Oral composition comprising nattokinase

Abstract

To provide an oral composition containing nattokinase and water and capable of suppressing pH change caused by preservation.SOLUTION: In the oral composition, at least one kind of amino acid selected from the group consisting of glutamine, glycine, glutamic acid and tryptophan is formulated together with nattokinase and water to suppress pH change caused by preservation.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to an oral composition comprising nattokinase and water, which can suppress pH changes during storage. [Background technology]

[0002] Thrombosis is a pathological condition in which blood clots form in blood vessels, obstructing blood flow in the circulatory system, and is known to be a factor in the development of serious diseases such as cerebral infarction, myocardial infarction, and pulmonary infarction. Conventionally, methods for preventing or treating thrombosis have been used, such as administering drugs such as antiplatelet agents, anticoagulants, and thrombolytic agents to prevent thrombus formation or dissolve thrombus. However, these drugs are accompanied by side effects and require administration under the supervision of a physician, and therefore cannot be taken easily and on a daily basis.

[0003] Meanwhile, natto, a traditional Japanese food, has been reassessed as a health food since it was reported to contain nattokinase, which has thrombolytic activity. However, natto has a distinctive odor and stickiness, and many people do not eat natto. Therefore, to facilitate the intake of nattokinase, nattokinase has been formulated into food products such as capsules and tablets. Such nattokinase-containing foods are useful for self-medication because they can be easily taken daily without the need for medical supervision.

[0004] Various techniques for formulating nattokinase into oral compositions have been reported. For example, Patent Document 1 reports that a food composition containing a freeze-dried milk fermentation product, nattokinase, and a food-safe carrier is easy to ingest and provides beneficial effects derived from the milk fermentation product and nattokinase. Patent Document 2 also reports that a granular soybean processed food with an average particle size of 100 to 500 μm, obtained by granulating a powder mixture containing 40 to 80% by mass of soybean powder, 0.5 to 15% by mass of nattokinase powder, and 3 to 30% by mass of oligosaccharides, has no natto odor and exhibits good dispersibility in liquid and creamy foods.

[0005] However, little research has been conducted on the storage stability of oral compositions containing nattokinase and water. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] WO 02 / 76240 [Patent Document 2] Japanese Patent Application Laid-Open No. 2005-130727 Summary of the Invention [Problem to be solved by the invention]

[0007] The present inventors have conducted studies to develop an oral composition containing nattokinase and water, and have found that the oral composition has a problem in that the pH decreases over time.

[0008] Therefore, an object of the present invention is to provide an oral composition which contains nattokinase and water and which can suppress pH changes during storage. [Means for solving the problem]

[0009] The present inventors have conducted extensive research to solve the above problems and have found that by incorporating at least one amino acid selected from the group consisting of glutamine, glycine, glutamic acid, and tryptophan into an oral composition together with nattokinase and water, pH changes during storage can be suppressed. Based on this finding and through further research, the present invention has been completed.

[0010] That is, the present invention provides the following aspects. Item 1. An oral composition comprising (A) nattokinase, (B) at least one amino acid selected from the group consisting of glutamine, glycine, glutamic acid, and tryptophan, and (C) water. Item 2. The oral composition according to Item 1, which has a pH of 8 to 11. Item 3. The oral composition according to Item 1 or 2, which is a food product. Item 4. A method for stabilizing the pH of an oral composition containing nattokinase and water, comprising: The method, wherein the oral composition contains (A) nattokinase, (B) at least one amino acid selected from the group consisting of glutamine, glycine, glutamic acid, and tryptophan, and (C) water. Item 5. Used to stabilize the pH of an oral composition containing nattokinase and water, A pH stabilizer containing at least one amino acid selected from the group consisting of glutamine, glycine, glutamic acid, and tryptophan as an active ingredient. [Effects of the Invention]

[0011] The oral composition of the present invention can suppress pH changes during storage even while containing nattokinase and water. DETAILED DESCRIPTION OF THE INVENTION

[0012] 1. Oral Composition The oral composition of the present invention is characterized by containing (A) nattokinase, (B) at least one amino acid selected from the group consisting of glutamine, glycine, glutamic acid, and tryptophan, and (C) water. The oral composition of the present invention is described in detail below.

[0013] [(A) Nattokinase] The oral composition of the present invention contains nattokinase (sometimes referred to as component (A)). Nattokinase is an enzyme that has a fibrinolytic activity and is produced by Bacillus subtilis var. natto.

[0014] The nattokinase used in the present invention can be obtained by a known production method. Specific production methods for nattokinase include a method of culturing Bacillus subtilis natto, a method of obtaining it from a transformant incorporating a gene encoding nattokinase, and a method of synthesizing it by chemical synthesis. The nattokinase used in the present invention may be obtained by any production method, but from the viewpoint of reducing production costs, etc., nattokinase obtained by a method of culturing Bacillus subtilis natto is preferred.

[0015] The nattokinase used in the present invention may be a purified product, or may be in an unpurified state as long as it is edible. For example, when using nattokinase obtained by culturing Bacillus subtilis natto, it may be an extract of the culture of Bacillus subtilis natto. Furthermore, it may be nattokinase obtained by subjecting a culture of Bacillus subtilis natto to ion exchange chromatography, gel filtration chromatography, hydrophobic chromatography, or the like to purify the nattokinase, or it may be nattokinase obtained by subjecting a culture of Bacillus subtilis natto to a crude purification process such as solid-liquid separation as necessary, followed by removal of water or drying.

[0016] Nattokinase is commercially available as a powder product containing excipients, a crude product, a purified product, etc., and these commercially available products can also be used as nattokinase in the present invention.

[0017] In the oral composition of the present invention, the content of component (A) may be appropriately determined depending on the form of the oral composition, etc., and, for example, the amount of nattokinase per 1 g of the oral composition of the present invention is 100 FU or more, preferably 300 to 20,000 FU, more preferably 500 to 10,000 FU, even more preferably 800 to 8,000 FU, and particularly preferably 1,000 to 5,000 FU.

[0018] In the present invention, the "FU" indicating the activity of nattokinase is a fibrinolytic activity unit according to the standards for natto culture extract foods published by the Japan Health and Nutrition Food Association on January 15, 2003.

[0019] [(B) glutamine, glycine, glutamic acid, and / or tryptophan] The oral composition of the present invention contains, in addition to nattokinase, at least one amino acid selected from the group consisting of glutamine, glycine, glutamic acid, and tryptophan (sometimes referred to as component (B)). By allowing nattokinase and these amino acids to coexist in the presence of water, the oral composition of the present invention can suppress pH changes during storage.

[0020] The amino acid used as component (B) may be in the L-, D-, or DL-form, but is preferably in the L-form. Furthermore, of the amino acids used as component (B), glutamic acid may be in the form of a salt such as a sodium salt.

[0021] As component (B), one amino acid selected from glutamine, glycine, glutamic acid, and tryptophan may be used alone, or two or more amino acids may be used in combination.

[0022] Among these components (B), glutamine, glycine, and glutamic acid are preferred, and glutamine is more preferred, from the viewpoint of more effectively suppressing pH changes during storage.

[0023] The content of component (B) in the oral composition of the present invention may be appropriately set depending on the formulation form of the oral composition, etc., and may be, for example, 0.1 to 40% by weight, preferably 1 to 30% by weight, and more preferably 5 to 20% by weight.

[0024] In the oral composition of the present invention, the ratio of component (B) to component (A) is not particularly limited, but examples thereof include 0.01 to 5 g, preferably 0.01 to 1 g, and more preferably 0.01 to 0.5 g of component (B) per 10,000 FU of component (A).

[0025] [(C)Water] The oral composition of the present invention contains water (sometimes referred to as component (C)) as a base or an additive component. The content of component (C) in the oral composition of the present invention may be appropriately determined depending on the formulation form of the oral composition, and may be, for example, 10 to 98 wt %, preferably 50 to 95 wt %, and more preferably 60 to 90 wt %.

[0026] [Other ingredients] The oral composition of the present invention may contain other nutritional components or pharmacological components in addition to the above-mentioned components. Such nutritional components and pharmacological components are not particularly limited as long as they are usable in foods and oral pharmaceuticals, and examples thereof include vitamins, amino acids other than those mentioned above, minerals, carbohydrates, fatty acids, flavorings, seasonings, plant extracts, antioxidants, hypoglycemic agents, anticholesterol agents, immunostimulants, etc. These components may be used alone or in combination of two or more. The content of these components is appropriately determined depending on the type of components used and the intended use of the oral composition.

[0027] Furthermore, in order to prepare the oral composition of the present invention into a desired formulation, bases and additives may be included, as necessary, in addition to the above-mentioned components. Such bases and additives are not particularly limited as long as they are usable in foods and pharmaceuticals, and examples thereof include fats and oils, waxes, hydrocarbons, fatty acids, higher alcohols, water-soluble polymers, surfactants, lower alcohols, polyhydric alcohols, pH adjusters, buffers, antioxidants, preservatives, thickeners, and chelating agents. These may be used alone or in combination of two or more. The content of these bases and additives is appropriately determined depending on the types of components used and the intended use of the oral composition.

[0028] [pH] The pH of the oral composition of the present invention may be appropriately set within a range that allows edibility, such as a pH of 3 to 11. In conventional techniques, the higher the pH of an oral composition containing nattokinase and water, the more pronounced the pH change during storage. However, the present invention makes it possible to effectively suppress pH change during storage, even at high pH. In view of the effects of the present invention, the pH of the oral composition of the present invention is preferably alkaline, specifically, pH 8 to 11, and more preferably pH 9 to 11. In the present invention, the pH is measured at a temperature of 20°C.

[0029] [Dosage form / preparation type] The dosage form of the oral composition of the present invention is not particularly limited as long as it can be orally ingested or administered, and may be either semi-solid or liquid, and may be appropriately determined depending on the type and use of the oral composition.

[0030] The formulation of the oral composition of the present invention is not particularly limited as long as it can be orally ingested or administered, and specific examples include foods and oral medicines.

[0031] When the oral composition of the present invention is formulated into a food product, the aforementioned ingredients may be prepared as desired, either alone or in combination with other food materials or additives. Examples of such foods include general foods and beverages, as well as foods for specified health uses, foods with nutrient function claims, foods with functional claims, and foods for patients. The form of these foods and beverages is not particularly limited, but specific examples include supplements such as jelly; and beverages such as nutritional drinks, soft drinks, carbonated drinks, and lactic acid drinks. In the case of soft capsules, the oral composition of the present invention is used as the contents of the soft capsule.

[0032] When the oral composition of the present invention is formulated into an oral pharmaceutical preparation, the aforementioned components may be prepared into a desired form either as is or in combination with other additives. Specific examples of such oral pharmaceutical preparations include soft capsules, jellies, syrups, liquids, etc. In the case of soft capsules, the oral composition of the present invention is used as the contents of the soft capsules.

[0033] 2. pH stabilization method and pH stabilizer The pH stabilization method of the present invention is a method for stabilizing the pH of an oral composition containing nattokinase and water, characterized in that the oral composition contains (A) nattokinase, (B) at least one amino acid selected from the group consisting of glutamine, glycine, glutamic acid, and tryptophan, and (C) water.

[0034] Furthermore, the pH stabilizer of the present invention is used to stabilize the pH of an oral composition containing nattokinase and water, and is characterized in that it contains, as an active ingredient, (B) at least one amino acid selected from the group consisting of glutamine, glycine, glutamic acid, and tryptophan.

[0035] The pH stabilization method and pH stabilizer of the present invention make it possible to suppress pH changes that occur during storage of an oral composition containing nattokinase and water. The types and amounts of ingredients used in the pH stabilization method and pH stabilizer of the present invention, as well as specific embodiments, are as described in the section "1. Oral Composition" above. [Example]

[0036] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0037] Test Example 1 Oral compositions were prepared with the compositions shown in Table 1. 20 g of the resulting oral compositions were filled into glass bottles (φ30 × 65 mm, Maruemu screw tube No. 6) and stored at 40°C or 50°C in the dark for 1 week. The pH of the oral compositions before and after storage was measured using a pH meter (HORIBA, F-52), and the pH change was calculated by subtracting the pH value after storage from the pH value before storage.

[0038] The results are shown in Table 1. The oral composition containing nattokinase and water but no amino acids showed a significant decrease in pH after storage (Comparative Example 1). Furthermore, oral compositions containing nattokinase and water, even when containing arginine, proline, or tyrosine as an amino acid, were unable to sufficiently suppress pH changes after storage (Comparative Examples 2 to 4). In contrast, oral compositions containing nattokinase and water that contained glycine, sodium glutamate, glutamine, or tryptophan were able to sufficiently suppress pH changes after storage (Examples 1 to 4). In particular, when glutamine was included, pH changes after storage were significantly suppressed (Example 3).

[0039] [Table 1]

Claims

[Claim 1] An oral composition comprising: (A) nattokinase; (B) at least one amino acid selected from the group consisting of glutamine, glycine, glutamic acid, and tryptophan; and (C) water. Finished product.