WO2005120541A1 - Process for producing protein having its antihypertensive activity enhanced - Google Patents

Process for producing protein having its antihypertensive activity enhanced Download PDF

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Publication number
WO2005120541A1
WO2005120541A1 PCT/JP2005/010643 JP2005010643W WO2005120541A1 WO 2005120541 A1 WO2005120541 A1 WO 2005120541A1 JP 2005010643 W JP2005010643 W JP 2005010643W WO 2005120541 A1 WO2005120541 A1 WO 2005120541A1
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Prior art keywords
protein
sugar
blood pressure
meat
modified
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PCT/JP2005/010643
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French (fr)
Japanese (ja)
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Hiroki Saeki
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Hiroki Saeki
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Priority to JP2006514573A priority Critical patent/JPWO2005120541A1/en
Publication of WO2005120541A1 publication Critical patent/WO2005120541A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/618—Molluscs, e.g. fresh-water molluscs, oysters, clams, squids, octopus, cuttlefish, snails or slugs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A23L33/18—Peptides; Protein hydrolysates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/60—Fish, e.g. seahorses; Fish eggs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/612—Crustaceans, e.g. crabs, lobsters, shrimps, krill or crayfish; Barnacles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1706—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from fish
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to the fields of food processing, such as the fishery processing industry and the meat processing industry, and further to the fields of health foods, pharmaceutical products, and iridani products.
  • Proteins are basic nutrients for animals to survive together with lipids and carbohydrates, and have conventionally been positioned as a source of amino acids constituting living bodies.
  • proteins have various functions of regulating not only the value as a nutrient but also the metabolic activity of a living body.
  • the bioregulatory function of this protein is considered to be due to a bioactive peptide derived from food protein by the action of gastrointestinal proteases.
  • a steroid-binding peptide that regulates serum cholesterol metabolism derived from soy protein: Sugano, bioregulatory function of food, pp33-41, Gakkai Shuppan Center, 1992
  • Opioid peptide casein: Yoshikawa et al. Agri Biol. Chem. 48, 3185-, 1984.
  • Non-patent document 1 plant protein: Fukudome et al. FEBS Lett. 296, 107-111, 1984
  • Non-patent document 2 Angiotensin I converting enzyme (ACE) inhibitory peptide that suppresses blood pressure elevation, milk casein: Maruyama et al. Agri Biol.
  • Non-patent document 3 plant protein: Miyoshi et al. Agric. Biol. Chem., 55, 13 13-1318, 1991 (Non-patent document 4). Katsuo section: Suezuna, Nissui journal 65, 92-96, 1999 (Non-patent document 5), Wakame: Suetsuna et al. Nutr. Biochem, 11, 450-454, 2000 (Non Patent Literature 6). Patent Literatures 1-7, etc. Used for functional foods.
  • Patent Document 1 Japanese Patent Application Laid-Open No. 05-306296
  • Patent Document 2 Patent No. 3401280 Derived from seafood
  • Patent Document 3 Japanese Patent Laid-Open No. 05-331191
  • Patent Document 4 JP-A-06-345664 Derived from cheese whey
  • Patent Document 5 Patent No. 3129523 Ovalbumin-derived
  • Patent Document 6 Toku 2001-84948 derived from milk
  • Patent Document 7 JP-A-06-277090 derived from casein
  • Non-patent literature l Yoshikawa et al. Agric. Biol. Chem., 48, 3185-, 1984.
  • Non-Patent Document 2 Fukudome et al. FEBS Lett.296, 107-111, 1984
  • Non-Patent Document 3 Maruyama et al. Agric. Biol. Chem., 46, 1393-1394, 1982.
  • Non-Patent Document 4 Miyoshi et al. Agric. Biol. Chem., 55, 1313-1318, 1991
  • Non-Patent Document 5 Suezuna, Nissui Magazine 65, 92-96, 1999
  • Non-Patent Document 6 Suetsuna et al. J. Nutr. Biochem
  • the present inventors focused on muscle protein, which is the most common animal protein source, to enhance the function of the above-mentioned functional digestive peptide as much as possible, and to efficiently function the functional peptide. Investigations were conducted to determine whether or not the drug could be used effectively, and as a result, a method that could effectively improve blood pressure regulation was developed.
  • the present inventors have linked various saccharides to muscle proteins via the Maillard reaction, and realized their water-solubility, stabilization, modification of emulsifying ability, and the like. This sugar-modified protein is considered for various uses as food.
  • This lasting effect is characteristic of the fish meat protein obtained in the present invention.
  • a protein or meat having an excellent blood pressure regulating function can be efficiently prepared.
  • the protein of the present invention when eaten while contained in food, produces a functional peptide having an excellent blood pressure regulating action in the digestive tract to regulate blood pressure. Therefore, it is not necessary to prepare digestive peptides for the first time, and by enhancing the bioregulatory function of daily familiar foods such as meat and muscle proteins, it can be used for various processed foods. , Without any special awareness A diet that benefits from the fruits can be provided.
  • FIG. 1 shows changes in sensitivity of muscle proteins to digestive enzymes caused by sugar modification.
  • Glycosylated muscle protein (lysine modification rate 8.0%) bound to alginate oligosaccharides equivalent to 7.8% by weight of salmon muscle is digested with pepsin (pH 2.0) for 3 hours, and further digested with trypsin for 3 hours (PH7. 0).
  • pepsin pH 2.0
  • trypsin trypsin for 3 hours
  • FIG. 2 Changes in digestibility of fish meat protein caused by alginate oligosaccharide modification. Digestion of a sugar-modified muscle protein (referred to as lysine modification rate 8.0%) to which alginate oligosaccharide equivalent to 7.8% of the weight of salmon muscle was digested with pepsin (pH 2.0), and further digested with trypsin for 3 hours ( PH 7.0), and the molecular weight distribution of the digest was examined by gel filtration analysis (Vo: exclusion limit molecular weight 2500). It can be seen that the peptide distribution at the arrow is significantly different from the normal fish meat ( ⁇ ).
  • FIG. 3 Blood pressure-regulating function of sugar-modified muscle protein obtained by the present invention.
  • Glucose-modified muscle protein (sugar equivalent to 7.8% by weight of salmon muscle) is bound to systolic blood pressure (mouth) of SHR rat before administration. ) was orally administered at 170 () and 670 mg ( ⁇ ⁇ ⁇ ) per kg body weight, and a rapid decrease in blood pressure was observed.
  • untreated salmon meat is mixed with the same amount of sugar (see: 670 mg / kg body weight as a protein), the blood pressure is slightly reduced, and the effect of the present invention can be remarkably observed.
  • FIG. 4 shows the blood pressure-inhibiting function of the sugar-modified muscle protein obtained by the present invention.
  • 10-week-old SHR rats were orally dosed daily with glucose-modified muscle protein (conjugated with sugar corresponding to 7.8% by weight of salmon muscle) for 15 and 28 days.
  • glucose-modified muscle protein conjugated with sugar corresponding to 7.8% by weight of salmon muscle
  • ⁇ glucose-modified muscle protein
  • ⁇ systolic blood pressure gradually increased with age.
  • 70 mg (A) / kg body weight suppressed blood pressure elevation.
  • 170mg (mouth) Administered daily no increase in blood pressure occurred.
  • the present invention is intended to change the reactivity of digestive enzymes as a substrate by binding reducing sugars to meat or protein, thereby imparting an excellent blood pressure regulating action.
  • the present invention provides, for example, (1) a method of lowering blood pressure, which comprises mixing a protein with a reducing sugar, dehydrating the mixture, and maintaining a water content of 0.25 to 6% in an environment of 30 to 70 ° C.
  • a method for preparing a sugar-modified protein for use in blood pressure reduction comprising: (2) mixing a protein with a reducing sugar, dehydrating the mixture, and maintaining the environment at a relative humidity of 70% or less and an environment of 30 to 70 ° C. Methods for preparing the sugar-modified protein are included.
  • a Maillard reaction is caused between a reactive lysine residue of the protein and the reducing end of the reducing saccharide, and a covalent bond is formed between the two.
  • the relative humidity can be set to a range of 70% or less (Example 5).
  • a mixture of protein and sugar is dehydrated. Specifically, heat treatment is performed at a low humidity of 10% relative humidity, or freeze drying, spray drying, and reduction. By treatment such as pressure drying or a combination thereof, the water content of meat or a mixture of protein and sugar can be reduced to 6% or less. Preferably, freeze-drying is desirable. Moisture content power of a mixture of meat or protein and sugar Even if it exceeds 6% at the end of the dehydration treatment, at a relative humidity of 35% or less, 30 to 70 ° C, more specifically, for example, 40 ° By keeping the temperature between C and 70 ° C, the water content is kept within 6%. You can also. It should be noted that meat and muscle proteins are water-soluble by binding reducing sugars under the conditions of this treatment.
  • a protein is mixed with a reducing sugar in the range of 1: 0.5 to 10 and freeze-dried to adjust the water content to about 0.6-3%. It is kept at a constant temperature and humidity of 40 to 60 ° C and a relative humidity of about 35% for several hours to 4 days.
  • Lysine modification rate in the protein When it reaches about -40%, the reaction is stopped by cooling (chilling on ice) to bind the desired amount of reducing sugar to the protein (that is, sugar modification). Can be.
  • Binding of a reducing saccharide to a reactive lysine residue of a meat or protein in this way results in a change in the higher order structure of the protein, affecting its various properties.
  • the digestibility of fish meat protein changes due to the binding of sugar chains of 2% or more of the reactive lysine residues.
  • the meat or sugar-modified protein sugar-modified by the method of the present invention can be used for lowering blood pressure.
  • Proteins that can be used in the present invention include various proteins. Specific examples include muscle protein, ovalbumin, protamine, soy protein, and the like. Muscle proteins include those of all living organisms such as fish meat, animal meat, shellfish, and squid. These can be used even if they are thoroughly washed, and food ingredients other than muscle proteins such as lipids and water-soluble low molecular weight ingredients can be contained at all. Muscle proteins include myosin, actin, tropomyosin, troponin and the like. As protamine, for example, those derived from fish testis, specifically, salmon testis Protamine can be mentioned.
  • Meats that can be used in the present invention include the above-described fish meat, animal meat, shellfish, squid, and any other living organisms that have been minced.
  • Shredding means cutting the above meat by various means, for example, including homogenizing treatment and minced meat treatment, preferably passing through a mesh of 5 mm, more preferably 3 mm or less. It is desirable to chop or mince to the extent.
  • Examples 1 and 2 as examples of reducing sugars that can be used in the present invention, the results for alginate oligosaccharides having an average degree of polymerization of 6 were shown. A similar effect can be expected for carbohydrates (reducing sugars). Which reducing sugar to use depends on the purpose of product development and the associated cost-effectiveness.
  • the reducing saccharides usable in the present invention include monosaccharides (glucose, ribose and the like), oligosaccharides having an average degree of polymerization of 20 or less and having a reducing end, such as alginic acid oligosaccharides and chitosan oligosaccharides. Of the reducing oligosaccharides.
  • a thermally unstable protein for example, a muscle protein of a fish that lives in a cold water area
  • protein modification is suppressed in the process of water regulation and in the process of sugar modification.
  • a denaturing inhibitor for example, sorbitol pertrehalose.
  • the protein denaturation inhibitor is particularly effective when the reducing saccharide to be added has a small effect on preventing protein denaturation (eg, alginate oligosaccharide).
  • a reducing saccharide having a denaturation-preventing effect such as glucose
  • the mixing ratio (weight) of the meat or muscle protein and the alginate oligosaccharide (reducing sugar) in the preparation process of the sugar-modified protein is preferably in the range of 1: 0.1 to 1: 1 ⁇ . In fact, it is only necessary to change the digestibility of proteins by sugar modification.
  • the sugar-modified protein or the sugar-modified meat prepared by the method of the present invention can be basically used as a food material because the sugar-modified protein or sugar-modified meat is prepared using reagents in the production process. This is in accordance with the object of the present invention, that is, the advanced use of the bioregulatory function of a protein obtained when eaten as a food.
  • the sugar-modified protein or sugar-modified meat treated by the method of the present invention can also be made water-soluble, so that it has good digestibility and absorbability and can be easily mixed with other food and beverage materials.
  • the blood pressure lowering protein or the blood pressure lowering meat of the present invention acts as a blood pressure lowering factor.
  • the blood pressure lowering protein or the blood pressure lowering meat of the present invention can be administered orally as it is.
  • the protein for lowering blood pressure or meat for lowering blood pressure of the present invention may be added to or mixed with other foods as a food, or added to or mixed with a beverage to obtain a beverage. Ingestion is also possible.
  • a hypotensive agent When used as a hypotensive agent, it can be mixed with a preparation-like carrier to prepare a preparation. For example, tablets, capsules, granules, and powders can be used.
  • Additives include sugars, sugar alcohols (eg, lactose, glucose, mannitol, dextrin, cyclodextrin, sucrose), polysaccharides (starch, sodium carboxymethylcellulose, hydroxypropyl starch, calcium carboxymethylcellulose, methino).
  • Resenorelose hydroxypropynolesenorelose, hydroxypropinolemethinoresenorelose,;), gelatin, gums (gum arabic), synthetic polymers (polyvinylpyrrolidone, polyvinyl alcohol), talc, tragacanth, bentonite, veegum, Examples include sorbitan fatty acid esters, sodium lauryl sulfate, glycerin, fatty acid glycerin esters, propylene glycol and the like.
  • the protein for lowering blood pressure or meat for lowering blood pressure of the present application is desirably ingested from 0.05 g to 2 g, preferably from O.lg to lg per kg of body weight per day as a protein amount.
  • the protein for lowering blood pressure of the present invention can be taken continuously for 7 to 21 days or at intervals of about 2 days.
  • the present invention further includes an antihypertensive agent or a hypotensive agent containing, as an active ingredient, an antihypertensive protein or an antihypertensive meat produced by the above-mentioned preparation method.
  • the administration method is the same as the above-mentioned method of ingesting the blood pressure lowering protein or the blood pressure lowering meat.
  • the salmon muscle was minced with a meat chopper to a size that passed through a 2 mm (JIS-8811) sieve.
  • an alginate oligosaccharide (14 g) equivalent to the amount of muscle protein (14% wet weight) contained in it and sorbitol (14 g) as a protein freezing and denaturation inhibitor were mixed, and then lyophilized to remove water. Adjusted to%. Then, after keeping at 60 ° C (35% relative humidity) for 3 hours, the alginate oligosaccharide reacts with 8% of lysine residues in salmon muscle and reacts with glycosylated protein (sugar equivalent to 7.8% by weight). Formed a bond).
  • Heifers stored at 4 ° C for 7 days after slaughter were trimmed into lean meat and washed three times with 5 volumes of physiological saline.
  • 100 g of the obtained washed meat 200 mL of an aqueous solution containing glucose equivalent to 5 times the weight of the muscle protein mass (10.2% wet weight) contained therein was added.
  • the mixture was kneaded, spread thinly and freeze-dried (water content: 1.4%). Subsequently, the protein was kept at 50 ° C (5% relative humidity) for 12 hours, and 61% of the lysine residues in the protein reacted with glucose.
  • SHR rats are model animals whose blood pressure gradually increases with growth.
  • the same sugar-modified fish meat (P-7.8) as in Example 2 was orally administered once daily at 70 and 170 mg per body weight, and changes in blood pressure were investigated.
  • the systolic blood pressure of normal SHR rats increased by 13 mmHg in 4 weeks, whereas that of rats continuously treated with sugar-modified fish meat significantly inhibited the increase in blood pressure. did it.
  • the blood pressure lowering effect that occurs immediately after the administration of sugar-modified fish meat was not impaired at all.
  • Ovalbumin (mainly ovalbumin) was obtained by acid precipitation of white leghorn egg white at pH 5.6, followed by centrifugation, suspension in lOmMNaCl, and neutralization with HC1 to recover. This protein solution was adjusted to 100 mg / ml, then 0.1 M maltose was dissolved and lyophilized. Then, the maltose was immediately bound to the ovalbumin molecule by keeping it at 60 ° C and a relative humidity of 65% for 4 days. Further, unreacted maltose was removed by ammonium sulfate fractionation.
  • ovalbumin obtained as described above has a 53% reduction in the effective lysine, and when subjected to pepsin treatment at a 1/500 weight ratio, the protein degradation mode differs, indicating that Confirmed by acrylamide gel electrophoresis analysis. Therefore, this sugar-modified protein
  • 10-week-old male SHR rats (240-260 g in weight) with hypertension were orally administered lOOOOmg / body weight, and 2 hours later, systolic blood pressure decreased by 22 mmHg. This effect was maintained for at least 6 hours.

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Abstract

Preparation/purification of functional peptides through zymolysis of food requires labor and cost. Even at a stage of crude purification, the merchandise is relatively expensive. Further, there is the probability that produced functional peptides are decomposed by a digestive fluid to result in loss of efficacy. For coping with these, an excellent blood pressure regulating activity is imparted by realizing binding of a reducing sugar to meat or protein to thereby change the activity thereof as a substrate to digestive enzymes.

Description

明 細 書  Specification
血圧降下作用を増強したタンパク質の製造方法  Method for producing protein with enhanced blood pressure lowering action
技術分野  Technical field
[0001] 本発明は、水産加工業、食肉加工業等の食品加工分野、更には、健康食品、医薬 品及びィ匕成品の分野に関わる。  [0001] The present invention relates to the fields of food processing, such as the fishery processing industry and the meat processing industry, and further to the fields of health foods, pharmaceutical products, and iridani products.
背景技術  Background art
[0002] タンパク質は脂質、糖質とともに動物が生存するための基本栄養素であり、従来は 生体を構成するアミノ酸の供給源として位置づけられてきた。  [0002] Proteins are basic nutrients for animals to survive together with lipids and carbohydrates, and have conventionally been positioned as a source of amino acids constituting living bodies.
[0003] しかし近年、タンパク質は、栄養素としての価値だけでなく生体の代謝活動等を調 節するさまざまな機能を持つことが明らかとなってきている。このタンパク質の生体調 節機能は多くの場合、消化管プロテアーゼの作用によって食品タンパク質力 派生 する生理活性ペプチドに起因すると考えられる。  [0003] In recent years, however, it has become clear that proteins have various functions of regulating not only the value as a nutrient but also the metabolic activity of a living body. In many cases, the bioregulatory function of this protein is considered to be due to a bioactive peptide derived from food protein by the action of gastrointestinal proteases.
[0004] たとえば、血清コレステロール代謝を調節するステロイド結合性ペプチド（大豆タン パク質由来:菅野、食品の生体調節機能、 pp33-41、学会出版センター、 1992)、鎮 痛'鎮静作用に関わる外因性ォピオイドペプチド (カゼイン: Yoshikawaら Agri Biol. Chem. 48,、 3185-, 1984. (非特許文献 1)、植物タンパク質： Fukudomeら FEBS Lett. 296、 107-111、 1984 (非特許文献 2)、 血圧上昇を抑制するアンジォテンシン I変 換酵素（ACE)阻害ペプチド、牛乳カゼイン： Maruyamaら Agri Biol. Chem., 46, 139 3-1394 1982. (非特許文献 3)、植物タンパク質： Miyoshiら Agric. Biol. Chem., 55, 13 13-1318,1991 (非特許文献 4) .カツォ節：末綱、日水誌 65、 92-96、 1999 (非特許 文献 5)、 ワカメ： Suetsunaら J. Nutr. Biochem, 11, 450-454,2000 (非特許文献 6) .下 記特許文献 1—7など)などが知られており、各種の健康'機能性食品に利用されて いる。  [0004] For example, a steroid-binding peptide that regulates serum cholesterol metabolism (derived from soy protein: Sugano, bioregulatory function of food, pp33-41, Gakkai Shuppan Center, 1992) Opioid peptide (casein: Yoshikawa et al. Agri Biol. Chem. 48, 3185-, 1984. (Non-patent document 1), plant protein: Fukudome et al. FEBS Lett. 296, 107-111, 1984 (Non-patent document 2) Angiotensin I converting enzyme (ACE) inhibitory peptide that suppresses blood pressure elevation, milk casein: Maruyama et al. Agri Biol. Chem., 46, 139 3-1394 1982. (Non-patent document 3), plant protein: Miyoshi et al. Agric. Biol. Chem., 55, 13 13-1318, 1991 (Non-patent document 4). Katsuo section: Suezuna, Nissui journal 65, 92-96, 1999 (Non-patent document 5), Wakame: Suetsuna et al. Nutr. Biochem, 11, 450-454, 2000 (Non Patent Literature 6). Patent Literatures 1-7, etc. Used for functional foods.
特許文献 1 :特開平 05-306296 カツォ内臓由来  Patent Document 1: Japanese Patent Application Laid-Open No. 05-306296
特許文献 2 :特許第 3401280号 魚介類由来  Patent Document 2: Patent No. 3401280 Derived from seafood
特許文献 3 :特開平 05-331191 鰹節由来  Patent Document 3: Japanese Patent Laid-Open No. 05-331191
特許文献 4:特開平 06-345664 チーズホエー由来 特許文献 5 :特許第 3129523号 卵白アルブミン由来 Patent Document 4: JP-A-06-345664 Derived from cheese whey Patent Document 5: Patent No. 3129523 Ovalbumin-derived
特許文献 6 :特再 2001-884948 牛乳由来  Patent Document 6: Toku 2001-84948 derived from milk
特許文献 7 :特開平 06-277090 カゼイン由来  Patent Document 7: JP-A-06-277090 derived from casein
非特許文献 l :Yoshikawaら Agric. Biol. Chem., 48, 3185-, 1984.  Non-patent literature l: Yoshikawa et al. Agric. Biol. Chem., 48, 3185-, 1984.
非特許文献 2 : Fukudomeら FEBS Lett. 296, 107-111, 1984  Non-Patent Document 2: Fukudome et al. FEBS Lett.296, 107-111, 1984
非特許文献 3 : Maruyamaら Agric. Biol. Chem., 46, 1393-1394, 1982.  Non-Patent Document 3: Maruyama et al. Agric. Biol. Chem., 46, 1393-1394, 1982.
非特許文献 4 : Miyoshiら Agric. Biol. Chem., 55, 1313-1318,1991  Non-Patent Document 4: Miyoshi et al. Agric. Biol. Chem., 55, 1313-1318, 1991
非特許文献 5 :末綱， 日水誌 65, 92-96, 1999  Non-Patent Document 5: Suezuna, Nissui Magazine 65, 92-96, 1999
非特許文献 6 : Suetsunaら J. Nutr. Biochem  Non-Patent Document 6: Suetsuna et al. J. Nutr. Biochem
発明の開示  Disclosure of the invention
発明が解決しょうとする課題  Problems to be solved by the invention
[0005] 従来力ものタンパク質由来の消化ペプチドがもつ生体調節機能を利用するために は、 2つの問題があった。  [0005] There have been two problems in using bioregulatory functions of digestive peptides derived from powerful proteins.
[0006] ひとつは、機能性ペプチドを栄養補助食品として摂取するためには、まず、タンパク 質から、機能性ペプチドを調製する必要がある。ところが、食品を酵素分解して機能 性ペプチドを調製 '精製するには手間と費用がかかり、たとえ粗精製の段階でも比較 的高価な商品となる。また、製造した機能性ペプチドがさらに消化液で分解されて効 力を失う可能性もあった。  [0006] First, in order to ingest a functional peptide as a dietary supplement, it is necessary to first prepare the functional peptide from a protein. However, preparing and purifying functional peptides by enzymatically decomposing foods is troublesome and expensive, and even at the stage of crude purification, it is a relatively expensive product. In addition, there was a possibility that the produced functional peptide was further degraded by digestive juice and lost its efficacy.
[0007] 他方、生体内で機能性消化ペプチドを作り出す食品を習慣的に喫食し、体内で消 化により機能性ペプチドを生じさせるためには、まず、効率的に体内で目的とする機 能を発現する機能性ペプチドを生じる食品を探索しなければならない。さらに、食品 として摂取する以上、効果の期待できる量を日常的に摂取できることも必要である。  [0007] On the other hand, in order to habitually eat a food that produces a functional digestive peptide in the living body and generate a functional peptide by digestion in the body, firstly, the desired function in the body must be efficiently performed. Foods that produce the functional peptide to be expressed must be sought. In addition, it is necessary to be able to take the expected amount of effect on a daily basis as long as it is consumed as food.
[0008] このように、現有技術での消化ペプチドの調製は、克服すべき点が多ぐこれらの 制限を一挙に解決するためには、普段から多く食べられているタンパク質性食品の 生体調節機能を高める何らかの技術開発が必要と考えられる。  [0008] As described above, the preparation of digested peptides using existing technologies has many points to be overcome. In order to overcome these limitations at once, the bioregulatory function of protein foods, which are usually eaten frequently, is required. It is considered necessary to develop some technology to increase the quality.
課題を解決するための手段  Means for solving the problem
[0009] そこで、発明者らは、動物性蛋白源として最も一般的である筋肉タンパク質に着目 し、上記した機能性消化ペプチドの機能をできるだけ高め、効率的に機能性べプチ ドを有効利用できないか検討をおこない、その結果、血圧調節作用を効果的に改善 できる方法を開発した。 [0009] Therefore, the present inventors focused on muscle protein, which is the most common animal protein source, to enhance the function of the above-mentioned functional digestive peptide as much as possible, and to efficiently function the functional peptide. Investigations were conducted to determine whether or not the drug could be used effectively, and as a result, a method that could effectively improve blood pressure regulation was developed.
[0010] 本件発明者らは、メイラード反応を介してさまざまな糖類を筋肉タンパク質に結合さ せ、その水溶化、安定化、乳化能の改変などを実現化させてきた。この糖修飾タンパ ク質は、食品としてのさまざまな用途が考えられている。  [0010] The present inventors have linked various saccharides to muscle proteins via the Maillard reaction, and realized their water-solubility, stabilization, modification of emulsifying ability, and the like. This sugar-modified protein is considered for various uses as food.
[0011] 新しい食品素材を開発'利用する際には、その安全性の確認と同時に、消化吸収 性の評価を行なう必要がある。そこで、本件発明者らはこの糖修飾タンパク質の消化 性を検討した。その結果、消化管で分泌される主要な消化酵素、すなわち胃で分泌 されるペプシンに対してはやや消化抵抗性を有し、一方、小腸で消化されるトリプシ ンの作用をうけてほぼ完全に消化されると 、う特性を見!、だした（図 1)。  [0011] When developing and using a new food material, it is necessary to evaluate its digestibility and absorbability while confirming its safety. Therefore, the present inventors examined the digestibility of this sugar-modified protein. As a result, it is somewhat digestive resistant to the major digestive enzyme secreted in the gastrointestinal tract, pepsin secreted in the stomach, while almost completely protected from the action of trypsin digested in the small intestine. When digested, they began to see the characteristics! (Figure 1).
[0012] この知見は、糖分子を結合させることによって筋肉タンパク質のもつ「消化されやす さ」はほとんど損なわれていないものの、消化酵素に対する感受性が変化したことを 示している。すなわち、消化'吸収過程で生成する消化ペプチドが異なることが明ら かである。実際、ゲル濾過分析によって（図 2)、消化パターンが異なることが簡単に 確認できた。これは、糖修飾によって新たな機能性消化ペプチドを体内で生成させう る可能性を示している。そこで本発明者らは、この糖修飾タンパク質の血圧調節作用 を詳細に検討した。 [0012] This finding indicates that the susceptibility to digestive enzymes was altered by the attachment of sugar molecules, although the "digestibility" of muscle proteins was hardly impaired. In other words, it is clear that the digested peptide generated in the digestion-absorption process is different. In fact, gel filtration analysis (Figure 2) could easily confirm that the digestion pattern was different. This indicates the possibility of generating a new functional digested peptide in the body by sugar modification. Therefore, the present inventors have studied in detail the blood pressure regulating action of this glycosylated protein.
[0013] その結果、図 3に示すように、魚肉タンパク質本来の持っている血圧調節作用が著 しく増強されて!、ると!/、う従来に全く報告例のな!、新事実を見 、だした。  [0013] As a result, as shown in Fig. 3, the blood pressure regulating action inherent to fish meat protein is significantly enhanced! I'm out.
[0014] さらに得られた血圧上昇抑制効果が、少なくとも 8時間持続することも確認できた。  [0014] It was also confirmed that the obtained blood pressure increase suppression effect lasted for at least 8 hours.
この持続効果は本発明で得られた魚肉タンパク質の特徴である。  This lasting effect is characteristic of the fish meat protein obtained in the present invention.
発明の効果  The invention's effect
[0015] 本件発明により、優れた血圧調節機能を有するタンパク質又は肉類を、効率的に 調製することができる。本発明のタンパク質は食品に含まれている状態で喫食するこ とにより、消化管内で優れた血圧調節作用を有する機能性ペプチドを生成して血圧 を調節する。そのため、あら力じめ消化ペプチドを調製する必要がなぐまた肉類や 筋肉タンパク質等という日常的に身近な食品の生体調節機能を増強したことによって 、さまざまな加工食品への利用が可能であることから、特別に意識することなくその効 果の恩恵を受ける食生活を提供することができる。 [0015] According to the present invention, a protein or meat having an excellent blood pressure regulating function can be efficiently prepared. The protein of the present invention, when eaten while contained in food, produces a functional peptide having an excellent blood pressure regulating action in the digestive tract to regulate blood pressure. Therefore, it is not necessary to prepare digestive peptides for the first time, and by enhancing the bioregulatory function of daily familiar foods such as meat and muscle proteins, it can be used for various processed foods. , Without any special awareness A diet that benefits from the fruits can be provided.
[0016] 本明細書は本願の優先権の基礎である日本国特許出願 2004-173963号の明細書 および Zまたは図面に記載される内容を包含する。  [0016] This description includes part or all of the contents as disclosed in the description and Z or drawings of Japanese Patent Application No. 2004-173963, which is a priority document of the present application.
図面の簡単な説明  Brief Description of Drawings
[0017] [図 1]糖修飾によって起きる筋肉タンパク質の消化酵素に対する感受性変化。 サケ 筋肉の 7.8%重量に相当するアルギン酸オリゴ糖を結合させた糖修飾筋肉タンパク質 (リジン修飾率 8.0%)をペプシンで 3時間消化 (pH2.0)後、さらにトリプシンで 3時間消 化 (PH7.0)した。それぞれの消化率は、消化画分中の窒素量力も算出した。この結 果は、糖分子を結合させることによって筋肉タンパク質のもつ「消化されやすさ」はほ とんど損なわれて 、な 、ものの、消化酵素に対する感受性が変化したことを示して ヽ る。  FIG. 1 shows changes in sensitivity of muscle proteins to digestive enzymes caused by sugar modification. Glycosylated muscle protein (lysine modification rate 8.0%) bound to alginate oligosaccharides equivalent to 7.8% by weight of salmon muscle is digested with pepsin (pH 2.0) for 3 hours, and further digested with trypsin for 3 hours (PH7. 0). For each digestibility, the nitrogen content in the digested fraction was also calculated. This result indicates that the “digestibility” of the muscle protein was almost impaired by binding the sugar molecule, but the sensitivity to digestive enzymes was changed.
[図 2]アルギン酸オリゴ糖修飾によって起きる魚肉タンパク質の消化性の変化。 サケ 筋肉の 7.8%重量に相当するアルギン酸オリゴ糖を結合させた糖修飾筋肉タンパク質 (參：リジン修飾率 8.0%)をペプシンで 3時間消化 (pH2.0)後、さらにトリプシンで 3時 間消化 (PH7.0)し、その消化物の分子量分布をゲル濾過分析 (Vo：排除限界分子量 2500)によって調べた。通常の魚肉（〇）と比べて矢印部分のペプチド分布が大きく 異なっているのがわかる。  [Figure 2] Changes in digestibility of fish meat protein caused by alginate oligosaccharide modification. Digestion of a sugar-modified muscle protein (referred to as lysine modification rate 8.0%) to which alginate oligosaccharide equivalent to 7.8% of the weight of salmon muscle was digested with pepsin (pH 2.0), and further digested with trypsin for 3 hours ( PH 7.0), and the molecular weight distribution of the digest was examined by gel filtration analysis (Vo: exclusion limit molecular weight 2500). It can be seen that the peptide distribution at the arrow is significantly different from the normal fish meat (〇).
[図 3]本発明で得た糖修飾筋肉タンパク質の血圧調節機能 投与前の SHRラットの 収縮期血圧（口）に対し、糖修飾筋肉タンパク質 (サケ筋肉の 7.8%重量に相当する 糖を結合させた)を体重 lkgあたり 170 (〇）および 670mg (△)経口投与すると、血圧の 速やかな低下が観察された。未処理のサケ肉に同量の糖を混合した場合 (參：タンパ ク質としての投与量 670mg/kg体重）は、血圧の低下は僅かであり、本発明の効果が 顕著に観察できる。  [Fig. 3] Blood pressure-regulating function of sugar-modified muscle protein obtained by the present invention. Glucose-modified muscle protein (sugar equivalent to 7.8% by weight of salmon muscle) is bound to systolic blood pressure (mouth) of SHR rat before administration. ) Was orally administered at 170 () and 670 mg (あ た り) per kg body weight, and a rapid decrease in blood pressure was observed. When untreated salmon meat is mixed with the same amount of sugar (see: 670 mg / kg body weight as a protein), the blood pressure is slightly reduced, and the effect of the present invention can be remarkably observed.
[図 4]本発明で得た糖修飾筋肉タンパク質の血圧上昇抑制機能。 10週齢 SHRラッ トに対して、糖修飾筋肉タンパク質 (サケ筋肉の 7.8%重量に相当する糖を結合させ た）を、 15日間および 28日間、毎日経口投与した。まず未投与の SHRラット（〇）で は、加齢に伴って徐々に収縮期血圧の上昇が観察された。これに対して、体重 lkgあ たり 70mg (A)を毎日投与した場合には、血圧上昇が抑制された。さらに、 170mg (口） を毎日投与した場合には、血圧の上昇が全く起こらな力つた。（*:危険率 5%、 **:危 険率 1%) FIG. 4 shows the blood pressure-inhibiting function of the sugar-modified muscle protein obtained by the present invention. 10-week-old SHR rats were orally dosed daily with glucose-modified muscle protein (conjugated with sugar corresponding to 7.8% by weight of salmon muscle) for 15 and 28 days. First, in untreated SHR rats (〇), systolic blood pressure gradually increased with age. In contrast, daily administration of 70 mg (A) / kg body weight suppressed blood pressure elevation. In addition, 170mg (mouth) Administered daily, no increase in blood pressure occurred. (*: Risk rate 5%, **: risk rate 1%)
発明を実施するための最良の形態  BEST MODE FOR CARRYING OUT THE INVENTION
[0018] 本件発明は、肉類又はタンパク質に還元糖類を結合させることによって消化酵素に 対する基質としての反応性を変化させ、それによつて優れた血圧調節作用を付与す るというものである。 [0018] The present invention is intended to change the reactivity of digestive enzymes as a substrate by binding reducing sugars to meat or protein, thereby imparting an excellent blood pressure regulating action.
[0019] 本願発明には、例えば、（1)タンパク質を還元糖類と混合後、脱水し、 30〜70°Cの 環境下で水分含量を 0.25〜6%に維持することを特徴とする血圧降下用糖修飾タン パク質の調製方法、及び (2)タンパク質を還元糖類と混合後、脱水し、相対湿度 70 %以下でかつ 30〜70°Cの環境に保持することを特徴とする血圧降下用糖修飾タン パク質の調製方法が包含される。  [0019] The present invention provides, for example, (1) a method of lowering blood pressure, which comprises mixing a protein with a reducing sugar, dehydrating the mixture, and maintaining a water content of 0.25 to 6% in an environment of 30 to 70 ° C. A method for preparing a sugar-modified protein for use in blood pressure reduction, comprising: (2) mixing a protein with a reducing sugar, dehydrating the mixture, and maintaining the environment at a relative humidity of 70% or less and an environment of 30 to 70 ° C. Methods for preparing the sugar-modified protein are included.
[0020] 以下に、肉類又はタンパク質に還元糖類を結合させることによるタンパク質の血圧 降下作用を増強する具体的方法を説明する。  Hereinafter, a specific method for enhancing the blood pressure lowering effect of a protein by binding a reducing sugar to meat or protein will be described.
[0021] [タンパク質を還元糖類で修飾する方法]  [Method of Modifying Protein with Reducing Sugar]
肉類又はタンパク質に還元糖類を結合させる方法としては、タンパク質の反応性リ ジン残基と還元糖類の還元末端の間でメイラード反応を起こさせ、両者の間に共有 結合を生じさせる。この際、反応を速やかに進行させるには肉類又はタンパク質と糖 の混合物の水分を 6%以下に調節する、又は相対湿度 35%以下の環境に 40°C以上 で保持することが望まし ヽ (本研究者による特許公開： 2003-169634)が、タンパク質 の種類によってはこれに限られず、相対湿度を 70%以下の範囲とすることもできる（ 実施例 5)。  As a method of binding a reducing saccharide to meat or protein, a Maillard reaction is caused between a reactive lysine residue of the protein and the reducing end of the reducing saccharide, and a covalent bond is formed between the two. At this time, in order to make the reaction proceed promptly, it is desirable to adjust the water content of the meat or the mixture of protein and sugar to 6% or less, or to maintain the environment at a relative humidity of 35% or less at 40 ° C or more. However, depending on the type of protein, the relative humidity can be set to a range of 70% or less (Example 5).
[0022] 水分の調節方法としては、例えば、タンパク質と糖の混合物を脱水処理するが、具 体的には、相対湿度 10%の低湿度下での加熱処理、又は凍結乾燥、噴霧乾燥、減 圧乾燥等の処理あるいはこれらを組み合わせて処理することにより、肉類又はタンパ ク質と糖の混合物の水分を 6%以下にすることができる。好適には凍結乾燥処理が 望ましい。肉類又はタンパク質と糖の混合物の水分含量力 脱水処理終了時点で 6 %を上回るものであったとしても、相対湿度 35%以下で、 30〜70°C、より具体的には 、例えば、 40°C以上 70°C以下に保持することにより、水分含量を 6%以下の範囲に することもできる。なお、肉類及び筋肉タンパク質は、本処理の条件下で還元糖を結 合させることによって水溶ィ匕される。 [0022] As a method for adjusting the water content, for example, a mixture of protein and sugar is dehydrated. Specifically, heat treatment is performed at a low humidity of 10% relative humidity, or freeze drying, spray drying, and reduction. By treatment such as pressure drying or a combination thereof, the water content of meat or a mixture of protein and sugar can be reduced to 6% or less. Preferably, freeze-drying is desirable. Moisture content power of a mixture of meat or protein and sugar Even if it exceeds 6% at the end of the dehydration treatment, at a relative humidity of 35% or less, 30 to 70 ° C, more specifically, for example, 40 ° By keeping the temperature between C and 70 ° C, the water content is kept within 6%. You can also. It should be noted that meat and muscle proteins are water-soluble by binding reducing sugars under the conditions of this treatment.
[0023] メイラード反応の制御については、例えば、タンパク質を還元糖と 1 : 0.5から 10の範 囲で混合して凍結乾燥し、水分量を 0.6-3%程度に調節する。これを恒温恒湿度下 4 0〜60°C、相対湿度 35%程度に数時間〜 4日間保持する。これによつて、タンパク質 のリジン残基と糖の還元末端の間でメイラード反応を起こさせることができる。タンパク 質中のリジン修飾率力 -40%程度になった時点で冷却 (氷蔵）して反応を停止する ことにより、 目的にあった量の還元糖をタンパク質に結合させる（すなわち糖修飾する )ことができる。  For the control of the Maillard reaction, for example, a protein is mixed with a reducing sugar in the range of 1: 0.5 to 10 and freeze-dried to adjust the water content to about 0.6-3%. It is kept at a constant temperature and humidity of 40 to 60 ° C and a relative humidity of about 35% for several hours to 4 days. This allows a Maillard reaction to occur between the lysine residue of the protein and the reducing end of the sugar. Lysine modification rate in the protein When it reaches about -40%, the reaction is stopped by cooling (chilling on ice) to bind the desired amount of reducing sugar to the protein (that is, sugar modification). Can be.
[0024] [血圧降下作用]  [0024] [Hypertensive action]
このようにして肉類又はタンパク質の反応性リジン残基に還元糖類を結合させると、 タンパク質の高次構造に変化が生じ、そのさまざまな性質に影響がおよぶ。たとえば アルギン酸オリゴ糖を結合させた場合には、反応性リジン残基の 2%以上の糖鎖が結 合することによって魚肉タンパク質の消化性に変化が生じ、その結果、以下に説明す る実施例 1と 2に示されるように血圧降下調節作用の増強効果が認められる。したが つて、本願発明の方法で糖修飾された肉類又は糖修飾タンパク質は、血圧降下のた めに用いることができる。  Binding of a reducing saccharide to a reactive lysine residue of a meat or protein in this way results in a change in the higher order structure of the protein, affecting its various properties. For example, when an alginate oligosaccharide is bound, the digestibility of fish meat protein changes due to the binding of sugar chains of 2% or more of the reactive lysine residues. As shown in 1 and 2, the effect of enhancing the blood pressure lowering regulation effect is observed. Therefore, the meat or sugar-modified protein sugar-modified by the method of the present invention can be used for lowering blood pressure.
[0025] なお糖修飾反応を継続し続けると、メイラード反応生成物を介してタンパク質間の 重合が起こり、結果として消化性の低下に伴って増強した血圧調節作用は徐々に減 少することも確認できた (実施例 2)。  [0025] It was also confirmed that, when the sugar modification reaction was continued, polymerization between proteins occurred via the Maillard reaction product, and as a result, the blood pressure regulating effect enhanced with a decrease in digestibility was gradually reduced. (Example 2)
[0026] [原材料]  [0026] [Raw materials]
本発明で使用できるタンパク質としては、種々のタンパク質が挙げられる力 具体的 には、筋肉タンパク質、卵白アルブミン、プロタミン、大豆タンパク質などを挙げること ができる。筋肉タンパク質としては、魚肉、畜肉、貝類、イカ類などあらゆる生物の筋 肉タンパク質が挙げられる。これらは良く洗浄しても利用するのはもちろん、脂質や水 溶性低分子成分など筋肉タンパク質以外の食品成分が含まれていても全く差し支え がない。筋肉タンパク質には、ミオシン、ァクチン、トロポミオシン、トロポニン等が包含 される。プロタミンとしては、例えば、魚類精巣由来のもの、具体的には、サケ精巣由 来のプロタミンを挙げることができる。 Proteins that can be used in the present invention include various proteins. Specific examples include muscle protein, ovalbumin, protamine, soy protein, and the like. Muscle proteins include those of all living organisms such as fish meat, animal meat, shellfish, and squid. These can be used even if they are thoroughly washed, and food ingredients other than muscle proteins such as lipids and water-soluble low molecular weight ingredients can be contained at all. Muscle proteins include myosin, actin, tropomyosin, troponin and the like. As protamine, for example, those derived from fish testis, specifically, salmon testis Protamine can be mentioned.
[0027] 本願発明で使用できる肉類には、上記した魚肉、畜肉、貝類、イカ類などあらゆる 生物の筋肉細切りした筋肉が含まれる。細切りとは、上記肉を種々の手段で切断す ることを意味し、例えば、ホモジナイズ処理及び挽肉処理などが含まれ、好適には 5ミ リ、更に好適には 3ミリ以下の網目を通過する程度にまで細切り、あるいはミンチとす ることが望ましい。  [0027] Meats that can be used in the present invention include the above-described fish meat, animal meat, shellfish, squid, and any other living organisms that have been minced. Shredding means cutting the above meat by various means, for example, including homogenizing treatment and minced meat treatment, preferably passing through a mesh of 5 mm, more preferably 3 mm or less. It is desirable to chop or mince to the extent.
[0028] 本発明で使用できる還元糖類の例として実施例 1、 2では、平均重合度 6のアルギ ン酸オリゴ糖についての結果を示したが、実施例 3に示すように還元性を有する他の 糖質 (還元糖)においても同様の効果が期待できる。どの還元糖類を利用するかは、 商品開発の目的とそれに伴う対費用効果によって決定すればよい。  [0028] In Examples 1 and 2 as examples of reducing sugars that can be used in the present invention, the results for alginate oligosaccharides having an average degree of polymerization of 6 were shown. A similar effect can be expected for carbohydrates (reducing sugars). Which reducing sugar to use depends on the purpose of product development and the associated cost-effectiveness.
[0029] 本件発明で使用できる還元糖類としては、単糖 (グルコース、リボースなど)、平均重 合度 20以下のオリゴ糖類で還元末端を有しているもの、例えば、アルギン酸オリゴ糖 、キトサンオリゴ糖などの還元性オリゴ糖が挙げられる。  [0029] The reducing saccharides usable in the present invention include monosaccharides (glucose, ribose and the like), oligosaccharides having an average degree of polymerization of 20 or less and having a reducing end, such as alginic acid oligosaccharides and chitosan oligosaccharides. Of the reducing oligosaccharides.
[0030] 本件発明で熱的に不安定なタンパク質 (たとえば冷水域に棲息する魚類の筋肉タ ンパク質)を利用する場合には、水分調節の過程や糖修飾の過程でタンパク質の変 性を抑制するために還元糖類と同時に変性防止剤を混合することが望まし 、。本件 発明におけるタンパク質変性防止剤としては、ソルビトールゃトレハロース等が挙げら れる。タンパク質変性防止剤は、添加する還元糖類のタンパク質変性防止効果が小 さい場合 (たとえば、アルギン酸オリゴ糖等）に特に有効である。なおグルコースのよう に、変性防止効果を有する還元糖類を用いる場合には、他の変性防止剤との併用 は不要である。  [0030] In the present invention, when a thermally unstable protein (for example, a muscle protein of a fish that lives in a cold water area) is used, protein modification is suppressed in the process of water regulation and in the process of sugar modification. In order to achieve this, it is desirable to mix a denaturing inhibitor with the reducing saccharide. Examples of the protein denaturation inhibitor in the present invention include sorbitol pertrehalose. The protein denaturation inhibitor is particularly effective when the reducing saccharide to be added has a small effect on preventing protein denaturation (eg, alginate oligosaccharide). When a reducing saccharide having a denaturation-preventing effect, such as glucose, is used, it is not necessary to use it in combination with another denaturation inhibitor.
[0031] 糖修飾タンパク質の調製過程における肉類又は筋肉タンパク質とアルギン酸オリゴ 糖 (還元糖)の混合比（重量）は、のぞましくは 1 : 0.1〜1 : 1Οの範囲である力 その組 成自体には特段の指定はなぐ要は糖修飾によってタンパク質の消化性に変化が生 じさえすればよい。  [0031] The mixing ratio (weight) of the meat or muscle protein and the alginate oligosaccharide (reducing sugar) in the preparation process of the sugar-modified protein is preferably in the range of 1: 0.1 to 1: 1Ο. In fact, it is only necessary to change the digestibility of proteins by sugar modification.
[0032] [用途、使用方法]  [0032] [Uses and usage]
本発明の方法で調製された糖修飾タンパク質又は糖修飾肉類は、その製造過程 で試薬類を用いて ヽな 、ので基本的に食品素材としての利用が可能であり、それゆ え、本発明の目的である、食品として喫食した際に得られるタンパク質の生体調節機 能の高度な活用に合致して 、る。 The sugar-modified protein or the sugar-modified meat prepared by the method of the present invention can be basically used as a food material because the sugar-modified protein or sugar-modified meat is prepared using reagents in the production process. This is in accordance with the object of the present invention, that is, the advanced use of the bioregulatory function of a protein obtained when eaten as a food.
[0033] また本発明の方法で処理された糖修飾タンパク質又は糖修飾肉類は水溶性にもで きるので、消化吸収性が良ぐ更に、他の食品飲料材料と容易に混合できる。  [0033] The sugar-modified protein or sugar-modified meat treated by the method of the present invention can also be made water-soluble, so that it has good digestibility and absorbability and can be easily mixed with other food and beverage materials.
[0034] 本願発明の血圧降下用タンパク質又は血圧降下用肉類は、血圧降下因子として 作用する。本願発明の血圧降下用タンパク質又は血圧降下用肉類は、経口で、その まま投与することが可能である。  [0034] The blood pressure lowering protein or the blood pressure lowering meat of the present invention acts as a blood pressure lowering factor. The blood pressure lowering protein or the blood pressure lowering meat of the present invention can be administered orally as it is.
[0035] 更に、本願発明の血圧降下用タンパク質又は血圧降下用肉類は、他の食品に添 カロして、又は混合して、食品として摂取することも、飲料に添加又は混合して飲料とし て摂取することも可能である。又血圧降下剤として用いる場合は、製剤様担体と混合 し製剤とすることができる。例えば、錠剤、カプセル剤、顆粒剤、散剤とすることができ る。添加剤としては、糖類'糖アルコール類 (例えば、乳糖、ブドウ糖、マンニット、デ キストリン、シクロデキストリン、庶糖）、多糖類 (デンプン、カルボキシメチルセルロー スナトリウム、ヒドロキシプロピルデンプン、カルボキシメチルセルロースカルシウム、メ チノレセノレロース、ヒドロキシプロピノレセノレロース、ヒドロキシプロピノレメチノレセノレロース 、；)、ゼラチン、ガム類 (アラビアゴム）、合成高分子 (ポリビュルピロリドン、ポリビュル アルコール）、タルク、トラガント、ベントナイト、ビーガム、ソルビタン脂肪酸エステル、 ラウリル硫酸ナトリウム、グリセリン、脂肪酸グリセリンエステル、プロピレングリコール等 が挙げられる。  [0035] Further, the protein for lowering blood pressure or meat for lowering blood pressure of the present invention may be added to or mixed with other foods as a food, or added to or mixed with a beverage to obtain a beverage. Ingestion is also possible. When used as a hypotensive agent, it can be mixed with a preparation-like carrier to prepare a preparation. For example, tablets, capsules, granules, and powders can be used. Additives include sugars, sugar alcohols (eg, lactose, glucose, mannitol, dextrin, cyclodextrin, sucrose), polysaccharides (starch, sodium carboxymethylcellulose, hydroxypropyl starch, calcium carboxymethylcellulose, methino). Resenorelose, hydroxypropynolesenorelose, hydroxypropinolemethinoresenorelose,;), gelatin, gums (gum arabic), synthetic polymers (polyvinylpyrrolidone, polyvinyl alcohol), talc, tragacanth, bentonite, veegum, Examples include sorbitan fatty acid esters, sodium lauryl sulfate, glycerin, fatty acid glycerin esters, propylene glycol and the like.
[0036] 本願の血圧降下用タンパク質又は血圧降下用肉類は、 1日あたり、タンパク質量と して、体重 lkgあたり 0.05gから 2g、好適には O. lgから lg摂取することが望ましい。本 願発明の血圧降下用タンパク質は、 7日から 21日連続して、又は、 2日程度の間隔を 置 、て摂取することも可能である。  [0036] The protein for lowering blood pressure or meat for lowering blood pressure of the present application is desirably ingested from 0.05 g to 2 g, preferably from O.lg to lg per kg of body weight per day as a protein amount. The protein for lowering blood pressure of the present invention can be taken continuously for 7 to 21 days or at intervals of about 2 days.
[0037] 更に、本願発明は、前述した調製方法によって製造された血圧降下用タンパク質 又は血圧降下用肉類を有効成分としてふくむ抗高血圧剤又は血圧降下剤も包含す る。その投与方法は、上述した、血圧降下用タンパク質又は血圧降下用肉類の摂取 方法と同様である。  [0037] The present invention further includes an antihypertensive agent or a hypotensive agent containing, as an active ingredient, an antihypertensive protein or an antihypertensive meat produced by the above-mentioned preparation method. The administration method is the same as the above-mentioned method of ingesting the blood pressure lowering protein or the blood pressure lowering meat.
[0038] 次に本件発明の方法を実施例によって詳細に説明する。 実施例 1 Next, the method of the present invention will be described in detail with reference to examples. Example 1
[0039] サケ筋肉への血圧調節機能付与 (糖修飾タンパク質の安全性、糖修飾タンパク質の 投与量が本発明の効果におよぼす影響）  [0039] Addition of blood pressure regulating function to salmon muscle (safety of sugar-modified protein, effect of dosage of sugar-modified protein on effect of the present invention)
サケ筋肉を 2mm目（JIS-8811)のふるいを通過するサイズまでミートチョッパーで細 切した。この魚肉 100g対してそれに含まれる筋肉タンパク質量（14%湿重量）と等量 のアルギン酸オリゴ糖（14g)と、タンパク質冷凍変性防止剤としてソルビトール（14g) を混合した後、凍結乾燥によって水分を 4.2%に調節した。続いて 60°C (相対湿度 3 5%)で 3時間保持したところ、アルギン酸オリゴ糖はサケ筋肉中の 8%のリジン残基と 反応して糖修飾タンパク質 (重量比で 7.8%に相当する糖が結合)を形成した。  The salmon muscle was minced with a meat chopper to a size that passed through a 2 mm (JIS-8811) sieve. To 100 g of this fish meat, an alginate oligosaccharide (14 g) equivalent to the amount of muscle protein (14% wet weight) contained in it and sorbitol (14 g) as a protein freezing and denaturation inhibitor were mixed, and then lyophilized to remove water. Adjusted to%. Then, after keeping at 60 ° C (35% relative humidity) for 3 hours, the alginate oligosaccharide reacts with 8% of lysine residues in salmon muscle and reacts with glycosylated protein (sugar equivalent to 7.8% by weight). Formed a bond).
[0040] この糖修飾タンパク質の消化酵素に対する感受性を調べた。まず、ペプシンで 3時 間消化 (PH2.0)後、さらにトリプシンで 3時間消化 (pH7.0)した。それぞれの消化率は 、消化画分中の窒素量力も算出した。結果を図 1に示すが、サケの筋肉タンパク質が アルギン酸オリゴ糖修飾を受けることによって、その感受性に変化が生じたことが分 かる。更に、消化物の分子量分布をゲル濾過分析 (Vo :排除限界分子量 2500)によ つて調べた。結果を図 2に示す力 このように、糖修飾の前後で消化物の分布が異な ることを確認した。 [0040] The sensitivity of this sugar-modified protein to digestive enzymes was examined. First, it was digested with pepsin for 3 hours (PH2.0), and further digested with trypsin for 3 hours (pH 7.0). For each digestibility, the amount of nitrogen in the digested fraction was also calculated. The results are shown in FIG. 1 and show that salmon muscle protein was modified by alginate oligosaccharide modification to change its sensitivity. Further, the molecular weight distribution of the digest was examined by gel filtration analysis (Vo: exclusion limit molecular weight 2500). The results are shown in Fig. 2. Thus, it was confirmed that the distribution of digests was different before and after the sugar modification.
[0041] また、この糖修飾タンパク質の消化吸収性を、 4週齢の雄 SDラットを用いた飼育試 験で検討した。その結果、 4週間の飼育中、通常の配合飼料と全く差異のない体重 増加を示すことが確認できた。  [0041] The digestion and absorption of this sugar-modified protein was examined in a breeding test using 4-week-old male SD rats. As a result, during breeding for 4 weeks, it was confirmed that the body weight gained was not completely different from that of a normal compound feed.
[0042] そこで、この糖修飾タンパク質の血圧調節機能を調べるため、高血圧症状を呈して V、る 10週齢の雄 SHRラット（体重 220〜260g)に体重あたり 170mgを経口投与したとこ ろ、 2時間後に収縮期血圧が 24 mmHg低下し、この効果は少なくとも 6時間維持され た。さらに体重あたり 670mgを経口投与した実験区では、収縮期血圧が最大 35mmHg 低下し、 8時間経過後も 30 mmHgの低下効果を維持し続けていた。なお、糖修飾して いないタンパク質に上記試料に含まれるのと同量の糖類を混合して SHRラットに負荷 したところ、収縮期血圧の低下範囲は最大で 6mmHgであり、実験区との間には有為 な差異が認められた (危険率 1%)。以上の結果は、アルギン酸オリゴ糖修飾によって 魚肉タンパク質の血圧調節機能が著しく増強されたことを示している（図 3)。 実施例 2 [0042] Therefore, in order to examine the blood pressure regulating function of this glycosylated protein, 170 mg / body weight was orally administered to 10-week-old male SHR rats (body weight 220 to 260 g) exhibiting hypertensive symptoms. After hours, systolic blood pressure dropped by 24 mmHg and this effect was maintained for at least 6 hours. In the experimental group administered orally at 670 mg / body weight, the systolic blood pressure decreased by up to 35 mmHg, and the effect of reducing 30 mmHg was maintained even after 8 hours. When the same amount of saccharide as that contained in the above sample was mixed with unmodified sugar protein and loaded on SHR rats, the range of decrease in systolic blood pressure was at most 6 mmHg. Was significantly different (risk ratio 1%). These results indicate that the modification of alginate oligosaccharides significantly enhanced the blood pressure regulating function of fish meat proteins (Figure 3). Example 2
[0043] サケ筋肉への血圧調節機能付与 (2) (タンパク質に結合した還元糖類の量が本発明 の効果におよぼす影響）  Provision of blood pressure regulating function to salmon muscle (2) (Effect of amount of reducing sugars bound to protein on effect of the present invention)
実施例 1と同様の方法で反応時間を 1.5時間、 3時間、さらに 48時間変化させて、糖 結合量がそれぞれタンパク質重量の 3.0% (P-3.0)、 7.8% (P-7.8)、 13.0% (P-13.0)、 2 0.4% (P-20.4)である糖修飾タンパク質を調製し、これらを 10週齢の雄 SHRラット（体 重 240〜260g)に体重あたり 170mgを経口投与した (糖結合量は糖修飾タンパク質を いったん精製後、フエノール硫酸法によって測定した)。その結果、 P-3.0、 P-7.8で は投与 1時間後に収縮期血圧がそれぞれ 16mmHgと 22mmHg低下し、さらに 4時間後 にはいずれも最大で 28mmHgの減少を示した。さらに、糖結合量を増加させた P- 13.0 でも全く同様の血圧上昇抑制効果が確認できた。一方、糖を修飾していないタンパク 質に上記試料に含まれるのと同量の糖類を混合して SHRラットに負荷したところ、収 縮期血圧は投与 1時間後では全く変化せず、投与 8時間後までの低下は最大で 7 m mHgであった。なお P-20.4では、収縮期血圧は投与 1時間後に 17 mmHgまで低下し た力 それ以上の減少は見られなかった。 P-3.0、 P-7.8, P- 13.0および P- 20.4の糖 によるリジン修飾率はそれぞれ 4.0%、 8.2%、 14.8%および 26.0%で、特に P- 20.4で はメイラード反応の進行に伴う著し 、褐変化が観察できた。他の 3サンプルとは異なり 、 P-20.4では SDS ポリアクリルアミドゲル電気泳動分析によってタンパク質の重合が 認められ、トリプシン キモトリブシンによる消化率の低下（実施例 1に準じて行った） が起こっていた。このようにリジン修飾率 4.0%のタンパク質 (P-3.0)においても糖修 飾による筋肉タンパク質の血圧調節機能の増強が確認できたが、 P-20.4のように褐 変化して過度にメイラード反応が進行すると、その効果が徐々に損なわれることが明 らかとなつた。  In the same manner as in Example 1, the reaction time was changed for 1.5 hours, 3 hours, and further 48 hours, and the amount of sugar linkage was 3.0% (P-3.0), 7.8% (P-7.8), and 13.0% of the protein weight, respectively. (P-13.0) and 20.4% (P-20.4) of sugar-modified proteins were prepared, and these were orally administered to 10-week-old male SHR rats (body weight 240-260 g) at a dose of 170 mg / body weight (sugar bond The amount was determined by the phenol-sulfuric acid method after purifying the sugar-modified protein once). As a result, in P-3.0 and P-7.8, the systolic blood pressure decreased by 16 mmHg and 22 mmHg, respectively, 1 hour after administration, and further decreased by 28 mmHg at maximum after 4 hours. In addition, it was confirmed that P-13.0, in which the amount of sugar linkages was increased, had exactly the same effect of suppressing blood pressure increase. On the other hand, when the same amount of saccharide as that contained in the above sample was mixed with unmodified sugar protein and loaded on SHR rats, the systolic blood pressure did not change at all 1 hour after administration, and The drop over time was a maximum of 7 mmHg. At P-20.4, systolic blood pressure decreased to 17 mmHg 1 hour after administration. No further decrease was seen. The lysine modification rates of the P-3.0, P-7.8, P-13.0, and P-20.4 saccharides were 4.0%, 8.2%, 14.8%, and 26.0%, respectively. , A brown change could be observed. Unlike the other three samples, in P-20.4, protein polymerization was observed by SDS polyacrylamide gel electrophoresis, and the digestibility by trypsin chymotrypsin was reduced (performed according to Example 1). In this way, it was confirmed that sugar modification enhances the blood pressure regulating function of muscle proteins even with a protein with a lysine modification rate of 4.0% (P-3.0), but as shown in P-20.4, it browns and excessive Maillard reaction occurs. It became clear that its effect gradually diminished as it progressed.
実施例 3  Example 3
[0044] 経産牛とグルコース [0044] Multiparous beef and glucose
と畜後 7日間 4°Cで保管した経産牛のもも肉をトリミングして力も挽き肉にし、 5倍量 の生理食塩水で 3回洗浄した。得られた洗浄肉 100gに対してそれに含まれる筋肉タ ンパク質量（10.2%湿重量）の 5倍重量に相当するグルコースを含む水溶液 200mLを 加えて練り込み、薄く延ばして凍結乾燥した (水分含量 1.4%)。続いて 50°C (相対湿 度 5%)で 12時間保持したところ、タンパク質中のリジン残基の 61%がグルコースと反 応した。この糖修飾タンパク質の血圧調節機能を調べるため、高血圧症状を呈して いる 10週齢の雄 SHRラット（体重 230〜288g)に体重あたり 700 mgを経口投与したとこ ろ、 2時間後に収縮期血圧が 21mmHg低下し、この効果は少なくとも 6時間持続した。 一方、糖修飾していないタンパク質に上記試料に含まれるのと同量の糖類を混合し て SHRラットに負荷しても、収縮期血圧は有為な低下を示さな力つた。この結果より、 グルコース修飾による経産牛肉タンパク質の血圧調節機能の増強が確認できた。 実施例 4 Heifers stored at 4 ° C for 7 days after slaughter were trimmed into lean meat and washed three times with 5 volumes of physiological saline. For 100 g of the obtained washed meat, 200 mL of an aqueous solution containing glucose equivalent to 5 times the weight of the muscle protein mass (10.2% wet weight) contained therein was added. In addition, the mixture was kneaded, spread thinly and freeze-dried (water content: 1.4%). Subsequently, the protein was kept at 50 ° C (5% relative humidity) for 12 hours, and 61% of the lysine residues in the protein reacted with glucose. To examine the blood pressure-regulating function of this glycosylated protein, 700 mg / body weight was orally administered to 10-week-old male SHR rats (body weight 230-288 g) exhibiting hypertension. The effect decreased by 21 mmHg and lasted for at least 6 hours. On the other hand, when SHR rats were loaded with the same amount of saccharide as that contained in the above-mentioned sample in a protein that had not been sugar-modified, the systolic blood pressure was significantly reduced. From these results, it was confirmed that glucose modification enhances the blood pressure regulating function of multiparous beef protein. Example 4
[0045] 連続長期投与の影響 (加齢に伴う血圧上昇の抑制効果）  [0045] Effects of continuous long-term administration (effect of suppressing blood pressure increase with aging)
SHRラットは成長に伴って徐々に血圧が上昇していくモデル動物である。 10週齢 の雄 SHRラットを 4週間飼育するにあたり、実施例 2と同じ糖修飾魚肉（P-7.8)を体 重あたり 70および 170 mgを 1日 1回経口投与し、血圧の変化を調査した。その結果、 図 4に示すように、通常の SHRラットの収縮期血圧が 4週間で 13 mmHg増加したの に対し、糖修飾魚肉を投与しつづけたラットでは、血圧上昇を有意に抑制することが できた。さらに，このような継続投与をおこなっても，糖修飾魚肉の投与直後に起きる 血圧の低下効果は全く損なわれな力つた。  SHR rats are model animals whose blood pressure gradually increases with growth. When breeding 10-week-old male SHR rats for 4 weeks, the same sugar-modified fish meat (P-7.8) as in Example 2 was orally administered once daily at 70 and 170 mg per body weight, and changes in blood pressure were investigated. . As a result, as shown in Fig. 4, the systolic blood pressure of normal SHR rats increased by 13 mmHg in 4 weeks, whereas that of rats continuously treated with sugar-modified fish meat significantly inhibited the increase in blood pressure. did it. Furthermore, even with such continuous administration, the blood pressure lowering effect that occurs immediately after the administration of sugar-modified fish meat was not impaired at all.
実施例 5  Example 5
[0046] 卵タンパク質への血圧調節機能付与  [0046] Addition of blood pressure regulating function to egg protein
卵白アルブミン（主成分はオボアルブミン）は白色レグホンの卵白を pH 5.6で酸沈 殿した後、遠心分離で回収し、 lOmMNaClに懸濁後 HC1で中和し回収した。このタン ノ ク質溶液を 100mg/mlに調製し、続いて 0.1Mマルトースを溶解して凍結乾燥した。 そして、直ちに 60°C、相対湿度 65%に 4日間保持して卵白アルブミン分子にマルトー スを結合させた。さらに硫安分画によってこの糖修飾タンパク質力 未反応のマルト ースを除去した。  Ovalbumin (mainly ovalbumin) was obtained by acid precipitation of white leghorn egg white at pH 5.6, followed by centrifugation, suspension in lOmMNaCl, and neutralization with HC1 to recover. This protein solution was adjusted to 100 mg / ml, then 0.1 M maltose was dissolved and lyophilized. Then, the maltose was immediately bound to the ovalbumin molecule by keeping it at 60 ° C and a relative humidity of 65% for 4 days. Further, unreacted maltose was removed by ammonium sulfate fractionation.
[0047] 上記によって得た卵白アルブミンは 53%の有効性リジンが減少しており、 1/500重 量比のペプシン処理を行ったところ、タンパク質の分解様式が異なって 、ることを SDS -ポリアクリルアミドゲル電気泳動分析によって確認した。そこで、この糖修飾タンパク 質の血圧調節機能を調べるため、高血圧症状を呈している 10週齢の雄 SHRラット（ 体重 240〜260g)に体重あたり lOOOmgを経口投与したところ、 2時間後に収縮期血圧 が 22 mmHg低下し、この効果は少なくとも 6時間維持された。糖修飾していない卵白 アルブミンに上記試料に含まれるのとほぼ同量のマルトースを混合して SHRラットに 負荷しても収縮期血圧の低下範囲は最大で 8mmHgであり、実験区との間には有為 な差異が認められた (危険率 1 %)。 [0047] The ovalbumin obtained as described above has a 53% reduction in the effective lysine, and when subjected to pepsin treatment at a 1/500 weight ratio, the protein degradation mode differs, indicating that Confirmed by acrylamide gel electrophoresis analysis. Therefore, this sugar-modified protein To examine the quality of blood pressure regulating function, 10-week-old male SHR rats (240-260 g in weight) with hypertension were orally administered lOOOOmg / body weight, and 2 hours later, systolic blood pressure decreased by 22 mmHg. This effect was maintained for at least 6 hours. Even if the same amount of maltose as that contained in the above sample was mixed with non-sugar-modified ovalbumin and loaded on SHR rats, the reduction range of systolic blood pressure was 8 mmHg at the maximum. Significant difference was observed (risk ratio 1%).
[0048] 以上の結果は、糖修飾によって卵白アルブミンに血圧調節機能が付加されたことを 示している。 [0048] The above results indicate that sugar modification has added a blood pressure regulating function to ovalbumin.
[0049] 本明細書で引用した全ての刊行物、特許および特許出願をそのまま参考として本 明細書にとり入れるものとする。  [0049] All publications, patents and patent applications cited in this specification are incorporated herein by reference in their entirety.

Claims

請求の範囲 The scope of the claims
[I] タンパク質を還元糖類と混合後、脱水し、 30〜70°Cの環境下で水分含量を 0.25〜6 %に維持することを含む血圧降下用糖修飾タンパク質の調製方法。  [I] A method for preparing a glucose-modified protein for lowering blood pressure, comprising mixing a protein with a reducing saccharide, dehydrating the mixture, and maintaining a water content of 0.25 to 6% in an environment of 30 to 70 ° C.
[2] タンパク質を還元糖類と混合後、脱水し、相対湿度 70%以下でかつ 30〜70°Cの環 境に保持することを含む、血圧降下用糖修飾タンパク質の調製方法。  [2] A method for preparing a sugar-modified protein for lowering blood pressure, comprising mixing a protein with a reducing saccharide, dehydrating the mixture, and maintaining the relative humidity at 70% or less and in an environment of 30 to 70 ° C.
[3] タンパク質力 アルブミン、ミオシン、プロタミン、大豆タンパク質又は筋肉タンパク質 力も選ばれる請求項 1又は 2の血圧降下用糖修飾タンパク質の調製方法。  [3] The method for preparing a sugar-modified protein for lowering blood pressure according to claim 1 or 2, wherein protein power is selected from albumin, myosin, protamine, soy protein or muscle protein.
[4] 脱水を水分含量が 10%以下となるまで行う請求項 1〜3いずれか 1項記載の方法。  [4] The method according to any one of claims 1 to 3, wherein the dehydration is performed until the water content becomes 10% or less.
[5] 還元糖類が、還元性単糖、又は還元性オリゴ糖である請求項 1〜4 ヽずれか 1項記 載の方法。  [5] The method according to any one of claims 1 to 4, wherein the reducing saccharide is a reducing monosaccharide or a reducing oligosaccharide.
[6] 請求項 1から 5いずれか 1項記載の方法で調製された血圧降下用糖修飾タンパク 質。  [6] A sugar-modified protein for lowering blood pressure prepared by the method according to any one of claims 1 to 5.
[7] 軟体動物又は甲殻類の筋肉、魚肉、又は畜肉から選ばれた肉類を細切りし、還元 糖類と混合後、脱水し、相対湿度 70%以下でかつ 30〜70°Cの環境に保持することを 含む、血圧降下用糖修飾肉類の調製方法。  [7] Meats selected from mollusc or crustacean muscle, fish meat, or animal meat are minced, mixed with reducing sugars, dehydrated, and kept in an environment at a relative humidity of 70% or less and 30 to 70 ° C. A method for preparing sugar-modified meat for lowering blood pressure, comprising:
[8] 軟体動物又は甲殻類の筋肉、魚肉、又は畜肉由来の筋肉タンパク質を還元糖類と 混合後、脱水し、相対湿度 70%以下でかつ 30〜70°Cの環境に保持することを含むに よる血圧降下用糖修飾肉類の調製方法。 [8] Molecule or crustacean muscle, fish meat, or muscle protein derived from animal meat is mixed with reducing sugars, dehydrated, and kept in an environment at a relative humidity of 70% or less and 30 to 70 ° C. Of sugar-modified meat for lowering blood pressure according to the present invention.
[9] 脱水を水分含量が 10%以下になるまで行う請求項 7又は 8記載の方法。 [9] The method according to claim 7 or 8, wherein the dehydration is performed until the water content becomes 10% or less.
[10] 還元糖類が、還元性単糖、または、還元性オリゴ糖である請求項 7〜9 ヽずれか 1 項記載の方法。 [10] The method according to any one of claims 7 to 9, wherein the reducing saccharide is a reducing monosaccharide or a reducing oligosaccharide.
[II] 請求項 7〜10いずれ力 1項記載の方法で調製された血圧降下用糖修飾肉類。  [II] A sugar-modified meat for lowering blood pressure, prepared by the method according to claim 1.
[12] 請求項 6記載の血圧降下用糖修飾タンパク質を含む飲食品。 [12] A food or drink comprising the blood sugar lowering protein according to claim 6.
[13] 請求項 11記載の血圧降下用糖修飾肉類を含む飲食品。  [13] A food or drink comprising the sugar-modified meat for lowering blood pressure according to claim 11.
[14] 請求項 6記載の血圧降下用糖修飾タンパク質又は請求項 11記載の血圧降下用糖 修飾肉類を有効成分として含む抗高血圧剤。  [14] An antihypertensive agent comprising, as an active ingredient, the blood sugar lowering modified protein according to claim 6 or the blood sugar lowering modified meat according to claim 11.
[15] タンパク質と糖のメイラード反応で生じる糖修飾タンパク質を有効成分として含む抗 高血圧剤。 肉類と糖のメイラード反応で生じる糖修飾肉類を有効成分として含む抗高血圧剤。 血圧降下に有効である旨の表示を付した請求項 12又は 13記載の飲食品。 [15] An antihypertensive agent containing, as an active ingredient, a sugar-modified protein produced by a Maillard reaction between protein and sugar. An antihypertensive agent comprising as an active ingredient a sugar-modified meat produced by a Maillard reaction between meat and sugar. 14. The food or drink according to claim 12 or claim 13, wherein the food or drink is indicated to be effective for lowering blood pressure.
PCT/JP2005/010643 2004-06-11 2005-06-10 Process for producing protein having its antihypertensive activity enhanced WO2005120541A1 (en)

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