US20180133268A1 - Compositions for a medical device comprising exopolysaccharide-producing bacterial strains in association with gums and/or gelatines - Google Patents
Compositions for a medical device comprising exopolysaccharide-producing bacterial strains in association with gums and/or gelatines Download PDFInfo
- Publication number
- US20180133268A1 US20180133268A1 US15/848,812 US201715848812A US2018133268A1 US 20180133268 A1 US20180133268 A1 US 20180133268A1 US 201715848812 A US201715848812 A US 201715848812A US 2018133268 A1 US2018133268 A1 US 2018133268A1
- Authority
- US
- United States
- Prior art keywords
- streptococcus thermophilus
- vegetable
- composition
- gum
- dsm
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000001580 bacterial effect Effects 0.000 title claims abstract description 56
- 239000000203 mixture Substances 0.000 title claims abstract description 54
- 229920002444 Exopolysaccharide Polymers 0.000 title claims abstract description 40
- 229920000159 gelatin Polymers 0.000 title claims abstract description 40
- 235000019322 gelatine Nutrition 0.000 title claims abstract description 40
- 229920001938 Vegetable gum Polymers 0.000 claims abstract description 33
- 241001465754 Metazoa Species 0.000 claims abstract description 25
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 20
- 238000011065 in-situ storage Methods 0.000 claims abstract description 13
- 241000194020 Streptococcus thermophilus Species 0.000 claims description 60
- 239000001828 Gelatine Substances 0.000 claims description 28
- 235000010491 tara gum Nutrition 0.000 claims description 23
- 239000000213 tara gum Substances 0.000 claims description 23
- 241000894006 Bacteria Species 0.000 claims description 15
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- ZNOZWUKQPJXOIG-XSBHQQIPSA-L [(2r,3s,4r,5r,6s)-6-[[(1r,3s,4r,5r,8s)-3,4-dihydroxy-2,6-dioxabicyclo[3.2.1]octan-8-yl]oxy]-4-[[(1r,3r,4r,5r,8s)-8-[(2s,3r,4r,5r,6r)-3,4-dihydroxy-6-(hydroxymethyl)-5-sulfonatooxyoxan-2-yl]oxy-4-hydroxy-2,6-dioxabicyclo[3.2.1]octan-3-yl]oxy]-5-hydroxy-2-( Chemical compound O[C@@H]1[C@@H](O)[C@@H](OS([O-])(=O)=O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H]2OC[C@H]1O[C@H](O[C@H]1[C@H]([C@@H](CO)O[C@@H](O[C@@H]3[C@@H]4OC[C@H]3O[C@H](O)[C@@H]4O)[C@@H]1O)OS([O-])(=O)=O)[C@@H]2O ZNOZWUKQPJXOIG-XSBHQQIPSA-L 0.000 claims 9
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- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
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- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
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Classifications
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- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
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- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
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- A23L29/206—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of vegetable origin
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- A—HUMAN NECESSITIES
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/20—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents
- A23L29/275—Foods or foodstuffs containing additives; Preparation or treatment thereof containing gelling or thickening agents of animal origin, e.g. chitin
- A23L29/281—Proteins, e.g. gelatin or collagen
- A23L29/284—Gelatin; Collagen
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- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A61K36/18—Magnoliophyta (angiosperms)
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- A—HUMAN NECESSITIES
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- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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Definitions
- the present invention relates to a composition for a medical device comprising a specific mucoadherent gelling complex composed of EPS, exopolysaccharides of bacterial origin produced in situ in the gastrointestinal tract by specific selected bacterial strains, in association with vegetable gums and/or animal and/or vegetable gelatines.
- Said complex is capable of establishing a complete barrier effect of a mechanical type extending throughout the whole gastrointestinal tract and can be used as a medication for the prevention and treatment of all pathologies connected to a deficiency in the barrier effect in the gastrointestinal area due to a low production of mucus, such as, by way of non-exhaustive example, intestinal permeability and bacterial translocation.
- bacteria in general such as, for example, bacteria belonging to the species Streptococcus thermophilus , are sensitive to gastric juices and arrive, in the gastrointestinal tract in reduced concentrations and with little vitality.
- composition for a medical device having features as defined in the appended independent claim.
- compositions or a medical device comprising or, alternatively, consisting of gums of bacterial origin, in particular exopolysaccharides (EPS), in association with vegetable gums and/or animal and/or vegetable gelatines, said gums of bacterial origin being produced by said bacteria in situ in the gastrointestinal tract in the presence of said vegetable gums and/or animal and/or vegetable gelatines.
- EPS exopolysaccharides
- Said bacterial gum produced directly by the probiotic bacterial strains of the present invention together with the vegetable gums and/or the animal and/or vegetable gelatines, are capable of preserving and protecting the intestinal mucosa in such a way as to avoid, reduce or at least oppose the action of pathogenic bacteria which are deleterious for the mucosa itself.
- compositions or a medical device comprising or, alternatively, consisting of gums of bacterial origin, in particular exopolysaccharides, produced by said bacteria in situ in the gastrointestinal tract in association with vegetable gums and/or animal and/or vegetable gelatines.
- the Applicant has found a way to form a specific mucoadherent gelling complex, which is composed of EPS, exopolysaccharides of bacterial origin produced in situ in the gastrointestinal tract by specific selected bacterial strains, in association with vegetable gums and/or animal and/or vegetable gelatines.
- the subject matter of the present invention relates to a specific mucoadherent gelling complex composed of EPS, exopolysaccharides of bacterial origin produced in situ in the gastrointestinal tract by specific selected bacterial strains, in association with vegetable gums and/or animal and/or vegetable gelatines, for use as a medication for the prevention and treatment of all pathologies connected to a deficiency in the barrier effect in the gastrointestinal area due to a low production of mucus, preferably in the case of intestinal permeability and bacterial translocation, as claimed in the appended claims.
- compositions of the present invention For the sake of brevity, in the context of the present invention a composition or a medical device (composition for a medical device) will be referred to in general, in the remainder of the description, as “the compositions of the present invention”.
- compositions of the present invention comprise or, alternatively, consist of at least one probiotic bacterial strain which is a producer of exopolysaccharides (abbreviated EPS) in association with a vegetable gum and/or an animal and/or vegetable gelatine.
- EPS exopolysaccharides
- Said at least one strain of EPS-producing strains is selected from the group comprising the bacterial strains belonging to the genera Streptococcus, Lactobacillus and Bifidobacteria .
- Said at least one bacterial strain is selected preferably from the group comprising or, alternatively, consisting of probiotic bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus pentosus, Lactobaciilus acidophiius, Lactobacillus brevis, Lactobacillus reutei, Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus fermentum and Lactobacillus delbrueeckii.
- Said at least one bacterial strain is selected from the group comprising or, alternatively, consisting of probiotic bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus .
- Said probiotic bacterial strains must be EPS producers in situ in the gastrointestinal tract.
- said EPS-producing bacterial strains belong to the species Streptococcus thermophilus.
- compositions of the present invention comprise or, alternatively consist of one or two or three or four EPS-producing probiotic bacterial strains, selected from among the ones described, in association with a vegetable gum and/or an animal and/or vegetable gelatine.
- compositions of the present invention comprise or, alternatively, consist of one or two or three or four EPS-producing probiotic bacterial strains, selected from the group comprising or, alternatively, consisting of probiotic bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus in association with a vegetable gum and/or an animal and/or vegetable gelatine.
- said one or two or three or four EPS-producing bacterial strains belong to the species Streptococcus thermophilus.
- Embodiments comprising mixtures of two or three or four bacterial strains selected from among probiotic bacterial strains belonging to the species Streptococcus thermophilus and/or Lactobacillus plantarum and/or Lactobacillus rhamnosus in association with a vegetable gum and/or an animal and/or vegetable gelatine are also part of the present invention.
- a gum is a dehydrated or lyophilized or dried material in the form of a powder or fakes which on coming into contact with water produces a gum gel in water (aqueous gel) or a gum gelatine.
- a gum gel in water (aqueous gel) or a gum gelatine.
- an already prepared gel or gelatine can be validly used.
- the gums used are all gums for oral use which are allowed and used in food supplements and medical devices.
- the vegetable gum and/or the animal and/or vegetable gelatine is selected from the group comprising or, alternatively, consisting of Aloe, Aloe vera ( Aloe vera— Aloe barbadensis Miller, is a plant of the Aloaceae family), Aloe arborescens , alginates, xyloglucans (or xylogels), tannates, gelatine tannate, carrageenans, pectins, agar-agar and tara gum.
- the vegetable gum and/or the animal and/or vegetable gelatine is selected from the group comprising or, alternatively, consisting of Aloe arborescens , gelatine tannate and tara gum.
- gelatine tannate a complex of gelatine and tannic acid
- Gelatine tannate forms a mucoadhesive protective film of protein origin which protects the intestinal mucosa.
- a vegetable gum and/or an animal or vegetable gelatine undergoes a slow but inexorable degradation as it passes from the stomach to the intestine. The gum degrades and loses its effectiveness in restoring the physiological functions of the intestinal walls.
- This degradation is due to multiple factors, such as, for example pH, enzymes, attacks from endogenous bacterial flora, the effect of the gastroduodenal barrier and a dilution effect. Practically speaking, there is a loss of effectiveness that occurs progressively as the gelatine tannate passes through the gastrointestinal tract, also as the result of an attack by acid, bile salts, pancreatic juices and enzymes. When the gelatins tannate arrives in the colon it is in part degraded and thus less effective in protecting the walls of the intestine against pathogenic bacteria, which are able to penetrate it by means of their flagella.
- gum of bacterial origin produced in situ by the strains of the present invention selected from the group comprising or, alternatively, consisting of probiotic bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus , on the one hand, and a vegetable gum and/or an animal and/or vegetable gelatine, on the other hand, each have an effect of their own and they are complementary to each other.
- the first effect is a galling effect exerted by the vegetable gum and/or the animal and/or vegetable gelatine, and which is maximum in the stomach (maximum protection) and minimum in the colon due to the degradation and consequent loss of effectiveness in protecting inflamed intestinal mucosae.
- the second effect is a protective effect exerted by the gum of bacterial origin, in particular by exopolysaccharides (EPS) produced in situ by the strains of the present invention selected from the group comprising or, alternatively, consisting of probiotic bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus .
- EPS exopolysaccharides
- compositions or a medical device for use as a medication for the prevention and the treatment of all pathologies connected to a deficiency in the barrier effect in the gastrointestinal area due to a low production of mucus.
- compositions of the present invention are capable of restoring the barrier effect that was lost because of insufficient protection of the mucosa in the gastrointestinal tract.
- compositions of the present invention are capable of preventing and treating infections, inflammations and disorders of the gastrointestinal tract, pathogenic bacteria, candidiasis and intestinal permeability.
- composition of the present invention is capable of forming a specific mucoadherent gelling complex, composed of EPS, exopolysaccharides of bacterial origin (produced by selected strains as specified below, belonging in particular to the species Streptococcus thermophilus , e.g, Streptococcus thermophilus ST10-DSM 25246, Streptococcus thermophilus (YO4) DSM 16592 or mixtures thereof in a ratio by weight comprised from 1:2 to 2:1, preferably 1:1, and tara gum, a polysaccharide of vegetable origin.
- Said gelling complex is capable of establishing a barrier effect of a mechanical type extending throughout the whole gastrointestinal tract.
- the composition of the present invention is capable of forming a hydrogel within few minutes after ingestion, by virtue of its thixotropic characteristics, and of thereby creating, in the first part of the gastrointestinal tract, a barrier effect of a mechanical type against pathogenic bacteria and metabolites with proinflammatory action.
- This barrier effect is completed and extended for the entire length of the gastrointestinal tract by the presence of exopolysaccharides (EPS), produced in situ by probiotic bacterial strains belonging to the species Streptococcus thermophilus , as specified below, e.g.
- EPS exopolysaccharides
- Streptococcus thermophilus ST10 Streptococcus thermophilus ST10, Streptococcus thermophilus YO04 or mixtures thereof, which serve to increase the viscosity of the surrounding environment through an exclusively mechanical, self-regulated mechanism.
- the intake of the aforesaid bacteria conveys into the human intestine a source of molecules with a gelling activity, thus exerting an action which is totally complementary to that of tare gum.
- the above-mentioned mucoadherent gelling complex has an innovative property to be taken into consideration during its intestinal transit, tara gum (like all gums of vegetable origin) is progressively degraded by the resident microbiota, so that its mechanically opposing gelling power is progressively reduced.
- the presence, production and retention of the hydrophilic gel in the lumen of the organ can therefore for the first time be considered really complete, with a first area in which the action of the vegetable gum is maximum and a second area in which the action of the exopolysaccharides (EPS) is maximum.
- EPS exopolysaccharides
- the bacterial strains are selected from the group comprising or, alternatively, consisting of:
- the bacterial strains were deposited in accordance with the Budapest Treaty and are available to the public.
- the composition of the present invention comprises or, alternatively, consists of at least one bacterial strain selected from the group comprising or, alternatively, consisting of: Streptococcus thermophilus DSM 16590 (YO2), Streptococcus thermophilus DSM 16592 (YO4), Streptococcus thermophilus DSM 17843 (YO8) and Streptococcus thermophilus DSM 25246 (ST10) in association with a vegetable gum and/or an animal and/or vegetable gelatine selected from the group comprising or, alternatively, consisting of Aloe arborescens , gelatine tannate and tare gum.
- composition of the present invention comprises or, alternatively consists of Streptococcus thermophilus DSM 25246 (ST10) in association with a vegetable gum and/or an animal and/or vegetable gelatine selected from the group comprising or, alternatively, consisting of Aloe arborescens , gelatine tannate and tara gum; advantageously tara gun.
- ST10 Streptococcus thermophilus DSM 25246
- the composition of the present invention comprises or, alternatively, consists of: Streptococcus thermophilus DSM 25246 (ST10) and at least one strain selected from among Streptococcus thermophilus DSM 16590 (YO2), Streptococcus thermophilus DSM 18592 (YO4) and Streptococcus thermophilus DSM 17843 (YO8) in association with a vegetable gum and/or an animal and/or vegetable gelatine selected from the group comprising or, alternatively, consisting of Aloe arborescens , gelatine tannate and tara gum; advantageously tars gum.
- ST10 Streptococcus thermophilus DSM 25246
- ST10 Streptococcus thermophilus DSM 16590
- YO4 Streptococcus thermophilus DSM 18592
- YO8 Streptococcus thermophilus DSM 17843
- composition of the present invention comprises or, alternatively, consists of: Streptococcus thermophilus DSM 25246 (ST10) and Streptococcus thermophilus DSM 16592 (YO4) in association with a vegetable gum and/or an animal and/or vegetable gelatine selected from the group comprising or, alternatively, consisting of Aloe arborescens , gelatine tannate and tara gum; advantageously tare gum.
- ST10 Streptococcus thermophilus DSM 25246
- YO4 Streptococcus thermophilus DSM 16592
- probiotic bacteria belonging to the species Streptococcus thermophilus said bacteria are in a protected form (coated bacteria).
- the bacteria can be coated with one lipid coating (mono-coated) or two lipid coatings (bi-coated) of animal or vegetable origin (microencapsulated form).
- the lipid coating has a melting point comprised from 35 to 85° C., preferably from 45 to 75° C., even more preferably from 55 to 65° C.
- the bacteria can be inserted into a capsule, preferably made of soft or hard gelatine.
- the capsule can be coated with a gastroprotective film that is able to pass beyond the gastric barrier.
- the bacterial strains specified above are present in the composition of the present invention in an amount comprised from 0.1 to 50% by weight, preferably from 0.5 to 15% by weight, even more preferably from to 10%, relative to the total weight of the composition or supplement.
- said percentage depends on the pharmaceutical form it is desired to produce.
- the amount of said bacteria is greater than 30%, for example greater than 35%.
- the composition comprises a mixture of bacterial strains at a concentration comprised from 1 ⁇ 10 6 to 1 ⁇ 10 11 CFU/g, preferably from 1 ⁇ 10 8 to 1 ⁇ 10 10 CFU/g of mixture or individual bacterial strain.
- the composition comprises bacterial strains at a concentration comprised from 1 ⁇ 10 6 to 1 ⁇ 10 11 CFU/dose, preferably from 1 ⁇ 10 8 to 1 ⁇ 10 10 CFU/dose.
- the dose can be comprised from 0.2 to 10 g, for example, it can be 0.25 g, 1 g, 3 g, 5 g or 7 g.
- the bacterial strains can be present in the composition in solid form, for example in the form of a powder, dehydrated powder or lyophilized powder.
- Tablet 1 strain ST10-DSM 25246, excipients and tars gum.
- Tablet 2 strain ST10-DSM 25246, excipients and guar gum.
- Tablet 3 strain ST10-DSM 25246: and strain YO4-DSM 16592, excipients and tara gum.
- Tablet 4 strain ST10-DSM 25246 and strain YO4-DSM 16592, excipients and guar gum.
- Tablet 5 strain ST10-DSM 25246 and strain YO2-DSM 16590, excipients and tara gum.
- Tablet 6 strain ST10-DSM 25246 and strain YO2-DSM 16590, excipients and guar gum.
- Tablet 7 strain ST10-DSM 25246 and strain YO8-DSM 17843, excipients and tara gum.
- Tablet 8 strain ST10-DSM 25246 and strain YO8-DSM 17843, excipients and guar gum.
Abstract
A composition for a medical device is described. The composition comprises a specific mucoadherent gelling complex composed of EPS, exopolysaccharides of bacterial origin produced in situ in the gastrointestinal tract by specific selected bacterial strains, in association with vegetable gums and/or animal and/or vegetable gelatines. The complex is capable of establishing a complete barrier effect of a mechanical type extending throughout the whole gastrointestinal tract and can be used as a medication for the prevention and treatment of all pathologies connected to a deficiency in the barrier effect in the gastrointestinal area due to a low production of mucus, such as, by way of non-exhaustive example, intestinal permeability and bacterial translocation.
Description
- The present invention relates to a composition for a medical device comprising a specific mucoadherent gelling complex composed of EPS, exopolysaccharides of bacterial origin produced in situ in the gastrointestinal tract by specific selected bacterial strains, in association with vegetable gums and/or animal and/or vegetable gelatines. Said complex is capable of establishing a complete barrier effect of a mechanical type extending throughout the whole gastrointestinal tract and can be used as a medication for the prevention and treatment of all pathologies connected to a deficiency in the barrier effect in the gastrointestinal area due to a low production of mucus, such as, by way of non-exhaustive example, intestinal permeability and bacterial translocation.
- It is known that bacteria in general, such as, for example, bacteria belonging to the species Streptococcus thermophilus, are sensitive to gastric juices and arrive, in the gastrointestinal tract in reduced concentrations and with little vitality.
- Furthermore, it is known that pathogenic bacteria attack and penetrate the intestinal mucosa more easily when the intestinal mucosa is inflamed or when little mucus is present on the intestinal wall.
- There thus remains a need to be able to preserve, in sufficient number and in a good state of vitality, bacterial strains, such as, for example, bacteria belonging to the species Streptococcus thermophilus, which are already present in the bacterial flora of the intestine or are carried in the intestine. Moreover, there remains a need to preserve the intestinal mucosa in such a way as to avoid, reduce or at least oppose the action of pathogenic bacteria.
- The subject matter of the present invention relates to a composition for a medical device having features as defined in the appended independent claim.
- Preferred embodiments of the present invention will appear more clearly from the detailed description that follows and are claimed in the appended claims.
- The Applicant has found it useful to develop a composition or a medical device (composition for a medical device) comprising or, alternatively, consisting of gums of bacterial origin, in particular exopolysaccharides (EPS), in association with vegetable gums and/or animal and/or vegetable gelatines, said gums of bacterial origin being produced by said bacteria in situ in the gastrointestinal tract in the presence of said vegetable gums and/or animal and/or vegetable gelatines. Said bacterial gum produced directly by the probiotic bacterial strains of the present invention together with the vegetable gums and/or the animal and/or vegetable gelatines, are capable of preserving and protecting the intestinal mucosa in such a way as to avoid, reduce or at least oppose the action of pathogenic bacteria which are deleterious for the mucosa itself.
- In particular, the present invention relates to a composition or a medical device (composition for a medical device) comprising or, alternatively, consisting of gums of bacterial origin, in particular exopolysaccharides, produced by said bacteria in situ in the gastrointestinal tract in association with vegetable gums and/or animal and/or vegetable gelatines.
- The Applicant has found a way to form a specific mucoadherent gelling complex, which is composed of EPS, exopolysaccharides of bacterial origin produced in situ in the gastrointestinal tract by specific selected bacterial strains, in association with vegetable gums and/or animal and/or vegetable gelatines.
- The subject matter of the present invention relates to a specific mucoadherent gelling complex composed of EPS, exopolysaccharides of bacterial origin produced in situ in the gastrointestinal tract by specific selected bacterial strains, in association with vegetable gums and/or animal and/or vegetable gelatines, for use as a medication for the prevention and treatment of all pathologies connected to a deficiency in the barrier effect in the gastrointestinal area due to a low production of mucus, preferably in the case of intestinal permeability and bacterial translocation, as claimed in the appended claims.
- For the sake of brevity, in the context of the present invention a composition or a medical device (composition for a medical device) will be referred to in general, in the remainder of the description, as “the compositions of the present invention”.
- The compositions of the present invention comprise or, alternatively, consist of at least one probiotic bacterial strain which is a producer of exopolysaccharides (abbreviated EPS) in association with a vegetable gum and/or an animal and/or vegetable gelatine.
- Said at least one strain of EPS-producing strains is selected from the group comprising the bacterial strains belonging to the genera Streptococcus, Lactobacillus and Bifidobacteria. Said at least one bacterial strain is selected preferably from the group comprising or, alternatively, consisting of probiotic bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus pentosus, Lactobaciilus acidophiius, Lactobacillus brevis, Lactobacillus reutei, Bifidobacterium breve, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus fermentum and Lactobacillus delbrueeckii.
- Said at least one bacterial strain is selected from the group comprising or, alternatively, consisting of probiotic bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus. Said probiotic bacterial strains must be EPS producers in situ in the gastrointestinal tract.
- Advantageously, said EPS-producing bacterial strains belong to the species Streptococcus thermophilus.
- The compositions of the present invention comprise or, alternatively consist of one or two or three or four EPS-producing probiotic bacterial strains, selected from among the ones described, in association with a vegetable gum and/or an animal and/or vegetable gelatine.
- The compositions of the present invention comprise or, alternatively, consist of one or two or three or four EPS-producing probiotic bacterial strains, selected from the group comprising or, alternatively, consisting of probiotic bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus in association with a vegetable gum and/or an animal and/or vegetable gelatine.
- Advantageously, said one or two or three or four EPS-producing bacterial strains belong to the species Streptococcus thermophilus.
- Embodiments comprising mixtures of two or three or four bacterial strains selected from among probiotic bacterial strains belonging to the species Streptococcus thermophilus and/or Lactobacillus plantarum and/or Lactobacillus rhamnosus in association with a vegetable gum and/or an animal and/or vegetable gelatine are also part of the present invention.
- A gum is a dehydrated or lyophilized or dried material in the form of a powder or fakes which on coming into contact with water produces a gum gel in water (aqueous gel) or a gum gelatine. Alternatively, an already prepared gel or gelatine can be validly used.
- The gums used are all gums for oral use which are allowed and used in food supplements and medical devices.
- In one embodiment, the vegetable gum and/or the animal and/or vegetable gelatine is selected from the group comprising or, alternatively, consisting of Aloe, Aloe vera (Aloe vera—Aloe barbadensis Miller, is a plant of the Aloaceae family), Aloe arborescens, alginates, xyloglucans (or xylogels), tannates, gelatine tannate, carrageenans, pectins, agar-agar and tara gum.
- Advantageously, the vegetable gum and/or the animal and/or vegetable gelatine is selected from the group comprising or, alternatively, consisting of Aloe arborescens, gelatine tannate and tara gum.
- In one embodiment, use is made of gelatine tannate (a complex of gelatine and tannic acid), which acts by mechanical means to protect inflamed intestinal mucosae. Gelatine tannate forms a mucoadhesive protective film of protein origin which protects the intestinal mucosa. However, from the time it is ingested to the time it arrives at its destination in the intestine, a vegetable gum and/or an animal or vegetable gelatine undergoes a slow but inexorable degradation as it passes from the stomach to the intestine. The gum degrades and loses its effectiveness in restoring the physiological functions of the intestinal walls.
- This degradation is due to multiple factors, such as, for example pH, enzymes, attacks from endogenous bacterial flora, the effect of the gastroduodenal barrier and a dilution effect. Practically speaking, there is a loss of effectiveness that occurs progressively as the gelatine tannate passes through the gastrointestinal tract, also as the result of an attack by acid, bile salts, pancreatic juices and enzymes. When the gelatins tannate arrives in the colon it is in part degraded and thus less effective in protecting the walls of the intestine against pathogenic bacteria, which are able to penetrate it by means of their flagella.
- The Applicant has found that gum of bacterial origin, produced in situ by the strains of the present invention selected from the group comprising or, alternatively, consisting of probiotic bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus, on the one hand, and a vegetable gum and/or an animal and/or vegetable gelatine, on the other hand, each have an effect of their own and they are complementary to each other.
- The first effect is a galling effect exerted by the vegetable gum and/or the animal and/or vegetable gelatine, and which is maximum in the stomach (maximum protection) and minimum in the colon due to the degradation and consequent loss of effectiveness in protecting inflamed intestinal mucosae.
- The second effect is a protective effect exerted by the gum of bacterial origin, in particular by exopolysaccharides (EPS) produced in situ by the strains of the present invention selected from the group comprising or, alternatively, consisting of probiotic bacterial strains belonging to the species Streptococcus thermophilus, Lactobacillus plantarum or Lactobacillus rhamnosus. This second effect is minimum in the stomach and maximum in the colon, where the bacteria of the present invention, having arrived alive and vital and at a high concentration, produce, EPS in situ.
- Added together, these two mutually complementary effects ensure total coverage against bacterial infections in the stomach (due to the vegetable gum and/or the animal and/or vegetable gelatine) and in the gastrointestinal tract (due to the gum of bacterial origin).
- The subject matter of the present invention relates to a composition or a medical device (composition for a medical device) for use as a medication for the prevention and the treatment of all pathologies connected to a deficiency in the barrier effect in the gastrointestinal area due to a low production of mucus.
- The compositions of the present invention are capable of restoring the barrier effect that was lost because of insufficient protection of the mucosa in the gastrointestinal tract.
- The compositions of the present invention are capable of preventing and treating infections, inflammations and disorders of the gastrointestinal tract, pathogenic bacteria, candidiasis and intestinal permeability.
- The composition of the present invention is capable of forming a specific mucoadherent gelling complex, composed of EPS, exopolysaccharides of bacterial origin (produced by selected strains as specified below, belonging in particular to the species Streptococcus thermophilus, e.g, Streptococcus thermophilus ST10-DSM 25246, Streptococcus thermophilus (YO4) DSM 16592 or mixtures thereof in a ratio by weight comprised from 1:2 to 2:1, preferably 1:1, and tara gum, a polysaccharide of vegetable origin. Said gelling complex is capable of establishing a barrier effect of a mechanical type extending throughout the whole gastrointestinal tract.
- Thanks to the presence of the gellant tara gum, the composition of the present invention is capable of forming a hydrogel within few minutes after ingestion, by virtue of its thixotropic characteristics, and of thereby creating, in the first part of the gastrointestinal tract, a barrier effect of a mechanical type against pathogenic bacteria and metabolites with proinflammatory action. This barrier effect is completed and extended for the entire length of the gastrointestinal tract by the presence of exopolysaccharides (EPS), produced in situ by probiotic bacterial strains belonging to the species Streptococcus thermophilus, as specified below, e.g. Streptococcus thermophilus ST10, Streptococcus thermophilus YO04 or mixtures thereof, which serve to increase the viscosity of the surrounding environment through an exclusively mechanical, self-regulated mechanism. The intake of the aforesaid bacteria conveys into the human intestine a source of molecules with a gelling activity, thus exerting an action which is totally complementary to that of tare gum. The above-mentioned mucoadherent gelling complex has an innovative property to be taken into consideration during its intestinal transit, tara gum (like all gums of vegetable origin) is progressively degraded by the resident microbiota, so that its mechanically opposing gelling power is progressively reduced. The gradual decrease in the action of the vegetable gum is effectively compensated for by the gradual increase in the release, in the intestinal lumen, of exopolysaccharides (EPS), for example by the bacterial strain ST10 and/or YO04, which manifests its particular characteristics above all in the ileum and in the colon. As a result, the synergetic combination of tara gum and exopolysaccharides (EPS) ensures the presence of gelling molecules for the entire length of the gastrointestinal tract, thus maximizing and optimizing the mechanical barrier action of the product. The presence, production and retention of the hydrophilic gel in the lumen of the organ can therefore for the first time be considered really complete, with a first area in which the action of the vegetable gum is maximum and a second area in which the action of the exopolysaccharides (EPS) is maximum.
- In one embodiment, the bacterial strains are selected from the group comprising or, alternatively, consisting of:
-
- Streptococcus thermophilus DSM 16590 (YO2), deposited with the depositary institution DSMZ in Germany on 20 Jul. 2004,
- Streptococcus thermophilus DSM 16592 (YO4), deposited with the depositary institution DSMZ in Germany on 20 Jul. 2004,
- Streptococcus thermophilus DSM 17843 (YO8), deposited with the depositary institution DSMZ in Germany on 21 Dec. 2005,
- Streptococcus thermophilus DSM 25246 (ST10), deposited with the depositary institution DSMZ in Germany on 19 Sep. 2011,
- Streptococcus thermophilus SM 25247 (ST11), deposited with the depositary institution DSMZ in Germany on 19 Sep. 2011,
- Streptococcus thermophilus DSM 25282 (ST12), deposited with the depositary institution DSMZ in Germany on 19 Sep. 2011.
- The bacterial strains were deposited in accordance with the Budapest Treaty and are available to the public.
- In one embodiment, the composition of the present invention comprises or, alternatively, consists of at least one bacterial strain selected from the group comprising or, alternatively, consisting of: Streptococcus thermophilus DSM 16590 (YO2), Streptococcus thermophilus DSM 16592 (YO4), Streptococcus thermophilus DSM 17843 (YO8) and Streptococcus thermophilus DSM 25246 (ST10) in association with a vegetable gum and/or an animal and/or vegetable gelatine selected from the group comprising or, alternatively, consisting of Aloe arborescens, gelatine tannate and tare gum.
- In another embodiment, the composition of the present invention comprises or, alternatively consists of Streptococcus thermophilus DSM 25246 (ST10) in association with a vegetable gum and/or an animal and/or vegetable gelatine selected from the group comprising or, alternatively, consisting of Aloe arborescens, gelatine tannate and tara gum; advantageously tara gun.
- In another embodiment, the composition of the present invention comprises or, alternatively, consists of: Streptococcus thermophilus DSM 25246 (ST10) and at least one strain selected from among Streptococcus thermophilus DSM 16590 (YO2), Streptococcus thermophilus DSM 18592 (YO4) and Streptococcus thermophilus DSM 17843 (YO8) in association with a vegetable gum and/or an animal and/or vegetable gelatine selected from the group comprising or, alternatively, consisting of Aloe arborescens, gelatine tannate and tara gum; advantageously tars gum.
- In another embodiment, the composition of the present invention comprises or, alternatively, consists of: Streptococcus thermophilus DSM 25246 (ST10) and Streptococcus thermophilus DSM 16592 (YO4) in association with a vegetable gum and/or an animal and/or vegetable gelatine selected from the group comprising or, alternatively, consisting of Aloe arborescens, gelatine tannate and tara gum; advantageously tare gum.
- In the case of probiotic bacteria belonging to the species Streptococcus thermophilus, said bacteria are in a protected form (coated bacteria). The bacteria can be coated with one lipid coating (mono-coated) or two lipid coatings (bi-coated) of animal or vegetable origin (microencapsulated form). The lipid coating has a melting point comprised from 35 to 85° C., preferably from 45 to 75° C., even more preferably from 55 to 65° C.
- Alternatively, the bacteria can be inserted into a capsule, preferably made of soft or hard gelatine. The capsule can be coated with a gastroprotective film that is able to pass beyond the gastric barrier.
- The bacterial strains specified above are present in the composition of the present invention in an amount comprised from 0.1 to 50% by weight, preferably from 0.5 to 15% by weight, even more preferably from to 10%, relative to the total weight of the composition or supplement. However, said percentage depends on the pharmaceutical form it is desired to produce. For example, in the case of a capsule, the amount of said bacteria is greater than 30%, for example greater than 35%. In one embodiment, the composition comprises a mixture of bacterial strains at a concentration comprised from 1×106 to 1×1011 CFU/g, preferably from 1×108 to 1×1010 CFU/g of mixture or individual bacterial strain.
- In one embodiment, the composition comprises bacterial strains at a concentration comprised from 1×106 to 1×1011 CFU/dose, preferably from 1×108 to 1×1010 CFU/dose. The dose can be comprised from 0.2 to 10 g, for example, it can be 0.25 g, 1 g, 3 g, 5 g or 7 g. The bacterial strains can be present in the composition in solid form, for example in the form of a powder, dehydrated powder or lyophilized powder.
-
- 1. The viscosity of samples of serum fermented with probiotic bacterial strains belonging to the exopolysaccharide (EPS) producing species S. thermophilus was evaluated. The viscosity was measured by means of a viscometer which measures the rotation of a suitably sized disk within the sample to be tested: the more friction the disk encounters the slower its rotation, the set speed being equal. The result is expressed in centipoises (CPs), in association with a percentage SP, which is an expression of the goodness of the data (the method requires it to be greater than or equal to 15%). The culture medium is 10% reconstituted serum pasteurized at 80° C. for 20 minutes, into which the strains specified below were inoculated at a concentration of 3%: Streptococcus thermophilus DSM 16590 (YO2) Streptococcus thermophilus DSM 16592 (YO4), Streptococcus thermophilus DSM 17843 (YO8), Streptococcus thermophilus DSM 25246 (ST10), Streptococcus thermophilus DSM 25247 (ST11) and Streptococcus thermophilus DSM 25282 (ST12).
-
Viscosity 5 hours 24 hours PH Sample CPs SP % CPs SP % 5 hours 24 hours plain serum 0-10 1.5-2 40 9 6.03 5.95 (blank 1) serum + MO3 10 3.5 70 15 4.55 4.17 (bianco 2) serum + YO2-DSM 40 9 170 35.5 4.67 4.14 16590 serum + YO4-DSM 40 8.5 210 43.5 4.63 4.10 16592 serum + YO8-DSM 20 5.5 120 25.5 4.68 4.09 17843 serum + ST10-DSM 40 9 210 42.5 4.57 4.05 25246 serum + ST11-DSM 10 3.5 70 15 4.63 4.1 25247 serum + ST12-DSM 60 13.5 90 18.5 4.62 4.1 25282 - 2, Shown below are the analytic data found for a finished product in tablet form (tablets 1 to 8), based on identical mixtures which differed only in the gum used. Tara gum was used for tablets 1, 3, 5 and 7, whereas guar gum was used for tablets 2, 4, 6 and 8, the other ingredients and concentrations being equal.
- The above-mentioned tablets were prepared in an identical manner, using the same ingredients and the bacterial strains specified below.
- Tablet 1: strain ST10-DSM 25246, excipients and tars gum.
Tablet 2: strain ST10-DSM 25246, excipients and guar gum.
Tablet 3: strain ST10-DSM 25246: and strain YO4-DSM 16592, excipients and tara gum.
Tablet 4: strain ST10-DSM 25246 and strain YO4-DSM 16592, excipients and guar gum.
Tablet 5: strain ST10-DSM 25246 and strain YO2-DSM 16590, excipients and tara gum.
Tablet 6: strain ST10-DSM 25246 and strain YO2-DSM 16590, excipients and guar gum.
Tablet 7: strain ST10-DSM 25246 and strain YO8-DSM 17843, excipients and tara gum.
Tablet 8: strain ST10-DSM 25246 and strain YO8-DSM 17843, excipients and guar gum. - Compression tests were performed on the mixtures and the bacterial count was subsequently determined to evaluate the stress and mortality caused when forming the tablets.
-
Tablet Compression force Hardness CFU/g 1 (tara gum) 26 KN 6-7 kp 1.6 × 109 22 KN 4-6 kp 1.9 × 109 2 (guar gum) 22 KN 7-8 kp 0.9 × 109 3(tara gum) 26 KN 6-7 kp 1.7 × 109 22 KN 4-6 kp 2.0 × 109 4(guar gum) 22 KN 7-8 kp 1.1 × 109 5(tara gum) 26 KN 6-7 kp 1.7 × 109 22 KN 4-6 kp 2.1 × 109 6(guar gum) 22 KN 7-8 kp 1.0 × 109 7(tara gum) 26 KN 6-7 kp 1.6 × 109 22 KN 4-6 kp 1.9 × 109 8(guar gum) 22 KN 7-8 kp 0.9 × 109 - As can be observed, a higher count is obtained with tare gum than with guar gum under the same compression force of 22 KN; even when the compression force on the tare gum mixture is increased to 26 KN, the count obtained is nonetheless higher than the one obtained for the same mixture with guar gum.
Claims (13)
1.-15. (canceled)
16. A composition comprising
a mucoadherent gelling complex composed of
at least one exopolysaccharides-producing bacterial strain, in combination with a vegetable gum, an animal gelatin, and/or a vegetable gelatin,
the at least one exopolysaccharides-producing bacterial strain capable of producing exopolysaccharides in situ in a gastrointestinal tract of a subject to protect an intestinal mucosa from pathogenic bacteria.
17. The composition of claim 16 , wherein the at least one exopolysaccharide-producing bacterial strain is a mixture of bacteria selected from the group of bacteria belonging to the species Lactobacillus plantarum and/or Lactobacillus rhamnosus and/or Streptococcus thermophilus.
18. The composition of claim 16 , wherein the composition comprises at least one bacterial strain selected from the group consisting of:
Streptococcus thermophilus DSM 16590 (YO2), deposited with the depositary institution DSMZ in Germany on 20 Jul. 2004,
Streptococcus thermophilus DSM 16592 (YO4), deposited with the depositary institution DSMZ in Germany on 20 Jul. 2004,
Streptococcus thermophilus DSM 17843 (YO8), deposited with the depositary institution DSMZ in Germany on 21 Dec. 2005,
Streptococcus thermophilus DSM 25246 (ST10), deposited with the depositary institution DSMZ in Germany on 19 Sep. 2011,
Streptococcus thermophilus DSM 25247 (ST11), deposited with the depositary institution DSMZ in Germany on 19 Sep. 2011, and
Streptococcus thermophilus DSM 25282 (ST12), deposited with the depositary institution DSMZ in Germany on 19 Sep. 2011.
19. The composition of claim 18 , wherein the composition further comprises bacterial strains of Lactobacillus plantarum and/or Lactobacillus rhamnosus capable of producing exopolysaccharides in situ in the gastrointestinal tract of a subject to protect the intestinal mucosa from the action of pathogenic bacteria.
20. The composition of claim 16 , wherein the vegetable gum and/or vegetable gelatin is Aloe vera or Aloe arborescens.
21. The composition of claim 16 , wherein the vegetable gum and/or vegetable gelatin is an alginate or tara gum.
22. The composition of claim 16 , wherein the vegetable gum and/or vegetable gelatin is a xyloglucan or xylogel.
23. The composition of claim 16 , wherein the at least one exopolysaccharides-producing bacterial strain comprises at least one Streptococcus thermophilus strain selected from the group consisting of Streptococcus thermophilus DSM 16590 (YO2), Streptococcus thermophilus DSM 16592 (YO4), Streptococcus thermophilus DSM 17843 (YO8) and Streptococcus thermophilus DSM 25246 (ST10), and
the vegetable gum, the animal gelatin, and/or vegetable gelatin is selected from the group consisting of Aloe arborescens, gelatine tannate and tara gum.
24. The composition of claim 1, wherein the mucoadherent gelling complex comprises:
Streptococcus thermophilus DSM 25246 (ST10) in combination with a vegetable gum and/or a vegetable gelatin selected from the group consisting of Aloe arborescens and tara gum.
25. The composition of claim 1, wherein the mucoadherent gelling complex comprises:
Streptococcus thermophilus DSM 25246 (ST10) and at least one strain selected from the group consisting of Streptococcus thermophilus DSM 16590 (YO2), Streptococcus thermophilus DSM 16592 (YO4) and Streptococcus thermophilus DSM 17843 (YO8) in combination with a vegetable gum and/or a vegetable gelatin selected from the group consisting of Aloe arborescens and tara gum.
26. The composition of claim 1, wherein the mucoadherent gelling complex comprises:
Streptococcus thermophilus DSM 25246 (ST10) and Streptococcus thermophilus DSM 16592 (YO4) in combination with a vegetable gum and/or a vegetable gelatin selected from the group consisting of Aloe arborescens and tara gum.
27. The composition of claim 24 , where the vegetable gum and/or vegetable gelatin is tara gum.
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US15/848,812 US20180133268A1 (en) | 2012-07-30 | 2017-12-20 | Compositions for a medical device comprising exopolysaccharide-producing bacterial strains in association with gums and/or gelatines |
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ITMI2012A001328 | 2012-07-30 | ||
IT001328A ITMI20121328A1 (en) | 2012-07-30 | 2012-07-30 | COMPOSITION FOR MEDICAL DEVICE INCLUDING BACTERIA STRAINS PRODUCERS OF ESOPOLISACCHARIDES IN ASSOCIATION WITH GUMS AND / OR GELATINS. |
PCT/IB2013/001668 WO2014020408A1 (en) | 2012-07-30 | 2013-07-30 | Compositions for a medical device comprising exopolysaccharide-producing bacterial strains in association with gums and/or gelatines |
US201514417768A | 2015-01-27 | 2015-01-27 | |
US15/848,812 US20180133268A1 (en) | 2012-07-30 | 2017-12-20 | Compositions for a medical device comprising exopolysaccharide-producing bacterial strains in association with gums and/or gelatines |
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US14/417,768 Division US9889166B2 (en) | 2012-07-30 | 2013-07-30 | Treating low production of mucus in the gastrointestinal tract with S. thermophilus |
PCT/IB2013/001668 Division WO2014020408A1 (en) | 2012-07-30 | 2013-07-30 | Compositions for a medical device comprising exopolysaccharide-producing bacterial strains in association with gums and/or gelatines |
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US20180133268A1 true US20180133268A1 (en) | 2018-05-17 |
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US14/417,768 Expired - Fee Related US9889166B2 (en) | 2012-07-30 | 2013-07-30 | Treating low production of mucus in the gastrointestinal tract with S. thermophilus |
US15/848,812 Abandoned US20180133268A1 (en) | 2012-07-30 | 2017-12-20 | Compositions for a medical device comprising exopolysaccharide-producing bacterial strains in association with gums and/or gelatines |
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ITMI20121328A1 (en) | 2012-07-30 | 2014-01-31 | Probiotical Spa | COMPOSITION FOR MEDICAL DEVICE INCLUDING BACTERIA STRAINS PRODUCERS OF ESOPOLISACCHARIDES IN ASSOCIATION WITH GUMS AND / OR GELATINS. |
US20170027980A1 (en) | 2014-04-15 | 2017-02-02 | Novintethical Pharma Sa | Composition based on xyloglucan and proteins for the treatment of intestinal disorders |
CA2946464A1 (en) | 2014-05-05 | 2015-11-12 | Giovanni Mogna | Adjunctive therapy to chemotherapy treatments for tumors, acquired immunodeficiency syndrome and leukemias |
RU2730005C2 (en) * | 2014-11-26 | 2020-08-14 | Пробиотикал С.П.А | Strains of lactobacillus or bifidobacterium to maintain homeostasis |
ITUB20155700A1 (en) * | 2015-11-18 | 2017-05-18 | Probiotical Spa | Compositions with synergistic action between a mucus-adherent gelling complex against the passage of antigens, and anti-IL17 immunomodulating bacteria for use in the treatment of dependent autoimmune and neurodegenerative diseases IL17. |
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JP2002204669A (en) * | 2001-01-11 | 2002-07-23 | Toyo Shinyaku:Kk | Constipation ameliorative food containing kale processed product |
WO2005060937A1 (en) * | 2003-12-23 | 2005-07-07 | Chr. Hansen A/S | Compressed tablets comprising viable probiotic microorganisms |
JP2009511041A (en) | 2005-10-11 | 2009-03-19 | アニドラル エス.アール.エル. | Production method and use of non-allergenic probiotic bacteria medium |
CA2654457A1 (en) * | 2006-06-06 | 2007-12-13 | Mcgill University | Fermented milk product and use thereof |
CN101611738A (en) * | 2008-06-26 | 2009-12-30 | 遵义市乳制品有限公司 | Bifidobacterium multi-probiotics multi-functional yoghurt |
FI122247B (en) * | 2009-08-12 | 2011-10-31 | Vetcare Oy | Probiotic preparation for the prevention or treatment of dogs gastrointestinal disorders |
CN102100252A (en) * | 2009-12-18 | 2011-06-22 | 光明乳业股份有限公司 | Fermented dairy product and preparation method and raw material composition thereof, lactobacillus plantarum application |
CN101773221B (en) * | 2010-01-21 | 2012-07-25 | 蜡笔小新(天津)有限公司 | Synbiotics fruit jelly and production method thereof |
MY149012A (en) * | 2010-03-29 | 2013-06-28 | Univ Putra Malaysia | Bioencapsule and method thereof |
ES2350436B1 (en) * | 2010-07-21 | 2011-11-28 | Fundacion Leia, C.D.T. | MICROENCAPSULATED SYMBIOTIC MATERIAL |
ITMI20110934A1 (en) * | 2011-05-24 | 2012-11-25 | Cohen Miguel Angel Alonso | GELATINE TANNATE AND ITS ASSOCIATIONS FOR USE IN THE TREATMENT OF GASTROINTESTINAL INFLAMMATORY DISEASES |
CN102283334A (en) * | 2011-08-31 | 2011-12-21 | 西华大学 | Complex probiotic microcapsule capable of improving intestinal tract micro-ecology of small-sized dogs |
ITRM20110477A1 (en) * | 2011-09-09 | 2013-03-10 | Giovanni Mogna | COMPOSITION INCLUDING N-ACETYLCISTEIN AND / OR LYSOZYME MICROINCAPSULATE GASTROPROTECT IN ASSOCIATION WITH PROBIOTIC BACTERES ABLE TO RESTORE THE BARRIER EFFECT OF THE STOMACH THAT IS LOST DURING THE PHARMACOLOGICAL TREATMENT OF |
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PL2879685T3 (en) | 2018-03-30 |
WO2014020408A1 (en) | 2014-02-06 |
US20150202239A1 (en) | 2015-07-23 |
DK2879685T3 (en) | 2017-12-11 |
CA2879014A1 (en) | 2014-02-06 |
RU2646486C2 (en) | 2018-03-05 |
IN2015MN00094A (en) | 2015-10-16 |
EP2879685B1 (en) | 2017-09-20 |
CN104540512A (en) | 2015-04-22 |
RU2015104728A (en) | 2016-09-20 |
US9889166B2 (en) | 2018-02-13 |
BR112015002054A2 (en) | 2017-07-04 |
KR20150038435A (en) | 2015-04-08 |
ES2650455T3 (en) | 2018-01-18 |
EP2879685A1 (en) | 2015-06-10 |
PT2879685T (en) | 2017-12-12 |
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