Probiotics for Inhibiting and Preventing Progression of Renal Diseases, and Compositions for Inhibiting and Preventing Progression of Renal Diseases Comprising Same

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Probiotics for Inhibiting and Preventing Progression of Renal Diseases, and Compositions for Inhibiting and Preventing Progression of Renal Diseases Comprising Same (19) *EP003741376A1* (11) EP 3 741 376 A1 (12) EUROPEAN PATENT APPLICATION published in accordance with Art. 153(4) EPC (43) Date of publication: (51) Int Cl.: 25.11.2020 Bulletin 2020/48 A61K 35/741 (2015.01) A23L 33/135 (2016.01) C12N 1/20 (2006.01) A61P 13/12 (2006.01) (2006.01) (2006.01) (21) Application number: 18887708.8 C12R 1/225 C12R 1/23 (22) Date of filing: 13.12.2018 (86) International application number: PCT/KR2018/015883 (87) International publication number: WO 2019/117654 (20.06.2019 Gazette 2019/25) (84) Designated Contracting States: • LEE, Jong Hun AL AT BE BG CH CY CZ DE DK EE ES FI FR GB Seongnam-si, Gyeonggi-do 13595 (KR) GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO • LIM, Su Hwan PL PT RO RS SE SI SK SM TR Seongnam-si, Gyeonggi-do 13595 (KR) Designated Extension States: • KIM, Jeom Yong BA ME Seongnam-si, Gyeonggi-do 13595 (KR) Designated Validation States: • PARK, Sun Kyu KH MA MD TN Seongnam-si, Gyeonggi-do 13595 (KR) • JANG, Min Jung (30) Priority: 15.12.2017 KR 20170173590 Seongnam-si, Gyeonggi-do 13595 (KR) •LIM, Min Ju (71) Applicant: Green Cross WellBeing Corporation Seongnam-si, Gyeonggi-do 13595 (KR) Seongnam-si, Gyeonggi-do, 13595 (KR) (74) Representative: dompatent von Kreisler Selting (72) Inventors: Werner - • KIM, Su Ae Partnerschaft von Patent- und Rechtsanwälten Seongnam-si, Gyeonggi-do 13595 (KR) mbB • OH, Chang Taek Deichmannhaus am Dom Seongnam-si, Gyeonggi-do 13595 (KR) Bahnhofsvorplatz 1 50667 Köln (DE) (54) PROBIOTICS FOR INHIBITING AND PREVENTING PROGRESSION OF RENAL DISEASES, AND COMPOSITIONS FOR INHIBITING AND PREVENTING PROGRESSION OF RENAL DISEASES COMPRISING SAME (57) The present invention provides probiotics for in- for inhibiting and preventing the progression of a renal hibiting and preventing the progression of a renal disease disease comprising the same. The novel probiotics, the and a composition for inhibiting and preventing the pro- Lactobacillus acidophilus BP105 strain and the Lactoba- gression of a renal disease comprising the same; and a cillus salivarius BP121 strain exhibit excellent indoxyl sul- novel Lactobacillus acidophilus BP105 strain, a novel fate removal ability, p-cresol removal ability, and phos- Lactobacillus salivarius BP121 strain, and a composition phorus absorption ability. EP 3 741 376 A1 Printed by Jouve, 75001 PARIS (FR) EP 3 741 376 A1 Description [Technical Field] 5 [0001] This application claims the benefit of priority based on Korean Patent Application No. 10-2017-0173590, filed on December 15, 2017, and the entire contents disclosed in the literature of said Korean Patent Application are included as part of the present specification. [0002] The present invention relates to probiotics for inhibiting and preventing the progression of a renal disease and a composition for inhibiting and preventing the progression of a renal disease comprising the same; and a novel Lacto- 10 bacillus acidophilus BP105 strain, a novel Lactobacillus salivarius BP121 strain, and a composition for inhibiting and preventing the progression of a renal disease comprising the same. [Background Art] 15 [0003] Due to the increase in the elderly population, the number of patients with adult diseases such as diabetes and hypertension is on the rise. These diabetes and hypertension are the most common causes of chronic renal failure, and the number of patients with chronic renal failure due to them is also rapidly increasing. [0004] Chronic renal disease is increasing in prevalence rate worldwide, and is known to be a very serious disease with a prevalence rate of 14% in the United States and a prevalence rate of 10% in China. The number of patients with 20 chronic renal disease in Korea is about 170,000 (2015), which is reported to have increased by 107% compared to 2008, and as of 2015, the medical expenses of patients related to chronic renal disease are also reported to amount to about KRW 1.56 trillion. [0005] Chronic renal disease is an irreversible disease with no underlying treatment, and 90% of patients with chronic renal disease progress to end-stage renal failure. In the case of end-stage renal failure, hemodialysis, peritoneal dialysis, 25 and kidney transplantation is performed as renal replacement therapy. Therefore, since it is important to inhibit the progression of renal failure at the beginning of symptoms, effective renal disease progression inhibitors and renal disease prevention agents are desired. [0006] It is generally known that in the body of patients with renal failure, blood levels of uremic toxins such as indoxyl sulfate and p-cresol, which are renal failure progression factors or vascular dysfunction factors, are high, and blood 30 creatinine levels and neutral fat levels, which are indicators of renal dysfunction, are elevated. [0007] Among them, indoxyl sulfate and p-cresol have been reported as uremic toxins that have been proven to be renal failure progression factors, and the blood levels of indoxyl sulfate in patients with chronic renal failure are very high compared to those in healthy people. [0008] Indoxyl sulfate is a substance that progresses and exacerbates a renal disease and causes cardiovascular 35 disease and glomerulosclerosis as described above, and thus it is thought that by lowering the blood levels of indoxyl sulfate in patients with renal failure, the disability of renal function may be remarkably reduced and the progression of renal failure may be inhibited. On the other hand, uremic toxins such as indoxyl sulfate and p-cresol are substances that have high binding power with proteins and thus cannot be removed even by the renal replacement therapy. [0009] Therefore, it is known that a spherical adsorptive carbon as a conventional renal failure progression inhibitor 40 adsorbs indole, which is a precursor of indoxyl sulfate, in the intestinal tract, and excretes it in feces, thereby lowering the blood levels of indoxyl sulfate. As a result, in addition to inhibiting the progression of renal failure, it has been reported that the mortality due to the onset of cardiovascular diseases involved in renal failure was also lowered. [0010] However, it has been confirmed that the spherical adsorptive carbon is not only that internal use is burdensome because of the need to take 6 g, or 30 capsules per day, but also that many patients want to stop taking medicine since 45 symptoms such as abdominal distention and constipation are severe and its long-term internal use is accompanied by very large pain, as side effects. [0011] For these reasons, there is a demand for a novel medicament that relieves the pain or burden of the patient with less dosage and without causing abdominal distention or constipation. [0012] In addition, patients with chronic renal failure develop a hyperphosphatemia due to a phenomenon in which 50 phosphorus discharge ability decreases and the blood phosphorus greatly increases. If the blood phosphorus increases, it stimulates the parathyroid gland to secrete parathyroid hormone in order to keep the ratio of calcium and phosphorus relatively, which releases calcium from the bones. If this phenomenon is maintained, more calcium is released from the bones, and the bone is weakened, and thus the quality of life rapidly decreases due to renal osteoporosis accompanied by osteoporosis. Therefore, in patients with chronic renal failure, managing the blood phosphorus concentration is directly 55 related to the quality of life, and management is desired from the beginning of the disease. [0013] The standard of the blood phosphorus concentration of healthy people is 5.5 mg/dL or less, and most patients with chronic renal failure are educated to eat foods with a low phosphorus content, and additionally take a phosphorus binding agent during meals to prevent the phosphorus in the food from being absorbed into the body. However, it is a 2 EP 3 741 376 A1 reality that it is not easy to control the blood phosphorus concentration, so that only 40-50% of total hemodialysis patients have been reported to have achieved the target blood phosphorus concentration. [0014] On the other hand, drugs for treating the increase in phosphorus in the blood include a calcium-based phos- phorus binding agent, a drug in the form of replacing the phosphorus binding agent, and the like. Phosphorus binding 5 agent, which is a drug that inhibits the rise in the blood phosphorus concentration by binding with phosphorus in food in the intestine and excreting it in feces, controls the blood phosphorus concentration, but has the disadvantages that the blood calcium concentration is increased, side effects such as dyspepsia and constipation are caused, and the drug price is expensive. [0015] Probiotics-based drugs using a strain that absorbs phosphorus have been introduced as the drug in the form 10 of replacing the phosphorus binding agent. However, studies of probiotics to remove uremic toxins are insufficient, and management of uremic toxins is the most important in inhibiting and preventing progression of renal disease. The probiotics-based drugs as introduced so far are in a state of insufficient reliability for effect and safety to replace other conventional drugs. [0016] Therefore, it is an urgent situation to develop a safe and effective method of replacing existing spherical ad- 15 sorptive carbon with large side effects, removing uremic toxins in the body, and discharging phosphorus. [Prior Art Document] [Patent Document] 20 [0017] Korean Patent No. 10-1684289 [Disclosure] 25 [Technical Problem] [0018] The present invention has been devised to solve the above problems of the prior art, and its object is to provide probiotics for inhibiting and preventing the progression of a renal disease and a composition for inhibiting and preventing the progression of a renal disease comprising the same; and a novel Lactobacillus acidophilus BP105 strain, a novel 30 Lactobacillus salivarius BP121 strain, and a composition for inhibiting and preventing the progression of a renal disease comprising the same, which are free from side effects such as dyspepsia and constipation, have excellent indoxyl sulfate removal ability, p-cresol removal ability, phosphorus absorption ability, and the like, and are safe for the human body.
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