WO2003026685A1 - Agents ameliorant le metabolisme lipidique dans le foie - Google Patents

Agents ameliorant le metabolisme lipidique dans le foie Download PDF

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Publication number
WO2003026685A1
WO2003026685A1 PCT/JP2002/009570 JP0209570W WO03026685A1 WO 2003026685 A1 WO2003026685 A1 WO 2003026685A1 JP 0209570 W JP0209570 W JP 0209570W WO 03026685 A1 WO03026685 A1 WO 03026685A1
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WO
WIPO (PCT)
Prior art keywords
liver
lipid metabolism
group
improving
enzyme
Prior art date
Application number
PCT/JP2002/009570
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English (en)
Japanese (ja)
Inventor
Nobuhiro Fukuda
Masanobu Sakono
Toshihiro Nakamori
Hitoshi Furuta
Michihiro Sugano
Original Assignee
Fuji Oil Company, Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Fuji Oil Company, Limited filed Critical Fuji Oil Company, Limited
Priority to JP2003530320A priority Critical patent/JPWO2003026685A1/ja
Publication of WO2003026685A1 publication Critical patent/WO2003026685A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/01—Hydrolysed proteins; Derivatives thereof
    • A61K38/011—Hydrolysed proteins; Derivatives thereof from plants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics

Definitions

  • the present invention relates to an agent for improving lipid metabolism of hepatic uchida, which promotes oxidation in the liver to decrease triglyceride content in the liver and suppresses secretion of triglyceride from the liver.
  • proteins and their hydrolysates are known as lipid metabolism improvers. It is known that plant proteins, particularly soy protein, are superior to animal proteins in improving the lipid metabolism of proteins. As for these protein hydrolysates (peptides), those derived from various proteins are known as follows, and their effects are various.
  • examples of lipid improving agents other than the hydrolyzate of soybean protein include, for example, JP-A-52-83186 (new polypeptide), JP-A-04-149137 (diet agent), and JP-A-06-183.
  • JP-A-52-83186 new polypeptide
  • JP-A-04-149137 diet agent
  • JP-A-06-183 Japanese Patent Application Laid-Open No. 211690/2001 (Feedings for blood lipid suppression derived from casein)
  • Japanese Patent Application Laid-Open No. 11-80006 Lipid Absorption Inhibitor
  • JP-A 2000-228967 lipid metabolism processed food
  • soy protein is not only excellent in nutritional properties among vegetable proteins, but also has various physiological activities in recent years, and is a food material that has attracted attention as a physiological function agent.
  • the effect of lowering body fat percentage on soybean protein has already been confirmed, but its mechanism is not known other than to suppress the activity of fatty acid synthase in the liver (Iriya et al. J. Nu tr., 126, 380, 19996).
  • Japanese Patent Application Laid-Open No. 5-87052 states that lipid metabolism-improving agents have the effect of lowering the fat content and the amount of fat droplets in the liver. This is because the fat content to be absorbed is reduced to suppress the activity, and the fat content in the serum is reduced. This is not the effect of changing the lipid metabolism activity itself in the liver.
  • Japanese Patent Application Laid-Open No. H04-149137 (diet) is known as a protein-hydrolyzed low molecular weight peptide, which is composed mainly of dipeptides and tripeptides, and has fat accumulation. It mentions the inhibitory effect and the weight gain inhibitory effect, but does not mention the effect of improving liver metabolism.
  • Japanese Patent Application Laid-Open No. 10-203994 discloses a bioactive composition in which a soybean protein-degraded peptide having a molecular weight of 500 to 5000 increases neutral fat in blood and HDL-cholesterol. However, there is no mention of the effect of improving lipid metabolism in the liver.
  • soybean protein hydrolyzate peptide mixture
  • a soybean protein hydrolyzate oligopeptide mixture
  • Japanese Patent Application Laid-Open No. 1-269456 Japanese Patent Application Laid-Open No. 3-272694.
  • it has been disclosed that it is involved in the metabolism of cholesterol and triglycerides.
  • the mechanism of lowering triglyceride was not clear.
  • the present invention is intended to reduce the triglyceride content in the liver by increasing trioxidation in the liver, and to improve the lipid metabolism in the liver by suppressing the secretion of tridaliceride from the liver. It was completed and put out. Purpose of the invention
  • the present invention enhances lipid metabolism in the liver, in particular, increases trioxidation in the liver to reduce triglyceride content in the liver and suppresses triglyceride secretion from the liver, among lipid metabolism improvements.
  • the aim was to improve lipid metabolism in the liver. Disclosure of the invention
  • the present inventors have conducted research using a liver perfusion system extracted from the liver, and, while continuing intensive research, have found that soy protein is higher than casein, and that soy protein is higher than casein. It has been found that the enzymatically degraded product does not change the amount of fatty acid absorption itself and suppresses the accumulation and secretion of triglyceride in the liver.
  • the present invention is an agent for improving lipid metabolism in the liver, comprising an enzymatically decomposed product of soybean protein as an active ingredient.
  • Lipid metabolism by this agent enhances -6-oxidation in the liver and lowers the content of tridaliceride in the liver, and in particular, lipid metabolism suppresses the secretion of triglyceride from the liver.
  • the average peptide chain length of the enzyme hydrolyzate of soybean protein is preferably 2 to 20, more preferably 5 to 10.
  • soybean protein which is an active ingredient of the lipid metabolism improving agent of the present invention.
  • the enzyme decomposition product of soy protein used in the present invention can be obtained by decomposing soy protein with an enzyme.
  • the enzyme digest of soy protein preferably has an average peptide chain length of 2 to 20 and more preferably an average peptide chain length of 5 to 10.
  • the enzymatically degraded soybean protein having such an average chain length can increase the [3] oxidation in the liver and significantly reduce the triglyceride content in the liver.
  • the enzymatically decomposed product of soybean protein having such an average chain length can suppress secretion of triglyceride from the liver.
  • Enzymatic degradation products can be obtained by hydrolyzing soybean protein in an aqueous system (soybean protein slurry or solution) using an enzyme (proteolytic enzyme).
  • soybean protein of the present invention soymilk, concentrated soybean protein, isolated soybean protein, defatted soybean, soybean whey protein, or the like can be used as a material that can be obtained at a low cost.
  • isolated soybean protein is preferable.
  • concentration of the soybean protein solution to be subjected to the enzyme treatment is suitably 1% by weight to 30% by weight, preferably 5 to 15% by weight, more preferably 8 to 12% by weight. Although a low concentration does not interfere with enzymatic decomposition, it is not preferable because the productivity is reduced. If the concentration of the soybean protein solution is too high, a large amount of enzyme is required to decompose sufficiently, probably because the polymerization of the degraded protein hydrolysates becomes stronger. Is not preferred.
  • the enzyme used in the present invention is suitably an enzyme containing a proteolytic enzyme (protease), and exoprotease or endprotease may be used alone or in combination, and may be of animal, plant or microbial origin. .
  • proteolytic enzyme proteolytic enzyme
  • exoprotease or endprotease may be used alone or in combination, and may be of animal, plant or microbial origin.
  • serine proteases trypsin, chymotrypsin derived from animals, subtilisin derived from microorganisms, lipoxypeptidase, etc.
  • thiol proteases papain, fusin, promelain, etc. derived from plants
  • carboxyproteases Animal-derived pepsin
  • Protein FN derived from Aspergillus oryzae (manufactured by Daiwa Kasei Co., Ltd.), “actinase” derived from Streptomyces griseus (manufactured by Kaken Pharmaceutical Co., Ltd.), Examples include “ALALASE” (manufactured by Novozymes Japan Ltd.) and “Protin A” (manufactured by Daiwa Kasei Co., Ltd.) derived from Bacillus subtilis.
  • enzymes containing endprotease include “Puguchi Thease” (manufactured by Amano Pharmaceutical Co., Ltd.) and “Protin AC-10” (manufactured by Daiwa Kasei Co., Ltd.).
  • Proteases 11 can be mentioned as an example of the proteolytic enzyme containing the enzyme and the end protease.
  • the hydrolysis conditions of the present invention vary somewhat depending on the type of protease used, but it is generally preferable to use an amount sufficient to hydrolyze soybean protein in the working pH range and working temperature range of the protease.
  • the pH is preferably 5 to 10, preferably 6 to 9, since salt formation due to neutralization can be reduced.
  • the degree of hydrolysis is suitably an average peptide chain length of 2 to 20, preferably 5 to 10.
  • Means for separating and removing insoluble decomposed products from the enzyme-decomposed solution of soybean protein may be by means of a filter press, membrane separation, or other means, but the most common method is a combination of centrifugation and membrane separation.
  • the enzymatically degraded soybean protein obtained by separating and removing the insoluble decomposed product from the enzymatically decomposed soybean protein solution promotes the oxidation of 3 in the liver than the enzymatically degraded product of soybean protein in an aqueous system.
  • the present invention is an agent for improving lipid metabolism in the liver, which contains an enzyme hydrolyzate of soybean protein produced as described above as an active ingredient.
  • the mechanism of improving lipid metabolism is different from that of a conventional enzyme digest of a protein.
  • the mechanism for improving lipid metabolism is to increase i3 oxidation in the liver to reduce triglyceride content in the liver.
  • the agent for improving lipid metabolism in the liver of the present invention is an agent for reducing triglyceride content in the liver.
  • the lipid metabolism improving mechanism suppresses secretion of triglyceride from the liver.
  • the agent for improving lipid metabolism in the liver of the present invention is a triglyceride secretion inhibitor from the liver.
  • soybean protein is superior in improving lipid metabolism than animal protein, and if it is known that a conventional soybean protein enzymatic degradation product is superior in improving lipid metabolism, as in the present invention, Mechanism was not elucidated.
  • the present invention relates to an agent for decreasing triglyceride content in liver and an agent for inhibiting Z or triglyceride secretion from liver.
  • the agent for improving lipid metabolism in the liver of the present invention is a triglyceride reducing agent that is extremely safe and has no fear of side effects because it contains an enzyme-decomposed product of soybean protein-derived soybean protein as an active ingredient, and is mixed with various foods. It can be taken in drink form or tablet form. As it is a safe food ingredient, there is no adverse effect from overdose, and 0.5 g per person as a guide for daily intake A suitable amount is 50 g, preferably about 3 to 15 g. ⁇ Example ⁇
  • the sedimentation component was separated and removed by adjusting the feed rate at 100 liters Z to SEPARATOR.
  • the obtained supernatant liquid was sterilized at 140 ° C for 8 seconds by blowing steam at 8 parts by weight / cm2 pressure, and the liquid was further filtered with a 0.22 micron filter (manufactured by Kyno Corporation). The mixture was filtered and dried by spray drying. In addition, this
  • Rats were purchased from Sprague-Dawley (SD) male rats (4 weeks old, weighing 70-80 g) from Kudo Co., Ltd. (Kumamoto). After preliminary breeding for 6 to 10 days, the animals are divided into 4 groups: casein group, soy protein group, soy protein enzyme decomposition group D-1, and soy protein enzyme decomposition group D-3. They were fed. The temperature of the breeding room was maintained at 22 to 24 ° C, and the light period was from 7:00 to 19:00. Feed and deionized water were provided ad libitum. After 4 weeks of feeding, rat isolated liver was perfused. Sprague-Dawley (SD) male rats with an initial weight of 130-140 g were allowed to freely ingest a diet prepared according to AIN76 for 4 weeks, and the liver was isolated and subjected to a perfusion experiment.
  • SD Sprague-Dawley
  • the protein content was calculated as nitrogen, casein 20%, soybean protein (Fujipro_R, manufactured by Fuji Oil Co., Ltd.) 19.63%, soybean protein digest D-1 20.18% and soybean protein digest D —3 was added at 19.29%.
  • 3-cornstarch 15%, DL-methionine 0.3%, cellulose 5%, corn oil 5%, mineral mixture 3.5%, pitamine mixture 1%, choline bitartrate 0.2% are added, and sucrose is added 100% It was prepared so that
  • the isolated liver perfusion method perfusion was performed for 4 hours at a constant temperature of 37 ° C by a recirculation method.
  • the rat is portal vein under Nembutal anesthesia
  • a glass catheter was placed in the upper hepatic vena cava and tied with a thread, and the liver was isolated.
  • the isolated liver was perfused with krebs-Henseleit buffer containing 1.5% albumin, 25% bovine erythrocytes and 25 mM glucose.
  • the ketone body was measured by an enzymatic method after deproteinizing the perfusate with perchloric acid.
  • Triglyceride (TG) concentration in the liver was significantly lower in the soy protein group, D-1 group and D-3 group than in the casein group.
  • Total cholesterol (TC) levels were significantly lower in the soy protein group than in the casein group.
  • the results were similar between the D-3 group and the Casein group.
  • the ester content% was significantly lower in the soybean protein group than in the casein group. No clear differences in phospholipid (PL) levels were observed between the groups. (Table 6) Secretion of TG by the liver
  • Isolate soy protein (Fuji Oil Co., Ltd., "New Fujipro-R") 30 parts by weight of 9% aqueous solution of pH 7.0, and proteolytic enzyme (Daiwa Kasei Co., Ltd., "Protin AC-10”) ) And hydrolyze at 50 ° C for 5 hours (15% TCA solubility 85%), and then centrifuge at 100 liters Z in a high-speed centrifuge (SB-7, WESTFALIA SEPARATOR) capable of continuous processing. The sediment component generated by adjusting the liquid sending speed was separated and removed. The obtained supernatant solution was sterilized by blowing steam at a pressure of 8 kg / cm for 7 seconds at 140 ° C. The solution was then filtered through a 0.22 micron (Kunoichi Co., Ltd.) filter and dried by spray drying to dry the powder. I let it. The average chain length of this LD-3 was 7.0.
  • Rats were purchased from Sprague-Dawley (SD) male rats (4 weeks old, weighing 70-80 g) from Kudo Co., Ltd. (Kumamoto). After pre-breeding for 6 to 10 days, it is divided into 5 groups: casein group, soy protein group, soy protein enzyme decomposition group HD-1, soy protein enzyme decomposition LD-3, and soy protein enzyme decomposition LD-5 They were fed the following diets for 4 weeks. The temperature of the breeding room was maintained at 22 to 24 ° C, and the light period was from 7:00 to 19:00. Feed and deionized water were provided ad libitum.
  • rats were sacrificed by decapitation and ingested liver and adipose tissue. Adipose tissue ingested fat around the kidney and epididymis.
  • the rats were fed Sprague-Dawley (SD) male rats with an initial weight of 130-140 g freely for 2 weeks on feed prepared according to AIN76.
  • SD Sprague-Dawley
  • the protein content is 20% casein in terms of nitrogen, soy protein (manufactured by Fuji Pro-R Fuji Oil Co., Ltd.) 19.63%, soy protein digest HD-1 20.18% and soy protein digest 19.29% of LD-3 and 21.71% of LD-5 were added.
  • soy peptide produced from soy protein has a strong effect of promoting fatty acid trioxidation in the liver to promote fatty acid degradation and inhibiting secretion of TG synthesized in the liver. . '' Industrial applicability
  • the amount of fatty acid absorption itself is not changed by the experiment of the perfusion system of the liver taken out from the liver, and the fat in the liver is not changed.
  • the fat in the liver is not changed.
  • symptoms of a disease caused by abnormal lipid metabolism in the liver eg, a disease caused by excessive accumulation of triglycerides in the body: risk of fatty liver, cirrhosis of the liver, etc.). It has become possible to reduce and prevent harm.
  • the enzyme-decomposed product of soybean protein of the present invention is also effective as an active ingredient of a lipid metabolism improving agent as an extremely safe and functional material (including not only for pharmaceuticals but also for foods).

Abstract

L'invention concerne des agents permettant d'améliorer le métabolisme lipidique dans le foie . Ces agents contiennent un produit de digestion enzymatique de protéine de soja permettant d'abaisser la teneur en triglycérides dans le foie et d'inhiber la sécrétion de triglycérides dans ce foie. L'utilisation de ces agents permet d'accélérer la β-oxydation dans le foie, c'est à dire, d'accélérer la digestion d'acides gras et de consommer ainsi la graisse accumulée sous forme de graisse corporelle, ce qui a pour effet une diminution de la graisse corporelle
PCT/JP2002/009570 2001-09-21 2002-09-18 Agents ameliorant le metabolisme lipidique dans le foie WO2003026685A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
JP2003530320A JPWO2003026685A1 (ja) 2001-09-21 2002-09-18 肝臓内の脂質代謝改善剤

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JP2001-288874 2001-09-21
JP2001288874 2001-09-21

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WO2003026685A1 true WO2003026685A1 (fr) 2003-04-03

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006068191A1 (fr) * 2004-12-21 2006-06-29 Fuji Oil Company, Limited Méthode de production de bières et peptide de soja pour la production de bières

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6011425A (ja) * 1983-06-30 1985-01-21 Fuji Oil Co Ltd コレステロ−ル低下性蛋白加水分解物及びその製造法
JPH01269456A (ja) * 1988-04-20 1989-10-26 Fuji Oil Co Ltd スポーツ用食品
JPH02200165A (ja) * 1989-01-31 1990-08-08 Snow Brand Milk Prod Co Ltd 血清脂質の改善作用を有する栄養剤組成物
EP0420979A1 (fr) * 1988-02-02 1991-04-10 Hankyu-Kyoei Bussan Co., Ltd. Agent ameliorant le metabolisme des lipides et procede d'utilisation
JPH0451872A (ja) * 1990-06-14 1992-02-20 Fuji Oil Co Ltd ペプチド混合物及び経腸栄養組成物
JPH07188284A (ja) * 1993-12-28 1995-07-25 Ito Ham Kk 血中トリグリセリド濃度上昇抑制ペプチド及び当該ペプチドを有効成分として含む血中トリグリセリド濃度上昇抑制剤
JPH10203994A (ja) * 1997-01-27 1998-08-04 Ichimaru Pharcos Co Ltd 生理活性作用組成物

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6011425A (ja) * 1983-06-30 1985-01-21 Fuji Oil Co Ltd コレステロ−ル低下性蛋白加水分解物及びその製造法
EP0420979A1 (fr) * 1988-02-02 1991-04-10 Hankyu-Kyoei Bussan Co., Ltd. Agent ameliorant le metabolisme des lipides et procede d'utilisation
JPH01269456A (ja) * 1988-04-20 1989-10-26 Fuji Oil Co Ltd スポーツ用食品
JPH02200165A (ja) * 1989-01-31 1990-08-08 Snow Brand Milk Prod Co Ltd 血清脂質の改善作用を有する栄養剤組成物
JPH0451872A (ja) * 1990-06-14 1992-02-20 Fuji Oil Co Ltd ペプチド混合物及び経腸栄養組成物
JPH07188284A (ja) * 1993-12-28 1995-07-25 Ito Ham Kk 血中トリグリセリド濃度上昇抑制ペプチド及び当該ペプチドを有効成分として含む血中トリグリセリド濃度上昇抑制剤
JPH10203994A (ja) * 1997-01-27 1998-08-04 Ichimaru Pharcos Co Ltd 生理活性作用組成物

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006068191A1 (fr) * 2004-12-21 2006-06-29 Fuji Oil Company, Limited Méthode de production de bières et peptide de soja pour la production de bières
JPWO2006068191A1 (ja) * 2004-12-21 2008-06-12 不二製油株式会社 ビール類の製造方法及びビール類製造用大豆ペプチド

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