WO2007140230A2 - Methods of use and nutritional compositions of touchi extract - Google Patents

Methods of use and nutritional compositions of touchi extract Download PDF

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Publication number
WO2007140230A2
WO2007140230A2 PCT/US2007/069624 US2007069624W WO2007140230A2 WO 2007140230 A2 WO2007140230 A2 WO 2007140230A2 US 2007069624 W US2007069624 W US 2007069624W WO 2007140230 A2 WO2007140230 A2 WO 2007140230A2
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WIPO (PCT)
Prior art keywords
patient
composition
dietary regime
prebiotic
probiotic
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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PCT/US2007/069624
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French (fr)
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WO2007140230A3 (en
Inventor
Anne Falk
Norman Alan Greenberg
Kala Kaspar
Julie Swanson
Zamzam Roughead (Fariba)
Kevin Burke Miller
Satya Jonnalagadda
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Novartis Pharma GmbH Austria
Nestec SA
Novartis AG
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Novartis Pharma GmbH Austria
Nestec SA
Novartis AG
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Priority to BRPI0712087-7A priority Critical patent/BRPI0712087A2/en
Priority to US12/300,426 priority patent/US8815312B2/en
Priority to MX2008015031A priority patent/MX2008015031A/en
Priority to CA002655665A priority patent/CA2655665A1/en
Priority to EP07815041A priority patent/EP2021011A2/en
Priority to AU2007267560A priority patent/AU2007267560B2/en
Application filed by Novartis Pharma GmbH Austria, Nestec SA, Novartis AG filed Critical Novartis Pharma GmbH Austria
Priority to JP2009512294A priority patent/JP2009538342A/en
Publication of WO2007140230A2 publication Critical patent/WO2007140230A2/en
Publication of WO2007140230A3 publication Critical patent/WO2007140230A3/en
Anticipated expiration legal-status Critical
Priority to ZA2008/10849A priority patent/ZA200810849B/en
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L11/00—Pulses, i.e. fruits of leguminous plants, for production of food; Products from legumes; Preparation or treatment thereof
    • A23L11/50—Fermented pulses or legumes; Fermentation of pulses or legumes based on the addition of microorganisms
    • A—HUMAN NECESSITIES
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    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L11/00—Pulses, i.e. fruits of leguminous plants, for production of food; Products from legumes; Preparation or treatment thereof
    • A23L11/70—Germinated pulse products, e.g. from soy bean sprouts
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
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    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
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    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
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    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Definitions

  • the present invention relates generally to nutrition and more particularly to a method of use and nutritional compositions containing ⁇ -glucosidase inhibitors, and more specifically Touchi Extract.
  • Touchi Extract is a water-extract powder of fermented soybeans. Touchi Extract is derived from soybeans that have been fermented with Aspergillus Oryzae. Touchi Extracthas been shown to inhibit ⁇ -glucosidase activity leading to lower blood glucose concentrations and HbAIc values in individuals with type 2 diabetes, similar to Acarbose and Voglibose. Touchi Extract inhibits ⁇ -glucosidase exclusively and does not inhibit other digestive enzymes like amylase, pepsin, trypsin, chymotrypsin or lipase.
  • Metabolic Syndrome/Syndrome X is a cluster of metabolic risk factors, including elevated blood glucose, glucose intolerance, insulin resistance, elevated triglycerides, elevated LDL-cholesterol, low high-density lipoprotein (HDL) cholesterol, elevated blood pressure, abdominal obesity, pro-inflammatory states, and pro-thrombotic states.
  • Individuals with metabolic syndrome are at increased risk of cardiovascular disease and coronary heart disease and other diseases related to plaquing of the artery walls and type 2 diabetes.
  • cardiovascular disease and coronary heart disease Some of the risk factors of cardiovascular disease and coronary heart disease include impaired fasting glucose, elevated blood lipids (Total cholesterol, LDL-cholesterol, Triglycerides), low HDL- cholesterol, obesity, type 2 diabetes, elevated blood pressure, insulin resistance, and proinflammatory and pro-thrombotic factors.
  • the present invention relates to a method of use, composition or dietary regimen containing ⁇ -glucosidase inhibitors, and more specifically Touchi Extracts. Touchi Extract and
  • GLP-I glucagon-like peptide- 1
  • GLP-2 glucagon-like peptide-2
  • GLP-I acts to stimulate glucose-dependent insulin secretion, and pancreatic beta-cell proliferation and neogenesis.
  • the increased plasma concentration of GLP-I will improve glycemic control by stimulating insulin secretion in addition to the effect from Touchi Extract in delaying the appearance of glucose in the blood.
  • GLP -2 acts to enhance intestinal structure and function by improving crypt-villus architecture and increasing enzyme and transporter activities.
  • the increased plasma concentration of GLP-2 will improve intestinal structure and function and reduce intestinal inflammation.
  • the combination of Touchi Extract and/or other ⁇ -glucosidase inhibitors with flavanols may improve endothelial function by improving glycemic control and vasodilation.
  • Diabetes starting from early insulin resistance, to late exogenous insulin dependence can be positively effected by Touchi Extract and /or other ⁇ - glucosidase inhibitors.
  • Touchi Extract and /or other ⁇ - glucosidase inhibitors.
  • ⁇ - glucosidase inhibitors inhibits the breakdown of carbohydrates, thus prolonging the time carbohydrates are present in the intestine and thereby delaying the post-prandial rise in blood glucose levels.
  • This slower increase in post-prandial blood glucose concentrations can thus slow/delay the beta-cell secretion of insulin and thus minimize exposure of the body cells to high concentrations of insulin, thus contributing to improving insulin sensitivity and decreasing insulin resistance.
  • Touchi Extract and/or other ⁇ -glucosidase inhibitors will act to improve glycemic control, improve satiety and delay gastric emptying further improving satiety in addition to the effect from Touchi Extract in delaying the appearance of glucose in the blood via actions of GLP-I.
  • Touchi Extract and/or other ⁇ -glucosidase inhibitors inhibit the breakdown of carbohydrates, thus prolonging the time carbohydrates are present in the intestine and thereby delaying the post-prandial rise in blood glucose concentrations thus mitigating some of the sequelae of this syndrome.
  • Touchi Extract and/or other ⁇ -glucosidase inhibitors are their ability to stimulate GLP-I, which in turn stimulates beta-cell insulin secretion and can thus help lower blood glucose concentrations, and contribute to lower blood lipids, inflammation and thrombotic factors, blood pressure and abdominal obesity.
  • Both insulin-resistance and chronic obstructive pulmonary disease (COPD) are linked to inflammatory conditions and oxidative stress.
  • Providing Touchi Extract and/or other ⁇ - glucosidase inhibitors will benefit the individual through reduction of insulin secretion and hyperglycemia which lead to exacerbation of the condition.
  • the increased plasma concentration of GLP -2 from the Touchi Extract will help restore intestinal function in patients with malabsorption secondary to mucosal degeneration and will help optimize intestinal function including nutrient absorption in patients following bowel resection, including those with short-bowel syndrome and post-surgery for gastrointestinal malignancy and ulcerative colitis. Further, Touchi Extract will help restore normal intestinal function including the integrity of the gut barrier disrupted by intestinal inflammation.
  • probiotics and/or prebiotics can further improve the intestinal structure and function, and reduce inflammation as well as increase the immune response presented below.
  • Touchi Extract will help manage aberrant glucose and lipid metabolism through its mechanism of slowing down glucose metabolism and absorption and, thus, decrease some of the complications associated with Human Immunodeficiency Virus.
  • CF Cystic Fibrosis
  • Touchi Extract could be used to reduce post-prandial glucose excursions, therefore decrease insulin spikes and thus be helpful in managing the type 2 diabetes that is frequent in non-alcoholic steatohepatitis patients.
  • Touchi Extract could be helpful in decreasing endogenous production of triglycerides, and therefore may play a role in helping manage the accumulation of fat in the liver, since the natural action of insulin is to lower the blood sugar concentration through entry of the glucose into the cells or by storage of the glucose, sometimes as fats, such as triglycerides.
  • Touchi Extract in oral nutritional supplements (ONS) for critical care patients will improve glycemic control and reduce the risk of infections and other complications and improve the quality and rate of wound healing.
  • OTS oral nutritional supplements
  • PCOS Polycystic Ovarian Syndrome
  • Touchi Extract will help manage the post prandial glucose excursion and minimize the complications of this part of Polycystic Ovarian Syndrome, including infertility.
  • Touchi Extract will help manage the post prandial glucose excursion, therefore modulating plasma insulin spikes, and minimize the endothelial dysfunction leading to erectile dysfunction.
  • flavanols epicatechin and catechin compounds from cocoa, wine, green tea, . . .
  • flavanols may improve endothelial function by improving glycemic control and vasodilation.
  • ranges are used as a shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range.
  • the phrase "at least one of refers to the selection of any one member individually or any combination of the members.
  • the conjunction “and” or “or” can be used in the list of members, but the "at least one of phrase is the controlling language.
  • at least one of A, B, and C is shorthand for A alone, B alone, C alone, A and B, B and C, A and C, or A and B and C.
  • TE Touchi Extract
  • ⁇ -glucosidase inhibitor shall be interpreted to include Touchi Extract in all instances.
  • a dietary regimen includes, but is not limited to, a combination of food and/or drink items that fall into certain parameters (i.e. food and/or drink items that when taken together, contain a ratio of fat to protein of 1 : 1).
  • mammal includes, but is not limited to rodents, aquatic mammals, domestic animals such as dogs and cats, farm animals such as sheep, pigs, cows, and horses, and humans. Wherein the term mammal is used, it is contemplated that it also applies to other animals that are capable of the effect exhibited or intended to be exhibited, by the mammal.
  • Diabetes refers to states of physiologic function that fall along a continuum from euglycemic and normal insulin production and function to insulin dependency and pancreatic exhaustion, including, but not limited to: impaired glucose tolerance, insulin resistance, decreased insulin sensitivity, insulin dependence, including type 1 and type 2 Diabetes Mellitus.
  • Co-morbities of diabetes include, but are not limited to: cardiovascular disease, dyslipidemia, retinopathies, changes in collagen tissue, inflammation, and insulin resistance.
  • the present invention relates to a method of use, composition or dietary regimen containing ⁇ -glucosidase inhibitors, and more specifically Touchi Extract.
  • ⁇ -Glucosidase Inhibitors And Touchi Extract Touchi Extract TE
  • other ⁇ -glucosidase inhibitors due to their ability to inhibit carbohydrate breakdown, it is believed will act to increase the plasma concentration of glucagon- like peptide- 1 (GLP-I) and glucagon-like peptide-2 (GLP-2).
  • GLP-I is a hormone that is secreted from the endocrine L cells located in the distal small intestine and colon. GLP-I acts to stimulate glucose-dependent insulin secretion, and beta-cell proliferation and neogenesis. GLP-I is secreted in response to nutritional, hormonal and neural stimulation, with the primary stimulus being enteral nutrition.
  • Touchi Extract is a natural ⁇ - glucosidase inhibitor that inhibits the breakdown of carbohydrates, prolonging the time carbohydrates are present in the intestine. Therefore, a greater amount of carbohydrates may reach the distal small intestine and interact with the L cells to stimulate GLP-I secretion.
  • GLP-I and GLP-2 glucose reaches the distal small intestine it may be fermented producing short-chain fatty acids that trigger the production and secretion of GLP-I and GLP-2, and/or the sodium dependent transport of glucose across the brush border membrane of the L cell can trigger the secretion of GLP-I and GLP-2.
  • the increased plasma concentration of GLP-I will improve glycemic control in addition to the effect from Touchi Extract in delaying the appearance of glucose in the blood.
  • GLP-2 is a hormone that is secreted from the endocrine L cells located in the distal small intestine and colon. GLP-2 acts to enhance intestinal structure and function by improving crypt- villus architecture and increasing enzyme and transporter activities. GLP-2 is secreted in response to nutritional, hormonal and neural stimulation, with the primary stimulus being enteral nutrition.
  • Touchi Extract is a natural ⁇ -glucosidase inhibitor that inhibits the breakdown of carbohydrates, prolonging the time carbohydrates are present in the intestine. Therefore, a greater amount of carbohydrates may reach the distal small intestine and interact with the L cells to stimulate GLP-2 secretion. The increased plasma concentration of GLP-2 will improve intestinal structure and function and reduce intestinal inflammation.
  • Diabetes An estimated 175 million people suffer from type 2 diabetes around the world. Diabetes is the fourth leading case of death worldwide, and complications associated with diabetes include blindness, amputations, kidney failure, heart attack and nerve damage. These complications are related to hyperglycemia, defined as elevated concentrations of blood glucose. Hyperglycemia and hyperinsulinemia causes damage to the microvascular, resulting in endothelial dysfunction and potential blindness, kidney failure and nerve damage.
  • Diabetic nephropathy occurs in 20-40% of individuals with diabetes, with -43,000 people with diabetes begin treatment for kidney failure each year. Hyperglycemia is an independent risk factor for the incidence and progression of retinopathy. Neuropathy may develop very early in individuals with type 2 diabetes. The progression of diabetic nephropathy, retinopathy and neuropathy can be prevented by tight glycemic and blood pressure control.
  • the combination of Touchi Extract and/or other ⁇ -glucosidase inhibitors with flavanols may improve endothelial function by improving glycemic control and vasodilation.
  • flavanols i.e. epicatechin and catechin compounds from cocoa, wine, green tea
  • This combination may have a significant effect on improving the delay in the progression of the microvascular complications associated with diabetes.
  • CVD cardiovascular disease
  • CVD coronary heart disease
  • CVD cardiovascular disease
  • CVD coronary heart disease
  • risk factors For example, individuals with high blood pressure (i.e., > 140/90 mmHg), a known CVD risk factor, are at a greater risk for developing type 2 diabetes than are individuals having normal blood pressure.
  • HDLC high density lipoprotein cholesterol
  • TG triglyceride
  • diabetes itself may be considered a risk factor for CVD, as it has been shown that persons with type 2 diabetes have a high incidence of death at time of acute myocardial infarction and have a relatively poor prognosis for long-term survival after myocardial infarction.
  • CVD cardiovascular disease
  • Insulin resistance is a generalized metabolic disorder, in which the body cannot use insulin efficiently. Insulin resistance occurs when the normal amount of insulin secreted by the pancreas is not able to unlock the door to cells and thus blood glucose concentrations increase while the cells are deprived of glucose (energy). To maintain a normal blood glucose and energy supply to the cells, the pancreas secretes additional insulin. When the body cells resist or do not respond to even high concentrations of insulin, glucose builds up in the blood resulting in high blood glucose or type 2 diabetes. Touchi Extract and/or other ⁇ - glucosidase inhibitors, inhibits the breakdown of carbohydrates, thus prolonging the time carbohydrates are present in the intestine and thereby delaying the post-prandial rise in blood glucose concentrations. This slower increase in post-prandial blood glucose concentrations can thus slow/delay the beta-cell secretion of insulin and thus minimize the exposure of the body cells to high concentrations of insulin, thus contributing to improving insulin sensitivity and decreasing insulin resistance.
  • Touchi Extract and/or other ⁇ - glucosidase inhibitors will act to increase the plasma concentration of GLP-I and GLP -2 as described above.
  • the increased plasma concentration of GLP-I will improve glycemic control, improve satiety and delay gastric emptying further improving satiety in addition to the effect from Touchi Extract in delaying the appearance of glucose in the blood.
  • GLP- 1 concentrations are reported to be reduced in obese individuals. Therefore, the additional Touchi Extract and/or other ⁇ - glucosidase inhibitors to weight loss supplements or other medical food products, the levels of GLP-I could be increased and returned to normal levels.
  • Touchi Extract and/or other ⁇ - glucosidase inhibitors inhibit the breakdown of carbohydrates, thus prolonging the time carbohydrates are present in the intestine and thereby delaying the post-prandial rise in blood glucose concentrations.
  • This slower increase in blood glucose concentrations can play a critical role in regulating many of risk factors associated with metabolic syndrome.
  • Lower blood glucose concentrations result in: 1. lower concentrations of insulin secretion; 2. lower rates of conversion of carbohydrates to lipids (triglycerides, VLDL- cholesterol, LDL-Cholesterol); 3. lower abdominal obesity; 4. lower insulin resistance; 5. lower blood pressure; 6. lower levels of inflammation and thrombotic factors, all of which in turn can lower the risk of chronic diseases associated with metabolic syndrome.
  • GLP-I Another potential role of Touchi Extract is its ability to stimulate GLP-I, which in turn increases satiety to aid in weight loss ot weight maintenance.
  • GLP-I stimulates beta-cell insulin secretion and can thus help lower blood glucose concentrations, and contribute to lowered blood lipids, inflammation and thrombotic factors, blood pressure and abdominal obesity.
  • Touchi Extract and/or other ⁇ -glucosidase inhibitors inhibits the breakdown of carbohydrates, thus prolonging the time carbohydrates are present in the intestine and thereby delaying the post-prandial rise in blood glucose concentrations.
  • This slower increase in blood glucose concentrations can play a critical role in regulating many of the risk factors associated with metabolic syndrome.
  • Lower blood glucose concentrations result in: 1. lower concentrations of insulin secretion; 2. lower rates of conversion of carbohydrates to lipids (triglycerides, VLDL- cholesterol, LDL-Cholesterol); 3. lower abdominal obesity; 4. lower insulin resistance; 5. lower blood pressure; 6. lower levels of inflammation and thrombotic factors, all of which in turn can lower the risk of cardiovascular disease.
  • Touchi Extract and/or other ⁇ -glucosidase inhibitors are their ability to stimulate GLP-I, which in turn stimulates beta-cell insulin secretion and can thus help lower blood glucose concentrations, and contribute to lowered blood lipids, inflammation and thrombotic factors, blood pressure and abdominal obesity.
  • COPD Chronic Obstructive Pulmonary Disease
  • GLP-2 is a hormone that is secreted from the endocrine L cells located in the distal small intestine and colon. GLP-2 acts to enhance intestinal structure and function by improving crypt- villus architecture and increasing enzyme and transporter activities. GLP-2 is secreted in response to nutritional, hormonal and neural stimulation, with the primary stimulus being enteral nutrition.
  • Touchi Extract is a natural ⁇ -glucosidase inhibitor that inhibits the breakdown of carbohydrates, prolonging the time carbohydrates are present in the intestine. Therefore, a greater amount of carbohydrates may reach the distal small intestine and interact with the L cells to stimulate GLP-2 secretion.
  • the increased plasma concentration of GLP-2 will stimulate intestinal adaptation, improving the structure and function of the intestine, including, but not limited to, absorption of nutrients and water, secretion of protective mucins and immunoglobins, and improved barrier- protection against pathogenic bacteria.
  • Touchi Extract will help restore intestinal function in patients with malabsorption secondary to mucosal degeneration associated with: cancer chemo- or radiation-therapy
  • TPN Total Parenteral Nutrition
  • TPN transition patients acute illness-related gut dysfunction critically ill & septic patients burn & trauma patients surgical & medical patients acute pancreatitis intestinal inflammation in active inflammatory bowel disease
  • Touchi Extract will help optimize intestinal function including nutrient absorption in patients following bowel resection, including those with short-bowel syndrome and post- surgery for gastrointestinal malignancy and ulcerative colitis.
  • Touchi Extract will help restore normal intestinal function including the integrity of the gut barrier disrupted by intestinal inflammation.
  • Patients with an inflammation- compromised gut barrier include: acute illness-related gut dysfunction critically ill & septic patients burn & trauma patients surgical & medical patients acute pancreatitis intestinal inflammation in active IBD cancer chemo- or radiation-therapy
  • Touchi Extract will help manage complications in these patients which include infection by pathogenic gut bacteria and diarrhea.
  • Specific disease states that could benefit include inflammatory bowel disease (Crohn's disease and ulcerative colitis), irritable bowel syndrome, short-bowel syndrome, malabsorption, diarrhea, constipation and gut atrophy due to transition from parenteral to enteral nutrition or radiation/chemotherapy.
  • inflammatory bowel disease Crohn's disease and ulcerative colitis
  • irritable bowel syndrome short-bowel syndrome
  • malabsorption diarrhea
  • constipation constipation
  • gut atrophy due to transition from parenteral to enteral nutrition or radiation/chemotherapy.
  • probiotics preferably Lactobacillus reuteri
  • probiotics and prebiotics to increase the gut structure and function as the concentration of GLP-2 would be increased, optimal amounts of butyrate would be produced through fermentation and the probiotic can have direct effects on the gut integrity and immune response to insult.
  • Specific prebiotics could include but not be limited to fructooligosaccharides (FOS), galactooligosaccharides (GOS), inulin and partially hydrolyzed guar gum.
  • Specific probiotics could include but not be limited to L. reuteri, E.
  • HIV Human immunodeficiency virus
  • HAART Human immunodeficiency virus infected individuals receiving highly active antiretroviral therapy (HAART) experience metabolic abnormalities including hyperlipidemia and insulin resistance. The combination of these findings has been termed the lipodystrophy syndrome. Because HAART is helping to extend the lives of HIV patients, there is a growing concern of increased cardiovascular risk in lipodystrophic individuals given the co-morbid derangements in glucose and lipid homeostasis. The use of Touchi Extract will help manage aberrant glucose and lipid metabolism through its mechanism of slowing down glucose metabolism and absorption and, thus, decrease some of the complications associated with HAART.
  • Cystic fibrosis is characterized by thick secretions in a number of organs, including the pancreas. Most patients with CF have obstruction of the pancreatic ducts, often leading to insufficient endocrine function, such as insufficient insulin availability. This insufficiency can lead to CF-related diabetes.
  • Touchi Extract to reduce post-prandial glucose excursions could be helpful in managing CF-related diabetes by reducing the need for excess insulin secretion.
  • NASH Non-alcoholic steatohepatitis
  • Non-alcoholic steatohepatitis is an advanced stage of fatty liver disease in the absence of alcohol abuse. It is frequently associated with type 2 diabetes, metabolic syndrome, obesity, hyperlipidemia, and extensive small bowel resection. Insulin resistance plays a central role in the development of this type of fatty liver disease. These patients have high postprandial triglyceride levels. Touchi Extract could be used to reduce post-prandial glucose excursions, therefore decreasing insulin spiking and thus be helpful in managing the type 2 diabetes that is common in NASH patients.
  • Touchi Extract could be helpful in decreasing endogenous production of triglycerides, and therefore may play a role in helping manage the accumulation of fat in the liver, since the natural action of insulin is to lower the blood sugar concentration through entry of the glucose into the cells or by storage of the glucose, sometimes as fats, such as triglycerides.
  • Stress induced hyperglycemia is a common problem in those experiencing physiological, physical, psychiatric, traumatic, and /or iatrogenic stress.
  • the critical care patient requires intensive glucose monitoring and insulin administration to decrease hyperglycemia due to insulin resistance.
  • Touchi Extract enables a lower post prandial peak glucose to occur due to delayed enzyme action on carbohydrate polymers and oligosaccharides.
  • Improved glycemic control in critical care patients has been proven to improve outcomes, for example, faster and stronger wound healing, fewer infections, and decreased complications.
  • the use of Touchi Extract in oral nutritional supplements for critical care patients will improve glycemic control and reduce the risk of infections and other complications and improve the quality and rate of wound healing.
  • PU Pressure ulcers
  • the skin of the elderly is typically thinner and susceptible to failure under pressure. Individuals with diabetes have an increased risk of PU and they also take longer to recover and heal after a PU has developed.
  • the use of Touchi Extract to maintain better glucose concentrations aids in prevention and healing of PUs.
  • PCOS Polycystic Ovarian Syndrome
  • PCOS is a health problem that can affect a woman's menstrual cycle, fertility, hormones, insulin production and resistance, heart, blood vessels, and appearance. Specifically, PCOS patients are at high risk for type 2 diabetes.
  • PCOS is typically managed pharmaceutically with the use of Glucophage (Metformin) and other biguanides that act by decreasing hepatic glucose production and improve insulin sensitivity. Biguanides have been shown to increase the rate of pregnancies in women that suffer from PCOS and infertility. The use of Touchi Extract will help manage the post prandial glucose excursion and minimize the complications of this part of PCOS.
  • Glucophage Metformin
  • Biguanides have been shown to increase the rate of pregnancies in women that suffer from PCOS and infertility.
  • the use of Touchi Extract will help manage the post prandial glucose excursion and minimize the complications of this part of PCOS.
  • Erectile dysfunction appears to be highly prevalent in individuals with diabetes (around 50% at 50 years of age) and more severe than in the rest of the population. Its etiology is multifactorial in this subset of patients. ED is highly correlated to multiple vascular risk factors and can be considered as a manifestation of endothelial dysfunction in general, alerting the physician to look at underlying silent coronary bed atherosclerosis. It is also dependent on the poor control of diabetes and on the presence of its chronic complications. Because of the multiple etiologies of ED in individuals with diabetes, a multifactorial approach is warranted to get an optimal response in treating such patients.
  • Touchi Extract will help manage the post prandial glucose excursion, therefore modulating plasma insulin spikes, and minimize the endothelial dysfunction leading to ED.
  • the combination of Touchi Extract with flavanols may improve endothelial function by improving glycemic control and vasodilation. This combination may have a significant effect on improving the delay in the progression of the microvascular complications associated with diabetes as well as individuals with endothelial dysfunction without diabetes.

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Abstract

Disclosed is a method and composition for nutritional compositions containing -glucosidase inhibitors, and more specifically Touchi Extract and its uses in the treatment of many disorders. These disorders include diabetes, hyperlipidemia, obesity, Metabolic syndrome/Syndrome X, COPD, malabsorption, Crohn's disease, diarrhea, constipation, irritable bowel syndrome, human immunodeficiency virus, cystic fibrosis, non-alcoholic steatohepatitis, polycystic ovarian syndrome including associate infertility, and erectile dysfunction. Further, -glucosidase inhibitors, and more specifically Touchi Extract can be used to aid healing in critical care patients and for general wound healing. Additionally, -glucosidase inhibitors, including Touchi Extract can be used to enhance athletic performance.

Description

METHODS OF USE AND NUTRITIONAL COMPOSITIONS OF TOUCHI EXTRACT
TECHNICAL FIELD
The present invention relates generally to nutrition and more particularly to a method of use and nutritional compositions containing α-glucosidase inhibitors, and more specifically Touchi Extract.
BACKGROUND OF THE INVENTION
Touchi Extract (TE) is a water-extract powder of fermented soybeans. Touchi Extract is derived from soybeans that have been fermented with Aspergillus Oryzae. Touchi Extracthas been shown to inhibit α-glucosidase activity leading to lower blood glucose concentrations and HbAIc values in individuals with type 2 diabetes, similar to Acarbose and Voglibose. Touchi Extract inhibits α-glucosidase exclusively and does not inhibit other digestive enzymes like amylase, pepsin, trypsin, chymotrypsin or lipase.
In the past 25 years, US obesity rates have more than doubled. In 2000, the US prevalence of obesity was estimated to be 31%. The obesity epidemic is not limited to the US population. In the past 15 years, the prevalence of obesity among the majority of European populations has also increased 10 to 40%. Numerous studies have linked obesity with an increased risk of premature mortality, demonstrating that the probability of death increases as excess body weight increases. Obesity now accounts for approximately 112,000 deaths per year in the US, second only to tobacco use among preventable causes of death. It has been clearly demonstrated that weight loss alleviates symptoms and reduces the severity of many chronic conditions associated with obesity, including: hypertension, coronary heart disease, type 2 diabetes, osteoarthritis and sleep apnea. Moreover, weight loss prevents future illnesses by controlling underlying risk factors. Reducing body weight has been shown to protect against cardiovascular disease by lowering blood pressure, total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides
Similarly, Metabolic Syndrome/Syndrome X is a cluster of metabolic risk factors, including elevated blood glucose, glucose intolerance, insulin resistance, elevated triglycerides, elevated LDL-cholesterol, low high-density lipoprotein (HDL) cholesterol, elevated blood pressure, abdominal obesity, pro-inflammatory states, and pro-thrombotic states. Individuals with metabolic syndrome are at increased risk of cardiovascular disease and coronary heart disease and other diseases related to plaquing of the artery walls and type 2 diabetes. Some of the risk factors of cardiovascular disease and coronary heart disease include impaired fasting glucose, elevated blood lipids (Total cholesterol, LDL-cholesterol, Triglycerides), low HDL- cholesterol, obesity, type 2 diabetes, elevated blood pressure, insulin resistance, and proinflammatory and pro-thrombotic factors.
SUMMARY OF THE INVENTION
The present invention relates to a method of use, composition or dietary regimen containing α-glucosidase inhibitors, and more specifically Touchi Extracts. Touchi Extract and
other α-glucosidase inhibitors, as a result of their ability to inhibit carbohydrate breakdown, will act to increase the plasma concentration of glucagon-like peptide- 1 (GLP-I) and glucagon-like peptide-2 (GLP-2).
GLP-I acts to stimulate glucose-dependent insulin secretion, and pancreatic beta-cell proliferation and neogenesis. The increased plasma concentration of GLP-I will improve glycemic control by stimulating insulin secretion in addition to the effect from Touchi Extract in delaying the appearance of glucose in the blood.
GLP -2 acts to enhance intestinal structure and function by improving crypt-villus architecture and increasing enzyme and transporter activities. The increased plasma concentration of GLP-2 will improve intestinal structure and function and reduce intestinal inflammation.
In addition, the combination of Touchi Extract and/or other α-glucosidase inhibitors with flavanols (i.e. epicatechin and catechin compounds from cocoa, wine, grape seed and green tea) may improve endothelial function by improving glycemic control and vasodilation.
Diabetes, starting from early insulin resistance, to late exogenous insulin dependence can be positively effected by Touchi Extract and /or other α- glucosidase inhibitors. Touchi Extract
and/or other α- glucosidase inhibitors, inhibits the breakdown of carbohydrates, thus prolonging the time carbohydrates are present in the intestine and thereby delaying the post-prandial rise in blood glucose levels. This slower increase in post-prandial blood glucose concentrations can thus slow/delay the beta-cell secretion of insulin and thus minimize exposure of the body cells to high concentrations of insulin, thus contributing to improving insulin sensitivity and decreasing insulin resistance.
For obesity, Touchi Extract and/or other α-glucosidase inhibitors will act to improve glycemic control, improve satiety and delay gastric emptying further improving satiety in addition to the effect from Touchi Extract in delaying the appearance of glucose in the blood via actions of GLP-I. In Metabolic Syndrome/Syndrome X, Touchi Extract and/or other α-glucosidase inhibitors, inhibit the breakdown of carbohydrates, thus prolonging the time carbohydrates are present in the intestine and thereby delaying the post-prandial rise in blood glucose concentrations thus mitigating some of the sequelae of this syndrome.
Another potential role of Touchi Extract and/or other α-glucosidase inhibitors is their ability to stimulate GLP-I, which in turn stimulates beta-cell insulin secretion and can thus help lower blood glucose concentrations, and contribute to lower blood lipids, inflammation and thrombotic factors, blood pressure and abdominal obesity.
Both insulin-resistance and chronic obstructive pulmonary disease (COPD) are linked to inflammatory conditions and oxidative stress. Providing Touchi Extract and/or other α- glucosidase inhibitors will benefit the individual through reduction of insulin secretion and hyperglycemia which lead to exacerbation of the condition.
The increased plasma concentration of GLP -2 from the Touchi Extract will help restore intestinal function in patients with malabsorption secondary to mucosal degeneration and will help optimize intestinal function including nutrient absorption in patients following bowel resection, including those with short-bowel syndrome and post-surgery for gastrointestinal malignancy and ulcerative colitis. Further, Touchi Extract will help restore normal intestinal function including the integrity of the gut barrier disrupted by intestinal inflammation.
The addition of probiotics and/or prebiotics can further improve the intestinal structure and function, and reduce inflammation as well as increase the immune response presented below.
In the case of commercially available sports products, excess blood sugar is stored for later use, a state which may actually cause hypoglycemia that could negatively impact athletic performance. Extending the period over which carbohydrates are metabolized to monosaccahrides for absorption through the use of Touchi Extract and/or other α-glucosidase inhibitors is thought to increase the endurance potential of athletes consuming the product.
The use of Touchi Extract will help manage aberrant glucose and lipid metabolism through its mechanism of slowing down glucose metabolism and absorption and, thus, decrease some of the complications associated with Human Immunodeficiency Virus.
Most patients with Cystic Fibrosis (CF) have obstruction of the pancreatic ducts, often leading to insufficient endocrine function, such as insufficient insulin availability. This insufficiency can lead to CF-related diabetes. The use of Touchi Extract to reduce post-prandial glucose excursions could be helpful in managing Cystic fibrosis -related diabetes.
Touchi Extract could be used to reduce post-prandial glucose excursions, therefore decrease insulin spikes and thus be helpful in managing the type 2 diabetes that is frequent in non-alcoholic steatohepatitis patients. In addition, Touchi Extract could be helpful in decreasing endogenous production of triglycerides, and therefore may play a role in helping manage the accumulation of fat in the liver, since the natural action of insulin is to lower the blood sugar concentration through entry of the glucose into the cells or by storage of the glucose, sometimes as fats, such as triglycerides.
The use of Touchi Extract in oral nutritional supplements (ONS) for critical care patients will improve glycemic control and reduce the risk of infections and other complications and improve the quality and rate of wound healing. The same rational for tube feedings containing Touchi Extract can be assumed.
Elevated blood glucose concentrations are known to delay wound healing. The use of Touchi Extract to reduce the post prandial glucose excursion will minimize the impaired healing, including pressure ulcers. Polycystic Ovarian Syndrome (PCOS)
The use of Touchi Extract will help manage the post prandial glucose excursion and minimize the complications of this part of Polycystic Ovarian Syndrome, including infertility.
The use of Touchi Extract will help manage the post prandial glucose excursion, therefore modulating plasma insulin spikes, and minimize the endothelial dysfunction leading to erectile dysfunction. In addition, the combination of Touchi Extract with flavanols (epicatechin and catechin compounds from cocoa, wine, green tea, . . . ) may improve endothelial function by improving glycemic control and vasodilation.
The illustrative aspects of the present invention are designed to solve the problems herein described and other problems not discussed, which are discoverable by a skilled artisan.
DETAILED DESCRIPTION
As used throughout, ranges are used as a shorthand for describing each and every value that is within the range. Any value within the range can be selected as the terminus of the range. When used, the phrase "at least one of refers to the selection of any one member individually or any combination of the members. The conjunction "and" or "or" can be used in the list of members, but the "at least one of phrase is the controlling language. For example, at least one of A, B, and C is shorthand for A alone, B alone, C alone, A and B, B and C, A and C, or A and B and C.
All values contained throughout this application, including the claims are deemed to be approximate, whether or not the term "about" is used, unless specifically stated as exact. The use of the term Touchi Extract (TE) shall be interpreted to mean any α-glucosidase inhibitor that would exhibit the same property in a nutritional composition or dietary regime.
The use of the term α-glucosidase inhibitor shall be interpreted to include Touchi Extract in all instances.
A dietary regimen includes, but is not limited to, a combination of food and/or drink items that fall into certain parameters (i.e. food and/or drink items that when taken together, contain a ratio of fat to protein of 1 : 1).
The term "mammal" includes, but is not limited to rodents, aquatic mammals, domestic animals such as dogs and cats, farm animals such as sheep, pigs, cows, and horses, and humans. Wherein the term mammal is used, it is contemplated that it also applies to other animals that are capable of the effect exhibited or intended to be exhibited, by the mammal.
Diabetes as used herein refers to states of physiologic function that fall along a continuum from euglycemic and normal insulin production and function to insulin dependency and pancreatic exhaustion, including, but not limited to: impaired glucose tolerance, insulin resistance, decreased insulin sensitivity, insulin dependence, including type 1 and type 2 Diabetes Mellitus.
Co-morbities of diabetes include, but are not limited to: cardiovascular disease, dyslipidemia, retinopathies, changes in collagen tissue, inflammation, and insulin resistance.
The present invention relates to a method of use, composition or dietary regimen containing α-glucosidase inhibitors, and more specifically Touchi Extract.
α-Glucosidase Inhibitors And Touchi Extract Touchi Extract (TE) and other α-glucosidase inhibitors, due to their ability to inhibit carbohydrate breakdown, it is believed will act to increase the plasma concentration of glucagon- like peptide- 1 (GLP-I) and glucagon-like peptide-2 (GLP-2).
GLP-I is a hormone that is secreted from the endocrine L cells located in the distal small intestine and colon. GLP-I acts to stimulate glucose-dependent insulin secretion, and beta-cell proliferation and neogenesis. GLP-I is secreted in response to nutritional, hormonal and neural stimulation, with the primary stimulus being enteral nutrition. Touchi Extract is a natural α- glucosidase inhibitor that inhibits the breakdown of carbohydrates, prolonging the time carbohydrates are present in the intestine. Therefore, a greater amount of carbohydrates may reach the distal small intestine and interact with the L cells to stimulate GLP-I secretion. It is believed that when glucose reaches the distal small intestine it may be fermented producing short-chain fatty acids that trigger the production and secretion of GLP-I and GLP-2, and/or the sodium dependent transport of glucose across the brush border membrane of the L cell can trigger the secretion of GLP-I and GLP-2. The increased plasma concentration of GLP-I will improve glycemic control in addition to the effect from Touchi Extract in delaying the appearance of glucose in the blood.
GLP-2 is a hormone that is secreted from the endocrine L cells located in the distal small intestine and colon. GLP-2 acts to enhance intestinal structure and function by improving crypt- villus architecture and increasing enzyme and transporter activities. GLP-2 is secreted in response to nutritional, hormonal and neural stimulation, with the primary stimulus being enteral nutrition. Touchi Extract is a natural α-glucosidase inhibitor that inhibits the breakdown of carbohydrates, prolonging the time carbohydrates are present in the intestine. Therefore, a greater amount of carbohydrates may reach the distal small intestine and interact with the L cells to stimulate GLP-2 secretion. The increased plasma concentration of GLP-2 will improve intestinal structure and function and reduce intestinal inflammation.
Diabetes/Microvascular Complications (Kidney/Eye/Nerve)
An estimated 175 million people suffer from type 2 diabetes around the world. Diabetes is the fourth leading case of death worldwide, and complications associated with diabetes include blindness, amputations, kidney failure, heart attack and nerve damage. These complications are related to hyperglycemia, defined as elevated concentrations of blood glucose. Hyperglycemia and hyperinsulinemia causes damage to the microvascular, resulting in endothelial dysfunction and potential blindness, kidney failure and nerve damage.
Diabetic nephropathy occurs in 20-40% of individuals with diabetes, with -43,000 people with diabetes begin treatment for kidney failure each year. Hyperglycemia is an independent risk factor for the incidence and progression of retinopathy. Neuropathy may develop very early in individuals with type 2 diabetes. The progression of diabetic nephropathy, retinopathy and neuropathy can be prevented by tight glycemic and blood pressure control.
In addition, the combination of Touchi Extract and/or other α-glucosidase inhibitors with flavanols (i.e. epicatechin and catechin compounds from cocoa, wine, green tea) may improve endothelial function by improving glycemic control and vasodilation. This combination may have a significant effect on improving the delay in the progression of the microvascular complications associated with diabetes.
Correlation Between Diabetes and Risk Factors for Cardiovascular Disease Diabetes and cardiovascular disease (CVD) and/or coronary heart disease (CHD) share a number of risk factors. For example, individuals with high blood pressure (i.e., > 140/90 mmHg), a known CVD risk factor, are at a greater risk for developing type 2 diabetes than are individuals having normal blood pressure. Similarly, individuals with high density lipoprotein cholesterol (HDLC) concentrations of 35 mg/dL or less or triglyceride (TG) concentrations of 250 mg/dL or more, both known risk factors for CVD, are also at an increased risk for developing Type 2 diabetes.
In addition, diabetes itself may be considered a risk factor for CVD, as it has been shown that persons with type 2 diabetes have a high incidence of death at time of acute myocardial infarction and have a relatively poor prognosis for long-term survival after myocardial infarction. The data above suggest, therefore, that it is advisable to treat an individual with diabetes as though he or she was at increased risk for CVD, even if the individual does not have other CVD risk factors.
Insulin Resistance
Insulin resistance is a generalized metabolic disorder, in which the body cannot use insulin efficiently. Insulin resistance occurs when the normal amount of insulin secreted by the pancreas is not able to unlock the door to cells and thus blood glucose concentrations increase while the cells are deprived of glucose (energy). To maintain a normal blood glucose and energy supply to the cells, the pancreas secretes additional insulin. When the body cells resist or do not respond to even high concentrations of insulin, glucose builds up in the blood resulting in high blood glucose or type 2 diabetes. Touchi Extract and/or other α- glucosidase inhibitors, inhibits the breakdown of carbohydrates, thus prolonging the time carbohydrates are present in the intestine and thereby delaying the post-prandial rise in blood glucose concentrations. This slower increase in post-prandial blood glucose concentrations can thus slow/delay the beta-cell secretion of insulin and thus minimize the exposure of the body cells to high concentrations of insulin, thus contributing to improving insulin sensitivity and decreasing insulin resistance.
Obesity
Due to its ability to inhibit carbohydrate breakdown, it is proposed that Touchi Extract and/or other α- glucosidase inhibitors will act to increase the plasma concentration of GLP-I and GLP -2 as described above. The increased plasma concentration of GLP-I will improve glycemic control, improve satiety and delay gastric emptying further improving satiety in addition to the effect from Touchi Extract in delaying the appearance of glucose in the blood. In addition, GLP- 1 concentrations are reported to be reduced in obese individuals. Therefore, the additional Touchi Extract and/or other α- glucosidase inhibitors to weight loss supplements or other medical food products, the levels of GLP-I could be increased and returned to normal levels.
Metabolic Syndrome/Syndrome X
Touchi Extract and/or other α- glucosidase inhibitors, inhibit the breakdown of carbohydrates, thus prolonging the time carbohydrates are present in the intestine and thereby delaying the post-prandial rise in blood glucose concentrations. This slower increase in blood glucose concentrations can play a critical role in regulating many of risk factors associated with metabolic syndrome. Lower blood glucose concentrations result in: 1. lower concentrations of insulin secretion; 2. lower rates of conversion of carbohydrates to lipids (triglycerides, VLDL- cholesterol, LDL-Cholesterol); 3. lower abdominal obesity; 4. lower insulin resistance; 5. lower blood pressure; 6. lower levels of inflammation and thrombotic factors, all of which in turn can lower the risk of chronic diseases associated with metabolic syndrome. Another potential role of Touchi Extract is its ability to stimulate GLP-I, which in turn increases satiety to aid in weight loss ot weight maintenance. In addition, GLP-I stimulates beta-cell insulin secretion and can thus help lower blood glucose concentrations, and contribute to lowered blood lipids, inflammation and thrombotic factors, blood pressure and abdominal obesity.
Heart Health/Cardiovascular Disease/Elevated Lipids
Touchi Extract and/or other α-glucosidase inhibitors, inhibits the breakdown of carbohydrates, thus prolonging the time carbohydrates are present in the intestine and thereby delaying the post-prandial rise in blood glucose concentrations. This slower increase in blood glucose concentrations can play a critical role in regulating many of the risk factors associated with metabolic syndrome. Lower blood glucose concentrations result in: 1. lower concentrations of insulin secretion; 2. lower rates of conversion of carbohydrates to lipids (triglycerides, VLDL- cholesterol, LDL-Cholesterol); 3. lower abdominal obesity; 4. lower insulin resistance; 5. lower blood pressure; 6. lower levels of inflammation and thrombotic factors, all of which in turn can lower the risk of cardiovascular disease. Another potential role of Touchi Extract and/or other α-glucosidase inhibitors is their ability to stimulate GLP-I, which in turn stimulates beta-cell insulin secretion and can thus help lower blood glucose concentrations, and contribute to lowered blood lipids, inflammation and thrombotic factors, blood pressure and abdominal obesity.
Chronic Obstructive Pulmonary Disease (COPD) Chronic Obstructive Pulmonary Disease patients suffer from inflammation and blockage of the lungs which decreases their ability to supply oxygen to tissues. Increased resting energy expenditure is common in COPD and it is often assumed that wasting is the consequence of an imbalance between energy intake and expenditure. Cross-sectional studies have noted that subjects with diabetes have lower lung function than individuals without diabetes. In addition, both insulin-resistance and COPD are linked to inflammatory conditions and oxidative stress. Carbon dioxide is the end-product of glucose metabolism by mitochondria. As a result, COPD patients on high carbohydrate diets have to exchange more carbon dioxide from their lungs. Providing Touchi Extract and/or other α-glucosidase inhibiters will benefit the individual through reduction of hyperglycemia which leads to exacerbation of the condition caused by oxidative stress increased by blood glucose fluctuations.
Gut Integrity/Intestinal Adaptation
GLP-2 is a hormone that is secreted from the endocrine L cells located in the distal small intestine and colon. GLP-2 acts to enhance intestinal structure and function by improving crypt- villus architecture and increasing enzyme and transporter activities. GLP-2 is secreted in response to nutritional, hormonal and neural stimulation, with the primary stimulus being enteral nutrition. Touchi Extract is a natural α-glucosidase inhibitor that inhibits the breakdown of carbohydrates, prolonging the time carbohydrates are present in the intestine. Therefore, a greater amount of carbohydrates may reach the distal small intestine and interact with the L cells to stimulate GLP-2 secretion. The increased plasma concentration of GLP-2 will stimulate intestinal adaptation, improving the structure and function of the intestine, including, but not limited to, absorption of nutrients and water, secretion of protective mucins and immunoglobins, and improved barrier- protection against pathogenic bacteria.
Thus, Touchi Extract will help restore intestinal function in patients with malabsorption secondary to mucosal degeneration associated with: cancer chemo- or radiation-therapy
Total Parenteral Nutrition (TPN)-related gut atrophy (TPN transition patients) acute illness-related gut dysfunction critically ill & septic patients burn & trauma patients surgical & medical patients acute pancreatitis intestinal inflammation in active inflammatory bowel disease
Thus, Touchi Extract will help optimize intestinal function including nutrient absorption in patients following bowel resection, including those with short-bowel syndrome and post- surgery for gastrointestinal malignancy and ulcerative colitis.
Further, Touchi Extract will help restore normal intestinal function including the integrity of the gut barrier disrupted by intestinal inflammation. Patients with an inflammation- compromised gut barrier include: acute illness-related gut dysfunction critically ill & septic patients burn & trauma patients surgical & medical patients acute pancreatitis intestinal inflammation in active IBD cancer chemo- or radiation-therapy
In effect, Touchi Extract will help manage complications in these patients which include infection by pathogenic gut bacteria and diarrhea.
Specific disease states that could benefit include inflammatory bowel disease (Crohn's disease and ulcerative colitis), irritable bowel syndrome, short-bowel syndrome, malabsorption, diarrhea, constipation and gut atrophy due to transition from parenteral to enteral nutrition or radiation/chemotherapy.
GI Health/Probiotics
The addition of probiotics, preferably Lactobacillus reuteri, can further improve the intestinal structure and function and reduction in inflammation as well as increase the immune response previously noted with L. reuteri. In addition, there is the possibility of a combination of TE, probiotics and prebiotics to increase the gut structure and function as the concentration of GLP-2 would be increased, optimal amounts of butyrate would be produced through fermentation and the probiotic can have direct effects on the gut integrity and immune response to insult. Specific prebiotics could include but not be limited to fructooligosaccharides (FOS), galactooligosaccharides (GOS), inulin and partially hydrolyzed guar gum. Specific probiotics could include but not be limited to L. reuteri, E. coli Nissle 1917, L. rhamnosus GG, L. casei, L. johnsonii, L. salivarius, Bifidobacteria breve, B. bifidus, and Sacchromyces Boulardi. Athletic Performance Enhancement
Both physically trained and novice athletes performing moderate exercise (cycling, jogging, swimming, etc) require a steady source of carbohydrate to maintain activity for extended periods. Commercially available sports products describe how the energy in their product is quickly metabolized and available for use. However, quickly absorbed carbohydrates increase blood sugar which in turn increases insulin activity. The natural action of insulin is to lower the blood sugar concentration through promoting entry of the glucose into the cells or by storage of the glucose. In the case of commercially available sports products, the excess blood sugar is then stored for later use, a state which may actually cause hypoglycemia that could negatively impact athletic performance. Extending the period over which carbohydrate is metabolized to glucose for absorption through the use of Touchi Extract and/or other α- glucosidase inhibitors is suggested to increase the endurance potential of athletes consuming the product.
Human immunodeficiency virus (HIV)
Human immunodeficiency virus infected individuals receiving highly active antiretroviral therapy (HAART) experience metabolic abnormalities including hyperlipidemia and insulin resistance. The combination of these findings has been termed the lipodystrophy syndrome. Because HAART is helping to extend the lives of HIV patients, there is a growing concern of increased cardiovascular risk in lipodystrophic individuals given the co-morbid derangements in glucose and lipid homeostasis. The use of Touchi Extract will help manage aberrant glucose and lipid metabolism through its mechanism of slowing down glucose metabolism and absorption and, thus, decrease some of the complications associated with HAART.
Cystic Fibrosis
Cystic fibrosis (CF) is characterized by thick secretions in a number of organs, including the pancreas. Most patients with CF have obstruction of the pancreatic ducts, often leading to insufficient endocrine function, such as insufficient insulin availability. This insufficiency can lead to CF-related diabetes. The use of Touchi Extract to reduce post-prandial glucose excursions could be helpful in managing CF-related diabetes by reducing the need for excess insulin secretion.
Non-alcoholic steatohepatitis (NASH)
Non-alcoholic steatohepatitis is an advanced stage of fatty liver disease in the absence of alcohol abuse. It is frequently associated with type 2 diabetes, metabolic syndrome, obesity, hyperlipidemia, and extensive small bowel resection. Insulin resistance plays a central role in the development of this type of fatty liver disease. These patients have high postprandial triglyceride levels. Touchi Extract could be used to reduce post-prandial glucose excursions, therefore decreasing insulin spiking and thus be helpful in managing the type 2 diabetes that is common in NASH patients. In addition, Touchi Extract could be helpful in decreasing endogenous production of triglycerides, and therefore may play a role in helping manage the accumulation of fat in the liver, since the natural action of insulin is to lower the blood sugar concentration through entry of the glucose into the cells or by storage of the glucose, sometimes as fats, such as triglycerides. Critical Care
Stress induced hyperglycemia is a common problem in those experiencing physiological, physical, psychiatric, traumatic, and /or iatrogenic stress. The critical care patient requires intensive glucose monitoring and insulin administration to decrease hyperglycemia due to insulin resistance. Touchi Extract enables a lower post prandial peak glucose to occur due to delayed enzyme action on carbohydrate polymers and oligosaccharides. Improved glycemic control in critical care patients has been proven to improve outcomes, for example, faster and stronger wound healing, fewer infections, and decreased complications. The use of Touchi Extract in oral nutritional supplements for critical care patients will improve glycemic control and reduce the risk of infections and other complications and improve the quality and rate of wound healing. The same rationale for tube feedings containing Touchi Extract can be assumed. The tube feeding is often disrupted due to the need to do something with the patient. Higher feed rates in the hours available for feeding will may cause hyperglycemia. Touchi Extract will reduce the degree of hyperglycemia.
Wound Healing
Elevated blood glucose concentrations, malnutrition and aging are known to delay wound healing. Patients with diabetes are a higher risk for developing peripheral neuropathy over time. This leads to a lack of sensation in the limbs, particularly the feet and lower legs. As a result of the lack of sensation in peripheral neuropathy, an irritation will often go unnoticed until a wound occurs. The healing of such wounds is difficult for a patient with diabetes The use of Touchi Extract to reduce the post prandial glucose excursion will minimize the impaired healing. The diabetic develops peripheral vascular disease with time which will cause delayed healing. They also have a less efficient conversion of arginine to NO and citrulline.
Pressure ulcers (PU) are caused by the failing of skin over bony points on malnourished and inactive persons. The skin of the elderly is typically thinner and susceptible to failure under pressure. Individuals with diabetes have an increased risk of PU and they also take longer to recover and heal after a PU has developed. The use of Touchi Extract to maintain better glucose concentrations aids in prevention and healing of PUs.
Polycystic Ovarian Syndrome (PCOS)
PCOS is a health problem that can affect a woman's menstrual cycle, fertility, hormones, insulin production and resistance, heart, blood vessels, and appearance. Specifically, PCOS patients are at high risk for type 2 diabetes. PCOS is typically managed pharmaceutically with the use of Glucophage (Metformin) and other biguanides that act by decreasing hepatic glucose production and improve insulin sensitivity. Biguanides have been shown to increase the rate of pregnancies in women that suffer from PCOS and infertility. The use of Touchi Extract will help manage the post prandial glucose excursion and minimize the complications of this part of PCOS.
Erectile dysfunction (ED)
Erectile dysfunction (ED) appears to be highly prevalent in individuals with diabetes (around 50% at 50 years of age) and more severe than in the rest of the population. Its etiology is multifactorial in this subset of patients. ED is highly correlated to multiple vascular risk factors and can be considered as a manifestation of endothelial dysfunction in general, alerting the physician to look at underlying silent coronary bed atherosclerosis. It is also dependent on the poor control of diabetes and on the presence of its chronic complications. Because of the multiple etiologies of ED in individuals with diabetes, a multifactorial approach is warranted to get an optimal response in treating such patients. The use of Touchi Extract will help manage the post prandial glucose excursion, therefore modulating plasma insulin spikes, and minimize the endothelial dysfunction leading to ED. In addition, the combination of Touchi Extract with flavanols (epicatechin and catechin compounds from cocoa, wine, green tea, . . . ) may improve endothelial function by improving glycemic control and vasodilation. This combination may have a significant effect on improving the delay in the progression of the microvascular complications associated with diabetes as well as individuals with endothelial dysfunction without diabetes.
It should be appreciated that the present invention is not limited to the specific embodiments described above, but includes variations, modifications and equivalent embodiments defined by the following claims.

Claims

What is claimed is: 1 • A composition comprising at least one α-glucosidase inhibitor.
2. A composition as claimed in claim 1 wherein said α-glucosidase inhibitor is Touchi extract.
3. A composition as claimed in claim 1 further comprising at least one flavanol.
4. A composition as claimed in claim 2 further comprising at least one flavanol.
5. A composition as claimed in claim 3 or claim 4 wherein said flavanols are at least one of epicatechin and catechin compounds.
6. A composition as claimed in claim 3 or claim 4 wherein said flavanols originate from at least one of cocoa, wine or green tea.
7. A composition as claimed in claim 1, claim 2, claim 3, or claim 4 further comprising at least one prebiotic.
8. A composition as claimed in claim 7 wherein said prebiotic is at least one of FOS, GOS, inulin and partially hydrolyzed guar gum.
9. A composition as claimed in claim 1, claim 2, claim 3, or claim 4 further comprising at least one probiotic.
10. A composition as claimed in claim 9 wherein said probiotic is at least one L. reuteri, E. coli Nissle 1917, L. rhamnosus GG, L. casei, L. johnsonii, L. salivarius, bifidobacteria breve, B. bifidus, and sacchromyces boulardi..
11. A composition as claimed in claim 1, claim 2, claim 3, or claim 4 further comprising at least one probiotic and at least one prebiotic.
12. A composition as claimed in claim 11 wherein:
(a) said prebiotic is at least one of FOS, GOS, inulin and partially hydrolyzed guar gum; and
(b) said probiotic is at least one L. reuteri, E. coli Nissle 1917, L. rhamnosus GG, L. casei, L. johnsonii, L. salivarius, bifidobacteria breve, B. bifϊdus, and sacchromyces boulardi..
13. A dietary regime comprising at least one α-glucosidase inhibitor.
14. A dietary regime as claimed in claim 13 wherein said α-glucosidase inhibitor is Touchi extract
15. A dietary regime as claimed in claim 13 further comprising at least one flavanol.
16. A dietary regime as claimed in claim 14 further comprising at least one flavanol.
17. A dietary regime as claimed in claim 15 or claim 16 wherein said flavanols are at least one of epicatechin and catechin compounds.
18. A dietary regime as claimed in claim 15 or claim 16 wherein said flavanols originate from at least one of cocoa, wine or green tea.
19. A dietary regime as claimed in claim 13, claim 14, claim 15, or claim 16 further comprising at least one prebiotic.
20. A dietary regime as claimed in claim 19 wherein said prebiotic is at least one of FOS, GOS, inulin and partially hydrolyzed guar gum.
21. A dietary regime as claimed in claim 13, claim 14, claim 15, or claim 16 further comprising at least one probiotic.
22. A dietary regime as claimed in claim 21 wherein said probiotic is at least one L. reuteri, E. coli Nissle 1917, L. rhamnosus GG, L. casei, L. johnsonii, L. salivarius, bifidobacteria breve, B. bifidus, and sacchromyces boulardi..
23. A dietary regime as claimed in claim 13, claim 14, claim 15, or claim 16 further comprising at least one probiotic and at least one prebiotic.
24. A dietary regime as claimed in claim 23 wherein:
(a) said prebiotic is at least one of FOS, GOS, inulin and partially hydrolyzed guar gum; and
(b) said probiotic is at least one L. reuteri, E. coli Nissle 1917, L. rhamnosus GG, L. casei, L. johnsonii, L. salivarius, bifidobacteria breve, B. bifidus, and sacchromyces boulardi..
25. A method of treatment of a patient that can benefit from at least one α-glucosidase inhibitor.
26. The method as claimed in claim 25 wherein said α-glucosidase inhibitor is Touchi extract.
27. The method as claimed in claim 25 further comprising at least one flavanol.
28. The method as claimed in claim 26 further comprising at least one flavanol.
29. The method as claimed in claim 25 or claim 26 wherein said flavanols are at least one of epicatechin and catechin compounds.
30. The method as claimed in claim 25 or claim 26 wherein said flavanols originate from at least one of cocoa, wine or green tea.
31. The method as claimed in claim 25, claim 26, claim 27, or claim 28 further comprising at least one prebiotic.
32. The method as claimed in claim 31 wherein said prebiotic is at least one of FOS, GOS, inulin and partially hydrolyzed guar gum.
33. The method as claimed in claim 25, claim 26, claim 27, or claim 28 further comprising at least one probiotic.
34. The method of treatment of a patient that can benefit from as claimed in claim 33 wherein said probiotic is at least one L. reuteri, E. coli Nissle 1917, L. rhamnosus GG, L. casei, L. johnsonii, L. salivarius, bifidobacteria breve, B. bifidus, and sacchromyces boulardi..
35. The method of treatment as claimed in claim 25, claim 26, claim 27, or claim 28 further comprising at least one probiotic and at least one prebiotic.
36. The method as claimed in claim 35 wherein:
(a) said prebiotic is at least one of FOS, GOS, inulin and partially hydrolyzed guar gum; and
(b) said probiotic is at least one L. reuteri, E. coli Nissle 1917, L. rhamnosus GG, L. casei, L. johnsonii, L. salivarius, bifidobacteria breve, B. bifidus, and sacchromyces boulardi..
37. A method as claimed in claim 25, claim 26, claim 27, or claim 28 wherein said patient has at least one of the following: Diabetes, increased insulin resistance, decreased insulin sensitivity, co-morbidities of diabetes, cardiovascular disease, coronary heart disease, could benefit from decreased lipoproteins, hyperinsulinemia, hyperlipidemia, has or at risk for fatty liver, obesity, abdominal obesity, would benefit from improve satiety, would benefit from delay gastric emptying, Metabolic Syndrome/Syndrome X, COPD, would benefit from improved structure and function of the intestine, malabsorption, intestinal inflammation in active inflammatory bowel disease, Crohn's disease, diarrhea, constipation, gut atrophy due to transition from parenteral nutrition, gut atrophy due to radiation therapy, gut atrophy due to radiation therapy chemotherapy, irritable bowel syndrome, benefit from enhance athletic performance, human immunodeficiency virus, cystic fibrosis, non-alcoholic steatohepatitis, is a Critical Care Patient, has a wound that is or needs assistance in healing, Polycystic Ovarian Syndrome (PCOS), Erectile Dysfunction or erectile dysfunction secondary to diabetes.
38. A method as claimed in claim 37 wherein said lipoproteins are at least one of triglycerides, VLDL cholesterol and LDL cholesterol.
39. A method as claimed in claim 37 wherein said patient with hyperinsulinemia has at least one of: pro-inflammatory state or prothrombotic state.
40. A method as claimed in claim 37 wherein said patient has malabsoption from at least one of: cancer, chemo- therapy, radiation-therapy, TPN-related gut atrophy, acute illness-related gut dysfunction, being critically ill, septic, being burned, trauma, secondary to surgery, secondary to medicine, or acute pancreatitis.
41. A method as claimed in claim 37 wherein said patient has irritable bowel syndrome from at least one of: post bowel resection, short bowel syndrome, ulcerative colitis, gastrointestinal cancers, intestinal inflammation, acute illness-related gut dysfunction, being critically, being septic, being burned, trauma, surgery, medicine, acute pancreatitis, intestinal inflammation, cancer, chemo- therapy, or radiation- therapy.
42. A method as claimed in claim 37 wherein said Critical Care patient can benefit from at least one of faster and stronger wound healing, fewer infections, and decreased complications.
43. A method as claimed in claim 37 wherein said patient has a wound that is or needs assistance in healing and can benefit from at least one of: faster and stronger wound healing, fewer infections and decreased complications.
44. A method as claimed in claim 37 wherein said PCOS patient has infertility associated with the PCOS.
45. A method of administering to a patient a composition comprising administering the composition of any one of claims 1-12.
46. A method of administering to a patient a composition as claimed in claim 45 wherein said patient is a mammal.
47. A method of administering to a patient a composition as claimed in claim 45 wherein said patient is a human.
48. A method of administering to a patient a dietary regime comprising administering the dietary regime of any one of claims 13-24.
49. A method of administering to a patient a dietary regime as claimed in claim 48 wherein said patient is a mammal.
50. A method of administering to a patient a dietary regime as claimed in claim 48 wherein said patient is a human.
51. A method of administering to a patient a dietary regime as claimed in claim 48 wherein said dietary regime is a food or beverage or combination thereof.
52. A kit comprising at least one of a food or beverage or combination thereof dietary regime of any one of claims 13-24.
PCT/US2007/069624 2006-05-26 2007-05-24 Methods of use and nutritional compositions of touchi extract Ceased WO2007140230A2 (en)

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CA002655665A CA2655665A1 (en) 2006-05-26 2007-05-24 Methods of use and nutritional compositions of touchi extract
EP07815041A EP2021011A2 (en) 2006-05-26 2007-05-24 Methods of use and nutritional compositions of touchi extract
AU2007267560A AU2007267560B2 (en) 2006-05-26 2007-05-24 Methods of use and nutritional compositions of Touchi Extract
BRPI0712087-7A BRPI0712087A2 (en) 2006-05-26 2007-05-24 methods of use and nutritional compositions of rouchi extract
JP2009512294A JP2009538342A (en) 2006-05-26 2007-05-24 Method for using touchi extract and nutritional composition
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Cited By (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009021740A2 (en) 2007-08-15 2009-02-19 Sanofis-Aventis Substituted tetrahydronaphthalenes, process for the preparation thereof and the use thereof as medicaments
WO2010071421A1 (en) * 2008-12-17 2010-06-24 N.V. Nutricia Probiotics for the treatment and/or prevention of pulmonary hypertension
JP2010184909A (en) * 2009-02-13 2010-08-26 Rheology Kino Shokuhin Kenkyusho:Kk Functional composition and pharmaceutical or health food comprising the composition
WO2010110374A1 (en) * 2009-03-26 2010-09-30 ビオフェルミン製薬株式会社 Agent for enhancing hypoglycemic activity
WO2011107494A1 (en) 2010-03-03 2011-09-09 Sanofi Novel aromatic glycoside derivatives, medicaments containing said compounds, and the use thereof
WO2011157827A1 (en) 2010-06-18 2011-12-22 Sanofi Azolopyridin-3-one derivatives as inhibitors of lipases and phospholipases
WO2011161030A1 (en) 2010-06-21 2011-12-29 Sanofi Heterocyclic substituted methoxyphenyl derivatives having an oxo group, method for producing same, and use thereof as gpr40 receptor modulators
WO2012004270A1 (en) 2010-07-05 2012-01-12 Sanofi Spirocyclically substituted 1,3-propane dioxide derivatives, methods for the production thereof and use of the same as medicament
WO2012004269A1 (en) 2010-07-05 2012-01-12 Sanofi (2-aryloxy-acetylamino)-phenyl-propionic acid derivatives, method for producing same and use thereof as pharmaceuticals
WO2012010413A1 (en) 2010-07-05 2012-01-26 Sanofi Aryloxy-alkylene substituted hydroxyphenyl hexynoic acids, methods for the production thereof and use of the same as medicament
WO2012120052A1 (en) 2011-03-08 2012-09-13 Sanofi Oxathiazine derivatives substituted with carbocycles or heterocycles, method for producing same, drugs containing said compounds, and use thereof
WO2012120054A1 (en) 2011-03-08 2012-09-13 Sanofi Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120055A1 (en) 2011-03-08 2012-09-13 Sanofi Di- and tri-substituted oxathiazine derivates, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120053A1 (en) 2011-03-08 2012-09-13 Sanofi Branched oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
WO2012120056A1 (en) 2011-03-08 2012-09-13 Sanofi Tetrasubstituted oxathiazine derivatives, method for producing them, their use as medicine and drug containing said derivatives and the use thereof
CN102935092A (en) * 2010-06-09 2013-02-20 景岳生物科技股份有限公司 Novel lactobacillus and composition thereof and application of lactobacillus in preparation of medicines for improving diabetes and complications thereof
EP2567959A1 (en) 2011-09-12 2013-03-13 Sanofi 6-(4-Hydroxy-phenyl)-3-styryl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
WO2013037390A1 (en) 2011-09-12 2013-03-21 Sanofi 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
WO2013045413A1 (en) 2011-09-27 2013-04-04 Sanofi 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors
US10391130B2 (en) 2015-06-15 2019-08-27 4D Pharma Research Limited Compositions comprising bacterial strains
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US10744166B2 (en) 2015-11-23 2020-08-18 4D Pharma Research Limited Compositions comprising bacterial strains
US10851137B2 (en) 2013-04-10 2020-12-01 4D Pharma Research Limited Polypeptide and immune modulation
US10987387B2 (en) 2017-05-24 2021-04-27 4D Pharma Research Limited Compositions comprising bacterial strain
US11007233B2 (en) 2017-06-14 2021-05-18 4D Pharma Research Limited Compositions comprising a bacterial strain of the genus Megasphera and uses thereof
US11013773B2 (en) 2011-07-14 2021-05-25 4D Pharma Research Limited Lactic acid bacterial strains
US11123378B2 (en) 2017-05-22 2021-09-21 4D Pharma Research Limited Compositions comprising bacterial strains
US11123379B2 (en) 2017-06-14 2021-09-21 4D Pharma Research Limited Compositions comprising bacterial strains
US11224620B2 (en) 2016-07-13 2022-01-18 4D Pharma Plc Compositions comprising bacterial strains
US11266698B2 (en) 2011-10-07 2022-03-08 4D Pharma Research Limited Bacterium for use as a probiotic for nutritional and medical applications
CN114426938A (en) * 2022-02-08 2022-05-03 江南大学 Lactobacillus plantarum CCFM1202 with the function of relieving PCOS and its application
US11389493B2 (en) 2015-06-15 2022-07-19 4D Pharma Research Limited Compositions comprising bacterial strains
CN115364126A (en) * 2021-05-17 2022-11-22 上海交通大学医学院附属仁济医院 Application of lactobacillus reuteri in preparation of medicine for treating polycystic ovarian syndrome
US11723933B2 (en) 2014-12-23 2023-08-15 Cj Bioscience, Inc. Composition of bacteroides thetaiotaomicron for immune modulation
US12048720B2 (en) 2017-06-14 2024-07-30 Cj Bioscience, Inc. Compositions comprising bacterial strains

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1319655B1 (en) 2000-11-15 2003-10-23 Eurand Int PANCREATIC ENZYME MICROSPHERES WITH HIGH STABILITY AND RELATIVE PREPARATION METHOD.
DK2079445T3 (en) 2007-02-20 2016-02-15 Allergan Pharmaceuticals Internat Ltd Stable digestive compositions
WO2009109856A2 (en) 2008-03-07 2009-09-11 Axcan Pharma Inc. Method for detecting infectious parvovirus in pharmaceutical preparations
US8784884B2 (en) * 2009-09-17 2014-07-22 Stephen Perrett Pancreatic enzyme compositions and methods for treating pancreatitis and pancreatic insufficiency
JP5752359B2 (en) * 2010-02-25 2015-07-22 富士フイルム株式会社 Weight gain inhibiting composition and food containing the same
KR20140019292A (en) 2010-10-01 2014-02-14 아프탈리스 파르마 리미티드 Enteric coated, low-strength pancrelipase formulations
SG191392A1 (en) 2010-12-31 2013-08-30 Abbott Lab Methods for decreasing the incidence of necrotizing enterocolitis in infants, toddlers, or children using human milk oligosaccharides
ES2804258T3 (en) 2010-12-31 2021-02-05 Abbott Lab Procedures to reduce the incidence of oxidative stress using human milk oligosaccharides, vitamin C and anti-inflammatory agents
US11446316B2 (en) * 2011-07-22 2022-09-20 Abbott Laboratories Galactooligosaccharides for preventing injury and/or promoting healing of the gastrointestinal tract
ES2558756T3 (en) 2011-08-08 2016-02-08 Aptalis Pharma Limited Method for dissolution test of solid compositions containing digestive enzymes
CN104023560A (en) 2011-08-29 2014-09-03 雅培制药有限公司 Human milk oligosaccharides for preventing gastrointestinal injury and/or promoting gastrointestinal healing
CN103169075B (en) * 2011-12-21 2015-06-24 光明乳业股份有限公司 Fermented bean product fermented by lactobacillus plantarum ST-III and alpha-glucosidase inhibitor
US10184121B2 (en) 2013-06-28 2019-01-22 Allergan Pharmaceuticals International Limited Methods for removing viral contaminants from pancreatic extracts
RU2679832C2 (en) 2013-08-09 2019-02-13 Аллерган Фармасьютикалз Интернэйшнл Лимитед Digestive enzyme composition suitable for enteral administration
ES2754428T3 (en) * 2013-12-18 2020-04-17 Thylabisco Ab Use of thylakoids to reduce appetite for appetizing food
MA41020A (en) 2014-11-25 2017-10-03 Evelo Biosciences Inc PROBIOTIC AND PREBIOTIC COMPOSITIONS, AND THEIR METHODS OF USE FOR MODULATION OF THE MICROBIOME
CN107224584A (en) * 2016-03-25 2017-10-03 上海来益生物药物研究开发中心有限责任公司 A kind of probiotic composition and its application
CN108684420A (en) * 2018-05-21 2018-10-23 贵州曌梅果蔬种植有限公司 The implantation methods of cyanogen salidroside content in a kind of reduction cherry fruit
CN110721275B (en) * 2019-11-22 2021-10-08 黑龙江省中医药科学院 Composition for improving metabolic syndrome
WO2022244842A1 (en) * 2021-05-19 2022-11-24 Kagami株式会社 Composition for regulating carbohydrate metabolism, and method for assessing carbohydrate metabolism conditions of subject

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3911366B2 (en) * 1999-07-01 2007-05-09 日本サプリメント株式会社 α-Glucosidase inhibitor
JP2000072687A (en) 1998-08-26 2000-03-07 Nippon Synthetic Chem Ind Co Ltd:The α-glucosidase inhibitor
US6080401A (en) * 1998-11-19 2000-06-27 Reddy; Malireddy S. Herbal and pharmaceutical drugs enhanced with probiotics
CA2405377C (en) * 2000-04-18 2014-04-01 Societe Des Produits Nestle S.A. Nutritional modules
RU2182008C1 (en) * 2000-10-20 2002-05-10 Самойленко Игорь Иннокентьевич Perorally, rectally or intravaginally injected composition containing alive bacteria
US20020187219A1 (en) * 2001-03-29 2002-12-12 The Procter & Gamble Co. Low glycemic response compositions
JP4921681B2 (en) * 2001-11-14 2012-04-25 川澄化学工業株式会社 Preventive drugs
FR2834214B1 (en) * 2001-12-28 2004-09-24 Lipha PHARMACEUTICAL COMPOSITION COMPRISING AN ALPHA-GLUCOSIDASE INHIBITOR AND 4-OXO-BUTANOIC ACID AND ITS USE FOR TREATING DIABETES
EP1384483A1 (en) * 2002-07-23 2004-01-28 Nestec S.A. Probiotics for treatment of irritable bowel disease (IBS) through improvement of gut neuromuscular function
US6942857B2 (en) * 2002-08-09 2005-09-13 Bioneer Corporation Microorganisms for preventing and/or treating obesity or diabetes mellitus
US20040037868A1 (en) * 2002-08-20 2004-02-26 Minich Deanna M. Select prebiotics for use in weight attenuation message and method of communication
US7108869B2 (en) * 2002-11-07 2006-09-19 Access Business Group International Llc Nutritional supplement containing alpha-glucosidase and alpha-amylase inhibitors
JP4322813B2 (en) * 2003-03-31 2009-09-02 カウンシル・オブ・サイエンティフィック・アンド・インダストリアル・リサーチ Hypoglycemic food and method for producing the same
JP2004323469A (en) * 2003-04-28 2004-11-18 Ezaki Glico Co Ltd Medicinal composition and food for prevention and treatment of type ii diabetes
US20050277657A1 (en) * 2004-06-15 2005-12-15 Dusan Ninkov Method of protection of biologically active essential oils and pharmaceutical composition for weight control and enhance fat burning in adults, adolescents and children
DE102004035373B3 (en) * 2004-07-21 2006-03-30 Südzucker AG Mannheim/Ochsenfurt Improved cocoa mixtures
US20060051435A1 (en) * 2004-08-19 2006-03-09 Udell Ronald G Nutritional supplement for body fat reduction
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