Composition containing fibers and mulberry

Abstract

A combination formulation of fiber and mulberry ingredients is disclosed for controlling glycemic response, promoting weight loss, and / or inhibiting fat mass gain, as well as compositions containing the combination as active ingredients, their uses, and methods of using the same. The fiber and mulberry ingredients mutually enhance or act synergistically to achieve the above uses.

Description

Technical Field

[0001] The present invention relates to a composition containing fiber and mulberry, the use of the composition, and a method of using the same. In particular, the present invention is a combined composition containing fiber and mulberry components as the only active ingredients, which mutually enhance or act synergistically for the maintenance of blood glucose including both fasting blood glucose and postprandial blood glucose, for the management of blood glucose, for the promotion of weight loss, for the suppression of body fat increase, and / or for the prevention or treatment of obesity.

Background Art

[0002] Obesity, as well as related metabolic disorders including dyslipidemia and hyperglycemia, have become major global concerns, especially for the middle-aged and elderly. Chronic hyperglycemia causes damage to various tissues and organs of the body, leading to acute and / or chronic complications such as dehydration, electrolyte abnormalities, nutritional deficiencies, renal function decline, nerve or fundus lesions, cardiovascular and cerebrovascular diseases, and diabetic foot lesions.

[0003] Over the past few decades, the prevalence of obesity has been increasing and spreading worldwide. Approximately 1 billion people worldwide are overweight or obese, a condition that increases mortality, mobility, and economic costs. Obesity progresses when energy intake exceeds energy consumption, and the excess energy is mainly stored as fat in adipose tissue. Weight loss and prevention of weight gain can be achieved by reducing energy intake or bioavailability, increasing energy consumption, and / or reducing storage as fat. Obesity is a serious threat to health because it is associated with a range of chronic diseases including diabetes, atherosclerosis, degenerative disorders, airway diseases, and some cancers.

[0004] Diabetes mellitus, commonly known as diabetes, is a carbohydrate metabolism disorder resulting from insufficient insulin production or decreased insulin sensitivity. Diabetes is often characterized as type 1 or type 2. The main symptom of type 2 diabetes is excessive postprandial blood glucose levels due to insufficient phase 1 insulin secretion. Individuals with type 2 diabetes have a reduced or absent response to and regulation of elevated blood glucose levels, which would occur in healthy individuals, resulting in a rapid and excessive rise in postprandial blood glucose. This is particularly important given the established correlation between effective glycemic control in diabetic individuals and the risk of developing cardiovascular or circulatory disease or disorder, especially microvascular and macrovascular complications resulting from such disease or disorder. Therefore, controlling postprandial blood glucose in diabetic individuals is a crucial step in preventing the development of cardiovascular or circulatory disease and, naturally, the subsequent development of cardiovascular-related conditions such as retinopathy, neuropathy, and nephropathy.

[0005] Fasting blood glucose is one of the common indices in diabetes diagnosis, reflecting the function of the β-cells of the islets of Langerhans and representing the basal insulin secretion function. Generally, fasting blood glucose levels of 6.1-7.0 mmol / L indicate a transitional stage from normal to diabetes, and appropriate diet and physical therapy, especially when combined with hypoglycemic agents, can normalize blood glucose and prevent the onset of diabetes. Therefore, maintaining good control of fasting blood glucose has significant advantages in preventing diabetes.

[0006] Therefore, maintaining or managing blood glucose levels, including both fasting and postprandial blood glucose, is crucial in the prevention or treatment of diabetes and related diseases, such as microvascular and macrovascular disorders, cerebrovascular diseases, circulatory disorders, and associated complications including retinopathy, neuropathy, and nephropathy.

[0007] Numerous methods exist that individuals can try to effectively control blood glucose levels, including both fasting and postprandial blood glucose, which commonly occur in diabetes. Such methods often involve dietary and lifestyle changes, as well as the use of insulin and / or other medications designed to ultimately control blood glucose levels. However, many individuals require the use of injectable insulin and / or oral medications, all of which are costly and, in some cases, lead to undesirable side effects.

[0008] Various efforts have been made in the art to develop pharmaceuticals or nutritional compositions that exhibit beneficial effects on blood glucose management or maintenance. For example, Chinese Patent Application Publication No. 104473152(A) discloses a biological medicinal food equivalent to a physical method using acarbose for reducing postprandial blood glucose. The application provides at least five components: barley glucan, mulberry leaves, yam, konjac, and oat powder, which fully utilize the advantages of all raw materials to produce the claimed effect. International Publication No. 2013 / 078658 reports the effect of mulberry juice on blood glucose levels after consumption of carbohydrates with a high glycemic index. European Patent Application Publication No. 3145332(A1) reports the reduction of postprandial blood glucose and insulin spikes after administration of a composition containing a combination of white kidney bean extract, mulberry extract, and green coffee extract 15 minutes before a carbohydrate meal.

[0009] Therefore, there is a need for compositions or methods that complement standard treatment for diabetes mellitus, reduce reliance on insulin or other medications, or provide useful options for effectively controlling blood glucose levels, including both fasting and postprandial glucose. There is also a need for compositions or methods that can support weight management.

[0010] Furthermore, there is a need for nutritional compositions that help reduce dependence on insulin or other medications, or that provide useful options for effectively assisting in the control of blood glucose levels, including both fasting and postprandial blood glucose. There is also a need for nutritional compositions that can help promote weight loss and / or suppress fat gain, and that can help prevent or treat obesity.

[0011] Therefore, an object of the present invention is to provide a novel combination or composition having desired control over blood glucose levels, including both fasting blood glucose and postprandial blood glucose, which can promote weight loss and / or suppress fat mass increase, or at least a useful alternative. [Overview of the project]

[0012] The inventors have surprisingly found that a combination formulation of fiber and mulberry components, when administered to subjects in need, can improve insulin sensitivity and glucose tolerance, specifically control and regulate blood glucose levels, promote weight loss, and suppress fat accumulation. When used in combination, fiber and mulberry mutually enhance or act synergistically to control and regulate blood glucose levels, promote weight loss, and / or suppress fat accumulation in subjects more effectively than fiber or mulberry alone. The combination or composition may contain less fiber or mulberry than required when either is used alone. The mulberry component may be mulberry plant material, mulberry extract, or a combination thereof. In preferred embodiments, the mulberry component is mulberry leaf extract (MLE). The fiber is preferably soluble fiber. The soluble fiber may be selected from the group consisting of FOS, GOS, inulin, β-glucan, indigestible maltodextrin, acacia gum, partially hydrolyzed guar gum (PHGG), polydextrose, and combinations thereof. In a preferred embodiment, the fiber includes PHGG. In one embodiment, the fiber is selected from the group consisting of FOS, inulin, acacia gum, PHGG, or combinations thereof. In a specific embodiment, the fiber is a combination of FOS, inulin, acacia gum, and PHGG.

[0013] In a first aspect of the present invention, a combination formulation of fiber and mulberry component is provided, wherein the mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof.

[0014] A second aspect of the present invention provides a combination formulation of fiber and mulberry components, wherein the mulberry component is a mulberry plant material, mulberry extract, or a combination thereof for maintaining blood glucose, including both fasting blood glucose and postprandial blood glucose, for managing blood glucose, for promoting weight loss, and / or for suppressing fat accumulation.

[0015] A third aspect of the present invention provides a composition comprising fiber and a mulberry component for maintaining blood glucose, including both fasting blood glucose and postprandial blood glucose, for managing blood glucose, for promoting weight loss, and / or for suppressing fat accumulation, wherein the mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof.

[0016] A fourth aspect of the present invention provides a composition comprising fiber and mulberry components that assists in controlling blood glucose levels, including both fasting blood glucose and postprandial blood glucose, assists in promoting weight loss and / or suppressing the increase in body fat mass, and assists in the treatment or prevention of obesity.

[0017] A fifth aspect of the present invention provides the use of the above-mentioned combination formulation or composition for producing an agent for maintaining blood glucose, including both fasting blood glucose and postprandial blood glucose, for managing blood glucose, for promoting weight loss, and / or for suppressing fat mass increase.

[0018] A sixth aspect of the present invention provides the use of the above composition for manufacturing a health product to assist in controlling blood glucose levels, including both fasting and postprandial blood glucose, in reducing weight and / or suppressing the increase in body fat, and / or to assist in the prevention or treatment of obesity.

[0019] A seventh aspect of the present invention provides the use of fiber for the preparation of a composition administered with a mulberry component for maintaining blood glucose, including both fasting blood glucose and postprandial blood glucose, for managing blood glucose, for promoting weight loss, and / or for suppressing an increase in body fat mass, wherein the mulberry component is mulberry plant material, mulberry extract, or a combination thereof.

[0020] An eighth aspect of the present invention provides the use of a mulberry component for the preparation of a composition administered with fiber for maintaining blood glucose, including both fasting blood glucose and postprandial blood glucose, for managing blood glucose, for promoting weight loss, and / or for suppressing fat gain, wherein the mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof.

[0021] A ninth aspect of the present invention provides a method for maintaining or managing blood glucose in a subject requiring maintenance or management of blood glucose, including both fasting blood glucose and postprandial blood glucose, comprising administering to the subject a mutually reinforcing amount of fiber together with a mutually reinforcing amount of mulberry component, preferably such that the amounts of both components synergistically produce a greater technical effect than their additive effect, and the mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof. Also provided is a method for promoting weight loss and / or suppressing fat gain in a subject requiring weight loss, comprising administering to the subject a mutually reinforcing amount of fiber together with a mutually reinforcing amount of mulberry component to produce a greater technical effect than either component alone, wherein the mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof.

[0022] In each of the preferred embodiments described above, the mulberry component is mulberry leaf extract (MLE).

[0023] In each specific embodiment of the above-described aspects, the fiber and mulberry components are used as the sole active ingredients and / or administered orally.

[0024] Therefore, the combination formulations, compositions, uses, and methods of the present invention provide natural or nutritional options that can contribute to maintaining optimal blood glucose control in subjects who are prediabetic, have impaired glucose tolerance, have fasting hyperglycemia, or have type 2 diabetes or related complications including retinopathy, neuropathy, nephropathy, etc. These advantages are also advantageously achieved in such individuals without experiencing many of the complications often associated with the administration of oral antidiabetic drugs. The combination formulations, compositions, uses, and methods of the present invention also provide an effective means to support weight management.

Brief Description of the Drawings

[0025] In the figure, MLE refers to the mulberry leaf extract as described in the examples. [Figure 1] Shows fasting serum insulin concentration in male C57BL / 6 mice. Values are mean ± standard error of the mean, n = 10, **p < 0.01 vs. comparative control. [Figure 2] Shows fasting serum glucose concentration in male C57BL / 6 mice. Values are mean ± standard error of the mean, n = 10, **p < 0.01 vs. comparative control. [Figure 3] Shows glucose AUC in male C57BL / 6 mice after OGTT. Values are mean ± standard error of the mean, n = 10, **p < 0.01 vs. comparative control. [Figure 4] Shows (A)(B) final body weight, (C)(D) weight gain in male C57BL / 6 mice after 4 weeks of treatment. Values are mean ± standard error of the mean, n = 10, *p < 0.05, **p < 0.01. [Figure 5] Shows (A)(B) epididymal fat mass and (C)(D) perirenal fat mass in male C57BL / 6 mice after 4 months of treatment. Values are mean ± standard error of the mean, n = 10, *p < 0.05, **p < 0.01.

Modes for Carrying Out the Invention

[0026] In a first aspect of the present invention, a combination formulation of fiber and mulberry component is provided, wherein the mulberry component is mulberry plant material, mulberry extract, or a combination thereof. The fiber is preferably a soluble fiber. The fiber may be FOS, GOS, inulin, β-glucan, indigestible maltodextrin, partially hydrolyzed guar gum (PHGG), polydextrose, or any combination thereof. In a preferred embodiment, the fiber includes PHGG. In one embodiment, the fiber is selected from the group consisting of FOS, inulin, acacia gum, PHGG, or a combination thereof.

[0027] In further embodiments of the present invention, the mulberry plant material may be derived from any Morus species, including but not limited to Morus alba L., Morus nigra L., Morus celtidifolia Kunth, Morus rubra L., hybrid forms of Morus alba and Morus rubra, Morus australis, Morus laevigata, and combinations thereof.

[0028] In further embodiments of the present invention, the mulberry plant material is derived from various parts of the mulberry tree, including bark (trunk, twigs, or roots), roots, buds, twigs, young shoots, leaves, and fruits.

[0029] In further embodiments of the present invention, the mulberry material may be in the form of an extract or a dried powder, such as a dried powder ground from various parts of a mulberry tree.

[0030] In further embodiments of the present invention, the extract of mulberry plant material (hereinafter referred to as "mulberry extract") may be derived from the whole or any part of the plant, such as bark (trunk, twigs, or roots), roots, buds, twigs, shoots, leaves, fruits, or a combination thereof. The raw material may be fresh, frozen, or dried material. After filtration or dialysis, the extract may be used as a liquid or a dry solid.

[0031] In further embodiments of the present invention, the mulberry plant material or extract thereof is a mulberry leaf extract or a pulverized mulberry leaf powder. In preferred embodiments, the mulberry component is a mulberry leaf extract.

[0032] In a further embodiment of the present invention, the mulberry extract is prepared by a procedure known in the art, for example, by extracting a mulberry material, which includes all or part of a mulberry plant, with a solvent such as alcohol (e.g., n-butanol, ethanol, etc.) and / or water.

[0033] In further embodiments of the present invention, the weight ratio of fiber to mulberry component may be in the range of about 1:10 to about 40:1, preferably about 1:1 to about 30:1, more preferably about 4:1 to about 25:1, for example about 4:1 to about 20:1, for example about 5:1 to about 10:1, or for example about 25:1.

[0034] In a further embodiment of the present invention, the combination formulation is in the form of a powder.

[0035] A second aspect of the present invention provides a combination formulation as defined above for maintaining blood glucose, including both fasting blood glucose and postprandial blood glucose, for managing blood glucose, for promoting hepatic detoxification, and / or for suppressing hepatic oxidative damage.

[0036] In further embodiments, the combination formulations are useful for the prevention and / or treatment of hyperglycemia and / or related conditions, such as prediabetes, diabetes and especially type 2 diabetes, impaired glucose tolerance, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and / or the prevention or treatment of obesity, and can therefore be used to manufacture agents for the treatment and / or prevention of the above conditions.

[0037] A third aspect of the present invention provides a composition comprising fiber and a mulberry component for maintaining blood glucose, including both fasting blood glucose and postprandial blood glucose, for managing blood glucose, for promoting weight loss, and / or for suppressing fat accumulation, wherein the mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof.

[0038] A fourth aspect of the present invention provides a composition comprising fiber and a mulberry component that can be used to produce nutrients for the above purposes, which assist in controlling blood glucose levels, promoting weight loss and / or suppressing fat accumulation, and assisting in the prevention or treatment of obesity, wherein the mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof.

[0039] In further embodiments of the third and fourth aspects of the present invention, all specific definitions of the fibers and mulberry components also apply to the compositions, as described above for the combination formulations.

[0040] In further embodiments of the present invention, the composition is useful for the prevention and / or treatment of hyperglycemia and / or related conditions, such as prediabetes, diabetes and especially type 2 diabetes, impaired glucose tolerance, diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy, and / or for the prevention or treatment of obesity.

[0041] In a further embodiment of the present invention, the composition is for oral administration.

[0042] In further embodiments of the present invention, the composition most typically comprises about 5% to about 95% fiber, with dry weight of the composition comprising about 10% to about 95%, about 50% to about 90%, about 70% to about 90%, about 80% to about 90%, and about 95% fiber.

[0043] In further embodiments of the present invention, the composition may typically contain about 1% to about 50% mulberry components, comprising about 2% to about 30% by dry weight of the composition, for example, about 5% to about 20%, and also about 10% to about 15%. In other embodiments, the composition may contain about 1% to about 10% mulberry components, comprising about 1% to about 5%, also about 1% to about 4%, and also about 1% to about 2% by weight of the composition. The mulberry components are mulberry plant material, mulberry extract, or a combination thereof.

[0044] In further embodiments of the present invention, the composition further comprises a filler material, a fat source, a protein source, a flowing agent, a stabilizer, a preservative, an antioxidant, an acid, a buffer, a sweetener, an intense sweetener, a colorant, a flavoring agent, a flavor enhancer, an emulsifier, an anti-caking agent, a lubricant, or any combination thereof.

[0045] A fourth aspect of the present invention provides the use of the above-defined combination formulations for maintaining blood glucose, including both fasting blood glucose and postprandial blood glucose; for managing blood glucose; for promoting hepatic detoxification; and / or for suppressing oxidative damage to the liver; for example, for the prevention and / or treatment of hyperglycemia and / or related conditions, such as prediabetes, diabetes and particularly type 2 diabetes, impaired glucose tolerance, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and / or for the prevention or treatment of obesity.

[0046] A fifth aspect of the present invention provides the use of fiber for the preparation of a composition administered together with a mulberry component, wherein the mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof, for the maintenance of blood glucose, including both fasting blood glucose and postprandial blood glucose, for the management of blood glucose, for the promotion of weight loss and / or the suppression of fat mass increase, for example, for the prevention and / or treatment of hyperglycemia and / or related conditions, such as prediabetes, diabetes and especially type 2 diabetes, impaired glucose tolerance, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and / or for the prevention or treatment of obesity.

[0047] A sixth aspect of the present invention provides the use of a mulberry component, wherein the mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof, for the production of a composition to be combined with fiber for the purpose of maintaining blood glucose, including both fasting blood glucose and postprandial blood glucose, for blood glucose management, for promoting weight loss and / or suppressing fat mass increase, for example, for the prevention and / or treatment of hyperglycemia and / or related conditions, such as prediabetes, diabetes and especially type 2 diabetes, impaired glucose tolerance, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and / or for the prevention or treatment of obesity.

[0048] A seventh aspect of the present invention provides a method for maintaining blood glucose, including both fasting and postprandial blood glucose, for blood glucose management, for promoting weight loss, and / or for suppressing fat mass increase, for example, for the prevention and / or treatment of hyperglycemia and / or related conditions, such as prediabetes, diabetes and particularly type 2 diabetes, impaired glucose tolerance, diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and / or for the prevention or treatment of obesity, in subjects requiring the following treatment, comprising administering to the subject a mutually reinforcing amount of fiber together with a mutually reinforcing amount of mulberry components, wherein the mulberry components are mulberry plant material, mulberry extract, or a combination thereof, and preferably the amounts of both components synergistically produce a greater technical effect than their additive effect.

[0049] In further embodiments of each of the above aspects of the present invention, the fiber and mulberry component are used as the sole active ingredient, wherein the mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof.

[0050] For clarity, it should be understood that certain features of the present invention described above and below in the context of separate embodiments may also be provided in combination in a single embodiment. Conversely, various features of the present invention described in the context of a single embodiment for brevity may be provided separately or in any partial combination.

[0051] definition As used herein, the term “combination formulation” means that combination partners (a) and (b) can be administered independently or in various predetermined combinations of combination partners (a) and (b) in distinct amounts, i.e., simultaneously, sequentially, or separately. The combination partners may, for example, be administered simultaneously or at different times, i.e., at different points in time and at equal or different time intervals relative to any given combination partner. Combination partners (a) and (b) may be contained in the same composition together with excipients, additives, or other components useful for the proposed use; or combination partners (a) and (b) may be administered or applied in separate compositions and through different routes of administration to obtain a combined therapeutic effect. Preferably, combination partners (a) and (b) are contained in the same composition.

[0052] As used herein, the terms “to treat” or “to cure” in relation to any disease or disorder mean, in one embodiment, improving the disease or disorder (i.e., delaying, preventing, or reducing the onset of the disease or at least one of its clinical symptoms). In another embodiment, “to treat” or “to cure” means alleviating or improving at least one physical parameter, including one that is not perceptible to the patient. In yet another embodiment, “to treat” or “to cure” means modulating the disease or disorder physically (e.g., stabilizing a recognizable symptom), physiologically (e.g., stabilizing a physical parameter), or both. In yet another embodiment, “to treat” or “to cure” means preventing or delaying the onset, onset, or progression of the disease or disorder.

[0053] As used herein, the term "mulberry plant material" means any whole plant or any part thereof derived from a plant of the genus Morus.

[0054] Body Mass Index, or BMI, is the ratio of weight in kilograms to the square of height in meters.

[0055] Obesity is defined as a condition in which the accumulation of natural energy stored in the adipose tissue of animals, particularly humans and other mammals, increases to a point associated with certain health conditions or increased mortality. Obese is defined as an adult human having a BMI greater than 30.

[0056] In the context of this invention, "weight loss" refers to a reduction in overall body weight. Weight loss may, for example, represent a decrease in overall body weight in an effort to improve physical strength, health, and / or appearance.

[0057] "Weight management" or "weight maintenance" refers to maintaining one's overall body weight. For example, weight management may refer to maintaining a BMI within the normal range of 18.5 to 25.

[0058] As used herein, the terms “enhance” or “enhance” mean an increase in the corresponding pharmacological activity or therapeutic effect, respectively. The enhancement of one component of the combination according to the present invention by the simultaneous administration of another component according to the present invention means that a greater effect is achieved than that achieved by either component alone.

[0059] As used herein, the terms “synergistic” or “synergistic” mean that when ingredients are taken together, they produce a combined effect greater than the sum of the effects of each ingredient when taken individually.

[0060] As used herein, the words “comprises,” “comprising,” and similar words should not be interpreted as exclusive or exhaustive. In other words, they are intended to mean “including, but not limited to.”

[0061] Where used herein, the term "and / or" as used in the context of "X and / or Y" should be interpreted as "X" or "Y," or "X and Y."

[0062] As used herein, the term “about” when referring to measurable values ​​such as quantities means that it includes variations of ±20%, or in some cases ±10%, or in some cases ±5%, or in some cases ±1%, or in some cases ±0.1%, from the specified value, and such variations are appropriate for the disclosed composition.

[0063] Where used herein, any percentages and ratios refer to the weight of the entire formulation or composition unless otherwise specified. All such weights for the listed components are based on their activity levels and, therefore, do not include solvents or by-products that may be present in commercially available materials unless otherwise specified.

[0064] The numerical ranges used herein are intended to include all digits and subsets of digits that fall within that range, whether expressly disclosed or not. Furthermore, these numerical ranges should be interpreted as providing support for claims that cover any digit or subset of digits within that range. For example, a disclosure of 1 to 10 should be interpreted as supporting ranges such as 1 to 8, 3 to 7, 4 to 9, 3.6 to 4.6, and 3.5 to 9.9.

[0065] Unless otherwise specified or expressly meant to be incompatible by the context in which they are referred, any reference to a single feature or single limitation of the Invention shall include a corresponding set of features or limitations, and any reference to a set of features or limitations shall include a corresponding single feature or single limitation.

[0066] The combinations, compositions, and methods of the present invention may include, consist of, or essentially consist of, the elements and features of the present invention described herein, as well as any additional or optional components, elements, or features that are useful in pharmaceutical or nutritional applications in any way described herein or otherwise.

[0067] No reference to prior art documents in this specification should be construed as an acknowledgment that such prior art is well known or that it forms part of a general understanding common in the art.

[0068] Unless otherwise specified, all technical and scientific terms, specialized terms, and acronyms used herein have meanings that are generally understood by those skilled in the art in the field(s) of the present invention or the field(s) in which the terms are used.

[0069] fiber The combination formulations and compositions of the present invention contain fiber. Any dietary fiber, including soluble and insoluble fiber, known or otherwise suitable for use in oral products, is also suitable for use herein, insofar as such sources are compatible with the other selected components of the composition or otherwise made to be compatible. However, the fiber is not β-glucan.

[0070] Preferably, one or more soluble fibers are used.

[0071] The beneficial effects of fiber on the glucose response have been widely reported. Non-limiting examples of suitable soluble fibers include FOS, GOS, inulin, indigestible maltodextrin, partially hydrolyzed guar gum, polydextrose, and combinations thereof.

[0072] Advantageously, the fibers can also act as filler materials to increase the bulk properties of the composition.

[0073] The fibers, when combined with the mulberry material or extract thereof described herein, can mutually enhance or preferably synergistically control and regulate blood glucose levels so as to delay glucose absorption into the bloodstream, thereby increasing the time it takes for a given amount of glucose to enter the bloodstream.

[0074] In one embodiment, the fiber contains PHGG. In another embodiment, the fiber is a combination of FOS, inulin, and acacia gum. In a specific embodiment, the fiber is a combination of FOS, inulin, acacia gum, and PHGG.

[0075] In another embodiment, the fiber is selected from polydextrose or indigestible maltodextrin (such as Fibersol2 (trademark) (Archer Daniels Midland Company)). In one embodiment, the composition comprises soluble fiber and mulberry extract in a fiber:mulberry extract ratio of about 1:1 to about 30:1, preferably about 4:1 to about 10:1.

[0076] In another embodiment, the fiber is a combination of FOS, inulin, and acacia gum, optionally further combined with PHGG, and the composition comprises the fiber and mulberry extract in a fiber:mulberry extract ratio of about 4:1 to about 30:1, for example, about 25:1.

[0077] Mulberry extract This invention involves the use of mulberry components. These components may be mulberry plant materials, mulberry extracts, or combinations thereof. Mulberry plant materials have been used for centuries in traditional Chinese medicine as common agents to treat various conditions, including diabetes, atherosclerosis, and cancer, and to enhance the immune system through potent antioxidant activity. Studies have shown that mulberry plant materials contain a variety of physiologically active components, including flavonoids, polyphenols, polysaccharides, α-glucosidase inhibitors, fagomine, GABA, and 1-deoxynojirimycin (DNJ). Therefore, they may be useful in the prevention or treatment of cardiovascular disease, dyslipidemia, diabetes, obesity, and anti-aging.

[0078] Any source of mulberry components known or otherwise suitable for human use is also suitable for use herein, insofar as such source is also compatible with other selected components of the composition or otherwise made to be compatible. The mulberry components may be mulberry plant material, mulberry extract, or a combination thereof.

[0079] The mulberry components applicable to the present invention may be derived from any species of the genus Morus, including but not limited to Morus alba L., Morus nigra L., Morus celtidifolia Kunth, Morus rubra L., hybrids of Morus alba and Morus rubra, Morus australis, Morus laevigata, and combinations thereof.

[0080] The mulberry components applicable to the present invention may be derived from various parts of the mulberry tree, including bark (trunk, twigs, or roots), roots, buds, twigs, young shoots, leaves, fruits, or combinations thereof. The mulberry material may be in the form of, for example, a dried powder, such as a dried powder ground from various parts of the tree. The plant raw material for the mulberry extract may be fresh, frozen, or dried mulberry material. The extract may be used as a liquid or a dried concentrated solid. Typically, such an extract contains at least about 1% w / v or more of 1-DNJ.

[0081] Preferably, the mulberry component used in the present invention is mulberry leaf or mulberry leaf extract (MLE in the figure).

[0082] Mulberry extract can be prepared by known procedures in the art, for example, by extracting dried mulberry leaf powder with water or a 70%-80% aqueous ethanol solution at 60°C for 2 hours, and then dissolving the extract in 0.25 mol·L. -1 The eluent can be concentrated by passing it through an ion exchange resin that elutes with ammonia water, and the eluent can be further extracted with n-butanol, concentrated, and dried to obtain a mulberry leaf extract. References for this embodiment include Chao Liu et al., Comparative analysis of 1-deoxynojirimycin contribution degree to α-glucosidase inhibitory activity and physiological distribution in Morus alba L, Industrial Crops and Products, 70(2015) p309-315; Wenyu Yang et al., Studies on the methods of analyzing and extracting total alkaloids in mulberry, Lishizhen Medicine and Materia Medical Research, 2008(5); and Chinese Patent Application Publication No. 104666427.

[0083] The mulberry components applicable to the present invention, such as mulberry leaf extract, may be commercially available, for example, those from Naturex Ltd, Karallief Inc, USA, ET-Chem, China, Nanjing NutriHerb BioTech Co., Ltd, China, or Phynova Group Ltd.

[0084] The compositions of the present invention may contain an amount of mulberry component sufficient to enhance, or preferably synergistically interact with, the β-glucan component of the composition in providing the desired effect. However, the composition most typically contains about 0.5% to about 50% by weight of mulberry component, comprising about 2% to about 30% by weight of the composition, for example, about 5% to about 20% by weight of mulberry component, also comprising about 10% to about 15% by weight. In other embodiments, the composition may contain about 1% to about 10% by weight of mulberry component, comprising about 1% to about 5% by weight of the composition, also comprising about 1% to about 4% by weight, also comprising about 1% to about 2% by weight. The mulberry component is a mulberry plant material, a mulberry extract, or a combination thereof.

[0085] In one embodiment of the present invention, the composition contains at least 1 mg of 1-deoxynojirimycin (DNJ) per gram of dry weight of the composition, preferably at least 1 mg of DNJ per gram of dry weight of the composition, preferably at least 2 mg of DNJ per gram of dry weight of the composition, preferably at least 3 mg of DNJ, preferably at least 4 mg of DNJ, more preferably at least 5 mg of DNJ, for example at least 6 mg of DNJ. In another embodiment of the present invention, the composition contains about 1 to about 20 mg of DNJ per gram of dry weight of the composition, preferably about 2 mg to about 10 mg of DNJ per gram of dry weight of the composition. In yet another embodiment of the present invention, the composition contains about 5 to about 10 mg of DNJ per gram of dry weight of the composition, preferably about 5 mg to about 8 mg of DNJ per gram of dry weight of the composition, for example at about 6 mg to about 7 mg of DNJ per gram of dry weight of the composition.

[0086] In one embodiment, the composition is administered to an individual in servings that provide at least about 1 mg of DNJ per serving, preferably at least about 5 mg of DNJ, and more preferably at least about 10 mg of DNJ per serving. In some embodiments, up to 50 mg of DNJ per serving of the composition is administered. In some embodiments, up to 100 mg of DNJ per serving of the composition may be administered.

[0087] The weight ratio of mulberry component to fiber in this composition or combination formulation may be in the range of 1:30 to 1:1, preferably including 1:40 to 1:1, and more preferably 1:10 to 1:4.

[0088] Combination formulations With respect to the present invention, “combination formulation” means that combination partner (a) fiber and combination partner (b) mulberry component can be administered independently or in various predetermined combinations of (a) and (b) in distinct amounts, then the fiber and mulberry component may be administered simultaneously, for example, or at different times, i.e., at different times and at equal or different time intervals relative to either of them. The fiber and mulberry component may be included in the same composition as excipients, additives, or other components useful for the proposed use; or combination partners (a) and (b) may be administered or applied in separate compositions and through different routes of administration to obtain a combined therapeutic effect.

[0089] Concurrent administration may be performed, for example, in the form of one predetermined combination of (a) and (b), or by administering (a) and (b) simultaneously if they are prescribed independently.

[0090] Continuous use (administration) preferably means the administration of one component of the combination at one point in time, and the administration of the other component at another point in time, i.e., in a staggered manner, such that the combination exhibits a greater effect (particularly an enhancing or synergistic effect) than a single component administered independently.

[0091] Separate use (administration) preferably means administering the components of the combination independently at different time points, and preferably means that components (a) and (b) are administered in such a way that there is no overlap in measurable blood concentrations of both compounds (at the same time).

[0092] Furthermore, preferably, two or more combinations of continuous administration, separate administration, and simultaneous administration are also possible, such that the combination components exhibit a therapeutic effect that exceeds the effect found when the combination components are used independently at time intervals so large that no synergistic effect on their therapeutic effects is observed.

[0093] For example, to address the needs of a subpopulation of patients receiving treatment, or the needs of an individual patient, which may vary depending on the patient's specific disease, age, sex, weight, etc., the ratio of the total amount of combination partner (a) fiber to the total amount of combination partner (b) mulberry component administered in the combination formulation can be changed.

[0094] Preferably, at least one beneficial effect, for example, mutual enhancement of the effects of combination partners (a) fiber and (b) mulberry component, specifically, an effect greater than the additive effect that could be achieved for this reason by each of the combined drugs at a lower dose than would be acceptable in the case of treatment with the individual drugs alone without combination, and an additional beneficial effect, for example, fewer side effects or combined therapeutic effects at ineffective doses of one or both combination partners (a) and (b), and very preferably, a strong enhancement or synergistic effect of combination partners (a) and (b).

[0095] composition In this invention, "composition" means a composition containing a combination of fibers and mulberry components.

[0096] The compositions of the present invention may contain optional additional components, including one or more conventional food additives (synthetic or natural), such as fillers, acidulants, thickeners, buffers or agents for pH adjustment, chelating agents, colorants, emulsifiers, additives, flavoring agents, minerals, penetrating agents, preservatives, stabilizers, texturers, and vitamins. The optional components may be added in any suitable amount.

[0097] Suitable compositions for the present invention may be in the form of powders, granules, tablets, chewable tablets, softgels, sachets, solutions (e.g., tonics), liquid suspensions, emulsions, or concentrates.

[0098] The compositions of the present invention may be administered to humans or animals, particularly to any site in the gastrointestinal tract, by any preferred method. Intestinal administration, oral administration, and administration through a tube or catheter are all included in this disclosure.

[0099] Optional components The combination formulation or composition of the present invention may further comprise other optional agents useful for maintaining blood glucose, managing blood glucose, detoxifying by the liver, or protecting the liver.

[0100] The combination formulation or composition may further contain minerals suitable for use in nutritional products. Non-limiting examples include phosphorus, sodium, chloride, magnesium, manganese, iron, copper, zinc, iodine, calcium, potassium, chromium, chromium picolinate, molybdenum, selenium, and combinations thereof.

[0101] The combination formulation or composition may further contain any vitamin or other similar material suitable for use in humans or animals. Non-limiting examples include carotenoids (e.g., β-carotene, zeaxanthin, lutein, lycopene), biotin, choline, inositol, folic acid, pantothenic acid, vitamin A, thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), pyridoxine (vitamin B6), cyanocobalamin (vitamin B12), ascorbic acid (vitamin C), vitamin D, vitamin E, vitamin K, and various salts, esters, or other derivatives thereof, and any combination thereof. Vitamin C, vitamin D, and / or vitamin B12 are particularly useful in this composition. In preferred embodiments, the composition is supplemented with one or more vitamins and / or minerals selected from vitamin C, vitamin B3, zinc, or any combination thereof.

[0102] use The combination formulation according to the present invention is effective in reducing blood glucose levels.

[0103] Accordingly, the combination formulations, compositions, uses, and methods of the present invention may be used for the prevention and / or treatment of hyperglycemia and / or related conditions, such as prediabetes, diabetes and especially type 2 diabetes, impaired glucose tolerance, impaired insulin sensitivity, diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy.

[0104] The combination formulations, compositions, uses, and methods according to the present invention may be further used for weight management.

[0105] The combination formulations, compositions, uses, and methods according to the present invention may be further used to promote weight loss and / or suppress fat gain.

[0106] The combination formulations, compositions, uses, and methods according to the present invention may be further used for the prevention or treatment of obesity.

[0107] The compositions of the present invention can assist in maintaining and managing blood glucose levels, preferably in lowering blood glucose, promoting weight loss, suppressing fat accumulation, and assisting in the prevention or treatment of obesity. It should be noted that embodiments and features described in the context of one aspect of the present invention also apply to other aspects of the invention.

[0108] All patent and non-patent documents cited in this application are incorporated into this application exactly as they appear in the documents.

[0109] Although the present invention has been described by examples, it should be understood that modifications and alterations can be made without departing from the scope of the invention as defined in the claims. Furthermore, where known equivalents exist for certain features, such equivalents are incorporated as if they were specifically referred to herein.

[0110] The present invention will be further described with reference to the following embodiments. It will be understood that the claimed invention is not intended to be limited in any form by these embodiments. [Examples]

[0111] The implementation of this invention will utilize the prior art known to those skilled in the art and available unless otherwise indicated.

[0112] The following examples illustrate various embodiments of the Disclosure, and are not limiting. The examples are given solely for illustrative purposes and should not be construed as limiting, as many variations are possible without departing from the spirit and scope of the Disclosure. In all examples, the concentrations of the components are given as w / w% based on the overall product formulation.

[0113] Example 1 Materials: The mulberry leaf extract used in this study was purchased from Naturex Ltd. The extract was a selective extract of mulberry leaves containing 1% DNJ. The raw materials for Fiber B (FOS, inulin, acacia gum + PHGG) and Fiber A (FOS, inulin, acacia gum) were purchased from Taiyo Ltd (partially hydrolyzed guar gum), Jebsen & Co. Ltd (acacia gum), and BENEO. Ltd (inulin, fructooligosaccharides).

[0114] animal Male C57 / BL6 mice weighing 20-25g, 30 days old, were purchased from a commercial breeder (SLAC, Shanghai) and housed in a 12-hour light-dark cycle, 22°C, and SPF (Specific Parasite Free) environment. All mice were fed solid food for 7 days to allow them to adapt to the environment and diet. Overweight models were created by feeding them a high-fat diet (HFD) (45% kcal fat content). Mice were randomly assigned to seven groups (10 mice per group): (i) control group (solid feed), (ii) HFD group (high-fat diet (HFD), 45% kcal fat content as in Example 2), (iii) HFD containing 200 mg / kg / day of mulberry leaf extract (MLE), (iv) HFD containing 5 g / kg / day of fiber A, (v) HFD containing 5 g / kg / day of fiber B, (vi) HFD containing a combination of MLE / fiber A, and (vii) HFD containing a combination of MLE / fiber B. The dosage for each component combination was the same as for the single-component groups. Treatment was administered orally simultaneously with the HF diet. The body weight and food intake of the mice were recorded twice a week. Four months after treatment and HFD feeding, the mice were sacrificed, and blood, liver, muscle, and adipose tissue were collected and frozen at -75°C. In addition, epididymal fat and perirenal fat were immediately excised and weighed. All procedures were carried out in accordance with the United States Public Health Services Guide for the Care and Use of Laboratory Animals, and every effort was made to minimize the suffering and number of animals used in this study.

[0115] Oral glucose tolerance test (OGTT) Oral glucose tolerance tests (OGTTs) were performed consciously before the start of treatment and one week before slaughter to avoid stress on the animals' physical systems. OGTTs (2.5 g maltose / kg body weight) were administered according to previously reported methods. All mice were fasted overnight prior to the OGTT. Blood was collected from the orbital vein at 0, 5, 15, 30, 60, 120, and 180 minutes after oral administration of maltose. Plasma glucose concentrations were measured by the glucose oxidase method.

[0116] Blood biochemical assays Serum levels of insulin, leptin, IL-1, IL-6, free fatty acids, triglycerides, cholesterol, HDL-cholesterol, and LDL-cholesterol, as well as fecal free fatty acid levels, were measured using standard clinical assays.

[0117] statistical analysis Data are presented as mean ± standard error of the mean. Statistical significance was assessed by one-way ANOVA followed by LSD post-hoc analysis. The significance level was set at p<0.05 for all comparisons.

[0118] Effects on insulin sensitivity Mouse serum was collected after sacrifice. Serum glucose (A) and insulin (B) were measured. Oral glucose tolerance tests (OGTT) were performed one week before mouse sacrifice. Blood was collected from the orbital vein 0, 15, 30, 60, 120, and 180 minutes after oral glucose administration. As seen in Figures 1, 2, and 3, HFD significantly increased fasting glucose, OGTT, and insulin content in mice, and this increase was significantly reduced by MLE and fiber (Figures 1-3, values ​​mean ± standard error of mean, N=10, **p<0.01 vs. control). The combination of MLE and fiber was more effective than treatment alone (Figures 1-3). The combination of MLE and fiber B had a synergistic effect on insulin content compared to treatment alone (Figure 1).

[0119] The effect of HFD on body weight During a 4-month period of HFD feeding and various supplementation, the body weight of mice was measured twice a week. It was found that HFD significantly increased body weight, while both MLE and fiber successfully reduced body weight (Figure 4). The combination of MLE and fiber was more effective than monotherapy (Figure 4). The most significant effect on weight loss was observed with the combination of MLE and fiber B (Figures 4B, 4D).

[0120] Effects on epididymal fat mass and perirenal fat mass Similar to the results for weight gain, both MLE and fiber were found to successfully reduce epididymal fat mass and perirenal fat mass. The combination of MLE and fiber was more effective than treatment alone (Figures 5A, 5C). The combination of MLE and fiber B was synergistic compared to treatment alone (Figures 5B, 5D). Values ​​are mean ± standard error of the mean, N=10. *p<0.05, **p<0.01 vs. control.

Claims

1. A combination preparation of fiber and mulberry components, or a composition containing fiber and mulberry components, for use in maintaining blood glucose levels, for use in managing blood glucose levels, or for supporting weight loss and / or weight maintenance, The mulberry component is mulberry leaf extract, A combination formulation or composition in which the aforementioned fibers include FOS, inulin, and acacia gum.

2. A combination formulation or composition according to claim 1, for use in the prevention or treatment of obesity.

3. The combination formulation or composition according to claim 1 or 2, wherein the mulberry component is derived from Morus alba L., Morus nigra L., Morus celtidifolia Kunth, Morus rubra L., a hybrid of Morus alba and red mulberry, Morus australis, Morus laevigata, and combinations thereof.

4. A combination formulation or composition according to any one of claims 1 to 3, wherein the weight ratio of fiber to mulberry component is in the range of 20:1 to 1:

1.

5. The combination formulation or composition according to any one of claims 1 to 4, wherein the fiber further comprises partially hydrolyzed guar gum (PHGG).

6. The combination formulation or composition according to any one of claims 1 to 5, wherein the combination formulation or composition is in the form of a powder, paste, liquid, or tablet.

7. The combination formulation or composition according to any one of claims 1 to 6, wherein the combination formulation or composition contains 5% to 95% of the fiber by dry weight of the combination formulation or composition, and contains 0.5% to 50% of the mulberry component by dry weight of the combination formulation or composition.

8. The combination formulation or composition according to any one of claims 1 to 7, wherein the combination formulation or composition contains 70% to 90% of the fibers by dry weight of the combination formulation or composition.

9. The combination formulation or composition according to any one of claims 1 to 7, wherein the combination formulation or composition contains 10% to 15% of the mulberry component by dry weight of the combination formulation or composition.

10. The combination formulation or composition according to any one of claims 1 to 7, wherein the combination formulation or composition contains 70% to 90% of the fiber by dry weight of the combination formulation or composition, and contains 10% to 15% of the mulberry component by dry weight of the combination formulation or composition.

11. The combination formulation or composition according to any one of claims 1 to 7, wherein the combination formulation or composition contains 80% to 90% of the fiber by dry weight of the combination formulation or composition, and contains 10% to 15% of the mulberry component by dry weight of the combination formulation or composition.

12. The use of a combination formulation of fiber and mulberry components, or a composition containing fiber and mulberry components, for the manufacture of a drug for maintaining blood glucose, managing blood glucose, or promoting weight loss and / or suppressing fat accumulation, The mulberry component is mulberry leaf extract, The aforementioned fiber contains FOS, inulin, and acacia gum.

13. The use according to claim 12, wherein the agent is for preventing and / or treating hyperglycemia and / or related conditions selected from prediabetes, diabetes, impaired glucose tolerance, abnormal fasting blood glucose, impaired insulin sensitivity, diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy, and / or for preventing and / or treating obesity.

14. The use according to claim 12 or 13, wherein the fiber further comprises partially hydrolyzed guar gum (PHGG).

15. The use of a combination formulation of fiber and mulberry components, or a composition containing fiber and mulberry components, for manufacturing health products to assist in controlling blood glucose levels, promoting weight loss, and / or suppressing fat accumulation, The mulberry component is mulberry leaf extract, The aforementioned fiber contains FOS, inulin, and acacia gum.

16. The use according to claim 15, wherein the fiber further comprises partially hydrolyzed guar gum (PHGG).

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