NEW FORMULATION OF LACTOBACILLUS STRAINS FOR THE TREATMENT AND PREVENTION OF HELICOBACTER PYLORI COLONISATION IN THE UPPER AIRWAYS AND THE DIGESTIVE SYSTEM

Abstract

The invention relates to new compositions for the treatment and prevention of Helicobacter pylori colonisation of the oral cavity, the upper airways, the oesophagus, and the digestive system, wherein the formulation is preferably composed in the form of a chewing gum.

Claims

1. A composition comprising a physiologically effective dose of Lactobacillus cells in the form of a) a chewing gum, b) another preparation with prolonged residence time in the mouth, or c) a preparation with application in the upper airways, for the treatment of H. pylori colonisation of the upper airways, the oesophagus, and/or the digestive system.

2. The composition according to claim 1, wherein the Lactobacillus cells are selected from the group Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus lactis, Lactobacillus helveticus, Lactobacillus acidophilus, Lactobacillus bulgaricus, Lactobacillus delbrueckii, Lactobacillus casei, Lactobacillus paracasei, Lactobacillus pentosus, Lactobacillus rhamnosus and Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus brevis, Lactobacillus fermentum, Lactobacillus viridescens and/or Bifidobacterium bifidum.

3. The composition according to claim 1, comprising an effective dose of Lactobacillus cells per application between 10.sup.3 and 10.sup.13 cells in living, viable, dead, or fragmented forms as cell wall constituents or isolated cell wall molecules respectively from 1×10.sup.3 to 1×10.sup.13 cells per application.

4. The composition according to claim 3, comprising an effective dose of Lactobacillus cells per application between 10.sup.9 and 10.sup.11 cells in living, viable, dead, or fragmented forms as cell wall constituents or isolated cell wall molecules respectively from 10.sup.9 to 10.sup.11 cells per application.

5. The composition according to claim 1, comprising Lactobacillus reuteri as filed under DSM 17648 in the form of a chewing gum for the treatment of H. pylori colonisation of the oral cavity, the upper airways, the oesophagus, the stomach, and the intestine.

6. The composition according to claim 1, comprising Lactobacillus cells in viable or dead form.

7. The composition according to claim 1 in an administration form, selected from buccal tablets (also muco-adhesive buccal tablets) or orodispersible tablets, oral active ingredient films, gargle solutions or concentrates (incl. powders/tablets for the production), mouth rinses or concentrates (incl. powders/tablets for the production), gingival cleaning solutions, oromucosal preparations, such as drops, gel, liquids, pastes, solutions, sprays, and/or suspensions, sublingual preparations, such as sprays, tablets, films, lozenges or candies, powders or granules for oral application, preparations for nasal application, such as nose drops, liquid nose sprays, nose powders, semi-solid preparations for nasal application, nose rinses, or nose inhalers.

Description

EXAMPLES

1) Composition of the Gum Base

[0036]

TABLE-US-00001 Gum base 22-26% Xylitol  8-12% Plasticiser max. 2% Anticaking agent (E-551) max. 2% Antioxidant (BHT) max. 260 ppm Sorbitol up to 100%

2) Composition of the Chewing Gums According to the Invention

[0037] Lactobacillus cells, e.g., L. reuteri DSM 17648 50 mg/gum

TABLE-US-00002 Gum base Hig PWD-01 .sup. 90% Gum (in gum base) 21.6% Sorbitol (in gum base) 57.6% Xylitol (in gum base) 10.5% Flavour (mint) Var. additives ad 100% 

[0038] Typically, 50 mg L. reuteri include 5×10.sup.9 cells.

3) Application of the Chewing Gums According to the Invention

[0039] a) Probands with chronic periodontal disease and H. pylori colonisation in dental plaques of deep gingival pockets receive 4-6 chewing gums according to Example 2 per day, which are chewed preferably in the morning, at midday, in the afternoon, and the evening for 20-40 minutes each after the meals. After chewing four to six chewing gums, an average reduction of the H. pylori density in dental plaque samples and mouth rinsing samples by 20% was observed. [0040] b) Probands with chronic periodontal disease and evidence of H. pylori in dental plaque of deep gingival pockets and simultaneously present dyspepsis receive 4 to 6 chewing gums according to Example 2 per day, which are chewed preferably in the morning, at midday, in the afternoon, and the evening for 20-40 minutes each after the meals. After 28 days, significantly less H. pylori in dental plaques is detected, clinical signs of periodontal disease have been significantly improved for more than half of the patients, dyspeptic complaints have been significantly improved for 80% of the patients.

4) Production of Buccal Films

[0041] a) The films are produced by the modified casting solvent vaporisation method (Angela Abruzzo et al., Pharmaceutics 2020, 12(3), 241). HPMC (2.5 wt. %) is dissolved in PG-containing water (1 wt. %), and the solution is stirred for 8 h until a viscous, gel-type solution is formed (viscosity 9100 mPa.Math.s, pH 6.3). Optionally, biodegradable and simultaneously physiologically tolerated polymers for delaying the dissolution (e.g., polylactic acid, polyvinyl alcohol, xanthan gum) may be added to the solution. Then, the viscous solution is left for at least 8 hours at room temperature, in order to assure a clear, bubble-free gel. The bubble-free gel (6.7 g) was poured onto a Petri dish (5 cm diameter) and dried in the oven at 50° C. for 5 h. After this time, the dried Lactobacillus preparation is applied onto one side of the film (loaded side). Glass rings of suitable size (height, 1 cm; diameter, 1 cm) are used to include a sufficient amount (10 mg, corresponding to 9.21±0.25 log CFU) of Lactobacillus cells and to cut the film into the final administration forms. Ultimately, the Petri dish is brought for at least one day into an exsiccator at 20° C., in order to complete the film formation (up to constant weight). [0042] The further characterisation of the buccal film is performed according to Angela Abruzzo et al., Pharmaceutics 2020, 12(3), 241. [0043] b) Probands with chronic periodontal disease and evidence of H. pylori in dental plaque of deep gingival pockets and simultaneously present dyspepsia receive 5 of the above buccal films, which are placed preferably in the morning, at midday, in the afternoon, and the evening respectively into the oral cavity (inner side of the cheek) and dissolved there over a period of time of 2-30 minutes. [0044] Here, too, significantly less H. pylori in dental plaques is detected after 28 days, clinical signs of periodontal disease have been significantly improved for more than half of the patients, dyspeptic complaints have been significantly improved for more than 75% of the patients.