Composition for use in removing Fusobacterium and / or Streptococcus
A platinum nanoparticle and electrolyzed water composition addresses the ineffectiveness of current treatments by selectively removing Fusobacterium and Streptococcus while promoting Faecalibacterium, effectively treating diseases like colon cancer and inflammatory bowel disease.
Patent Information
- Application Number
- JP2023116028
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2023-07-14
- Publication Date
- 2026-01-05
- Estimated Expiration
- 2043-07-14
AI Technical Summary
Existing treatments for diseases caused by Fusobacterium and Streptococcus bacteria, such as colon cancer, inflammatory bowel disease, and esophageal cancer, are ineffective and often cause side effects by eliminating beneficial bacteria, such as antibiotics, which do not effectively address the underlying issues of bacterial imbalance.
A composition containing platinum nanoparticles and electrolyzed water is used to selectively remove Fusobacterium and Streptococcus bacteria while promoting the growth of beneficial bacteria like Faecalibacterium, thereby treating or preventing associated diseases.
The composition effectively reduces harmful bacteria and promotes beneficial bacteria, providing therapeutic benefits without causing side effects typically associated with antibiotics.
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Abstract
Description
[Technical Field]
[0001] The present invention relates to a composition used for removing Fusobacterium and / or Streptococcus bacteria, treating or preventing diseases caused by these bacteria, and treating or preventing colon cancer, esophageal cancer, inflammatory bowel disease, infective endocarditis, bacteremia, periodontal disease, or dental caries. [Background technology]
[0002] Fusobacterium is a bacterium that mainly inhabits the oral cavity and is known to cause periodontal disease, but recent research has revealed that it is also involved in a variety of diseases.
[0003] Since the early 2010s, numerous reports have emerged suggesting that Fusobacterium nucleatum may be involved in the carcinogenesis of colorectal cancer (e.g., Non-Patent Document 1). The mechanism by which Fusobacterium nucleatum is associated with carcinogenesis is said to be related to FadA and Fap2 expressed by Fusobacterium nucleatum. It is also thought to be related to the progression of colorectal cancer by evading lymphocyte attacks on cancer cells and by avoiding apoptosis. Furthermore, Fusobacterium nucleatum is associated with promoting cell proliferation, and its influence on tumor suppressor genes through overexpression of microRNAs has also been discussed (Non-Patent Document 2).
[0004] Inflammatory bowel disease (IBD), broadly classified as ulcerative colitis (UC) and Crohn's disease (CD), has been considered an autoimmune disease characterized by immune dysfunction, in which inflammatory cells, primarily lymphocytes, attack the intestinal mucosa, resulting in inflammation and ulcers. However, the theory that IBD is an intestinal bacterial infection has gained traction based on the following evidence: spontaneous immune dysfunction enteritis does not occur under sterile conditions; the intestinal mucosa of IBD patients is overpopulated with bacteria; harmful bacteria predominate over beneficial bacteria in the intestinal flora compared with normal individuals; genetic polymorphism analysis has revealed a high incidence of genetic polymorphisms associated with impaired bacterial clearance and mucosal defense mechanisms; IBD patients have a reduced tolerance to intestinal bacteria, leading to an exaggerated immune response (inflammation); and Toll-like receptors (TLRs), the main components of innate immunity, are expressed in the intestinal epithelium, many of which use bacteria as their ligands (Non-Patent Document 3).
[0005] More specifically, it has been reported that the detection rate of Fusobacterium varium in inflamed mucosal areas is significantly higher in UC patients than in healthy individuals, and that serum antibody titers are also significantly higher in UC patients. Furthermore, immunohistochemical staining has demonstrated that Fusobacterium varium is present at a higher rate in inflamed mucosal areas than in patients with other diseases or healthy individuals (Non-Patent Document 4).
[0006] Furthermore, Fusobacterium varium exhibits cytotoxicity to Vero cells despite the absence of the Vero toxin gene. This is due to the cytotoxicity of butyric acid produced by this bacterium. It has also been reported that butyric acid produced by this bacterium induces apoptosis and induces UC-like lesions in mice (Non-Patent Document 5). Furthermore, it has been confirmed that Fusobacterium varium adheres to and invades colonic mucosal cells, and has the effect of significantly promoting the production of inflammatory cytokines such as IL-8 and TNFα from the mucosa (Non-Patent Document 6). Based on the above, it is believed that this bacterium causes inflammation in addition to ulcers, leading to ulcerative colitis. It has been reported that when Fusobacterium varium antibody-positive UC patients were administered a combination of three antibacterial drugs sensitive to the bacteria (amoxicillin, tetracycline, and metronidazole; ATM therapy) to eradicate Fusobacterium varium, improvements in UC symptoms and endoscopic and histopathological findings were observed (Non-Patent Document 7).A similar report was also made in a multicenter, double-blind, placebo-controlled study of over 200 patients (Non-Patent Document 8). Based on the above, Fusobacterium varium is thought to be the causative bacterium of UC.
[0007] Fusobacterium nucleatum has also been cited as a causative bacterium of CD (Non-Patent Document 3). It has been reported that this bacterium was detected in endoscopic biopsy mucosa of CD in 10 out of 17 cases (58.8%), and all cases were invasive to cells (Non-Patent Document 9).
[0008] Fusobacterium nucleatum has also been reported to be associated with esophageal cancer. Specifically, it has been reported that Fusobacterium nucleatum is present in significantly higher concentrations in esophageal cancer tissue than in normal esophageal mucosa, that the presence of Fusobacterium nucleatum is significantly associated with tumor stage, and that a significant relationship between the bacterium and the chemokine CCL20 has been observed. This suggests that the bacterium contributes to the aggressive behavior of tumors through the activation of chemokines such as CCL20 (Non-Patent Document 10).
[0009] Fusobacterium prausnitzii has attracted attention as a probiotic that consumes acetic acid, produces beneficial butyric acid, and improves intestinal barrier function. It has been reported that this bacterium is associated with inflammatory bowel disease (IBD) because its occupancy levels were reduced in both feces and mucosal samples from CD patients (Non-Patent Document 11). Furthermore, administration of this bacterium to mice has been shown to suppress the onset of IBD (Non-Patent Document 12).
[0010] Streptococcus mutans, a major pathogenic bacterium responsible for dental caries, is known to cause bacteremia and infective endocarditis. Recent studies have also revealed that it can exacerbate inflammatory bowel disease (IBD). Observation of the peritoneal cavity of mice intravenously injected with Streptococcus mutans revealed signs of enteritis, and administration of Streptococcus mutans into the bloodstream of a mouse model of enteritis exacerbated the condition. It has been reported that a key factor in this mechanism is that strains of Streptococcus mutans with mutations in their surface polysaccharide antigens exhibit reduced phagocytosis by leukocytes, making them less likely to be eliminated from the bloodstream for extended periods. Furthermore, another important factor is that collagen-binding proteins present on the bacterial surface allow the bacteria to localize to liver tissue and be directly taken up by liver parenchymal cells (Non-Patent Document 13). This promotes the production of cytokines, including IFN-γ, which induces an imbalance in the immune system, thereby exacerbating IBD.
[0011] Infective endocarditis caused by Streptococcus bovis has been reported to frequently develop colorectal cancer (Non-Patent Documents 14-22). One study suggested that the presence of bile acids could promote colony formation by Streptococcus bovis, replacing enterococci, leading to carcinogenesis (Non-Patent Document 22). Another study suggested that the cell wall extract antigen (WEA) of Streptococcus bovis stimulates the production of IL-8 and COX-2 in human colonic epithelial Caco-2 cells, leading to phosphorylation of mitogen-activated protein (MAP) kinase. Overproduction of COX-2 promotes prostaglandin production, cell proliferation, angiogenesis, and apoptosis suppression, leading to the induction of cancer from a precancerous state (Non-Patent Documents 23-25). Furthermore, WEA has been shown to potently promote precancerous lesions in azoxymethane-treated mice (Non-Patent Document 26). Furthermore, it has been reported that this bacterium strongly promotes colon adenoma to colon cancer by inducing NF-κB (Non-patent Document 27).
[0012] Streptococcus anginosus, a bacterium also detected in endocarditis, is said to be a risk factor for esophageal cancer. It has been reported that this bacterium has been detected in esophageal cancer tissue, and that when esophageal cancer patients are compared with normal individuals, the risk of esophageal cancer increases by approximately 33 times when Streptococcus anginosus is detected in dental plaque (Non-Patent Document 28). [Prior art documents] [Non-patent literature]
[0013] [Non-Patent Document 1] Genome Res.2012;22:299-306 [Non-patent document 2] Journal of Enterobacteriaceae 35:1-11, 2021 [Non-patent document 3] Modern Media Vol. 60 No. 11 2014 [Intestinal Microflora] 325 [Non-patent document 4] J.Gastroenterol.Hepatol.,2002;17:849-853. [Non-Patent Document 5] GUT,2003;52:79-83. [Non-patent document 6] Int. J. Cancer, 1995;27:400-406. [Non-Patent Document 7] Scand J Gastroenterol 2005;40:1334-1342. [Non-patent document 8] Trial.Am J Gastroenterol.2010;105:1820-1829. [Non-Patent Document 9] Inflammatory Bowel Diseases 2011;17:1971-1978. [Non-Patent Document 10] Clin Cancer Res (2016) 22 (22): 5574-5581. [Non-Patent Document 11] Frontiers in Microbiology 8: 1889. (2017-09-29) [Non-Patent Document 12] Medical Science Digest October 2019 Special Edition [Non-Patent Document 13] Journal of Pediatric Dentistry 52(4): 471-479 2014 471 [Non-Patent Document 14] N Engl J Med 1977; 297: 800-803. [Non-Patent Document 15] Arq Gastroenterol,2002; 39: 177-180. [Non-Patent Document 16] J Med Assoc State Ala 1951; 162-166. [Non-Patent Document 17] Jpn. J. 1989; 78: 835-839. [Non-Patent Document 18] Arch Surg 2004;139:760-765. [Non-Patent Document 19] Treatment 2008; 90: 96-100. [Non-Patent Document 20] Am J Cardiol 2001; 88: 871-875. [Non-Patent Document 21] Clin Infect Dis 2004;38: 1394-1400. [Non-Patent Document 22] Cytokine 2000;12:26-31. [Non-Patent Document 23] Proc Natl Acad Sci USA 115:E283-E291,2018. [Non-Patent Document 24] J. Exp. Clin. Cancer Res. 2011;30:1-1 [Non-Patent Document 25] Lancet Oncol. 2011;12:504-12. [Non-Patent Document 26] Carcinogenesis. 2004;25:1477-8 [Non-Patent Document 27] BMC Cancer. 2009;19:40 [Non-patent document 28] Cancer Vol.127,Issue 4,February 15,2021,pp512-519 [Non-Patent Document 29] Microorganisms 2022, 10(3), 664 Summary of the Invention [Problem to be solved by the invention]
[0014] Recent research has revealed that intestinal bacteria are deeply involved in colon cancer, inflammatory bowel disease, and esophageal cancer. Fusobacterium spp., widely known as periodontal disease bacteria, and Streptococcus spp., widely known as causative bacteria of dental caries, infective endocarditis, and bacteremia, have attracted attention as causative bacteria of these diseases. In light of the above, an objective of the present invention is to provide a novel technology for removing Fusobacterium spp. and / or Streptococcus spp. [Means for solving the problem]
[0015] Through the diligent research efforts of the present inventors, it was discovered for the first time that platinum nanoparticles and electrolyzed water are effective in removing Fusobacterium and Streptococcus. The present invention was completed based on this new discovery, and is specifically as follows.
[0016] [1] A composition used for removing Fusobacterium and / or Streptococcus, comprising platinum nanoparticles and / or electrolyzed water as active ingredients. [2] The composition described in [1], which is further used to promote the growth of bacteria of the genus Faecalis. [3] A composition containing platinum nanoparticles and / or electrolyzed water as active ingredients, used for treating or preventing diseases caused by Fusobacterium and / or Streptococcus. [4] A composition containing platinum nanoparticles and / or electrolyzed water as active ingredients, used for the treatment or prevention of colon cancer, inflammatory bowel disease, esophageal cancer, infective endocarditis, bacteremia, periodontal disease, or dental caries. [5] The composition according to [4], wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease. [6] The composition described in any one of [1] to [5], for use by administering to a carrier of Fusobacterium and / or Streptococcus. [7] The composition described in [6], wherein the carrier is a person who has Fusobacterium and / or Streptococcus in the oral cavity and / or a person who has Fusobacterium and / or Streptococcus in the intestines. [8] The composition according to any one of [1] to [7], wherein the platinum nanoparticles are dispersed in the electrolyzed water. [9] The composition according to any one of [1] to [8], which is a drinking composition or a mouthwash composition. [Effects of the Invention]
[0017] According to the present invention, Fusobacterium and / or Streptococcus can be removed, and therapeutic or preventive effects can be obtained for diseases caused by these bacteria, specifically colon cancer, inflammatory bowel disease, esophageal cancer, infective endocarditis, bacteremia, periodontal disease or dental caries. DETAILED DESCRIPTION OF THE INVENTION
[0018] The composition of the present invention contains platinum nanoparticles and / or electrolyzed water as active ingredients.
[0019] In the present invention, "platinum nanoparticles" refer to platinum particles having a diameter of 100 nm or less. Platinum nanoparticles can be produced by any method and device known in the art.
[0020] The average particle size of the platinum nanoparticles is preferably 5 nm or less, more preferably 4.5 nm or less, even more preferably 4 nm or less, and even more preferably 3 nm or less. The average particle size is preferably 0.5 nm or more, more preferably 0.75 nm or more, and even more preferably 1.0 nm or more.
[0021] In this specification, the average particle size is a particle size calculated by a model numerical analysis using small-angle X-ray scattering.
[0022] Alkaline electrolyzed water is produced when an aqueous electrolyte solution such as a weak saline solution is electrolyzed. In the present invention, it is preferable to use alkaline electrolyzed water produced on the cathode side during electrolysis. The pH of the alkaline electrolyzed water is preferably 8 to 11, more preferably 9 to 10, and even more preferably 9.0 to 9.5.
[0023] When the composition of the present invention contains platinum nanoparticles as an active ingredient, its form is not particularly limited, and may be liquid, solid, semi-solid, or the like. When the composition is in liquid or semi-solid form, it can be prepared by dispersing platinum nanoparticles in any dispersion medium such as water. When provided as a solid formulation such as a tablet or capsule, it can be prepared by mixing the platinum nanoparticles, which are the active ingredient, with any excipient and molding as necessary.
[0024] When the composition of the present invention is provided as a liquid composition, the concentration of platinum nanoparticles in the entire composition is preferably 0.02 μg / mL or more, even more preferably 0.024 μg / mL or more, and even more preferably 0.03 μg / mL or more. Furthermore, the concentration of platinum nanoparticles in the entire composition is preferably 0.1 μg / mL or less, more preferably 0.096 μg / mL or less, even more preferably 0.09 μg / mL or less, even more preferably 0.08 μg / mL or less, even more preferably 0.076 μg / mL or less, even more preferably 0.07 μg / mL or less, and even more preferably 0.06 μg / mL or less.
[0025] When made into a solid formulation, the content of platinum nanoparticles per tablet is preferably 0.01 mg or more, more preferably 0.016 mg or more, even more preferably 0.02 mg or more, even more preferably 0.024 mg or more, and even more preferably 0.03 mg or more. The content of platinum nanoparticles per tablet is preferably 0.1 mg or less, more preferably 0.096 mg or less, even more preferably 0.09 mg or less, even more preferably 0.08 mg or less, even more preferably 0.076 mg or less, even more preferably 0.07 mg or less, and even more preferably 0.06 mg or less.
[0026] When electrolyzed water is used as an active ingredient, the composition of the present invention is preferably in a liquid or semi-solid form. The composition of the present invention may be in a form consisting of electrolyzed water itself, or in a form of a mixture with any other liquid or solid component. Potable electrolyzed water can be produced using known methods and equipment.
[0027] In a preferred embodiment of the present invention, both platinum nanoparticles and electrolyzed water are contained as active ingredients. That is, the platinum nanoparticles may be in the form of a dispersion prepared by dispersing the platinum nanoparticles in electrolyzed water. The preferred concentration range of the platinum nanoparticles in the dispersion is as described above.
[0028] The composition of the present invention may be provided in a form that can be prepared immediately before use. That is, it may be provided as a kit containing a first formulation containing platinum nanoparticles and a second formulation containing electrolyzed water. In this case, the first formulation is mixed with the second formulation at the time of use to prepare the composition of the present invention immediately before use.
[0029] The composition of the present invention may contain other known ingredients (such as flavoring agents, odorants, pH adjusters, excipients, thickeners, fragrances, food dyes, sweeteners, dietary fiber, vitamins, preservatives, and antioxidants) to the extent that the effects of the invention are not impaired.
[0030] The composition of the present invention can be used to remove Fusobacterium, including Fusobacterium nucleatum and / or Fusobacterium varium.
[0031] The composition of the present invention can also be used to remove Streptococcus bacteria, including one or more species selected from Streptococcus mutans, Streptococcus bovis, and Streptococcus anginosus.
[0032] The compositions of the present invention can be used to eliminate Fusobacterium and / or Streptococcus. In a preferred embodiment, the compositions of the present invention are used to eliminate Fusobacterium and Streptococcus.
[0033] Furthermore, the composition of the present invention can be used to remove Fusobacterium and / or Streptococcus bacteria in the intestines and / or oral cavity. In other words, the composition of the present invention can be used to suppress the occupancy rate of Fusobacterium and / or Streptococcus bacteria in the intestinal flora and / or oral flora.
[0034] The composition of the present invention can also be used to promote the growth of bacteria of the genus Fusobacterium. Examples of bacteria of the genus Fusobacterium whose growth is promoted by the composition of the present invention include Fusobacterium prausnitzii.
[0035] In addition, the composition of the present invention can be used to promote the growth of Faecalibacterium in the intestine. In other words, the composition of the present invention can be used to increase the occupancy rate of Faecalibacterium in the intestinal flora.
[0036] The composition of the present invention can be administered to carriers of Fusobacterium, more specifically, Fusobacterium nucleatum and / or Fusobacterium varium. Subjects to whom the composition of the present invention is preferably applied include those who carry Fusobacterium in their intestines and / or oral cavity.
[0037] The composition of the present invention can be administered to a carrier of one or more species of Streptococcus, more specifically, Streptococcus mutans, Streptococcus bovis, and Streptococcus anginosus. Subjects to whom the composition of the present invention is preferably administered include those who carry Fusobacterium and / or Streptococcus in their intestines and / or oral cavity.
[0038] Fusobacterium and Streptococcus are known to be pathogens of various diseases. Since the composition of the present invention has the effect of removing Fusobacterium and Streptococcus, the composition of the present invention can be used for treating or preventing diseases caused by Fusobacterium and / or Streptococcus.
[0039] Specifically, the composition of the present invention can be used for the treatment or prevention of colon cancer, inflammatory bowel disease, esophageal cancer, infective endocarditis, bacteremia, periodontal disease, or dental caries. Inflammatory bowel disease to be treated or prevented by the present invention includes ulcerative colitis and Crohn's disease.
[0040] In this specification, "prevention" refers to the act of administering the active ingredient of the present disclosure to a healthy person who has not developed a disease, for example, with the aim of preventing the onset of the disease. "Treatment" refers to the act of administering the active ingredient to a person (patient) who has developed a disease. "Treatment" includes not only fundamental treatment, but also alleviation of symptoms and suppression of disease progression.
[0041] The composition of the present invention can be used for the treatment or prevention of colon cancer, inflammatory bowel disease, esophageal cancer or periodontal disease caused by Fusobacterium bacteria, more specifically, Fusobacterium nucleatum and / or Fusobacterium varium.
[0042] The composition of the present invention can be used for the treatment or prevention of colon cancer, inflammatory bowel disease, esophageal cancer or periodontal disease by removing Fusobacterium bacteria, more specifically Fusobacterium nucleatum and / or Fusobacterium varium.
[0043] The composition of the present invention can be used for the treatment or prevention of colon cancer, esophageal cancer, inflammatory bowel disease, infective endocarditis, bacteremia, or dental caries caused by one or more pathogens selected from the genus Streptococcus, more specifically, Streptococcus mutans, Streptococcus bovis, and Streptococcus anginosus.
[0044] The composition of the present invention can be used for the treatment or prevention of colon cancer, esophageal cancer, inflammatory bowel disease, infective endocarditis, bacteremia, or dental caries by removing one or more species of Streptococcus, more specifically, Streptococcus mutans, Streptococcus bovis, and Streptococcus anginosus.
[0045] The composition of the present invention is intended to inhibit the intestinal activity of Fusobacterium genus, more specifically Fusobacterium nucleatum and / or Fusobacterium varium, and / or One or more species selected from Streptococcus mutans, Streptococcus bovis, and Streptococcus anginosus are removed, and It can be used for the treatment or prevention of inflammatory bowel disease by promoting the growth of bacteria of the genus Faecalibacterium, more specifically Faecalibacterium prausnitzii.
[0046] Methods that involve administering antibiotics, such as ATM therapy, eliminate not only bad bacteria but also good bacteria, causing side effects such as fever and poor health. On the other hand, the composition of the present invention has the effect of eliminating harmful bacteria such as Fusobacterium and Streptococcus, while promoting the growth of beneficial bacteria such as Faecalibacterium. In other words, the composition of the present invention has the effect of improving the balance of the intestinal bacterial flora, and is therefore advantageous in that it does not cause side effects such as those that occur during antibacterial treatment.
[0047] The composition of the present invention is preferably provided in the form of a drinkable composition or a mouthwash composition. In particular, when used to remove Fusobacterium and / or Streptococcus bacteria in the intestines, it is preferably provided in the form of a drinkable composition. Furthermore, when used to remove Fusobacterium and / or Streptococcus bacteria in the oral cavity, it is preferably provided in the form of a mouthwash composition.
[0048] The composition of the present invention, which contains platinum nanoparticles as an active ingredient, is preferably ingested so that the daily intake of platinum nanoparticles is 10 μg or more, more preferably 12 μg or more, even more preferably 15 μg or more, even more preferably 18 μg or more, even more preferably 20 μg or more, even more preferably 22 μg or more, even more preferably 25 μg or more, even more preferably 28 μg or more, and even more preferably 30 μg or more. The upper limit of the daily intake of platinum nanoparticles can be set at, for example, 50 μg or less.
[0049] The composition of the present invention containing electrolyzed water as an active ingredient is preferably ingested in an amount of 500 mL or more, more preferably 1 L or more per day. There is no particular upper limit to the amount of electrolyzed water that can be ingested.
[0050] The period of continuous intake of the composition of the present invention is preferably 1 week or more, more preferably 2 weeks or more, even more preferably 3 weeks or more, even more preferably 4 weeks or more, even more preferably 5 weeks or more, even more preferably 6 weeks or more, even more preferably 7 weeks or more, and even more preferably 8 weeks or more. There is no upper limit to the duration of continuous intake. [Example]
[0051] The present invention will be described in more detail below with reference to examples, but the technical scope of the present invention is not limited to the following examples.
[0052] Fecal samples were collected from 34 subjects who had installed alkaline electrolyzed water purifiers at home and consumed alkaline electrolyzed water daily, and the intestinal microbiota was analyzed using amplicon sequencing targeting the 16s rDNA partial base sequence. The occupancy rates of Fusobacterium, Streptococcus, and Faecalis bacterium in the intestinal microbiota are shown in Table 1 (data in the "1st" row).
[0053] Furthermore, based on the analysis data of the intestinal microbiota, the 34 subjects were classified into the following enterotypes A to E, as defined by the method described in Non-Patent Document 29.
[0054] <Type A> This type is dominated by Ruminococcus. The proportion of Streptococcus is second only to type D. <Type B> This type is rich in Bacteroides. Faecalibacterium is higher than Type C, which also has a high concentration of Bacteroides, but is not significantly higher than Types A, D, and E. This type is rich in butyric acid bacteria. <Type C> Bacteroides is the most prevalent type, and Faecalibacterium is the lowest of the five types. Fusobacterium and Proteus are the highest. <Type D> This type has a significantly higher proportion of Bifidobacterium bacteria. It also has the highest proportion of Streptococcus bacteria among the five types. <Type E> This type is dominated by Prevotella, and is the type that has the highest number of healthy individuals among the five types.
[0055] As a result, of the 34 subjects, 6 were classified as Type A, 13 as Type B, 5 as Type C, 3 as Type D, and 7 as Type E.
[0056] A total of 34 subjects were instructed to drink 1.5 L of the alkaline electrolyzed water dispersion containing platinum nanoparticles per day for eight weeks. At the end of the drinking period, fecal samples were analyzed, and the intestinal microbiota was analyzed using amplicon sequencing targeting the 16s rDNA partial base sequence. The occupancy rates of Fusobacterium, Streptococcus, and Faecalis bacterium in the intestinal microbiota are shown in Table 1 (data in the "Second Time" row).
[0057] The average particle size of the platinum nanoparticles in the dispersion is 2 nm, and 30 μg of platinum nanoparticles are dispersed in 1.5 L of alkaline electrolyzed water. The average particle size of the platinum nanoparticles is calculated by model numerical analysis using small-angle X-ray scattering.
[0058] Table 1 shows the carrier rate (proportion of carriers of the target bacteria among all subjects) and carrier rate (average value calculated for the occupancy rate of the target bacteria in the intestinal flora of carriers) of Fusobacterium, Streptococcus, and Faecalibacterium, obtained by analyzing the intestinal flora of 1,803 subjects randomly selected in advance (mother data, M data).The carrier rate and carrier rate obtained from the first and second analyses, as well as the fluctuation rate (value obtained by subtracting the previous carrier rate from the subsequent carrier rate, dividing the difference by the previous carrier rate and multiplying by 100) are also shown.
[0059] [Table 1] *1 The rate of change calculated using the carriage rate obtained in the first analysis as the pre-value and the carriage rate obtained in the second analysis as the post-value. *2 The rate of change calculated using the carrier rate in the mother data as the pre-value and the carrier rate obtained in the second analysis as the post-value.
[0060] The carrier rate of Fusobacterium was 0.43% in the mother data, but was 0.32% in the first analysis after continued consumption of alkaline electrolyzed water (Table 1). If we assume that the carrier rate in the mother data is the initial value, the results shown in Table 1 indicate that alkaline electrolyzed water is effective in removing Fusobacterium.
[0061] Furthermore, the carriage rate of Fusobacterium was 0.19% in the second analysis after continued consumption of alkaline electrolyzed water with dispersed platinum nanoparticles, and considering that the rate of change was significantly lower at -42.70% between the first and second analyses, the results in Table 1 indicate that platinum nanoparticles are effective in removing Fusobacterium.
[0062] The change rate for Fusobacterium was -56.98% in "M data vs. second time" (Table 1). Furthermore, in the group of subjects classified as enterotype C, which is considered to have a particularly high proportion of Fusobacterium, a change rate of -100% was achieved in "M data vs. second time." These results demonstrate that alkaline electrolyzed water with dispersed platinum nanoparticles exhibits a significantly superior effect in removing Fusobacterium.
[0063] The carrier rate of Streptococcus in the mother data was 3.22%, while in the first analysis after continued consumption of alkaline electrolyzed water it was 1.22% (Table 1). If we assume that the carrier rate in the mother data is the initial value, the results shown in Table 1 indicate that alkaline electrolyzed water is effective in removing Streptococcus.
[0064] Furthermore, the carriage rate of Streptococcus was 0.72% in the second analysis after continued consumption of alkaline electrolyzed water with dispersed platinum nanoparticles, and considering that the rate of change was significantly lower at -40.59% between the first and second analyses, the results in Table 1 indicate that platinum nanoparticles are effective in removing Streptococcus.
[0065] The change rate for Streptococcus was -77.57% in "M data vs. second time" (Table 1). Furthermore, in the subject group classified as type D enterotype, which is considered to have a particularly high occupancy rate of Streptococcus, a change rate of -96% was achieved in "M data vs. second time", showing the highest change rate (removal rate) of all enterotypes. These results demonstrate that alkaline electrolyzed water with dispersed platinum nanoparticles exhibits a significantly superior effect in removing Streptococcus.
[0066] Furthermore, the carrier rate of Faecalibacterium was 5.80% in the mother data, but was 7.42% in the first analysis after continued consumption of alkaline electrolyzed water (Table 1). If we assume that the carrier rate in the mother data is the initial value, the results shown in Table 1 indicate that alkaline electrolyzed water has the effect of promoting the growth of Faecalibacterium.
[0067] Furthermore, the carrier rate of Faecalibacterium was 85% in the first analysis after continuous drinking of alkaline electrolyzed water, but increased to 91% in the second analysis after continuous drinking of alkaline electrolyzed water with dispersed platinum nanoparticles (Table 1). This result indicates that platinum nanoparticles have the effect of promoting the growth of Faecalibacterium.
[0068] When taken together with the result that the fluctuation rate of Faecalibacterium bacteria was 23.27% in "M data vs. second time", it was shown that alkaline electrolyzed water with dispersed platinum nanoparticles has a significantly excellent effect of promoting the growth of Faecalibacterium bacteria.
[0069] From the above results, it can be concluded that the composition of the present invention containing platinum nanoparticles and / or electrolyzed water as active ingredients has excellent effects in removing Fusobacterium and Streptococcus. Furthermore, this test demonstrated that the composition of the present invention is effective in treating or preventing diseases caused by Fusobacterium or Streptococcus, specifically colon cancer, inflammatory bowel disease, esophageal cancer, infective endocarditis, bacteremia, periodontal disease, and dental caries.
[0070] Furthermore, from the above results, it can be concluded that the composition of the present invention containing platinum nanoparticles and / or electrolyzed water as active ingredients has an excellent effect of promoting the growth of Faecalibacterium. Considering that Faecalibacterium is attracting attention as a probiotic for the treatment or prevention of inflammatory bowel disease, it can be said that the composition of the present invention can effectively treat or prevent inflammatory bowel disease through the synergistic effect of removing Fusobacterium and promoting the growth of Faecalibacterium. [Industrial Applicability]
[0071] The composition of the present invention can be used industrially as a drinkable composition or a mouthwash composition used to remove Fusobacterium and / or Streptococcus bacteria.
Claims
1. A composition used for removing Fusobacterium and / or Streptococcus from intestinal flora, comprising platinum nanoparticles as an active ingredient.
2. A composition used for removing Fusobacterium and / or Streptococcus bacteria, comprising platinum nanoparticles as an active ingredient, and further used for promoting the growth of Fusobacterium bacteria.
3. The composition described in claim 1 or 2, further used for the treatment or prevention of inflammatory bowel disease.
4. The composition of claim 3, wherein the inflammatory bowel disease is ulcerative colitis or Crohn's disease.
5. 3. The composition according to claim 1 or 2, for administration to carriers of Fusobacterium and / or Streptococcus.
6. The composition according to claim 5, wherein the carrier has Fusobacterium and / or Streptococcus in its intestines.
7. The composition according to claim 1 or 2, wherein the platinum nanoparticles are dispersed in electrolyzed water.
8. 3. The composition according to claim 1 or 2, which is a drinkable composition.
Citation Information
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