JPH05276896A - Peptide mixture having high fisher ratio, its production and nutrient-supplying composition for hepatic disease patient - Google Patents

Abstract

PURPOSE:To obtain the subject mixture containing branched amino acids and aromatic amino acids in specific amounts, having a high Fisher ratio and useful for hepatic disease patients by denaturing a protein having a high amino acid score, hydrolyzing the product, subjecting the reaction product to a solid-liquid separation and subsequently treating the product with an adsorbing agent. CONSTITUTION:A protein (preferably a whey protein-purified product, a whey protein fraction and/or their treated product) having a high amino acid score is denatured with an acid, alkali, etc., hydrolyzed with an endoprotease, etc., if necessary, subjected to a solid-liquid separation, and subsequently treated with an adsorbing agent such as a synthetic adsorbent to obtain the objective mixture having a branched amino acid/aromatic amino acid molar ratio of >=10, a branched amino acid content of >=15-20wt.% an aromatic amino acid content of <0.1-2.0wt.% and an average mol.wt. of several hundreds/several thousands.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION The present invention has many essential amino acids obtained by subjecting an animal protein having a high amino acid score as a raw material to hydrolysis with an enzyme to specifically remove only aromatic amino acids. The present invention relates to a peptide mixture having a high Fischer ratio and a method for producing the same, and a composition containing the peptide mixture having a high Fischer ratio, particularly a nutritional supplement composition for a patient with liver disease.

[0002]

2. Description of the Related Art It has long been known that amino acids in the body show abnormalities during liver injury, especially during decompensation of liver cirrhosis. Iber et al. (J. Clin. Lab. Med.,
50: 417-425, 1957) is an aromatic amino acid AAA (Tyr, Phe), methionine (M) during liver failure.
et) increased. On the other hand, Zinnemu
an et al. (Amer. J. Dig. Dis., 14:11.
8-126, 1969) reported a decrease in the branched chain amino acid BCAA (Val, Leu, Ile) during the decompensated period of cirrhosis. 1974 Fischer et al. (Amer.
J. Surg. , 127: 40-47, 1974) is B
Decrease in CAA and increase in AAA ie BCAA / AAA
By positively linking the amino acid imbalance, which is a decrease in the molar ratio, with the onset of hepatic encephalopathy and correcting the amino acid imbalance, that is, as a nutritional intake source, BCA
High A content, low AAA and Met content, BCA
It has been reported that hepatic encephalopathy is improved by providing a nitrogen source having a high A / AAA molar ratio (Fisher ratio).

Therefore, an amino acid preparation in which purified amino acids mainly containing Val, Leu and Ile are mixed to prepare a high BCAA / AAA molar ratio is known. That is,
Originally, proteins are used by being decomposed into free amino acids by the action of proteolytic enzymes in the living body. Therefore, it is said that free amino acids are easily absorbed in vivo and have a good nutritional effect, especially in postoperative patients with poor digestion and absorption ability. JP-A-64-83017 and JP-A-3-22366 disclose amino acid preparations for patients with liver failure.

[0004] However, such amino acid preparations are difficult to eat due to their strong chemical taste and are expensive, so that the price of the product itself is also high. JP-A-56-68374 shows an example in which purified amino acid is added to fruit juice or agar to facilitate ingestion. Also, since the amino acid mixture is an electrolyte, the osmotic pressure becomes high,
Formulation at high concentrations is very difficult.

On the other hand, it is known that oligopeptides, which are hydrolysates of proteins, are taken up into cells in the intestinal tract of the small intestine, decomposed into free amino acids in the cells and absorbed. Recently, enzymatically decomposing animal and plant proteins such as egg white and casein into a hydrolyzate with a high peptide content,
Many attempts have been made to utilize this as a nitrogen source.
For example, Japanese Patent Application Laid-Open No. 57-11910 discloses an enteral nutritional preparation in which purified amino acid in a specific ratio is further added to casein or gelatin and a gelatin hydrolyzate. Further, JP-A-2-295463 shows an example of a liver function improving food material using an egg white hydrolyzate.

According to these examples, since the protein is decomposed by an enzyme into a peptide or oligopeptide state, the BCAA / AAA molar ratio of this peptide mixture depends on the molar ratio of the constituent amino acids of the protein itself. It will be. In other words, it can be said that the nutritional value as a nitrogen source depends largely on the raw material protein.

Furthermore, if a protein originally having a low AAA content, that is, a high BCAA / AAA molar ratio is used, the protein source is suitable as a nitrogen source for patients with liver diseases, and it can be decomposed by an enzyme. If it is in a peptide form, the digestive absorbability will be further improved. Therefore, a peptide mixture obtained by degrading a protein having a high BCAA / AAA molar ratio with an enzyme also has a high BCAA / AAA molar ratio and good digestion and absorption properties, and is therefore considered to be suitable as a nitrogen source for liver disease patients. However, in foods or food ingredients that are available daily, the B
The CAA / AAA molar ratio is not so high. JJP
As shown in EN 3 (2) 109-117 (1981), BCAA / AAA molar ratio is about 0.8 to 3.0 for plant proteins and about 2.1 to 3.4 for animal proteins. Is.

JP-A-2-300137 discloses an example of a protease hydrolyzate of glycomacropeptide derived from animal milk κ casein. According to this example, the fact that the glycomacropeptide consisting of 64 amino acid residues obtained by allowing rennet to act on κ casein theoretically does not contain an aromatic amino acid is utilized. However, for example, when cow milk protein is used, a method for purifying κ casein containing only about 13% of the total casein of milk and a method for obtaining a glycomacropeptide from the obtained κ casein are industrially quite difficult. That κ
Only about 1.5% of the glycomacropeptide can be obtained from casein, the industrial production method is considerably difficult, and the amino acid balance of the constituent peptides other than BCAA is biased. Yes, it is considered difficult to actually manufacture.

In JP-A-3-272694, animal proteins such as casein, egg white and albumin, and vegetable proteins such as soybean and wheat are enzymatically decomposed in a neutral range, and AAA is obtained from the enzymatic decomposition product using an adsorbent. By adsorbing, BC
Examples of oligopeptides with increased AA / AAA molar ratio are disclosed. According to this example, it is shown that an AAA-rich oligopeptide is released from isolated soybean protein or lactalbumin, and this AAA-rich oligopeptide is selectively adsorbed using activated carbon.

However, if these adsorbents are used alone, AA
Removal of A, especially tyrosine, is insufficient, and activated carbon does not selectively adsorb only AAA, but adsorbs many peptides, resulting in a large loss as a nitrogen source in the production process. I will end up. Further, the activated carbon once used is difficult to be completely regenerated even if an acid or an alkali is used, which is industrially difficult. Further separated and removed AAA
Conventionally, no consideration has been given to amino acid constitutions other than.

[0011]

Means for Solving the Problems As a result of intensive research aimed at solving the above-mentioned problems, the present inventors have compared the constituent amino acids in various animal and plant proteins, and obtained peptides obtained by degrading them with various proteolytic enzymes. The degree of lower molecular weight of
Ultrafiltration method, RO fractionation method, gel filtration method, and adsorption and removal efficiency of released AAA by using various resins such as activated carbon, synthetic adsorbent, ion exchange resin, etc. As a result, oligopeptide mixture having the following composition However, they have found that they can be an effective nitrogen source for diet therapy for patients with liver disease, and that a composition using this nitrogen source is suitable as a nutritional supplement or therapeutic diet for patients with liver disease.

That is, among the various animal and plant proteins, the protein having the highest BCAA / AAA molar ratio and the excellent balance of the constituent amino acids and having a high amino acid score is used, and the protein is used as an endoprotease and an exoprotease. In order to release only AAA using the method, heat denaturation of protein, acid denaturation, centrifugation, and isoelectric focusing by cooling and holding are used in combination with the enzymatic decomposition method, and the released AAA and AAA are included. In order to remove the peptide, it is possible to obtain a peptide mixture having a high BCAA / AAA molar ratio and an excellent balance of amino acids constituting the whole by separating with a specific resin, and containing the peptide mixture. By using various compositions, the amino acid pattern in plasma of patients with liver disease can be determined. With fine BCAA / AAA molar ratio is corrected, it is possible to improve the nutritional status of the patient,
It has been found that the composition is suitable as a nutritional supplement or therapeutic diet for patients with liver diseases.

The present invention is based on these findings.

In the present invention, a peptide mixture having a high Fisher ratio is suitable as a peptide mixture that can be used in a nutritional supplement composition for patients with liver diseases. Successful production of a high peptide mixture has been successful, specifically, using milk whey protein as a raw material, a branched chain amino acid / aromatic amino acid molar ratio of 10 or more, and a branched chain amino acid of 15 to 15
The present invention succeeded in actually obtaining a peptide mixture having 20% by weight or more, aromatic amino acids of 0.1 to less than 2.0% by weight, and an average molecular weight of several hundreds to several thousands.

The present invention makes this point an important point, and its specific embodiment will be described as follows.

(1) A branched amino acid / aromatic amino acid molar ratio of 10 or more obtained by degrading a protein having a high amino acid score with an enzyme and a branched amino acid of 15 to 20% by weight.
As described above, the peptide mixture characterized in that the aromatic amino acid is 0.1 to less than 2.0% by weight and the average molecular weight is several hundred to several thousand.

(2) A method for producing a peptide mixture, which comprises denaturing a protein having a high amino acid score, hydrolyzing it with an enzyme, and then treating it with an adsorbent to selectively adsorb and remove AAA.

(3) A protein having a high amino acid score is heat-denatured and acid-denatured in a water system, and then enzymatically decomposed with endoprotease and exoprotease, insoluble matter is removed by a centrifugation method, and then ice-cooled. A method for producing a peptide mixture, which comprises removing the precipitated tyrosine by the isoelectric focusing method, treating with an adsorbent, concentrating if necessary, and drying.

(4) A weak acidic cation exchange resin is used as one of the methods for removing free aromatic amino acids or a peptide mixture containing aromatic amino acids from a peptide mixture obtained by enzymatically decomposing a protein having a high amino acid score. A method for producing a peptide mixture, which comprises using, after reacting at acidic pH, filtering, collecting first-eluting fractions, concentrating if necessary, and drying.

(5) A branched-chain amino acid / aromatic amino acid molar ratio of 10 or more and a branched-chain amino acid of 15 to 20% by weight, which is obtained by decomposing a protein having a high amino acid score with an enzyme.
As described above, a nutritional supplement composition for a liver disease patient containing a peptide mixture characterized in that the aromatic amino acid is 0.1 to less than 2.0% by weight and the average molecular weight is several hundreds to several thousands.

(6) A branched-chain amino acid / aromatic amino acid molar ratio of 10 or more obtained by decomposing a protein having a high amino acid score with an enzyme, and a branched-chain amino acid of 15 to 20% by weight.
As described above, the aromatic amino acid is 0.1 to less than 2.0% by weight, the average molecular weight is several hundred to several thousand, the peptide mixture as a nitrogen source, 5 to 90% by weight on a dry weight basis,
Carbohydrates 5 to 90% by weight based on dry weight, lipids 0 to
A nutraceutical composition for patients with liver diseases, characterized by containing 20% by weight.

Suitable proteins for preparing the peptide mixture of BCAA / AAA of the present invention having a high molar ratio are:
In addition to having a high BCAA / AAA molar ratio contained in the protein, since it is finally used as a nutritional supplement composition for patients with liver diseases, it is rich in essential amino acids as amino acids other than AAA to be removed. The one with the highest score is suitable.

Usually, BCAA is used as a preparation for patients with liver diseases.
It is essential that the / AAA molar ratio is at least 5 or more, and the higher this value is, the more preferable. Further, the BCAA / AAA molar ratio in the commercial preparation for patients with liver diseases is usually 20 or more. In addition, muscle protein-BCAA decomposition is promoted after surgery, and the degree has reached three times that at the time of fasting.
It is necessary for the synthesis of proteins and albumin in vivo, and is essential for the acute phase protein synthesis during inflammation.
The higher the BCAA / AAA molar ratio, the better.

As a protein raw material suitable for producing a peptide mixture having a high BCAA / AAA molar ratio of the present invention, the BCAA / AAA molar ratio contained in the protein is at least 4 or more and it is essential as a constituent amino acid. Any protein derived from animals, plants or microorganisms may be used as long as it is rich in amino acids and has a high amino acid score.

The BCAA / AAA molar ratio of the constituent amino acids contained in a normal protein is only about 0.8 to 3.0 as described above. However, especially cheese whey produced when purifying cheese from milk, whey protein obtained by concentrating and purifying the protein fraction contained therein,
Alternatively, β-lactoglobulin obtained by further fractionating and purifying the protein fraction from whey protein has the highest amino acid score of 100, and has a BCAA / AAA molar ratio of more than 4. Is the most suitable protein for.

In the present invention, whey protein is used, and casein whey and sweet whey, which are by-products when producing casein and cheese from milk, are used as raw materials, and all of them are used as whey protein. To be done. Examples of whey proteins include purified whey protein products, whey protein fractions, and processed products thereof (processed such as concentration, dilution, pasting, and drying). Examples of the whey (whey) protein purified product include whey (whey) protein concentrate and whey (whey) protein isolate.

Whey Protein Concentrate (Whey Prot
Ein Concentrate (hereinafter sometimes referred to as “WPC”) refers to a dried product of a liquid obtained by concentrating whey produced as a by-product during the production of cheese or casein and separating lactose to crystallize. This WPC contains 35-80% of its content of protein, of which about 60% is β-lactoglobulin, about 20% is α-lactalbumin, and about 13% is immunoglobulin. It is usually neutral.

Whey Protein Isolate (Whey Prot
ein Isolate (hereinafter sometimes referred to as “WPI”) is a distinction from WPC.
It is an undenatured whey protein that has been demineralized by electrodialysis etc. and separated to a higher degree of purity, and has much less ash, fat, and carbohydrates. Especially, the fat content is less than 1%.

Further, whey (whey) protein fraction refers to all those fractionated by casein whey, sweet whey decaseinized and delactose-digested, for example, α-lactalbumin, β-lactoglobulin and the like. It is illustrated.

The peptide mixture having a high BCAA / AAA molar ratio of the present invention is obtained by enzymatically decomposing the protein having a high BCAA / AAA molar ratio to release and remove the AAA and the peptide moiety containing AAA. be able to.

In the present invention, these proteins are heated in an aqueous system, or are acid or alkaline so as to facilitate hydrolysis by an enzyme and release of AAA and a peptide moiety containing AAA, as will be described later. It is necessary to denature it by placing it under conditions. This facilitates the action of the enzyme on the protein, and thus the release of AAA or the peptide portion containing AAA.

Endoproteases and exoproteases are used as enzymes for hydrolyzing proteins. It is difficult to release the AAA or the peptide portion containing AAA with only the endoprotease, and the exoprotease alone cannot reduce the molecular weight of the protein to obtain the desired peptide mixture.

A combination of endoprotease and exoprotease as shown in the present invention,
Furthermore, the peptide mixture of the present invention can be obtained by treatment with an adsorbent described below. The peptide mixture thus obtained has almost no bitterness, astringency, or amino acid odor, and is suitable as a nitrogen source for patients with liver diseases.

The endoprotease used in the present invention may be any enzyme of animal origin, plant origin or microorganism origin, as long as it is an enzyme that acts on the peptide bond at the C-terminus or N-terminus of AAA or the peptide moiety containing AAA. I do not care. For example, pepsin or chymotrypsin produced from pig or bovine internal organs is a suitable enzyme to be used in the present invention because it mainly cleaves the peptide bond at the C-terminal side of AAA in the protein.

In the present invention, one or more endoproteases can be used in combination. Since only one type of endoprotease does not necessarily act on the C-terminal or N-terminal peptide bond of all AAA or peptide moieties containing AAA contained in a protein, it is desirable to use different types of endoprotease in combination. ..

As the exoprotease used in the present invention, any enzyme of animal origin, plant origin, or microorganism origin can be used as long as it is an enzyme that sequentially acts on the peptide bond at the C-terminus or N-terminus of AAA or a peptide moiety containing AAA. But it doesn't matter. For example, carboxypeptidase A produced from the internal organs of pigs or cattle acts from the C-terminal side of a peptide bond having an aromatic amino acid or a branched chain amino acid as a side chain, and thus is suitable as an enzyme used in the present invention.

The degree of enzymatic decomposition is such that the working temperature and working time are such that the average molecular weight of the peptide mixture solution after enzymatic decomposition is 5000 or less, preferably 200 to 3000.
Adjust the substrate / enzyme ratio.

As the adsorbent used in the present invention, any adsorbent that specifically adsorbs AAA can be used. As an example, a synthetic adsorbent, an ion exchange resin, activated carbon or the like can be used. Activated carbon is often used because it adsorbs amino acids such as hydrophobic amino acids such as AAA well. However, synthetic adsorbents and ion exchange resins are easy to use from the viewpoint of industrial regeneration process. For example, a crosslinked polymer obtained by polymerizing, polycondensing, or copolymerizing various organic polymerizable monomers, or a crosslinked polymer obtained by polymerizing or polycondensing various polymerizable monomers and then crosslinking. The combined porous synthetic adsorbent is used for separation and purification of various substances, especially pharmaceuticals and foods. For example, "Diaion" HP10, HP20, H
P21, HP30, HP40, HP50, "Diaion" HP2MG (manufactured by Mitsubishi Kasei Co., Ltd.) and Amberlite XAD-2, XAD-4, XAD-7, XAD-8.
(Rohm & Haas Co., Ltd.) and the like.
It is well known that such synthetic adsorbents adsorb amino acids.

In the present invention, a weakly acidic cation exchange resin can be used for separating AAA by reacting it with an enzymatic decomposition solution under acidic conditions. Conventionally, weakly acidic cation exchange resins have been used at pH 6 to pH 10, but under these acidic conditions, the carboxyl groups, which are the functional groups of weakly acidic cation exchange resins, are not dissociated. Therefore, it is possible to separate the AAA and the peptide containing AAA released by the effect of the hydrophobic interaction. Specifically, pH is 2.0 or higher.
When the enzymatic degradation solution of the protein is continuously supplied to a column packed with a weakly acidic cation exchange resin at 0 or less, preferably pH 3.5 or more and pH 4.5 or less, highly hydrophobic AAA and a peptide containing AAA are obtained. Is adsorbed on the resin and elutes later. Therefore, most of AAA and AAA were collected by a so-called advanced chromatographic separation method in which a fraction from the point where the AAA and the peptide containing almost no AAA began to flow out from the column effluent to the time when the peptide containing AAA and the peptide containing AAA began to flow out was obtained. Only peptides that do not contain can be obtained.

In order to make the adsorbing and removing effect of these adsorbents more efficient, after the enzymatic decomposition of the protein solution is completed, the insoluble matter is removed by centrifugation and the low solubility of tyrosine itself is utilized. After adjusting the pH with tyrosine, tyrosine is precipitated by keeping the enzyme-decomposed solution at a low temperature of 10 ° C. or lower, preferably at a low temperature of 0 to 4 ° C., and it is possible to further reduce AAA by removing it by centrifugation. it can.

The peptide mixture used in the present invention can be obtained through the steps as described above, but if necessary, the treatment liquid in the final step can be desalted, concentrated, sterilized, or dried.

The peptide mixture of the present invention can be used as an oral agent for patients with liver disease or as a nitrogen source for a therapeutic diet for diet therapy.

The nutritional supplement composition for patients with liver diseases of the present invention contains the above-mentioned peptide mixture, and is a known oral agent for patients with liver diseases or diet therapy except that a nitrogen source comprising the peptide mixture is used. Similar to the therapeutic food for use, it is produced by adding nitrogen compounds as various protein sources, carbohydrates, lipids, vitamins, minerals, and other additives as necessary, or by using them in combination. Does not matter.

As the protein source, milk whey protein having a high amino acid score, animal protein such as ovalbumin and egg white globulin, and vegetable protein such as soybean protein can be used.

As the carbohydrate, known monosaccharides, oligosaccharides, polysaccharides, dietary fiber and the like can be used. Examples thereof include glucose, maltose, sucrose, lactose, isomaltose, starch and dextrin.

As the lipid, known coconut oil, corn oil, cottonseed oil, lard, palm oil, peanut oil, safflower oil, soybean oil, sunflower oil, coconut oil, MCT oil, fish oil, etc., or a fatty acid composition is adjusted. Therefore, a modified fat obtained by mixing various kinds of the above fats can be exemplified.

The composition according to the present invention is not only used for patients with liver diseases as described above, but can also be used for sick people and infants with impaired liver function, as well as for temporary use due to drinking or the like. It can be used for a person with impaired liver function, and of course, it can be used by a healthy person to prevent the impaired liver function. Therefore, the composition according to the present invention is used in a pharmaceutical type, as well as a beverage, a food, a nutritious food, a functional food, a food for specified health use, a drink, etc. It can be widely used for the elderly, people after illness, and healthy people.

[0048]

EXAMPLES The present invention will be described in more detail with reference to Examples below, but the present invention is not limited to these Examples unless the gist thereof is exceeded.

[0049]

Example 1 Milk whey protein isolate (WPI) (LE
100 parts by weight (hereinafter, abbreviated as "part") manufactured by SUEUR Co. "BE-PRO" was dissolved in 2000 parts of water and heated at 90 ° C for 10 minutes. After cooling, the pH was adjusted to 1. with citric acid and hydrochloric acid.
Adjust to 8 to 2.0 and use the enzyme (A / S ORTHANA
KEMISK FABRIK “Pepsin”).
5 parts were added and enzymatically decomposed at 37 to 38 ° C for 24 hours. After decomposing the enzyme, it was heated at 80 to 85 ° C. for 30 minutes to deactivate the enzyme, and then an aqueous sodium hydroxide solution was added to adjust the pH to 7.5. Neutrase 0.5L (NOVO INDUST
(Manufactured by RI AS) was added thereto, and enzymatically decomposed at 42 to 43 ° C for 6 hours. After decomposing the enzyme, the mixture was heated at 80 to 85 ° C. for 30 minutes to inactivate the enzyme, and then an aqueous citric acid solution was added to p
H was set to 4.0. Carboxypeptidase W (manufactured by Pentel Co., Ltd.) was added in an amount of 1.0 part and enzymatically decomposed at 42 to 43 ° C. for 4 hours. After decomposing the enzyme, it was heated at 80 to 85 ° C for 30 minutes to inactivate the enzyme, then cooled with ice and left at 4 ° C overnight.
Centrifugation (5,000 RPM × 30 minutes) was performed to remove insoluble materials and amino acids such as precipitated tyrosine. The obtained supernatant is used as CM-SEPHADEX C-2.
The solution was passed through a column filled with 5 and the first eluted fraction was collected. The obtained fractions are batch sterilized (75 ℃, 30
Min) and then lyophilized to obtain a peptide mixture.

The above-mentioned enzyme-decomposed peptide mixture (hy
Peptide mixture (HF peptide) obtained by freeze-drying after further fractionation with dro WPI 1)
The amino acid composition of s1) is shown in Table 1 below.

[0051]

[Table 1]

From the above results, hydro WPI 1
And HF peptides 1 each branched chain amino acid / aromatic amino acid (BCAA / AAA) molar ratio, and branched chain amino acid (BCAA), aromatic amino acid (A
The concentration of AA) was as shown in Table 2 below.

[0053]

[Table 2]

[0054]

Example 2 Milk whey protein isolate (WPI) (LE
100 parts by weight (hereinafter, abbreviated as "part") manufactured by SUEUR Co. "BE-PRO" was dissolved in 2000 parts of water and heated at 90 ° C for 10 minutes. After cooling, the pH was adjusted to 7.0, 1.0 part of an enzyme (“Amano N” manufactured by Amano Pharmaceutical Co., Ltd.) was added, and the enzyme was decomposed at 50 ° C. for 5 hours. After decomposing the enzyme, the mixture was heated at 85 ° C. for 15 minutes to inactivate the enzyme, and then a citric acid aqueous solution was added to adjust the pH to 4.
It was set to 0. Carboxypeptidase W (Pentel Co., Ltd.)
(Manufactured by K.K.) was added and enzymatically decomposed at 42 to 43 ° C for 3 hours. After decomposing the enzyme, the enzyme was inactivated by heating at 80 to 85 ° C for 10 minutes, then cooled with ice and left at 4 ° C overnight. Centrifugation (5,000 RPM × 30 minutes) was performed to remove insoluble materials and amino acids such as precipitated tyrosine. Activated carbon (“Shirasagi” manufactured by Takeda Pharmaceutical Co., Ltd.) 10 was added to the obtained supernatant.
(W / W)% was dispersed and stirred for 30 minutes. Activated carbon was removed using a doubled filter cloth, and the obtained supernatant fraction was batch sterilized (75 ° C., 30 minutes) and then freeze-dried to obtain a peptide mixture.

The above-mentioned enzyme-decomposed peptide mixture (hy
Peptide mixture (HF peptide) obtained by freeze-drying after further fractionation with dro WPI 2)
The amino acid composition of s2) is shown in Table 3 below.

[0056]

[Table 3]

[0057]

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to produce a palatable peptide mixture as a nitrogen source suitable for patients with liver diseases. The peptide mixture can be widely used as a nitrogen source for various therapeutic preparations used for patients with liver diseases and therapeutic diets for diet therapy. In addition, it can be widely used for other people with impaired liver function, and of course, can be widely used for health purposes by healthy people for the purpose of preventing liver function deterioration.

Since the peptide mixture of the present invention has a low AAA content and a high BCAA content, it improves the in vivo protein and albumin synthesizing ability, promotes protein synthesis in muscle tissue and suppresses degradation, and enhances protein synthesizing ability in the liver. It can be expected to promote, inhibit the brain transport of AAA at the blood-brain barrier, promote the synthesis of epinephrine in the brain, and decrease the production of norepinephrine (octopamine, β-phenylethanolamine).

Since the composition for patients with liver diseases of the present invention mainly contains a peptide mixture as a nitrogen source, it is well absorbed from the digestive tract and has a lower osmotic pressure as compared with the amino acid mixture. Therefore, diarrhea and the like can be avoided, and even when taken orally, the taste is good and the burden on the patient is small. In addition, the amino acid pattern and BCAA / AAA molar ratio in plasma of patients with liver disease can be significantly improved.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁵ Identification number Internal reference number FI technical display location C12P 21/06 8214-4B (72) Inventor Yu Kuwata 1-21-3 Sakaemachi, Higashimurayama-shi, Tokyo Meiji Dairy Products Co., Ltd. Central Research Institute (72) Inventor Ryoro Yamamoto 1-21-3 Sakaemachi, Higashimurayama, Tokyo Meiji Dairy Products Co., Ltd. Central Research Institute

Claims (7)

[Claims] 1. A branched chain amino acid / aromatic amino acid molar ratio of 10 or more, a branched chain amino acid of 15 to 20% by weight or more, and an aromatic amino acid of 0.1 to 2.0, which are obtained by degrading a protein with an enzyme. A peptide mixture characterized by being less than wt% and having an average molecular weight of hundreds to thousands. 2. The method according to claim 1, wherein a protein having a high amino acid score is denatured, hydrolyzed with an enzyme, and if necessary, solid-liquid separation is performed, and then treated with an adsorbent. Process for producing peptide mixture. 3. The method according to claim 2, wherein the protein having a high amino acid score is milk whey protein. 4. The method according to claim 3, wherein a purified whey protein product, a whey protein fraction and / or a processed product thereof is used as the milk whey protein. 5. The purified whey protein is whey protein concentrate (WPC) or whey protein isolate (WPI), and the whey protein fraction is β-lactoglobulin or α-lactalbumin. The manufacturing method according to claim 4, wherein 6. A composition comprising the peptide mixture according to claim 1. 7. The composition according to claim 6, wherein the composition is a nutritional supplement composition for patients with liver disease.