Production method of fermented milk products with high bioavailability

Encapsulating ET/EA sources in pH-sensitive materials for fermented milk products ensures high bioavailability and urolithin formation by releasing them in the intestine, addressing low bioavailability and interaction issues, and utilizing fruit industry wastes.

WO2026135649A2PCT designated stage Publication Date: 2026-06-25T C ANKARA UNIVERSITESI REKTORLUGU

Patent Information

Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
T C ANKARA UNIVERSITESI REKTORLUGU
Filing Date
2025-12-17
Publication Date
2026-06-25

AI Technical Summary

Technical Problem

Existing methods fail to effectively enhance the bioavailability of ellagitannins (ET) and ellagic acid (EA) in fermented milk products, leading to low urolithin formation and limited health benefits due to their degradation and interaction with milk proteins, and they are not utilized from valuable fruit industry wastes like pomegranate juice sediment.

Method used

Encapsulating lyophilized pomegranate juice sediment or similar sources with pH-sensitive materials like carboxymethyl cellulose and chitosan, adding them to fermented milk products, which release ET/EA in the intestine to be converted into urolithin by gut microbiota, thereby promoting urolithin formation and avoiding interaction with milk components.

Benefits of technology

Enhances the bioavailability and formation of urolithin in the body, maintaining product stability and preventing antimicrobial effects, thus maximizing health benefits from ET/EA sources.

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Abstract

The invention relates to a production method of fermented milk products having high bioavailability and promoting urolithin formation in the body.
Need to check novelty before this filing date? Find Prior Art

Description

[0001] DESCRIPTION

[0002] PRODUCTION METHOD OF FERMENTED MILK PRODUCTS WITH HIGH BIO AVAILABILITY

[0003] Technical Field

[0004] The invention relates to a production method of fermented milk products having high bioavailability and promoting urolithin formation in the body.

[0005] Prior Art

[0006] Ellagitannins (ET) and ellagic acid (EA) are naturally found in high amounts in many foods and food wastes. It has been determined that these components exhibit high antioxidant activity under in vitro conditions. However, it has been determined in in vivo studies that the bioavailability of the ET group is very low or even nonexistent. [1]

[0007] ET shows resistance against degradation in the stomach, only a portion of it is hydrolyzed to EA and is absorbed in the small intestines. Consequently, free EA and a large amount of unabsorbed ET reach the colon and are metabolized into urolithins by the gut microbiota. [2] However, due to human gut microbiotas showing great variability from individual to individual, urolithin is not formed at the same rate in all humans, and even forms in very small amounts in a significant portion of them. [3, 4] For this reason, even if many people consume foods rich in ET content, they cannot benefit from the very valuable health benefits provided by urolithin. For example, it has been reported that the formed urolithins inhibit cancer cells thanks to their antiproliferative and pro-apoptotic effects. [5] However, individuals in whom urolithin formation does not occur will not be able to benefit from this advantage. The effect on cancer is just one of the numerous health benefits of urolithin. The articles prepared by D’Amico et al. (2021) [9] and Garcia- Villalba et al. (2022) [3] can be examined for the effects of urolithin on health. The water solubility of urolithin, which has many health benefits, is very low, and this causes a decrease in oral bioavailability. [4] That is, the formation of urolithin in the intestine is required to be promoted instead of oral intake. Furthermore, it has been determined that urolithin degrades at a significant rate in a short time (24 hours) even at room temperature. [6] These properties make the direct application of urolithin in the food industry almost impossible. [7, 4]

[0008] Pomegranate, strawberry, muscadine grape, walnut, ginger, blackberry, raspberry, cloudberry, boy senberry, and all kinds of food industry wastes thereof (such as peel, pulp, and sediment) are significant sources of ET and EA. [8]

[0009] The patent document numbered EP2836077B1 discloses a new fermented milk product containing microcapsules and a method developed for its preparation. It presents a method comprising the encapsulation / microencapsulation of natural (fruit juices rich in Vitamin C, in which pomegranate juice is also found) and synthetic Vitamin C with different components and adding them to fermented milk products. The main subject in this patent is to produce a Vitamin C-enriched fermented milk product. Since Vitamin C stability is very low, the main purpose of the encapsulation here is to increase the stability of this component. Encap sulation / microencapsulati on and the production of fermented milk products are known in the state of the art.

[0010] The patent document numbered KR102514059B1 discloses an EFC fermented pomegranate composition containing a high amount of ellagic acid and gallic acid with increased absorption into the body to improve bone health or female menopausal symptoms, its use as a skin whitening, wrinkle improvement, or antioxidant function, and its production using the EFC method.

[0011] When the studies existing in the prior art are examined, a need has been felt for the development of the production method of fermented milk products subject to the invention, having high bioavailability and promoting urolithin formation in the body. Objectives of the Invention

[0012] The object of this invention is to develop a production method of fermented milk products having high bioavailability and promoting urolithin formation in the body.

[0013] Another object of this invention is to develop a production method of fermented milk products enabling the utilization of a valuable fruit juice industry waste such as pomegranate juice sediment obtained from natural sedimentation, which has never been used as a food ingredient before.

[0014] Detailed Description of the Invention

[0015] A production method of fermented milk products having high bioavailability and promoting urolithin formation in the body, and comprises; encapsulating the lyophilized pomegranate juice sediment obtained from natural sedimentation, adding the encapsulated powder to the fermented milk product immediately before consumption.

[0016] In the method subject to the invention, firstly; ET / EA sources will be encapsulated with an encapsulation material (Besides carboxymethyl cellulose and chitosan, the coating can also be any other encapsulant.) soluble at intestinal pH. Subsequently, the obtained powder product will be packaged (like single-serving instant coffee / mayonnaise / ketchup packaging).

[0017] Specifically in the invention, lyophilized pomegranate juice sediment has been used. However, instead of lyophilized pomegranate juice sediment, ginger or lyophilized pomegranate, pomegranate peel, strawberry, muscadine grape, blackberry, raspberry can be used.

[0018] Thanks to the encapsulation process, ET / EA: - will not be able to harm the beneficial microorganisms in the milk product,

[0019] - will not be able to bind to the casein in the milk product,

[0020] - will be released into the intestinal environment and converted into urolithin by the gut microbiota directly supported by yogurt microorganisms.

[0021] As the 2nd stage, the obtained powder product will be added to the fermented milk product. Beneficial microorganisms that will convert ET / EA into urolithin will be found in the fermented milk product. *

[0022] *The fermented milk product may have been produced traditionally or by being enriched with probiotics. (Such as probiotic yogurt, kefir, etc. found in the art).

[0023] Urolithin, which has numerous health benefits, is a component with low water solubility. Furthermore, its oral bioavailability is also very low. Therefore, the direct addition of this component to products with high water content is not rational. In this case, a portion of the urolithin will degrade and a portion will settle to the bottom of the product. And, this will be perceived as a defect by the consumer. For this reason, the direct addition of urolithin to the fermented milk product has not been considered. Instead, the ET / EA source, which will be converted into urolithin by the probiotic in the milk products and the gut microbiota, will be encapsulated and will be added to the product before consumption.

[0024] The food industry is in search of an effective method for the purpose of promoting the formation of urolithin in the human body / improving its bioavailability. Currently, there is a significant deficiency in this regard. The proposed invention offers a solution exactly at this point.

[0025] After the consumption of the product obtained by the method subject to the invention, the material used in the encapsulation of ET / EA (for example, carboxymethyl cellulose) will dissolve when the pH is above 5, that is, after reaching the intestine, and these components will be released into the intestine. Since fermented milk products contain a significant amount of microorganisms converting these components into urolithin (probiotic count at least 106cfu / g, TFC Communique on Fermented Milk Products), the rate of conversion of these components into urolithin in the intestine will be increased significantly.

[0026] There are two important purposes of encapsulating the ET and EA source. The first of these is that ET and EA are compounds exhibiting high antimicrobial properties. Therefore, in the fermented milk product environment, if they come into contact with the beneficial bacteria in the fermented milk products, they can cause their inactivation. Because, in a study

[0010] where kefir production enriched with pomegranate juice was performed, it was observed that the microorganisms in the kefir were inactivated in a short time by means of the ellagitannins in the pomegranate. For this reason, ETZEA will be encapsulated with an encapsulation material (such as carboxymethyl cellulose) having the property of not dissolving in fermented milk products. In this way, these components will not be able to be released into the fermented milk environment, and consequently, they will not be able to exhibit antimicrobial properties.

[0027] The second reason is the decrease in their bioavailability due to ET / EA being capable of interacting with proteins also found in fermented milk products and becoming water-insoluble complexes as a result of this interaction. [1]

[0028] In order to prevent this, it is required to prevent the direct release of ETZEA into the fermented milk product environment. The encapsulation material to be used as the encapsulation material (such as carboxymethyl cellulose) starting to dissolve above pH 5 will prevent the release of these components into the fermented milk product environment (generally having pH values varying between 4.0 and 4.6).

[0029] References:

[0030] 1. Gonzalez-Sarrfas, A., Garda- Villalba, R., Nui'iez-Sanchez, M. A., Tome- Carneiro, J., Zafrilla, P., Mulero, J., ... & Espfn, J. C. (2015). Identifying the limits for ellagic acid bioavailability: A crossover pharmacokinetic study in healthy volunteers after consumption of pomegranate extracts. Journal of Functional Foods, 19, 225-235.

[0031] 2. Xian, Y., Fan, R., Shao, J., Toney, A. M., Chung, S., & Ramer-Tait, A. E. (2021). Polyphenolic fractions isolated from red raspberry whole fruit, pulp, and seed differentially alter the gut microbiota of mice with diet-induced obesity. Journal of Functional Foods, 76, 104288.

[0032] 3. Garcia- Villalba, R., Gimenez-Bastida, J. A., Cortes-Martfn, A., Avila-Galvez, M. A., Tomas-Barberan, F. A., Selma, M. V., ... & Gonzalez-Sarrfas, A. (2022). Urolithins: a comprehensive update on their metabolism, bioactivity, and associated gut microbiota. Molecular Nutrition & Food Research, 66, 2101019.

[0033] 4. Hu, Y., Zhang, L., Wei, L. F., Lu, F. Y., Wang, L. H., Ding, Q., ... & Tu, Z. C. (2023). Liposomes encapsulation by pH driven improves the stability, bioaccessibility and bioavailability of urolithin A: A comparative study. International Journal of Biological Macromolecules, 253, 127554.

[0034] 5. Landete, J. M. (2011). Ellagitannins, ellagic acid and their derived metabolites: A review about source, metabolism, functions and health. Food Research International, 44, 1150-1160.

[0035] 6. Korczak, M., Roszkowski, P., Granica, S., & Piwowarski, J. P. (2022). Conjugates of urolithin A with NSAIDs, their stability, cytotoxicity, and antiinflammatory potential. Scientific Reports, 12, 11676.

[0036] 7. Ryu, D., Mouchiroud, L., Andreux, P. A., Katsyuba, E., Moullan, N., Nicolet- dit-Felix, A. A., ... & , Auwerx, J. (2016). Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents. Nature Medicine, 22, 879-888.

[0037] 8. Larrosa, M., Gonzalez-Sarrfas, A., Garda-Conesa, M. T., Tomas-Barberan, F. A., & Espfn, J. C. (2006). Urolithins, ellagic acid-derived metabolites produced by human colonic microflora, exhibit estrogenic and antiestrogenic activities. Journal of Agricultural and Food Chemistry, 54, 1611-1620. 9. Amico, D., Andreux, P. A., Valdes, P., Singh, A., Rinsch, c., & Auwerx, J. (2021). Impact of the natura! compound urolithin A on health, disease, and aging. Trends in Molecular Medicine, 27, 687-699.

[0038] 10. Kabakci, S. A., Turkyilmaz, M., & Ozkan, M. (2020). Changes in the quality of kefir fortified with anthocyanin-rich juices during storage. Food Chemistry, 326,

[0039] 126977.

Claims

CLAIMS1. A production method of fermented milk products having high bioavailability and promoting urolithin formation in the body, characterized in that it comprises; encapsulating the lyophilized pomegranate juice sediment obtained from natural sedimentation, adding the encapsulated powder to the fermented milk product immediately before consumption.

2. The method according to claim 1, characterized in that ginger or lyophilized pomegranate, pomegranate peel, strawberry, muscadine grape, blackberry, or raspberry are used instead of lyophilized pomegranate juice sediment.