A COMPOSITION BASED ON A COMBINATION OF POMEGRANATE EXTRACT AND PROBIOTICS, ENABLES THE IN SITU PRODUCTION OF UROLITIN A.

Abstract

This invention relates to an oral composition containing pomegranate extract with ellagitannin and / or ellagic acid, which allows for the delivery of pomegranate extract to the distal part of the gastrointestinal tract with limited premature degradation in the gastric environment, and for the in situ formation of Urolitin A in the intestinal environment, facilitated by at least one probiotic strain that participates in or supports the conversion of ellagitannin and / or ellagic acid to Urolitin A. The composition in question is based on a configuration in which the pomegranate extract core is structured as granules coated with a pH-sensitive enteric polymer film, and these granules are physically separated from the probiotics, even though they are in the same dosage form. In an alternative configuration, uncoated pomegranate extract and at least one probiotic strain can be co-structured in a delayed-release capsule.This reduces the risk of premature biotransformation during shelf life; release and biotransformation are initiated in the intestinal environment.

Description

BASED ON A COMBINATION OF POMEGRANATE EXTRACT AND PROBIOTICS, AND IN SITU. A COMPOSITION THAT ENABLES THE OBTAINING OF UROLITHIN A. TECHNICAL FIELD The invention belongs to the technical field of pharmaceutical and nutraceutical / food supplement formulations, targeted release of gastrointestinal ellagitannin and / or ellagic acid into the intestine in the environment that enables, participates in, or facilitates the conversion of Urolitin to A. supporting in situ Urolitin A production in the gut via at least one probiotic strain It relates to a composition aimed at providing support. PREVIOUS TECHNIQUE Plant sources containing ellagitannin and / or ellagic acid, especially pomegranate fruit and pomegranate seeds. Following oral ingestion of the derived extracts, hydrolysis occurs in the gastrointestinal system. can undergo biotransformation processes, and as a result of these processes, the intestines in a technique where urolithin derivatives (especially Urolitin A) can be formed by the microbiota It is known that ellagitannins are hydrolyzed to ellagic acid in the intestinal environment. it is possible and ellagic acid is also involved in the enzymatic activities of intestinal microorganisms. By passing through successive transformation steps, it becomes various urolite intermediates and final urolites. It is accepted that transformation is possible. However, this transformation is only possible if... The fact that it cannot be explained by chemical breakdown suggests that the main determining factor is the gut microbiota. It is also generally understood that there are differences in composition, functional capacity, and between individuals. This is a known phenomenon in technology. In the known state of the art, despite the same ellagitannin / ellagic acid input, in individuals Urolith formation can occur at different levels, and even have no distinct final stages in some individuals. It is known that urolith formation cannot be observed. This situation is due to the gut microbiota. Species diversity, the presence of microorganisms that undergo specific transformation stages. or absence, whether these microorganisms are present in the gut in sufficient concentrations. and can vary depending on factors such as diet / lifestyle. Therefore, ellagitannin Consumption of a plant extract rich in nutrients can lead to consistent and predictable changes in every individual. It does not ensure the formation of Urolitin A at the level indicated, and the production capacity of Urolitin is determined by the "microbiota". It is known to have a "dependent" quality. This variability means that product effectiveness varies from person to person. differentiation and a standard biological output (e.g., a specific level of Urolitin A) This can lead to the inability to guarantee the security of the product. On the other hand, in the current state of the technique, uroliths can be directly (as isolated / pure components) There are also approaches to administering them in supplement form. However, urolithins... direct application; raw material supply and production cost, stability, formulation various challenges such as requirements and the sustainability of the targeted biological effect It may include. Furthermore, the approach of administering uroliths externally is used in some applications. It is based on providing the final metabolite rather than mimicking the "natural metabolic pathway". to support certain expected physiological processes through interaction with the microbiota This can be limited in terms of its function. Therefore, in the relevant technical field, uroliths of the intestine are being studied in depth. Approaches based on the production of biotransformation products in their natural environment are attracting interest. In the current state of the art, extracts with high polyphenol content, such as pomegranate extract... its stability in the gastrointestinal system may be limited, and particularly low levels in the gastric environment. Due to pH and enzymatic conditions, the active precursor compounds (ellagitannin / ellagic acid) are only partially formed. It is acknowledged that it may break down or fail to reach the desired area in sufficient quantity. This situation determines the amount of substrate required for the transformation that is intended to take place in the intestine. It can lower and therefore limit the formation of Urolitin A. Therefore In the current technique, plant extracts are preserved under gastric conditions and released in the intestine. controlled-release solutions such as enteric coatings and pH-sensitive polymers to provide this. It is among the known options. However, enteric coating alone It does not eliminate inter-individual variability in microbiota-induced transformation and a delivery solution aimed solely at better transport of the substrate to the target area It offers. In the current state of the technique, the aim is to compensate for inter-individual microbiota differences. The use of probiotic strains is also a common approach. Probiotic applications include: Supporting specific metabolic functions in the gut, making substrates more effective. such as breaking down or facilitating specific biotransformation steps They can be recommended for these purposes. However, maintaining the viability of probiotic strains and production... its stability during processing and storage, and against stressors such as stomach acid and bile salts 3 such as overcoming obstacles and reaching the target intestinal region with a sufficient number of live cells. The challenges are well known in the field of technology. These challenges of probiotics are addressed in formulation strategies. (drying method, preservatives, microencapsulation, packaging barrier, water activity) (control, etc.) shows high dependence. In addition, the plant substrate in the technique When probiotics are formulated together in the same product (such as pomegranate extract), It is acknowledged that undesirable interactions may occur during the product's shelf life. Especially in conditions where humidity cannot be controlled or the packaging barrier is inadequate, oxidation of polyphenols, decrease in probiotic viability, chemical change of substrate, and Results such as instability of the microenvironment within the product can be observed. Also, substrate-related issues may occur. Direct contact with probiotics can lead to premature / undesirable conversion under certain conditions. can contribute to reactions or batch-to-batch variability in quality parameters This can be considered a theoretical risk. Therefore, in technology, the same dosage form is used. Physical separation in products containing multiple functional components, multiphase transport. Factors such as architecture, granule / coating technologies, and packaging barriers affect product stability. It is known to be important in this respect. As one of the studies in the relevant technical field, patent number US20240382539 A1, to increase the conversion of ellagic acid to Urolitin A via the gut microbiota This patent relates to the use of an intestinal probiotic. The aim of this patent is to specifically target EA. those that cannot metabolize at all or metabolize with low efficiency (metabotype 0 and / or B) By enhancing the metabolism of ellagic acid to Urolitin A in individuals, it increases the yield of Urolitin A. The aim is to increase it. To achieve this, it is possible to modify the metabolite of ellagic acid. selected probiotic strains (single or in combination) and their combination with ellagic acid It contains a pharmaceutical composition in which it is included together (e.g., Lactobacillus acidophilus, L. plantarum, L. rhamnosus; Bifidobacterium breve / bifidum / longum; Bacteroides fragilis / vulgatus; Megasphaera elsdenii; Ruminococcus gnavus; Weissella confusa; Enterococcus faecalis; Akkermansia muciniphila). As one of the studies in the relevant technical field, patent number EP3733858 A1 is a By removing the hydroxyl group at the 8-position of urolithin through microorganisms This patent relates to a production method for converting another type of Urolith into a different one. Its aim is to remove the -OH group, particularly at the 8-position, from the first urolith. second Urolith (e.g., from Urolith C to isoUrolith A and / or from Urolith A to Urolith B) is to ensure that it is obtained through biotransformation. To achieve this, the first 4 a microorganism capable of producing a secondary urolith in a solution containing urolith (preferably using the genus Slackia; e.g., Slackia heliotrinireducens DSM 20476) fermentation / biotransformation step; and if necessary, ellagic acid and / or ellagitannin, etc. Before raw materials, Gordonibacter and / or Clostridium are used for the production of Urolitin C / A. It involves a multi-stage production method in the same system with microorganisms. A BRIEF DESCRIPTION OF THE INVENTION The present invention aims to eliminate the aforementioned disadvantages and to contribute to the relevant technical field. to bring new advantages, precursors such as ellagitannin and / or ellagic acid in pomegranate extract oral ingestion of compounds and the release of ellagitannin and / or ellagic acid in the intestinal environment At least one of the following: enables, participates in, or supports the conversion of urolithin to A. Supporting the formation of Urolitin A in the gut environment in conjunction with probiotic strains It is related to a composition. One aim of the invention is to investigate the ellagitannin and / or ellagic acid content in pomegranate extract and its effect on stomach acid and by limiting premature breakdown under upper gastrointestinal conditions, efficient transport of the contents into the intestinal environment and / or delayed release The goal is to create a composition that ensures its delivery to the intestinal tract. Another aim of the invention is to address urolithins resulting from inter-individual microbiota differences. A. In order to reduce production variability, ellagitannin and / or ellagic acid in the intestine in the environment that enables, participates in, or facilitates the conversion of Urolitin to A. at least one supporting probiotic strain in a controlled manner at the same dosage form The goal is to create a composition in which these elements are present. All the purposes mentioned above and those that will emerge from the detailed explanation below. The present invention aims to realize a multi-component and controlled solution suitable for oral administration. It is a composition with a release character. Accordingly, the composition, in a structure, is ellagitannin pH-sensitive enteric seed granules containing pomegranate extract with and / or ellagic acid structuring it in the form of enteric-coated granules coated with a polymer film and the aforementioned Ellagitannin and / or ellagic acid in the intestinal environment together with granules to Urolitin A at least one probiotic that enables, participates in, or supports this transformation It contains the strain. In an alternative configuration, the composition is uncoated pomegranate 5. extract and at least one of the probiotic strains in question, in a delayed-release capsule. This may involve the co-structuring of the release capsule (DR-Caps). Thus Pomegranate extract is protected from premature release and / or released with a delayed release in the gastric environment. It is delivered to the intestinal region, released in a targeted manner, and acts as a catalyst in the gut via probiotics. In situ Urolitin A production is supported. A feature of the possible formulation of the invention is that enteric-coated pomegranate granules are probiotic. physically separated from each other in phases and together in the same dosage form. despite the presence of direct contact between the granule core and probiotics This is to limit unwanted / premature biotransformations during shelf life. the risk is reduced and the transformation is initiated primarily in the intestinal environment. is provided. Another possible configuration of the invention involves the probiotic phase being composed of ellagitannin and / or The conversion of ellagic acid to urolithin A in the intestinal environment is facilitated by, participates in, or is related to this process. formulated to include at least one probiotic strain that supports conversion and total a live cell load at a level that will enable effective transformation in the target intestinal region It is the preservation of ellagitannin / ellagic acid metabolism in the intestine. Progression in direction A is supported and a more consistent metabolite among users. A formation profile is obtained. In some formulations, the probiotic strain in question is Lactobacillus plantarum, Bifidobacterium. pseudocatenulatum, Gordonibacter urolithinfaciens, Gordonibacter pamelaeae, Streptococcus thermophilus, Enterococcus faecium, Enterocloster aldenensis, Enterocloster asparagiformis, Enterocloster bolteae, Enterocloster citroniae, Enterocloster It can be at least one of the following species: Clostridioformis and / or Enterocloster lavalensis. DETAILED DESCRIPTION OF THE INVENTION This detailed description of the invention defines a method that enables the in situ isolation of Urolitin A. It is related to composition and is solely aimed at a better understanding of the subject, nothing else. This is explained with examples that will not create a limiting effect. 6 Within the scope of this invention, direct oral administration of Urolitin A affects the upper digestive system. Due to the limitations in breakdown and absorption in these sections, the desired effect is not achieved at a sufficient level. a precursor component structure containing pomegranate extract, given that its acquisition may be difficult. It is configured accordingly. Based on this, the precursor component structure in question uses pomegranate as the active ingredient. It contains extract. Pomegranate extract contains ellagitannin and / or other precursor compounds for the production of Urolitin A. It contains ellagic acid. Within the scope of this invention, pomegranate extract is used as the active ingredient; dry extract, It can be found in at least one of the following solid forms: powder, granules and / or other particulate matter. In addition, the ellagitannin and / or ellagic acid content of the extract in question is standardized. This can be achieved through standardization, reducing batch-to-batch variations and improving composition. This is important in terms of making its functional effectiveness more consistent. The content of ellagitannin and / or ellagic acid can be determined using appropriate analytical methods, for example. This can be determined through chromatographic analysis. The invention involves physically separating the precursor component from the probiotic component. structuring, direct interaction between components throughout the storage process limiting the stability of ellagitannin and / or ellagic acid content in pomegranate extract to protect, reduce the risk of early loss of probiotic viability and premature This is preferred in order to prevent biotransformation from initiating within the product. Therefore, even if pomegranate extract and probiotic components are present together in the same dosage form, biotransformation primarily targets the gastrointestinal system, particularly the intestine. A structure is being created that is conducive to its realization in this environment. The invention includes "physically separate structuring", with a precursor component and a probiotic. Although the components are present together in the same dosage form, they form a single homogeneous phase. separate physical populations that will not form and will limit direct contact. This indicates that the precursor component should be arranged in this way. Accordingly, the precursor component containing pomegranate extract, Probiotics can be structured in the form of a core, granules, and / or coated particles. The component exists as a separate powder, particle, granule, and / or coated particle population. They can be found in the same sachet, capsule, or similar oral dosage form. Even when they are present together, the probiotic component pomegranate extract is constantly exposed to the bare surface. and not in widespread direct contact; the precursor component has its own carrier / core structure and preferably protected within the cladding system. This physically separate configuration; 7 precursor component in enteric coated granules, lined cores, coated particles or presented as similar individual carrier units, while the probiotic component is separate from them. This can be achieved by having the particle population located within the same chamber. Alternatively, this separation can be achieved through a two-compartment sachet, a two-compartment capsule, and a multi-phase filling architecture. and / or dosage forms in which the components are arranged in separate layers or separate phases This can also be ensured. Thus, the precursor component and the probiotic component are supplied together until the moment of use. They can be kept separate from each other, but are presented to the user together within the same product format. This structure allows for the presentation of unwanted premature changes within the product. interactions and premature conversion reactions that may occur during storage It is possible to limit this; however, the precursor compounds in pomegranate extract In the intestinal environment, it combines with probiotic components to promote the formation of Urolitin A. Its participation in the biotransformation process is supported. Thus, the composition's shelf life... remaining stable throughout its lifespan and functioning in the target area after use. A balanced technical structure is achieved between them. The precursor component that is the subject of the invention has at least one component in a preferred application. The matrix can exist as a core structure containing a matrix carrier. The matrix in question... The carrier ensures the homogeneous distribution of the precursor component within the core structure, the granule. and / or obtaining the particle form and ensuring the physical stability of the structure It can be selected to support this. Accordingly, maltodextrin as the matrix carrier. and / or cyclodextrin and / or gum arabic, at least one of these groups may be used. The precursor component core that is the subject of the invention contains at least one primer layer. It may include. This primer layer is located between the core structure and the coating layer. to increase the adhesion of the coating to the core and improve core surface properties an intermediate film layer for regulation and, when necessary, limiting moisture penetration It can be configured as such. The most preferred application is hydroxypropyl methylcellulose and / or as a primer layer. At least one substance from the polyvinylpyrrolidone group can be used. Within the scope of the invention, a configuration is created in which the precursor component core is configured in a coated form. This can be achieved. Nuclear coating leads to premature release of the precursor component in the gastric environment. and limit its degradation, support its transport throughout the gastrointestinal system, and 8 To provide controlled opening in the intestinal region where pH conditions become suitable. It is important in terms of protection. In addition, the coating in question protects the core structure during the storage process. Premature interaction between components by reducing direct contact with the probiotic component. It can help reduce the risk. The coating used for the precursor component within the scope of this invention applies throughout the gastrointestinal tract. A pharmaceutically acceptable enteric film former that is sensitive to varying pH conditions. They are selected from polymers. The stomach environment is acidic, with a pH value generally between 1-3. pH levels are generally between 5.5 and 7.0 in the gut. It is rising. Therefore, the coating is insoluble or very insoluble in acidic stomach conditions. pH- The aim is to exhibit a sensitive structure. The coating polymer must be from the group of cellulose derivatives and / or cellulose esters and / or one of the groups of acrylic acid-based copolymers containing a carboxyl group and / or carboxyl It can be one of the group of methacrylic acid-based copolymers containing this group. The coating its thickness, film integrity, and dissolution threshold will limit dissolution under gastric conditions, and It can be adjusted to provide the desired opening under intestinal pH conditions. The composition subject to the invention includes, in addition to the configured precursor core, ellagitannin. and / or participates in the conversion of ellagic acid to urolithin A in the intestinal environment. or contains one or more probiotic strains that support this transformation. When multiple strains are used together, they contribute to different stages of the transformation pathway. the emergence of functional effects that provide and / or support each other in the gut ecosystem It is possible for it to emerge. In preferred setups, the probiotic strain in question; Lactobacillus plantarum, Bifidobacterium pseudocatenulatum, Gordonibacter urolithinfaciens, Gordonibacter pamelaeae, Streptococcus thermophilus, Enterococcus faecium, Enterocloster aldenensis, Enterocloster asparagiformis, Enterocloster bolteae, Enterocloster citroniae, Enterocloster clostridioformis and / or Enterocloster lavalensis It can be at least one of these types. In a preferred application of the invention, the probiotic component may be present in one or more forms. It may contain strains of the Gordonibacter genus. A more preferred approach is... Gordonibacter urolithinfaciens and / or 9 as probiotic components in the composition At least one strain of Gordonibacter pamelaeae may be present. These strains... The reason for its preference is the presence of precursor compounds derived from ellagitannin and / or ellagic acid. supporting the conversion of uroliths, particularly Urolitin A, in the intestinal environment. They can contribute to the biotransformation capacity. This allows the composition to... This can help achieve the intended functional effect more consistently. If preferred, probiotic strains are also available in coated form. This This helps to support the stability of probiotics and their tolerance to gastrointestinal conditions. It can be provided. Information on the dissolution threshold of coating materials that can be used within the scope of this invention. Since they fall within the known state of the art, they are detailed here. It is not specified. Accordingly, in accordance with the determined pH values, the thickness and amount of the coating specific to the targeted release region of the composition, Its integrity can be determined. Accordingly, the coating ensures that the precursor component is present in the target region. by supporting the presentation of favorable conditions for the formation of Urolitin A in the intestinal environment It can contribute to its formation. The invention includes the composition, precursor component and probiotic component, as well as It may include at least one flow-regulating component present throughout the composition. The subject is the flow regulator component, improving the free-flow properties of the composition. to reduce clumping, increase the homogeneity of the mixture, and especially in sachet filling. Included in the composition to support dosage accuracy in filling processes. This can be done. In this context, the flow regulator component is microcrystalline cellulose and / or It may contain silica. This ensures the physical stability of the composition and ease of use. It can be supported. The composition that is the subject of the invention is orally administered, and the components are gastrointestinal. transport within the system as intended and the creation of a suitable micro-environment for transformation It is considered as a regulation aimed at this. Accordingly, the composition is administered orally. It is presented in a dosage form suitable for administration. Accordingly, the composition is: in sachet, capsule, delayed-release capsule, tablet, granule mixture and / or powder mixture form. This is possible. The composition in sachet form can be taken with water or a suitable liquid. It is possible. If in capsule, delayed-release capsule or tablet form, 10 The composition can be swallowed directly. The chosen dosage form... the expected behavior of the composition components in the gastrointestinal system and together It can be structured to support the conditions of presence. The invention includes composition, single-chamber sachet, capsule or delayed-release capsule. It can be presented in this form, or in an alternative configuration as a two-compartment sachet and / or two-compartment. It can also be structured in capsule form. In a two-compartment structure, the coated precursor The component core and the probiotic component are physically in more distinctly separate compartments. This reduces the likelihood of contact between components during the storage process. This approach reduces the risk of premature interactions between components. This can contribute to limiting [the spread of the virus] and thus supporting stability. While a single-chamber design can offer ease of production and use as well as cost advantages, two-chamber designs... The reservoir form is particularly useful in applications where stability is a primary requirement. It can offer advantages. The composition that is the subject of the invention also includes other auxiliary components to provide specific functions. It may contain, according to this, humectant compounds as auxiliary components, and taste / sensory compounds. Property-modifying compounds, stability-enhancing compounds, anti-caking compounds and / or at least one of the filler material groups may be used. These compounds are located in... Depending on the composition, moisture and oxygen permeability during packaging. Barrier-type packaging options that restrict storage can be used. Its stability can be supported. Within the scope of the invention, in a structure, the precursor component core is the matrix carrier of pomegranate extract. It is a structure in which the components are homogeneously distributed. The matrix is ​​located within the core. The weight ratios of the carrier components can be determined according to the application. The invention In a possible configuration, the matrix carrier is the core of the mixture that forms the precursor component. It can constitute between 30% and 60% of the total weight by weight. This nucleus The ratios in the composition are determined according to the selected standardization level of the pomegranate extract and the targeted physical outcome. It can be adapted according to the granule properties. The composition subject to the invention consists entirely of pomegranate extract as the active component groups. Probiotic components can be present together, and the weight ratio of these two component groups is important. This can be determined according to the application. In a possible configuration of the invention, pomegranate extract 11 The weight ratio between the coated core and the probiotic component is 2:1 to 8:1. It can be within this range. Coated granules containing pomegranate extract, in the intestine Adequate substrate presentation provides the necessary precursor component for biotransformation. For this purpose, the amount can be kept higher than the amount of probiotic component. Probiotic component Since it provides the biological capacity to carry out the transformation, the targeted Urolitin A in an amount that will provide a sufficient live cell load to support its formation It can be found. With regard to the indications for the composition that is the subject of the invention, Urolitin A in situ in the intestine. Such approaches aimed at supporting the formation of mitochondria; mitochondrial functions and Supporting cellular energy metabolism, physiological processes associated with aging support, support muscle function and physical endurance, post-exercise supporting recovery processes, protecting general health and well-being, and It can be used in applications aimed at supporting immune functions. Furthermore, in individuals with a low capacity for Urolitin A formation originating from the gut microbiota Increasing the potential for urolithin A formation and reducing inter-individual differences. It is possible to evaluate the composition in applications related to food. In this context, the composition of food It is presented in the form of a supplement, nutraceutical or food for special medicinal purposes. It is possible. - Sample Production Flow The example application described below is aimed at obtaining the composition that is the subject of the invention. This demonstrates a representative application and is intended solely to help better understand the subject. It is directed towards and does not limit the scope of the invention. Standardization of pomegranate extract The ellagitannin and / or ellagic acid content of pomegranate extract is determined by analytical methods. and can be brought within the targeted standardization range. In a structure, the target range is... This can be approximately 20% based on ellagitannin equivalent. 12 Preparation of the matrix carrier In order to create the precursor component kernel, a matrix consisting of carrier components is formed. The system can be prepared. In this example application, maltodextrin is used as the matrix carrier. Cyclodextrin and a film-forming / binding polymer can be used together. In a formulation, maltodextrin constitutes the total composition of the mixture that forms the core precursor component. approximately 30% by weight of cyclodextrin, approximately 10% by weight of film The binder polymer may be present in an amount of approximately 5% by weight. Distribution of pomegranate extract in a matrix carrier system. The pomegranate extract, standardized in the previous processing step, is placed inside the matrix carrier system. is dispersed and / or mixed until a homogeneous distribution is obtained. Homogenization can be applied. In this example application, the homogenization time is... It can take approximately 15 minutes. Obtaining precursor component core granules. The homogenous mixture obtained from the previous processing steps is dried and particle formed. for the purpose of transforming the core into granules and / or particles by spray drying method. This can be achieved. In this example application, the spray drying inlet temperature is approximately 150 °C. The outlet temperature can be approximately 80 °C. Application of the primer layer To enhance the adhesion of the enteric film layer onto the precursor component core granules, and A primer layer can be applied if necessary to limit moisture penetration. In the example application, hydroxypropyl is used as a film-forming polymer in the primer layer. Methylcellulose can be used. 13 Application of enteric coating pH-sensitive enteric film-forming polymer on precursor component core granules. A polymer layer can be applied. In this example application, the polymer layer material is used. Eudragit® can be used. The coating is applied using the fluidized bed coating method. It is applicable, and the coating can be approximately 10% by weight. Here The specified weight ratio is the initial core of the granules resulting from the coating process. It represents the weight gain achieved relative to the weight. Preparation and stabilization of the probiotic component. The probiotic strains to be used within the scope of the sample are prepared, collected, and distributed separately. They can be dried. In a formulation, these probiotic strains contain ellagitannin and / or The conversion of ellagic acid to urolithin A in the intestinal environment is facilitated by, participates in, or is related to this process. These can be selected from probiotic microorganisms that support the transformation. Some The probiotic strains in question in these formulations are Lactobacillus plantarum and Bifidobacterium. pseudocatenulatum, Gordonibacter urolithinfaciens, Gordonibacter pamelaeae, Streptococcus thermophilus, Enterococcus faecium, Enterocloster aldenensis, Enterocloster asparagiformis, Enterocloster bolteae, Enterocloster citroniae, Enterocloster It may contain at least one of the species Clostridioformis and / or Enterocloster lavalensis. The total live cell load of probiotics is approximately 10¹¹ per use in a setup. It can be within the CFU range. Performing the mixing process With the coated precursor core granules obtained in the previous processing step The probiotic component is mixed homogeneously with a mixer that applies low shear force. It can be mixed and at least one flow factor is required to support the flow properties of the composition. A regulatory component can be added. A flow regulatory component in a structure. It can be microcrystalline cellulose. 14 Filling the resulting composition into sachets. The resulting composition can be packaged in sachet form via automatic filling and / or capsule, preferably a delayed-release capsule (DR-Caps), inside It can be filled. Packaging is a barrier that restricts the passage of moisture and / or oxygen. This can be achieved using specialized materials. In this example application, the goal is... The filling ratio will be approximately 8 g of coated granules and approximately 2 g of probiotic component. It can be selected in this way. Enteric performance control The invention includes testing the dissolution behavior to verify the function of the enteric coating. This can be done by immersing the coated granules in 0.1 N HCl for 2 hours. The goal is to achieve a dissolution rate of less than 10%. This criterion is crucial for the coating. It limited premature release under gastric conditions and the precursor component in an acidic environment. This serves to demonstrate that it can be preserved. Subsequently, in a pH 6.8 environment for 30 minutes or more. The goal is to achieve complete dissolution in a short time. This criterion depends on the intestinal pH of the coating. by expanding under these conditions, the antecedent component becomes accessible in the appropriate region. It serves for verification purposes. Probiotic viability test In order for the composition to maintain its intended biotransformation capacity, probiotics are necessary. The aim is to verify the viability of the strains. In this context, probiotic viability, This can be determined by counting the number of colony-forming units (CFU). CFU count indicates the composition. This indicates whether or not it delivers the targeted live cell load at the time of use. Also, end-of-life stability assessment of sachet, capsule and / or delayed-release capsule. Whether viability is maintained throughout the storage process can be monitored. Accelerated The stability conditions that can be used are a temperature of 40 °C and a relative humidity of 75%. These conditions; predicting the risk of loss of viability of the product during its shelf life and packaging It is used to evaluate the stability performance of the formulation. The scope of protection of the invention is specified in the claims attached hereto, and these details are strictly adhered to. The explanation cannot be limited to those given for illustrative purposes. Because a technically skilled person... the person, without deviating from the main theme of the invention, in light of what has been described above, similar It is clear that these structures can emerge.

Claims

1. To promote the in situ formation of Urolitin A in the intestinal environment. It is a composition suitable for oral administration, and its characteristic feature is; a precursor component containing pomegranate extract with ellagitannin and / or ellagic acid with its core Conversion of ellagitannin and / or ellagic acid to Urolitin A in the intestinal environment at least one probiotic strain that provides, participates in, or supports this transformation It contains a probiotic component and the core precursor component and the probiotic component are physically separate It is structured in this way.

2. A composition that conforms to Claim 1, characterized by the fact that at least one of the precursor component kernels It contains a matrix carrier.

3. A composition conforming to Claim 2, characterized by its function as a matrix carrier. maltodextrin and / or cyclodextrin and / or gum arabic group at least one of the following It includes.

4. A composition conforming to claim 2 or 3, characterized by its precursor component kernel. The matrix carrier constitutes 30% to 60% by weight of the total weight of the mixture that forms it. It is located within a certain range.

5. A composition that conforms to any of the previous requirements, and its characteristic is; antecedent The component core is insoluble or very insoluble under the acidic pH conditions of the stomach environment. exhibiting limited solubility and soluble when pH increases in the intestinal environment or It is coated with a pH-sensitive enteric coating that makes it permeable.

6. It is a composition that conforms to claim 5, and its characteristic is that the precursor component kernel, It contains at least one lining layer located between the core and the enteric coating.

7. A composition conforming to claim 6, characterized by its function as a primer layer. It contains hydroxypropyl methylcellulose and / or polyvinylpyrrolidone. 17 8. A composition conforming to any of claims 5-7, characterized by its enteric nature. coatings containing cellulose derivatives and / or cellulose esters and / or carboxyl groups acrylic acid-based copolymers and / or methacrylic acid-based copolymers containing a carboxyl group It must contain at least one of the copolymers group.

9. A composition that conforms to any of the previous requirements, characterized by its wording. The subject is the probiotic strain Lactobacillus plantarum, Bifidobacterium pseudocatenulatum, Gordonibacter urolithinfaciens, Gordonibacter pamelaeae, Streptococcus thermophilus, Enterococcus faecium, Enterocloster aldenensis, Enterocloster asparagiformis, Enterocloster bolteae, Enterocloster citroniae, at least one of the species Enterocloster clostridioformis and / or Enterocloster lavalensis It involves one of them.

10. A composition conforming to claim 9, characterized by its probiotic component. at least one strain of Gordonibacter Urolitinfaciens and / or Gordonibacter pamelaeae It involves one of them.

11. A composition that conforms to any of the previous requirements, and its characteristic is: probiotic component in the form of particles coated with a protective coating It is the presence of.

12. A composition that conforms to any of the preceding requirements, and its characteristic is; antecedent The weight ratio between the core component and the probiotic component should be between 2:1 and 8:

1. It is within the range.

13. A composition that conforms to any of the previous requirements, and its characteristic is: It must contain at least one flow regulator component.

14. A composition conforming to claim 13, characterized by its function as a flow-regulating component. It must contain at least one of microcrystalline cellulose and / or silica.

15. A composition that meets any of the previous requirements, and whose characteristic is: moisture. retaining compounds and / or taste / sensory property modifier compounds and / or stability 18 enhancing compounds and / or anti-caking compounds and / or fillers It must include at least one of the following groups.

16. A composition that conforms to any of the previous requirements, and its characteristic is; sachet. and / or capsules and / or delayed-release capsules and / or tablets and / or granules It is in the form of a mixture and / or a powder mixture.

17. A composition conforming to claim 16, characterized by its precursor component kernel. a delayed-release capsule (DR-Caps) containing a probiotic component It is in the form of...

18. A composition conforming to claim 16, characterized by its two-compartment sachet. and / or being in the form of a two-compartment capsule and containing a precursor component core. This involves keeping the probiotic components in separate compartments.

19. Food supplement and / or composition conforming to any of the previous requests. Use as a nutraceutical and / or food for special medicinal purposes.