JPH10101568A - Improving medicine for cerebral function, and nutritient composition - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject medicine which can display more excellent improving effect for cerebral function and is a preventive drug from dementia and defects of memory occurring in old age, by combining a ganglioside with a polyunsaturated fatty acid. SOLUTION: This medicine contains a ganglioside (preferably ganglioside GM3 ) and a polyunsaturated fatty acid (docosahexaenoic acid and arachidonic acid). It is preferable that these components contain the GM3 and the polyunsaturated fatty acid in amounts of 0.2mg-500mg and 5mg-500mg, respectively, per 100g of the composition (solid form). Further, the content ratio between docosahexaenoic acid and arachidonic acid may be preferably 10:1 to 1:2. A nutritious composition containing this medicine can be orally or parenterally administrated to young children, adults and further senile.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a brain function improving agent comprising ganglioside and polyunsaturated fatty acid. More specifically, the present invention relates to a brain function improving agent in which ganglioside is G _M3 and polyunsaturated fatty acids are docosahexaenoic acid and arachidonic acid. Further, the present invention relates to a nutritional composition containing a brain function improving agent. INDUSTRIAL APPLICABILITY The brain function improving agent of the present invention and a nutritional composition containing the same are useful as an agent for preventing and / or treating dementia, memory disorder and the like caused by old age.

[0002]

2. Description of the Related Art In recent years, Japan has entered a rapidly aging society. According to the Ministry of Health and Welfare's entrance dynamic survey and estimation (edited by the Ministry of Health and Welfare Institute for Population Affairs, Collection of Demographic Data, 1993),
In two years, the population aged 65 and over is expected to exceed 25%, and cerebrovascular disorders and dementia are expected to increase.
For this reason, research and development of cerebral function improving drugs (cerebral circulation and metabolism improving drugs, anti-dementia drugs) are being promoted mainly by pharmaceutical manufacturers in the treatment of these brain diseases, and various drugs including cinnarizine, citicoline, and tacrine have been promoted. Pharmaceuticals have been launched (BioIndustry, 11, 410, 1994). Naturally, these drugs are intended for patients with diseases, but from the viewpoint of preventing these diseases, it is necessary to pay attention to foods taken daily. In addition, health management from infancy will be necessary in the future. However, almost no drugs have been developed so far that can be easily taken by infants and the elderly and have a function of improving the function of the brain while suppressing a decrease in brain function.

[0003] Past research has clarified various components having a brain function improving effect. However, if it becomes a component that can be used for food and has no side effects, it will be limited to some extent. Examples include phospholipids such as lecithin, and nucleic acids such as nucleotides and nucleosides. But,
Even if such a component is ingested, a remarkable effect is not obtained. For this reason, gangliosides and polyunsaturated fatty acids have been attracting attention as new components for improving brain function. Ganglioside is a general term for glycosphingolipids containing sialic acid, and is a component in which saccharides such as glucose, galactose, and sialic acid are bonded to ceramide composed of sphingosine and fatty acids. In addition, these gangliosides are contained abundantly in cell membranes of brain and nervous system tissues. The body hips have _GM3 , _GD3 , _GM2 , _GM1 ,
Gangliosides such as G _D2 , G _D1a , G _D1b, and G _T1a are included. One of the characteristics of gangliosides is that they have a large number of molecular species and are rich in diversity. The effect of gangliosides is to inhibit the pathogenic E. coli from adhering to intestinal mucosal cells (Idota et al., Biosci. Biotec
h. Biochem., 59, 69 (1995)). Furthermore, the effect that it and G _M3 which G _M1 to neutralize cholera toxin prevent infection of influenza virus (Kawakami et al., Food and development, 30, 10 (1995)) are known, Kambi from these effects A nutritional composition that suppresses infection of Lactor and diarrhea caused by infection (Japanese Patent Laid-Open No. 5-276894), and milk powder to which ganglioside is added to prevent infection and diarrhea (Japanese Patent Publication
No. 6-85684). Furthermore, the effect of promoting peripheral blood lymphocyte proliferation and immunoglobulin production (Kima
Ta et al., Eur. J. Immunol., 24, 2910 (1993)) and the action of promoting differentiation of macrophages and the like (Saito et al., Journal of the Japanese Society of Agricultural Chemistry, 67, 1750 (1993)). Also, ganglioside is abundant in the brain and nervous system, suggesting that it is involved in the function of nerve cells. Gangliosides have central and peripheral nerve regeneration and promoting effects (Nishino et al., Metabolism, 26, Extra Issue, 279 (1989)), and therefore gangliosides are used in the treatment of stroke, Parkinson's disease, or Alzheimer's dementia. It has also been reported that it is effective (Palo et al., Mol. Chem. Neuropathol., 21, 41 (199
4), and Svennerholm, Life Sci., 5, 2125 (1994)).

[0004] On the other hand, polyunsaturated fatty acids that have received attention in recent years include n-6 fatty acids represented by linoleic acid and α-
It is divided into n-3 fatty acids represented by linolenic acid, and is contained not only in a large amount in biological membrane phospholipids but also as a precursor of prostaglandins and leukotrienes, and is involved in the maintenance and regulation of life. . Also, recent studies have drawn attention to its involvement in brain function because the upper queen's polyunsaturated fatty acids are high in the brain and nervous system. The brain contains about 5 to 10% and about 10 to 15% of docosahexaenoic acid (DHA) and arachidonic acid, respectively, per fatty acid (Neuringer, Nutrition Reviews, 51, 238 (1995);
Farguharson et al., Lancet Japanese Version, 8 (1993.3)),
It is characteristic that these fatty acids are most contained in the brain in tissues constituting the living body. As for the relationship between these fatty acids and brain function, it is known that, for example, when DHA is ingested into rats, the lightness discrimination learning ability is improved (Fujimoto, Food Science, No. 161, 41 (1991)). Also, NMDA
Studies on the effects on receptors and acetylcholine release have been seen, and the mechanism of action on brain functions is being elucidated.

[0005]

DISCLOSURE OF THE INVENTION The present inventors have intensively searched for a substance that improves brain function naturally, and as a result, have taken ganglioside and polyunsaturated fatty acids in combination to take each of the substances alone. It has been found that it has a better brain function-improving effect when taken or when compared to conventionally known brain function-improving substances. Accordingly, an object of the present invention is to provide a brain function improving agent comprising ganglioside and a polyunsaturated fatty acid, and a nutritional composition containing the same.

[0006]

SUMMARY OF THE INVENTION The present invention relates to a brain function improving agent comprising ganglioside and polyunsaturated fatty acid. Specifically, the present invention relates to a brain function improving agent in which ganglioside is _GM3 and polyunsaturated fatty acids are docosahexaenoic acid and arachidonic acid. Further, the present invention relates to a nutritional composition containing these brain function improving agents. INDUSTRIAL APPLICABILITY The brain function improving agent of the present invention and a nutritional composition containing the same are useful as agents for preventing dementia, memory impairment and the like caused by old age.

[0007]

The gangliosides used in the Detailed Description of the Invention The present invention, mono-gangliosides sialic acid was 1 molecule binding (G _M3, G _M1, etc.), two molecules bound disialoganglioside (G _D3, G _D1b, etc.), A trisialoganglioside ( _GT1a or the like) having three molecules bonded _thereto can be _exemplified .
Of these gangliosides, _GM3 is most preferably used. Regarding the method of preparing _GM3 used in the present invention, since these are contained in a large amount in brain and nervous system cells, they can be extracted from the brain of mammals.
As shown in 279379, milk-derived ganglioside G
The _D3 available a method for preparing a large quantity of G _M3 by hydrolysis. A method for preparing a large amount of G _M3 by hydrolyzing ganglioside G _D3 derived from milk is disclosed in Japanese Patent Application Laid-Open No. 63-269992, in which a large amount of G _D3 is prepared and then sialidase is reacted with acid or acid. by desialylated, it can be mass-prepared G _M3.
The polyunsaturated fatty acid used in the present invention may have 18 carbon atoms.
As long as it has three or more double bonds,
Preferably, DHA, EPA, α-linolenic acid, γ-linolenic acid, dihomo-γ-linolenic acid, arachidonic acid, particularly preferably DHA and arachidonic acid are used. Sources of these fatty acids include fish oil such as bonito oil and tuna oil, perilla oil, soybean oil, perilla oil, rapeseed oil, evening primrose oil, borage oil, and polyunsaturated using microorganisms and algae. Fats and oils with an increased fatty acid content, phospholipids such as egg yolk lecithin and the like are used. G _M3 is 100 g of the composition
The amount is preferably 0.5 to 500 mg per (solid), particularly preferably 1 to 50 mg per 100 g (solid) of the composition. DHA and arachidonic acid are preferably in composition 1
5 to 500 mg per 100 g (solid), particularly preferably 25 to 100 mg per 100 g (solid) of the composition. At this time, the content ratio of DHA and arachidonic acid is preferably 10: 1 to 1: 2, particularly preferably 2: 1 to 1: 2.
A ratio of 1 is good. Further, in order to further enhance the effects of the brain function improving agent of the present invention, other components such as phospholipids such as lecithin and nucleic acids such as nucleotides may be combined.

The nutritional composition containing the cerebral function improving agent of the present invention can be orally or parenterally administered to infants, adults, and the elderly. When administered orally, the form is not particularly limited, but tablets and capsules using appropriate excipients and carriers, or infant formulas, follow-up milks, infant formulas such as mature formulas, etc. It can be added to milk formulas, milk formulas for premature babies, milk formulas for special diseases, or oral / enteral nutritional supplements according to various disease states. At this time, since the polyunsaturated fatty acid is unstable to oxidation, an antioxidant can be used.
Further, since fish oil and the like have a peculiar odor, a masking agent, a flavor and the like may be used. Among the nutritional compositions containing the cerebral function improving agent of the present invention, especially infant formulas will be described in detail below. Infant formula contains protein, lipids,
Consists of sugars, vitamins and minerals. Examples of proteins include casein, whey protein concentrate, whey protein isolate, α-casein, β-casein, β-
Milk protein fractions such as lactoglobulin and α-lactalbumin, soy protein, and hydrolysates thereof are used. As lipids, animal fats and oils such as milk fat, vegetable fats and oils such as soybean oil, fractionated oils thereof, hydrogenated oils, and transesterified oils are used. Carbohydrates include starch, soluble polymorphs, dextrin, sucrose,
Lactose, glucose and other various oligosaccharides can be used. For information on vitamins and minerals, see the Japan International Dairy Federation, Codex Standards and Special Hygiene Work Regulations for Special Purpose Foods, Infants and Infants, CAC / VOL.IX First Edition and Supplement 1, 2, 3, 4 (1992).
3), “Food and Science Co., Ltd., 1993 Edition Designated Item Food Additives Handbook (Revised 31st Edition) (1993)”, “Food and Science Co., Ltd., Notification of Food Additives and Food Material Natural Products Handbook (No. 12th edition) (1992).
Minerals are used. That is, as the vitamin, vitamin A, vitamin B, vitamin D, vitamin E, vitamin K, folic acid, pantothenic acid, β-carotene, nicotinamide and the like are used. As minerals, calcium, magnesium, potassium, sodium, iron,
Copper, zinc, iodine, manganese, selenium and the like are used. In addition, to increase nutritional value, arginine,
Amino acids such as taurine, nucleotides, cholesterol, lactoferrin and the like may be added. The mixing ratio of proteins, fats, carbohydrates, vitamins and minerals is not particularly limited, but is 5 to 40% by weight, 5 to 40% by weight, 30 to 80% by weight, 0.005 to
It is preferably 5% by weight, preferably 0.005 to 5% by weight. These components are generally used to produce ordinary infant formula, but in order to enhance the _GM3 and polyunsaturated fatty acids of the present invention, a material with an increased _GM3 content is used. Alternatively, it can be obtained by mixing, homogenizing, sterilizing, and concentrating fats and oils containing DHA and / or arachidonic acid. or,
The obtained milk preparation may be spray-dried to obtain milk powder.

The preparations or compositions containing these cerebral function improving agents of the present invention are administered as preventive agents for dementia and memory impairment caused by old age such as Alzheimer's disease and Birkinson's disease. These preparations or compositions can be safely administered to humans and animals because most of the main raw materials are natural products and each component is known to have almost no side effects.

[0010]

The present invention will be described in more detail with reference to the following examples, which are merely illustrative, and do not limit the present invention.

[0011]

Example 1 Production of Tablets Ganglioside ( _GM3 ) 0.8 g Docosahexaenoic acid 0.25 g Arachidonic acid 0.15 g Potato starch 10 g Talc 8.8 g 6% HPC lactose 180 g ２００ Total 200g Mix each component, ganglioside 4mg, DHA1.2
500mg containing 5mg and 0.75mg arachidonic acid
Of tablets were produced.

[0012]

Example 2 Production of Capsules 0.2 g Ganglioside ( _GM3 ) Docosahexaenoic acid 0.3 g Arachidonic acid 0.2 g Potato starch 55 g Lactose 40 g Hydroxypropyl cellulose 3 g Magnesium stearate 1.3 g ───────────── Total 100g Each component was mixed well and filled into No. 1 capsule to produce 300 capsules.

[0013]

Example 3 Preparation of Infant Formula Milk Powder ( 1 ) 7.5 kg of whey protein concentrate and 44 kg of lactose were dissolved in 240 kg of skim milk, and 1 kg of each of minerals and water-soluble vitamins were dissolved in the solution. 23.9 g of adjusted fat containing fat-soluble vitamins was mixed. Furthermore, the mix solution, G _M3 10 g and DHA, arachidonic acid-containing oil (DHA, arachidonic acid content are each 10%, DH
A: Arachidonic acid = 1: 1) 200 g was added, mixed, homogenized, sterilized, concentrated, and dried to obtain 100 kg of milk powder. In the milk powder, 10 g of G _M3 , DHA and arachidonic acid were 2 g each.
0 g each was contained.

[0014]

Example 4 Preparation of Infant Formula Milk Powder 3.8 kg of 2 whey powder, 100 g of lactose, and 100 g of water-soluble vitamins and minerals were dissolved in 20 kg of hot water. Preparation fat 23.9g containing this skim milk 3.7kg and fat-soluble vitamins were mixed, further G _M3 2 g and D
HA, arachidonic acid-containing fat (DHA, arachidonic acid content is 20% and 5%, DHA: arachidonic acid = 4: 1)
50 g was added, mixed, homogenized, sterilized, concentrated and dried to obtain 100 kg of milk powder. During the milk powder, G _M3 2g and DHA,
Arachidonic acid was contained in 10 g and 2.5 g.

[0015]

Test Example 1 Brain Function Improving Effect Test The brain function improving effect according to the present invention was evaluated by animal experiments using rats. That is, SD male rats (4 weeks of age) weighing 100 to 120 g were allowed to freely ingest foods from Group A to Group G daily, and a memory / learning test was performed 12 months later using a Morris-type water maze. Table 1 shows the composition of the food taken by each group. The Morris water maze test was performed four times a day for one week,
In the 28th test, the time required to reach the goal in the pool (reaction latency) was measured, and the effects of food from the group A to the group G were compared. On the other hand, it can be determined that the shorter the reaction latency, the more effective the brain function was. The results are shown in FIG.

[0016]

[Table 1]

As a result, in the case of a normal naturally aged rat,
When the test is repeated four times a day for seven days, the reaction latency, which is the time required to reach the goal in the pool, is usually about 30 seconds (anitex, 6, 13 (1995)). In the group that received the cerebral function improver, the response latency was significantly lower than that. On the other hand, other than the G _M3 ganglioside and G
_The group receiving _M3 alone had little effect. In addition, the effect was weak even in the group in which DHA or arachidonic acid alone and _GM3 were taken. From the above results, the cerebral function improving agent of the present invention, that is, ganglioside G _M3 and D
By combining HA and arachidonic acid, a remarkable effect of improving brain function was observed.

[0018]

Therefore, the effectiveness of the brain function improving agent provided by the present invention was confirmed. INDUSTRIAL APPLICABILITY The brain function improving agent of the present invention and a nutritional composition containing the same are useful as agents for preventing dementia, memory impairment and the like caused by old age.

[Brief description of the drawings]

FIG. 1 shows the cerebral function improving effect (reaction latency by a Morris water maze test) of a composition containing the cerebral function improving agent of the present invention and various components in Example 3.

Claims (5)

[Claims] 1. A brain function improving agent comprising ganglioside and a polyunsaturated fatty acid. Wherein the ganglioside is G _M3, claim 1
The cerebral function improving agent according to the above. 3. The brain function improving agent according to claim 1, wherein the polyunsaturated fatty acid is docosahexaenoic acid and arachidonic acid. 4. The composition 100 g (solid) per G _M3 0.2mg~500mg, and polyunsaturated fatty acids 5m
The brain function improving agent according to any one of claims 1 to 3, which comprises g to 500 mg. 5. A ganglioside, docosahexaenoic acid,
And a nutritional composition containing arachidonic acid and having a brain function improving action.