TW201717783A - Materials and methods for improving gastrointestinal health - Google Patents

Abstract

Described herein is a composition comprising a mixture of a probiotic composition and a prebiotic composition, wherein the probiotic composition comprises the bacterium Bacillus coagulans and wherein the prebiotic composition comprises a plant-based fiber, a resistant starch and a short-chain oligosaccharide. Uses of the compositions described herein for maintaining or improving gastrointestinal health is also contemplated.

Description

Materials and methods for improving gastrointestinal health Cross-references to related applications

The present application claims the benefit of U.S. Provisional Application Serial No. 62/203,566, filed on Aug.

Probiotic microorganisms are generally understood to be beneficially affecting the host's microorganisms by improving the microbial balance in the host's intestine. In general, it is believed that the probiotic organisms produce an organic acid, such as lactic acid and acetic acid which inhibit the growth of C. perfringens, such as (Clostridium perfringens) and Helicobacter pylori (Helicobacter pylori) of pathogens. It is therefore believed that probiotics can be used to treat and prevent conditions caused by pathogens or imbalances in gut microbes. It is also believed that the probiotic microorganism inhibits the growth and activity of spoilage bacteria, and thus produces toxic amine species, and it activates the host's immune function.

Probiotics have been administered to mammals for many years in foods such as fermented dairy products such as yogurt and inoculated pasteurized liquid milk. In addition to yogurt, there are also commercially available infant and larger infant formulas containing probiotic microorganisms, such as the BIO NAN® formula (available from Societe de Produits Nestle SA). In addition, various products including probiotic microorganisms including cereals and nutritional bars have recently been commercially available.

Especially preferred species with their ability to form spores (e.g., Bacillus coagulans (Bacillus coagulans)) Bacillus species embodiments of the present invention. The ability to form spores allows the bacterial species to resist heat and other conditions, provide a long shelf life for the product formulation, and cope with the survival and clustering of tissue in the gastrointestinal tract under conditions of pH, salinity, and the like. In addition, additional useful properties of many Bacillus species include non-pathogenic, aerobic, facultative, and heterotrophic, thus making such bacterial species safe and capable of easily clustering into the gastrointestinal tract.

The Gram-positive rod of B. coagulans has a cell diameter greater than 1.0 μm, and the sporangia expands to varying degrees, but no companion crystals are formed. Bacillus coagulans is a non-pathogenic Gram-positive spore- forming bacterium that produces L(+) lactic acid (dextrorotatory) under isotype fermentation conditions. It has been isolated from natural sources such as heat treated soil samples that are inoculated into the culture medium (see, for example, Bergey's Manual of Systemic Bacteriology, Vol. 2, Sneath, PHA et al., ed., Williams & Wilkins, Baltimore, Md., 1986). . The purified Bacillus coagulans strain acts as an enzyme source including: endonuclease (e.g., U.S. Patent No. 5,200,336); amylase (U.S. Patent No. 4,980,180); lactase (U.S. Patent No. 4,323,651) and ring-maltose- Dextrin-based transferase (U.S. Patent No. 5,102,800). Bacillus coagulans has also been utilized to produce lactic acid (U.S. Patent No. 5,079,164). Bacillus coagulans strains have been combined (also referred to as lactic acid bacteria spores (Lactobacillus sporogenes); Sakaguti & Nakayama , ATCC No.31284) of the other lactic acid-producing bacteria and Bacillus natto (Bacillus natto) to generate steam from the fermented soybean food product (US Patent No. 4,110,477). Bacillus coagulans GBI-30 strain (ATCC No. PTA-6086) has been previously described in U.S. Patent Nos. 7,713,726 and 8,277,799. Bacillus coagulans strains are also used as animal feed additives for poultry and livestock to reduce disease and improve feed utilization, and thus increase the growth rate of animals (International Patent Application No. WO 93/14187 and WO 94/11492). In particular, Bacillus coagulans strains have been used as universal nutritional supplements and agents to control constipation and dysentery in humans and animals.

Poor gastrointestinal health results from a variety of causes that can cause diarrhea, poor stool quality, or other symptoms. In addition, animals must digest foods efficiently and properly to maintain good gastrointestinal health. However, poor gastrointestinal health interferes with normal food digestion and adversely affects animal health and optimal condition.

Nutritional studies conducted in the 1970s showed that different carbohydrates had different effects on blood glucose (sugar) levels after consumption. These findings evoke the general assumption that all "complex" carbohydrates (starch) produce a reduced blood glucose response compared to "simple" sugars and explore the carbonization of diets that have modulated diabetes for more than thirty years. The clinical significance of the compound exchange table. These exchange tables are based on the assumption that portions of different foods containing equal amounts of carbohydrate will produce the same blood glucose response.

Thus, the glycemic index (GI) has been developed to rank equal carbohydrate fractions of different foods based on their extent of increasing blood glucose levels after consumption. Foods with high GI values contain rapidly digested carbohydrates that produce rapid and large-scale rises and falls in blood glucose levels. In contrast, foods with low GI values contain slowly digested carbohydrates that produce a gradual, relatively slow rise in blood glucose levels and thus control postprandial glycemic response.

Studies over the past two decades have confirmed that the blood sugar effect of food cannot be accurately predicted by the type and amount of carbohydrates it contains. This is because the rate at which carbohydrates are digested and released into the bloodstream is affected by many factors such as the natural form of the food, its fat, protein and fiber content, and the chemical structure of its carbohydrates. For this reason, foods that look similar in the same food group and different odors of the same food can have completely different effects on blood glucose levels.

GI research has important implications for the health of the food industry and people. Scientists now agree that the terms "complex carbohydrates" and "sugars" commonly found in food labels have little nutritional and physiological significance. The World Health Organization has recently published a consensus report stating that these terms should be removed from food labels and replaced with the overall digestible carbohydrate content of the food and its GI value to help people choose foods that will reduce the overall blood sugar impact of their diet. Currently, many nutritionists refer to the glycemic index when designing a more flexible diet for people with diabetes. In addition, GI values are being used in scientific research to examine the relationship between the overall glycemic effects of a person's usual diet and the risk of developing certain diseases over time. The results from large epidemiological studies show that long-term consumption of a hyperglycemic diet increases the risk of developing diabetes, heart disease and certain cancers that induce high blood glucose and insulin levels and recurrent surges. In contrast, results from both epidemiological studies and experimental studies have shown that a low GI diet can reduce the risk of these diseases, improve blood glucose control and insulin sensitivity, and lower high blood lipid levels in people with diabetes. And can be used for weight control. Recently, it has been shown that a high GI diet enhances body fat storage in healthy people to a greater extent than an equivalent calorie low GI diet, which may reflect a greater degree of insulin secretion and lower satiety associated with high GI foods. Type II diabetes and coronary heart disease continue to be the leading cause of disease and death in industrialized countries.

A GI value of 100 represents a reference value for an equal amount of pure glucose. Think to have small Foods with a GI value of 55 are low GI foods. A food having a GI value of 56-69 is a medium or moderate GI food, and a food having a GI value of 70 or more is a high GI food.

A high GI diet is not recommended for people with glucose regulation problems. In addition, a high GI diet can cause many health concerns.

Current methods of maintaining and improving gastrointestinal health often include improving the diet, administering various foods believed to achieve gastrointestinal health, or administering various drugs believed to be useful for maintaining or improving gastrointestinal health. Although their methods have been demonstrated to be useful herein, there are still more effective methods for maintaining and improving gastrointestinal health in the art.

It is also desirable in the art to help prevent and treat lower GI foods for diseases associated with hyperglycemia.

The present disclosure is directed to a blend of probiotic compositions and prebiotic compositions for maintaining or improving gastrointestinal health in a mammalian subject. The present disclosure also provides methods and materials for controlling postprandial glycemic responses in humans and other mammals by consuming the blend of probiotic and prebiotic compositions.

According to an aspect of the present invention, there is provided a composition comprising a mixture of a probiotic composition and a prebiotic composition, wherein the probiotic composition comprises Bacillus coagulans and wherein the prebiotic composition comprises plant based fibers, resistant Starch and short chain oligosaccharides. In some embodiments, the bacterium is Bacillus coagulans GBI-30 strain (ATTC designation number PTA-6086). The plant-based fibers in the prebiotic composition can be any plant-based fibers known in the art. In some embodiments, the plant based fiber is selected from the group consisting of plant fibers derived from soybean, inca, pea, potato, rice, konjac, oat, guar, pectin, and plantain. Similarly, the resistant starch in the prebiotic composition can be any resistant starch known in the art. In some embodiments, the resistant starch is a sugar-free anti-digested dextrin having an average degree of polymerization of 18. In some embodiments, the resistant starch is selected from the group consisting of resistant dextrin derived from corn. Likewise, the short chain oligosaccharide can be any short chain oligosaccharide known in the art. In some embodiments, the short chain oligosaccharide is selected from the group consisting of fructooligosaccharides (FOS), galactooligosaccharides (GOS), and low polymers of fructose, glucose, galactose, or combinations thereof. In some embodiments, the short-chain oligosaccharide is FOS, such as FOS comprising a linear catechol linked to a β 2-1 linkage of terminal glucose and having a degree of polymerization of 3-5. In some embodiments, the FOS is selected from the group consisting of canetriose (glucose-fructose-fructose or GF ₂ ), mycoplasma erythritol (GF ₃ ), fructosyl-mycotic erythritol (GF ₄ ), GF ₅ or a group consisting of GF _{5+m (where m = 1 - 100)} .

Compositions comprising a mixture of a probiotic composition and a prebiotic composition disclosed herein may be suitable for administration to any form of the mammalian subject. In some embodiments, the composition is in the form of a lozenge, powder or liquid. If provided as a powder, it is specifically contemplated to combine the powder with a suitable liquid (eg, a liquid dairy product, a fruit or vegetable juice, a blended fruit or vegetable juice product, etc.).

In another aspect, disclosed herein is a powder formulation comprising Bacillus coagulans GBI-30 strain (ATTC No. PTA-6086) in an amount of 1 x 10 ⁶ CFUs-1 x 10 ¹⁴ CFUs, at 0.1 g- Approximately 25 g of the resistant dextrin, the plant based fiber in an amount from 0.1 g to about 25 g, and the fructooligosaccharide in an amount from 0.1 g to about 25 g.

In another aspect, disclosed herein is a powder formulation comprising Bacillus coagulans GBI-30 strain (ATTC No. PTA-6086) in an amount of about 1 x 10 ⁹ CFUs, in an amount of about 3.7 g Dextrin, plant-based fiber in an amount of about 1.3 g, and fructooligosaccharide in an amount of 1.2 g. In some embodiments, the powder formulation further comprises inulin.

In another aspect, herein is disclosed a powder formulation which comprises an amount of from about 1 x 10 ⁹ CFUs of Bacillus coagulans GBI-30 strains (ATTC designated No. PTA-6086), in an amount of from about 5g of resistant paste Fine and fructose in an amount of 1.2g. In some embodiments, the powder formulation further comprises inulin.

In another aspect, disclosed herein is a method of maintaining or improving gastrointestinal health in a mammalian subject, comprising administering to the subject a composition comprising a mixture of a probiotic composition and a prebiotic composition Wherein the probiotic composition comprises Bacillus coagulans and wherein the prebiotic composition comprises plant based fibers, resistant starch and short chain oligosaccharides. In some embodiments, the mammalian subject is a human.

The compositions may be consumed in the form of lozenges, powders or liquids and may be consumed separately or with other foods or beverages.

This application is incorporated by reference into the disclosure of commonly owned and co-pending USSN___ (Attorney Docket No. 32550/49446A) filed on August 9, 2016, which requires a provisional filing dated August 11, 2015. The benefit of the application Serial No. 62/203,564, the disclosure of which is incorporated herein by reference.

[Details of the Invention]

The present disclosure is directed to a blend of a probiotic composition and a prebiotic composition for maintaining or improving gastrointestinal health in a mammalian subject. According to one aspect of the invention described herein, there is provided a composition comprising a mixture of a probiotic composition and a prebiotic composition, wherein the probiotic composition comprises Bacillus coagulans and wherein the prebiotic composition comprises a plant base Fiber, resistant starch and short chain oligosaccharides.

Probiotic composition

As used herein, the term "probiotic" refers to a microorganism that forms at least a portion of a transient or endogenous flora and thereby exhibits a beneficial prophylactic and/or therapeutic effect on the host organism. It is generally known in the art that the probiotic is clinically safe (i.e., not pathogenic). By way of example, but not limited to, any particular mechanism, the prophylactic and/or therapeutic effects of the acidogenic bacteria of the present invention are partially produced by competitive inhibition of pathogen growth due to: (i) its superior clustering ability; Ii) parasitic undesirable microorganisms; (iii) generating acids (eg, lactic acid, acetic acid, and other acidic compounds) and/or other extracellular products having antimicrobial activity; and (iv) different combinations thereof. It should be noted that the above products and activities of the acidogenic bacteria of the present invention act synergistically to produce the beneficial probiotic action disclosed herein.

Bacillus coagulans cultures were deposited with the following primary international strains: Agricultural Research Service Culture Collection; Russian Collection of Microorganisms; Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (German Collection of Microorganisms and Cell Cultures, VKM DSMZ); American Type Culture Collection ( ATCC); Finnish Microorganism Collection (University of Goteborg, Sweden); Japan Collection of Microorganisms (JCM); and Japan Federation for Culture Collection.

Various Bacillus coagulans strains currently available from the American Type Culture Collection (ATCC, Rockville, Md.) include the following accession numbers: Bacillus coagulans Hammer NRS 727 (ATCC No. 11014); Bacillus coagulans Hammer strain C (ATCC) No. 11369); Bacillus coagulans Hammer (ATCC No. 31284); and Bacillus coagulans Hammer NCA 4259 (ATCC No. 15949). Purified Bacillus coagulans were also purchased from Deutsche Sarumlung von Mikroorganismen und Zellkuturen GmbH (Braunschweig, Germany) using the following accession numbers: Bacillus coagulans Hammer 1915 (DSM No. 2356); Bacillus coagulans Hammer 1915 (DSM No. 2383, corresponding to ATCC number) 11014); Bacillus coagulans Hammer (DSM No. 2384, corresponding to ATCC No. 11369); and Bacillus coagulans Hammer (DSM No. 2385, corresponding to ATCC No. 15949). Bacillus coagulans can also be obtained from commercial suppliers such as Sabinsa Corporation (Piscataway, NJ) or KK Fertation (Kyoto, Japan).

Such coagulating spore strains and their growth requirements have been previously described (see, for example, Baker, D. et al., 1960. Can. J. Microbiol. 6: 557-563; Nakamura, H. et al., 1988. Int. J.Svst. Bacteriol. 38: 63-73). In addition, various Bacillus coagulans strains can also be isolated from natural sources (e.g., heat treated soil samples) using well known procedures (see, for example, Bergey's Manual of Systemic Bacteriology, Vol. 2, p. 1117, Sneath, PHA et al. , Williams & Wilkins, Baltimore, Md., 1986).

In view of the fact that the bacteria were originally labeled as spore lactic acid bacteria as originally described, Bacillus coagulans was initially incorrectly characterized as Lactobacillus (see, Nakamura et al., 1988. Int. J. Syst. Bacteriol. 38: 63-73). . However, since Bacillus coagulans produces spores and excretes L(+)-lactic acid via metabolism, the initial classification is not appropriate, and these two aspects provide key features for their utility. Instead, these developmental and metabolic aspects required the lactic acid bacteria classified as Bacillus, and thus rename it.

In some embodiments, the Bacillus coagulans provided in the compositions and used in the methods described herein are Bacillus coagulans GBI-30 strains (ATCC No. PTA) as described in U.S. Patent Nos. 7,713,726 and 8,277,799. -6086), the disclosure of which is incorporated herein by reference in its entirety.

In some embodiments, the probiotic composition described herein comprises from 1 x 10 ³ to about 1 x 10 ¹⁴ CFU (eg, 1 x 10 ³ , 1 x 10 ⁴ , 1 x 10 ⁵ , 1 x 10 ⁶ , 1 x 10 ⁷ , 1 x 10 ⁸ , 1 x 10 ⁹ , 1 x 10 ¹⁰ , 1 x 10 ¹¹ , 1 x 10 ¹² , 1 x 10 ¹³ or 1 x 10 ¹⁴ ) of the amount of live plant bacteria or spores B. coagulans strain GBI-30 (ATCC designation number PTA-6086). In some embodiments, the probiotic composition described herein comprises a Bacillus coagulans GBI-30 strain (ATCC No. PTA-6086) in an amount of about 1 x ¹⁰⁹ CFU of live phytobacterial or spore.

Prebiotic composition

In addition to the probiotic composition, the compositions described herein also comprise a prebiotic composition. "Prebiotics" are one or more indigestible substances that provide beneficial physiological effects to the host by selectively stimulating a limited number of bacteria for growth or activity during consumption (Gibson GR, Roberfroid M B. Dietary modulation of the human colonic Microbiota: introduced the concept of prebiotics. J Nutr. June 1995; 125(6): 1401-12). Prebiotics are usually saccharides that are not digested or substantially indigestible by humans or another mammal and are used to promote probiotic growth in the viscera, increase probiotic adhesion in the viscera, replace pathogens or be probiotics (symbiotic) ) or selected to provide the symbiotic bacteria can ferment carbohydrates and increase the dose of microorganisms in their gastrointestinal tract (Notably, Lactobacillus, Bacillus coagulans, Listeria and Feder (bifidobacteria)) of the level. Prebiotics can be saccharides that are not digestible by humans or other mammalian hosts and can act as indigestible fibers in the diet. This indigestibility is due to the lack of human enzymes that break down some or all of the prebiotic oligosaccharides as they pass through the digestive tract. When the prebiotic reaches the small intestine and the colon, bacteria that produce one or more enzymes that can digest the prebiotic can break down the prebiotic into simple sugars that the bacteria can use.

Suitable prebiotics can include one or more of a carbohydrate, a carbohydrate monomer, a carbohydrate oligomer, or a carbohydrate polymer. In one embodiment, the prebiotics are non-digestible saccharides comprising non-digestible monosaccharides, non-digestible oligosaccharides or non-digestible polysaccharides. In one embodiment, the oligosaccharide or sugar unit of the polysaccharide may be linearly linked or may be a chain having one or more side branches. The length of the oligosaccharide or polysaccharide may vary from source to source. In one embodiment, a small amount of glucose may also be included in the chain. In another embodiment, the prebiotic composition can be partially hydrolyzed or contain an individual sugar moiety that is a component of the primary oligosaccharide.

In some embodiments, the prebiotic composition comprises plant based fibers, resistant starch, and short chain oligosaccharides. The plant-based fibers in the prebiotic composition can be any plant-based fibers known in the art. In some embodiments, the plant based fiber is selected from the group consisting of plant fibers derived from soybean, inca, pea, potato, rice, konjac, oat, guar, pectin, and plantain.

Similarly, the resistant starch in the prebiotic composition can be any resistant starch known in the art. The term "resistant starch" as used herein refers to the sum of starch and starch digestion products that are not absorbed in the small intestine of healthy humans but enter the large intestine. Depending on the context, this is defined as a percentage of the total starch of the grain or a percentage of the total starch content in the food. Therefore, the resistant starch excludes products which are digested and absorbed in the small intestine. Resistant starches include physically inaccessible starch (RS1 form), resistant native starch granules (RS2), retrograded starch (RS3), and chemically modified starch (RS4). In some embodiments, the resistant starch is a sugar-free anti-digestion having an average degree of polymerization of 18. dextrin. In some embodiments, the resistant starch is selected from the group consisting of resistant dextrin derived from wheat, corn, or other plant sources. According to a preferred aspect of the invention, the resistant dextrin is produced from corn such as that obtained from FM06 from Roquette, Keokuk, IA.

Also, the short-chain oligosaccharide wherein the short-chain oligosaccharide is selected from the group consisting of low-polymers of fructooligosaccharides (FOS), galactooligosaccharides (GOS) or fructose, glucose, galactose or other sugar molecules alone or in combination thereof Group. In some embodiments, the short-chain oligosaccharide is FOS, such as a FOS comprising a β 2-1 linked linear chain of fructose bonded to terminal glucose and having a degree of polymerization of 3-5. In some embodiments, the FOS is selected from the group consisting of canetriose (glucose-fructose-fructose or GF ₂ ), mycoplasma erythritol (GF ₃ ), fructosyl-mycotic erythritol (GF ₄ ), GF ₅ or a group consisting of GF _{5+m (where m = 1 - 100)} . According to one aspect of the invention, the short chain oligosaccharide is a linear chain of β 2-1 linkages of fructose bonded to terminal glucose, which is commercially available as Nutraflora® from Ingredion, Westchester, IL.

In another aspect, disclosed herein is a powder formulation comprising Bacillus coagulans GBI-30 strain (ATTC No. PTA-6086) in an amount of from 1 x 10 ⁶ CFUs to 1 x 10 ¹⁴ CFUs, at 0.1 g- An amount of resistant dextrin of about 25 g, plant-based fibers in an amount from 0.1 g to about 25 g, and fructooligosaccharides in an amount from 0.1 g to about 25 g.

In another aspect, disclosed herein is a powder formulation comprising Bacillus coagulans GBI-30 strain (ATTC No. PTA-6086) in an amount of about 1 x ¹⁰⁹ CFUs, in an amount of about 3.7 g Dextrin, plant-based fibers in an amount of about 1.3 g, and fructooligosaccharides in an amount of 1.2 g. In some embodiments, the powder formulation further comprises inulin.

In another aspect, disclosed herein is a powder formulation comprising a Bacillus coagulans GBI-30 strain (ATTC No. PTA-6086) in an amount of about 1 x 10 ⁹ CFUs, a resistant paste in an amount of about 5 g. Fine and fructose in an amount of 1.2g. In some embodiments, the powder formulation further comprises inulin.

Route of administration

It is specifically contemplated to use a gel, suspension, aerosol spray, capsule, lozenge, powder or semi-solid formulation (e.g., a suppository) to administer a composition described herein to the gastrointestinal tract. Administration of a composition comprising an active probiotic lactic acid producing bacterium effective to prevent or treat a pathogenic bacterial infection typically consists of from about 10 mg to 10 g of the therapeutic composition per dose of 1-10 doses over a period of from one day to one month. Administration is usually from once every twelve hours to once every four hours. In the preferred embodiment, the therapeutic composition is administered 2-4 times daily, from about 0.1 g to 5 g per dose, for from 1 to 7 days.

In some embodiments, a composition comprising a prebiotic composition and a probiotic composition described herein is incorporated into a food product. The term "food" as used herein refers to any substance that contains nutrients that can be taken up by an organism to produce energy, promote health and optimal conditions, stimulate growth, and sustain life. The term "fortified food" as used herein refers to a food product that has been modified to include a composition comprising a prebiotic composition and a probiotic composition as described herein, which provides, in addition to the basic functions of supplying nutrients, such as health/most Good state - the benefit of promoting and / or preventing / reducing / treating the nature of the disease.

Compositions comprising a prebiotic composition and a probiotic composition can be incorporated into any food product. Exemplary foods include, but are not limited to, protein powder (meal shake animals), baked goods (pastries, biscuits, crackers, bread, scones and muffins), dairy products (including but not limited to cheese, sour Cheese, custard, rice pudding, mousse, ice cream, frozen yogurt, frozen custard), desserts (including but not limited to sorbet, sorbet, water ice, granitas and frozen purees), smearing Food/margarine, pasta and other cereal products, meal replacement products, nutrition bars, trail mix, granola, beverages (including but not limited to fruit tarts, water or dairy drinks and Soy-based beverages and breakfast cereals such as cereals. For beverages, the compositions comprising the prebiotic composition and the probiotic composition described herein can be provided in dissolved, suspended, emulsified form or as a solid.

In one embodiment, the fortified food product is a meal replacement product. The term "dietary substitute" as used herein refers to a fortified food intended to replace a normal meal. Nutritional bars and beverages intended to constitute a dietary substitute are types of dietary substitutes. The term also includes products that are consumed as part of a dietary replacement weight loss or weight management program, such as snack products that are not intended to be a substitute for the overall meal, but which may be used in conjunction with other such products to replace the meal or otherwise Used in the program. These latter products typically have a calorie content of 50-500 kcal/serv.

In another embodiment, the food product is a dietary supplement. The term "dietary supplement" as used herein refers to a substance that is ingested by the mouth containing a "dietary ingredient" intended to be supplemented. The term "dietary ingredients" includes, but is not limited to, compositions comprising prebiotic compositions and probiotic compositions as described herein as well as vitamins, minerals, herbs or other botanicals, amino acids and such as enzymes, organ tissues, glands And metabolite substances.

In yet another embodiment, the food product is a medical food product. The term "medical food" as used herein, is meant to be formulated as a specific dietary control that is consumed or administered entirely under the supervision of a physician and intended for use in a disease or condition for which the medical science is based on recognized scientific principles. The evaluation establishes a unique nutritional need.

In yet another embodiment, a composition comprising a probiotic composition and a prebiotic composition described herein is incorporated into a pharmaceutical product or composition. A pharmaceutical composition comprising a prophylactically or therapeutically effective amount of a composition described herein and usually one or more pharmaceutically acceptable carriers or excipients (It is discussed below).

The present disclosure contemplates compositions comprising a probiotic composition and a prebiotic composition as described herein, in some embodiments, pulverized, tableted, encapsulated, or otherwise formulated for oral administration. The compositions can be provided as pharmaceutical compositions, nutritional medicine compositions (e.g., dietary supplements) or as food or beverage additives, as defined by the U.S. Food and Drug Administration. The dosage form of the above composition is not particularly limited. For example, liquid solutions, suspensions, emulsions, lozenges, pills, capsules, sustained release formulations, powders, suppositories, liposomes, microparticles, microcapsules, sterile isotonic aqueous buffer solutions, and the like, are all contemplated as suitable dosage forms.

The compositions generally comprise one or more suitable diluents, fillers, salts, disintegrating agents, binders, lubricants, glidants, wetting agents, controlled release matrices, pigments, flavoring agents, carriers, excipients Buffers, stabilizers, solubilizers, commercial auxiliaries and/or other additives known in the art.

Any pharmaceutically acceptable (i.e., sterile and acceptable non-toxic as known in the art) liquid, semi-solid or solid diluent can be employed as a pharmaceutical vehicle, excipient or vehicle. Exemplary diluents include, but are not limited to, polyoxyethylene sorbitan monolaurate, magnesium stearate, calcium phosphate, mineral oil, cocoa butter and cocoa butter, methyl hydroxybenzoate and propyl hydroxybenzoate, talc Powder, alginate, carbohydrates, especially mannitol, alpha-lactose, anhydrous lactose, cellulose, sucrose, dextrose, sorbitol, modified dextran, gum arabic and starch.

Pharmaceutically acceptable fillers can include, for example, lactose, microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, calcium sulfate, dextrose, mannitol, and/or sucrose. Salts including calcium triphosphate, magnesium carbonate and sodium chloride may also be included as a filler in the pharmaceutical composition.

Adhesives can be used to hold the compositions together to form a hard lozenge. Exemplary binders include materials derived from organic products such as acacia, tragacanth, starch, and gelatin. Other suitable binders include methylcellulose (MC), ethylcellulose (EC), and carboxymethylcellulose (CMC).

In some embodiments, the fortified food product further comprises a bioavailability enhancer for increasing absorption of one or more absorbable natural products by the body. The bioavailability enhancer can be a natural or synthetic compound. In one embodiment, the fortified food product comprising the composition described herein further comprises one or more bioavailability enhancers to enhance the bioavailability of one or more bioactive natural products.

Natural bioavailability enhancers include ginger, parsley extract, capsicum extract, and chitosan. The active compounds in ginger are 6-gingerol and 6-ginger brain. Artemisia oil can also be used as a bioavailability enhancer (US Patent Application 2003/022838). Piperine is a compound derived from pepper ( Piper nigrum or Piper longum ) which acts as a bioavailability enhancer (see U.S. Patent No. 5,744,161). Piperine is commercially available under the trade name Bioperine® (Sabinsa Corp., Piscataway, NJ). In some embodiments, the natural bioavailability enhancer is present in an amount from about 0.02% to about 0.6% by weight based on the total weight of the fortified food.

Examples of suitable synthetic bioavailability enhancers include, but are not limited to, surfactants comprising those consisting of PEG esters, such as under the trade names: Gelucire®, Labrafil® and Labrasol®, Lauroglycol®, Pleurol Oleique® (Gattefosse Surfactants available under Corp., Paramus, NJ) and Capmul® (Abitec Corp., Columbus, Ohio).

The amount of the composition and the administration regimen are based on various factors related to the purpose of administration, such as human or animal age, sex, weight, hormone levels or other camps of humans or animals. Raise your needs. In some embodiments, the composition is administered to a mammalian subject in an amount from about 0.001 mg/kg body weight to about 1 g/kg body weight.

A typical regimen can include multiple doses of the composition. In one embodiment, the composition is administered once daily. The composition can be administered to an individual at any time. In some embodiments, the composition is administered at the same time as or prior to consumption of the meal or under a consumption meal.

All US patents, US patent application publications, US patent applications, foreign patents, foreign patent applications, and non-patent publications listed in this specification and/or application data sheet are cited in full. The manner is incorporated herein.

It is to be understood that the specific embodiments of the invention have been described by

Example 1 Evaluation of Survival Rate and Metabolic Activity of Bacillus Coagulans GBI-30 (ATTC No. PTA-6086) in an In Vitro Model of Stomach and Small Intestine

Digestion experiments to assess the survival and metabolic activity of Bacillus coagulans were performed as described in Maathuis et al., Beneficial Microbes, 1:31-36, 2010, in which Bacillus coagulans GBI-30 (ATTC No. PTA-6086) was Survival and metabolic activity during combination with the prebiotic composition described herein in the upper gastrointestinal tract are tested in an in vitro model of the stomach and small intestine (the disclosure of which is incorporated herein by reference in its entirety) in the Test in the model. The study was performed in the TNO dynamic multi-chamber system (TIM-1) of the stomach and small intestine, as described in Minekus et al. Appl. Microbiol. and Biotechnol., 53: 108-114, 1999, the disclosure of which is incorporated by reference. The manner is incorporated herein. It is expected that samples that have received both the probiotic composition and the prebiotic composition described herein will have a higher survival rate than samples that do not receive the prebiotic composition.

Example 2 Effect of fecal microbiota on subjects after dietary supplementation with prebiotic/probiotic blends

The experiments described in Nyangale et al., Anaerobe, 30: 75-81, 2014, the disclosure of which is hereby incorporated by reference in its entirety, in its entirety, in its entirety The test composition (where the probiotic composition or prebiotic composition was used as a control) was administered to human volunteers. It is expected that feces obtained from a subject who has received a composition comprising a prebiotic composition and a probiotic composition will have a larger Bacillus coagulans GBI compared to a subject receiving one of the control compositions. 30 (ATTC No. PTA-6086) group.

Example 3 Effect of glycemic index on subjects after dietary supplementation with prebiotic/probiotic blends

According to this example, a prebiotic/probiotic blend ( Bacillus coagulans and prebiotic fibers (plant based fibers, resistant starch and short chain oligosaccharides)) according to the invention is tested to determine when present in the inclusion of proteins comprising Inca The effect of the non-soybean-based nutrient shake drink or the soy protein-containing nutrient shake drink in the protein combination of pea protein, rice protein and potato protein on the glycemic index (GI). The glycemic index is a value associated with a particular type of food that indicates the effect of the food on human blood glucose (sugar) levels. GI indicates an overall increase in blood glucose levels after consumption of food.

The trial was conducted using the internationally recognized GI method (Joint FAO/WHO Report. Carbohydrates in Human Nutrition. FAO Food and Nutrition, Paper 66. Rome: FAO, 1998.), which has been tested by small experimental studies and large multi-center studies. Knot obtained Confirmation (Wolever TMS et al, Determination of the glycemic index values of foods: an interlaboratory study. European Journal of Clinical Nutrition 2003; 57: 475-482). The experimental procedures used in this study were based on international standards for conducting human ethical research and approved by the Medical Ethics Review Committee of Sydney University.

A group of ten healthy non-smokers aged 18-65 were recruited from the University of Sydney staff and student groups. (Using the kinetic basis (90%) sample size calculations from data from many published GI studies, if there is a significant difference (1.0 standard deviation unit difference for GI), then a set of at least ten people will be required in the study. Significant differences in GI values between test and reference foods were found.) Exclude the following individuals who volunteered to participate in the study: overweight or underweight; avoid eating; abnormal glucose tolerance; any disease or food allergy; or regular Ingestion of drugs other than standard contraceptives. The group participating in the study consisted of six males and four females. The mean age of the subjects was 26.4 years (range: 19.9-34.8 years) and the group had a mean body mass index (BMI) score of 21.2 kg/m2 (range: 19.4-24.7 kg/m2). The BMI score is a measure of the body weight about height. The BMI value of 18-25.0 kg/m2 is within the healthy body weight range.

Test food

Glucose (reference food)

Nutrient shake drink, soy (vanilla) - shaker preparation

Nutrient shake drink, non-soy (vanilla) - shaker preparation

Nutrient shake drink, non-soybean (vanilla)-blender preparation

According to this example, as a partially hydrolyzed corn and as a FM06 from Roquette, Keokuk, IA, a resistant starch dextrin, a linear chain of β 2-1 linked as a fructose bonded to terminal glucose as Nutraflora® from Ingredion , a prebiotic component of a short chain oligosaccharide commercially available from Westchester, IL, and a probiotic comprising at least one billion live CFU of Bacillus coagulans GBI-30 incorporated into a soy and non-soy nutrient shake drink, the shake drink further comprising Plant-based dietary fiber in the amounts presented in Table 1 below. In the case of a soy nutrient shake drink, the fiber is primarily soy fiber, which is naturally accompanied by the extracted soy protein. In the case of non-soybean shake drinks, the fibers are primarily fibers that accompany the presence of pea protein and inca protein in the shake beverage composition. These shake drinks contain other proteins, carbohydrates, fats, vitamins and other nutrients. The calorie number and other nutritional information sets are listed in Table 2 below. In each case, the amount of fibers totaled 6 g/min.

Each test portion of the nutrient shake drink was prepared immediately prior to the need according to the manufacturer's instructions. For the two shake beverages prepared using the shaker method, the appropriate amount of powder and cold water were placed in a plastic shake container and thoroughly mixed by hand shaking for 1 minute until combined. For shake beverages prepared using the blender process, the appropriate amount of powder and cold water were placed in the blender and thoroughly mixed for 20 seconds until combined. Various prepared shake drinks were supplied to the subject along with 250 mL of fresh water. The subject is required to consume all of the supplied fluid.

A standard method was used to determine the GI value of the food, and a portion of the food containing 25-50 grams of effective carbohydrates was fed to a group of 10 healthy persons in the morning after fasting overnight. A fasted blood sample is obtained and the food is subsequently consumed, after which additional blood samples are obtained at regular intervals during the next two hours. In this way, an overall increase in blood glucose (glucose) produced by the food over a two hour period can be measured.

The same procedure is repeated after the same group has consumed a portion of the reference food (pure glucose in water) containing an equal amount of available carbohydrates. The GI value of the test food can then be calculated by expressing the two hour blood glucose response for the test food as a percentage of the reaction produced by the reference food (GI value of glucose = 100). Thus, the GI value of a food product is a relative measure indicating how the blood glucose level rises after eating a particular food product compared to the high blood glucose response produced by the same amount of carbohydrate in the form of glucose. The equivalent carbohydrate portion of the test food and the reference food is used in the GI study because the carbohydrate is a nutrient that directly causes an increase in blood glucose levels in the food.

In the study, the ten healthy individuals consumed reference foods at three separate times and consumed one of the test foods at only one time. Therefore, the subjects completed 6 trial phases. The reference food is consumed in the first, fourth and sixth experimental stages, and the test food is in between Spend in random order. Each stage is completed on a separate morning with at least one day between subsequent stages.

For each subject, the glucose concentration in the plasma fraction of each of the eight plasma samples collected during each two-hour test period was analyzed in duplicate. A two-hour blood glucose response curve was constructed for each of the reference samples and test sample stages for each subject using an average plasma glucose concentration for each of their blood samples. The two fasted blood samples were averaged to provide a baseline glucose concentration.

The incremental area (iAUC) under each two hour plasma glucose curve was then calculated to obtain a single value representing the overall increase in plasma glucose in the subject as a result of ingesting the food during the two hour period. The GI value of each test product was then obtained by dividing its two-hour blood glucose iAUC value for each test sample by its average two-hour blood glucose iAUC value for the reference food and multiplying by 100 to obtain a percentage value (Equation 1). Calculated by each subject. Due to differences in body weight and metabolism, blood glucose response to the same food can vary from person to person. The use of a reference food to calculate a GI value reduces the change in blood glucose results between the subject and the same food caused by such natural differences. Thus, the GI value for the food varies from subject to subject to a lesser extent than the subject's glucose AUC value for the food.

Results and conclusions

25 grams of carbon for reference foods and three prepared vibrating shake beverage products The average two hour plasma glucose response profile for the water compound fraction is shown in Figure 1. The reference food is rapidly absorbed, producing a high peak plasma glucose concentration and a maximum overall glycemic response within 30 minutes. All three test foods produced significantly lower peak plasma glucose concentrations and overall glycemic response compared to the reference food. Different preparations (manual shaking with the blender) did not affect the GI value.

The three shake beverages prepared with a shaker or blender produced an average GI value of 26-39 which completely attributed these products to the low GI category (Table 3). Using glucose as a reference food (GI = 100), foods having a GI value of less than 55 are currently considered low GI foods. The food having a GI value of 56-69 is a medium GI food, and the food having a GI value of 70 or more is a high GI food. Thus, the shake beverages will be suitable for consumption by a person with difficult blood glucose regulation in a controlled amount.

GI values are measured using portions of foods and beverages containing 25-50 grams of digestible carbohydrates, but these may not be similar to the amount of such products normally consumed by people in a normal environment. As long as you know its GI value, you can calculate the glycemic load (GL) value of carbohydrate-containing foods of any size. The GL value of the food or beverage is calculated according to Equation 2 below.

The GL value of the test food of Equation 2 = (the amount of carbohydrate in each serving x GI value) / 100

Similar to the GI value, the GL value can be used to help people identify which type and how much food will produce a relatively low blood sugar response after consumption - with diabetes and suffering from diabetes An important consideration for people at risk of illness. Currently, it is agreed that the GL value of 10 or lower is low GL; the GL value of 11-19 is a medium GL value; and the GL value of 20 or higher is a high GL value. The GL values for each of the standard parts tested in this study are listed below:

1. Life Shake Vanilla (soybean) (prepared by shaker) (43g / serving +250mL water): (12g carbohydrate x 26 GI) / 100 = 3

2. Vanilla Vibrant Shake Drink (Non-Soybean) (Prepared by shaker) (45g / serving + 250mL water): (12g carbohydrate x 39 GI) / 100 = 5

3. Vanilla Vibrant Shake Drink (non-soybean) (blender preparation) (45g / serving + 250mL water): (12g carbohydrate x 35 GI) / 100 = 4

The three shake beverages tested in this study produced GL values of 3-5, which attributed these products to the low GL category. Thus, it is apparent that a shake drink containing the composition of the present invention has a reduced blood glucose response despite its total calories, sugar and total carbohydrate content.

Example 4 Effect of blending on the survival rate of probiotics

According to this example, the effect of medium speed and high speed blending on the viability of B. coagulans GBI-30 strain was determined. Specifically, a 43 gram sample of a non-soybean vanilla shake drink sample containing about one billion CFU of GBI-30 Bacillus coagulans was mixed with 240 ml of skim milk at a medium speed and a high speed for 15 seconds at about 4 ° C in a blender. And 1 minute blending time and mixing in a shaker bottle and shaking by hand. CFU counts were measured after 7 days of incubation at 30 °C, followed by colonies. It was determined that there was no significant difference in the count and thus the survival rate, indicating that the survival rate was not affected by the blending.

Those skilled in the art of practicing the present invention are considering their presently preferred embodiments. I expect to think of many changes and changes afterwards. Therefore, only the limitations imposed on the scope of the invention are limited by the scope of the appended claims.

Figure 1 depicts the mean plasma glucose response profile for the equivalent carbohydrate portion of the reference food and the three protein products containing the probiotic and prebiotic compositions, shown as changes in plasma glucose from the fasted baseline level.

Claims (19)

A composition comprising a mixture of a probiotic composition and a prebiotic composition, wherein the probiotic composition comprises Bacillus coagulans and wherein the prebiotic composition comprises plant based fibers, resistant starch and short chains Oligosaccharides. The composition of claim 1, wherein the bacterium is Bacillus coagulans GBI-30 (ATTC No. PTA-6086). The composition of claim 1, wherein the plant-based fiber is selected from the group consisting of soybean, indica, pea, potato, rice, konjac, oat, guar, pectin and plantain. a group of people. The composition of claim 1, wherein the resistant starch is selected from the group consisting of resistant dextrin derived from wheat, corn or other plant sources. The composition of claim 1, wherein the short-chain oligosaccharide is selected from the group consisting of fructooligosaccharides (FOS), galactooligosaccharides (GOS), and fructose, alone or in any combination, A low polymer of glucose, galactose or other sugar molecules. The composition of claim 5, wherein the short chain oligosaccharide is FOS. The composition of claim 6, wherein the FOS is selected from the group consisting of canetriose (glucose-fructose-fructose or GF ₂ ), mold nystose (GF ₃ ), fructosyl-mold A group consisting of aldose sugar (GF ₄ ), GF ₅ or GF _{5+m (where m = 1 to 100)} and combinations thereof. The composition of claim 1, which is in the form of a lozenge, a powder or a liquid. A method of maintaining or improving gastrointestinal health in a mammalian subject, comprising administering to the subject a composition comprising a mixture of a probiotic composition and a prebiotic composition, wherein the probiotic composition comprises Bacillus coagulans And wherein the prebiotic composition comprises a plant Base fiber, resistant starch and short chain oligosaccharides. The method of claim 10, wherein the bacterium is Bacillus coagulans GBI-30 (ATTC No. PTA-6086). The method of claim 10, wherein the plant-based fiber is selected from the group consisting of fibers derived from soybean, inca, pea, potato, rice, konjac, oat, guar, pectin, and plantain. The method of claim 10, wherein the resistant starch is selected from the group consisting of resistant dextrin derived from wheat, corn or other plant sources. The method of claim 10, wherein the short-chain oligosaccharide is selected from the group consisting of fructooligosaccharides (FOS), galactooligosaccharides (GOS), and fructose, glucose, galactose or other sugar molecules, alone or in any combination. a group of low polymer compositions. The method of claim 13, wherein the short-chain oligosaccharide is FOS. The method of claim 14, wherein the FOS is selected from the group consisting of canetriose (glucose-fructose-fructose or GF ₂ ), mold erythritol (GF ₃ ), fructosyl-mold erythritol ( A group consisting of GF ₄ ), GF ₅ or GF _{5+m (where m=1-100)} and combinations thereof. The method of claim 10, which is in the form of a lozenge, a powder or a liquid. The method of claim 10, wherein the composition is administered to the mammalian subject in an amount from about 0.001 mg/kg to about 1 g/kg. The method of claim 10, wherein the composition is administered to the mammalian subject daily. The method of claim 10, wherein the composition is administered to the mammalian subject at least three days a week.