Cognitive function reduction inhibiting agent

Abstract

To provide a novel cognitive function reduction inhibiting agent.SOLUTION: A cognitive function reduction inhibiting agent for healthy persons is a decomposed guar gum product which has an average molecular weight of 1.0×103 to 2.0×105, the decomposed guar gum product being in the range of the average molecular weight of 70 mass% or more. A 1 mass% aqueous solution of the decomposed guar gum product has a viscosity of 50 mPa s or less as measured at 25°C and at 60 rpm with a Brookfield viscometer. The decomposed guar gum product is obtained by hydrolyzing galactomannan polysaccharide into a low molecular form with a microorganism-derived β-mannanase, the galactomannan polysaccharide being contained in guar-derived albumen and having a content ratio between galactose and mannose (galactose: mannose) in a range of 1:1.3 to 1:2.1. The decomposed guar gum product has a dietary fiber content defined by an enzyme-HPLC method of at least 70 mass%.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] The present invention relates to a cognitive function reduction inhibitor and is directed to healthy elderly people (especially those 60 years old or older).

Background Art

[0002] Cognitive function is a general term for intellectual functions for performing "cognition" that includes elements such as perception, judgment, imagination, inference, decision-making, memory, and language understanding. It means a function of recognizing the current situation, manipulating language, and performing memory, learning, calculation, and prediction based on information obtained from the outside through some or all of the five senses (seeing, hearing, smelling, tasting, touching). As a decline in cognitive function, dementia is known. Dementia is a disease that develops due to the death and functional decline of brain cells caused by aging, and the symptoms gradually become severe in proportion to the degree of decline in cognitive function. Even before developing dementia, it is inevitable that cognitive function will be reduced more or less due to aging. Research and development have been conducted to improve or suppress the decline in cognitive function. For example, Patent Document 1 discloses the effects of aged garlic extract. In addition, although a technique for reducing stress disorders has been disclosed in the guar gum degradation product (Patent Document 2), no technique related to cognitive function has been known.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Disclosure of the Invention

Problems to be Solved by the Invention

[0004] The present invention has been made in view of the above problems, and an object thereof is to provide a novel cognitive function reducing inhibitor and the like.

Means for Solving the Problems

[0005] The present inventor has found that a composition containing a specific guar gum degradation product has an effect of suppressing cognitive function reduction in the elderly (especially 60 years old or more), and has basically completed the present invention. Thus, the cognitive function reducing inhibitor for persons 60 years old or more according to the present invention is a guar gum degradation product in which those within the range of the average molecular weight of 1.0×10 3 ~2.0×10 5 are contained in an amount of 70% by mass or more, and the viscosity of a 1% by mass aqueous solution when measured at 25°C and 60 rpm using a B-type viscometer is 50 mPa·s or less, and the guar gum degradation product is contained in the endosperm derived from guar, and the content ratio of galactose to mannose (galactose:mannose) is in the range of 1:1.3 to 1:2.1, and is obtained by hydrolyzing a galactomannan polysaccharide with a microorganism-derived β-mannanase to reduce the molecular weight, and is characterized by containing at least 70% by mass of the dietary fiber content defined by the enzyme-HPLC method.

[0006] In the present invention, it is preferable that the cognitive function is one or more selected from visual memory, general memory, verbal memory, cognitive function speed, reaction time, cognitive flexibility, and executive function. As described above, the cognitive function includes elements such as perception, judgment, imagination, inference, decision-making, memory, and language understanding. It has been found that the inhibitor of the present invention is effective particularly for visual memory, general memory, verbal memory, cognitive function speed, reaction time, cognitive flexibility, and executive function among these cognitive functions. In the present invention, it is possible to provide a food or drink product or a pharmaceutical product containing a cognitive function reduction inhibitor. The food or drink product includes foods and beverages, and examples thereof include dietary supplements, health foods, foods for specified health uses, foods with functional claims, therapeutic foods, comprehensive health foods, supplements, tea beverages, coffee beverages, juices, soft drinks, drink preparations, cooked rice, bread, noodles, dairy products, processed egg products, processed fishery and livestock products, confectionery, fats and oils and processed fat and oil products, seasonings, prepared foods, etc. The pharmaceutical product includes pharmaceuticals or quasi-drugs, and is preferably an oral preparation or an enteral preparation, and can be in the form of a liquid preparation, tablet, granule, pill, syrup, etc.

Advantages of the Invention

[0007] According to the present invention, a novel cognitive function reduction inhibitor can be provided.

Brief Description of the Drawings

[0008]

Figure 1

Figure 2

Modes for Carrying Out the Invention

[0009] Next, embodiments of the present invention will be described with reference to the charts. However, the technical scope of the present invention is not limited by these embodiments, and can be implemented in various forms without changing the gist of the invention. "Guar gum" means a water-soluble natural polysaccharide obtained from the endosperm (specifically, cotyledons) of guar beans, and is a polysaccharide having a side chain of one molecule of galactose attached to two linearly bonded molecules of mannose. The average molecular weight is about 2.0×10 5 ~3.0×10 5 . Physiological effects such as blood sugar level elevation inhibitory effect, cholesterol lowering effect, and bowel movement improvement effect are known for guar gum. In the present invention, the guar gum hydrolyzate means a water-soluble dietary fiber obtained by using beans derived from the annual leguminous plant guar (scientific name: Cyanopsis tetragoloba) used for food in India, Pakistan, etc. as a raw material, and hydrolyzing and reducing the molecular weight of the galactomannan polysaccharide contained in its endosperm. The method for hydrolyzing guar gum is not particularly limited, such as an enzymatic decomposition method or an acid decomposition method, but the enzymatic decomposition method is preferable from the viewpoint of easily adjusting the molecular weight of the hydrolyzate.

[0010] The enzyme used in the enzymatic decomposition method is not particularly limited as long as it is an enzyme that hydrolyzes the mannose straight chain, but it is preferable to use β-mannanase derived from Aspergillus spp. or Rhizopus spp. The average molecular weight distribution of the guar gum hydrolyzate has an upper limit value of 2.0×10 5 or less, preferably 1.0×10 5 or less, more preferably 2.5×10 4 or less. The lower limit value of the average molecular weight distribution of the guar gum hydrolyzate is 1.0×10 2 or more, preferably 2.0×10 3 or more. When the average molecular weight exceeds 2.0×10 5 , the viscosity becomes too high and it becomes difficult to contain it in food and drink products. The method for measuring the molecular weight distribution is not particularly limited. For example, polyethylene glycol (average molecular weight: 2×10 2 , 2×10 3 , 2×10 4 and 1×10 5 ) is used as a molecular weight marker, and there is a method using gel filtration chromatography method, etc. The guar gum degradation product of the present invention is preferably one in which those within the above average molecular weight range are contained in an amount of 70% by mass or more, more preferably 80% by mass or more.

[0011] Galactose is a type of monosaccharide classified as an aldohexose, with the molecular formula C6H 12 O6 and a molecular weight of 180 (both the same as glucose). The configuration is such that the -OH groups at the 2-position (the second from the top in the Fischer projection formula) and 5-position are in the same direction, and the 3-position and 4-position are in opposite directions. The configuration at the 5-position of D-galactose is the same as that of D-glyceraldehyde. Mannose is a type of monosaccharide classified as an aldohexose, with the molecular formula C6H 12 O6 and a molecular weight of 180 (both the same as glucose). The configuration is such that the -OH groups at the 2-position and 3-position are in the same direction, and the 4-position and 5-position are in opposite directions. The configuration at the 5-position of D-mannose is the same as that of D-glyceraldehyde. Mannose is not metabolized much in humans and hardly enters the glycolysis system when ingested orally.

[0012] "Cognition" means the process by which a human perceives an object in the external world and then judges or interprets what it is. "Cognitive function" means the function of cognition, that is, the higher-order functions of the brain including, for example, perception, judgment, imagination, inference, decision-making, memory, calculation, understanding, learning, thinking, and language. It is inevitable that the cognitive function of the elderly declines compared to that of the younger generation. However, in the present invention, the target is healthy elderly people aged 60 years or older, excluding those with "dementia". The cognitive function reducing inhibitor of the present invention can be orally ingested as it is or mixed with foods, beverages, etc. The dosage of the cognitive function reducing inhibitor for oral ingestion is not particularly limited, but is 0.5 g to 70 g (preferably 3 g to 30 g, more preferably 6 g to 18 g) per adult per day. As described above, the cognitive function includes many functions. In the present invention, it is preferably targeted at the reduction of one or more selected from visual memory, general memory, verbal memory, cognitive function speed, reaction time, cognitive flexibility, and executive function.

[0013] <Preparation of Guar Gum Degradate (PHGG)> Example 1 After adding 0.1N hydrochloric acid to 900 g of water to adjust the pH to 4.5, 0.2 g of β-mannanase derived from commercially available Aspergillus bacteria and 100 g of guar gum powder were added and mixed. This mixture was reacted at 40°C to 45°C for 24 hours. After the reaction, it was heated at 90°C for 15 minutes to inactivate the enzyme. The reaction solution was separated by suction filtration to remove insoluble matters, and the obtained transparent solution was concentrated under reduced pressure (Yamato evaporator). A 20 mass% product was obtained as the solid content. This was dried using a spray dryer (manufactured by Okawara Chemical Industries Co., Ltd.) to obtain 65 g of guar gum degradate as a powder. The guar gum degradate was dissolved in water to obtain an aqueous solution with a concentration of 0.5 (w / v)%. As molecular weight markers, polyethylene glycols (average molecular weights: 2×10 2 、2×10 3 、2×10 4 and 1×10 5 ) were used, and the average molecular weight was determined to be approximately 20,000 using gel filtration chromatography (column: YMC-Pack Diol-120, detector: differential refractometer). Those with molecular weights of 1.0×10 3 to 2.0×10 5 were contained at 80 mass% or more. Also, when the viscosity of a 1 mass% aqueous solution was measured at 25°C and 60 rpm using a B-type viscometer, it was 8 mPa·s. When the content ratio of galactose to mannose (galactose: mannose) was measured, it was 1:1.7. When the dietary fiber content was measured by the enzyme-HPLC method, it was 90 mass%.

[0014] Example 2 After adding 0.1 N hydrochloric acid to 900 g of water to adjust the pH to 3, 0.15 g of commercially available β-mannanase derived from Aspergillus bacteria and 100 g of guar gum powder were added and mixed. This mixture was reacted at 40°C to 45°C for 24 hours. After the reaction, it was heated at 90°C for 15 minutes to inactivate the enzyme. The reaction solution was filtered and separated by suction filtration, and the transparent solution obtained by removing the insoluble matter was concentrated under reduced pressure (using an evaporator manufactured by Yamato). As a solid content, a 20% by mass product was obtained. This was dried using a spray dryer (manufactured by Okawara Chemical Industries Co., Ltd.) to obtain 68 g of a guar gum degradation product as a powder. When the average molecular weight of the guar gum degradation product was determined in the same manner as in Example 1, it was about 2.5×10 4 It was. From the results of the HPLC chart, the molecular weight was 1.0×10 3 ~2.0×10 4 And 80% by mass or more of it was contained. Also, when the viscosity of a 1% by mass aqueous solution was measured at 25°C and 60 rpm using a B-type viscometer, it was 10 mPa·s. When the content ratio of galactose to mannose (galactose:mannose) was measured, it was 1:1.8. When the dietary fiber content was measured by the enzyme-HPLC method, it was 89% by mass.

[0015] Example 3 After adding 0.1 N hydrochloric acid to 900 g of water to adjust the pH to 4, 0.25 g of commercially available β-mannanase derived from Aspergillus bacteria and 100 g of guar gum powder were added and mixed. This mixture was reacted at 50°C to 55°C for 12 hours. After the reaction, it was heated at 90°C for 15 minutes to inactivate the enzyme. The reaction solution was filtered and separated by suction filtration, and the transparent solution obtained by removing the insoluble matter was concentrated under reduced pressure (using an evaporator manufactured by Yamato). As a solid content, a 20% by mass product was obtained. This was dried using a spray dryer (manufactured by Okawara Chemical Industries Co., Ltd.) to obtain 70 g of a guar gum degradation product as a powder. When the average molecular weight of the guar gum degradation product was determined in the same manner as in Example 1, it was about 1.5×10 4 It was. From the results of the HPLC chart, the molecular weight was 1.0×10 3~2.0×10 5 contained 80 mass% or more of those.

[0016] Also, when the viscosity of a 1 mass% aqueous solution was measured at 25°C and 60 rpm using a B-type viscometer, it was 9 mPa·s. When the content ratio of galactose to mannose (galactose:mannose) was measured, it was 1:2.0. When the dietary fiber content was measured by the enzyme-HPLC method, it was 88 mass%. Example 4 According to the description of the example in JP-A-5-117156 (page 4, line 3 to page 4, line 10), a guar gum degradation product was prepared. When the average molecular weight was determined according to Example 1, it was 5.5×10 3 Also, when the viscosity of a 1 mass% aqueous solution was measured at 25°C and 60 rpm using a B-type viscometer, it was 2.8 mPa·s. When the content ratio of galactose to mannose (galactose:mannose) was measured, it was 1:1.9.

[0017] <Test method> To verify the effect of PHGG on the elderly, a placebo-controlled double-blind randomized parallel group comparison test was conducted. 91 healthy subjects aged 60 or older were recruited, and excluding 22 subjects who did not meet the selection criteria and 3 subjects who withdrew from participation, 66 subjects were randomly divided into two groups of 33 each, and they were made to ingest a placebo group (placebo powder food (dextrin)) or a subject group (5 g / day of PHGG of Example 1) every day for 12 weeks. However, during the start or the period of the test, there were subjects who did not receive the allocation offer (1 subject in the subject group), subjects who could not be followed up (2 subjects in the placebo group, 3 subjects in the subject group), so statistical analysis was performed on 31 subjects in the placebo group and 30 subjects in the subject group. At week 0 and week 12, 10 types of tests (language memory test, visual memory test, finger tapping test, SDC test, Stroop test, attention shift test, sustained processing test, facial expression recognition test, logical thinking test, 4-part sustained processing test) were conducted using Cognitrax. Through these tests, the standardized scores of each cognitive domain (neurocognitive index (NCI), general memory, language memory, visual memory, cognitive function speed, reaction time, general attention, cognitive flexibility, processing speed, executive function, social cognition, logical thinking, working memory, sustained attention, simple attention, motor speed) were obtained.

[0018] <Test Results> Table 1 shows a summary table of the cognitive function tests. The time point when the test food group showed a higher value than the placebo group was after 12 weeks (test food group: 99.6 ± 15.8, placebo group: 90.5 ± 15.4, inter-group difference: 9.1, P = 0.023). Figure 1 shows the comparison of data (NCI, general memory, language memory, cognitive function speed, reaction time, cognitive flexibility, processing speed, executive function) regarding 8 cognitive domains in which significant differences were observed between before the start of the test (0w) and after the end of the test (12w) in the PHGG group among the standardized scores of the above 16. Significant improvement was observed due to the administration of PHGG. Also, Figure 2 shows the results of visual memory in which a significant difference was observed between the placebo group and the test food group.

[0019]

Table 1

[0020] As is clear from these results, it was found that in the test food group, the cognitive function (especially visual memory after 12 weeks) was significantly improved compared to the placebo group. Also, it was found that for general memory, language memory, cognitive function speed, reaction time, cognitive flexibility, and executive function, there was a significant improvement in the test food group after 12 weeks of intake. Thus, according to this embodiment, a novel cognitive function reducing inhibitor or the like can be provided.

Claims

1. The average molecular weight is 1.0×10 ３ to 2.0×10 ５ , and it is a guar gum degradation product containing 70% by mass or more of those within the range of the average molecular weight, and the viscosity of a 1% by mass aqueous solution when measured at 25°C and 60 rpm using a B-type viscometer is 50 mPa·s or less, The guar gum degradation product is obtained by hydrolyzing a galactomannan polysaccharide contained in the endosperm derived from guar, with a content ratio of galactose to mannose (galactose:mannose) in the range of 1:1.3 to 1:2.1, using a microorganism-derived β-mannanase to reduce its molecular weight, and contains at least 70% by mass of dietary fiber content defined by the enzyme-HPLC method. It is a cognitive function reduction inhibitor for healthy individuals.

2. The cognitive function reduction inhibitor according to Claim 1, wherein the healthy individual is 60 years old or older.

3. The cognitive function reduction inhibitor according to Claim 1, wherein the cognitive function is one or more selected from visual memory, general memory, verbal memory, cognitive function speed, reaction time, cognitive flexibility, and executive function.

4. Food and drink containing the cognitive function reduction inhibitor according to Claim 1 or 2.

5. Pharmaceutical containing the cognitive function reduction inhibitor according to Claim 1 or 2.

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