Oral hygiene preparation comprising lactobacillus strains and MCT oil as active ingredients and its use for the treatment of teeth grinding

Abstract

The invention relates to an oily liquid preparation comprising probiotic cells derived from Lactobacillus rhamnosus and Lactobacillus reuteri strains, combined with vitamin A, vitamin E and peppermint essential oil, all mixed in a medium -chain triglyceride (MCT) oil. This preparation can be used in various applications, such as in medicaments, mouthwashes, dietary supplements, or for anti-inflammatory purposes.

Description

[0001] ORAL HYGIENE PREPARATION COMPRISING LACTOBACILLUS STRAINS AND MCT OIL AS ACTIVE INGREDIENTS AND ITS USE FOR THE TREATMENT OF TEETH GRINDING

[0002] The invention relates to a preparation which comprises the following, simultaneously dissolved in MCT oil: vitamin A promoting epithelial regeneration and the immune system, vitamin E protecting the cells against oxidative stress and Lactobacillus reuterii and rhamnosus supporting the healthy microbiome of the oral and gut flora, and also comprises peppermint oil. The preparation can be used for the treatment of teeth grinding.

[0003] THE STATE OF THE ART

[0004] Oral hygiene products play a key role in maintaining a healthy oral cavity and preventing dental problems. These products, including toothpastes, mouthwashes, dental floss, and toothbrushes, help remove plaque, prevent tooth decay, and contribute to maintaining fresh breath. Regular and proper oral care is not only important from an aesthetic point of view, but also for the prevention of gum diseases such as gingivitis and periodontal diseases. Proper oral hygiene habits and the use of suitable products can contribute to preserve long-term dental and gum health and maintain overall well-being.

[0005] Probiotics are live microorganisms, such as bacteria or yeast, that have a positive effect on health when consumed in sufficient amounts. According to the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO), these microorganisms support the functioning of the human body, for example, digestion and the immune system (see Anna Zawistowska-Rojek, Stefan Tyski in Are Probiotics Really Safe for Humans?, Pol J Microbiol., 2018;67(3):251-258). Lactic acid bacteria have long been used for this purpose. These bacteria produce lactic acid, which helps maintain the balance of the gut flora and improves digestion. Probiotics can therefore promote gut health by supporting the development and maintenance of a healthy gut flora, which is important for overall health. Some oral hygiene products contain probiotics that provide beneficial bacterial strains to maintain oral health. These bacterial strains help maintain the balance of the oral microbiome, reduce the growth of harmful bacteria, and contribute to maintaining healthy teeth and gums. Some commonly used bacterial strains are the following. Lactobacillus reuteri is one of the most commonly used probiotic strains in oral hygiene and it can reduce gingivitis and plaque formation and suppress harmful bacteria. The Streptococcus salivarius strain can help eliminate bad breath and inhibit the growth of pathogenic bacteria in the oral cavity. It is often found in probiotic mouthwashes. Lactobacillus rhamnosus is another probiotic that helps suppress bacteria that cause tooth decay and improve gum health. The Bifidobacterium lactis strain primarily supports oral cavity and gum health and can help prevent periodontal diseases. Lactobacillus casei helps reduce gum inflammation and defend against bacteria that cause tooth decay. PT118530A discloses a preparation of natural origin and a method for inhibiting cariogenic (causing tooth decay) microorganisms. The method involves three main steps, the first of which is to extract antimicrobial agents from chamomile. The preparation also contains mineral salts obtained from natural mineral water. The obtained preparation is effective against Candida albicans and Streptococcus mutans microorganisms at a concentration between 0.5 and 5.0 mg / ml. The mixture also significantly inhibits biofilm formation (by 80-90%), thus controls the growth of these bacteria. It is also important that the preparation does not inhibit the growth of beneficial bacteria in the mouth, such as Lactobacillus casei, Lactobacillus plantarum, and Lactobacillus reuteri.

[0006] According to another study (see Lee, H. J., Hong, J. K., Kim, J. K., Kim, D. H., Jang, S. W., Han, S. W., & Yoon, I. Y. (2021) in Effects of Probiotic NVP-1704 on Mental Health and Sleep in Healthy Adults: An 8-Week Randomized, Double-Blind, Placebo-Controlled Trial, Nutrients, 13(8), 2660), probiotics may play a potential role in improving mental health and sleep, as demonstrated by the probiotic preparation NVP-1704, which contains Lactobacillus reuteri NK33 and Bifidobacterium adolescentis NK98 bacterial strains, in atotal amount of 2.5 billion CFU. The bacteria are freeze-dried with maltodextrin as a carrier. In the clinical trial, participants took two capsules daily for eight weeks, which significantly improved mental health and sleep quality, reduced symptoms of depression and anxiety, and lowered the levels of inflammatory biomarkers. In addition, favourable changes were observed in the composition of the gut microbiome. A further study (see Wauters, L., Van Oudenhove, L., Accarie, A., Geboers, K., Geysen, H., Toth, J., Luypaerts, A., Verbeke, K., Smokvina, T., Raes, J., Tack, J., & Vanuytsel, T. (2022) in Lactobacillus rhamnosus CNCM 1-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial, Gut Microbes, 14(1), 2031695.) aimed to investigate whether the probiotic Lactobacillus rhamnosus CNCM 1-3690 reduces subjective academic stress in healthy adults. The study was randomized and placebo -controlled, where participants received either the probiotic or a placebo. Participants were administered the probiotic or placebo for a specified period of time while their stress levels were monitored. The results of the study also supported the potential role of probiotics in reducing stress. In light of the literature described here, it is not obvious that teeth grinding, often associated with anxiety, cannot be successfully treated with the above described Lactobacillus reuteri and Lactobacillus rhamnosus strains alone. We have conducted extensive research on this topic, the results of which provide an explanation for the phenomenon mentioned herein and highlight that our solution for treating teeth grinding is not obvious and has solved a previously unsolved technical problem.

[0007] EP3324928B1 discloses a self-fihn-forming composition in powder form, for use as a medicament or in dental care, which self-film -forms under agitation in the presence of a liquid medium. Its components include at least one gelifier agent and / or bioadhesive agent providing viscosity and adhesive properties, such as starches, rubber-based ingredients, or cellulose derivatives. It also contains at least one Pediococcus strain, which is a lactic acid bacterium and may have a prebiotic effect. The composition is suitable for the treatment of peri-implantitis or mucositis. The scope of invention also includes a kit comprising the composition and a device for its application.

[0008] US11998479B2 discloses a method for reducing the likelihood of dental caries and halitosis. The disclosed method recommends the use of two types of bacterial preparations. The first preparation contains biofilm -forming bacteria, such as from the genus Rothia. The second preparation contains oral probiotics, such as Lactobacillus and Streptococcus species, as well as zinc -based compounds and bioactive flavonoids (e.g., quercetin, hesperidin). These reduce the pH of the mouth and disrupt the formation of biofilm by pathogenic bacteria. The preparation can be used in the form of toothpaste, mouthwash, chewing gum, or other formulations.

[0009] HU009368T2A describes a preparation containing Lactobacillus reuteri strains that can be used in the oral cavity. During the production process, two strains, Lactobacillus reuteri Prodentis (ATCC PTA- 5289) and Lactobacillus reuteri FJ3 (ATCC PTA-5290), are selected, which have antimicrobial and antiinflammatory effects, adhere to oral mucin, and produce vitamin KI. The selected strains can be used for reducing gum bleeding and relieving gum inflammation. The preparation contains 105to 108colonyforming units of lactic acid bacteria daily, which are administered orally to the patient. The preparation may also contain other active ingredients that help treat or prevent gum bleeding and inflammation.

[0010] MCT oil is a medium-chain triglyceride (MCT) oil most commonly derived from coconut oil or palm oil. MCT fatty acids are digested more quickly than long -chain fatty acids, allowing the body to utilize them as an immediate source of energy. It has been shown that 12 weeks of MCT intake resulted in positive changes in the composition of the microbiom and reduced the level of inflammatory cytokines (see Xu, Q., Li, H., Liu, Y., Zhang, P., Zhang, Y., Zhang, X., & Liu, Y. (2022) in Medium-chain triglycerides reduce diarrhoea with improved immune status and gut microbiomics in tunnel workers in China. Asia Pacific Journal of Clinical Nutrition, 31(2), 229-241.). Animal studies have shown that MCT oil can reduce anxious behaviour and improve social behaviour in animals. This effect is likely to be mediated by the stabilization of ketone production and the dopaminergic system (see Hollis, F., Mitchell, E. S., Canto, C., Wang, D., & Sandi, C. (2018) in Medium chain triglyceride diet reduces anxiety-like behaviors and enhances social competitiveness in rats. Neuropharmacology, 138, 245-256, and Miura, A., Yamanashi, T., Kajitani, N., Fukuda, S., Tsunetomi, K., Matsuo, R., Nishiguchi, T., Pu, S., Nakada, Y., Shirayama, Y., Watanabe, K., Kaneko, K., & Iwata, M. (2025) in Medium-Chain Triglyceride Administration Induces Antidepressant Effects in Animal Models by Increasing Beta-Hydroxybutyrate Levels. Yonago Acta Medica, 68(1), 58-67). Our comparative experiments indicate that MCT oil alone is not capable of providing reassuring results in the treatment of teeth grinding.

[0011] The term bruxism refers to teeth grinding, which affects 30 to 40% of the population. Teeth grinding usually occurs at night, but in many cases also during the day. This involuntary muscle activity can lead to tooth wear, jaw problems, and headaches. Teeth grinding can become so severe that abrasion and attrition can cause the bite to sink, transforming the muscle -jaw joint-dentition unit, which can lead to joint pain, muscle pain, difficulty in chewing, and thus digestive problems. The lips become thinner, and the larger overlapping area at the comers of the lips becomes more susceptible to infection and cracking. Sleep quality often deteriorates, which further increases stress levels. Dental restorations may break. There are several methods of treating bruxism, selected based on the underlying causes. A common solution is the use of night dental guards and stress management techniques. In severe cases, botox injections or other muscle relaxants can reduce jaw muscle activity, thereby reducing teeth grinding. Lifestyle changes, such as reducing caffeine and alcohol consumption, can also be helpful in relieving symptoms. One problem with bite raising splints is whether the patient actually wears them and whether they admit if they do not. Another problem is that pathogens can easily grow and multiply on plastic surfaces lacking of proper cleaning and can become a source of more infection in people with poor oral hygiene. Therefore, there is a great need for causal therapy for teeth grinding, and the state of the art does not describe a preparation containing Lactobacillus strains that could be used in the treatment of bruxism.

[0012] TECHNICAL PROBLEM TO BE SOLVED BY THE INVENTION

[0013] The above state of the art does not provide an actually effective solution for the treatment of teeth grinding. It can be seen that neither the MCT oil nor Lactobacillus reuteri and Lactobacillus rhamnosus strains alone show an effective therapeutic effect in improving teeth grinding conditions - this was also proven by our comparative experiments disclosed in the present invention. The technical problem to be solved by the invention is based on the difficult-to-explain phenomenon that although there is a professional consensus that teeth grinding is often associated with or related to anxious behaviour, and both MCT oil treatment and the use of Lactobacillus reuteri and Lactobacillus rhamnosus strains can demonstrate promising results in reducing and eliminating anxiety, none of the aforementioned active ingredients is suitable for ensuring the successful treatment of teeth grinding on their own.

[0014] THE RECOGNITION UNDERLYING THE INVENTION

[0015] During the application of the preparation according to our invention, we found that even after two weeks of once daily continuous mouth rinsing with 5 ml of the preparation, it reduces and / or eliminates the patient's teeth grinding. This result is surprising in light of the fact that the applied active ingredients are not capable of reducing teeth grinding on their own. Depending on the germ count, the preparation of the invention reduces or eradicates aggressive and facultative pathogenic flora in the oral cavity. Among its positive effects, it is important to note that it begins to transform or establish a normal oral flora, reduces signs of inflammation, reduces halitosis, i.e. bad breath, and reduces the pain caused by canker sores and facilitates their healing. It also facilitates post-operative wound healing in the oral cavity, on the lips, and on the skin surface, and treats leukoplakia. It stimulates bowel function, eliminates constipation and reduces reflux symptoms. In several cases, sore throat relief was also reported after pharyngeal rinsing. It promotes the development of healthy oral and gut flora. Without wishing to support our invention with a single explanation, we attribute the unexpected additional effects of the preparation according to the invention, namely the unexpected positive results achieved in the treatment of teeth grinding, to the two bacterial strains used and to the additional active ingredients that enhance the effect in an unexpected degree.

[0016] BRIEF DESCRIPTION OF THE INVENTION

[0017] 1. An oily, liquid preparation comprising the following, per 100 grams of the preparation: a) as active ingredient, 1.0 • 108— 1.0 • IO10, preferably 5.0 • 108-5.0 • 109, more preferably 1.0 • 109- 3.0 - 109, more preferably about 1.5 • 109simultaneously applied active cells derived from Lactobacillus rhamnosus and Lactobacillus reuteri strains, wherein the ratio of the strains to each other is 10:90%- 90: 10%, preferably 25:75%-75:25%, more preferably about 50:50%; b) as active ingredient, 100 to 20,000 pg, preferably 200 to 18,000 pg, more preferably about 600- 15,000 pg of vitamin A; c) as active ingredient, 1 to 500 mg, preferably 5 to 250 mg, more preferably about 9 to 225 mg of vitamin E; d) 0.1 to 100 mg, preferably 1.0 to 50 mg, more preferably 1.5 to 37.5 mg of peppermint essential oil; where components a) to d) are mixed in oil, preferably in a medium -chain triglyceride oil (MCT oil).

[0018] 2. The preparation according to point 1 for use in the treatment, reduction or elimination of teeth grinding.

[0019] The use of the preparation according to point 1 in the manufacture of a drug for administration to a subject for inducing a biological response during the treatment of teeth grinding, characterised in that the dosage regimen of the drug is the following: the therapeutic amount of the drug, preferably at least 1.5 ml, preferably 5 ml of the preparation according to claim 1 or 2 is administered at least once daily for the period necessary to induce the maximum biological response, preferably for at least 5 days.

[0020] 4. The use according to point 3, characterized by the following dosage regimen: the therapeutic amount of the preparation according to point 1 or 2, preferably at least 1.5 ml, more preferably 5 ml is administered at least once daily for approximately one month, twice daily, with a pre-treatment with Lactobacillus and Bifidobacterium in lysed form.

[0021] DETAILED DESCRIPTION OF THE INVENTION

[0022] In the case of the preparation according to the invention, the formulation of the oily liquid preparation involves the integration of several active ingredients. For example, the preparation comprises probiotic cells from Lactobacillus rhamnosus and Lactobacillus reuteri strains, vitamin A, vitamin E, and peppermint essential oil. These ingredients are mixed in a medium-chain triglyceride (MCT) oil, which serves as the medium for the preparation. The MCT oil, preferably obtained from coconut oil or palm kernel oil, acts as a carrier that facilitates the homogeneous distribution of the active ingredients in the preparation. According to the specification of the MCT oil, its fatty acid composition is 55 to 65% caprylic acid (C8) and 35 to 45% capric acid (CIO) fatty acids. In addition, the oil contains up to 2% caproic acid (C6), up to 3% lauric acid (C12), and up to 1% myristic acid.

[0023] One embodiment of the invention contains 50-50% Lactobacillus rhamno sus and Lactobacillus reuteri strains as 1.5 • 109active cells, 600 pg of vitamin A, 9 mg of vitamin E, 1.5 mg of peppermint essential oil, and MCT oil.

[0024] The invention makes the oily liquid preparation suitable for using as a medicament.

[0025] The invention makes the oily liquid preparation suitable for using for anti-inflammatory purposes.

[0026] The preparation according to the invention is suitable for treating inflammatory oral cavity problems where mechanical cleaning is not sufficient to eliminate various aggressive, pathogenic, or facultative pathogenic bacteria and antibiotic therapy is also necessary. For patients, the use of the oral hygiene preparation according to the invention in a single daily 5 ml rinse effectively reduced oral cavity symptoms without the need for antibiotics. The reduction of inflammation and thus the reduction of bleeding is achieved by the use of the preparation according to the invention, i.e. by causal therapy. Accordingly, pathogenic bacteria are reduced or completely eradicated and instead the growth of Lactobacillus and other normal flora is promoted. Based on our results in reference example 2, regular daily use of the preparation according to the invention eliminates the need for antibiotic therapy.

[0027] The invention makes the oily liquid preparation suitable for using in the treatment of leukoplakia.

[0028] According to one embodiment of the invention, the oily liquid preparation is applied as a mouthwash.

[0029] According to one embodiment of the invention, the oily liquid preparation is used in the treatment of teeth grinding and bruxism. In a study of 40 patients, we found that in the gut flora of these patients Lactobacillus was absent or present in only negligible amounts. Out of them, 38 patients with good stress tolerance were suitable for participation in the gut flora study. The results were the following: 29 of the 38 patients provided stool samples, thus they could have been evaluated. 23 of the patients had a. Lactobacillus species count of 106CFU / g, which is below the normal range. 20 of the patients had radically reduced counts, i.e. below 2 • 104CFU / g, 2 patients had 2 • 104CFU / g, and 1 patient had 6 • 104CFU / g. The second largest difference was regarding Enterococcus species, with 22 patients having 104— 105CFU / g instead of the minimum 109CFU / g. The third difference was regarding Bifidobacterium species. The smallest difference was below 107CFU / g. In case of the 2 patients whose Lactobacillus count was sufficient or at the threshold, the number of Bifidobacteria and Enterococci was below the threshold. In addition, the results showed other symptoms indicating inflammation, such as lactose intolerance, indicating functional intestinal problems. Based on the analysis of the results, our invention suggests Lactobacillus supplementation as a therapeutic recommendation for patients suffering from teeth grinding who have low Lactobacillus counts.

[0030] According to one embodiment of the invention, the MCT oil used in the preparation is derived from coconut oil or palm kernel oil, providing a stable and healthy carrier oil. The oily liquid preparation according to the invention may contain one or more additional ingredients selected from sweeteners, flavourings, preservatives, and stabilizers, allowing for the customization of taste and shelf life.

[0031] According to one embodiment of the invention, the preparation is available in the form of a solution, suspension or emulsion, ensuring versatile application and use. It should be noted that our preparation is more suitable than preparations providing Lactobacillus in solid form for ensuring the beneficial effects of Lactobacillus, because as opposed to the capsule formulation, the biofilm-like coating of our preparation is more suitable to help the beneficial bacteria adhere to the mucous membrane.

[0032] EXAMPLES

[0033] Example 1: Oral hygiene preparation containing Lactobacillus strains

[0034] The following preparation was produced as follows:

[0035] MCT oil was used as a base, into which Lactobacillus rhamnosus and Lactobacillus reuteri bacterial cultures, powdered vitamins, and peppermint oil were mixed in in that order with careful stirring until they were homogeneously distributed.

[0036] - 1.5 • 109active cells from Lactobacillus rhamnosus and Lactobacillus reuteri strains, in a 50-50% ratio;

[0037] - 600 microgram vitamin A;

[0038] - 9 mg vitamin E;

[0039] 1.5 mg peppermint essential oil;

[0040] - MCT oil.

[0041] Reference example 2: Use of an oral hygiene preparation containing Lactobacillus strains to reduce inflammation

[0042] The preparation according to the invention was used for the treatment of inflammatory oral cavity problems wherein mechanical cleaning is not sufficient to eliminate various aggressive, pathogenic or facultative pathogenic bacteria, and antibiotic therapy is also necessary. This is rendered unnecessary by the daily regular use of the preparation according to the invention.

[0043] The reduction of inflammation and thus the reduction of bleeding is achieved through causal therapy. Accordingly, the pathogenic bacteria are reduced or completely eradicated and the growth of Lactobacillus and other normal flora is promoted. L. reuteri is well known for its ability to produce vitamin K, which in this case is considered an adjunctive symptomatic treatment. Patients were administered the oral hygiene preparation according to the invention, which effectively reduced oral problems without the need for antibiotics. The antimicrobial and anti-inflammatory properties of the lactic acid bacteria in the preparation contributed to the restoration of the oral flora and helped prevent the growth of pathogens. As a result, the condition of the patients improved significantly, demonstrating that the use of suitable oral hygiene products can be an effective alternative to antibiotic treatments. Tables 1 to 4 below show the conditions before and after the use of the oral hygiene preparation containing Lactobacillus strains. On average, 1 month elapsed between the two samples. The treatment comprises rinsing with 5 ml of the preparation according to the invention once daily. The composition of the preparation is shown in Example 1.

[0044] Table 1. Sampling results before treatment and after treatment with the oral hygiene preparation containing Lactobacillus strains

[0045] Patient No. 1 Before treatment After treatment

[0046] Aggregatibacter 102102(few colonies) actinomycetemcomitans Fusobacterium nucleatum 104103

[0047] Peptostreptococcus micros 104103

[0048] Actinomyces viscosus 104103

[0049] Table 2. Sampling results before treatment and after treatment with the oral hygiene preparation containing Lactobacillus strains

[0050] Patient No. 2 Before treatment After treatment

[0051] Prevotella intermedia 1030

[0052] Fusobacterium nucleatum 1030

[0053] Actinomyces odontolyticus 0 103

[0054] Capnocytophaga 103103

[0055] Normal flora 1040, .S', constellatus 103

[0056] Table 3. Sampling results before treatment and after treatment with the oral hygiene preparation containing Lactobacillus strains

[0057] Patient No. 3 Before treatment After treatment

[0058] Aggregatibacter 1020 actinomycetemcomitans

[0059] Actinomyces viscosus 1030

[0060] Normal flora 104103

[0061] E. coli 0 102

[0062] Table 4. Sampling results before treatment and after treatment with the oral hygiene preparation containing Lactobacillus strains.

[0063] Patient No. 4 Before treatment After treatment

[0064] Aggregatibacter 102few colonies 0 actinomycetemcomitans

[0065] Porphyromonas gingivalis 1040 Prevotella intermedia 1030

[0066] Actinomyces viscosus 103102

[0067] Actinomyces odontolyticus 0 102

[0068] Normal flora 0 102

[0069] Example 3: Use of a preparation containing Lactobacillus strains in the treatment of teeth grinding

[0070] The first human trial took place between 2021 and 2023 as part of a project supported by the NHKIH, regarding the use of a preparation containing Lactobacillus strains in the treatment of bruxism. The trial involved 59 healthy, teeth grinding patients aged between 20 and 55 who underwent psychological screening. Patients with poor stress tolerance were identified by psychologists and they were not allowed to participate in the gut flora study, as stress itself is known to increase intestinal permeability and to disrupt the balance of the gut flora. 38 patients with good stress tolerance were eligible to participate in the gut flora study. In patients with poor stress tolerance, stress alone can cause teeth grinding, which masks the effect of the administered preparation or prevents it from exercising any effect at all. The gut flora of patients with good stress tolerance was examined using the PCR method. The gut flora test included the following: Escherichia coli, Escherichia coli Biovare, Proteus species, Klebsiella species, Pseudomonas species, Enterobacter species, Serratia species, Hafnia species, Enterococcus species, Bifidobacterium, Lactobacillus, Clostridium, Candida species, Candida albicans, Geotrichium candidum. In addition, the following were studied: the colour, consistency, pH, fat-, nitrogen-, sugar-, and water content, pancreatic elastase- and bile acid content of the stool, data indicating inflammation and immunity, secretory IgA, calprotectin, alpha- 1 -antitrypsin, and zonulin content, which characterizes intestinal wall permeability. Two patients who bruxed for until several years before but were not undergoing dental rehabilitation at the time of the study and had good stress tolerance were used as controls. In their case, no treatment for teeth grinding was necessary, and their gut flora results were compared with the gut flora of the studied teeth grinder patients, as a control.

[0071] The results were the following: 29 of the 38 patients provided stool samples, therefore these could be evaluated. 23 of the patients had a. Lactobacillus species count of 106CFU / g, which is below the normal range. 20 of the patients had radically reduced counts, i.e. below 2 • 104CFU / g, 2 patients had 2 • 104CFU / g, and 1 patient had 6 • 104CFU / g.

[0072] The second largest difference was regarding Enterococcus species, with 22 patients having 104- 105CFU / g instead of the minimum 109CFU / g. The third difference was regarding Bifidobacterium species. The smallest difference was below 107CFU / g. In case of the 2 patients whose Lactobacillus count was sufficient or at the threshold, the number of Bifidobacteria and Enterococci was below the threshold.

[0073] In addition, the results showed other symptoms indicating inflammation, such as lactose intolerance, indicating functional intestinal problems. Based on the analysis of the results, our invention suggests Lactobacillus supplementation as a therapeutic recommendation for patients suffering from teeth grinding who have low Lactobacillus counts. The results of the patients’ samples are shown in Tables 5 and 6.

[0074] Most probiotic microorganisms, such as Lactobacillus, Bifidobacterium, Lactococcus, and some yeasts, have a "generally recognized as safe" (GRAS) status, which means these strains are widely recognized as safe for human consumption. However, there are microorganisms such as Streptococcus, Enterococcus, and bacteria belonging to the Bacillus group, which do not have GRAS status but are still used as probiotics. This is important because the safety and effectiveness of probiotics depend on the strain, as only certain specific strains have a probiotic effect and not all bacteria belonging to a given genus.

[0075] Our complex preparation helps restore the balance of the gut flora, thus reduces teeth grinding. Based on our results, the absence of Lactobacillus plays a role in teeth grinding, which explains why individuals who are otherwise naturally stress-resistant grind their teeth, and opens up a therapeutic path for a widespread problem that has so far only been treated symptomatically in dentistry.

[0076] Table 5. Results obtained from the examination of samples from the patients participating in the study.p. Enterococcus sp. Bifidibacterium sp. Lactobacillus sp. Other bacteria (CFU / g)

[0077] Patient (CFU / g) (CFU / g) (CFU / g) range 106to l07lO’ to lO11105to l07

[0078] Control 1

[0079] Control 2 108Clostridium 106 / 105

[0080] 3 6 • 108<104Clostridium 2 • 106

[0081] 4 3 • 1083 • 108<104Geotrichium cand. 2 • 103

[0082] 5 6 • 108<104

[0083] 6 <104<4 • 108<104

[0084] 7 <1044 IO8<104Enterobacter <

[0085] 8 <104AH <104

[0086] 9 <104<107<104

[0087] 10 <104AH <104

[0088] 11 <1044 IO7<104

[0089] 12 6 • 105<104

[0090] 13 6 • 1044 • 107Candida l ■ 103 / 103max /

[0091] 14 9 • 105<108

[0092] 15 <104

[0093] 16 8 107<104Klebsiella 1 • 105 / 104 1

[0094] 17 8 • 108<104

[0095] 18 <1047 • 108<104

[0096] 19 2 • 105H <104Klebsiella 4 • 106

[0097] 8 • 1086 • 104Geotrichium cand l ■ 105

[0098] Enterobacter 107 / <104

[0099] 21 <1046 • 108<104

[0100] 22 <1042 • 104

[0101] 23 <1043 • 108<104

[0102] 24 4 • 1053 • 108<104Cand. 105, Geotr. 105

[0103] 25 <104<104Bacteroides 9 • 108 / 109 /

[0104] 2^ 8 • 1086 • 104Enterobact. 107

[0105] Geotrichium cand. 2 10

[0106] 27 2 • 1053 • 108<104

[0107] 28 Klebsiella 4 • 106

[0108] 29 <1046 • 108<104

[0109] 23 / 27 significantly decreased

[0110] Total 22 / 27 18 / 27 value

[0111] Table 6. Results obtained from the examination of samples from patients participating in the study. pH Fat Sugar Nitrogen calprotectin alpha-1- zonulin Flora status

[0112] Patient (g / 100 g) (g / 100 g) (g / 100 g) (mg / 1) antitrypsin (ng / ml) range 5.8 to 6.5 <3.5 <2.5 <1 <50 <27.5 <55 <3 / 9< high diversity /

[0113] Control 1 6.9 7 2

[0114] Control 2 6.6 5 2.6 7

[0115] 3 7.3 5.1 3.4 31.5 57.7 9

[0116] 4 6.8 3.7 3.4 11

[0117] 5 7 3.6 3.1 10

[0118] 6 6.8 4.2 3.4 34.1 9

[0119] 7 6.5 3.5 3 10

[0120] 8 7.1 6.6 3.4 56.1 37.7 87 9

[0121] 9 6.9 3.9 2.6 44.2 83 11

[0122] 10 7.9 102 12

[0123] 11 7.2 3.3 28.8 102 11

[0124] 12 6.8 9.7 30.1 72 5

[0125] 13* 7.3 4.2 3.1 74.2 35.2 74.8 7

[0126] 14 4.6 60.9 7

[0127] 15 7.5 5.4 3.3 99.5 65.5 6

[0128] 16 6.8 4.9 3 36.6 78 10

[0129] 17 7.6 4.6 3.3 35.5 65.1 8

[0130] 18 7.1 4.9 4.6 54.9 10

[0131] 19 7.1 7.2 2.6 1.1 75.6 50.7 83.2 11

[0132] 20 7.1 5.9 3.3 90.6 13

[0133] 21 6.9 3.7 3.4 134.8 8

[0134] 22 6.5 35.8 64.3 9

[0135] 23 6.6 3.6 3.7 95 9

[0136] 24 7.1 5.3 3.1 68 12

[0137] 25** 6.9 4.8 3.4 415.1 68 11

[0138] 26 7.1 5.9 3.3 90.6 13

[0139] 27 8.1 4.4 3 10

[0140] 28 7.1 5.3 11

[0141] 29 6.9 3.7 3 134 8

[0142] Total 27 / 27 27 / 27 26 / 27

[0143] . . . . . . . . . 4 / 29 high 12 / 29 high 20 / 27 high high high ” ” Based on Table 4, it can be concluded that in the majority of patients who have good stress tolerance but grind their teeth (23 out of 27 cases), a reduced presence of Lactobacillus was observed. Teeth grinding patients treated with Lactobacillus self-reported that their symptoms improved or disappeared as a result of the treatment (in 2 out of 7 cases the symptoms improved and in 5 cases they disappeared; see above).

[0144] Example 4: The use of a preparation containing Lactobacillus strains, and the use of MCT oil and Lactobacillus as a control in the treatment of teeth grinding

[0145] Restoring the balance in the gut flora of patients, including the reduced number of Lactobacillus, may improve teeth grinding. In our preliminary research, as in example 6, examining 29 cases, the patients typically experienced less teeth grinding. In contrast, in untreated patients, teeth grinding did not stop on its own.

[0146] In order to clarify the effect of the other ingredients besides Lactobacillus, the following study was conducted: the patients were administered Lactobacillus alone, MCT oil alone, and the oil-based liquid preparation according to the invention.

[0147] Table 7. Examination of the individual components used alone

[0148] Teeth grinding

[0149] Type of treatment Unchanged Reduced Eliminated

[0150] Untreated 4 0 0

[0151] MCT oil 3 1 0

[0152] Lactobacillus 1 3 0

[0153] The preparation according 0 2 3 to the invention

[0154] The use of MCT oil resulted in a reduction of teeth grinding in one patient, presumably because MCT oil improves the gut microbiome, reduces inflammation, and supports the immune system, however, there is no scientific evidence that MCT oil has a direct effect on teeth grinding (bruxism).

[0155] Based on the data shown in the table, teeth grinding was reduced in two other cases after taking Lactobacillus, but a Lactobacillus treatment alone is not always sufficient because the live flora cannot always colonize the irritated intestinal mucosa. Regeneration of the mucous membrane is necessary for colonization by the live flora.

[0156] The Lactobacillus strains, the MCT oil and the other (vitamin) active ingredients in the oily, liquid preparation according to the invention surprisingly show a synergistic effect. Without limiting the meaning of our invention to a single explanation, we suggest the following. MCT oil, by reducing inflammation and supporting the immune system, helps the dopaminergic system. Vitamin A regenerates the intestinal mucosa, which needs to renew itself very quickly and can sometimes become permeable due to irritation, thus in these cases it plays a significant role. Vitamin E strengthens the immune system, which is of key importance in the intestines, and in cases of inflammation and irritation, the intestinal wall can become permeable, and in such cases vitamin E’s role in the immune system and its antioxidant effect is even more important. Peppermint oil in minimal doses, in 0.2 ml 3 times per day (»0.6 ml / day) can be effective in relieving the symptoms of IBS (irritable bowel syndrome) (PMID: 9430014). In children, 0.3 ml (~6 drops) per day has also been shown to be effective and the effect is due to its antispasmodic and carminative properties. These patients often show symptoms of IBS.

[0157] INDUSTRIAL APPLICABILITY

[0158] The preparation according to the invention can be used in a therapy for the treatment of teeth grinding.

Claims

PATENT CLAIMS1. An oily, liquid preparation comprising the following ingredients, per 100 grams of the preparation: a) as active ingredient, 1.0 • 108— 1.0 • IO10, preferably 5.0 • 108-5.0 • 109, more preferably 1.0 • 109- 3.0 - 109, more preferably about 1.5 • 109simultaneously applied active cells derived from Lactobacillus rhamnosus and Lactobacillus reuteri strains, wherein the ratio of the strains to each other is 10:90%- 90: 10%, preferably 25:75%-75:25%, more preferably about 50:50%; b) as active ingredient, 100 to 20,000 pg, preferably 200 to 18,000 pg, more preferably about 600- 15,000 pg of vitamin A; c) as active ingredient, 1 to 500 mg, preferably 5 to 250 mg, more preferably about 9 to 225 mg of vitamin E; d) 0.1 to 100 mg, preferably 1.0 to 50 mg, more preferably 1.5 to 37.5 mg of peppermint essential oil; where components a) to d) are mixed in oil, preferably in a medium -chain triglyceride oil (MCT oil).

2. The preparation according to Claim 1 for use in the treatment, reduction or elimination of teeth grinding.

3. The use of the preparation according to Claim 1 in the manufacture of a drug for administration to a subject for inducing a biological response during the treatment of teeth grinding, characterised in that the dosage regimen of the drug is the following: the therapeutic amount of the drug, preferably at least 1.5 ml, preferably 5 ml of the preparation according to claim 1 or 2 is administered at least once daily for the period necessary to induce the maximum biological response, preferably for at least 5 days.

4. The use according to Claim 3, characterized in that the following dosage regimen is used: the therapeutic amount of the preparation according to Claim 1 or 2, preferably at least 1.5 ml, more preferably 5 ml is administered at least once daily for approximately one month, twice daily, with a pre -treatment with Lactobacillus and Bifidobacterium in lysed form.

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