JPH03251154A - Composition for supplying nutrition - Google Patents

Abstract

PURPOSE:To obtain a nutrition supplying composition suitable for patients of muscular dystrophy, comprising a given amount of oligopeptide mixture having a specific composition prepared by hydrolyzing animal protein with an enzyme, by controlling the blended amount of each of nitrogen compound, carbohydrate and lipid. CONSTITUTION:Animal protein is hydrolyzed with an enzyme (e.g. endoprotease or exoprotease) to produce an oligopeptide mixture which has 200-5,000 average molecular weight, <=35wt.% free amino acid, a molar ratio of branched-chain amino acid/aromatic amino acid of >=7 and an amino acid composition wherein an amount of brnched-chain amino acid is 15-25wt.% and an amount of aromatic amino acid is 0.1-2.5wt.%. Then 5-70wt.% oligopeptide substance (dried weight) is blended with a nitrogen compound, a carbohydrate and a lipid so as to give 10-90wt.% nitrogen compound, 10-80wt.% carbohydrate and 0-15wt.% lipid to produce a nutrition supplying composition.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a nutritional supplement composition, and more specifically, a nutritional supplement composition particularly suitable as a nutritional supplement or therapeutic food for patients with muscular dystrophy or during biological invasion. relating to things.

Conventional technology and its problems Muscular dystrophy (PMD) is a group of diseases that have a primary disease in the muscles themselves.They are mainly characterized by progressive degeneration of skeletal muscles, and develop on a genetic basis. It is a disease. Examining the amino acid composition in the blood of muscular dystrophy patients, even when protein intake sufficiency is not necessarily poor, the ratio of essential amino acids to non-essential amino acids (E/N ratio), which is an indicator of malnutrition, is reduced. An abnormality in protein amino acid metabolism is considered. In addition, it has been reported that the concentration of branched chain amino acids (BCAA: valine, leucine, isoleucine, etc.) in the blood is lower than that of normal humans (Kumiko Hirano, Bulletin of the Faculty of Life Sciences, Osaka University, 34).
; 253-259.1986) This report suggests the need to increase the BCAA concentration in the blood. Furthermore, there is a report that BCAA supplementation has the effect of suppressing muscle decline in patients with amyotrophic lateral sclerosis (ALS), a type of muscular dystrophy.
Plailakis A, N al: Lancet, M
ay 7; 1015-1018.1988).

In addition, in order to prolong the lives of patients with muscular dystrophy, it is necessary to provide sufficient energy and protein to slow down weight loss, but it is not easy to increase the amount of food eaten by patients with occlusal disorders. , single-dose high-energy, high-protein supplementation is required.

On the other hand, during times of stress, especially surgical invasion, wounds, burns,
A typical metabolic change during biological invasion, such as during sepsis, is increased catabolism of protein metabolism. In other words, body proteins such as skeletal muscle, visceral smooth muscle, and subcutaneous collagen tissue are broken down and consumed as an energy source, while at the same time acute-phase proteins (fibrinogen, haptoglobin,
Although it is reused for the biosynthesis of lysosomal enzymes, etc., it is generally used for proteolysis. As a result, urinary nitrogen excretion increases, nitrogen balance takes on a negative value, leading to weight loss and weakening recovery ability.

Goldberg (A, L, Goldberg)
are mainly branched-chain amino acids (B
CAA), a series of i
In the n viHo experiment, we reported for the first time that BCAA has the effect of inhibiting muscle protein breakdown or promoting synthesis.

Blackburn (G, L, B Iackbur
n) Raya Fisch
Since the late 1970s, using various invasive animal models, they have shown that protein metabolism during stress can be improved by administering an amino acid infusion with a high BCAA content.

Based on the results of these tests, in the 1980s B
An amino acid infusion containing a high concentration of CAA was prototyped and tested in the clinic, and clinically it was confirmed that it has a significant nutritional effect under stress.

Based on these findings, it is desired to develop nutritional foods with a high BCAA content for patients with muscular dystrophy or for use during biological invasion. However, conventional nutritional supplements containing amino acids as a protein source have problems such as excessively high osmotic pressure and the unique odor and bitterness of amino acids, making them unsuitable as oral nutritional supplements for humans.

The present invention has been made in view of the above-mentioned problems of the prior art, and its purpose is to enable oral and enteral administration such as through a tube, to achieve physiological digestion and absorption, and to have a high osmotic pressure. This is a nutritional supplement composition that can avoid the occurrence of diarrhea caused by food poisoning, and has no irritation or foreign taste, and that by ingesting the composition, amino acid imbalance in the blood can be corrected, and the nutritional status can be improved. It is an object of the present invention to provide a nutritional composition that can be used as a nutritional supplement.

Means for Solving the Problems The present inventor has conducted extensive research in order to achieve the above object. As a result, we have changed manufacturing conditions by hydrolyzing various animal and plant proteins with endopeptidase and exopeptidase to liberate aromatic amino acids (AAA: phenylalanine, tyrosine, etc.), and removing them by adsorption with synthetic adsorbents, activated carbon, etc. , ■ average molecular weight, ■ molar ratio (branched chain amino acids/aromatic amino acids), ■ characteristics of branched chain amino acids, ■ aromatic amino acid content, and ■ free amino acid content. A composition in which a predetermined amount of an oligopeptide mixture with a specific composition obtained by hydrolysis using a peptide is blended, and the blended amounts of total nitrogen compounds, carbohydrates, and lipids as a protein source are adjusted to a predetermined ratio is as follows. It has been found that it is effective as a nutritional composition that meets the purpose. By using the composition, the amino acid pattern in plasma and branched chain amino acids/
The molar ratio of aromatic amino acids (Fisher ratio) is corrected, maintaining the nutritional status of muscular dystrophy patients,
It is possible to delay the progression of the disease, increase resistance to complications and sequelae, and prolong life.Furthermore, by administering the nutritional composition, it is possible to suppress the breakdown of body proteins during biological invasion and to increase resistance to complications and sequelae. It has been found that the effect of promoting protein synthesis is exerted. The present invention was completed based on these findings.

That is, the present invention provides an average molecular weight of 1200 to 5000. Free amino acids are 35% by weight or less, (branched chain amino acids/aromatic amino acids) molar ratio is 7 or more, branched chain amino acids are 15 to 25% by weight and aromatic amino acids are 0.1 to 2% by weight in the total amino acid composition. ．．
5% oligopeptide mixture on a dry weight basis.
~70% by weight of the composition, wherein the content of total nitrogen compounds, carbohydrates, and lipids as a protein source in the composition is 10 to 90% by weight of nitrogen compounds on a dry weight basis.
, a nutritional supplement composition characterized by 10 to 80 weight percent carbohydrates and 0 to 15 weight percent lipids, a nutritional supplement composition for muscular dystrophy disease patients having the above composition, and a biologically invasive composition having the above composition. The present invention provides a nutritional supplement composition for use in the human body.

The oligopeptide mixture used in the present invention has an average molecular weight of 2
00 to 5,000, preferably 200 to 3,000. If the average molecular weight is less than 200, an amino acid taste will occur and the osmotic pressure will increase. Oligopeptide mixtures with an average molecular weight of 200 to 5,000 are easier to digest than proteins and amino acids.
It is characterized by rapid absorption and a better flavor than amino acids.

The oligopeptide mixture used in the present invention is BCAA/AA
The molar ratio of A is 7 or more, preferably 10 or more, more preferably 20 or more, and practically 45 or less. Oligopeptides made by simply enzymatically decomposing animal and plant proteins have a BCAA/AAA molar ratio of less than 7, but the oligopeptide mixture used in the present invention has a BCAA/AAA ratio of less than 7 by treating the protein hydrolyzate with an adsorbent. The molar ratio of AAA is as high as 7 or more.

The oligopeptide mixture used in the present invention contains 15 to 25% by weight of BCAA in the total amino acid composition, preferably 17 to 2% by weight.
5% seedlings is appropriate. Patients suffering from muscular dystrophy have low levels of BCAA in their blood, so it is effective to supplement them with BCAA. Furthermore, protein metabolism is improved by supplementing BCAA during biological invasion. The oligopeptide mixture used in the present invention has the effect of replenishing BCAA.

The oligopeptide mixture used in the present invention contains 0.1 to 2.5% by weight of AAA in the total amino acid composition, preferably 0.1% by weight.
~2.0% by weight is suitable. In patients with muscular dystrophy disease or when a living body is invaded, BCAA in the blood decreases and AAA increases, so it is necessary to reduce the supply of AAA. The oligopeptide mixture of the present invention has a low AAA content of 2.5% by weight or less.

In the oligopeptide mixture used in the present invention, since methionine has a bad odor, it is suitable to have a low concentration, and preferably the methionine content in the total amino acid composition is 0.5 to 1.
5% by weight, more preferably 0.5-1.2% by weight is suitable.

The oligopeptide mixture used in the present invention has a free amino acid content of 35% by weight or less, preferably 30% by weight or less, more preferably 15% by weight or less.

Although it is preferable to have as few free amino acids as possible, in the process of obtaining the oligopeptide mixture of the present invention, (1) enzymatic decomposition using a combination of endoprotease and exoprotease to extremely reduce bitterness, and (2) adsorption to adsorb and remove AAA. Because of the chemical treatment, less than 35% free amino acids are produced.

Furthermore, since the oligopeptide mixture used in the present invention is obtained by enzymatically decomposing proteins in the neutral (pH 6 to 8) range, it exhibits neutrality and can be used as is for muscular dystrophy diseases without separate pH adjustment. Alternatively, it can be used as a protein source in food or preparations for biological invasion.

The oligopeptide mixture used in the present invention has almost no bitterness and has a good flavor with umami, compared to the bitterness of conventionally known protein hydrolysates.

The reason for this is that the oligopeptide mixture of the present invention is obtained by simultaneously acting endoprotease and exoprotease on proteins, and the adsorbent treatment removes not only AAA components but also odor components, taste components, color components, etc. This is because they are also adsorbed and removed.

Therefore, whereas commercially available protein hydrolysates have a strong bitter taste (and are difficult to administer orally even when used as nutritional supplements), the oligopeptide mixture used in the present invention has the advantage of being easy to administer orally.

It is also whiter in color than that obtained by simply hydrolyzing protein.

The oligopeptide mixture used in the present invention as described above is
It can be obtained by enzymatically decomposing a protein in an aqueous system using endoprotease and exoprotease in a neutral range, treating it with an adsorbent, concentrating it if necessary, and drying it.

Examples of animal and vegetable proteins used as raw materials for the oligopeptide mixture include casein, egg white, albumin, kolaken, and gelatin, and examples of vegetable proteins include soybean protein, wheat protein, and barley protein. Examples include grain proteins such as adzuki bean protein, rye protein, corn protein, Zein, which is a prolamin protein that constitutes corn protein, and seaweed proteins such as kelp. Among these animal and plant proteins, preferably vegetable proteins with a low methionine content are suitable because the methionine content can be lowered through enzymatic decomposition and adsorption steps. Some animal proteins have a low methionine content, but vegetable proteins have a lower methionine content and a higher BCAA content than animal proteins, and soy protein in particular not only has a low methionine content but also a high BCAA content.
Since it has a high AA content, is industrially stable and easily available, it is suitable as a source for the oligopeptide mixture of the present invention.

In the present invention, among the above-mentioned protein raw materials, a protein raw material in which the methionine content of the oligopeptide mixture is 0.5 to 1.5% by weight (preferably 0.5 to 1.2% by weight) is suitable. .

Endoproteases and exoproteases can be used as enzymes that hydrolyze proteins. It is difficult to release AAA or AAA-rich oligopeptides using only endoproteases, and it is not possible to reduce the molecular weight of proteins using only exoproteases.
It is not possible to obtain the desired oligopeptide mixture.

In the production of an oligopeptide mixture, an oligopeptide mixture with almost no bitterness can be obtained by combining the simultaneous action of endoprotease and exoprotease and the treatment with an adsorbent described below. Normally, commercially available enzymatically digested proteins are bitter and difficult to administer orally, so they are mainly administered through the tube, but the oligopeptide mixture used in the present invention has almost no bitterness, so it can be used not only through the tube but also through the diet. It can be used as a protein source for oral preparations.

In the production of an oligopeptide mixture, endoproteases and exoproteases may be of the same or different origin and may be used in combination, but preferably they are of the same origin. For example, enzymes that have both exoprotease and endoprotease activities are more commonly found in microorganisms than in animals or plants.
derived from bacteria (P seudo genus, etc.),
Monas genus, etc.), actinomycetes (S trepjom7
ces, etc.), yeast (Saccharomyce, etc.)
Those derived from the genus S. etc.) are suitable.

Enzymatic decomposition can also be carried out in an acidic or alkaline region, but this requires a subsequent neutralization step and salts are produced, so a desalination step is required to reduce the ash content of the resulting oligopeptide mixture. , in the present invention, the neutral range (usually p
It is important to perform enzymatic decomposition at H6-8). That is, regardless of whether the optimal pH of endoprotease or exoprotease is acidic or alkaline, it is important to allow it to act in a neutral range. This is because there is no need for a subsequent neutralization step, and the resulting oligopeptide mixture also has a good flavor.

The degree of enzymatic decomposition is such that the average molecular weight of the oligopeptide mixture solution after enzymatic decomposition is 200 to 5000 (preferably 200 to 3000), and the free amino acid content is 35% by weight or less (preferably 30% by weight or less). , the temperature of action, the time of action, and the substrate/enzyme ratio can be adjusted.

The adsorbent used for producing the oligopeptide mixture is one that specifically adsorbs AAA, preferably one that also adsorbs methionine. For example, activated carbon, ion exchange resin, hydrophobic adsorption resin, etc. can be used. Adsorbent is AA
It can cover the entire circumference sufficiently to absorb A. for example,
The amount of commercially available activated carbon is approximately 20% by weight or more, preferably 50% by weight or more and 200% by weight or less based on the amount of crude protein after enzymatic decomposition. If the amount of adsorbent is too small, AAA cannot be adsorbed sufficiently, and if it is too large, a large amount of other amino acids and oligopeptides will be adsorbed, reducing the yield of the desired oligopeptide mixture.

The oligopeptide mixture solution obtained by removing the adsorbent using means such as centrifugation or filtration does not need to be neutralized and can be concentrated or dried as it is, and the ash content can be reduced to usually 15% by weight or less.

Through the above steps, the oligopeptide mixture used in the present invention can be obtained.

In addition, since these adsorbents alone are insufficient to remove aromatic amino acids, especially tyrosine, tyrosine can be further separated and removed by utilizing the low solubility properties of 1,000 rosin using isoelectric focusing methods. Aromatic amino acids can be lowered.

The oligopeptide mixture used in the present invention is obtained through the steps described above, but if necessary, after concentrating the treatment solution in the final step and adjusting the pH, acid treatment, amidase, deaminase, etc. The bitterness is reduced through enzyme treatment, and desalination treatment is performed using ion exchange membranes, ion exchange resins, etc.
It is preferable to further treat with activated carbon and evaporate to dryness to form a powder.

However, depending on the application, it can also be used as a solution.

The nutritional composition of the present invention has the above-mentioned oligopeptide mixture with the following predetermined m=, and the contents of total nitrogen compounds, carbohydrates, and lipids as protein sources are adjusted as follows. be.

That is, the blending amount of the oligopeptide mixture is 5 to 70% by weight, preferably 5 to 70% by weight, based on the dry weight of the composition of the present invention.
The content is preferably 20% by weight. In addition, the blending ratio of total nitrogen compounds, carbohydrates, and lipids as a protein source is based on the dry weight of the composition of the present invention: 10 to 90% by weight of nitrogen compounds, 10 to 80% by weight of carbohydrates, and 0 to 15% by weight of lipids. %, preferably 15 to 40% by weight of nitrogen compounds, 50 to 70% by weight of carbohydrates, and 3 to 10% by weight of lipids. The content of each of the nitrogen compounds, carbohydrates, and lipids in the composition of the present invention is the total amount of the components contained in the oligopeptide mixture and other components added.

By setting the composition of the present invention at the above-mentioned blending ratio,
It can correct the amino acid balance in the blood and improve nutritional status.

The nitrogen compound as a protein source constituting the composition of the present invention is
As long as it contains a predetermined amount of the above-mentioned specific oligopeptide mixture, the rest may be any of various known protein raw materials, amino acids, etc. Examples of the protein raw material include casein and salts such as sodium caseinate and calcium caseinate, enzymatic decomposition products of secondary caseins, soybean protein, and wheat protein enzymatic decomposition products. Furthermore, as the amino acid, branched chain amino acids such as valine, leucine, and isoleucine are preferred. These nitrogen compounds can be used singly or in combination of two or more.

From the viewpoint of nutritional effects, the nitrogen compound as a protein source is preferably blended so as to improve the amino acid score.

Furthermore, when the composition of the present invention is used as a nutritional supplement for patients with muscular dystrophy, it is preferable to incorporate taurine, which has been conventionally used as a therapeutic agent for muscular dystrophy.

The carbohydrate constituting the composition of the present invention may be any of various known carbohydrates in addition to those contained in the oligopeptide mixture, such as glucose, maltose, sucrose,
isomaltose, maltotetraose, maltotriose, maltopentaose, maltohexaose, lactose,
Examples include monosaccharides such as glycogen, dextrin, and starch, oligosaccharides, dietary fiber, and polysaccharides.

In addition to the lipids constituting the composition of the present invention, in addition to those contained in the oligopeptide mixture, various conventionally known lipids may be used, such as rice oil, cottonseed oil, corn oil, soybean oil, sunflower oil, cacao butter, sesame oil, safflower oil, peanut oil,
Any animal or vegetable oil such as butter, lard, coconut oil, nut oil, palm oil, rapeseed oil, or medium chain fatty acid (MCT) may be used, and vegetable oil is particularly preferred.

In addition to containing the above-mentioned three components as essential components, the composition of the present invention may further contain various conventional additives as required. Examples of such additives include various vitamins (
Vitamin A1 Vitamin B1, Vitamin B2, Vitamin B
6. Vitamin B12, vitamin C, vitamin D1, vitamin E1, niacin, folic acid, pantothenic acid, etc.), minerals (salts such as calcium, iron, potassium, sodium, magnesium, phosphorus, chlorine, etc.), synthetic fragrances and natural fragrances, etc. Flavorings, natural sweeteners (thaumatin, stevia, etc.)
Examples include sweeteners such as and synthetic sweeteners (saccharin, aspartame, etc.), colorants, emulsifiers, stabilizers, preservatives, etc., and each of these can be used singly or in combination of two or more.

Each of the above components is normally stored or distributed in a tightly mixed powder state sealed in a moisture-proof bag, bottle, can, etc., but if desired, it may be prepared as a liquid, Ze+J-1 granules, tablets, capsules, etc. It may be formulated in the following form.

When applying (ingesting) the nutritional composition of the present invention thus obtained, it is usually diluted with water to an appropriate concentration according to a conventional method to form a solution or jelly. This is also subjected to treatment such as heat sterilization or pressure heat sterilization as necessary.

The degree of dilution mentioned above can be determined arbitrarily, but usually when the nutritional solution is prepared in the form of a tube or oral nutritional solution, the resulting nutritional solution contains the composition of the present invention at a concentration of about 100 to 500 g/Ω, preferably about 15
The content is preferably 0 to 250 g/l.

The above nutritional solution is administered orally or directly into the stomach, duodenum or small intestine, and the jelly preparation is administered orally. The amount to be administered (intake) can be determined as appropriate depending on the disease state of the patient to whom it is administered, the intended treatment or nutritional improvement effect, etc.
- generally 30% dry weight of the composition of the invention per person per day
It is desirable to set it to about 150 g.

The composition of the present invention can also be used in conjunction with regular meals, taking into account the patient's preferences.

Effects of the Invention The nutritional supplement composition of the present invention mainly contains oligopeptides as a protein source, has a good flavor (no unpleasant bitterness, and is rapidly and well absorbed from the digestive tract). The occurrence of diarrhea due to high osmotic pressure is avoided.In addition, the blended oligopeptide mixture contains abundant branched chain amino acids and very little aromatic amino acids in its amino acid composition. , can significantly improve the amino acid pattern and Fisher ratio in plasma, and furthermore, since it contains protein sources, carbohydrates, and fats in a well-balanced manner, nutritional status can be improved.

Therefore, in patients with muscular dystrophy, ingestion of the composition of the present invention corrects the amino acid imbalance in the blood, and furthermore, it is possible to maintain a good nutritional status of the patient, delaying the progression of the disease, and causing complications and sequelae. It is possible to extend lifespan by increasing resistance to

In addition, by ingesting the composition of the present invention, the effect of suppressing body protein decomposition and promoting protein synthesis during biological invasion can be achieved, and the nutritional state can be maintained in good condition. It is also suitable for nutritional supplementation.

Example Embodiments of the present invention will be described below with reference to Examples.

Reference example 1 Isolated soybean protein (manufactured by Fuji Oil ■ [New Fuji Blow RJ)
Dissolve 100 parts by weight (hereinafter referred to as parts) in 1567 parts of water, add 2 parts of endopeptidase and a protease containing endopeptidase (pronase manufactured by Kaken Pharmaceutical Co., Ltd.), and add 5 parts by weight.
After enzymatic digestion for 5 hours at 0°C, 15 hours at 80-85°C.
After cooling to below 10°C, 100 parts of activated carbon (manufactured by Takeda Pharmaceutical Co., Ltd.) was added and stirred overnight to adsorb aromatic amino acids and oligopeptides rich in aromatic amino acids. , centrifugation (5000R, P, M, x30
minutes) to roughly remove the activated carbon, and then use a precision filtration membrane (manufactured by Asahi Kasei ■,
Completely remove activated carbon using 0.1μ) and sterilize (13
(7 seconds at 5°C) and spray-dried to obtain a powdered oligopeptide mixture. The pH of this 10% concentration aqueous solution is 6.3.
Met.

Tables 1 and 2 show the crude protein, ash, and amino acid compositions per dry solid content of the oligopeptide mixture before activated carbon adsorption (H3P) and after activated carbon adsorption (LAP).

In the table, amino acids shall follow the regulations of IUPAC, IUB or common symbols in the field, examples of which are listed below. Furthermore, in cases where optical isomers are possible for amino acids, etc., the L-isomer is not indicated unless otherwise specified.

Leu: leucine, He: isoleucine, Ala: alanine, Glu: glutamine, Thr: threonine, H
is: histidine, Ser: serine, G1y nigericin, Asn: asparaquine, Arg: arginine, Asp
: Aspartic acid, Pronibroline.

迶1 From the table above, the aromatic amino acids (AAA: phenylalanine, tyrosine), branched chain amino acids (BCAA: valine, leucine, isoleucine), BCAA/AAA molar ratio, and free amino acids (FAA) of LAP are shown in Table 3. It was as follows. In the table, AAASBCAA and methionine are in the middle of the total amino acid composition.

The molecular weight distribution shown in Table 3 was as shown in Figure 1. This measurement condition is TSKgel G3000PW (17.8mmφX
30cm) column containing 45% acetonitrile.
．． 1% trifluoroacetic acid as eluent, flow rate 0.3a
1/min. Detection was performed using UV at 220 nm, and was expressed by absorbance.

Further, the obtained LAP had no bitter taste at all and had a good taste with a slight taste.

Reference Example 2 Proteolytic enzymes, as shown in Table 4, Aspergi which contains both endoprotease and exoprotease
rAO8 (Type II
)” (manufactured by Seishin Pharmaceutical ■) and the same origin [Protease M
An oligopeptide mixture was obtained in the same manner as in Reference Example 1, except that 1 (manufactured by Ohno Pharmaceutical ■) was used. In the table, AAA, BC
AA and methionine are amounts in the total amino acid composition.

In addition, precipitated by high performance liquid chromatography of LAP 4 Table Comparison Reference Example 1
cilus S uNilus [Protin AC]
An oligopeptide mixture was obtained in the same manner as in Reference Example 2 using J (manufactured by Ohno Pharmaceutical ■).

The results are shown in Table 5. In the table, AAASBCAA and methionine are the amounts in the total amino acid composition.

It was found that it is difficult to release AAA using endoprotease alone.

Reference Example 3 An oligopeptide mixture was obtained in the same manner as in Reference Example 1 except that the amount of activated carbon used was changed as shown in Table 6. The results are also shown. In the table, AAA is the amount in the total amino acid composition.

Table 6 Activated carbon/soy protein A A A BCAA/AA
A molar ratio 10% by weight 3.0 6.020
2.5 7.5100 1
．． 9 10,0200 1.5 1
From 3.8 or above, it was appropriate to use activated carbon in an amount of 20% by weight or more based on the amount of soybean protein.

Reference Example 4 100 parts of isolated soybean protein ("Fujipro RJ") and 900 parts of water
4 parts of "Protease-M" were added, enzymatically decomposed at 50°C for 5 hours, and then heated at 80-85°C for 15 minutes to inactivate the enzyme. After cooling to room temperature, centrifugation (500
0 RPM x 30 minutes) to remove precipitated components to obtain 760 parts of oligopeptide solution. This is combined with a synthetic adsorbent (rsP-2
07J (manufactured by Mitsubishi Chemical Industries, Ltd.) was added and stirred for 5 hours to adsorb AAA and AAA-rich oligopeptides.
The synthetic adsorbent was removed by filtration and freeze-dried to obtain a powdered oligopeptide mixture.

Average molecular weight is 320, FAA is 24.3% by weight, AAA is 2.2% by weight in the total amino acid composition, and BCAA is 19.0%.
% by weight, methionine is 1.0% by weight, BCAA/AAA
The molar ratio was 11.6.

Reference Example 5 Isolated soybean protein [New Fuji Pro RJ (mentioned above) 100
1 part was dissolved in 900 parts of water, and to this was added ``protease-Ml''.
After adding 4 parts of (previously mentioned) and enzymatically decomposing it at 50°C for 5 hours, heat it at 80-85°C for 15 minutes to inactivate the enzyme.
After cooling to below 0°C, add 110 parts of activated carbon (manufactured by Takeda Pharmaceutical Co., Ltd.) and stir overnight to adsorb aromatic amino acids and aromatic amino acid-rich oligopeptides. A strain system (mixture of equal weights of Diaion 5K-116J and Sumitomo Chemical Co., Ltd. rKA890J) was added, and after stirring for 1 hour, the resin was separated in a furnace and desalted. This desalted solution (pH 5.2) was microfiltered and then spray-dried. This dried product had a good taste with no bitterness or off-taste except for a slight sourness, and showed the values shown in Table 7. In the table, the amounts of AAA, BCAA, and methionine are four in the total amino acid composition.

Table 7 80゜24゜3゜0゜20゜0゜28゜ Crude protein AA Ash AA BCAA Methionine BCAA/AAA 4% by weight 8% by weight 6% by weight 9% by weight 7% by weight 9% by weight 7 (mole ratio) Reference Example 6 An oligopeptide mixture was obtained in the same manner as in Reference Example 1 except that 100 parts of lactalbumin (Sunlacto N-2J (manufactured by Taiyo Kagaku ■) was dissolved in 1667 parts of water. The results are shown in Table 8. In the table, AAA, BCAA, and methionine are the amounts in the total amino acid composition.

Table 8 73.1% by weight 19.8% by weight 4.6% by weight 0.9% by weight 23.8% by weight 1.0% by weight 33.0 (molar ratio) Crude protein AA Ash AA BCAA Methionine BCAA/AAA Example 1 Using the oligopeptide mixture obtained in the above reference example, a nutritional supplement composition of the present invention was prepared by mixing each component so as to have the composition (g) shown in Table 9 below per 100 g of dry weight. .

Test Example-■ An oligopeptide mixture prepared in the same manner as in Reference Example 1 using isolated soybean protein as a raw material was used. Amino acid composition and other component amounts are as shown in Table 10.

6-week-old SD male rats (38 rats: body weight 213.0±9
．． After fasting for 18 hours, the test substance was orally administered. The test substance has a protein content of 1.35g
/kg, dissolved in 10 - ion-exchanged water, and administered using a catheter. Before administration, 30 minutes, 60 minutes after administration,
Blood was collected from the aorta under ether anesthesia at 120 minutes, 180 minutes, 240 minutes, and 360 minutes. Blood was immediately centrifuged and plasma was stored at -80°C. In addition, the gastrocnemius muscle of the right hind limb was removed before administration, 30 minutes, 60 minutes, 120 minutes, and 18°0 minutes after administration, frozen with a clamp cooled with liquid nitrogen, and then stored at -80°C.

For the sample for amino acid analysis, 200 μg of plasma was mixed with an equal amount of 6% sulfosalicylic acid, centrifuged at 3000 rpm for 10 minutes, the supernatant was frozen overnight, thawed, centrifuged again, and the supernatant was used. As a coloring reagent, Ninhydrin reagent L-8500 set manufactured by Wako Tsumugi Kogyo Kogyo 1 was used. The elution reagent is MCI BUFFERL manufactured by Mitsubishi Kasei Kan.
-8500-PF kit was used. The amino acid analyzer used was a new model L-8500 high-speed amino acid analyzer manufactured by Hitachi. D, A 60 mm x column was packed with Hitachi custom ion exchange resin (#26223 C).

The results for blood amino acids are shown in Figure 2, and the results for free amino acids in muscle fibers are shown in Figure 3.

Based on these results, we evaluated the oligopeptide mixture used in the present invention and found that the total amino acid concentration in blood, B
It was found that the CAA concentration and E/N ratio were increased, and the oligopeptide mixture had a high nutritional effect and was able to improve the amino acid pattern, Fisher ratio, etc. in the blood. Therefore, the composition of the present invention, in which nitrogen compounds as protein sources, carbohydrates, and lipids are blended in a well-balanced manner, has a high nutritional support effect and is particularly useful for nutritional support for muscular dystrophy disease patients or during biological invasion. I understand that there is something.

[Brief explanation of drawings]

Fig. 1 is a drawing showing the molecular weight distribution of the oligopeptide mixture obtained in Reference Example 1 by high performance liquid chromatography, Fig. 2 is a graph showing temporal changes in blood amino acid concentration in Test Example I, Fig. 3 is a graph showing temporal changes in free amino acid concentration in muscle tissue in Test Example I. (That's all) ゛・、ノ0 Ugo iB (public) Figure 2 Figure

Claims (3)

[Claims] (1) Average molecular weight obtained by enzymatic hydrolysis of animal and plant proteins, 200 to 5000, free amino acids 35% by weight or less, (branched chain amino acids/aromatic amino acids) molar ratio of 7 or more, and a fraction of the total amino acid composition. A composition containing 5 to 70% by weight on a dry weight basis of an oligopeptide mixture containing 15 to 25% by weight of branched chain amino acids and 0.1 to 2.5% by weight of aromatic amino acids, the composition comprising: The content of total nitrogen compounds, carbohydrates and lipids as a protein source is 10 to 90% by weight of nitrogen compounds and 10% of carbohydrates on a dry weight basis.
-80% by weight and 0-15% by weight of lipids. (2) The composition according to claim (1), which is a nutritional supplement composition for patients with muscular dystrophy. (3) Claim (1) which is a composition for nutritional support during biological invasion.
).