JP2003261456A - Brain aging-preventing agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a brain aging-preventing agent preventing or delaying the aging of the brain caused by aging. <P>SOLUTION: This brain aging-preventing agent contains L-arginine, phosphatidylserine, docosahexaenoic acid, ginkgo leaves or an extract of ginkgo leaves and tocopherol, and can contain usual pharmaceutically or veterinarily permissible carriers. The brain aging-preventing agent can be administered not only as a medicine but also as various forms e.g. forms of beverage and food such as a functional food and health food (including a beverage), or feed. <P>COPYRIGHT: (C)2003,JPO

Description

Description: TECHNICAL FIELD [0001] The present invention relates to an agent for preventing aging of the brain. The brain aging preventive agent of the present invention can be administered not only as a pharmaceutical, but also in various forms, for example, functional foods and health foods (including beverages), or as feeds in the form of food and drink. is there. [0002] As is well known, the function of the brain regresses with aging. Components in the brain are sensitive to aging and are therefore important in keeping the brain and nerve activity of the elderly healthy. In order to fully demonstrate the function of the brain,
It is important that the components in the brain or related substances are filled. [0003] L-arginine is a precursor of the neurotransmitter γ-aminobutyric acid (GABA). The level of γ-aminobutyric acid in the bone marrow fluid tends to decrease with aging, and is particularly low in brain diseases such as senile dementia, Parkinson's disease, and chorea. [0004] Phosphatidylserine (PS) is abundantly contained in the brain and is a precursor of acetylcholine. When acetylcholine is reduced, information cannot be transmitted smoothly, leading to impaired memory of the brain, causing dementia and Alzfimer. Many clinical tests on bovine brain PS obtained from bovine brain have been conducted in Europe and the United States, and all of them have been shown to be effective against senile dementia. Soybean transfer PS has been developed for bovine brain PS (Akio Kuroda et al., “Food Industry Bioreactor System Technology Research Association”, 1985, Research Report, No. 555
Pp. 570). As an effect of bovine brain PS on brain function, an effect of increasing brain glucose concentration has been reported (Bruni, A. et al., Nature, 260, 331).
-333, 1976). Regarding the cerebral function-improving effect of soybean metastatic PS, an intraperitoneal administration test in mice showed a similar increase in glucose concentration as that of bovine brain PS (S
akai, M .; J. et al. Nutr. Sci. Vitam
inol. , 42, 47-54, 1996), suggesting that they have the same pharmacological action even if the fatty acid composition is slightly different. [0005] Docosahexaenoic acid (DHA) is present in large amounts in the hippocampus, which is responsible for memory learning in the brain. It has also been reported that the amount of DHA in the hippocampus of a person who died of Alzfheimer's dementia was half that of a person of the same age who died of another disease [Hazumi Okuyama, "Your oil choice is wrong. "Heart Publishing Co., Ltd., pages 130-131, 1
993]. Ginkgo biloba extract [Extract of
The main components of Gimgo Biloba (EGB) are flavonoids (24%) and terpenoids (6%).
%). Flavonoids in EGB are
It increases glucose uptake and consumption by the brain and contributes to activation of cranial nerves. Further, with the administration of EGB, the total number of muscarinic receptors and γ-adrenergic receptors, which are metabolic activity indicators in the hippocampal nucleus related to memory in the cerebral cortex, significantly increases. Furthermore, EGB promotes the release of neurotransmitters such as catecholamine, epinephrine, and dopa, and is therefore considered to have an effect of promoting cognition and memory. Terpenoids significantly increase the concentration of γ-aminobutyric acid in the hippocampus and cerebral cortex, suggesting that they have an effect of activating the cerebral nervous system (Sasaki, KS, E).
urop. J. Pharmacol. , 367,165
-173, 1999). [0007] Tocopherol stabilizes biological membranes and eliminates active oxygen. The effect of prolonging the death of Alzfimer patients or progression to severe dementia has been recognized. [0008] Phosphatidylserine and DHA have heretofore been recognized for use as active ingredients in foods that improve brain learning and memory ability. No anti-aging or anti-aging effects have been studied. The present inventor conducted a study to obtain a substance having a function of measuring brain aging more accurately and preventing or delaying brain aging by newly determining an index for measuring brain aging. -It has been found that a combination of arginine, phosphatidylserine, DHA, ginkgo biloba or ginkgo biloba extract and tocopherol exerts a particularly remarkable effect. The present invention is based on such findings. These substances used as active ingredients in the present invention are presumed to contribute to the brain's intellectual functions, but are substances that are not known to prevent or delay aging of the brain and pass through the blood-brain barrier. Various functional components having different possible actions have been selected with a minimum number of components and to include all. An object of the present invention is to provide a novel agent for preventing brain aging, which can prevent or delay brain aging. [0009] The above-mentioned object is characterized in that it comprises L-arginine, phosphatidylserine, docohexaenoic acid, ginkgo biloba or ginkgo biloba extract, and tocopherol according to the present invention. The problem can be solved by an antiaging agent for the brain. The term “prevention of brain aging” as used herein means to prevent or delay aging of the brain caused by aging. DETAILED DESCRIPTION OF THE INVENTION The preventive agent for cerebral aging according to the present invention comprises as active ingredients (1) L-arginine, (2) phosphatidylserine, (3) docosahexaenoic acid, (4) ginkgo biloba or Ginkgo biloba extract and (5) tocopherol are all contained. The brain aging preventive agent of the present invention comprises (1) L-
It can consist of only five components: arginine, (2) phosphatidylserine, (3) docosahexaenoic acid, (4) ginkgo biloba or ginkgo biloba extract, and (5) tocopherol, or if desired, pharmaceutical or It may further comprise a conventional veterinarily acceptable carrier. The agent for preventing brain aging of the present invention can be administered to animals, preferably mammals (particularly humans). As L-arginine which is one of the active ingredients of the agent for preventing brain aging of the present invention, for example, a commercially available product can be used as it is, or if necessary, a commercially available product can be repurified by a known method and used. You can also. The origin of the phosphatidylserine which is one of the active ingredients of the agent for preventing cerebral aging of the present invention is not particularly limited. For example, bovine brain phosphatidylserine, soybean transfer phosphatid Zircerin, sabaphosphatidylserine, or the like can be used. As the phosphatidylserine used in the brain aging preventive agent of the present invention, for example, a commercially available product can be used as it is, or if necessary, a commercially available product can be re-purified by a known method. Docosahexaenoic acid (DHA), which is one of the active ingredients of the agent for preventing brain aging of the present invention, includes, for example, fish,
Crustaceans, marine animals, etc., contain a large amount. As the DHA used in the brain aging preventive agent of the present invention, for example, a DHA-containing fish oil obtained by deacidifying and decolorizing fish oil such as sardine, mackerel, skipjack, or tuna, and then concentrating and deodorizing the same is used. it can. DHA-rich fish oil obtained by further refining DHA-containing fish oil can be used, or DHA itself (purified substance) can be used. As the DHA-containing fish oil or DHA, a commercially available product can be used as it is, or if necessary, a commercially available product can be re-purified by a known method. Ginkgo biloba or Ginkgo biloba extract, which is one of the active ingredients of the agent for preventing brain aging of the present invention, is ginkgo biloba itself (eg, a dry powder) or a solvent extract thereof. As the solvent used for the extraction, for example, water or an organic solvent, for example, lower alcohols, ketones, hydrocarbons, ethers, chloroform, dichloromethane or the like can be mentioned, and it is preferable to use a hydrous alcohol. The ginkgo biloba extract can be used as it is as an extracted solution, or the obtained extract can be concentrated and used, or the obtained extract can be dried (for example, freeze-dried or Spray drying etc.)
It can also be used as a dried product obtained by performing the treatment, and its use form is not particularly limited. As the ginkgo biloba extract, a commercially available product can be used as it is, or if necessary, a commercially available product can be re-purified by a known method. For example, Ginkgo biloba extract EGb76, which can be purchased as a commercial product from Schwab, Germany
1 is a ginkgo biloba leaf extract (for example, about 20 g of ginkgo biloba extract obtained from 1 kg of ginkgo biloba) obtained by extracting and extracting ginkgo biloba with aqueous alcohol, followed by filtration and the like. By weight ratio,
It contains about 24% flavonoids and about 6% terpenoids, and the other 70% contains many compounds, such as nucleic acids or sugars. The EGb761 is used in Germany and France as a prescription drug (for example, for peripheral circulatory disorders or for improving cerebral blood circulation). As the tocopherol which is one of the active ingredients of the agent for preventing brain aging of the present invention, for example, natural vitamin E can be used. The tocopherol is not particularly limited. For example, tocopherol can be used at a high concentration from a vegetable oil containing tocopherol, or tocopherol itself (pure substance) can be used. . As the tocopherol-rich vegetable oil concentrate or tocopherol, a commercially available product can be used as it is, or if necessary, a commercially available product can be re-purified by a known method and used. In addition, as tocopherol used as an active ingredient of the brain aging preventive agent of the present invention, α, β, γ,
Alternatively, any homologue of σ can be used, and α-tocopherol is preferably used. Further, any optical isomer of d, l, or dl form can be used, and d
It is preferred to use a body. The dosage form of the agent for preventing cerebral aging of the present invention is not particularly limited, and examples thereof include powders, fine granules, granules,
Oral preparations such as tablets, capsules, suspensions, emulsions, syrups, extracts, or pills, or injections,
Parenteral preparations such as liquids for external use, ointments, suppositories, creams for topical administration, or eye drops can be mentioned. These oral preparations include, for example, gelatin, sodium alginate, starch, corn starch, sucrose, lactose, glucose, mannitol, carboxymethylcellulose, dextrin, polyvinylpyrrolidone, crystalline cellulose, soy lecithin, sucrose, fatty acid esters, talc, stearic acid. Excipients such as magnesium, polyethylene glycol, magnesium silicate, silicic anhydride, or synthetic aluminum silicate, binders, disintegrants, surfactants, lubricants, glidants, diluents, preservatives, coloring Using agents, flavors, flavors, stabilizers, humectants, preservatives, or antioxidants,
It can be manufactured according to a conventional method. Examples of parenteral administration include injection (subcutaneous, intravenous, etc.) and rectal administration. Of these, injections are most preferably used. For example, in preparing an injection, in addition to the active ingredient, for example, a water-soluble solvent such as physiological saline or Ringer's solution, a water-insoluble solvent such as vegetable oil or a fatty acid ester, an isotonic agent such as glucose or sodium chloride, Dissolution aids, stabilizers, preservatives, suspending agents, emulsifiers and the like can be optionally used. The agent for preventing cerebral aging of the present invention is not limited thereto, but L-arginine, phosphatidylserine, docosahexaenoic acid, ginkgo biloba extract, and tocopherol in total amount of 0.01 -10
0% by weight, preferably 0.1 to 80% by weight. The dose of the prophylactic agent for cerebral aging of the present invention can be appropriately determined according to the type of disease, age, sex, body weight, degree of symptom of the patient, or the method of administration. Or parenterally. The dosage of each active ingredient contained in the prophylactic agent for cerebral aging of the present invention is not particularly limited as long as it is an effective amount for the subject to be administered. With date, L-arginine 50mg
-20 g, phosphatidylserine 20-300 mg,
Docosahexaenoic acid 50-700 mg, Ginkgo biloba extract 40-480 mg, and tocopherol 50-200
It can be 0 mg. The administration form is not limited to pharmaceuticals, but may be given in various forms, for example, functional foods and health foods (including beverages), feeds, chewing gums and the like in the form of food and drink. It is. For example, L-arginine, phosphatidylserine, docosahexaenoic acid, ginkgo biloba or ginkgo biloba extract, and tocopherol are used as additives (eg, food additives) as desired foods (including beverages), feeds, chewing gums, and the like. Can be added. The form of the food for preventing brain aging, which is one embodiment of the agent for preventing brain aging of the present invention, is not particularly limited.
For example, tablets, granules, capsules, powders, gums, chocolates, candy, noodles, breads, cakes, biscuits, cooking oils, dressings, canned foods, retort foods, animal meat foods, fish paste products, margarine, butter, mayonnaise, or Normal food forms such as beverages can be employed. in particular,
Preferred are capsules, tablets, granules, cooking oils, dressings and the like. In the case of producing the brain aging preventive food, if necessary, for example, gelatin, methylcellulose, shellac or other coating agent, glycerin or fatty acid ester or other active agent, lactose, starch, or dextrin or the like The composition may contain ingredients, fats and oils, wax such as beeswax or rice sugar wax, or nutrient-enhancing components such as vitamins, minerals or amino acids. The present invention will now be described in detail with reference to examples, but these examples do not limit the scope of the present invention. Preparation Example 1 50 mg of L-arginine (Ajinomoto)
Phosphatidylserine-containing soybean oil extract (phosphatidylserine content = 20% by weight; Tama Biochemical) 10
0 mg, DHA-containing fish oil (DHA content = 46% by weight;
Tama Biochemical) 109mg, Ginkgo biloba leaf extract (EGb7)
61; Tama Biochemistry) 40 mg, and tocopherol-containing vegetable oil extract (total tocopherol content = 67% by weight)
75 mg, purified wheat germ oil (Nissin Flour Milling) 26 mg, beeswax (Yokoseki Yushi Kogyo) 25 mg, and glycerin fatty acid ester (RIKEN Vitamin) 25 mg were stirred and mixed to make uniform, and then a soft capsule having a capsule content of 450 mg was prepared. . The pure content of each active ingredient in one capsule was 50 mg of L-arginine, 20 mg of phosphatidylserine, 50.14 mg of DHA, 40 mg of ginkgo biloba extract, and 50.25 mg of total tocopherol. [Evaluation Example 1] The test for the effect of improving brain aging was carried out by self-scoring a questionnaire to a subject who was administered with the soft capsule prepared in Preparation Example 1 and containing the preventive agent for brain aging. The basic test items are items that are suitable for expressing the aging phenomenon of the brain of a healthy person due to senile changes with reference to the diagnostic scale for dementia, that is, (1) memory ability,
(2) register fabric, (3) attention, (4) concentration, (5) motivation, and (6) sleep. The questions shown in Table 1 were specifically asked. << Table 1 >> Items Content of question (1) Memory ability (i) Forgetting recent events from time to time (ii) Forgetting old memories and winning (iii) Even familiar phone numbers may be forgotten (2) Meiori (I) Sometimes mistaken place and time. (3) Attention. (I) Forget things around, such as glasses. (4) Concentration. (I) It is easy to make miscalculations and subtractions. (Ii) (5) Motivation (5) Motivation (i) Mood can sometimes be overwhelmed (ii) Angry (6) Sleep (i) Insufficient sleep ( ii) It is often tempting to take a nap. The administration of soft capsules was carried out for two months, dividing three tablets per day into one tablet after breakfast, one tablet after lunch, and one tablet after dinner. The subjects who received the soft capsule were 32 subjects (26 women and 6 men), the age composition was 35 to 83 years, and the average age was 65.3 years. Questionnaire surveys were conducted before the start of administration, one month after the start of administration, and two months after the start of administration. In the questionnaire survey before the start of the administration, responses to the questions shown in Table 1 were obtained regarding the presence or absence of subjective symptoms. In addition, in the questionnaire survey one or two months after the start of administration, only items that had subjective symptoms in the questionnaire before administration were evaluated in three stages: "good improvement", "slight improvement", and "unchanged". We had you reply by evaluation. In addition, for comparison, the subject 1 who received the placebo
The same questionnaire survey was conducted for 0 persons. The breakdown of 10 subjects for comparison is 7 women and 3 men
The age structure was 60 to 83 years old, and the average age was 66.4 years. Tables 2 and 3 show the results of the subjects who received the soft capsule. Table 2 shows the improvement rate for each brain health test item, and Table 3 shows the overall improvement rate. Also,
Table 4 shows the overall improvement rate for comparison (placebo).
In Table 2, the “number of cases” in the column of “administration period” of “one month” is the total number of responses to subjective questions for each question in a questionnaire survey before the start of administration,
That is, it is the total of the answers by the three-step evaluation in the questionnaire one month after the start of the administration. Further, in Table 2, the “number of cases” in the column of “administration period” of “2 months” is the total of the responses based on the three-stage evaluation in the questionnaire two months after the start of administration. Further, the “improvement rate (%)” in Table 2 refers to the “number of cases”
This is the total ratio (percentage) of the answers that answered "good improvement" and "slight improvement". In Table 3, “number of cases” is the total of “number of cases” in each test item shown in Table 2.
Further, in Table 3, the numerical value (and percentage) in the “good improvement” column is the sum of the “number of cases” for each test item in the “good improvement” column shown in Table 2 (and the “number of cases” in Table 3). (Percentage). Similarly, the numerical value in each column of “slightly improved” and “unchanged” is the sum of the “number of cases” for each test item in each column of “slightly improved” and “unchanged” shown in Table 2 (and Table 3 (Percentage of the “number”). In the comparative example (placebo group), the overall improvement rate was 5.6% in one month and 8.2% in two months (see Table 4). Compared with the comparative subjects, the subjects receiving the soft capsule containing the agent for preventing cerebral aging of the present invention exhibited improved brain health and aging. << Table 2 >> Test item Administration period No. of cases Good improvement Slight improvement Unchanged Improvement rate (%) Improvement of memory ability 1 month 41 4 16 21 48.8 2 months 36 5 18 13 63.9 Improvement of side cloth 1 Months 4 0 1 3 25.0 2 months 2 0 1 1 50.0 Improve attention 1 month 22 1 9 12 45.5 2 months 19 0 5 8 57.9 Improve concentration 1 month 16 0 8 8 50.0 2 months 21 6 7 8 61.9 Improve motivation 1 month 20 4 8 8 60.0 2 months 16 5 6 5 68.8 Improve sleep 1 month 31 8 9 14 54.8 2 months 33 14 12 7 78.8 [Table 3] Administration period Number of cases Good improvement Slight improvement Unchanged 1 month 134 17 (12.7%) 51 (38.1%) 66 (49. 2 months 127 36 (28.3%) 49 (38.6%) 42 (33.1%) << Table 4 >> Administration period No. of cases Good improvement Slight improvement Unchanged 1 month 540 (0.0%) 3 (5.6%) 51 (94.4%) 2 months 49 1 (2.0%) 3 (6.1%) 45 (91.8%) According to the agent for preventing brain aging of the present invention, aging of the brain can be prevented or delayed.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 31/685 A61K 31/685 A61P 25/00 A61P 25/00 25/14 25/14 25/16 25 / 16 25/28 25/28 39/06 39/06 43/00 107 43/00 107 121 121 // A23L 1/30 A23L 1/30 B Z 1/305 1/305 (72) Inventor Koichiro Hirotani Tokyo 1-8-8 Nihombashi Muromachi, Chuo-ku Chiba-ya Building WHITE Co., Ltd. (72) Inventor Shuji Wakao 7774 Minamikoma-gun, Yamanashi Pref. No. 11 No.4 F term in Yatron Co., Ltd. (reference) 2B150 AB03 DA37 DA46 DD31 DD57 4B018 MD11 MD19 MD26 MD61 ME10 4C086 AA01 AA02 BA09 DA40 MA03 MA04 MA16 MA52 NA14 ZA02 ZA15 ZA16 ZA22 ZB22 ZC37 ZC75 4C088 AB02 AC05 BA08 BA11 BA14 CA03 NA14 ZA02 ZA15 ZA16 ZA22 ZB22 ZC37 ZC75 4C206 AA01 AA02 DA05 HA32 MA03 MA04 MA11 MA13 MA24 MA36 MA72 NA14 ZA02 ZA15 ZA16 ZA22 ZB22 ZC37 ZC75

Claims (1)

Claims: 1. An agent for preventing aging of the brain, comprising L-arginine, phosphatidylserine, docosahexaenoic acid, ginkgo biloba or ginkgo biloba extract, and tocopherol.