Composition for feeding deterring method or for feeding deterrence, body weight reduction, fatty liver improvement and body fat reduction

Abstract

The present disclosure relates to a composition or meal for improving lifestyle-related disease / improving metabolic syndrome / reducing body weight and feeding deterrence. The present disclosure provides a method for improving lifestyle-related disease / improving metabolic syndrome / reducing body weight and feeding deterrence, the method including a step for providing a meal such that a polypeptide (or protein) having a molecular weight larger than the molecular weight normally present in the intestine or having the number of amino acids longer than the amino acid length normally present in the intestine is present for a prescribed time in the intestine.

Description

Method for suppressing food intake or composition for suppressing food intake, weight loss, improvement of fatty liver and reduction of body fat

[0001] The present disclosure relates to the improvement of lifestyle-related diseases, metabolic syndrome, weight loss, and appetite suppression by administering an enterically soluble formulation of a protein such as soybean protein and delivering undigested protein to the small intestine, and to an enterically soluble composition or diet used therefor.

[0002] Although many methods for suppressing food intake have been researched and developed, few have been successful. For example, although hypoglycemic and lipid-lowering drugs are already on the market, no clear weight-reduction effects have been confirmed by administering these drugs.

[0003] This disclosure is based on the hypothesis that undigested protein that reaches the small intestine in a state of indigestion may affect appetite and weight loss. In order to allow undigested protein to reach the small intestine directly, soy flour (soybean protein) formulated as an enteric-soluble formulation was administered to normal mice, and the effects on food intake and body weight were confirmed.

[0004] Accordingly, the present disclosure provides the following: [Item 1] A composition for improving lifestyle-related diseases, improving metabolic syndrome, reducing weight, and suppressing food intake, comprising a polypeptide (or protein) or a complex thereof having a molecular weight greater than that normally present in the intestine or a longer number of amino acids than that normally present in the intestine, or an active substance that produces the polypeptide or complex upon reaching the intestine. [Item 2] The composition according to any one of the above items, wherein the polypeptide (or protein) or complex thereof, or the active substance has an average molecular weight (weight average) x amount greater than a predetermined threshold upon reaching the intestine. [Item 3] The composition according to any one of the above items, wherein the composition is in a dosage form such that the average molecular weight (weight average) x amount of the active substance is greater than a predetermined threshold. [Item 4] The composition according to any one of the above items, wherein the active substance is formulated with a substance that interferes with digestion in the gastrointestinal tract before reaching the intestine, and wherein the average molecular weight (weight average) x amount is greater than a certain threshold. [Item 5] The composition according to any one of the above items, wherein the threshold is between 8,000 and 10,000. [Item 6] The composition according to any one of the above items, wherein the threshold value is 9,500. [Item 7] The composition according to any one of the above items, wherein the composition is in a dosage form coated to prevent digestion of the polypeptide or complex thereof, or the active substance to an amino acid length not exceeding that normally present in the stomach. [Item 8] The composition according to any one of the above items, wherein the composition is an enteric-coated formulation. [Item 9] The composition according to Item 7, wherein the dosage form is an enteric-coated capsule. [Item 9A] The composition according to Item 7, wherein the dosage form is an enteric-coated tablet. [Item 10] The composition according to any one of the above items, wherein the polypeptide (or protein) or complex thereof is formulated to remain in the intestine for about 2 hours or more. [Item 11] The composition according to any one of the above items, wherein the intestine includes the small intestine (preferably the upper part of the small intestine).[Item 12] The composition according to any one of the above items, wherein the composition is configured to prevent digestion of the polypeptide or complex thereof, or active substance in the stomach so that the molecular weight or amino acid length is reduced to a level normally present in the stomach. [Item 13] The composition according to any one of the above items, wherein the composition is formulated so that the polypeptide or active substance is administered in an amount of 100 mg or more. [Item 14] The composition according to any one of the above items, wherein the polypeptide or active substance is administered in an amount of 100 mg to 20 g / 60 kg body weight. [Item 15] The composition according to any one of the above items, wherein the polypeptide or active substance is formulated so that it is administered orally. [Item 16] The composition according to any one of the above items, wherein the polypeptide or protein has a molecular weight of 20 kDa or more (preferably 50 kDa or more) or a length of 150 amino acids or more (preferably 400 amino acids). [Item 17] The composition according to any one of the above items, wherein the polypeptide or complex thereof, or active substance comprises a processed protein. [Item 18] The composition according to any one of the above items, wherein the processed protein is an inactivated active protein. [Item 19] The composition according to any one of the above items, wherein the polypeptide or protein comprises an undigested protein. [Item 20] The composition according to any one of the above items, wherein the polypeptide or protein is derived from a legume, a grass, a Polygonaceae, a Labiatae, an Amaranthaceae plant, a milk protein, or an animal muscle. [Item 21] The composition according to any one of the above items, wherein the composition comprises a protein selected from the group consisting of whey protein, soy protein, and gelatin protein. [Item 22] The composition according to any one of the above items, wherein the composition is for treating obesity. [Item 23] The composition according to any one of the above items, wherein the composition is provided with a meal. [Item 24] The composition according to any one of the preceding items, wherein the composition is provided as a meal set.[Item 25] A method for improving lifestyle-related diseases, alleviating metabolic syndrome, reducing weight, and suppressing food intake, comprising the step of administering a polypeptide (or protein) or complex thereof having a molecular weight greater than that normally present in the intestine or a number of amino acids greater than that normally present in the intestine, or an active substance that produces said polypeptide or complex upon reaching the intestine, at a predetermined time before a meal or during a meal, and then having the subject eat the meal. [Item 25A] A method for improving lifestyle-related diseases, alleviating metabolic syndrome, reducing weight, and suppressing food intake, comprising the step of administering a polypeptide (or protein) having a molecular weight greater than that normally present in the intestine or a number of amino acids greater than that normally present in the intestine, at a predetermined time before a meal or during a meal, and then having the subject eat the meal. [Item 26] The method according to any one of the above items, wherein the predetermined time is between 0 minutes and 1 day. [Item 27] ​​The method according to any one of the above items, wherein the predetermined time is 2 hours or more. [Item 28] The method according to any one of the above items, further comprising the features of any one or more of items 1 to 24. [Item A1] A polypeptide (or protein) or its complex having a molecular weight greater than that normally present in the intestine or a number of amino acids greater than that normally present in the intestine, or an active substance that produces the polypeptide or its complex upon reaching the intestine, for use in improving lifestyle-related diseases, improving metabolic syndrome, weight loss, and suppressing food intake. [Item A2] The polypeptide (or protein) or its complex, or active substance described in any one of the above items, characterized in that the average molecular weight (weight average) multiplied by the amount upon reaching the intestine is higher than a predetermined threshold. [Item A3] The polypeptide (or protein) or its complex, or active substance described in any one of the above items, in a dosage form such that the average molecular weight (weight average) multiplied by the amount of the active substance is higher than a predetermined threshold.[Item A4] The polypeptide (or protein), or complex thereof, or active substance according to any one of the above items, wherein the active substance is formulated with a substance that inhibits digestion in the gastrointestinal tract before reaching the intestine, and wherein the average molecular weight (weight average) x amount is higher than a certain threshold. [Item A5] The polypeptide (or protein), or complex thereof, or active substance according to any one of the above items, wherein the threshold is 8,000 to 10,000. [Item A6] The polypeptide (or protein), or complex thereof, or active substance according to any one of the above items, wherein the threshold is 9,500. [Item A7] The polypeptide (or protein), or complex thereof, or active substance according to any one of the above items, wherein the polypeptide (or protein), or complex thereof, or active substance is in a dosage form coated to prevent digestion of the polypeptide or complex thereof, or active substance to a length of amino acids normally found in the stomach or less. [Item A8] The polypeptide (or protein), or complex thereof, or active substance according to any one of the above items, wherein the polypeptide (or protein), or complex thereof, or active substance is in an enteric-coated formulation. [Item A9] The polypeptide (or protein), or complex thereof, or active substance according to any one of the preceding items, wherein the dosage form is an enteric-coated capsule. [Item A9A] The polypeptide (or protein), or complex thereof, or active substance according to any one of the preceding items, wherein the dosage form is an enteric-coated tablet. [Item A10] The polypeptide (or protein), or complex thereof, or active substance according to any one of the preceding items, wherein the polypeptide (or protein), or complex thereof, is formulated so as to be present in the intestine for about 2 hours or more. [Item A11] The polypeptide (or protein), or complex thereof, or active substance according to any one of the preceding items, wherein the intestine includes the small intestine (preferably the upper part of the small intestine).[Item A12] The polypeptide (or protein), complex thereof, or active substance according to any one of the preceding items, wherein the polypeptide (or protein), complex thereof, or active substance is configured to be resistant to digestion in the stomach so that the molecular weight or amino acid length of the polypeptide or complex thereof is reduced to a level equal to or less than that normally present in the stomach. [Item A13] The polypeptide (or protein), complex thereof, or active substance according to any one of the preceding items, wherein the polypeptide (or protein), complex thereof, or active substance is formulated to be administered in an amount of 100 mg or more. [Item A14] The polypeptide (or protein), complex thereof, or active substance according to any one of the preceding items, wherein the polypeptide (or protein), complex thereof, or active substance is formulated to be administered in an amount of 100 mg to 20 g / 60 kg body weight. [Item A15] The polypeptide (or protein), complex thereof, or active substance according to any one of the preceding items, wherein the polypeptide (or protein), complex thereof, or active substance is formulated to be administered orally. [Item A16] The polypeptide (or protein), or a complex thereof, or active substance according to any one of the preceding items, wherein the polypeptide or protein has a molecular weight of 20 kDa or more (preferably 50 kDa or more) or a length of 150 amino acids or more (preferably 400 amino acids). [Item A17] The polypeptide (or protein), or a complex thereof, or active substance according to any one of the preceding items, wherein the polypeptide, or complex thereof, or active substance comprises a processed protein. [Item A18] The polypeptide (or protein), or a complex thereof, or active substance according to any one of the preceding items, wherein the processed protein is an inactivated active protein.[Item A19] The composition according to any one of the above items, wherein the polypeptide or protein comprises undigested protein. [Item A20] The polypeptide (or protein), or its complex, or active substance according to any one of the above items, wherein the polypeptide or protein is derived from legumes, grasses, Polygonaceae, Lamiaceae, Amaranthaceae, milk protein, or animal muscle. [Item A21] The polypeptide (or protein), or its complex, or active substance according to any one of the above items, comprising a protein selected from the group consisting of whey protein, soy protein, and gelatin protein. [Item A22] The polypeptide (or protein), or its complex, or active substance according to any one of the above items, which is for treating obesity. [Item A23] The polypeptide (or protein), or its complex, or active substance according to any one of the above items, which is provided with a meal. [Item A24] The polypeptide (or protein), or its complex, or active substance according to any one of the above items, which is provided as a meal set. [Item B1] Use of a polypeptide (or protein) or its complex, or an active substance that produces said polypeptide or complex upon reaching the intestine, having a molecular weight greater than that normally present in the intestine or having a longer number of amino acids than that normally present in the intestine, in the manufacture of a pharmaceutical for ameliorating lifestyle-related diseases, ameliorating metabolic syndrome, weight loss, and suppressing food intake. [Item B2] The use according to the above items, wherein the polypeptide (or protein) or its complex, or active substance is characterized in that its average molecular weight (weight average) multiplied by its amount upon reaching the intestine is higher than a predetermined threshold. [Item B3] The use according to any one of the above items, wherein the polypeptide (or protein) or its complex, or active substance is in a dosage form such that its average molecular weight (weight average) multiplied by its amount is higher than a predetermined threshold.[Item B4] The use according to any one of the above items, wherein the active substance is formulated with a substance that inhibits digestion in the digestive tract before reaching the intestine, and the average molecular weight (weight average) x amount is higher than a certain threshold. [Item B5] The use according to any one of the above items, wherein the threshold is 8,000 to 10,000. [Item B6] The use according to any one of the above items, wherein the threshold is 9,500. [Item B7] The use according to any one of the above items, wherein the polypeptide (or protein) or complex thereof, or active substance is in a dosage form coated to prevent the polypeptide or complex thereof, or active substance from being digested to a length of amino acids normally present in the stomach or less. [Item B8] The use according to any one of the above items, wherein the polypeptide (or protein) or complex thereof, or active substance is in an enteric-coated formulation. [Item B9] The use according to any one of the above items, wherein the dosage form is an enteric-coated capsule. [Item B9A] The use according to any one of the above items, wherein the dosage form is an enteric-coated tablet. [Item B10] The use according to any one of the above items, wherein the polypeptide (or protein) or complex thereof is formulated to be present in the intestine for about 2 hours or more. [Item B11] The use according to any one of the above items, wherein the intestine includes the small intestine (preferably the upper small intestine). [Item B12] The use according to any one of the above items, wherein the polypeptide (or protein) or complex thereof, or active substance is formulated to prevent digestion in the stomach such that the polypeptide or complex thereof, or active substance is reduced to a molecular weight or amino acid length not exceeding that normally present in the stomach. [Item B13] The use according to any one of the above items, wherein the polypeptide (or protein) or complex thereof, or active substance is formulated so that the polypeptide or active substance is administered in an amount of 100 mg or more. [Item B14] The use according to any one of the above items, wherein the composition is formulated so that the polypeptide or active substance is administered in an amount of 100 mg to 20 g / 60 kg body weight.[Item B15] The use according to any one of the above items, wherein the polypeptide (or protein) or its complex, or active substance is formulated so that the polypeptide or active substance is administered orally. [Item B16] The use according to any one of the above items, wherein the polypeptide or protein has a molecular weight of 20 kDa or more (preferably 50 kDa or more) or a length of 150 amino acids or more (preferably 400 amino acids). [Item B17] The use according to any one of the above items, wherein the polypeptide or its complex, or active substance comprises a processed protein. [Item B18] The use according to any one of the above items, wherein the processed protein is an inactivated active protein. [Item B19] The use according to any one of the above items, wherein the polypeptide or protein comprises an undigested protein. [Item B20] The use according to any one of the above items, wherein the polypeptide or protein is derived from a legume, a grass, a Polygonaceae, a Labiatae, a Amaranthaceae plant, milk protein, or animal muscle. [Item B21] The use according to any one of the above items, wherein the polypeptide or protein comprises a protein selected from the group consisting of whey protein, soy protein, and gelatin protein. [Item B22] The use according to any one of the above items, wherein the polypeptide or protein is for treating obesity. [Item B23] The use according to any one of the above items, wherein the polypeptide or protein is provided with a meal. [Item B24] The use according to any one of the above items, wherein the polypeptide or protein is provided as a meal set. [Item C1] A method for treating or preventing lifestyle-related diseases, metabolic syndrome, weight loss, and food intake suppression, comprising the step of administering a polypeptide (or protein) or a complex thereof having a molecular weight greater than that normally found in the intestine or a number of amino acids greater than that normally found in the intestine, or an active substance that produces the polypeptide or complex upon reaching the intestine, at a predetermined time before or during a meal, and then ingesting the meal.[Item C2] The method according to any one of the preceding items, wherein the polypeptide (or protein), or its complex, or active substance is characterized in that its average molecular weight (weight average) x amount is higher than a predetermined threshold upon reaching the intestine. [Item C3] The method according to any one of the preceding items, wherein the polypeptide (or protein), or its complex, or active substance is in a dosage form such that its average molecular weight (weight average) x amount is higher than a predetermined threshold. [Item C4] The method according to any one of the preceding items, wherein the active substance is formulated with a substance that inhibits digestion in the gastrointestinal tract before reaching the intestine, and wherein its average molecular weight (weight average) x amount is higher than a certain threshold. [Item C5] The method according to any one of the preceding items, wherein the threshold is 8,000 to 10,000. [Item C6] The method according to any one of the preceding items, wherein the threshold is 9,500. [Item C7] The method according to any one of the preceding items, wherein the polypeptide (or protein), or its complex, or active substance is in a dosage form coated to prevent digestion of the polypeptide or its complex, or active substance to a length of amino acids normally found in the stomach or shorter. [Item C8] The method according to any one of the above items, wherein the polypeptide (or protein), or complex thereof, or active substance is in an enteric-coated formulation. [Item C9] The method according to any one of the above items, wherein the dosage form is an enteric-coated capsule. [Item C9A] The method according to any one of the above items, wherein the dosage form is an enteric-coated tablet. [Item C10] The method according to any one of the above items, wherein the polypeptide (or protein), or complex thereof, or active substance is formulated to be present in the intestine for about 2 hours or more. [Item C11] The method according to any one of the above items, wherein the intestine includes the small intestine (preferably the upper part of the small intestine). [Item C12] The method according to any one of the above items, wherein the polypeptide (or protein), or complex thereof, or active substance is configured to not be digested in a way that would reduce the molecular weight or amino acid length of the polypeptide, complex thereof, or active substance to a level normally present in the stomach.[Item C13] The method of any one of the above items, wherein the polypeptide (or protein), or complex thereof, or active substance is formulated to be administered in an amount of 100 mg or more. [Item C14] The method of any one of the above items, wherein the polypeptide (or protein), or complex thereof, or active substance is formulated to be administered in an amount of 100 mg to 20 g / 60 kg body weight. [Item C15] The method of any one of the above items, wherein the polypeptide (or protein), or complex thereof, or active substance is formulated to be administered orally. [Item C16] The method of any one of the above items, wherein the polypeptide or protein has a molecular weight of 20 kDa or more (preferably 50 kDa or more) or a length of 150 amino acids or more (preferably 400 amino acids). [Item C17] The method of any one of the above items, wherein the polypeptide, or complex thereof, or active substance comprises a processed protein. [Item C18] The method according to any one of the above items, wherein the processed protein is an inactivated active protein. [Item C19] The method according to any one of the above items, wherein the polypeptide or protein comprises an undigested protein. [Item C20] The method according to any one of the above items, wherein the polypeptide or protein is derived from a legume, a grass, a Polygonaceae, a Labiatae, an Amaranthaceae, a milk protein, or an animal muscle. [Item C21] The method according to any one of the above items, wherein the polypeptide or protein comprises a protein selected from the group consisting of whey protein, soy protein, and gelatin protein. [Item C22] The method according to any one of the above items, wherein the polypeptide or protein is for treating obesity. [Item C23] The method according to any one of the above items, wherein the polypeptide or protein is provided with a meal. [Item C24] The method according to any one of the above items, wherein the polypeptide or protein is provided as a meal set.

[0005] It is contemplated that the present disclosure may provide one or more of the above-described features in combinations other than those explicitly stated. Still further embodiments and advantages of the present disclosure will be recognized by those skilled in the art upon reading and understanding the following detailed description, if necessary.

[0006] The present disclosure provides a technology for easily achieving improvement in lifestyle-related diseases, improvement in metabolic syndrome, weight loss, and food intake suppression. This allows for various therapeutic and preventive treatments, such as dietary therapy. The technology disclosed herein provides a new, inexpensive, and versatile means for solving medical economic problems, which can achieve a level of effectiveness not achievable with previously used drugs such as bofutsushosan and the lipid absorption inhibitor orlistat (Arai), which have low efficacy, or with some very expensive drugs (e.g., GLP-1-related preparations).

[0007] FIG. 1 shows the food intake suppression and body weight reduction effect of enteric-coated encapsulated defatted soy flour in Example 1. The vertical axis shows food intake (g), and the horizontal axis shows elapsed time (hours). Error bars indicate standard error SEM. Significant differences are indicated as follows: *: p<0.05, **: p<0.01, ***: p<0.005. FIG. 2 shows the food intake suppression and body weight reduction effect of enteric-coated encapsulated casein in Example 2. The vertical axis shows food intake (g), and the horizontal axis shows elapsed time (hours). Error bars indicate standard error SEM. Significant differences are indicated as follows: *: p<0.05, **: p<0.01, ***: p<0.005. FIG. 3 shows the food intake suppression and body weight reduction effect of enteric-coated encapsulated soy protein. The vertical axis shows food intake (g), and the horizontal axis shows elapsed time (hours). Error bars indicate standard error SEM. Significant differences are indicated as follows: *: p<0.05, **: p<0.01, ***: p<0.005. Figure 4 shows the food intake suppression and body weight reduction effects of encapsulated soy protein without enteric coating. The vertical axis indicates food intake (g), and the horizontal axis indicates elapsed time (hours). Error bars indicate standard error SEM. Significant differences are indicated as follows: *: p<0.05, **: p<0.01, ***: p<0.005. Figure 5 shows the food intake suppression and body weight reduction effects of encapsulated pea protein with enteric coating. The vertical axis indicates food intake (g), and the horizontal axis indicates elapsed time (hours). Error bars indicate standard error SEM. Significant differences are indicated as follows: *: p<0.05, **: p<0.01, ***: p<0.005. Figure 6 shows the food intake suppression effect of enteric-coated encapsulated heated chicken protein. The vertical axis shows food intake (g), and the horizontal axis shows elapsed time (hours). Error bars indicate standard error SEM. Significant differences are indicated as follows: *: p<0.05, **: p<0.01, ***: p<0.005. Figure 7 shows the food intake suppression effect of enteric-coated encapsulated whey protein. The vertical axis shows food intake (g), and the horizontal axis shows elapsed time (hours). Error bars indicate standard error SEM. Significant differences are indicated as follows: *: p<0.05, **: p<0.01, ***: p<0.005.Figure 8 shows the food intake suppression effect of enteric-coated encapsulated heated whey protein. The vertical axis shows food intake (g), and the horizontal axis shows elapsed time (hours). Error bars show standard error SEM. Significant differences are indicated as follows: *: p<0.05, **: p<0.01, ***: p<0.005. Figure 9-1 shows an example of the food intake suppression effect of enteric-coated encapsulated soy protein. The vertical axis shows food intake (g), and the horizontal axis shows the number of days elapsed (days). Error bars show standard error SEM. Figure 9-2 shows an example of the food intake suppression effect of enteric-coated encapsulated soy protein. The vertical axis shows body weight change (g), and the horizontal axis shows the number of days elapsed (days). Error bars show standard error SEM. Figure 9-3 shows another example of the food intake suppression effect of enteric-coated encapsulated soy protein. The vertical axis represents body weight (g), and the horizontal axis represents the number of days elapsed (days). Error bars represent standard error SEM. FIG. 10 is a diagram showing the process of whether the objective of the present disclosure can be achieved if the product of average molecular weight and content exceeds a certain value. FIG. 11 illustrates the hardware configuration of the ingredient adjustment support server of the present disclosure. FIG. 12 shows an example of a user information table of the present disclosure. FIG. 13 shows a dietary information table of the present disclosure.

[0008] Throughout this specification, singular expressions should be understood to include the plural concept unless otherwise specified. Thus, singular articles (e.g., "a," "an," "the," etc. in English) should be understood to include the plural concept unless otherwise specified. Furthermore, it should be understood that terms used in this specification are used in the sense commonly used in the art unless otherwise specified. Therefore, unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In case of conflict, the present specification (including definitions) will control.

[0009] (Definitions) We first explain the terms and general techniques used in this disclosure.

[0010] As used herein, the term "intestine" refers to the digestive tract below the stomach.

[0011] As used herein, the term "enteric coating" refers to preparation and formulation that prevents decomposition until the drug reaches the intestines, such as the stomach, and exposes the contents (e.g., proteins) contained in the drug in the digestive tract below the stomach.

[0012] As used herein, the term "molecular weight normally present in the intestine" refers to the molecular weight of a molecule (e.g., a protein) present when reaching the intestine after digestion in the body, when referring to a nutritional component obtained from a normally ingested diet. When a protein exists as a complex of multiple subunits, the term refers to the molecular weight of the entire complex (the complex itself). When referring to an active substance that produces the polypeptide or complex thereof upon reaching the intestine, the state before ingestion (pre-digestion) is not important. When referring to a protein or polypeptide, it can also be expressed as "having a number of amino acids longer than the amino acid length normally present in the intestine." The molecular weight normally present in the intestine may vary depending on the subject, but the overall molecular weight, including modifications such as sugar chains, is generally 20 kDa or more, or in terms of amino acid length, 150 amino acids or more, and preferably 50 kDa or more, or 400 amino acids or more.

[0013] As used herein, the terms "protein" and "polypeptide" are used interchangeably and refer to a polymer of amino acids. Proteins or polypeptides may be modified with sugars, lipids, or the like. Protein molecular weights are typically expressed in "Da" (Daltons), with 1 kDa = 1,000 Da. Protein molecular weights can be determined using standard methods known to those skilled in the art, including, but not limited to, mass spectrometry (e.g., ESI, MALDI) or calculations from known amino acid sequences and glycosylation. Proteins can be naturally occurring or non-naturally occurring, synthetic, or semi-synthetic. For proteins, a "molecular weight typically found in the intestine" refers to a total molecular weight, including glycans, of approximately 20 kDa or more, or a length of approximately 150 amino acids or more, preferably 50 kDa or more, or 400 amino acids or more, although the length may be longer if there are no glycans.

[0014] Polypeptides or proteins that can be used in the present disclosure include those derived from legumes, grasses, Polygonaceae, Labiatae, Amaranthaceae, milk proteins, and animal muscle, and more particularly, but are not limited to, milk proteins (e.g., cow's milk proteins, other mammalian milk proteins, etc.), plant proteins (e.g., soybean proteins, cereal proteins, rice milk proteins, other plant proteins, etc.), or any combination of such proteins. When contained in a formulation such as an enteric coated capsule or enteric coated formulation, it may be advantageous for the major component (e.g., 50% or more) to be composed of protein, although this is not limited thereto.

[0015] As used herein, "soy protein" (which may also be referred to as soy protein or soy protein) refers to any protein that may be derived from soybeans, regardless of whether the protein is actually derived from soybeans. The term "soy protein" also collectively refers to a mixture of two or more soy proteins derived from soybeans. For example, "soy protein" may be a mixture of soybean proteins.

[0016] As used herein, "milk protein" refers to whole milk casein, whey protein, protein fractions, hydrolyzed casein, whey protein fractions, and the like, as well as mixtures thereof.

[0017] As used herein, "whey protein" refers to a mixture of globular proteins isolated from whey. A typical example is a mixture of whey proteins in milk, with 20% of the protein being whey protein and 80% being casein. Approximately 10% of the solid components of whey are protein, and typical examples include, but are not limited to, β-lactoglobulin (up to 65%), α-lactalbumin (up to 25%), serum albumin (up to 8%), immunoglobulins, etc.

[0018] In this specification, "gelatin" refers to a substance made from a protein called collagen, which is found in large amounts in animal bones and skin.

[0019] As used herein, the term "processed protein" refers to a protein that has undergone some form of processing (heating, pressure, grinding, salt, organic solvents, polymer compounds, pH manipulation, functional group modification, etc.), unlike proteins provided in a raw state. Conventional processing can make proteins that are not suitable for human consumption edible. Examples of processed proteins include those in which active proteins (e.g., lactoferrin) have been inactivated or enzymes have been inactivated. While the original physiological activity may be retained, it is advantageous to inactivate toxic physiological activity. Such processed proteins also include proteins that have been insufficiently processed when raw proteins are made edible. During processing, proteins such as peas (which have intact DPP-4 inhibitory activity) may be processed so as not to lose their enzymatic activity. On the other hand, it is preferable to inactivate proteins that have harmful effects on the human body, such as trypsin inhibitors from soybeans (soybeans may be extracted by changing the pH). Without wishing to be bound by theory, it is better to heat it in order to avoid side effects (safety), and it may be processed in this way to make it suitable for consumption, and as a result, when it reaches the intestines, it may become any polypeptide (or protein) or complex thereof that has a molecular weight or amino acid length larger or longer than that normally present.

[0020] As used herein, "an active substance that produces a (specific) polypeptide or complex thereof upon reaching the intestine" refers to an active substance that produces a specific polypeptide or complex of interest upon reaching the intestine after ingestion via the stomach or the like, and the form is not particularly important as long as the desired product is produced upon reaching the intestine. Such a substance may be an active substance that produces a polypeptide (or protein) or complex thereof that has a molecular weight greater than that normally present in the intestine or a number of amino acids longer than that normally present in the intestine after digestion, or alternatively, may be a substance whose molecules are complexed upon reaching the intestine to have a molecular weight greater than that normally present in the intestine or a number of amino acids longer than that normally present in the intestine.

[0021] As used herein, "a polypeptide (or protein) or complex thereof having a molecular weight greater than that normally present in the intestine, or a number of amino acids longer than that normally present in the intestine" refers to any polypeptide (or protein) or complex thereof that is larger or longer than the molecular weight or amino acid length normally present when a protein, etc., ingested orally, is digested in the digestive tract or the like before reaching the intestine. Examples of such polypeptides (or proteins) or complexes thereof include undigested proteins, processed proteins, etc., and even proteins that do not have to be such special proteins may achieve similar activity by interacting with or encapsulating (e.g., in a capsule) with other substances.

[0022] As used herein, "an active substance that, upon reaching the intestine, produces a polypeptide (or protein) or complex thereof having a molecular weight greater than that normally present in the intestine or a number of amino acids greater than that normally present in the intestine" refers to any substance (which may be a complex) produced when a protein ingested, for example, is digested in the digestive tract before reaching the intestine, resulting in a polypeptide (or protein) or complex thereof having a molecular weight greater than that normally present or a length greater than that normally present at the time of reaching the intestine; this substance may also be referred to simply as "active substance" herein. Such active substances include processed proteins or complexes thereof that are less susceptible to denaturation in the stomach, etc., as well as proteins or complexes that are not specifically processed but are combined with other substances to become less susceptible to denaturation in the stomach, etc., resulting in a polypeptide (or protein) or complex thereof having a molecular weight greater than that normally present or a length greater than that normally present at the time of reaching the intestine. Such active substances may be substances that are resistant to digestion alone, or substances with a large molecular weight such that their molecular weight does not fall below that normally present even after digestion in the stomach. As a result of the complexation, the molecular weight may be configured so that it does not fall below the molecular weight that normally exists even after digestion in the stomach.

[0023] As used herein, "configured to be resistant to digestion in the stomach to a molecular weight or amino acid length below that normally present" refers to a configuration in which, even if digested in the stomach, the molecular weight or amino acid length will not be reduced to a molecular weight or amino acid length below that normally present when changed by a normal diet, and refers to, for example, being coated to prevent digestion in the stomach. As long as it is possible to achieve a molecular weight higher than that normally present in the intestine, which is one of the objects of the present disclosure, it can be understood that the effects of the present disclosure are achieved as long as the molecule is retained at an effective length in the intestine even if it is decomposed to a certain extent in the stomach.

[0024] As used herein, "coating" refers to the application of a thin film to the surface of an object to be coated. The coating material may be referred to as a coating agent. Coating agents are additives used to coat tablets, for example, with polymeric compounds. Coating agents are used to mask the bitter taste of pharmaceuticals, protect pharmaceuticals from moisture, and gradually release active ingredients. Coated tablets are typically produced by spraying a coating medium dispersion onto tablets in a rotating drum while simultaneously drying the dispersion solvent. Coating agents include sugar coating, water-soluble coating, enteric coating, and sustained-release coating, and are used for different purposes. Sugar coating is a technique for coating plain tablets with sugar or other materials. Film coating refers to the coating of tablets with water-soluble polymeric substances. Enteric coating is designed to prevent the active ingredient from being destroyed by stomach acid and dissolve in the small intestine rather than the stomach. Sustained-release coating refers to a coating that prolongs the drug's effect, thereby reducing the frequency of dosing. Sustained-release coatings include ethyl cellulose. Repetab: These tablets have an enteric coating on the inside and a sugar-coated outer layer. Coating agents include the Spastab type, which is a tablet made by compressing a granular drug coated for slow dissolution (sustained-release granules) with a drug that dissolves quickly (immediate-release granules), and the Spassule type, which is filled into a capsule. Diffusion-sustained-release dosage forms, which are coated with porous polymers, are also available. The drug gradually dissolves through small holes, allowing the drug to maintain its effectiveness for a long period of time. For more information, see https: / / engineer-education.com / coating-agent / #i.

[0025] As used herein, the term "enteric-coated formulation" refers to a formulation designed to release the active ingredient primarily in the small intestine, rather than in the stomach. Forms include tablets, capsules, and granules. To prepare these formulations, an acid-insoluble enteric base is typically used to form a coating. Enteric-coated formulations are classified as delayed-release formulations, which are modified-release formulations that delay the onset of active ingredient release. These techniques are described in the Japanese Pharmacopoeia and can be used to manufacture enteric-coated formulations. A common method for creating enteric coatings is to coat the formulation with a polymer that is insoluble at low pH but dissolves near neutral pH. Additives used in enteric-coated formulations include, but are not limited to, hypromellose phthalate, cellulose acetate phthalate, and methacrylic acid copolymer. The Japanese Pharmacopoeia specifies testing methods for enteric-coated formulations manufactured as pharmaceuticals, and these can be tested as appropriate. Examples include enteric-coated capsules and capsules containing enteric-coated granules.

[0026] As used herein, the term "enteric coated tablet" refers to a tablet formulated so that it does not substantially dissolve until it reaches the intestine but dissolves in the intestine.

[0027] As used herein, the term "enteric coated capsule" is also referred to as "enteric film-coated capsule," and refers to a capsule whose surface is coated with an enteric film. The capsule may be left as is, or an enteric granule-containing capsule containing granules coated with an enteric film may also be provided.

[0028] As used herein, "lifestyle-related diseases" refers to a general term for diseases that are closely related to lifestyle habits such as diet, exercise, rest, smoking, and alcohol consumption, and whose onset is a contributing factor. The term "lifestyle-related diseases" has been used since around 1996. It is a term that redefines stroke, cancer, and heart disease, previously referred to as adult diseases, by focusing on lifestyle factors. The term "NCDs (non-communicable diseases)," which includes chronic obstructive pulmonary disease (COPD), is also commonly used internationally, and these terms are used interchangeably in this disclosure. Lifestyle-related diseases are conditions in which risk factors such as obesity, hypertension, impaired glucose tolerance, and dyslipidemia accumulate in an individual. Visceral fat accumulation obesity, in particular, is at the forefront of the pathology. It is known that environmental factors are added to the genetic background, and that each risk factor is linked over time. Lifestyle-related diseases include cancer, heart disease, stroke, diabetes, and the like.

[0029] As used herein, "improvement of metabolic syndrome" refers to any action that improves metabolic syndrome, which is a disease that adversely alters the processing and distribution of major nutrients such as protein, fat, and carbohydrates in the body. Representative examples include visceral obesity (visceral obesity / abdominal obesity) accompanied by two or more of the following symptoms: hyperglycemia, hypertension, and dyslipidemia.

[0030] As used herein, "weight loss" refers to any condition that results in a reduction in weight, including the prevention of weight gain in a person who would otherwise be prone to weight gain.

[0031] As used herein, "feeding suppression" typically refers to the binding of various hormones, such as leptin, to neurons in the feeding center and intestinal peristalsis, which then issue commands to suppress feeding. This allows for the treatment or prevention of obesity. Prevention and treatment of metabolic disorders associated with obesity, such as hyperglycemia, hypertension, and dyslipidemia, as well as cardiovascular complications, nephropathy, and fatty liver, associated with these metabolic diseases, are also contemplated. While not limited to these, there are multiple hormones in general that act on the feeding center and on peripheral tissues by suppressing intestinal peristalsis, and all of these are considered to be within the scope of the present disclosure. For example, see https: / / kotobank.jp / image / dictionary / naikagaku10 / media / ASNKG0801050000_T01.png.

[0032] As used herein, a "therapeutically effective amount" is the minimum concentration required to effect a measurable improvement or prevention of any symptom or a particular condition or disorder, to effect a measurable extension of life expectancy, or to generally improve the patient's quality of life. The therapeutically effective amount will depend on the specific biologically active molecule and the specific condition or disorder being treated. The therapeutically effective amount of many of the proteins described herein can be determined by reference to this specification, or, if not established, the therapeutically effective amount of the protein can be determined by appropriate standard techniques that are well within the skill of a physician or other skilled artisan.

[0033] As used herein, "diet," "meal," "food," "food material," or "food product" refers to the general meaning of these terms and encompasses any product classified as a "food" by a national authority (e.g., the Ministry of Agriculture, Forestry and Fisheries and the U.S. Food and Drug Administration), including weight loss products, meal replacement products, dietary supplement products (e.g., liquid dietary supplements), and the like. Food includes any product that can be drunk or ingested directly, or any product that can be further mixed with other ingredients, further processed, etc. to form a drinkable or ingestable product. For example, food can be mixed with liquid to form a beverage, added to flour and baked to form a bakery product, etc. The food products of the present disclosure may be in a variety of forms, such as liquids, frozen or semi-frozen liquids, dietary supplements, nutritional bars, nutritional drinks, candy bars, powders (e.g., beverage powders, etc.), baked goods (e.g., cookies, cakes, etc.), puddings, sauces, gravies, soups, bouillon, consommé, cake frosting, ice cream, yogurt, custard, gelatin desserts, applesauce, cottage cheese, cereals, breads, cheese, cheese spreads, chocolate (e.g., milk chocolate), liquid beverages (e.g., fruit juices (e.g., apple juice, orange juice, grape juice, grapefruit juice, cranberry juice, etc.) and vegetable juices (e.g., tomato juice, carrot juice, etc.), fruit and / or vegetable juice blends, coffee, tea, milk, milkshakes, hot chocolate, espresso, cappuccino, latte, etc.).

[0034] As used herein, the terms "portion" or "serving" refer to an appropriate serving size of a food product, such as, for example, a nutritional beverage, nutritional formula, weight loss product, or meal substitute, as defined by the U.S. Food and Drug Administration (FDA) and the Nutrition Labeling and Education Act (NLEA) as set forth in 21 CFR §101 or any later edition of FDA regulatory regulations that may correspond to 21 CFR §101. This disclosure also adopts the NLEA definition of serving size as the amount of food typically eaten at one time. When the food product of this disclosure includes a nutritional beverage or liquid meal substitute, a representative serving size may be about 230 to about 530 mL. A single serving of a food product may be packaged, for example, in various types of "single serving" packages / containers known in the art.

[0035] As used herein, "edible" refers to any raw material, ingredient, additive, etc. that can be ingested and is safe for human consumption.

[0036] As used herein, the term "intestine" is understood in the broadest sense in the art to refer to the organ responsible for digesting and absorbing food, excreting feces, etc. The intestine is divided into the small intestine (duodenum, jejunum, and ileum) and the large intestine (cecum, colon (ascending colon, transverse colon, descending colon, sigmoid colon), rectum, etc.).

[0037] As used herein, the term "small intestine" refers to the long, narrow digestive tract that lies between the stomach and the large intestine and snakes through the abdominal cavity. From the oral side, it consists of the duodenum, jejunum, and ileum. Food is digested and transported through peristalsis, segmental movements, and nutrients and water are absorbed through the mucosal villi. "Molecular weights normally present in the small intestine" or "polypeptides (or proteins) or complexes thereof having a number of amino acids longer than the amino acid length normally present in the small intestine" refers to any polypeptide (or protein) or complex thereof that has a molecular weight or amino acid length greater than the molecular weight normally present when a protein or the like ingested by oral ingestion or the like is digested in the digestive tract leading to the small intestine and reaches the intestine.

[0038] As used herein, the "upper small intestine" refers to the duodenum and jejunum. The terms "a molecular weight normally present in the upper small intestine" and "a polypeptide (or protein) or a complex thereof having a longer number of amino acids than the amino acid length normally present in the upper small intestine" refer to any polypeptide (or protein) or a complex thereof that has a molecular weight or a longer or longer amino acid length than the molecular weight normally present when a protein or the like administered by oral ingestion or the like is digested in the digestive tract before reaching the upper small intestine and normally reaches the intestine.

[0039] As used herein, the term "supplement" is used interchangeably with the terms "dietary supplement," "nutritional supplement," "food supplement," "alimentary supplement," or "alimentary complement" and refers to a product or preparation intended to supplement the normal diet, consisting of a source of concentrated nutrients or other substances having a nutritional or physiological effect. Food supplements can be in single or combined form and can be sold in dosage forms, i.e., capsules, pills, tablets, and other similar forms, powder sachets, liquid ampoules and dropper bottles, and other similar forms of liquids and powders designed to be taken as a single dose. Nutritional supplements may contain a wide range of nutrients and other elements, including vitamins, minerals, amino acids, essential fatty acids, fiber, enzymes, plants and plant extracts in particular.Their role is to supplement the nutrient supply in the diet, so they should not be used as a substitute for a balanced diet, and their intake should not exceed the daily amount explicitly recommended by a doctor or nutritionist.Probiotic compositions can also be part of so-called "special group foods", that is, foods that meet specific nutritional needs.

[0040] As used herein, the term "excipient" refers to any component or compound of any of the compositions of the present disclosure, i.e., a substance that aids in the preparation of the composition in the sense of aiding in the delivery of the components of the present disclosure, stabilizing the components, and / or providing consistency or flavor to make it more pleasant. Thus, excipients may, by way of example and without limitation, have the function of binding components (e.g., starch, sugar, or cellulose), sweetening, coloring, protecting active ingredients (e.g., isolating active ingredients from air and / or moisture), filling a pill, capsule, or any other presentation, or disintegrating to facilitate the dissolution of ingredients, but are not limited to other excipients not listed in this paragraph.

[0041] As used herein, a "vehicle" or "carrier" is specifically an inert substance. The function of a carrier is to facilitate the incorporation of other ingredients or compounds, allow for better dosing and administration, and / or provide consistency and form to the composition. Thus, a carrier is a substance used in drugs or food to dilute any of the ingredients or compounds of the composition of the present disclosure to a given volume or weight, or a substance that can allow for better dosing and administration and / or provide consistency and form to drugs or food without diluting these ingredients or compounds. When the dosage form is liquid, a pharmaceutically acceptable carrier is a diluent. Carriers can be natural or non-natural. Examples of pharmaceutically acceptable carriers include, but are not limited to, water, saline, alcohol, vegetable oils, polyethylene glycol, gelatin, lactose, starch, amylose, magnesium stearate, talc, surfactants, silicic acid, viscous paraffin, flavor oils, monoglycerides and diglycerides of fatty acids, fatty acid esters, hydroxymethylcellulose, polyvinylpyrrolidone, etc.

[0042] As used herein, the terms "subject" and "object" are equivalent to the term "individual," and therefore both terms can be used interchangeably herein. "Subject" refers to any individual, as well as any animal belonging to any species. Examples of subjects include, but are not limited to, animals of commercial interest, such as birds (hens, ostriches, chicks, geese, partridges, etc.), rabbits, hares, pet animals (dogs, cats, etc.), sheep, goat cattle (goats, etc.), Sus scrofa (boars, pigs, etc.), equine livestock (horses, ponies, etc.), bovine animals (bulls, cows, castrated bulls, etc.); animals of hunting interest, such as bucks, deer, reindeer, etc.; and humans. However, in certain embodiments, the subject is a mammal, and in particular, the mammal is a human of any race, sex, or age.

[0043] As used herein, "instructions" (including package inserts and labels used by the U.S. FDA) are written instructions to a physician or other user on how to use the present disclosure. The instructions include instructions for administering the medicament or the like of the present disclosure. The instructions may also include instructions for intravenous administration (e.g., by injection) as the administration site. The instructions are prepared in accordance with a format specified by the regulatory agency of the country in which the present disclosure is implemented (e.g., the Ministry of Health, Labor and Welfare in Japan, the Food and Drug Administration (FDA) in the United States, etc.), and clearly state that they have been approved by the regulatory agency. The instructions are so-called package inserts or labels, and may be provided in paper form, but are not limited thereto, and may also be provided in the form of electronic media (e.g., a website provided on the Internet, a PDF, or email).

[0044] (Preferred Embodiments) A description of preferred embodiments will be given below, but it should be understood that this embodiment is an example of the present disclosure and that the scope of the present disclosure is not limited to such preferred embodiments. It should also be understood that those skilled in the art can easily make modifications, changes, etc. within the scope of the present disclosure by referring to the following preferred examples. Therefore, it is clear that those skilled in the art can make appropriate modifications within the scope of the present disclosure by taking into account the description in this specification. It should also be understood that the following embodiments of the present disclosure can be used alone or in combination.

[0045] (Technology for Improving Lifestyle-Related Diseases, Metabolic Syndrome, Weight Loss, and Food Intake Suppression) In one aspect, the present disclosure provides a composition or diet for improving lifestyle-related diseases, improving metabolic syndrome, weight loss, and food intake suppression, comprising a polypeptide (or protein) or complex thereof having a molecular weight greater than that normally present in the intestine or a number of amino acids longer than that normally present in the intestine, or an active substance that produces the polypeptide or complex upon reaching the intestine. The present disclosure provides a composition or diet for improving lifestyle-related diseases, improving metabolic syndrome, weight loss, and food intake suppression, by ingesting the polypeptide (or protein) or complex thereof having a molecular weight greater than that normally present in the intestine or a number of amino acids longer than that normally present in the intestine in a manner not intended in a normal diet, thereby enabling the polypeptide (or protein) or complex thereof to be present in the intestine. It is not necessary to specifically define an effective period for treatment or prevention; any effective period can be set. It is understood that the effect can be achieved by ingesting the composition in the same manner as a normal diet, and therefore no particular control of the period is necessary.

[0046] In another aspect, the present disclosure provides a method for improving lifestyle-related diseases, improving metabolic syndrome, weight loss, and suppressing food intake, which includes a step of feeding a diet containing a polypeptide (or protein) having a molecular weight greater than that normally present in the intestine, or a longer amino acid length than that normally present in the intestine, in such a way that it is produced in the intestine. It is not necessary to specifically define the effective period for treatment or prevention; any effective period can be set, and it is understood that the effect can be achieved by ingestion in the same way as a normal meal, so there is no need to particularly control the period.

[0047] In this specification, a predetermined time means a time during which the objectives of the present disclosure, for example, improvement of lifestyle-related diseases, improvement of metabolic syndrome, weight loss, and food intake suppression, are achieved, and it is understood that there is no need to specifically define an effective period for treatment or prevention, and any effective period can be set, and that since these can be achieved by ingesting the product in the same way as a normal meal, there is no particular need to control the period.

[0048] In the present disclosure, it has been found that for polypeptides (or proteins) having a molecular weight greater than that normally present in the intestine or having a longer number of amino acids than that normally present in the intestine, it is important that, before administration, the product of a certain predetermined amount and the molecular weight typically exceeds an index > threshold value (standard value).

[0049] A typical determination formula is whether a polypeptide (or protein) or its complex or substance is a suitable ingredient for the composition of the present disclosure by determining whether its average molecular weight (weight average) x amount is higher than a certain threshold value when "present in the intestine."

[0050] In another exemplary embodiment, a polypeptide (or protein) that, when it reaches the intestine in its pre-administration state, has a molecular weight greater than that normally present in the intestine, or a number of amino acids greater than that normally present in the intestine, can be determined by its average molecular weight (weight average) Mw × amount A being higher than a certain threshold value.

[0051] In the present disclosure, when the substance is provided in a dosage form that inhibits decomposition before reaching the intestine, such as by coating capsules, pills, or regular tablets, or by packaging fine granules or powders, the value of Mw (kDa) x amount A (mg) before administration in humans may be 8,000 or more, 8,500 or more, 9,000 or more, 9,500 or more, 10,000 or more, 11,000 or more, 11,500 or more, or 12,000 or more. The lower threshold value of the average molecular weight (weight average) x amount is not limited thereto, but is preferably usually in the range of 8,000 to 10,000, and in one embodiment, 9,500 may be set as the threshold, and values ​​such as 45,400, 14,900, 36,200, 37,700, 44,300, 9,900, and 21,900 may be used. Furthermore, although no particular upper limit is envisaged, possible values ​​include 100,000,000, 10,000,000, 1,000,000, 100,000, 80,000, 50,000, and the like.

[0052] While not wishing to be bound by theory, the reason for this value is that food intake and energy intake are essential for maintaining bodily functions, and it is assumed that the food intake suppression effect of the capsules disclosed herein will plateau and saturate at some stage. Biological reactions, such as enzyme activity and ligand binding to receptors, are also known to exhibit saturation, and it was thought that these could be similarly approximated by a saturation curve. The left side represents food intake suppression (%), and the right side is an equation approximating the saturation curve with the variables (average molecular weight (kDa) x capsule content (mg)). The R value is well-approximated at 0.6 or higher, indicating that the food intake suppression effect of the capsules is determined by the average molecular weight (kDa) and capsule content (mg). Based on this, as shown in this example, it is advantageous for Mw (kDa) x Amount A (mg) to be equal to or greater than a certain value.

[0053] In one embodiment, the polypeptide or complex thereof, or substance of the present disclosure comprises a processed protein. Such processed substances may include heated proteins, enzyme-treated proteins, processed indigestible proteins, processed indigestible proteins, processed digestion-resistant proteins, protected proteins, etc.

[0054] In one embodiment, it may be advantageous to formulate the active agent prior to administration with a substance that interferes with digestion before it reaches the intestine, the average molecular weight (weight average) times the amount of which is above a certain threshold. Such interfering substances include, but are not limited to, substances used in enteric formulations. Such materials include, for example, 1) cellulose polymers, such as shellac, cellulose acetate phthalate, hydroxypropyl cellulose, hydroxypropyl methylcellulose phthalate, and hydroxypropyl methylcellulose acetate succinate; 2) polyvinyl acetate phthalate, polymers and copolymers of acrylic acid, and methacrylic resins commercially available under the trade name "Eudragit" (registered trademark) (manufactured by Rohm Pharma Co., Ltd.), such as poly(ethyl acrylate-methyl methacrylate-triethylammonioethyl-methacrylate chloride) (Eudragit RS and Eudragit RL) and poly(ethyl acrylate-methyl methacrylate) (Eudragit NE); 3) alginates, alkali-soluble acrylic resins, hydroxypropyl methylcellulose phthalate, methacrylate-methacrylic acid copolymers, polyvinyl acetate phthalate, styrene-maleic acid copolymers, and the like; 4) Examples of suitable enteric polymers include, but are not limited to, cellulose acetate phthalate, alginate, alkali-soluble acrylic resins, hydroxypropyl methylcellulose phthalate, methacrylate-methacrylic acid copolymers, polyvinyl acetate phthalate, styrene-maleic acid copolymers, and mixtures thereof, while examples of suitable non-enteric polymers include cross-linked polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl cellulose, cross-linked sodium carboxymethylcellulose, carboxymethyl starch, polymers and copolymers of acrylic acid and methacrylic acid, polyesters, acid anhydride polymers, polymethyl vinyl ether / acid anhydride copolymers, potassium methacrylate-divinylbenzene copolymers, polyvinyl alcohol, glucan, scleroglucan, mannan, starch and its derivatives, β-cyclodextrin, cyclodextrin derivatives having linear and / or branched polymer chains, and mixtures thereof.It is understood that enteric properties can be exhibited when an enteric material is mixed with a non-enteric material, and the concentration of the enteric material is from about 0.1 to about 20% by weight, preferably from about 1 to 15% by weight, and more preferably from about 5 to 10% by weight, based on the weight of the composition.

[0055] In a preferred embodiment, the composition of the present disclosure is in a coated dosage form so that the polypeptide or complex thereof of the present disclosure, or the substance, is not digested to a length of amino acids not exceeding that normally found in the stomach.

[0056] In another aspect, the present disclosure provides a method for improving lifestyle-related diseases, improving metabolic syndrome, reducing weight, suppressing food intake, and the like in a subject, the method comprising the step of: A) providing to the intestine of the subject a polypeptide (or protein) having a molecular weight greater than that normally present therein.

[0057] In one aspect, the present disclosure provides use of a composition or diet containing a polypeptide (or protein) or a complex thereof having a molecular weight greater than that normally present in the intestine or a number of amino acids greater than that normally present in the intestine, or an active substance that produces the polypeptide or complex thereof upon reaching the intestine, for improving lifestyle-related diseases, improving metabolic syndrome, weight loss, and suppressing food intake.

[0058] In one embodiment, the intestine includes the small intestine (preferably the upper part of the small intestine). Without wishing to be bound by theory, it has been shown that the presence of other proteins in the small intestine, preferably the upper part of the small intestine, where proteins are normally absorbed, that have a molecular weight or amino acid length greater than or longer than those normally used to promote absorption unexpectedly results in a contact inhibitory effect, which contributes to the improvement of lifestyle-related diseases, metabolic syndrome, weight loss, and food intake suppression.

[0059] In one embodiment, the composition of the present disclosure is configured to prevent digestion of the polypeptide or its complex, or substance, so that the molecular weight or amino acid length is less than that normally present in the stomach. For example, this refers to the application of a coating that prevents digestion in the stomach. As long as it is possible to achieve a molecular weight greater than that normally present in the intestine, which is one of the objectives of the present disclosure, it can be understood that the effects of the present disclosure can be achieved even if it is decomposed to a certain extent in the stomach, as long as it is retained for an effective length in the intestine.

[0060] In another embodiment, the polypeptide or complex thereof, or substance of the present disclosure includes a processed protein. Such processed proteins include indigestible proteins.

[0061] In one embodiment, the processed protein of the present disclosure is an inactivated active protein, including, but not limited to, inactivated active proteins (e.g., lactoferrin).

[0062] In another embodiment, the present disclosure comprises a protein selected from the group consisting of whey protein, soy protein, and gelatin protein.

[0063] In one embodiment, the composition of the present disclosure is in a dosage form coated to prevent digestion of the polypeptide or its complex, or substance, so that the polypeptide or its complex or substance is reduced to an amino acid length not exceeding that normally present in the stomach. Examples of such dosage forms include enteric-coated preparations, such as enteric-coated capsules and capsules containing enteric-coated granules. Typical examples of coating agents that dissolve under the neutral conditions of the small intestine include hydroxypropyl cellulose phthalate and cellulose acetate phthalate.

[0064] The enteric coating layer may be formed using an enteric coating base containing an enteric coating polymer in an amount of 20 to 80% by weight, where the polymer contained in the enteric coating base may be in an amount of 20 to 60% by weight, 40 to 80% by weight, 40 to 60% by weight, 35 to 45% by weight, 55 to 65% by weight, about 40% by weight, or about 60% by weight.

[0065] If the enteric coating layer is approximately 5 parts by weight or less based on 100 parts by weight of the core, there is a possibility that the active ingredient may dissolve in the stomach. On the other hand, if the enteric coating layer is 9 parts by weight or more based on 100 parts by weight of the core, there is a possibility that the absorption rate of the active ingredient in the body may decrease, it may take a long time to reach an effective concentration, and the intended effect may not be properly achieved. The content range of the enteric coating layer according to the present disclosure is preferably such that the dissolution rate of the active ingredient can be controlled so that it is stably delivered to the target site and that it can be dissolved to fully exert its effect. The enteric coating layer may be formed using an enteric coating base containing an enteric coating polymer in an amount of 20 to 80% by weight. In this case, the polymer contained in the enteric coating base may be present in an amount of 20 to 60% by weight, 40 to 80% by weight, 40 to 60% by weight, 35 to 45% by weight, 55 to 65% by weight, about 40% by weight, or about 60% by weight. If the enteric coating layer is 5 parts by weight or less based on 100 parts by weight of the core, there is a possibility that the active ingredient may be dissolved in the stomach. On the other hand, if the enteric coating layer is 9 parts by weight or more based on 100 parts by weight of the core, there is a possibility that the dissolution of the active ingredient in the body may be reduced, taking a long time to reach an effective concentration, and the effect may not be properly exerted. The content range of the enteric coating layer according to the present disclosure is preferably such that the dissolution rate of the active ingredient can be controlled so that it can be stably delivered to the absorption site in vivo and the dissolution can be sufficient to exert the effect.

[0066] The thickness of the coating layer of the enteric coating agent may be 20 μm to 90 μm, 30 μm to 80 μm, 30 μm to 50 μm, 60 μm to 80 μm, 35 μm to 50 μm, 65 μm to 80 μm, 35 μm to 80 μm, or 40 μm to 75 μm. In this case, the thickness of the coating layer of the enteric coating agent may be the thickness of the enteric coating layer or the thickness of the coating layer including the seal coating layer and the enteric coating layer.

[0067] The enteric coating agent can be prepared by a conventional tablet manufacturing method such as a conventional dry / wet granulation method, a direct powder compression method, or a direct compression method in the case of a tablet, and is preferably prepared by a direct compression method. The enteric coating agent can include a powder form, and is preferably prepared as a solid-form enteric coating agent, but it is not impossible to prepare it in a liquid form, and this is not excluded from the scope of the right.

[0068] The enteric coated agents may be administered as an individual therapeutic agent, may be administered in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or in multiple doses.

[0069] The enteric coating agent of the present disclosure can be prepared by a method including the steps of: preparing a mixture by mixing an active ingredient and pharmaceutically acceptable additives; preparing a core by directly compressing the mixture; and enteric-coating the core. In this case, the enteric coating is advantageously, but not limited to, performed in an amount of 6 to 9 parts by weight of an enteric coating layer based on 100 parts by weight of the core. The method may further include a seal-coating step prior to the enteric-coating step. In this case, the enteric-coating step and / or the seal-coating step may be performed at 20°C to 50°C, 20°C to 40°C, and preferably at about 25°C to 35°C.

[0070] In this way, enteric coatings can be used to create a barrier that controls the region along the GI tract where the active ingredient(s) are released and absorbed. Enteric coatings can include, for example, polymers that disintegrate at different rates depending on pH. Enteric coatings can include, for example, cellulose acetate phthalate, cellulose acetate trimellitate, methyl acrylate-methacrylic acid copolymer, cellulose acetate succinate, hydroxymethylcellulose, hydroxylpropylmethylcellulose phthalate, methyl methacrylate-methacrylic acid copolymer, ethyl acrylate-methacrylic acid copolymer, methacrylic acid copolymer series C, polyvinyl acetate-phthalate, cellulose acetate phthalate, polyvinyl acetate phthalate, carboxymethylethylcellulose, copolymerized methacrylic acid / methacrylic acid methyl ester, such as materials known under the trade names EUDRAGIT® L12.5, L100 or EUDRAGIT® S12.5, S100, or similar compounds used to obtain enteric coatings. Aqueous colloidal polymer dispersions or redispersions can also be applied, such as EUDRAGIT® L 30D-55, EUDRAGIT® L100-55, EUDRAGIT® S100, EUDRAGIT® Preparation 4110D (Rohm Pharma); AQUATERIC®, AQUACOAT® CPD 30 (FMC); KOLLICOAT® MAE® 30D and 30DP (BASF); EASTACRYL® 30D (Eastman Chemical).

[0071] In certain embodiments, the enteric coating comprises anionic, cationic, or neutral copolymers based on methacrylic acid, methacrylic / acrylic esters, or derivatives thereof. Cationic polymers are often used for taste masking and to achieve high bioavailability of active ingredients due to their low solubility in the oral cavity (pH 5.8-7.4) and high solubility in the stomach (pH 1-3.5), respectively. Anionic polymers have higher water solubility at basic pH than at acidic pH and are used to protect active ingredients from acid degradation in the stomach and / or enzymatic digestion in the intestine.

[0072] In certain embodiments, the enteric coating comprises an ethyl acrylate-methacrylic acid copolymer. Commercially available enteric coatings include Opadry® AMB, ethyl acrylate-methacrylic acid copolymer (e.g., ACRYL-EZE®), dimethylaminoethyl methacrylate-butyl methacrylate-methyl methacrylate copolymer (2:1:1), or poly(methacrylic acid-co-methyl methacrylate) copolymer, and poly(methacrylic acid-co-methyl methacrylate) copolymer (e.g., EUDRAGIT®). In certain embodiments, the enteric coating may comprise about 0.1% to about 10%, about 1% to about 10%, about 5% to about 10%, about 5% to about 20%, about 8% to about 15%, about 8% to about 18%, about 10% to about 12%, or about 12% to about 16% of the dosage form (e.g., capsule, tablet, or pellet) by weight.

[0073] In certain embodiments, the compositions or dosage forms of the present disclosure are prepared as capsules containing the substances of the present disclosure, which may be enteric coated, where the capsules are enteric coated for delivery to the upper intestine. In certain embodiments, the substances of the present disclosure are mixed as a blend to prepare a powder composition, which is then enteric coated with a cationic copolymer. For example, materials of the present disclosure can be coated with a cationic polymer comprising dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate in a 2:1:1 ratio (EUDRAGIT® E100); a cationic copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate in a 2:1:1 ratio (EUDRAGIT® EPO); a cationic copolymer based on dimethylaminoethyl methacrylate, butyl methacrylate, and methyl methacrylate in a 2:1:1 ratio (EUDRAGIT® E12,5), an anionic copolymer based on methacrylic acid and ethyl acrylate (EUDRAGIT® L100-55 (ACRYL-EZE®)), or the like.

[0074] In certain embodiments, materials of the present disclosure are mixed as a blend to prepare a powder composition, which is then enteric coated with an anionic copolymer. For example, a powder blend of bacterial and fungal strains of the present disclosure can be coated with an anionic copolymer comprising methacrylic acid and methyl methacrylate (e.g., EUDRAGIT® L100, EUDRAGIT® S100, EUDRAGIT® L / S (25 / 75, 50 / 50, or 75 / 25 ratios)) or an anionic copolymer comprising methacrylic acid and ethyl acrylate (EUDRAGIT® L100-55 (ACRYL-EZE®)). Further, but non-limiting examples of coatings for colonic delivery include EUDRAGIT® L100-55, EUDRAGIT® L30D-55, PlasACRYL® HTP 20, EUDRAGIT® L12,5, EUDRAGIT® FS 100, EUDRAGIT® FS 30D, and PlasACRYL® T20.

[0075] In certain embodiments, the materials of the present disclosure are mixed as a blend to prepare granules or pellets, which are enteric coated.

[0076] In certain embodiments, the materials of the present disclosure can be enteric coated for time-controlled delivery throughout the GI tract to increase efficacy. For example, compositions or dosage forms can be coated with EUDRAGIT® RL 100, EUDRAGIT® RL PO, EUDRAGIT® RL 30D, EUDRAGIT® RL 12.5, EUDRAGIT® RS 100, EUDRAGIT® RS PO, EUDRAGIT® RS 30D, EUDRAGIT® RS 12.5, EUDRAGIT® NE 30D, EUDRAGIT® NE 40D, and / or EUDRAGIT® NM 30D.

[0077] An exemplary method of producing an oral dosage form includes mixing the materials of the present disclosure with the appropriate materials to be combined in the dosage form.

[0078] The enteric coating layer may further contain additives such as excipients, binders, disintegrants, antioxidants, surfactants, lubricants, plasticizers, and pigments. The enteric coating step can be carried out using a coating solution in which the enteric coating base and / or pharmaceutically acceptable additives are dissolved in a solvent. The solvent can be one or a combination of two or more selected from the group consisting of purified water, alcohol, alkyl acetate, dimethylformamide, dimethyl sulfoxide, acetone, anisole, acetic acid, butyl methyl ether, ethyl ether, ethyl formate, formic acid, pentane, heptane, methyl ethyl ketone, and methyl isobutyl ketone. Coating can be carried out by known means. For example, in the case of spray coating, a pan coating device, a drum coating device, a fluidized bed coating device, or an agitated fluidized bed coating device can be used. Sprayers attached to such devices can include air sprayers, airless sprayers, and three-fluid sprayers. In the case of the dry type, for example, a centrifugal fluidized coating device, a pan coating device, a fluidized bed coating device, a centrifugal electric fluidized bed coating device, etc. can be used.

[0079] In one embodiment, the composition of the present disclosure may contain the polypeptide or substance in an amount of 100 mg to 10 g / 60 kg body weight or more, and although there is no particular upper limit, up to 20 g is usually acceptable. The appropriate amount varies depending on the subject, but can be determined appropriately by those skilled in the art, and the composition is formulated to be administered in an appropriate amount.

[0080] In one embodiment, the polypeptide or protein may have an overall molecular weight, including modifications such as sugar chains, of 20 kDa or more, preferably 25 kDa or more, 30 kDa or more, 35 kDa or more, 40 kDa or more, 45 kDa or more, 50 kDa or more, or 60 kDa or more, or a length of 125 amino acids or more, preferably 150 amino acids or more, 175 amino acids or more, 200 amino acids or more, 250 amino acids or more, 300 amino acids or more, 350 amino acids or more, 400 amino acids or more, 450 amino acids or more, or 500 amino acids or more.

[0081] In one embodiment, the polypeptide or protein includes a processed protein or an undigested protein, which may be advantageously an inactivated protein, particularly a protein whose toxicity has been inactivated.

[0082] In preferred embodiments, the polypeptides or proteins of the present disclosure include those derived from legumes, grasses, Polygonaceae, Labiatae, Amaranthaceae, milk proteins, and animal muscles, and more particularly, milk proteins (e.g., cow's milk proteins, other mammalian milk proteins, etc.), vegetable proteins (e.g., soybean proteins, cereal proteins, rice milk proteins, other vegetable proteins, etc.), or any combination of such proteins, and preferably whey proteins, soybean proteins, and gelatin proteins.

[0083] In the present disclosure, food intake suppression includes the purpose of treating obesity, improving lifestyle-related diseases, improving metabolic syndrome, and reducing weight.

[0084] In one embodiment, the method of the present disclosure includes administering a composition of the present disclosure.

[0085] In another embodiment, the present disclosure provides a method for administering the drug once a day, preferably before each meal. Effective treatments may also be administered once every two days, once every three days, or once a week. The upper and lower limits can be set arbitrarily, with lower limits including 7, 10, 12, 15, 18, 21, 25, 28, and 30 days, and upper limits including 25, 28, 30, 33, 35, 40, 45, and 50 days.

[0086] (Administration method) In one aspect, the present disclosure provides a method for treating or preventing or improving a subject, comprising feeding the composition of the present disclosure so that the polypeptide (or protein) that has a molecular weight larger than that of the molecular weight normally present in the intestine or has a longer amino acid number than that of the amino acid length normally present in the intestine is produced in the intestine.To realize the present disclosure, medicine or supplement can be configured to realize this method.The present disclosure can be realized by administering the composition of the present disclosure before a meal.

[0087] In one embodiment, it may be advantageous to administer the compound any time before a meal, such as at least 15 minutes, 30 minutes, 45 minutes, 1 hour, 2 hours, 4 hours, or more.

[0088] (Pharmaceuticals) The composition of the present disclosure may contain other optional components within a range that does not impair the effects of the present disclosure. Examples of the optional components include binders, excipients, lubricants, flavorings, flavoring agents (sweeteners, acidulants, etc.), pigments, stabilizers, coating agents (including those other than enteric coating agents), plasticizers, masking agents, etc., and these may be used alone or in appropriate amounts in combination of two or more.

[0089] Examples of binders that can be used include starch, pregelatinized starch, sucrose, gelatin, gum arabic powder, methyl cellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, pullulan, and dextrin.

[0090] Examples of excipients that can be used include low-substituted hydroxypropyl cellulose, corn starch, lactose, talc, crystalline cellulose (such as Ceolus), powdered sugar, sugar alcohols such as mannitol, and light anhydrous silicic acid.

[0091] Examples of lubricants include magnesium stearate, calcium stearate, polyethylene glycol, talc, stearic acid, sucrose fatty acid esters, sodium stearyl fumarate, etc. Examples of flavorings include menthol, limonene, plant essential oils (peppermint oil, mint oil, lychee oil, orange oil, lemon oil, etc.), etc.

[0092] Examples of sweeteners include saccharin sodium, aspartame, stevia, dipotassium glycyrrhizinate, acesulfame potassium, thaumatin, and sucralose.

[0093] Examples of sour seasonings that can be used include citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, lactic acid, and salts thereof.

[0094] Examples of coating agents that can be used include hydroxypropylmethylcellulose, hydroxyethylcellulose, polyvinyl alcohol, carboxymethylcellulose, ethylcellulose, and Opadry (trade name) (manufactured by Nippon Colorcon LLC).

[0095] As the plasticizer, for example, polyethylene glycol, triacetin, etc. can be used.

[0096] Examples of the masking agent that can be used include titanium oxide and talc.

[0097] The administration form of the present disclosure is not particularly limited. Examples include oral administration (e.g., oral administration, sublingual administration, etc.), parenteral administration (intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, nasal administration, pulmonary administration, etc.), etc. Among these, a less invasive administration form is preferred, and oral administration (intake) is more preferred from the viewpoint of effectively improving the disturbance or deterioration of the intestinal environment.

[0098] Examples of dosage forms of orally administered agents (internal medications) or compositions for oral administration (internal compositions) include liquid (liquid), syrup (syrup), tablets (tablets, tablets), capsules (capsules), powder (granules, fine granules), soft capsules (soft capsules with a gelatin base or the like), hard capsules (hard capsules), liquid (liquid), syrup (syrup), solid, semi-liquid, cream, and paste.

[0099] The method of making the present disclosure into a formulation is not particularly limited, and can be carried out by a conventional method depending on the formulation.For example, when an active ingredient is used in the present disclosure, the active ingredient and other ingredients can be mixed as is, or some or all of the ingredients can be granulated or coated and then mixed to produce a granular mixture, which can be used as a granule (granule, fine granule, powder).In addition, the granular mixture can be compressed into tablets, and if necessary, coated to form tablets.

[0100] Embodiments of the present disclosure may also be in the form of solids or viscous liquid foods, including food condiments (e.g., spreads, sauces, jams, jellies, coffee creamers, ketchup, mustard, or sweeteners), chocolate syrup, baking or cooking ingredients (e.g., fat or oil substitutes, butter or margarine substitutes), beverages (e.g., espresso, shakes, ice cream-based drinks), fluid cheeses, cream cheeses, dips, dressings, frozen desserts (e.g., ice cream, fudge bars, frozen yogurt), puddings, flavored refrigerated doughs (e.g., cookies, breads, brownies), dairy or soy-based smoothies, yogurt or yogurt-based drinks, frozen yogurt, soy milk, soups, and the like.

[0101] Artificial sweeteners may also be added to foods to enhance the sensory properties of the formulation. Examples of suitable artificial sweeteners may include saccharin, aspartame, acesulfame K, sucralose, etc. Food embodiments of the present disclosure may also include flavorings and / or colorings to provide foods with an appealing appearance and an acceptable taste for oral consumption. Examples of useful flavors typically include, for example, strawberry, peach, butter pecan, chocolate, banana, raspberry, orange, blueberry, and vanilla.

[0102] Embodiments of the present disclosure may also include fat. Suitable fats or fat sources may include any known or otherwise safe for use in oral nutritional products, non-limiting examples of which include coconut oil, palm oil, soybean oil, corn oil, peanut oil, low-erucic acid rapeseed oil (canola oil), olive oil, safflower oil, high-oleic acid safflower oil, MCT oil (medium-chain triglycerides), sunflower oil, high-oleic acid sunflower oil, sesame oil, palm oil and palm kernel oil, palm olein, fish oil, cottonseed oil, flaxseed oil, cocoa butter, and combinations thereof. Many commercial sources of the fats listed above are readily available and known to those skilled in the art. The fat component comprises, in whole or in part, polyunsaturated fatty acids, which include polyunsaturated fatty acid esters or other natural or synthetic sources, including short-chain (fewer than about 6 carbon atoms per chain) fatty acids with two or more carbon:carbon double bonds, medium-chain (about 6-18 carbon atoms per chain) fatty acids, and long-chain (having at least about 20 carbon atoms per chain) fatty acids, including n-3 (omega-3) and n-6 ​​(omega-6) polyunsaturated fatty acids. Non-limiting examples of polyunsaturated fatty acids suitable for use in the present disclosure include alpha-linolenic acid (ALA, C18:3n-3), stearidonic acid (C18:4n-3), eicosapentaenoic acid (EPA, C20:5n-3), docosapentaenoic acid (C22:5n-3), docosahexaenoic acid (DHA, C22:6n-3), linoleic acid (C18:2n-6), gamma-linolenic acid (GLA, C18:3n-6), eicosadienoic acid (C20:2n-6), arachidonic acid (ARA, C20:4n-6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), and combinations thereof.

[0103] Embodiments of the present disclosure may also include flavorants, the concentrations of which may vary substantially depending on the flavors and other ingredients selected, and the desired flavor profile or intensity. Any flavor known or otherwise suitable for use in foods may be used in the present disclosure, provided such flavors are also compatible with other selected ingredients, materials, additives, etc.

[0104] Such flavors may be natural or synthetic and may be provided by single or multiple flavor sources. Flavors used in foods are most typically combinations of many ingredients to provide the desired flavor associations.

[0105] Non-limiting examples of suitable flavorings include enzymatically modified flavors (e.g., dairy flavors), fermented flavors (e.g., dairy flavors), reaction flavors (e.g., chocolate, caramel), natural extracts (e.g., vanilla, coffee, chocolate), and combinations thereof. Non-limiting examples of other specific flavorings suitable for use in the present disclosure include butter pecan flavor, orange, lemon, lime, apricot, grapefruit, yuzu, sudachi, apple, grape, strawberry, pineapple, banana, peach, melon, apricot, plum, cherry, raspberry, blueberry, butter, vanilla, tea, coffee, cocoa or chocolate, mint, peppermint, spearmint, peppermint, ajwain, ajowan, anise, angelica, fennel, allspice, cinnamon, chamomile, mustard, cardamom, kimchi, ginger ... Included may be challah, cumin, cloves, pepper, coriander, sassafras, savory, Japanese pepper, perilla, juniper berry, ginger, star anise, horseradish, thyme, tarragon, dill, chili pepper, nutmeg, basil, marjoram, rosemary, bay leaf, wasabi, beef, pork, chicken, fish, shellfish, dried and smoked fish, seaweed, wine, whiskey, brandy, rum, gin, liqueurs, floral flavors, onion, garlic, cabbage, carrot, celery, mushroom, tomato, and combinations thereof.

[0106] Embodiments of the present disclosure may further include other optional ingredients, raw materials, materials, additives, etc., which may modify the physical, chemical, aesthetic, or processing characteristics of the food product. Many such optional ingredients, raw materials, materials, additives, etc., known or otherwise suitable for use in other foods, may also be used in the food products of the present disclosure, provided that such optional ingredients, raw materials, materials, additives, etc. are safe for human consumption and are compatible with the essential and other ingredients, raw materials, materials, additives, etc. present in the food product. Non-limiting examples of other optional ingredients include preservatives, antioxidants, pharmaceutically active agents, colorants, additional flavors, etc.

[0107] Embodiments of the present disclosure may further include vitamins or related nutrients, non-limiting examples of which include vitamin A, vitamin C (e.g., ascorbic acid, which may also function as an antioxidant), vitamin E, vitamin K, thiamine, riboflavin, pyridoxine, vitamins B1, B2, B12, etc., carotenoids (e.g., beta-carotene, zeaxanthin, lutein, lycopene), niacin, folic acid, pantothenic acid, biotin, choline, inositol, salts / conjugates and derivatives thereof, and combinations thereof.

[0108] Food product embodiments of the present disclosure may further include other vitamins or related nutrients, non-limiting examples of which include vitamin A, vitamin C (e.g., ascorbic acid, which may also function as an antioxidant), vitamin E, vitamin K, thiamine, riboflavin, pyridoxine, vitamins B1, B2, B12, etc., carotenoids (e.g., β-carotene, zeaxanthin, lutein, lycopene), niacin, folic acid, pantothenic acid, biotin, choline, inositol, salts / conjugates and derivatives thereof, and combinations thereof.

[0109] Food product embodiments of the present disclosure may also be substantially free of any optional ingredient, raw material, material, additive, etc. described herein. In this context, the term "substantially free" means that the selected product contains less than a functional amount of any ingredient, raw material, material, additive, etc., including zero percent by weight of such any ingredient, raw material, material, additive, etc.

[0110] (Embodiment in the case of a meal set) In one aspect, the present disclosure can be provided in the form of a meal. Compared to regular meals, the formula meals used in weight loss dietary therapy have small portions that make it difficult to feel full even after eating one meal, but combining them with protein capsules, which are a representative example of the composition of the present disclosure, by taking them beforehand is thought to be a good way to improve the rate of treatment continuation.

[0111] (Pharmaceutical Embodiment) In one aspect, the present disclosure can be provided in the form of a pharmaceutical. Such forms include nutritional supplements, in which case the method of administration can be specified to be carried out by ingestion of a meal or composition so as to produce in the intestine a polypeptide (or protein) having a molecular weight greater than that normally present in the intestine or a longer amino acid length than that normally present in the intestine, as is a feature of the present disclosure. Examples of such products include liquid nutritional supplements that are deficient in methionine, tryptophan, and niacin. Examples include Ensure Liquid (Abbott) and Racol NF Combined Enteral Liquid (Otsuka Pharmaceutical).

[0112] For example, the composition of a product such as Ensure Liquid (sodium caseinate, sodium calcium caseinate, soy protein isolate, corn oil, soy lecithin, dextrin, refined white sugar, retinol palmitate, cholecalciferol, tocopheryl acetate, phytonadione, ascorbic acid, thiamine chloride hydrochloride, riboflavin, pyridoxine hydrochloride, cyanocobalamin, choline chloride, folic acid, nicotinamide, calcium pantothenate, biotin, sodium bicarbonate, magnesium chloride, potassium citrate, tricalcium phosphate, potassium chloride, sodium citrate hydrate, zinc sulfate hydrate, ferrous sulfate hydrate, manganese chloride, copper sulfate) or its ingredients (protein, fat, carbohydrates, vitamin A, vitamin D, vitamin E, vitamin K, vitamin C, vitamin B １ , Vitamin B ２ , Vitamin B ６ , Vitamin B １２This can be achieved by omitting the missing components of the present disclosure from among the following: choline, folic acid, niacin, pantothenic acid, biotin, sodium, potassium, chlorine, calcium, phosphorus, magnesium, manganese, copper, zinc, and iron (see https: / / www.abbott.co.jp / content / dam / corp / abbott / ja-jp / our-products / ani / if-ensure-14.pdf).

[0113] In another aspect, the present disclosure provides a device or system for designing a diet for improving lifestyle-related diseases, improving metabolic syndrome, weight loss, and appetite suppression, the device including a calculation unit that calculates a diet (also referred to as a combined adjusted diet) that combines a polypeptide (or protein) having a molecular weight larger than that normally present in the intestine or a number of amino acids longer than that normally present in the intestine with a composition configured to be produced in the intestine, and a display unit that displays the calculated diet. Such a design can be realized, for example, by using a timer that notifies the time to take the medication before meals or a recommended number of tablets to be taken based on weight, and these values ​​can be calculated.

[0114] A device or system according to one embodiment of the present disclosure is a system for assisting in adjusting meal components, comprising one or more computer processors, the one or more computer processors performing, in response to execution of readable instructions, the steps of calculating or determining an adjustment for a combined adjusted meal, and presenting to the user a screen on which a predetermined object having an appearance based on the calculation or determination is displayed.

[0115] It is theoretically possible to create an AI using supervised machine learning, using the amount of nutrients of each component ingested in a meal, including the components targeted by the present disclosure, as input data, and specific parameters (e.g., improvement of lifestyle-related diseases, improvement of metabolic syndrome, weight loss, and food intake suppression) as output data, and to predict output from input data that has no answer. It is understood that this requires a certain amount of data and can be implemented by incorporating AI-related techniques.

[0116] In another aspect, the present disclosure provides a method for designing a diet for improving lifestyle-related diseases, improving metabolic syndrome, weight loss, and food intake control, the method comprising calculating a combination of adjusted diets and their respective components.

[0117] A method according to one embodiment of the present disclosure is a method executed by one or more computers for assisting in the adjustment of dietary components, comprising the steps of calculating or determining an adjustment of dietary components, and presenting to the user a screen on which a predetermined object having an appearance based on the adjustment or determination of dietary components is displayed.

[0118] In another aspect, the present disclosure provides a program for causing a computer to implement a method for designing a diet for improving lifestyle-related diseases, improving metabolic syndrome, weight loss, and food intake control, the method comprising calculating combined adjusted diets and their compositions, etc., and displaying the calculated diets.

[0119] A program according to one embodiment of the present disclosure is a program for assisting in calorie management, which causes one or more computers to perform the steps of calculating or determining adjustments to dietary components, and presenting to the user a screen on which a predetermined object having an appearance based on the calculation or determination is displayed.

[0120] Specific embodiments will be described below with reference to the drawings (FIGS. 11 to 13).

[0121] First, we will explain the hardware configuration of the composition adjustment support server 10. The server 10 is configured as a general computer, and as shown in Fig. 11, includes a computer processor 11, a main memory 12, an input / output I / F 13, a communication I / F 14, and a storage (storage device) 15, and these components are electrically connected via a bus or the like (not shown).

[0122] The computer processor 11 is configured as a CPU, a GPU, or the like, and loads various programs stored in the storage 15 or the like into the main memory 12 and executes various instructions included in the programs. The main memory 12 is configured, for example, by a DRAM or the like.

[0123] The input / output I / F 13 includes various input / output devices for exchanging information with an operator, etc. The input / output I / F 13 includes, for example, information input devices such as a keyboard and a pointing device (e.g., a mouse, a touch panel, etc.), audio input devices such as a microphone, and image input devices such as a camera. The input / output I / F 13 also includes an image output device such as a display, and an audio output device such as a speaker.

[0124] The communication I / F 14 is implemented as hardware such as a network adapter, various communication software, or a combination of these, and is configured to enable wired or wireless communication via a communication network 20 or the like.

[0125] The storage 15 is configured, for example, with a magnetic disk, flash memory, etc. The storage 15 stores various programs, including an operating system, and various data. For example, as shown in FIG. 11 , the storage 15 includes a user information table 151 for managing information about users of the composition adjustment support service, a meal information table 152 for managing information about meals, a task information table 153 for managing information about tasks (e.g., exercise) for burning calories, a user-specific meal management table 154 for managing information about meals for each user, and a user-specific task management table 155 for managing information about tasks for each user. Furthermore, for example, the storage 15 stores a server-side program 40 according to an embodiment of the present disclosure. The program 40 is a program that causes a computer to function as part or all of a system for providing the composition adjustment support service. At least a portion of the server-side program 40 may be configured to be executed on the user terminal 30 via a web browser or other application.

[0126] In this embodiment, the composition adjustment supporting server 10 may be configured using a plurality of computers each having the above-described hardware configuration. For example, the server 10 may be configured by one or a plurality of server devices.

[0127] The composition adjustment support server 10 configured in this manner functions as a web server and an application server, executes various processes in response to requests from a web browser or other application installed on the user terminal 30, and transmits screen data (e.g., HTML data) and control data according to the results of the processes to the user terminal 30. The user terminal 30 displays a web page or other screen based on the received data.

[0128] Next, we will explain the hardware configuration of the user terminal 30. The user terminal 30 is configured as a general computer, and as shown in Fig. 11, it includes a computer processor 31, a main memory 32, an input / output I / F 33, a communication I / F 34, and a storage (storage device) 35, and these components are electrically connected via a bus or the like (not shown).

[0129] The computer processor 31 is configured as a CPU, a GPU, or the like, and loads various programs stored in the storage 35 or the like into the main memory 32 and executes various instructions included in the programs. The main memory 32 is configured, for example, by a DRAM or the like.

[0130] The input / output I / F 33 includes various input / output devices for exchanging information with an operator, etc. The input / output I / F 33 includes, for example, information input devices such as a keyboard and a pointing device (e.g., a mouse, a touch panel, etc.), audio input devices such as a microphone, and image input devices such as a camera. The input / output I / F 33 also includes an image output device such as a display, and an audio output device such as a speaker.

[0131] The communication I / F 34 is implemented as hardware such as a network adapter, various communication software, or a combination of these, and is configured to enable wired or wireless communication via the communication network 20 or the like.

[0132] The storage 35 is configured by, for example, a magnetic disk or a flash memory, etc. The storage 35 stores various programs including an operating system, various data, etc. The programs stored in the storage 35 can be downloaded from an application market, etc., and installed.

[0133] In this embodiment, the user terminal 30 may be configured as a smartphone, a tablet terminal, a wearable device, a personal computer, or the like.

[0134] A user operating the user terminal 30 configured in this manner can use the component adjustment support service provided by the server 10 by communicating with the server 10 via a web browser or other application installed in the storage 35, etc.

[0135] Next, the functions of the ingredient adjustment support server 10 of this embodiment configured as described above will be described. As shown in Fig. 11, the computer processor 11 of the server 10 is configured to function as an ingredient adjustment support unit 111 by executing instructions included in a program (e.g., at least a part of the server-side program 40) loaded into the main memory 12. The ingredient adjustment support unit 111 also has a meal registration unit 112 and a task registration unit 113.

[0136] The component adjustment support unit 111 is configured to execute various processes related to the support of the user for component adjustment. For example, the component adjustment support unit 111 transmits screen data and control data of various screens related to the support of component adjustment to the user terminal 30, executes various processes in response to operation input by the user via the screens displayed on the user terminal 30, and transmits screen data, control data, etc. according to the results of the processes to the user terminal 30.

[0137] The meal registration unit 112 is configured to execute various processes related to meal registration. For example, the meal registration unit 112 registers the meal contents (menu) input by the user in the per-user meal management table 154. The input meal contents are, for example, individually selected by the user from multiple meals (menus) managed in the meal information table 152, or automatically identified through analysis of photographed images of the meal (menu).

[0138] The task registration unit 113 is configured to execute various processes related to task registration. For example, the task registration unit 113 registers a task set for a user in the per-user task management table 155. The task to be set is, for example, individually selected by the user from among multiple tasks managed in the task information table 153, or is automatically identified in accordance with a predetermined rule.

[0139] In this embodiment, the ingredient adjustment support unit 111 is configured to determine the difference between the user's calorie expenditure and calorie intake over a predetermined period. For example, the ingredient adjustment support unit 111 calculates the components of a meal based on the details of the registered meals. Furthermore, for example, the ingredient adjustment support unit 111 calculates the components of a meal based on the user's basic information, the nutritional components of the registered meals, and, if necessary, the details of completed tasks. The calculated components of a meal can also be referred to as estimated or predicted values.

[0140] The components constituting the diet include, for example, essential nutrients (proteins, lipids, carbohydrates), vitamins, minerals, etc., as well as the composition and each component of the present disclosure that is the subject of the present disclosure. Of these, the basal metabolic rate and calorie expenditure, as well as the amount of required nutrients and the required amount of each component of the combined and adjusted diet, are calculated based on the user's basic information (physical information, lifestyle, etc.).

[0141] The ingredient adjustment support unit 111 is also configured to present information other than food, such as additional medicines or supplements that should be taken. For example, the ingredient adjustment support unit 111 transmits screen data and control data of the screen to the user terminal 30.

[0142] In this way, the ingredient adjustment support server 10 of this embodiment calculates or determines the combination-adjusted diet and each composition, etc., and presents to the user a screen displaying nutritional component objects having an appearance based on the calculation or determination, so that the user can intuitively know through the objects whether or not there is a need to increase or decrease the combination-adjusted diet and each composition, etc. In other words, the ingredient adjustment support server 10 supports easy management of the combination-adjusted diet and each composition, etc.

[0143] In this embodiment, an object relating to each component of the combined adjusted meal may be displayed in various ways. For example, the object may be configured to be displayed in a first way when each component of the combined adjusted meal is in excess, and in a second way when the combined adjusted meal and each component are missing. The first and second ways may differ in at least one of shape, size, color, and visual effect (including animation effect). This configuration allows the user to know the magnitude relationship between the combined adjusted meal and each component through the display mode of the object.

[0144] Furthermore, the objects such as the combined adjusted meal and each component may be configured to have a size corresponding to the amount or level of the combined adjusted meal and each component in a predetermined period. For example, the larger the display of the object, the larger the area of ​​the object, and the smaller the display, the smaller the area. This configuration allows the user to know the size of the combined adjusted meal and each component through the object.

[0145] Furthermore, objects such as the combination adjusted meal and each composition may be configured so that at least a portion thereof is displayed in association with one or more registered tasks. For example, objects such as the combination adjusted meal and each composition may have a size corresponding to the amount and necessity of the combination adjusted meal and each composition over a predetermined period, and a portion associated with a task may have a size corresponding to the corresponding calorie consumption (calorie consumption of the associated task). Furthermore, objects such as the combination adjusted meal and each composition may be configured so that a portion associated with a task is divided by task. For example, when calorie intake is greater than calorie expenditure, one or more tasks set to consume at least a portion of the surplus calorie intake are displayed in association with a portion of the calorie difference object corresponding to the surplus (e.g., information identifying the task is added). This configuration helps the user intuitively understand the correspondence between the difference (e.g., the surplus intake) between the combination adjusted meal and each composition and the task.

[0146] In this embodiment, the task registration unit 113 can be configured to manage the completion of registered tasks. In this case, the objects, such as the combination-adjusted meal and each composition, can be configured so that portions associated with the task change in response to the completion of the task. For example, the task registration unit 113 can be configured to accept an input of the completion of the task via a screen displayed on the user terminal 30, and the portion of the calorie difference object associated with the completed task changes in response to the acceptance of the input of the task completion (for example, disappears with an animation effect). This configuration provides the user with enjoyment in response to the completion of the task, which can encourage continued use of the ingredient adjustment support service.

[0147] In this embodiment, the predetermined period for which the combined adjusted diet and each composition are calculated or determined can be set to various periods. For example, the predetermined period can be configured as a period from a predetermined start point to the current time. The predetermined start point includes, for example, the start point of management of the combined adjusted diet and each composition (e.g., the start point of using the service), and the timing when the difference is subsequently cleared (initialized) (e.g., cleared every day, week, month, year, etc.). This configuration makes it possible to notify the user of information based on the intake amounts of the combined adjusted diet and each composition from the predetermined start point to the current time.

[0148] In this embodiment, various timings can be set as the timing for calculating or determining the adjusted combination diet and each component, etc. For example, the ingredient adjustment support unit 111 can be configured to reflect the amounts of the adjusted combination diet and each component, etc. corresponding to the diet registered by the diet registration unit 112 in the recommended amounts for a predetermined period. This configuration makes it possible to update the amount or necessity of the adjusted combination diet and each component, etc., every time the diet content is registered.

[0149] The adjusted combination meal and each component corresponding to a meal can be referred to as a recommended value (or upper limit) for the adjusted combination meal and each component for one meal, set based on the daily reference values ​​for the adjusted combination meal and each component, for example, allocated to three meals. For example, the total value of the basal metabolic rate and daily calorie expenditure can be set as the reference value for the adjusted combination meal and each component for one day. The user may also be allowed to arbitrarily set the proportion allocated to each meal. The amount of the adjusted combination meal and each component corresponding to a meal can be calculated, for example, by adding up the components of each menu item that constitutes the meal (e.g., managed in the meal information table 152).

[0150] Furthermore, the task registration unit 113 may be configured to suggest to the user a task for burning calories in response to the registration of the meal details by the meal registration unit 112. For example, the task to be suggested to the user may be identified based at least on various information associated with the user (e.g., the purpose of ingredient adjustment, physical information, physical condition information, etc.). In this case, for example, for a user set to a predetermined mode, a task for the predetermined mode may be suggested. The predetermined mode may be set as a mode corresponding to various conditions that may affect the user's physical condition or health, and may include, for example, a physiological mode. This configuration encourages the user to register appropriate tasks.

[0151] Next, a specific example of one aspect of the ingredient adjustment support server 10 of this embodiment having such functions will be described. The server 10 in this example provides a diet support service that supports users in dieting, and supports the user's ingredient adjustment in this service. First, the information managed by each table in this example will be described.

[0152] In this specification, "or" is used when "at least one or more" of the items listed in the sentence can be employed. The same applies to "alternative." In this specification, when it is specified that "within a range" of "two values," the range includes the two values ​​themselves.

[0153] All references cited herein, including scientific literature, patents, patent applications, and the like, are incorporated by reference in their entirety to the same extent as if each were specifically set forth.

[0154] The present disclosure has been described above by showing preferred embodiments for ease of understanding. The present disclosure will be described below based on examples. However, the above description and the following examples are provided for illustrative purposes only and are not intended to limit the present disclosure. Therefore, the scope of the present disclosure is not limited to the embodiments or examples specifically described herein, but is limited only by the scope of the claims.

[0155] The present disclosure will be specifically described in the following examples, but the present disclosure is not limited to these examples.

[0156] Example 1: [Effect of Enteric-Coated Capsule-Encapsulated Defatted Soybean Flour on Food Intake Suppression and Weight Loss] In this example, the effect of enteric-coated capsule-encapsulated defatted soybean flour on food intake suppression and weight loss was confirmed as an example.

[0157] Four mg of heated defatted soybean flour was encapsulated in a mouse capsule (TORPAC, size M) and coated twice with a 4% solution and twice with a 19% solution of EUDRAGIT-L100-55 using a prescribed method to create enteric-coated capsules. Mice (B6, male, 16 weeks old, n=10) housed individually per cage for at least one week were fasted overnight and then orally administered the enteric-coated capsules. The mice were immediately fed, and the remaining weight of the food was measured at 1, 2, 4, 8, and 24 hours. The difference from the weight of the food fed was used as the food intake. The weights of the mice were measured at the start of the test and at 24 hours after the test, and the body weight was recorded. The results are shown in Figure 1. Figure 1 shows the food intake suppression and weight loss effects of enteric-coated encapsulated defatted soybean flour.

[0158] In this example, the determination index Mw (kDa) x amount A (mg) of the present disclosure is 278.8, which is multiplied by 163 to give a human equivalent of 45,444.

[0159] As a result, as shown in FIG. 1, a strong decrease in food intake (P=0.03 Unpaired t) was observed 1 hour after the start of administration, and the effect of decreasing food intake continued for 6 hours and 24 hours.

[0160] Example 2 [Effect of Enteric-Coated Encapsulated Casein on Food Intake Suppression and Weight Loss] In this example, enteric-coated encapsulated casein was tested.

[0161] Enteric-coated capsules were prepared by encapsulating 2.3 mg of casein in a mouse capsule (TORPAC, size M) and coating it twice with a 4% solution and twice with a 19% solution using a prescribed method. Mice (B6, male, 16 weeks old, n=10) kept one per cage for at least one week were fasted overnight, and then orally administered the enteric-coated capsules. The mice were immediately fed, and the weight of the remaining food was measured after 1 hour, 2 hours, 4 hours, 8 hours, and 24 hours. The difference from the weight of the fed food was used as the food intake. The weight of the mice was measured at the start of the test and after 24 hours, and this was used as the body weight.

[0162] The results are shown in Figure 2. Figure 2 shows the food intake suppression and weight loss effects of enteric-coated encapsulated casein.

[0163] In this example, the determination index Mw (kDa) x amount A (mg) of the present disclosure is 91.3, which is multiplied by 163 to give a value of 14,882 for humans.

[0164] As a result, as shown in FIG. 2, an effect of reducing food intake was observed 1 hour after the start of administration, but the difference decreased after 2 hours or more, and no difference was observed after 24 hours.

[0165] Example 3 [Effect of Enteric-Coated Encapsulated Soy Protein on Food Intake Suppression and Body Weight Reduction] In this example, enteric-coated encapsulated soy protein was tested.

[0166] The soy protein used was heat-treated. 2.7 mg of soy protein was encapsulated in a mouse capsule (TORPAC, size M), and EUDRAGIT-L100-55 was coated twice with a 4% solution and twice with a 19% solution using a prescribed method to create enteric-coated capsules. Mice (B6, male, 16 weeks old, n = 20) housed individually per cage for at least one week were fasted overnight, and then orally administered the enteric-coated capsules. The mice were immediately fed, and the remaining weight of the food was measured at 1 hour, 2 hours, 4 hours, and 8 hours. The difference from the weight of the fed food was used as the food intake. The weights of the mice (n = 10) were measured at the start of the test and at 24 hours after the test, and were used as body weights. The results are shown in Figure 3. Figure 3 shows the food intake suppression and weight loss effects of enteric-coated encapsulated soy protein.

[0167] In this example, the determination index Mw (kDa) x amount A (mg) of the present disclosure is 222.2, which is multiplied by 163 to give a value of 36219 for humans.

[0168] As a result, as shown in Figure 3, a strong decrease in food intake was observed 1 to 2 hours after the start of administration (P = 0.01 (1 hour), P = 0.04 (2 hours) Unpaired t), and the food intake decrease effect continued for 8 hours. A tendency for a decrease in body weight gain was observed at 24 hours (P = 0.15 Unpaired t).

[0169] Comparative Example 1 [Effect of Non-Enteric-Coated Encapsulated Soy Protein on Food Intake Suppression and Body Weight Reduction] Heat-treated soy protein was used. 4 mg of soy protein was encapsulated in a mouse capsule (TORPAC, Size M). Mice (B6, male, 16 weeks old, n=20) kept one per cage for at least one week were fasted overnight, and then orally administered the non-enteric-coated capsules. The mice were immediately fed, and the weight of the remaining food was measured after 1 hour, 2 hours, 4 hours, and 8 hours. The difference from the weight of the fed food was used as the food intake. The weight of each mouse was measured at the start of the test and after 24 hours (n=10), and this was used as the body weight.

[0170] The results are shown in Figure 4. Figure 4 shows the food intake suppression and weight loss effects of encapsulated soy protein without enteric coating.

[0171] As a result, as shown in FIG. 4, when soy protein was encapsulated in a non-enteric coated capsule, it tended to increase food intake between 0 and 8 hours.

[0172] In this example, the determination index Mw (kDa) x amount A (mg) of the present disclosure is 40.25, which when converted to human values ​​is multiplied by 163, resulting in 6561.

[0173] Example 4 [Effect of Enteric-Coated Capsule-Encapsulated Heated Pea Protein on Food Intake Suppression and Weight Reduction] In this example, enteric-coated capsule-encapsulated heated pea protein was tested.

[0174] 3.5 mg of heated pea protein was encapsulated in a mouse capsule (TORPAC, size M), and EUDRAGIT-L100-55 was coated twice with a 4% solution and twice with a 19% solution using a prescribed method to create enteric-coated capsules. Mice (B6, male, 16 weeks old, n = 20) housed individually per cage for at least one week were fasted overnight, and then orally administered the enteric-coated capsules. The mice were immediately fed, and the weight of the remaining food was measured at 1 hour, 2 hours, 4 hours, and 8 hours. The difference from the weight of the fed food was used as the food intake. The weights of the mice (n = 10) were measured at the start of the test and at 24 hours after the test, and the body weight was recorded. The results are shown in Figure 5. Figure 5 shows the food intake suppression and body weight reduction effects of enteric-coated encapsulated pea protein.

[0175] As a result, as shown in Figure 5, when heated pea protein was encapsulated in an enteric-coated capsule, the amount of food intake significantly decreased between 0 and 2 hours, and also showed a tendency to decrease between 0 and 8 hours. (*: p<0.05 unpaired t test)

[0176] In this example, the determination index Mw (kDa) x amount A (mg) of the present disclosure is a value of 231. When converted to human values, this is multiplied by 163, resulting in a value of 37,653.

[0177] Example 5 [Effect of Enteric-Coated Capsule-Encapsulated Heated Chicken Protein on Food Intake Suppression and Body Weight Reduction] In this example, enteric-coated capsule-encapsulated heated chicken protein was examined.

[0178] Four mg of heated chicken protein was encapsulated in a mouse capsule (TORPAC, size M) and coated twice with EUDRAGIT-L100-55 in a 4% solution and twice with a 19% solution using a prescribed method to create enteric-coated capsules. Mice (B6, male, 16 weeks old, n = 20) housed individually per cage for over one week were fasted overnight and then orally administered the enteric-coated capsules. The mice were immediately fed, and the remaining weight of the food was measured at 1 hour, 2 hours, 4 hours, and 8 hours. The difference from the weight of the food fed was used as the food intake. The weights of the mice (n = 10) were measured at the start of the test and at 24 hours after the test, and the body weight was recorded. The results are shown in Figure 6. Figure 6 shows the food intake suppression effect of enteric-coated encapsulated heated chicken protein.

[0179] As a result, as shown in Figure 6, when the heated chicken protein was encapsulated in an enteric-coated capsule, food intake significantly decreased between 0 and 8 hours. (*: p<0.05 ***: p<0.005 unpaired t test)

[0180] In this example, the determination index Mw (kDa) x amount A (mg) of the present disclosure is a value of 272. When converted to human values, this is multiplied by 163, giving a value of 44,336.

[0181] Example 6 [Effect of Enteric-Coated Capsule-Encapsulated Whey Protein on Food Intake Suppression and Weight Reduction] In this example, enteric-coated capsule-encapsulated whey protein was examined.

[0182] Enteric-coated capsules were prepared by encapsulating 2.3 mg of whey protein in a mouse capsule (TORPAC, size M) and coating it twice with a 4% solution and twice with a 19% solution of EUDRAGIT-L100-55 using a prescribed method. Mice (B6, male, 16 weeks old, n=20) housed individually per cage for at least one week were fasted overnight, and then orally administered the enteric-coated capsules. The mice were immediately fed, and the remaining weight of the food was measured at 1 hour, 2 hours, 4 hours, and 8 hours. The difference from the weight of the fed food was used as the food intake. The weights of the mice (n=10) were measured at the start of the test and at 24 hours after the test, and the body weight was recorded. The results are shown in Figure 7. Figure 7 shows the food intake suppression effect of enteric-coated encapsulated whey protein.

[0183] As a result, as shown in Figure 7, when whey protein was encapsulated in an enteric-coated capsule, the amount of food intake tended to decrease between 0 and 1 hour (*: p<0.05 unpaired t test).

[0184] In this example, the determination index Mw (kDa) x amount A (mg) of the present disclosure is 60.72, which is multiplied by 163 to give a value of 9897.4 for humans.

[0185] Example 7 [Effect of Enteric-Coated Capsule-Encapsulated Heated Whey Protein on Food Intake Suppression and Weight Reduction] In this example, enteric-coated capsule-encapsulated heated whey protein was examined.

[0186] 2.3 mg of heated whey protein was encapsulated in a mouse capsule (TORPAC, size M), and EUDRAGIT-L100-55 was coated twice with a 4% solution and twice with a 19% solution using a prescribed method to create enteric-coated capsules. Mice (B6, male, 16 weeks old, n=20) kept individually per cage for over a week were fasted overnight, and then orally administered the enteric-coated capsules. The mice were immediately fed, and the remaining weight of the food was measured at 1 hour, 2 hours, 4 hours, and 8 hours. The difference from the weight of the fed food was used as the food intake. The weights of the mice (n=10) were measured at the start of the test and at 24 hours after the test, and the body weight was recorded. The results are shown in Figure 8. Figure 8 shows the food intake suppression effect of enteric-coated encapsulated heated whey protein.

[0187] As a result, as shown in Figure 8, when heated whey protein was encapsulated in an enteric-coated capsule, it significantly reduced food intake between 0 and 8 hours. (*: p<0.05 **: p<0.01 unpaired t test)

[0188] In this example, the determination index Mw (kDa) x amount A (mg) of the present disclosure is 134.42. When converted to human equivalents, this is multiplied by 163, giving a value of 21,910.

[0189] Example 8 [Effect of daily administration of enteric-coated encapsulated soy protein on suppressing food intake, reducing body weight and fat, and thus reducing liver weight] In this example, the effect of daily administration of enteric-coated encapsulated soy protein was investigated.

[0190] 4 mg of soy protein was enclosed in a mouse capsule (TORPAC, size M), and EUDRAGIT-L100-55 was coated twice with a 4% solution and twice with a 19% solution using a prescribed method to create an enteric-coated capsule. Mice (B6, male) were kept in cages of three mice and fed a high-fat diet for two months, and one capsule was administered orally every evening under conditions of free access to high-fat food. Body weight and food intake were measured immediately before administration (n=10).

[0191] As a result, no food intake reducing effect was observed, as shown in FIG. 9-1 (food intake), FIG. 9-2 (body weight change (g)), and FIG. 9-3 (body weight (g)) over time (days).

[0192] Example 9: Determination of Threshold Value In this example, a threshold value was calculated based on the process of whether the object of the present disclosure can be achieved if the product of the (weight) average molecular weight and the content exceeds a certain value.

[0193] (Methods and Materials) Each protein was dissolved in a 6M urea, 3M thiourea, and 1% SDS solution, heated at 60°C for 1 hour, and then heated at 98°C for 5 minutes. The protein was then separated on a 4-20% gradient SDS-page and stained with CBB. After destaining, the CBB-stained images were analyzed using a ChemDOC image analyzer, and the average molecular weight of each protein was calculated. The results are shown in the table below and in Figure 10.

[0194]

[0195] The average molecular weight was analyzed by SDS-page. (Laemmli, U.K., Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature, vol. 227, no. 5259, 680-685 (1970); for specific methods, see Foods 2023, 12(3), 667 Food Hydrocolloids 111 (2021) 106235.) Heating was performed at 121°C for 20 minutes.

[0196] (Discussion) Food intake and energy intake are essential for maintaining bodily functions, and it is expected that the food intake suppression effect of the capsules disclosed herein will reach a plateau and saturate at some stage. Biological reactions, such as enzyme activity and receptor-ligand binding, are also known to exhibit saturation, and it was thought that these could be similarly approximated by a saturation curve. The left side represents food intake suppression (%), and the right side is an equation approximating the saturation curve with the variables (average molecular weight (kDa) × capsule content (mg)). The R value was well-approximated at 0.6 or higher, indicating that the food intake suppression effect of the capsules is determined by the average molecular weight (kDa) and capsule content (mg). Note that the mouse values ​​can be extrapolated to human values ​​by multiplying them by 163 (J Basic Clin Pharma 2016;7:27-31).

[0197] (Example 10: Extrapolation to humans) Extrapolation to humans was confirmed by an actual example. 300 mg of heated soy protein was encapsulated in a gelatin capsule, and EUDRAGIT-L100-55 was coated twice with a 4% solution and twice with a 19% solution using a predetermined method to create an enteric-coated capsule. For control purposes, gelatin capsules without encapsulated protein were similarly prepared as enteric-coated capsules. Subjects were blinded to whether the capsules contained protein or not. They took four tablets of each capsule 30 minutes before lunch, and then 15 minutes later, they freely purchased a lunch box, and 30 minutes later, they ate lunch. As a result, on the day when they took capsules containing heated soy protein, they chose a soba noodle set (approximately 480 kcal), and on the day when they took capsules without the protein, they chose a fried chicken lunch box (approximately 800 kcal). Taking capsules containing heated soy protein resulted in a lunch selection with a 40% lower total calorie content. No side effects such as abdominal pain or diarrhea were observed.

[0198] From the above, it is believed that the composition of the present disclosure can support dieting in a natural way when taken before meals.

[0199] (Example 11: Non-formulation example) Heated whey protein (or soybean) was encapsulated in fine enteric-coated microcapsules and mixed with a normal diet (CE-2, Nippon Clea) and a high-fat diet (60% kcal-fat, Research diet). Mice (B6, male, 16 weeks old, n=20) kept one per cage for over a week were fasted overnight, and then orally administered the enteric-coated capsules. The mice were immediately fed, and the weight of the remaining food was measured after 1 hour, 2 hours, 4 hours, and 8 hours. The difference from the weight of the fed food was recorded as the food intake. The weights of the mice were measured at the start of the test and after 24 hours (n=10) and recorded as body weight. The results demonstrate the effectiveness of the present disclosure.

[0200] (Example 12: Vagus nerve afferent pathway) Heat-treated soy protein was used. 2.7 mg of soy protein or 2.3 mg of heated whey protein was encapsulated in a capsule for mice (TORPAC, size M), and coated twice with a 4% solution and twice with a 19% solution of EUDRAGIT-L100-55 by a predetermined method to prepare enteric-coated capsules.

[0201] B6 mice were fasted overnight and intraperitoneally administered 0.27 mg / kg atropine. After 10 minutes, they were anesthetized with a triple-drug mixture (0.3 mg / kg medetomidine, 4 mg / kg midazolam, and 5 mg / kg butorphanol) and subcutaneously administered 50 mg / kg capsaicin (5 ml / kg solution, 10% ethanol, 10% Tween 80, and 80% saline). Two days later, after a 4-hour fast, they were subcutaneously administered 75 mg / kg capsaicin under the same anesthesia. Two days later, they were intraperitoneally administered 5 mg / kg capsaicin under non-anesthesia without fasting. After a recovery period of at least one week, 0.1% ammonium hydroxide was instilled into the eyes, and the disappearance of the rapid eye-wipe response confirmed the loss of corneal chemosensation mediated by trigeminal afferent nerves. Next, after an overnight fast, 8 μg / kg of cholecystokinin-8 (CCK-8, 5 ml / kg) was administered intraperitoneally. 15 minutes after administration, food intake was measured at 30 minutes and 1 hour. The disappearance of the CCK-8-induced food intake reduction confirmed the destruction of capsaicin-sensitive afferent nerves. After a further two-day recovery period, the above capsules were orally administered after an overnight fast. 15 minutes after administration, food intake was measured at 30 minutes, 1, 2, 4, 8, and 24 hours. This confirmed whether the feeding-suppressing effect of the capsules was mediated by capsaicin-sensitive afferent nerves.

[0202] The significant food intake suppression effect observed in mice administered enteric-coated capsules of heated soy protein or heated whey protein up to 8 hours after the start of feeding was not observed in mice in which the vagal afferent pathways had been destroyed by capsaicin administration, and it can be concluded that the effect is mediated by the vagal afferent pathways.

[0203] From the above, it is believed that the composition of the present disclosure can support dieting in a natural way by taking it with meals.

[0204] (Note) As described above, the present disclosure has been illustrated using preferred embodiments thereof, but it is understood that the scope of the present disclosure should be interpreted solely by the scope of the claims. It is understood that the patents, patent applications, and other documents cited in this specification are incorporated by reference into this specification in their entirety as if the contents themselves were specifically set forth herein. This application claims priority to Japanese Patent Application No. 2023-193289, filed with the Japan Patent Office on November 13, 2023, the contents of which are understood to be incorporated by reference in their entirety into this application.

[0205] The present disclosure is effective in improving health and is useful in the pharmaceutical and food industries.

Claims

1. A composition for improving lifestyle-related diseases, improving metabolic syndrome, reducing body weight, and suppressing food intake, comprising a polypeptide or a complex thereof having a molecular weight greater than that normally present in the intestine, or a polypeptide having a number of amino acids greater than that normally present in the intestine, or an active substance that produces the polypeptide or a complex thereof upon reaching the intestine.

2. The composition according to claim 1, wherein the polypeptide or its complex, or the active substance has an average molecular weight (weight average) x amount higher than a predetermined threshold value when it reaches the intestine.

3. The composition of claim 1, wherein the composition is in a dosage form such that the active substance has an average molecular weight (weight average) times the amount higher than a predetermined threshold value.

4. The composition according to claim 3, characterized in that the active substance is formulated with a substance that interferes with digestion in the digestive tract before reaching the intestine, and its average molecular weight (weight average) x amount is higher than a predetermined threshold value.

5. The composition according to any one of claims 1 to 4, wherein the composition is in a dosage form coated to prevent digestion such that the polypeptide or its complex, or the active substance becomes an amino acid length or less that is normally present in the stomach.

6. The composition according to any one of claims 1 to 5, wherein the composition is an enteric formulation.

7. The composition of claim 5, wherein the dosage form is an enteric coated capsule.

8. The composition according to any one of claims 1 to 7, wherein the polypeptide or complex thereof is formulated to be present in the intestine for about 2 hours or more.

9. The composition of any one of claims 1 to 8, wherein the intestine comprises the small intestine.

10. A composition described in any one of claims 1 to 9, wherein the composition is configured to prevent digestion such that the polypeptide or complex thereof, or active substance is reduced to a molecular weight or amino acid length below that normally present in the stomach.

11. The composition of any one of claims 1 to 10, wherein the composition is formulated so that the polypeptide or active agent is administered in an amount of 100 mg or more.

12. The composition of any one of claims 1 to 11, wherein the composition is formulated so that the polypeptide or active agent is administered in an oral dosage form.

13. The composition of any one of claims 1 to 12, wherein the polypeptide or protein has a molecular weight of 20 kDa or more or a length of 150 amino acids or more.

14. The composition of any one of claims 1 to 13, wherein the polypeptide or complex thereof, or active substance comprises a processed protein.

15. The composition of claim 14, wherein the processed protein is an inactivated active protein.

16. The composition of any one of claims 1 to 15, wherein the polypeptide or protein is derived from a legume, a grass, a Polygonaceae, a Lamiaceae, an Amaranthaceae, a milk protein, or an animal muscle.

17. The composition of any one of claims 1 to 16, comprising a protein selected from the group consisting of whey protein, soy protein and gelatin protein.

18. The composition according to any one of claims 1 to 17, wherein the composition is for treating obesity.

19. The composition of any one of claims 1 to 18, wherein the composition is provided with a meal.

20. A method for improving lifestyle-related diseases, ameliorating metabolic syndrome, reducing body weight, and suppressing food intake, comprising the step of administering before a meal a polypeptide or complex thereof having a molecular weight larger than that normally present in the intestine, or a polypeptide having a number of amino acids longer than that normally present in the intestine, or an active substance which produces the polypeptide or complex when it reaches the intestine, and then having the patient eat a meal.

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