WO2016205394A1 - Mélanges probiotiques multi-souches pour le traitement de troubles gastro-intestinaux et l'amélioration ou l'entretien de la santé gastro-intestinale - Google Patents

Mélanges probiotiques multi-souches pour le traitement de troubles gastro-intestinaux et l'amélioration ou l'entretien de la santé gastro-intestinale Download PDF

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WO2016205394A1
WO2016205394A1 PCT/US2016/037664 US2016037664W WO2016205394A1 WO 2016205394 A1 WO2016205394 A1 WO 2016205394A1 US 2016037664 W US2016037664 W US 2016037664W WO 2016205394 A1 WO2016205394 A1 WO 2016205394A1
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dosage
probiotic
cfu
billion cfu
probiotics
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Dr. Neil ROSS
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Amnat Global Llc
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    • A—HUMAN NECESSITIES
    • 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
    • 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
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/733—Fructosans, e.g. inulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/742—Spore-forming bacteria, e.g. Bacillus coagulans, Bacillus subtilis, clostridium or Lactobacillus sporogenes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • 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

Definitions

  • probiotic and prebiotic blends are provided that allow survival through the GI tract and provide desired physiological results.
  • the probiotic blends may be used to treat one or more conditions in humans and animals.
  • probiotics may exert positive influence on the host through modulation of the endogenous ecosystem and stimulation of immune system as well as maintaining a healthy intestinal microflora.
  • health benefits are strain specific and vary by amount ingested and duration administered.
  • probiotic applications are limited because these bacteria are likely to be in a stressed state when they reach the colon due to exposure to diverse barriers in the host such as gastric acid and bile acids.
  • Commercial probiotics should be able to recover and compete with established microflora in the colon to provide colonization and benefits for the host, but such products can often fail to achieve the desired benefits.
  • One or more probiotic and prebiotic blends are provided that allow survival through the human gastrointestinal (GI) tract and provide desired physiological results and/or improvements in the host individual.
  • One or more embodiments in accordance with the present invention demonstrate that a unique blend of prebiotic with specific probiotic strain blends can survive the GI tract and deliver the physiological effects desired per each blend, for example to treat conditions selected from irritable bowel syndrome (IBS), diarrhea, and constipation.
  • IBS irritable bowel syndrome
  • a process is provided to determine in vitro functionality of probiotics and prebiotics for modeling survival in the human GI tract.
  • an in vitro simulation of a human gastrointestinal tract includes an oral cavity simulation.
  • the processes may be adapted for use based on the age of the human subject.
  • Certain probiotic formulations may be selected for use based in part on the age of the human subject.
  • an in vitro simulation of an animal gastrointestinal tract includes an oral cavity simulation.
  • a method of treating an individual for a condition selected from the group consisting of irritable bowel syndrome (IBS), diarrhea, constipation, bowel irregularity, allergic reactions, dermatitis, and reactions to antibiotic treatment comprising the step of administering to the individual in need of such treatment a probiotic composition, and optionally a prebiotic.
  • the probiotic composition may include a blend of at least two bacterial strains selected from the group consisting of Lactobacillus plantarum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus rhamnosus, Lactobacillus acidophilus, and Bacillus coagulans.
  • FIG. 1 depicts Trial #1 of one embodiment of an in vitro method.
  • the Flow chart provided shows the study design and transport through the various stages of digestion in the human gastrointestinal (GI) tract and the conditions and materials used to simulate in vitro the in vivo conditions.
  • GI human gastrointestinal
  • FIG. 2 in Table 1 depicts initial results in Trial #1 demonstrating survival of probiotic blends through a simulated human gastrointestinal tract (viability expressed in CFU/g).
  • the top portion of the table lists for each product: for each component strain the potency/dose (CFU) and the total bacteria (CFU) per product dose.
  • FIG. 3 depicts Trial #2 of another embodiment of an in vitro method.
  • the Flow chart provided shows the study design and transport through the various stages of digestion in the human gastrointestinal (GI) tract and the conditions and materials used to simulate in vitro the in vivo conditions.
  • GI human gastrointestinal
  • FIG. 4A in Table 2 depicts final results in Trial #2 demonstrating survival of probiotic blends through a simulated human gastrointestinal tract (viability expressed in CFU/g).
  • the top portion of the table lists for each product: for each component strain the potency/dose (CFU) and the total bacteria (CFU) per product dose. NT not tested.
  • FIG. 4B in Table 2 depicts final results in Trial #2 demonstrating survival of probiotic blends through a simulated human gastrointestinal tract (viability expressed in CFU/g).
  • FIG. 5 depicts total probiotic blend strain survival (total CFU) as a function of time during the stomach and intestinal simulation, respectively in an adolescent/pre-teen model. This generally demonstrates survival of probiotic blends through a simulated preteen GI tract.
  • FIG. 6 in Table 3 depicts final results in Trial #4 demonstrating survival of probiotic blends through a simulated canine (dog) gastrointestinal tract (viability expressed in CFU/g).
  • FIG. 7 depicts total probiotic blend strain survival (total CFU) as a function of time during the stomach and intestinal simulation, respectively in an older adult / senior model. This generally demonstrates survival of probiotic blends through a simulated aged adult / senior GI tract.
  • FIG. 8 in Table 4 depicts final results in Trial #5 demonstrating survival of probiotic blends through a simulated aged adult/ senior gastrointestinal tract (viability expressed in CFU/g).
  • a unique blend of prebiotic with specific probiotic strain blends is described herein which can survive the GI tract and deliver the physiological effects desired per each blend.
  • the present disclosure provides unique blends of prebiotic or probiotic products for children, adults, or domesticated pet animals, respectively, having specific probiotic strain blends that can survive the GI tract and deliver the physiological effects desired per each blend which are geared toward each subject group.
  • GI tract refers to the gastrointestinal tract or pathway in an individual including human, mammal, or domesticated animal.
  • the GI tract incudes at least the stomach and small intestine, and for test purposes can include the alimentary canal. Passage or transit through or residence in the GI tract is understood to proceed starting from the mouth (via chewing, mastication, liquid delivery, or swallowing, for example) and followed by ingestion to the stomach, then proceeding to the intestines. Colonization, growth, and maintenance of probiotic bacteria can occur in the GI tract, particularly in the intestines.
  • Useful bacterial strains for probiotic compositions can include, but are not limited to: Lactobacillus plantarum, Bifidobacterium bifidum, Bifidobacterium lactis, Lactobacillus rhamnosus, Lactobacillus acidophilus, Bacillus coagulans, and the like.
  • the term "multistrain” refers to a blend of two or more strains of viable bacterial species.
  • probiotic refers to viable microorganisms that promote or support a beneficial balance of the autochthonous microbial population of the gut.
  • Probiotics are defined as "live microorganisms that may confer a health benefit on the host.” These bacterial strains (e.g. multistrains) are becoming extremely popular, not only in alternative circles, but also within the scientific community.
  • Bots have discovered that the microbes that live within animal intestines are important to their health. Animal and human species host at least 1000 different species of bacteria and fungi, and maintaining the right populations of each species is essential. Therefore, maintaining intestinal flora with probiotics is a logical step.
  • Metchnikoff Nobel laureate who associated longevity with the consumption of fermented milk products. He postulated that the bacillus present could positively modify the bacterial community structure of the colon, thus contributing to human health status. While not intending to be bound by any theory, the present disclosure is in general agreement with the current understanding of probiotics as used in foods and nutritional/dietary supplements for animals and humans.
  • the microbial population of the intestine is a highly dynamic and complex ecosystem having an estimated 10 14 microorganisms representing more than 400 bacterial species. It has many functions in humans providing enzymes necessary for assimilation and/or synthesis of some nutrients, as well as in detoxifying certain harmful dietary compounds.
  • the gastrointestinal flora provides a natural barrier against pathogens and can stimulate bowel motility and the immune system.
  • Probiotic formulations and blends should be able to recover and compete with established microflora in the colon to provide colonization and benefits for the host. For this purpose, they can use help from prebiotics such as inulin.
  • the gut microbiome influences myriad host functions, including nutrient acquisition, immune modulation, brain development, and behavior. Although human gut microbiota are recognized to change as we age, information regarding the structure and function of the gut microbiome during childhood is limited.
  • the most commonly used strains of probiotics belong to the genera Lactobacillus and Bifidobacterium, L. rhamnosus GG, Saccharomyces boulardii, Bacillus clausii, mix of L. delbrueckii var bulgaricus, Streptococcus thermophilus, L. acidophilus, and Bifidobacterium bifidum, or Enterococcus faecium SF 68. Median duration of diarrhoea was significantly shorter and frequency was lower only in those children who received mixes of four bacterial strains.
  • Probiotics have recognized utility to mitigate the diarrheal side effects of antibiotics and to reduce the incidence of Clostridum difficile- associated colitis (Hickson, et al., "Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial,” BMJ 335(7610), 80 (2007); and Surawicz CM., "Role of probiotics in antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, and recurrent Clostridium difficile- associated diarrhea," J. Clin. Gastroenterol. 42(Suppl. 2), S64-S70 (2008)). Lifting the burden of infectious disease would be particularly beneficial in older populations.
  • Pet animals may include small or large domestic mammals, for example, but not limited to, dogs, cats, horses, sheep, cows or cattle (or other bovine species), horses, pigs, goats, rabbits, and the like. Also contemplated are small rodent species, including rats, mice, hamsters, gerbils, guinea pigs, and the like.
  • All dogs can benefit from probiotics, which aid digestion and modulate the immune system.
  • Probiotics produce short-chain fatty acids (SCFAs), which inhibit the growth and activity of harmful bacteria, such as E.
  • SCFAs short-chain fatty acids
  • Acute diarrhea in dogs is diarrhea that starts suddenly and usually resolves on its own.
  • Probiotics have been tested on several types of acute diarrhea, specifically diarrhea caused by dietary sensitivity and through the ingestion of an intestinal pathogen.
  • Treatment with Lactobacillus acidophilus in combination with the diarrhea-provoking food led to some improvement in bowel movements.
  • probiotics were applied as treatments for acute diarrhea caused by a stomach virus.
  • Dogs treated with a probiotic cocktail containing multiple species healed more quickly than dogs given a placebo.
  • Probiotic species known to benefit dogs include Bacillus coagulans.
  • Lactobacillus acidophilus improved frequency and quality of stools in sensitive dogs.
  • Lactobacillus rhamnosus strain GG (LGG) is effective in preventing and treating diarrhea in humans, and may benefit dogs as well.
  • Bifidobacterium animalis has been studied more in detail. It was chosen for further research because initial studies showed that it had an above-average ability to bind to the gut, a characteristic often associated with beneficial bacteria. Initial studies in dogs showed that it could reduce the pathogenicity of Salmonella typhiurium and Clostridia difficile; bacteria known to induce acute diarrhea. And later during a treatment study, it was found that it could help acute diarrhea resolve faster.
  • Dermatitis usually caused by a skin allergy.
  • To treat the dermatitis one needs to address the underlying immune problems.
  • the immune system considers a normally harmless substance as a threat.
  • contact of the allergen on the skin causes an immune reaction leading to the classic symptoms of inflammation: itching, redness and heat.
  • dogs that develop allergy are usually genetically predisposed to the condition. This means that prevention has to happen at a young age or even when the pups are still in the womb.
  • Probiotics are measured by colony forming units (CFUs). Few studies have been done to determine effective dosages, but these numbers are usually in the hundreds of millions or higher. If probiotics are being used to help with digestion, they should be taken with meals, but otherwise they may survive better if given between meals, particularly if taken with liquid that helps to dilute stomach acid and move them more quickly into the digestive tract (for example, given after the dog takes a big drink). Probiotics may be given short-term or long-term.
  • probiotics may exert positive influence on the host through modulation of the endogenous ecosystem and stimulation of immune system as well as maintaining a healthy intestinal microflora.
  • health benefits can be strain specific and vary by amount ingested and duration administered, even in pets.
  • probiotics can survive in vitro techniques, however, all studies do not include food as part of the system, or oral cavity saliva as part of the testing to show survival. As shown herein a unique combination of probiotic and prebiotic products can enhance survival to the lower intestine, first through in vitro testing, and then also by human clinical testing.
  • PROBIOTIC BLEND #5 i.e., LACTOBACILLUS PLANTARUM and
  • PROBIOTIC BLEND #7 i.e., LACTOBACILLUS RHAMNOSUS, BIFIDOBACTERIUM BIFIDUM, and LACTOBACILLUS ACIDOPHILUS (Nebraska Cultures) 10,000,000,000 cfu/gm
  • PRODURA i.e., BACILLUS COAGULANS (Nebraska Cultures) 15,000,000,000 cfu/gm
  • probiotics and inulin were added to 15cc of the simulated saliva, one dose of each probiotic per three samples. To this was added 2gm of amylase based on literature of content in saliva and incubated for 2 min at 37°C. Pull 1 ml sample of each and plate for total plate count concentration, calculate and document.
  • the samples are subsequently added to three by 300cc of simulated gastric fluid and pepsin at 3.99gm and mixed. 1 ml Samples are to be pulled at 0, 60, 90 and 120 minutes as per gastric emptying timing in the literature and these were plated to determine CFU/gm surviving this artificial stomach environment. The solution is to be tested every 10 minutes for pH and maintained at 2.5pH using NaOH or HC1, depending on the need.
  • the stomach simulation step solution is to be brought to intestinal pH using NaOH (pH 7.8). Also added were 0.5% bile salts (Oxgall) (estimated at 1 gm) and 0.1% pancreatin (estimated at 3.99gm). One milliliter samples were again removed after the time frame above (0, 8,12,24,36 hrs).
  • Lactobacillus Acidophilus DDS-1 (420.000 mg);
  • Probiotic Blend #7 1500.000 mg, i.e., 300 mg each strain
  • TRAVELER'S RELIEF / TRAVELER'S SUPPORT (diarrhea):
  • Lactobacillus Acidophilus DDS-1 (140.000 mg);
  • Probiotic Blend #5 495.000 mg, i.e., 450 mg Bifidobacterium bifidum, 45 mg
  • probiotics and inulin were added to 15cc of the simulated saliva, one dose of each probiotic per three samples. To this was added 2gm of amylase based on literature of content in saliva and incubated for 2 min at 37°C. Pull 1 ml sample of each and plate for total plate count concentration, calculate and document.
  • the stomach simulation step solution is to be pH adjusted to pH 7.8 using NaOH. Also added were 0.5% bile salts (Oxgall) (estimated at 1 gm) and 0.1% pancreatin (estimated at 3.99gm), as above. One milliliter samples were again removed after the time frame above (0, 8,12,24,36 hrs).
  • probiotic blends described herein may further contain Saccharomyses boulardii.
  • a safe and effective pharmaceutical or nutraceutical composition has been provided containing one or more probiotic bacterial strains as described.
  • a method of treating an individual for a condition selected from the group consisting of irritable bowel syndrome (IBS), diarrhea, constipation, bowel irregularity, and reactions to antibiotic treatment comprises the step of administering to the individual in need of such treatment a probiotic nutritional composition, and optionally a pharmaceutically or nutraceutically acceptable carrier, such as, for example a prebiotic.
  • the dosages of the probiotics are expected to be particularly effective when used in certain combinations, or as a blend. It is expected that certain probiotic (or prebiotic) blends containing bacterial strains will provide synergistic effects with regard to treating or preventing irritable bowel syndrome (IBS), diarrhea, constipation, bowel irregularity, reactions to antibiotic treatment, and the like.
  • the dosage range for certain probiotic compositions can range from about 200 Million CFU per dose to about 100 Billion CFU per dose. In one preferred embodiment, the probiotic products are to range from no less about than 200 Million CFU per dose to no more than about 100 Billion CFU per dose.
  • BIFIDOBACTERIUM BIFIDUM (ATCC 29521); dose: 2,500,000,000 CFU [00114] LACTOBACILLUS RHAMNOSUS (ATCC 393); dose: 3,000,000,000 CFU [00115] PRODURA, i.e., BACILLUS COAGULANS (B-3208); dose: 500,000,000 CFU [00116] SIMULATED SALIVA PICKERING CHEMICALS 1700-0302 Lot 502036 [00117] SIMULATED GASTRIC FLUID SIGMA CHEMICALS Fluka Lot BCBN3288V
  • America's Naturals LLC line to support the hypothesis that exogenously administered probiotics (Specific blends from America's Naturals as described herein) may survive their passage through the adolescent stomach and the small intestine and affect bacterial ecology and metabolism in the large intestine and colon.
  • An important aspect of this issue is to examine the various determinants and factors that allow for probiotic passage through the adolescent gut and enhancement of their metabolic activity.
  • Inulin derived from Agave, Fructooligosaccharide (FOS) and soluble Maltodextrin (Fibersol 2®) which have been shown to enhance the metabolic activity of probiotics, will also be used. Diet and specific nutritional factors have been shown to shape intestinal microflora and influence health thus standard diet conditions for and materials for children were used in the experimentation.
  • Bile dilutions were used to try and mimic normal bile addition to the intestine.
  • Step 1 measure out 15cc simulated saliva add 2 gm amylase mix for 5 minutes at 34 °C;
  • Step 2. weigh out inulin listed per each formulation blend and add to saliva and mix for 5 minutes;
  • Step 3 weigh out probiotic blends required per formulations, keep at 4 °C;
  • Step 4. add probiotic blends to saliva mixes and label by blend and mix for 2 minutes;
  • Step 5 pull 1 ml sample from mix plate on msg plate incubate at 34 °C for 2 hours, calculate cfu/gm anerobic; [00155] Step 6. measure out 250 cc simulated gastric fluid for each saliva mix, add pepsin (10.3 mg/ liter) to each mix slowly at 37 °C for 2 hours, pulling 1 ml samples of each at 30, 60. 90 minutes, test for cfu/gm as before, adjust pH with HC1 or NaOH, and take to/keep at pH 3.6;
  • Step 7 create simulated intestinal juice, add 0.1% pancreatin and 0.5% bile salts the gastric mix, maintain pH at 6.8 with HC1 or NaOHand keep at 37 °C; and
  • Step 8 pull samples of mixes at 8 hr., 12 hr., 24 hr. times and test cfu/gm of each at each time point.
  • probiotics and inulin were added to 15 cc of the simulated saliva, one dose of each probiotic per three samples. To this was added 2 gm of amylase based on literature of content in saliva and incubated for 2 min at 37 °C. 1 ml samples of each were pulled and tested for total plate count concentration, calculate and document.
  • the stomach simulation step solution was pH adjusted to pH 6.8 using NaOH. Also added were 0.5% bile salts (Oxgall) (estimated at 1 gm) and 0.1% pancreatin (estimated at 2.99gm). One ml samples were again removed after the time frame (8, 12, 24 hrs).
  • the initial concept was to filter the stomach solution through a 0.45-micron filter to collect the solid mater and move to simulated Intestinal fluid, however this was not practical and did not function.
  • the stomach solution was modified to intestinal fluid by addition of the enzymes and base to move the pH to 7.8. This is actually more realistic as what happens in the GI tract as the food moves down the system.
  • Amylase and oral conditions were considered relevant and the data shows it is relevant on the amount of probiotic that reaches the stomach.
  • Figure 5 depicts results of the data.
  • the total probiotics present in the final volume should be compared to the initial input content that was tested and it should be confirmed how many total CFU survived from input to the end time point. These results demonstrated the survival rate of probiotics in this test system. Compare also the results shown in Fig. 4 A (Table 2).
  • Figure 5 depicts the probiotic formulation kids Probiotic to survive the testing with a final total CFU in the solution of 9.25 x 10 9 CFU present from an initial input of 1.0 x 10 10 CFU, which is more than sufficient for colonization.
  • PRODURA i.e., BACILLUS COAGULANS (ARS #B3208); dose: 1,000,000,000 CFU
  • the aim of this study is to provide a test in support that Probiotics from America's Naturals line to support the hypothesis that exogenously administered probiotics (Specific blends from America's Naturals) may survive their passage through the stomach and the small intestine of a dog and affect bacterial ecology and metabolism in the large intestine and colon.
  • An important aspect of this issue is to examine the various determinants and factors that allow for probiotic passage through the gut and enhancement of their metabolic activity.
  • the effect of Maltodextrin (Fibersol2®) which has been shown to enhance the metabolic activity of probiotics, will also be used. Diet and specific nutritional factors have been shown to shape intestinal microflora and influence health thus standard diet conditions and materials were used in the experimentation.
  • Oral Cavity time 2 minutes' maximum with artificial saliva, Temperature 37 °C, pH 7.
  • Bile dilutions were used to try and mimic normal bile addition to the intestine.
  • the samples are subsequently added to three by 300 cc of simulated gastric fluid and pepsin at 3.99 gm and mixed. 1 ml Samples were pulled at 30, 60 and 90 minutes as per gastric emptying timing in the literature and these were plated to determine CFU/gm surviving this artificial stomach environment. The solution is to be tested every 10 minutes for pH and maintained at 1.8 pH using NaOH or HC1, depending on the need.
  • the stomach simulation step solution was pH adjusted to pH 6.7 using NaOH. Also added were 0.2% bile salts (Oxgall) (estimated at .3 gm) and 0.1% pancreatin (estimated at 2.5gm).
  • bile salts Oxgall
  • pancreatin estimated at 2.5gm
  • Amylase and oral conditions were considered relevant and the data shows it is relevant on the amount of probiotic that reaches the stomach; however, dogs and cats have no amylase, and only recently have domestic dogs shown the amylase gene, but at low levels.
  • America's Naturals LLC products (Branded as Family Flora Pet Balance) recovered and colonized the system at the end of the experiment as expected. This is what needs to happen for probiotics to survive to the lower GI tract in dogs.
  • Materials for In- Vitro Methods in Older Adults/ Seniors (Trial #5):
  • BIFIDOBACTERIUM BIFIDUM ATCC 29521
  • LACTOBACILLUS RHAMNOSUS ATCC 393
  • PRODURA i.e., BACILLUS COAGULANS (B-3208)
  • dose: 900,000,000 CFU [00238] L. PLANTARUM (LP-115 (400B)); dose: 900,000,000 CFU
  • the aim of this study is to provide an in vitro test using Probiotics from the America's Naturals LLC line to support the hypothesis that exogenously administered probiotics (Specific blends from America's Naturals as described herein) may survive their passage through the older adult/senior stomach and the small intestine and affect bacterial ecology and metabolism in the large intestine and colon.
  • An important aspect of this issue is to examine the various determinants and factors that allow for probiotic passage through the senior gut and enhancement of their metabolic activity.
  • the effect of Inulin derived from Agave which has been shown to enhance the metabolic activity of probiotics, will also be used. Diet and specific nutritional factors have been shown to shape intestinal microflora and influence health thus standard diet conditions for and materials for seniors were used in the experimentation.
  • Oral Cavity time 2 minutes' maximum with artificial saliva, Temperature 37 °C, pH 7.
  • Bile dilutions were used to try and mimic normal bile addition to the intestine.
  • Step 2. weigh out inulin listed per each formulation blend and add to saliva and mix for 5 minutes;
  • Step 3 weigh out probiotic blends required per formulations, keep at 4 °C;
  • Step 4. add probiotic blends to saliva mixes and label by blend and mix for 2 minutes;
  • Step 5 pull 1 ml sample from mix plate on msg plate incubate at 34 °C for 2 hours, calculate cfu/gm anerobic;
  • Step 6 measure out 250 cc simulated gastric fluid for each saliva mix, add pepsin (10.3 mg/ liter) to each mix slowly at 37 °C for 2 hours, pulling 1 ml samples of each at 30, 60. 90 minutes, test for cfu/gm as before, adjust pH with HC1 or NaOH, and take to/keep at H 3.6;
  • Step 7 create simulated intestinal juice, add 0.1% pancreatin and 0.5% bile salts the gastric mix, maintain pH at 6.8 with HC1 or NaOH and keep at 37 °C; and
  • Step 8 pull samples of mixes at 8 hi-., 12 hr., 24 hr. times and test cfu gm of each at each time point.
  • probiotics and inulin were added to 15 cc of the simulated saliva, one dose of each probiotic per three samples. To this was added 2 gm of amylase based on literature of content in saliva and incubated for 2 min at 37 °C. 1 ml samples of each were pulled and tested for total plate count concentration, calculate and document.
  • the stomach simulation step solution was pH adjusted to pH 6.8 using NaOH. Also added were 0.5% bile salts (Oxgall) (estimated at 1 gm) and 0.1% pancreatin (estimated at 3.99 gm). One ml samples were again removed after the time frame (8, 12, 24, 36 hrs).
  • Amylase and oral conditions were considered relevant and the data shows it is relevant on the amount of probiotic that reaches the stomach.
  • Amylase is left in the stomach fluid section as it is in normal humans.
  • Figure 7 depicts results of the data.
  • the total probiotics present in the final volume should be compared to the initial input content that was tested and it should be confirmed how many total CFU survived from input to the end time point. These results demonstrated the survival rate of probiotics in this test system. Compare also the results shown in Fig. 8 (Table 4).
  • Figure 7 depicts the probiotic formulation Family Flora Daily Balance Senior Probiotic to survive the testing with a final total CFU in the solution of 9 x 10 6 CFU present from an initial input of 1.0 x 10 10 CFU, which is more than sufficient for colonization.
  • the concept of testing probiotics for survival from the mouth to the intestine and colon is not a new concept. This experiment shows that the America's Naturals Senior Probiotic tested (Branded as Family Flora Senior Daily Balance) survived this in vitro test for probiotic survival to the colon and colonization. It appears the prebiotics (Inulin) did support recovery over time in the system, this needs to be further tested to confirm the hypothesis based on this data since two commercial products tested did not demonstrate late stage growth during testing.
  • probiotic (or prebiotic) blends will provide synergistic effects with regard to maintaining or improving gut or GI health.
  • the composition may also include an excipient, most preferably a nutraceutical or pharmaceutical excipient.
  • Compositions containing an excipient and incorporating one or more pribiotics can be prepared by procedures known in the art.
  • the composition can include one or more adjuvants, excipients, carriers, buffers, diluents, and/or other customary pharmaceutical auxiliaries.
  • probiotics can be formulated into tablets, capsules, powders, suspensions, solutions for oral administration and solutions for parenteral administration including intravenous, intradermal, intramuscular, and subcutaneous administration, and into solutions for application onto patches for transdermal application with common and conventional carriers, binders, diluents, and excipients.
  • the nutraceutical compositions of the present invention may be administered in combination with a pharmaceutically acceptable carrier.
  • the active ingredients in such formulations may comprise from 1 % by weight to 99% by weight, or alternatively, 0.1% by weight to 99.9% by weight.
  • “Pharmaceutically acceptable carrier” means any carrier, diluent or excipient that is compatible with ⁇ fhe other ingredients of the formulation and not deleterious to the user.
  • Useful excipients include, but are not limited to, microcrystalline cellulose, magnesium stearate, calcium stearate, any acceptable sugar (e.g., mannitol, xylitol), and the like, and for cosmetic use an oil-base is preferred.
  • Suitable dosage forms include tablets, capsules, solutions, suspensions, powders, gums, and confectionaries.
  • Sublingual delivery systems include, but are not limited to, dissolvable tabs under and on the tongue, liquid drops, and beverages.
  • Edible films, hydrophilic polymers, oral dissolvable films or oral dissolvable strips can be used.
  • Other useful delivery systems comprise oral or nasal sprays or inhalers, and the like.
  • probiotics in combination with a prebiotic may be further combined with one or more solid inactive ingredients for the preparation of tablets, capsules, pills, powders, granules or other suitable dosage forms.
  • the active agent may be combined with at least one excipient such as fillers, binders, humectants, disintegrating agents, solution retarders, absorption accelerators, wetting agents, absorbents, or lubricating agents.
  • excipients include magnesium stearate, calcium stearate, mannitol, xylitol, sweeteners, starch, carboxymethylcellulose, microcrystalline cellulose, silica, gelatin, silicon dioxide, and the like.
  • compositions and unit dosages thereof may thus be placed into the form of pharmaceutical compositions and unit dosages thereof.
  • forms include solids, and in particular tablets, filled capsules, powder and pellet forms, and liquids, in particular aqueous or non-aqueous solutions, suspensions, emulsions, elixirs, and capsules filled with the same, all for oral use, suppositories for rectal administration, and sterile injectable solutions for parenteral use.
  • Such pharmaceutical compositions and unit dosage forms thereof many comprise conventional ingredients in conventional proportions, with or without additional active compounds or principles, and such unit dosage forms may contain any suitable effective amount of the active ingredient commensurate with the intended daily dosage range to be employed.
  • compositions from a chemical compound of the present invention can be either solid or liquid.
  • Solid form preparations include powders, tablets, pills, capsules, cachets, suppositories, and dispersible granules.
  • a solid carrier can be one or more substances which may also act as diluents, flavoring agents, solubilizers, lubricants, suspending agents, binders, preservatives, tablet disintegrating agents, or an encapsulating material.
  • the carrier is a finely divided solid, which is in a mixture with the finely divided active component.
  • the active component is mixed with the carrier having the necessary binding capacity in suitable proportions and compacted in the shape and size desired.
  • the powders and tablets preferably may contain from five or ten to about seventy percent of the active compound.
  • Suitable carriers are magnesium carbonate, magnesium state, talc, sugar, lactose, pectin, dextrin, starch, gelatin, tragacanth, methylcellulose, sodium carboxymethlycellulose, a low melting wax, cocoa butter, and the like.
  • the term "preparation" is intended to include the formulation of the active compound with encapsulating material as carrier providing a capsule in which the active component, with or without additional carriers, is surrounded by a carrier, which is thus in association with it.
  • cachets and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges are included. Tablets, powders, capsules, pills, cachets, and lozenges can be used as solid forms suitable for oral administration.
  • Liquid preparations include solutions, suspensions, and emulsions, for example, water or water-propylene glycol solutions.
  • parenteral injection liquid preparations can be formulated as solutions in aqueous polyethylene glycol solution.
  • the chemical compound according to the present invention may thus be formulated for parenteral administration (e.g., by injection, for example bolus injection or continuous infusion) and may be presented in unit dose for administration in ampoules, pre-filled syringes, small volume infusion or in multi-dose containers with an added preservative.
  • the compositions may take such forms as suspensions, solutions, or emulsions in oily or aqueous vehicles, and may contain formulation agents such as suspending, stabilising and/or dispersing agents.
  • the active ingredient may be in powder form, obtained by aseptic isolation of sterile solid or by lyophilization from solution, for constitution with a suitable vehicle, e.g. sterile, pyrogen- free water, before use.
  • Aqueous solutions suitable for oral use can be prepared by dissolving the active component in water and adding suitable colorants, flavors, stabilizing and thickening agents, as desired.
  • Aqueous suspensions suitable for oral use can be made by dispersing the finely divided active component in water with viscous material, such as natural or synthetic gums, resins, methylcellulose, sodium carboxymethylcellulose, or other well known suspending agents.
  • compositions suitable for topical administration in the mouth includes lozenges comprising the active agent in a flavored base, usually sucrose and acacia or tragacanth; pastilles comprising the active ingredient in an inert base such as gelatin and glycerine or sucrose and acacia; and mouthwashes comprising the active ingredient in suitable liquid carrier.
  • compositions are applied directly to the nasal cavity by conventional means, for example with a dropper, pipette or spray.
  • the compositions may be provided in single or multi-dose form.
  • the compound In compositions intended for administration to the respiratory tract, including intranasal compositions, the compound will generally have a small particle size, for example, of the order of 5 microns or less. Such a particle size may be obtained by means known in the art, for example, by micronization.
  • the pharmaceutical preparations are preferably in unit dosage forms.
  • the preparation is subdivided into unit doses containing appropriate quantities of the active component.
  • the unit dosage form can be a packaged preparation, the package containing discrete quantities of preparation, such as packaged tablets, capsules, and powders in vials or ampoules.
  • the unit dosage form can be a capsule, tablet, cachet, or lozenges itself, or it can be the appropriate number of any of these in packaged form.
  • Tablets,- capsules and lozenges for oral administration and liquids for oral use are preferred compositions. Solutions or suspensions for application to the nasal cavity or to the respiratory tract are preferred compositions. Transdermal patches for topical administration to the epidermis are preferred.
  • the compounds may be administered by any route, including but not limited to oral, sublingual, buccal, ocular, pulmonary, rectal, and parenteral administration, or as an oral or nasal spray (e.g. inhalation of nebulized vapors, droplets, or solid particles).
  • Parenteral administration includes, for example, intravenous, intramuscular, intraarterial, intraperitoneal, intranasal, intravaginal, intravesical (e.g., to the bladder), intradermal, transdermal, topical, or subcutaneous administration.
  • parenteral administration includes, for example, intravenous, intramuscular, intraarterial, intraperitoneal, intranasal, intravaginal, intravesical (e.g., to the bladder), intradermal, transdermal, topical, or subcutaneous administration.
  • Also contemplated within the scope of the invention is the instillation of a pharmaceutical composition in the body of the patient in a controlled formulation, with systemic or local release of the drug to occur at
  • compositions of the invention may be those suitable for oral, rectal, bronchial, nasal, pulmonal, topical (including buccal and sub-lingual), transdermal, vaginal or parenteral (including cutaneous, subcutaneous, intramuscular, intraperitoneal, intravenous, intraarterial, intracerebal, intraocular injection or infusion) administration, or those in a form suitable for administration by inhalation or insufflations, including powders and liquid aerosol administration, or by sustained release systems.
  • sustained release systems include semipermeable matrices of solid hydrophobic polymers containing the compound of the invention, which matrices may be in form of shaped articles, e.g. films or microcapsules.
  • GI gastrointestinal
  • IBS Irritable bowel syndrome
  • IBS is one of the most frequent digestive tract disorders encountered by general practitioners and gastroenterologists.
  • IBS is a functional bowel disorder characterized by chronic and relapsing abdominal pain or discomfort associated with altered bowel habits.
  • the primary aim of any treatment is the relief of abdominal pain which can significantly impair the patient's quality of life.
  • the main treatment options for abdominal pain include anti-spasmodics or anti-depressants at low dose while anti-diarrheal or laxative drugs are given to improve transit disturbances.
  • all these options remain disappointing for the relief of abdominal pain.
  • Thetherapeutic efficacy in IBS is probably impacted by the heterogeneous pathogenesis of the disease which includes altered intestinal motility, visceral hypersensitivity, abnormal brain-gut interactions, food intolerance, altered intestinal permeability and postinfectious and/or inflammatory changes.
  • probiotics which are live microorganisms conferring health benefits to the host when ingested in adequate amounts.
  • Clinical evidence regarding the efficacy of some probiotics trains to improve IBS symptoms has recently emerged, although the mechanism of action of probiotics on IBS symptoms is not completely understood.
  • Some probiotics bind to small and large bowel epithelium and may produce substances with antibiotic properties, while others compete for attachment and thereby reduce invasion by pathogenic organisms.
  • Probiotics also modulate gastrointestinal luminal immunity by changing the cytokine and cellular milieu from a pro-inflammatory to anti-inflammatory state. They may also convert undigested carbohydrates into short chain fatty acids, which act as nutrients for colonocytes and affect gut motility.
  • Multi single-centre studies will be used to test the clinical efficacy of Bifidobacterium Bifidum ATCC 29521 and Lactobacillus plantarum ATCC 8014 along with 3.35gm of Inulin from Agave in IBS patients.
  • Two trials have demonstrated significant benefits in comparison with placebo on improvement of flatulence scores and a reduction of abdominal pain while the results of the third trial, based on only 12 patients, were not conclusive previously with DSM (L. plantarum 299v) (DSM 9843).
  • the aim of the present randomized, double-blind, placebo-controlled clinical trial was to assess the symptomatic efficacy of Lactobacillus plantarum in combination with Bifidobacterium Bifidum and inulin in a larger subset of IBS patients fulfilling the Rome III criteria and will compare to the listed trial. .
  • This study will be designed as a multicentre double blind, placebo-controlled study with parallel groups to assess the beneficial effects of a daily consumption of Colon Support on IBS symptoms. Treatment duration will be 4 wk with 3 follow-up visits at weekly intervals. The study protocol will be conducted in accordance with the Declaration of Helsinki and approved by the local Ethics Committee. All volunteers will be given written informed consent prior to participation in the study.
  • Participants over 200 will be recruited by general practitioners in multiple clinical centers. Subjects between 18-70 years of age with IBS according to the Rome M criteria will be eligible for inclusion. All subjects will receive a colonic examination at baseline to exclude any organic disease while an intestinal infection will be excluded by stool cultures in any patient in whom this diagnosis was suspected. Subjects with severe ⁇ chronic medical disease including colorectal and other gastrointestinal diseases will be excluded. Pregnant and breast-feeding women and patients with dietary habits which might interfere with the assessment of the study product or patients with known allergy to the study product components will also be excluded. Throughout the study, the subjects will not be allowed to consume any other probiotic and will be encouraged not to change their usual dietary and physical exercise habits.
  • the test product will be Colon Support with 15 Billion CFU Bifidobacterium Bifidum ATCC 29521 and 1.5 Billion CFU Lactobacillus plantarum ATCC 8014 along with 3.35gm of Inulin from Agave.
  • the test product contains 16.5 billion colony-forming units (cfu) in sachet form with no other ingredients except the prebiotic Inulin.
  • the control product contains 4gm of maltodextrin. Both the test and control products will have a similar appearance, texture and taste. Both products will be specifically prepared for the study and provided by America's Naturals (Fort Lauderdale, Florida).
  • VAS 1-10 visual analogue scale
  • Acute diarrhea affects millions of persons who travel to developing countries each year. Food and water contaminated with fecal matter are the main sources of infection. Bacteria such as enterotoxigenic Escherichia coli, enteroaggregative E. coli, Campylobacter, Salmonella, and Shigella are common causes of traveler's diarrhea (TD). Parasites and viruses are less common etiologies. Travel destination is the most significant risk factor for traveler's diarrhea. The efficacy of pretravel counseling and dietary precautions in reducing the incidence of diarrhea is unproven. Empiric treatment of traveler's diarrhea with antibiotics and loperamide is effective and often limits symptoms to one day.
  • Rifaximin a recently approved antibiotic, can be used for the treatment of traveler's diarrhea in regions where noninvasive E. coli is the predominant pathogen. In areas where invasive organisms such as Campylobacter and Shigella are common, fluoroquinolones remain the drug of choice. Azithromycin is recommended in areas with quinolone- resistant Campylobacter and for the treatment of children and pregnant women. (Am Fam Physician 2005; 71 :2095-100, 2107-8. Copyright ⁇ 2005 American Academy of Family Physicians.) 2096 American Family Physician www.aafp.org/afp Volume 71, Number 11, June 1, 2005.
  • E. coli such as enteroaggregative E. coli have been recognized as common causes of traveler's diarrhea.
  • Invasive pathogens such as Campylobacter, Shigella, and nontyphoid Salmonella are relatively common depending on the region, while Aeromonas and non-cholera Vibrio species are encountered less frequently.
  • Protozoal parasites such as Giardia lamblia, Entamoeba histolytica, and Cyclospora cayetanensis are uncommon causes of traveler's diarrhea, but increase in importance when diarrhea lasts for more than two weeks. Parasites are diagnosed more frequently in returning travelers because of longer incubation periods (often one to two weeks) and because bacterial pathogens may have been treated with antibiotics.
  • Rotavirus and noroviruses are infrequent causes of traveler's diarrhea, although noroviruses have been responsible for outbreaks on cruise ships.
  • Iodination or chlorination is acceptable but does not kill Cryptosporidium or Cyclospora, and increased contact time is required to kill Giardia in cold or turbid water.
  • Filters with iodine resins generally are effective in purifying water, although it is uncertain whether the contact time with the resin is sufficient to kill viruses.
  • Bottled water generally is safe if the cap and seal are intact.
  • Probiotics are a more natural approach to prophylaxis of traveler's diarrhea. Probiotics colonize the gastrointestinal tract and theoretically prevent pathogenic organisms from infecting the gut. Studies of Lactobacillus GG (Culturelle) have suggested protection rates of up to 47 percent. More studies are needed to confirm the efficacy of probiotic prophylaxis. This study of a combination of two well known probiotics and a well studied prebiotic will follow a well designed protocol to determine functionality.
  • This study will be designed as a multicentre double blind, placebo-controlled study with parallel groups to assess the beneficial effects of a daily consumption of TRAVELER'S RELIEF #2 on diarrhea symptoms. Treatment duration will be length of trips of patients by patient. The study protocol will be conducted in accordance with the Declaration of Helsinki and approved by the local Ethics Committee. All volunteers will be given written informed consent prior to participation in the study.
  • TRAVELER'S RELIEF #2 containing acidophilus ARS-B3208 and bacillus coagulans ARS #B3208 along with 4.85gm of Inulin from Agave in one Sachet of TRAVELER'S RELIEF #2 or placebo will be ingested daily with food, beginning 5 days prior to travel, throughout the trip (trip duration to be documented), and for 10 days after return. The Sachet can be taken any time of day.
  • the TRAVELER'S RELIEF #2 and placebo sachets will be identical in color, packaging, and smell.
  • Subjects will be randomly chosen to receive TRAVELER'S RELIEF #2 or placebo. Randomization will be performed in a block of size 4 using a random number generator.
  • Subjects are also offered antimicrobials (ciprofloxacin, levofloxacin, or azithromycin) to carry with them to treat TD if needed. They were instructed not to use antibiotics prophylactically. The subjects are instructed to continue taking the study drug even if TD develops and are initiating antibiotics and/or loperamide.
  • a letter is provided to the patient to allow carriage of the study drug across international borders. The letter also contains telephone numbers for on-call personnel in case subjects experience side effects or have questions during their trip, and all subjects enrolled in this study will provide written informed consent.
  • the test product will be TRAVELER'S RELIEF #2 with 20 Billion CFU acidophilus ARS-B3208 and 0.4 Billion CFU bacillus coagulans ARS #B3208 along with 4.85gm of Inulin from Agave.
  • the test product contains 20.5 billion colony-forming units (cfu) in sachet form with no other ingredients except the prebiotic Inulin.
  • the control product will contain 5gm of maltodextin. Both the test and control products will have a similar appearance, texture and taste. Both products will be specifically prepared for the study and provided by America's Naturals (Fort Lauderdale, Florida).
  • VAS 1-10 visual analogue scale
  • probiotics are beneficial in a range of gastrointestinal conditions, including infectious diarrhea and that related to antibiotic use.
  • Probiotics are defined as "live micro-organisms which when administered in adequate amounts confer a health benefit on the host" and include Lactobacillus and Bacillus species.
  • Diarrhea associated with antibiotic use and caused by Clostridium difficile is a complication of treatment with antimicrobial agents and occurs in about 5-25% of patients.
  • C difficile is responsible for around 15-25%) of all cases of diarrhea associated with antibiotic use, most occurring in older patients, usually in the two to three weeks after cessation of antibiotic treatment. Lactobacilli and Bacillus species have all been evaluated for the prevention or treatment.
  • a baseline stool sample will be collected to screen for asymptomatic C difficile carriage. Bowel movements were monitored with stool charts, which were checked every weekday for accuracy. When there is evidence of diarrhea a stool sample was analyzed for C difficile toxin. Once the antibiotic course is finished a final week of study dose was dispensed and a final follow-up date fixed for four weeks later. Patients who will be discharged taking antibiotics were provided with enough doses on discharge to cover the period they had to take antibiotics plus one week. researchers will follow up participants for four weeks from discharge with weekly phone calls to ask about diarrhea and compliance. If participants had diarrhea, the researchers will collect a further stool sample to check for C difficile toxin.
  • the placebo group receive a 5gm sachet of maltodextrin.
  • Patients will be recruited mainly from orthopaedic, medical, and care of the elderly wards, and included inpatients aged over 18 who are prescribed antibiotics (single or multiple antibiotics, oral or intravenous) and will be able to take food and drink orally.
  • antibiotics single or multiple antibiotics, oral or intravenous
  • Our exclusion criteria will be diarrhea on admission or within the preceding week, reported recurrent diarrhea, or bowel pathology that could result in diarrhea; intake of high risk antibiotics (clindamycin, cephalosporins, aminopenicillins) or more than two courses of other antibiotics in the past four weeks to exclude pre-existing diarrhea associated with antibiotic use; severe life threatening illness, immune-suppression, bowel surgery, artificial heart valve, history of rheumatic heart disease, or history of infective endocarditis5; regular probiotic treatment before admission; and lactose intolerance or intolerance to dairy products.
  • high risk antibiotics clindamycin, cephalosporins, aminopenicillins
  • the treatment group receive 15 Billion CFU Lactobacillus acidophilus ARS- B3208 and 200 Million CFU bacillus coagulans ARS #B3208 along with 4.95gm of inulin from Agave.
  • the placebo group received a sachet of 5 gm of Maltodextrin.
  • the test product will be Flora Renew with 15 Billion CFU acidophilus ARS- B3208 and 0.2 Billion CFU bacillus coagulans ARS #B3208 along with 4.95gm of Inulin from Agave.
  • the test product contained 15.2 billion colony- forming units (cfu) in sachet form with no other ingredients except the prebiotic Inulin.
  • the control product contained 5gm of maltodextin. Both the test and control products will have a similar appearance, texture and taste. Both products will be specifically prepared for the study and provided by America's Naturals (Fort Lauderdale, Florida).
  • VAS 1-10 visual analogue scale
  • Constipation is one of the most common—not to mention annoying— health problems we can face. In the United States, constipation accounts for seven million physician visits per year. Chronic constipation affects almost one in six adults. The costs to your quality of life are equally steep. A review of the medical literature published in 2010 showed that reduced quality of life from constipation was comparable to that caused by serious chronic conditions such as osteoarthritis and diabetes.
  • laxatives are not ideal because of their potentially adverse side effects, such as causing tolerance so that the intestine isn't as capable at releasing the stool on its own, melanosis coli (a disorder of pigmentation of the wall of the colon caused by prolonged use of laxatives) or cathartic colon (structural damage to the colon associated with stimulant laxatives).
  • Probiotics also help in achieving intestinal regularity.
  • Lactobacillus plantarum improved abdominal pain and normalized stool frequency in constipated patients with irritable bowel syndrome (IBS). The effect appeared to be strain specific, as Lactobacillus rhamnosus GG had more of a beneficial effect in IBS patients who predominantly had diarrhea.
  • Lactobacillus acidophilus ARS-B3208 Lactobacillus Rhamnosus ATCC 393 and Bifidobacterium Bifidum ATCC 29521 along with 4gm of Inulin from Agave for the daily use for regularity in a large subset of patients based on inclusion criteria.
  • This study will be designed as a multicentre double blind, placebo-controlled study with parallel groups of minimum 75 patients to assess the beneficial effects of a daily consumption of DAILY BALANCE #2 on regularity of bowel movements. Treatment duration will be 24 weeks with 4 follow-up visits at 6 week intervals. The study protocol will be conducted in accordance with the Declaration, of Helsinki and approved by the local Ethics Committee. All volunteers will be given written informed consent prior to participation in the study.
  • DAILY BALANCE #2 containing Lactobacillus acidophilus ARS-B3208, Lactobacillus Rhamnosus ATCC 393 and Bifidobacterium Bifidum ATCC 29521 along with 4gm of Inulin from Agave in one Sachet of Traveler's support or placebo will be ingested daily with food, beginning 5 days prior to travel, throughout the trip(trip duration to be documented), and for 10 days after return. The Sachet can be taken any time of day.
  • the DAILY BALANCE #2 and placebo sachets will be identical in color, packaging, and smell.
  • Subjects will be randomly selected to receive Traveler's Support or placebo. Randomization was performed in a block of size 4 using a random number generator.
  • Subjects aged 18 years or above and having mild to moderate irregularity issues are eligible for the trial. Additional exclusion criteria include: current use of antibiotic or antidiarrheal medication (ie, Pepto-Bismol, loperamide, etc.) or their use within 2 weeks prior, a history of inflammatory bowel disease (Crohn's disease or chronic ulcerative colitis), known bowel cancer, congenital or acquired immunocompromised states such as human immunodeficiency virus infection (HIV/AIDS), current or recent chemotherapy or immunomodulating agents (corticosteroids and TNF-a inhibitors), short-gut syndrome, use of oral typhoid vaccine within 48 hours of starting study, pregnancy, ongoing probiotic use, and previous participation in this study. Women of childbearing age are required to have a negative pregnancy test within 2 weeks of starting the study drug and are counseled not to get pregnant during the study period.
  • All enrolled subjects receive standard counseling and education about food and water precautions and self-management of diet. Subjects are also offered loperamide in case diarrhea initiated and was not controlled.
  • a letter is provided to the patient to allow carriage of the study drug across international borders. The letter also contains telephone numbers for on-call personnel in case subjects experience side effects or have questions during any trip, and all subjects enrolled in this study provide written informed consent.
  • test product will be DAILY BALANCE #2 with 6.8 Billion CFU
  • the test product will contain 20 billion colony-forming units (cfu) in sachet form with no other ingredients except the prebiotic Inulin.
  • the control product will contain 5gm of maltodextin. Both the test and control products will have a similar appearance, texture and taste. Both products will be specifically prepared for the study and provided by America's Naturals (Fort Lauderdale, Florida).
  • the primary endpoint will be the improvement of the frequency of bowel movements, alleviation of constipation and abdominal pain episodes. Secondary endpoints are expected to be changes in severity of abdominal pain, changes in frequency and severity of abdominal bloating and in feeling of incomplete rectal emptying as well as time of diarrhea episodes and less forced evacuation. Both frequency of abdominal pain and feeling of incomplete rectal emptying should be assessed weekly using a four-point scale ranging from 1 (only occasional symptom) to 4 (daily symptom).
  • VAS visual analogue scale

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Abstract

L'invention concerne un ou plusieurs mélanges probiotiques et prébiotiques qui permettent la survie à travers le tractus gastro-intestinal (GI) humain et donnent des résultats physiologiques souhaités. Plusieurs modes de réalisation démontrent qu'un mélange unique de prébiotiques avec des mélanges de souches probiotiques spécifiques peut survivre dans le tractus GI et fournir les effets physiologiques souhaités pour chaque mélange, par exemple pour traiter le syndrome du côlon irritable (IBS), la diarrhée et la constipation. En outre, l'invention concerne un procédé pour déterminer une fonctionnalité in vitro de probiotiques et de prébiotiques pour la modélisation de la survie dans le tractus GI de l'humain ou de l'animal de compagnie domestiqué.
PCT/US2016/037664 2015-06-15 2016-06-15 Mélanges probiotiques multi-souches pour le traitement de troubles gastro-intestinaux et l'amélioration ou l'entretien de la santé gastro-intestinale WO2016205394A1 (fr)

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