JPH05252899A - Increasing agent for omega-3-based fatty acid in biological tissue and nutritive composition containing the same - Google Patents

Abstract

PURPOSE:To provide the subject agent (a medicinal agent) capable of promoting learning ability development, containing, as active ingredient, a nucleotide mixture comprising cytidine monophosphate, uridine monophosphate, adenosine monophosphate, guanosine monophosphate, inosine monophosphate, etc. CONSTITUTION:The objective nutritive composition which contains the substances capable of increasing polyvalent unsaturated fatty acids (esp., omega-3-based fatty acids) such as arachidonic acid and docosahexaenoic acid in the cerebral cortex and also of promoting cerebral and nervous functions (e.g. learning ability development) can be obtained by incorporating a nutritive composition comprising proteins, fats, glucids, minerals and vitamins with, on a solid basis, 5-120mg/100g of a nucleotide mixture composed of 1.5-50mg/100g of cytidine monophosphate, 0-20mg/100g of uridine monophosphate, 0-15mg/100g of adenosine monophosphate, 0-15mg/100g of guanosine monophosphate, and 0-15mg/100g of inosine monophosphate.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an agent for increasing .omega.3 fatty acids in living tissues, which comprises a specific nucleotide mixture, and a nutritional composition containing the same. This product can be used as a variety of pathological diets, oral or enteral nutrition for preoperative and postoperative patients, and infant formula.

[0002]

2. Description of the Related Art Nucleotide is a component constituting a nucleic acid which is a gene body, and is an essential substance universally present in all living organisms. That is, it is considered that all living organisms including humans synthesize the required amount of nucleotides. However, there are many unknowns regarding its nutritional significance, and research is still in the process of development.

Under these circumstances, the few studies on the physiological effects of nucleotides provide us with the following information. For example, it has been known for a long time that nucleotides have so-called bifidobacterial growth activity, and that feeding of nucleotides to an infant forms an intestinal bacterial flora in which bifidobacteria are dominant (Kosaburo Ito, Kobe Medical University, 2
9, 1, 1968). In addition, it has been shown that orally-ingested nucleotides are deeply involved in immunocompetence. That is, the absence of dietary nucleotide suppresses the cellular immune function involving T cells (Rudolph et al Adv. Exp. Me.
d. Biol. 165, 175, 1984), and is known to increase the mortality of experimental animals due to Staphylococcus sepsis. The study also suggests that orally ingested nucleotides activate the function of natural killer cells and promote the development of immature immunocompetence, especially in infants.

Further, adenosine monophosphate, cytidine monophosphate, guanosine monophosphate, uridine monophosphate and inosine monophosphate are contained in a very limited blending ratio, that is, 1: 1:
At a molar ratio of 1: 3: 0.5, 1.32 mg, 1.12 mg, 1.49 mg, and 100 g of the powder product, respectively.
Breastfeeding milk containing 3.42 mg and 0.45 mg can stimulate the growth of Bifidobacterium bifidumum Ti, which is a characteristic bacterium in the intestines of breast-fed infants, and as a result, serum fatty acids. It is also reported that the composition is similar to that of breast-fed infants (Japanese Patent Publication No. 3-35894). However, this action and effect are manifested only at one specific blending ratio, and the same action and effect cannot always be expected if the blending ratio is changed. In addition, changes in serum fatty acid composition were observed in babies who infused infant formula containing specific amounts of adenosine monophosphate, cytidine monophosphate, guanosine monophosphate, uridine monophosphate, and inosine monophosphate. Even so, the significance of this, that is, the specific effect on the growth of the infant, remains unclear without any mention. Also, considering that the difference in the composition and content of nucleotides contained in human milk and animal milk is one of the major nutritional differences between them, the composition and content of nucleotides have a significant physiological effect. It is expected that it will be a factor that influences.

However, the effect of nucleotides on changes and functions of fatty acid composition in tissues and organs such as the brain is completely unknown.

On the other hand, polyunsaturated fatty acids such as arachidonic acid and docosahexaenoic acid are contained in the brain in a large amount and are known to be deeply involved in the functions of the brain and nervous system (L. Svenne.
r Holm; J, Lipid Resi, 9.570, 1968). These polyunsaturated fatty acids are synthesized in the body using linoleic acid or α-linolenic acid as a starting material, but humans including infants do not have sufficient synthetic ability and need to be taken orally. There is also an opinion. A technique has been disclosed in which these polyunsaturated fatty acids are orally ingested to increase these polyunsaturated fatty acids in the brain and further improve learning ability (JP-A-1-153629). .. Attempts have also been made to fortify polyunsaturated fatty acids in baby milk using fish oils such as sardine oil, but these fish oils contain large amounts of eicosapentaenoic acid, which is rarely found in breast milk, and prostaglandin. It has been shown to have potential adverse effects on gin metabolism and platelet aggregation. (ESPGAN Com
mittee on Nutrition Acta Pae diatr.scond; 80.887 1
991) Although attempts to ingest polyunsaturated fatty acids orally have been made in the past, methods for ingesting substances that promote polyunsaturated fatty acid synthesis activity, rather than direct ingestion, have been investigated. Not not.

[0007]

DISCLOSURE OF THE INVENTION The present inventors have diligently studied nucleotides in view of the above-mentioned conventional circumstances,
It was discovered that a specific nucleotide mixture is deeply involved in lipid metabolism without the involvement of intestinal bacteria and affects the fatty acid composition in tissues in vivo, particularly in the brain, and based on this, the present invention was completed.

The present invention changes the fatty acid composition in living tissues, particularly in the brain, by using nucleotides, and increases polyunsaturated fatty acids, particularly ω3 fatty acids, thereby improving the learning ability of the brain. It is an object of the present invention to provide a nutritional composition that promotes functional improvement of the nervous system.

[0009]

This object is achieved by the following means. That is, the present invention comprises, as an active ingredient, a nucleotide mixture containing at least cytidine monophosphate and containing at least one of uridine monophosphate, adenosine monophosphate, guanosine monophosphate, and inosine monophosphate. The present invention relates to an agent for increasing ω3 fatty acid in living tissue, wherein the present invention provides at least 1.5 m% or more of cytidine monophosphate per solid weight of the nutritional composition, and uridine monophosphate and adenosine monophosphate. 1.5 mg of one or more of phosphoric acid, guanosine monophosphate, and inosine monophosphate
A nucleotide-enriched nutritional composition having the action of increasing ω3 fatty acid in living tissue, which is obtained by adding the above.

In the present invention, cytidine monophosphate is 1.5 to 55 m%, uridine monophosphate is 0 to 20 m%, and adenosine monophosphate is 0 to 15 m based on the solid weight of the nutritional composition.
%, 0-15 m% guanosine monophosphate, 0-15 m% inosine monophosphate
It is a nucleotide-enriched nutritional composition characterized by containing it in a range of 120 m%.

According to the present invention, when an appropriate amount of a specific type of nucleotide is administered, the fat metabolism system is affected by a specific mechanism of action, and the fatty acid composition of tissues in the living body, particularly the brain, is changed. It was made based on the discovery that the omega series fatty acids of omega series specifically increase. This action effect is completely different from the prior art in that intestinal bacteria are not involved. According to the omega-3 fatty acid increasing agent and nutritional composition of the present invention,
It is possible to encourage the nervous system to improve its function, and to improve learning ability, for example. When applied as a nutritional composition to infant formula, oral or enteral nutritional agents, effects such as infant brain development, patient brain and nerve function recovery can be obtained without any problems in intake.

The present invention will be described in detail below.

First, the increase in ω3 fatty acid in living tissue achieved by the present invention will be described.

The term “in living tissue” does not mean that it is in serum or the like. Japanese Patent Publication No. 3-358 described in the prior art
No. 94 nucleotide-added artificial milk is one in which the nucleotides of the milk affect the intestinal flora and promote the growth of Bifidobacterium, resulting in a change in the fatty acid composition in serum. On the other hand, in the present invention, the involvement of intestinal bacteria is not required, and the involvement in the fat metabolism system itself changes the fatty acid composition in the living tissue rather than in the serum, which is a big difference. ..

That is, the fatty acid in serum and the fatty acid in tissue are not the same. Fatty acids in tissues undergo fat metabolism,
It is accumulated, and it takes a certain amount of time for changes to become apparent. It is believed that the nucleotide mixture according to the present invention stimulates specific polyunsaturated fatty acid synthesis activity.

However, the action of increasing ω3 fatty acid in living tissue according to the present invention does not mean that it is not involved in the change of fatty acid composition in serum, and that the action of fatty acid in serum causes the same change as fatty acid in living tissue. Conceivable.

Further, it is the brain where the effect of nucleotides is remarkably expressed in living tissues. In the rat experiment (described later in Examples), polyunsaturated fatty acids of cerebral cortical fatty acids were significantly increased, and in particular, ω3 fatty acids were increased.

That is, arachidonic acid, which is a ω6 type polyunsaturated fatty acid, and docosahexaenoic acid, which is a ω3 type polyunsaturated fatty acid, increase, but the ω6 / ω3 ratio decreases. It is known that the ω3 system is closely related to the production of physiologically active substances such as prostaglandins, which is different from the ω6 system. In order to improve the functions of the brain and nervous system, it is effective to increase the ω3 system together with the increase of polyunsaturated fatty acids.

The polyunsaturated fatty acids are linoleic acid (18: 2), α-linolenic acid (18: 3), arachidonic acid (20: 4) and eicosapentaenoic acid (20:
5), docosahexaenoic acid (22: 6), and other unsaturated fatty acids having two or more double bonds in the molecule. Linoleic acid and arachidonic acid are ω6 series, α-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid are ω3. It is a system. Although the omega series is represented by the position of the double bond from the end opposite to the -COOH end, the difference between the ω6 system and the ω3 system is related to the susceptibility to omega oxidation and the like, and has different physiological activities.

Administration of the ω3 fatty acid increasing agent in the living tissue of the present invention increased polyunsaturated fatty acids in the cerebral cortex from 16.1% in the control to 21.2 to 28.3% in rats, and ω6 / Ω3 ratio is 0.9 to 1.0,
The ability of synthesizing 3 series fatty acids was higher than that of ω6 series (Examples described later). As a result, the brain and nerve functions are improved, and the learning ability is improved, which is an epoch-making effect.

Next, the nucleotide according to the present invention will be described. This nucleotide contains at least cytidine monophosphate (CMP) and contains uridine monophosphate (UMP).
MP), adenosine monophosphate (AMP), guanosine monophosphate (GMP), and inosine monophosphate (IMP). The same effect can be obtained when nucleotides are added in the free form or in the form of sodium salt or potassium salt.
However, when the sodium salt or potassium salt of nucleotide is used, it is necessary to adjust the addition amount in consideration of the contained salt.

CMP, UMP, AMP, GMP, IMP
The molar ratio and the like are not particularly limited and can be set in a relatively wide range. However, CMP is an essential component, and at least one other kind is added to it.

In the rat experiment, the required expression amount of nucleotides is at least 1.5 m% or more of cytidine monophosphate based on the solid weight of feed, and uridine monophosphate, adenosine monophosphate, guanosine monophosphate, and inosine monophosphate. It was necessary to add 1.5 mg% or more of one or more kinds of phosphoric acid. That is, of the nucleotides, the amount of cytidine monophosphate is specifically important for the ability to synthesize ω3 fatty acids, and is required to be 1.5 m% or more (as solid matter) in the feed. Furthermore, in a limited manner, cytidine monophosphate is 1.5 to 55 m%, uridine monophosphate is 0 to 20 m%, adenosine monophosphate is 0 to 15 m%, and guanosine monophosphate is 0, based on the solid weight of feed. 〜15m%, inosine monophosphate 0 ~ 15m% nucleotide mixture 5 ~ 120
It was found that the inclusion in the range of m% is preferable for improving the learning ability. This amount is higher than conventional nucleotide-added artificial milk. For example, the above-mentioned Japanese Patent Publication 3-35
In 894, cytidine monophosphate is 1.12 mg / 100.
g, and the compounding ratio of each nucleotide was strictly defined. In order to affect the fat metabolism system and improve brain and nerve functions, more nucleotides than the amounts conventionally used are generally required. In the prior art, since the relationship between nucleotides and polyunsaturated fatty acids in the tissue was not recognized, it was not added more nucleotides than necessary, the improvement of the desired effect was not observed even if added a lot, Moreover, even if it was added accidentally, the recognition of the action and effect in the present invention was completely lacking.

The most preferred combination is one containing all the above nucleotides. Especially cytidine monophosphate is 3.
0-55 mg, uridine monophosphate 2.0-20 mg,
Adenosine monophosphate 1.5 to 15 mg, guanosine monophosphate 0.5 to 15 mg, inosine monophosphate 0.5
It is good to be in the range of 10 mg.

Although the above findings were surprising, the interaction between cytidine monophosphate and four other nucleotides, the mechanism of action involved in fatty acid synthesis, etc. are not clear.

Even if the amount of nucleotides added is increased more than necessary, no further improvement in brain and nerve functions such as learning ability is observed, and a umami taste is exhibited, which affects the taste of food. become. In particular, in order to administer nucleotides to rats by free feeding, adverse taste effects that prevent free intake must be eliminated.

The feed is a nutritional composition, and for humans, it can be used as, for example, various pathological diets, oral or enteral nutrition for preoperative and postoperative patients, modified milk for infants and the like. A desired nucleotide-enriched nutritional composition can be obtained by adding each nucleotide to these within the above range. By ingesting this with each meal, a certain amount of nucleotides can be ingested. Here, the nutritional composition means a protein, fat, carbohydrate, mineral, vitamin, etc., and may be in any form such as powder, granule, solid, liquid, semi-liquid or emulsion.

The preferable blending amount of each of the above-mentioned nucleotides is in terms of solid matter.
It may be diluted to about 50%. For example, 13
0.2% to 7.2 mg per 100 ml when the concentration is defined as%
Cytidine monophosphate, 0-2.6 mg uridine monophosphate, 0-2.0 mg adenosine monophosphate, 0-2.0
It consists of mg guanosine monophosphate, 0-2.0 mg inosine monophosphate. In particular, cytidine monophosphate is 0.4-
7.2 mg, uridine monophosphate 0.2-2.0 mg,
Adenosine monophosphate is preferably 0.2 to 2.0 mg, guanosine monophosphate is 0.06 to 2.0 mg, and inosine monophosphate is 0.06 to 2.0 mg.

On the other hand, a form not used as a nutritional composition is also possible. For example, a nucleotide mixture can be formulated as an active ingredient. That is, if necessary, excipients, emulsifiers, binders, taste components, pigments, etc. may be added to the nucleotide mixture and molded into capsules, tablets, granules or the like. In the formulated form, it is possible to take nucleotides independently of feeding behavior, and
This is convenient because there are almost no taste restrictions.
Further, the content can be freely set. However, the brain,
It is necessary to take a certain amount or more to improve the nerve function. 0.8 to 12 mg / 1 per 100 g body weight in rats
Daily intake produced favorable results. If the amount is too large, it is not required to improve the effect. The above-mentioned nucleotide addition amount range is based on the assumption that nucleotides will be taken in each meal in principle, and there is no problem with infant formulas used in place of breast milk, but in other cases. ,
That is, it is not possible to secure the required amount of nucleotide intake when separately ingested as a dietary supplement. Therefore, if the formulated nucleotide is used, it can be easily ingested separately from the meal, and thus has high utility. In the case of humans, it can be said that a preferable intake amount is about 5 to 260 mg / kg body weight per day.

A typical example of the use as a nutritional composition is infant formula. In this case, it may be possible to promote the brain development of the infant and improve the learning ability. However, the modified milk in this case does not contain the nucleotide mixture in order to approach the components of human milk (human milk). Incidentally, the average nucleotide content of breast milk was 1.2 mg / 100 g of cytidine monophosphate, 1.1 mg / 100 g of uridine monophosphate, 1.2 mg / 100 g of adenosine monophosphate, and 0 mg of guanosine monophosphate in terms of solid content. .3
mg / 100 g, inosine monophosphate 0.3 mg / 100
It is about g and partially overlaps with that of the present invention, but is different as a whole, and particularly, the content of cytidine monophosphate is low.

The ω3 fatty acid increasing agent in the biological tissue and the nutritional composition described above can be produced by known techniques. At this time, it may be carried out properly in consideration of the fact that the nucleotide is decomposed by phosphatase, that the phosphatase is easily inactivated by heat, and that the nucleotide has relatively heat resistance.

Since the development of brain and nerve function improvement occurs after a process of fat metabolism and accumulation in the body, it usually takes about 14 to 21 days after the start of ingestion of nucleotides.

[0033]

EXAMPLES Examples of the present invention will be shown below to clarify the effects thereof. Example 1 Casein 25.0%, Soybean oil 6.0%, Corn starch 51.5%, Sucrose 3.0%, Cellulose powder 8.
0%, mineral mixture 3.5%, vitamin mixture 1.0
The basic composition is 100% feed, and 100 g of this basic feed
Per cytidine monophosphate 26.0 mg, uridine monophosphate 2.8 mg, adenosine monophosphate 4.8 mg, guanosine monophosphate 3.2 mg, inosine monophosphate 3.2 mg
Rats (SD females, 4 weeks old) were allowed to freely ingest the feed prepared by adding the above, and then phospholipid fraction fatty acid analysis of the cerebral cortex was performed to compare it with the nucleotide-free feed intake group. The results shown in Table 1 were obtained. The total amount of nucleotides ingested by the rat was calculated to be 4.8 mg / 100 g / day per day based on 100 g of body weight.

[0034]

[Table 1] As for the phospholipid fatty acid composition of the cerebral cortex, it was confirmed that the content of polyunsaturated fatty acids such as arachidonic acid and docosahexaenoic acid increased and the ratio of ω6 fatty acid / ω3 fatty acid decreased, and that the ratio of saturated fatty acid and unsaturated fatty acid was nucleotide addition. It was also confirmed that there were differences such as low in the groups. Furthermore, similar rats (5 in each test group) were allowed to freely take a test meal having the above-mentioned composition.
We conducted a study on the learning ability using the water maze. In the test, the rat was allowed to swim from one point in the maze, the time required for finding and reaching the end point was measured, and the number of trials for memorizing the maze was determined. This test method was performed according to Yonekubo's method (Food Chemistry, 161, 47, 1991). Swimming was carried out 8 times a day for 4 days.
In the nucleotide-added group, the average was 13 seconds in the third trial on the second day, and the arrival time did not increase thereafter, and a maze was remembered, whereas in the nucleotide-free group, the arrival time after the fourth trial on the third day was reached. No increase was observed. It is considered that the intake of nucleotide increased the polyunsaturated voluntary acid in the brain and further affected the learning ability. Example 2 The same basic composition of feed as in Example 1 was supplemented with cytidine monophosphate 5
0.8 mg, uridine monophosphate 15.4 mg, adenosine monophosphate 11.6 mg, guanosine monophosphate 11.
The same study as in Example 1 was carried out by adding a nucleotide mixture consisting of 6 mg and 11.6 mg of inosine monophosphate. Rat total nucleotide intake is 12 mg / 100
It was g / 1 day. The fatty acid composition of the cerebral cortex was as shown in Table 2.

[0035]

[Table 2] Effects such as an increase in polyunsaturated fatty acids and a relative decrease in the ratio of ω6 fatty acid / ω3 fatty acid were observed as compared with the group of Example 1 in which no nucleotide was added. In addition, as a result of the water maze test, it was confirmed that in this experimental group, the maze was learned in the second trial on the second day.

Further, the amount of each nucleotide added was adjusted to
When a doubled feed was prepared and a study was conducted, a fatty acid composition similar to the above example was obtained, and the results of the water maze test were also similar. However, in this case, because of the umami derived from nucleotides, a decrease in taste is observed as a result of the sensory evaluation,
The rat's free intake behavior was suppressed and the total nucleotide intake was 18 mg / 100 g / day, which did not reach the above double level. Example 3 In the feed having the same basic composition as in Example 1, 3.0 mg of cytidine monophosphate, 2.3 mg of uridine monophosphate, 1.5 mg of adenosine monophosphate, 0.7 mg of guanosine monophosphate,
A similar study to Example 1 was carried out with the addition of a nucleotide mixture consisting of 0.7 mg of inosine monophosphate. The total nucleotide intake of the rat was 1.0 mg / 100 g / day. The fatty acid composition of the cerebral cortex was as shown in Table 3.

[0037]

[Table 3] Effects such as an increase in polyunsaturated fatty acids and a relative decrease in the ratio of ω6 fatty acid / ω3 fatty acid were observed as compared with the group of Example 1 in which no nucleotide was added. In addition, as a result of the water maze test, it was confirmed that in the present experimental group, the maze was learned in the fourth trial on the second day. Example 4 To the feed having the same basic composition as in Example 1, 1.5 mg of cytidine monophosphate, 1.5 mg of uridine monophosphate, 1.5 mg of adenosine monophosphate, 1.5 mg of guanosine monophosphate,
The same study as in Example 1 was conducted by adding 1.5 mg of inosine monophosphate (total nucleotide intake was 0.9 mg /
100 g / 1 day). The fatty acid composition of the cerebral cortex was as shown in Table 4.

[0038]

[Table 4] Effects such as an increase in polyunsaturated fatty acids and a relative decrease in the ratio of ω6 fatty acid / ω3 fatty acid were observed as compared with the group of Example 1 in which no nucleotide was added. In addition, as a result of the water maze test, it was confirmed that in the present experimental group, the maze was learned in the fifth trial on the second day. Example 5 In a feed having the same basic composition as in Example 1, cytidine monophosphate 3.0 mg, uridine monophosphate 0.0 mg, adenosine monophosphate 0.0 mg, guanosine monophosphate 2.0 mg,
The same study was performed as in Example 1 with the addition of 1.9 mg inosine monophosphate (total nucleotide intake 0.8 mg /
100 g / 1 day). The fatty acid composition of the cerebral cortex was as shown in Table 5.

[0039]

[Table 5] Effects such as an increase in polyunsaturated fatty acids and a relative decrease in the ratio of ω6 fatty acid / ω3 fatty acid were observed as compared with the group of Example 1 in which no nucleotide was added. In addition, as a result of the water maze test, it was confirmed that in the present experimental group, the maze was learned in the eighth trial on the second day. Example 6 4.0 mg of cytidine monophosphate, 0.9 mg of uridine monophosphate, 2.0 mg of adenosine monophosphate, 0 mg of guanosine monophosphate, 0 mg of inosine monophosphate were added to a feed having the same basic composition as in Example 1. The same study as in Example 1 was conducted (total nucleotide intake was 0.8 mg / 100 g).
/ 1 day). The fatty acid composition of the cerebral cortex was as shown in Table 6.

[0040]

[Table 6] Effects such as an increase in polyunsaturated fatty acids and a relative decrease in the ratio of ω6 fatty acid / ω3 fatty acid were observed as compared with the group of Example 1 in which no nucleotide was added. In addition, as a result of the water maze test, it was confirmed that the maze was learned in the seventh trial on the second day in the experimental group. Comparative Example 1 1.1 mg of cytidine monophosphate, 3.4 mg of uridine monophosphate, 1.7 mg of adenosine monophosphate, 1.5 mg of guanosine monophosphate were added to the feed having the same basic composition as in Example 1.
The same study as in Example 1 was conducted by adding 0.45 mg of inosine monophosphate (total intake of nucleotides was 1.0 mg).
/ 100 g / 1 day). The fatty acid composition of the cerebral cortex was as shown in Table 7.

[0041]

[Table 7] An increase in polyunsaturated fatty acids was recognized as compared with the nucleotide-free group of Example 1, but the ω6 fatty acid / ω3 fatty acid ratio was almost the same as that of the nucleotide-free group. In addition, as a result of the water maze test, in this experimental group, 3rd day 3
It was confirmed that the maze was learned in the second trial, and no significant difference in learning ability was observed between the nucleotide-free group and this experimental group. It is considered that this is because the total nucleotide intake was almost the same as that of the example of the present invention, but the intake of cytidine monophosphate was small.

[0042]

INDUSTRIAL APPLICABILITY The nutritional composition prepared according to the present invention increases polyunsaturated fatty acids such as arachidonic acid and docosahexaenoic acid in the brain, particularly ω3 fatty acids, and further functions of the brain and nervous system such as learning. It becomes possible to promote the development of ability.

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[Procedure amendment]

[Submission date] May 13, 1992

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be corrected] Claim 2

[Correction method] Change

[Correction content]

[Procedure Amendment 2]

[Document name to be amended] Statement

[Name of item to be corrected] Claim 3

[Correction method] Change

[Correction content]

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0009

[Correction method] Change

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[0009]

This object is achieved by the following means. That is, the present invention comprises, as an active ingredient, a nucleotide mixture containing at least cytidine monophosphate and containing at least one of uridine monophosphate, adenosine monophosphate, guanosine monophosphate, and inosine monophosphate. The present invention relates to an agent for increasing ω3 fatty acid in biological tissue, wherein the present invention provides at least 1.5 mg% or more of cytidine monophosphate based on the solid weight of the nutritional composition, and
1.5m of one or more of uridine monophosphate, adenosine monophosphate, guanosine monophosphate, and inosine monophosphate
A nucleotide-enriched nutritional composition having an action of increasing ω3 fatty acid in biological tissue, which is obtained by adding g % or more.

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] 0010

[Correction method] Change

[Correction content]

In the present invention, cytidine monophosphate is 1.5 to 55 mg %, uridine monophosphate is 0 to 20 mg %, and adenosine monophosphate is 0 to 15 per solid weight of the nutritional composition.
m g%, guanosine monophosphate 0~15m g%, nucleotide enhanced nutritional composition characterized in that inosine monophosphate is contained in a range of 5~120m g% a more composed nucleotide mix 0~15m g% Is.

[Procedure Amendment 5]

[Document name to be amended] Statement

[Name of item to be corrected] 0023

[Correction method] Change

[Correction content]

In the rat experiment, the required expression amount of the effect of nucleotide is at least 1.5 mg % or more of cytidine monophosphate per solid feed weight, and uridine monophosphate, adenosine monophosphate, guanosine monophosphate and inosine. It was necessary to add 1.5 mg% or more of one or more kinds of monophosphoric acid. That is, among nucleotides, the amount of cytidine monophosphate is specifically important for the ability to synthesize ω3 fatty acids, and is required to be 1.5 mg % (as solid matter) or more in the feed. Further, in a limited manner, cytidine monophosphate is 1.5 to 55 mg %, uridine monophosphate is 0 to 20 mg %, and adenosine monophosphate is 0 to 15 per solid weight of feed.
m g%, guanosine monophosphate 0~15m g%, of those which contain nucleotides mixture inosine monophosphate is formed of 0~15m g% in the range of 5~120m g% preferably relates improve learning ability results It appeared. This amount is higher than conventional nucleotide-added artificial milk. For example, in Japanese Patent Publication No. 3-35894, the cytidine monophosphate is 1.
It was 12 mg% , and the compounding ratio of each nucleotide was strictly defined. In order to affect the fat metabolism system and improve brain and nerve functions, more nucleotides than the amounts conventionally used are generally required. In the prior art, since the relationship between nucleotides and polyunsaturated fatty acids in the tissue was not recognized, it was not added more nucleotides than necessary, the improvement of the desired effect was not observed even if added a lot, Moreover, even if it was added accidentally, the recognition of the action and effect in the present invention was completely lacking.

[Procedure correction 6]

[Document name to be amended] Statement

[Correction target item name] 0024

[Correction method] Change

[Correction content]

The most preferred combination is one containing all the above nucleotides. Especially cytidine monophosphate is 3.
0-55mg % , uridine monophosphate 2.0-20mg
% , Adenosine monophosphate is 1.5 to 15 mg % , guanosine monophosphate is 0.5 to 15 mg % , and inosine monophosphate is 0.5 to 10 mg % .

[Procedure Amendment 7]

[Document name to be amended] Statement

[Name of item to be corrected] 0030

[Correction method] Change

[Correction content]

A typical example of the use as a nutritional composition is infant formula. In this case, it may be possible to promote the brain development of the infant and improve the learning ability. However, the modified milk in this case does not contain the nucleotide mixture in order to approach the components of human milk (human milk). In this connection, the average nucleotide content cytidine monophosphate 1.2 mg% in terms of solid content of the milk, uridine monophosphate 1.1 mg%, 1.2 mg adenosine monophosphate
%, Guanosine monophosphate 0.3 mg%, inosine monophosphate 0.3 mg% approximately, are different from the whole but not overlap those with a part of the present invention, especially cytidine monophosphate-containing low It has become a thing.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Masaharu Shimatani 3-1-2 Shinsayama, Sayama City, Saitama Prefecture Residence 303 Shinsayama (72) Inventor Tadashi Iwata 6083 No. 7 Furuyagami, Kawagoe City, Saitama Prefecture Kawagoe Green Park L1-207

Claims (3)

[Claims] 1. A nucleotide mixture containing at least cytidine monophosphate and at least one of uridine monophosphate, adenosine monophosphate, guanosine monophosphate and inosine monophosphate as an active ingredient. An agent for increasing ω3 fatty acid in living tissue, which is characterized in that 2. At least 1.5 m% of cytidine monophosphate based on the solid weight of the nutritional composition, and at least one of uridine monophosphate, adenosine monophosphate, guanosine monophosphate, and inosine monophosphate. A nucleotide-enriched nutritional composition having an action of increasing ω3 fatty acid in living tissue, which is obtained by adding 1.5 mg% or more. 3. Cytidine monophosphate is 1.5 to 55 m% and uridine monophosphate is 0 to 20 m based on the solid weight of the nutritional composition.
%, Adenosine monophosphate 0-15m%, guanosine monophosphate 0-15m%, inosine monophosphate 0-15m
% Of the nucleotide mixture is contained in the range of 5 to 120 m%.