarrhea, in the treatment of children with acute diarrhea, and in the treatment of Clostridium difficile -related diarrhea. In the same manner, Bifidobacterium longum is used in the treatment of neonatal necrotizing enterocolitis and radiation-induced diarrhea. In the product subject to the invention, only bacteria which have been proven to eliminate constipation by scientific studies have been used.

This situation is advantageous compared to the other similar situations due to the fact that the effects of the resulting product on the intestinal flora and structure are clearly known when compared to its known examples, due to its effect, its ability to be dosed and its effect on the organism. Description of the invention

The product developed in this invention is a synbiotic consisting of a combination of bacteria of which efficiency is proven in scientific studies and inulin, which is a dietary fiber (prebiotic). Inulin is a substance that increases development of Bifidobacterium and Lactobacillus- type bacteria in intestines when taken with a diet in low amounts, and has a stronger laxative effect compared to other prebiotics, and also attracts attention with its low cost.

Detailed description of the invention:

It is anticipated that probiotic market will increase more in the upcoming years. This market also covers a wide range of administration fields in milk, milk products, cereals, cooked food, dry food and fermented meat products. It is known that market size will increase due to the increase in disposable income and the increasing awareness towards healthy lifestyle. The increase in the prevalence of obesity disease such as diabetes together with unhealthy food consumption increases the demand for probiotic products. This growth is attributed to the increasing demand for nutrition supplements, and to the increasing elderly (geriatric) population due to obesity and intestinal health complications. Therefore, the product developed has been formulated for controlling constipation, especially in the elderly.

The product subject to the invention is a mixture each comprising lxlO ⁹ (one billion) cfu per gram Bifidobacterium bifidum BGN4, Bifidobacterium inf antis M-63, Bifidobacterium animalis spp lactis LMG 18314, Lactobacillus casei LMG P-20352, Lactobacillus plantarum LMG 26655 and 500 mg Inulin ( min 90%).

Microorganism composition of the product subject to the invention, which is developed against constipation.

The following types of microorganisms have been used so that the microorganism number of each of the microorganisms having 5 different effects per gram of each product prepared in sachet forms is at the level of 1 ^c 10 ⁹ cfu/g.

Bifidobacterium bifidum BGN4, Bifidobacterium infantis M-63, Bifidobacterium animalis spp lactis LMG 18314, Lactobacillus casei LMG P-20352, Lactobacillus plantarum LMG 26655 Prebiotic composition of the product subject to the invention, which is developed against constipation.

In each of the 5 -microorganism mixture prepared as a product, 500 mg of Inulin (min 90%) with prebiotic properties was added.

Preparation of the product mixture

Each type of microorganism, whose open formulation was determined above, was obtained as stock from the producing companies of which international certification numbers and product controls were certified as tested beforehand, and they were preserved in such a manner to specify the storage conditions and expiry dates for each on it. The design and technical infrastructure and equipment of the product subject to the invention were provided against contaminations by carrying out preliminary trial tests before the product preparation at necessary time intervals, and product development planning was made in accordance with legal legislations and introduced to the preparation areas.

The microorganisms, which are raw materials, are transferred to the mixing tanks with the control and measure programs taken beforehand against contamination of microorganism mixtures with special transfer vessel by carrying out their automatic weighing by the skilled - in-the-art and trained personnel, and they are mixed homogeneously with the help of a mixer. Likewise, after the composition of the inulin substance with prebiotic properties having a certification is obtained from registered companies, it is stored according to storage conditions stated in the label of the company from which raw material is obtained, and when the product will be prepared, it is weighed according to the quantity and marketing ways of the product to be produced, and transferred to the microorganism mix tank with transfer vessels in accordance with the regulations .

Prebiotic and lyophilized microorganism types which constitute the product are mixed thoroughly for 20-30 minutes in steel units inside the system where all kinds of contamination are prevented.

Herein, after the 5-microorganism mixture and the inulin to be used for prebiotic purposes are thoroughly homogenized, they are sent to a packaging unit by means of a valve and a transport system, and they are made ready with materials suitable for human consumption in sachet forms. The product is filled into capsules or sachets, when necessary. If required, tablet can be made into other forms.

Packaging materials are packaged with aluminum-coated paper, polyvinyl- or polyethylene- derivative materials, again in accordance with the legal legislations. In accordance with the label regulation, label information should indicate composition, expiry date, storage conditions, method of usage and dosage.

Samples are taken with random sampling method in the final products prepared, final product quality and product controls are performed, records are kept according to lot numbers, and products are tracked according to backtracking procedures in case of any product returns and problems. This process is maintained until homogeneity is ensured.

By means of this invention, unnecessary usage of bacterial strain, and thus the spread of antibiotic -resistance genes are prevented. Furthermore, the usage of random probiotic and prebiotic mixture has been avoided and its target-specific usage has been ensured.

By means of this invention, the production of healthier and antibiotic-free products in the microbiome and probiotic market, which are among the newly-growing markets will be contributed.