Patent Application: US-201715445790-A

Abstract:
the invention provides a method and composition for ameliorating or reducing the symptoms , signs , and markers and for the treatment of irritable bowel syndrome , inflammatory bowel disease or gastritis in a mammal in need thereof , said method comprising administering effective amounts of a pharmaceutically acceptable composition containing at least one probiotic microorganism strain comprising pediococcus for a time sufficient to ameliorate , reduce or treat at least one symptom , sign , or marker of irritable bowel syndrome , inflammatory bowel disease or gastritis .

Description:
in one aspect the compositions , methods , systems , etc ., herein are directed to providing probiotic compositions that are capable of reducing one or more signs or symptoms of ibs , ibd , and gastritis in individuals in need thereof . the signs and symptoms of gastritis , which can be reduced by the methods , compositions , etc . of the present invention , include : a gnawing or burning ache or pain ( indigestion ) in the upper abdomen that may become either worse or better with eating ; nausea ; vomiting ; loss of appetite ; belching or bloating ; a feeling of fullness in the upper abdomen after eating ; weight loss ; gastric ulcer ; duodenal ulcer ; inflammation of the stomach lining ; a positive test for urease in the stool ; a positive urea breath test . the signs and symptoms of ibs , which can be reduced by the methods , compositions , etc . of the present invention include : abdominal pain or cramping ; a bloated feeling ; gas ( flatulence ); diarrhea or constipation ; a change in frequency of bowel movements ; a change in appearance of bowel movements ; feelings of uncontrollable urgency to have a bowel movement ; and mucus in the stool . the signs and symptoms of ibd ( crohn &# 39 ; s disease , ulcerative colitis and indeterminate colitis ) that can be reduced by the methods , compositions , etc . of the present invention include : abdominal pain ; fever ; loss of appetite ; pain with passing stool ; diarrhea ; unintentional weight loss ; constipation ; rectal bleeding ; bloody stools ; intestinal inflammation , abscesses and fistulas ; and inflammation of the ileal pouch ( pouchitis ). it is not necessary that individuals have been diagnosed with a microbial infection in order to benefit from the compositions , methods , systems , etc ., herein . the compositions , formulations , methods , etc ., can be used as dietary supplements or as food additives or as pharmaceutical agents or otherwise as desired to reduce symptoms of ibs , ibd and gastritis . the methods herein include methods , kits , labels , systems , etc ., directed to labeling , marketing and otherwise providing the compositions to health care professionals and / or to consumers for use in reducing symptoms of ibs , ibd and gastritis . the inclusion of at least one strain of pediococcus in the composition is essential for this invention . in one embodiment , the composition is comprised of a mixture of a first microbial organism comprising at least one strain of pediococcus and at least one second microbial organism having a beneficial health effect in humans , wherein the second microbial organism is at least one of a bacterium or fungus . typically , at least one additional microbial organism is selected from the group comprising lactobacillus , bifidobacterium , streptococcus , or saccharomyces . in a further embodiment , the compositions are provided in capsules or other suitable administration formats , and a single capsule provides a full serving . in one example , each capsule comprises at least about 1 million and up to 150 billion colony forming units ( cfu ) of the pediococcus per 1 capsule serving and at least about 1 million cfu of the additional microorganism per 1 capsule serving . in another embodiment , the yield is about 150 billion cfu per gram of material . other yields can also be used as desired . in a further embodiment , the pediococcus strain is one or more of pediococcus acidilactici , pediococcus pentosaceus , pediococcus damnosus , pediococcus dextrinicus , pediococcus cerevisiae , or pediococcus parvulus . in another embodiment , the selected species of pediococcus is combined with one or more further probiotics . the additional probiotic may be any microorganism that has a beneficial health effect in humans . typically , the additional probiotic is one or more of : lactobacillus acidophilus , l . brevis , l . bulgaricus , l . casei , l . crispatus , l . curvatus , l . fermentum , l . gasseri , l . helveticus , l . johnsonii , l . paracasei , l . paraplantarum , l . pentosus , l . plantarum , l . reuteri , l . rhamnosus , l . salivarius , l . sakei , lactococcus lactis , leuconostoc lactis , ln . pseudomesenteroides , ln . mesenteroides , bifidobacterium adolescentis , b . animalis , b . bifidum , b . breve , b . lactis , b . longum , b . infantis , streptococcus thermophilus , saccharomyces boulardii , saccharomyces cereviseae , bacillus subtilis , b . coagulans ( frequently mislabeled as lactobacillus sporogenes ), b . licheniformis , b . cereus , enterococcus faecium , escherichia coli nessle 1917 , proprionibacterium acidipropionici , p . freudenreichii , p . jensenii , and p . thoenii . in a further embodiment , none of the probiotic organisms in the composition have been or are propagated or grown in media containing casein or gluten . in another further embodiment , the composition such as a dietary supplement is a dried powder , a tablet , or a gelatin capsule . exemplary methods for encapsulation of probiotics can be found , e . g ., in u . s . patent application no . 2007 / 0122397 and in the scientific literature . in one further embodiment , the composition is supplied along with an ingestible support material for human consumption . exemplary ingestible support materials include a cereal based product , rice cake , soy cake , food bar product , cold formed food bar product , custard , pudding , gelatin , rice milk , soy milk , yogurt , kefir , mashed fruit product , candy , candy bar , and applesauce . numerous methods for formulation of ingestible support materials with probiotics are known in the literature . in another embodiment the product can be a kit or system wherein the compositions , capsules , etc ., herein are contained in a pharmaceutically acceptable container and a written description , brochure , information sheet , catalog , or label explaining the product can reduce one or more symptoms of ibs , ibd or gastritis , and / or the product is free of casein and gluten and / or hypoallergenic . further , the product can be marketed together with the written description , brochure , information sheet , catalog , or label explaining the product can reduce one or more symptoms of ibs , ibd or gastritis / gastric ulcer , and / or the product is free of casein and gluten . in an additional embodiment the product is marketed together with a written description , brochure , information sheet , catalog , or label explaining that the product is hypoallergenic . “ probiotics ” within the context of the present invention is used in accord with its usual meaning , for example as selected , viable microbial dietary supplements that , when introduced in sufficient quantities , beneficially affect the human organism via their effects in the gastrointestinal tract ( holzapfel et al ., 2001 ; holzapfel & amp ; schillinger , 2002 ). the fao / who has adopted the definition of probiotics as “ live microorganisms which when administered in adequate amounts confer a health benefit on the host ”( fao / who guidelines , 2002 ). these beneficial bacteria may be found for example in milk or in milk processing factories , living or decaying plants , and also in the intestines of man and animals . currently , the best - studied probiotics are the lactic acid bacteria , particularly lactobacillus spp and bifidobacterium spp . lactobacillus is a genus of gram - positive facultative anaerobic bacteria . the genus lactobacillus currently comprises over 100 species and encompasses a wide variety of organisms . they are common and usually benign . in humans they are present in the vagina and the gastrointestinal tract , where they are symbiotic and make up a small portion of the gut flora ( tannock , 1999 ). studies in humans have been done with l . acidophilus , l . salivarius , l . johnsonii , l . casei , l . lactis , l . reuteri , l . plantarum , l . rhamnosus , l . brevis , l . gasseri , and other species and subspecies . the use of lactobacillus species in human studies has been extensively reviewed in the scientific literature , including the references provided herein . bifidobacterium is a genus of gram - positive anaerobic bacteria , currently comprised of 31 characterized species , 11 of which have been detected in human feces ( tannock , 1999 ). bifidobacteria are gram - positive , irregular or branched rod - shaped bacteria that are commonly found in the intestines of humans and most animals and insects . while b . infantis , b . brevi , and b . longum are the largest group of bacteria in the intestine of infants , bifidobacteria are said to be only the 3rd or 4th largest group in adults ( and comprise only 3 - 6 % of adult fecal flora ). bifidobacteria inhibit the growth of candida albicans , e . coli , and other pathogenic bacteria . b . infantis has been shown to dramatically reduce the symptoms of irritable bowel syndrome ( ibs ) ( whorwell et al ., 2006 ). lactobacilli and bifidobacteria have been examined for their effectiveness in the prevention and treatment of a diverse spectrum of gastrointestinal disorders . among other benefits , these organisms are thought to restore and maintain immune system function and gastrointestinal barrier function , and to reduce inflammation ( corthesy et al ., 2007 ; parvez et al ., 2006 ). the effects of lactobacillus and bifidobacterium in humans have been reviewed by jonkers & amp ; stockbruegger , 2007 ; lesbros - pantoflickova ; moayyedi et al ., 2010 ; gareau et al ., 2010 ; parvez et al ., 2006 ; lesbros - pantoflickova d , et al . 2007 ). midolo et al . ( 1995 ) reported that six strains of l . acidophilus and one strain of l . casei subsp . rhamnosus inhibited the growth of h . pylori growth in vitro . the administration of lactobacillus and bifidobacteria improves gastritis ; the effect is statistically significant but weak ( lesbros - pantoflickova d , et al . 2007 ). one product , known as vsl # 3 , has been shown to reduce the symptoms of ulcerative colitis and pouchitis ( inflammation of the ileal pouch ; reviewed by corthesy et al ., 2007 ). a probiotic / prebiotic mixture known as synbiotic 2000 had no effect on the postoperative recurrence of crohn &# 39 ; s disease ( chermesh , 2007 ). saccharomyces boulardii is a transient yeast probiotic long used to treat various types of diarrhea . it is a hardy , acid - resistant , temperature tolerant microorganism that is not affected by antibiotics . s . boulardii has been reported to have beneficial effects in patients with crohn &# 39 ; s disease , ibs , and gastritis ( guslandi et al ., 2000 ; choi et al ., 2011 ; szajewska et al ., 2010 ). pediococcus can be described as “ the only acidophilic , homofermentative , lactic acid bacteria that divide alternatively in two perpendicular directions to form tetrads ”( simpson and taguchi , 1995 ). phylogenetically , pediococcus and lactobacillus form a super - cluster that can be divided in to two sub - clusters . all species of pediococcus fall within the lactobacillus casei — pediococcus sub - cluster . morphologically , pediococci ( cocci ; 0 . 6 - 1 . 0 mm in diameter ) and lactobacilli ( rods ) are distinct . five species currently belong to the genus pediococcus : pediococcus acidilactici , pediococcus damnosus , pediococcus dextrinicus , pediococcus parvulus , and pediococcus pentosaceus . p . pentosaceus is used as an acid producing starter culture in sausage fermentations , cucumber and green bean fermentations , soya milk fermentations , and silage , and is a typical component of the microflora of most cheese varieties during ripening . pediococcus species have been used as probiotics in the livestock and pet industries ( u . s . patent appl . 20060008511 and 20070020328 ) and are generally recognized as safe for human consumption ( gras ) ( ishibashi & amp ; yamazaki , 2001 ). one strain of p . acidilactici ( lmg p - 21927 ) has been isolated from human feces ( speelmans et al ; u . s . patent appl . no . 2006 / 0165661 ; wo2004 / 110466 ). the antimicrobial effects of pediococcus on foodborne pathogens such as listeria have been determined . the antibacterial properties of pediococcus are due to bactericidal peptides known as pediocins , which are of great interest as food biopreservatives . several studies have been done to examine the effects of pediocins on h . pylori . kim et al . ( 2003 ) reported that purified pediocin po2 had weak activity against h . pylori , but midolo and coworkers ( 1995 ) found no effect of live pediococcus on h . pylori . none of the studies contemplate the use of live pediococcus for the treatment of gastritis , ibs or ibd in humans . we previously disclosed compositions and methods comprising pediococcus for use in humans ( u . s . published application no . 2011 / 0091431 whose contents are incorporated by reference herein ). the present invention specifies the use of these compositions and methods for reducing the signs and / or symptoms of gastritis , ibs and ibd in persons in need thereof . although not necessary to an understanding of the compositions , methods , etc ., herein the beneficial effects of our compositions in reducing symptoms of ibs , ibd and gastritis may result from an effect of pediococcus as an immune modulator , which reduces inflammation and enhances the host response against disease . the dosage of pediococcus is also important for successful colonization of the gastrointestinal tract . without being bound by theory , these properties may allow the pedioccoccus compositions herein to confer or restore a more normal neurogastrointestinal and immunological function in individuals with ibs , ibd and gastritis . therefore , individuals that have been diagnosed with ibs , ibd or gastritis may benefit from the new compositions . the compositions discussed herein may be administered , for example , as dietary supplements , food and beverage additives , food and beverage ingredients , and pharmaceutical agents . any suitable administration route can be used , typically alimentary / orally . the compositions discussed herein can include or be used in combination with compositions comprising digestive enzymes . for example , the compositions can be used in combination with a formulated combination of digestive enzymes known as enzymaid ™ ( kirkman labs , oregon ) and a wide variety of other formulations . typically , the digestive enzymes will be administered as a separate tablet or capsule or powder . a digestive enzyme formulation may if desired be given to a patient for a proscribed period of time prior to the initiation of treatment , for example for a period of 1 - 3 days to 1 - 4 weeks prior to initiation of treatment with the compositions described herein . examples of digestive enzyme formulations that are suitable for use in the present invention include , but are not limited to , the products from prothera inc . and klaire labs , inc . ( reno , nev . ), known as vitalzymes ™ complete ; vitalzymes ™ forte ; vitalzymes ™ chewables ; and serenaid ®, and any of the ingredients therein . the compositions described herein may be used subsequent to treatment with antibiotic or antifungal agents , or concomitantly with such treatments . the compositions discussed herein may be used in conjunction with a gluten - free and casein - free diet . thus , the methods and compositions of the present invention can be used in conjunction with any of the methods and compositions in houston ( u . s . pat . no . 6 , 447 , 772 ) and / or wilkinson ( u . s . pat . no . 6 , 251 , 391 ) including the serenaid ® brand enzyme product from prothera , inc . the compositions herein are preferably comprised of the following ingredients (% by relative cfu content ): pediococcus acidilactici 1 % to 99 % pediococcus pentosaceus 1 % to 99 % pediococcus damnosus 1 % to 99 % pediococcus dextrinicus 1 % to 99 % pediococcus parvulus 1 % to 99 % bifidobacterium lactis 1 % to 99 % bifidobacterium animalis 0 % to 99 % bifidobacterium adolescentis 0 % to 98 % bifidobacterium bifidum 0 % to 98 % bifidobacterium breve 0 % to 98 % bifidobacterium infantis 0 % to 98 % bifidobacterium longum 0 % to 98 % lactobacillus acidophilus 0 % to 98 % lactobacillus brevis 0 % to 98 % lactobacillus bulgaricus 0 % to 98 % lactobacillus casei 0 % to 98 % lactobacillus crispatus 0 % to 98 % lactobacillus curvatus 0 % to 98 % lactobacillus fermentum 0 % to 98 % lactobacillus gasseri 0 % to 98 % lactobacillus helveticus 0 % to 98 % lactobacillus johnsonii 0 % to 98 % lactobacillus paracasei 0 % to 98 % lactobacillus paraplantarum 0 % to 98 % lactobacillus pentosus 0 % to 98 % lactobacillus plantarum 0 % to 98 % lactobacillus reuteri 0 % to 98 % lactobacillus rhamnosus 0 % to 98 % lactobacillus sakei 0 % to 98 % lactobacillus salivarius 0 % to 98 % lactococcus lactis 0 % to 98 % leuconostoc lactis 0 % to 98 % leuconostoc pseudomesenteroides 0 % to 98 % leuconostoc mesenteroides 0 % to 98 % saccharomyces boulardii 0 % to 98 % saccharomyces cereviseae 0 % to 98 % streptococcus thermophilus 0 % to 98 % bacillus subtilis 0 % to 98 % bacillus coagulans 0 % to 98 % bacillus licheniformis 0 % to 98 % bacillus cereus 0 % to 98 % enterococcus faecium 0 % to 98 % escherichia coli nessle 1917 0 % to 98 % proprionibacterium acidipropionic 0 % to 98 % proprionibacterium freudenreichii 0 % to 98 % proprionibacterium jensenii 0 % to 98 % proprionibacterium thoenii 0 % to 98 % the above ingredients can also be present , for example , at ranges of more than 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 90 %, or less than 90 %, 80 %, 70 %, 60 %, 50 %, 40 %, 30 %, 20 %, 10 %. in one embodiment , the compositions contain the following amounts of ingredients per 1 capsule serving size , where cfu means a colony forming unit : pediococcus acidilactici 1 . 5 billion cfu ( 6 . 0 %) bifidobacterium breve 0 . 5 billion cfu ( 2 . 0 %) bifidobacterium infantis 0 . 5 billion cfu ( 2 . 0 %) lactobacillus paracasei 0 . 5 billion cfu ( 2 . 0 %) lactobacillus salivarius 0 . 5 billion cfu ( 2 . 0 %) bifidobacterium lactis 1 . 0 billion cfu ( 4 . 0 %) bifidobacterium longum 1 . 0 billion cfu ( 4 . 0 %) streptococcus thermophilus 1 . 0 billion cfu ( 4 . 0 %) lactobacillus bulgaricus 1 . 0 billion cfu ( 4 . 0 %) lactobacillus casei 2 . 5 billion cfu ( 10 . 0 %) lactobacillus plantarum 2 . 5 billion cfu ( 10 . 0 %) lactobacillus acidophilus 3 . 0 billion cfu ( 12 . 0 %) bifidobacterium bifidum 3 . 5 billion cfu ( 14 . 0 %) lactobacillus rhamnosus 6 . 0 billion cfu ( 24 . 0 %) it will be understood that a variety of different mixtures of lactobacillus , bifidobacterium , sachharomyces , lactococcus , and other probiotic organisms can be combined with pediococcus in various % compositions and doses that produce efficacious results ; the invention is not limited to the exact formulation described above . methods for formulation and encapsulation of bacteria have been reported , and such methods may be used in conjunction with this invention ( e . g . u . s . pat . appl . 2004 / 247580 ). in addition , the compositions , methods , etc ., herein can be formulated , made or used to include prebiotic agents that promote the growth of probiotic organisms in the gastrointestinal tract . suitable prebiotic agents include , but are not limited to , fructooligosaccharides , galactooligosaccharides , lactulose , β - glucan , inulin , pectin and resistant starch ( see , e . g ., paul et al ., u . s . pat . no . 6 , 241 , 983 ). the probiotic compositions of the invention are also formulated with other therapeutic agents such proton pump inhibitors selected from the group consisting of omeprazole , lansoprazole , rabeprazole , pantoprazole and esomeprazole and h2 - receptor antagonists selected from the group consisting of cimetidine , ranitidine , famotidine and nizatidine . a 38 year - old male patient with severe abdominal distention is treated daily with a capsule containing 200 million cfu of pedioccocus acidilactici . the patient is evaluated on a weekly basis and the patient reports improvement of the symptoms of abdominal distention . an 8 year - old boy with daily gas , abdominal craps , and constipation is treated by administering 2 capsules twice daily , each capsule containing a probiotic formulation containing pediococcus acidilactici 1 . 5 billion colony forming units ( cfu ), bifidobacterium breve 0 . 5 billion cfu , bifidobacterium infantis 0 . 5 billion cfu , lactobacillus paracasei 0 . 5 billion cfu , lactobacillus salivarius 0 . 5 billion cfu , bifidobacterium lactis 1 . 0 billion cfu , bifidobacterium longum 1 . 0 billion cfu , streptococcus thermophilus 1 . 0 billion cfu , lactobacillus bulgaricus 1 . 0 billion cfu , lactobacillus casei 2 . 5 billion cfu , lactobacillus plantarum 2 . 5 billion cfu , lactobacillus acidophilus 3 . 0 billion cfu , bifidobacterium bifidum 3 . 5 billion cfu , and lactobacillus rhamnosus 6 . 0 billion cfu and experiences complete resolution of symptoms after 3 weeks . the entire contents including the references cited therein of the references cited above and the following patents , published applications including all their foreign equivalents and journal publications are incorporated by reference in their entirety for all purposes to the same extent as if each individual patent , patent application or publication were so individually denoted . 1 . brandt l j , chey w d , foxx - orenstein a e , et al . an evidence - based position statement on the management of irritable bowel syndrome . am j gastroenterol 2009 ; 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19 suppl a : 5a - 36a . 36 . simpson w j , taguchi h . the genus pediococcus , with notes on the genera tetratogenococcus and aerococcus , in wood b j b , holzapfel w h ( eds ). the genera of lactic acid bacteria . 1995 ; pp . 125 - 172 ; chapman & amp ; hall , london . 37 . szajewska h , horvath a , piwowarczyk a . meta - analysis : the effects of saccharomyces boulardii supplementation on helicobacter pylori eradication rates and side effects during treatment . aliment pharmacol ther 2010 ; 32 ( 9 ): 1069 - 79 . 38 . tannock g w . identification of lactobacilli and bifidobacteria . current issues molec biol 1999 ; 1 : 53 - 64 . 39 . whorwell p j , altringer l , morel j , et al . efficacy of an encapsulated probiotic bifidobacterium infantis 35624 in women with irritable bowel syndrome . am j gastroenterol 2006 ; 101 : 1581 - 90 . although the present invention has been described with reference to specific details of certain embodiments thereof , it is not intended that such detail should be regarded as limitations upon the scope of the invention , except as and to the extent that they are included in the accompanying claims .