KR102285327B1 - Liver function and/or pancreatic function improving agent - Google Patents

Abstract

Provision of a medicament for improving pancreatic function and/or liver function occurring in a normal lifestyle. A liver function improving agent and/or pancreatic function improving agent under a high-fat diet and alcohol intake comprising a liver hydrolyzate as an active ingredient.

Description

Liver function and/or pancreatic function improving agent {LIVER FUNCTION AND/OR PANCREATIC FUNCTION IMPROVING AGENT}

The present invention relates to a liver function improving agent and/or a pancreatic function improving agent.

The pancreas produces and secretes several types of digestive enzymes, while also secreting insulin and glucagon that control blood sugar levels. Among them, insulin is a hormone that lowers blood sugar levels, and when the secretion of insulin is lowered, diabetes occurs.

As drugs that promote insulin secretion, sulfonylurea drugs, DPPIV inhibitors, GLP-1 analogs, and the like are known, but side effects such as hypoglycemia and weight gain have been reported.

In addition, the liver has functions such as production, detoxification, and excretion of bile, in addition to metabolism and storage of nutrients. Examples of the liver disease include viral hepatitis, alcoholic hepatitis, drug hepatitis, NASH, liver cancer, chronic hepatitis, liver cirrhosis, and the like.

As a therapeutic agent for liver disease, hepatoprotective agents, such as interferon, glutathione, and a glitylitin preparation, are known. Moreover, it is a reality that drug hepatitis models, such as a carbon tetrachloride liver disorder model, are employ|adopted for the screening of many liver disease therapeutic agents.

By the way, it is known that a liver hydrolyzate has the improvement effect|action of the liver function in chronic liver disease (nonpatent literature 1). It is thought that the said effect|action is based on the effect by the above-mentioned carbon tetrachloride liver disorder model (patent document 1).

Japanese Laid-Open Patent Publication No. 2002-80388

Gospelever Jang Yong-Jeong Brochure

However, the conventional screening method for a drug for treating liver disease is a drug hepatic disorder model, and does not reflect a state in which the liver function is actually reduced. Moreover, the state in which liver function fell in many cases arises from lifestyle including a normal diet, and the drug which improves this state does not exist. In addition, a decrease in the function of the pancreas, that is, an increase in blood sugar level is also often caused by lifestyle, and a safe drug for improving such a condition is also required.

Accordingly, an object of the present invention is to provide a drug for improving the pancreatic function and/or the liver function occurring in a normal lifestyle.

Therefore, the present inventors have studied variously to search for drugs that improve the liver and pancreas functional deterioration caused by eating habits, not the liver or pancreas functional deterioration caused by drugs such as carbon tetrachloride. As a result, high-fat diet in rats And by ingesting alcohol, he succeeded in making a model in which hepatic function and pancreas function are lowered in a short period of time, and by using this model, it was found that a hydrolyzate of the liver is useful as an agent for improving liver function and/or pancreatic function under high-fat diet and alcohol ingestion. and completed the present invention.

That is, the present invention provides the following [1] to [20].

[1] A liver function-improving agent under high-fat diet and alcohol intake, comprising a hydrolyzate of liver as an active ingredient.

[2] A pancreatic function improving agent comprising a hydrolyzate of liver as an active ingredient.

[3] The pancreatic function improving agent according to [2], which is a pancreatic function improving agent under high fat diet and alcohol intake.

[4] The pancreatic function improving agent according to [2] or [3], which is an insulin secretion disorder improving agent.

[5] An agent for improving liver function and pancreas function under a high-fat diet and alcohol intake, comprising a liver hydrolyzate as an active ingredient.

[6] Soy hydrolyzate for improving liver function under high fat diet and alcohol intake.

[7] Soy hydrolyzate for improving pancreatic function.

[8] The liver hydrolyzate according to [7], which is for improving pancreatic function under high-fat diet and alcohol intake.

[9] The liver hydrolyzate according to [7] or [8], which is for improving insulin secretion disorders.

[10] A hepatic hydrolyzate for improving liver function and pancreatic function under high-fat diet and alcohol intake.

[11] Use of hepatic hydrolyzate for the manufacture of a liver function improving agent under high fat diet and alcohol intake.

[12] Use of liver hydrolysates for the manufacture of pancreatic function improving agents.

[13] Use of [12], which is a use for the manufacture of a pancreatic function improving agent under high fat diet and alcohol intake.

[14] Use of the description [12] or [13], which is use for the manufacture of an agent for improving insulin secretion disorders.

[15] Use of hepatic hydrolysates for the manufacture of agents for improving liver function and pancreatic function under high-fat diet and alcohol intake.

[16] A method for improving liver function under a high-fat diet and alcohol intake, comprising administering a liver hydrolyzate.

[17] A method for improving pancreatic function, comprising administering a liver hydrolyzate.

[18] The method according to [17], which is a method for improving pancreatic function under high-fat diet and alcohol intake.

[19] The method according to [17] or [18], which is a method for improving insulin secretion disorders.

[20] A method for improving liver function and pancreatic function under a high-fat diet and alcohol intake, comprising administering a liver hydrolyzate.

The liver function and/or pancreatic function improving agent of the present invention improves the liver function and/or pancreatic function caused by high-fat diet and alcohol intake, which are normal dietary habits, and has high safety and can be ingested for a long period of time. In addition, the liver function and/or pancreatic function improvement effect caused by the intake of a high-fat diet and alcohol of the liver hydrolyzate is effective at a lower dose than that of the conventional carbon tetrachloride liver disorder model, and the action is clearly different.

BRIEF DESCRIPTION OF THE DRAWINGS It is a figure which shows the increase inhibitory effect of AST activity and ALT activity under a high-fat diet and alcohol intake of a liver hydrolyzate.
Fig. 2 is a diagram showing the effect of improving insulin secretion disorders under a high-fat diet and alcohol intake of a hepatic hydrolyzate.

The active ingredient of the liver function and/or pancreatic function improving agent of the present invention is a liver lysate. The liver hydrolyzate is also called liver hydrolysate, soy extract, liver decomposition extract, and liver hydrolyzate, but it is obtained by hydrolyzing liver with a digestive enzyme or the like, and is used as a drug for improving liver function. As soy sauce as a raw material, fresh soy sauce from non-human animals such as cattle, pigs, bonito and whales is used. It is preferable to concentrate and use the obtained hydrolyzate. Preferably, the liver hydrolyzate defined as the said pharmaceutical is mentioned.

The hydrolyzate of soy sauce contains various amino acids, nucleotides, vitamins, minerals, etc. with a low molecular weight peptide as the main component. More specifically, amino acids 19 to 78 mass%, peptides and proteins 17 to 73 mass%, sugars 1.8 to 11 mass%, lipids 0.005 to 0.04 mass%, nucleic acids 0.7 to 2.5 mass%, minerals 1.6 to 5.4 mass%, vitamins It is preferable to contain 0.03-0.2 mass % and 0.8 mass % or less of glutathione. In addition, amino acids 23 to 65 mass%, peptides and proteins 20 to 61 mass%, sugars 2.2 to 8.6 mass%, lipids 0.006 to 0.035 mass%, nucleic acids 0.9 to 2.1 mass%, minerals 1.9 to 4.5 mass%, vitamins 0.04 to 0.15 % by mass, more preferably containing 0.7% by mass or less of glutathione, 29 to 52% by mass of amino acids, 25 to 49% by mass of peptides and proteins, 2.8 to 6.9% by mass of saccharides, 0.008 to 0.03% by mass of lipids, 1.1 to 1.7 of nucleic acids It is more preferable to contain mass %, 2.4-3.6 mass % of inorganic substances, 0.05-0.12 mass % of vitamins, and 0.6 mass % or less of glutathione.

Among these components, the amino acid composition is: Ala 17 to 68 mg/g, Arg 0.6 to 4.4 mg/g, Asp 9 to 48 mg/g, Cystine 5 mg/g or less, Glu 18 to 63 mg/g, Gly 10 to 39 mg/g , His 3-17 mg/g, Ile 14-56 mg/g, Leu 26-98 mg/g, Lys 15-65 mg/g, Met 0.3-20 mg/g, Phe 13-46 mg/g, Pro 10-48 mg/g, Ser 12 to 49 mg/g, Thr 12 to 45 mg/g, Trp 3 to 13 mg/g, Tyr 1.6 to 41 mg/g, Val 18 to 71 mg/g are preferred. In addition, Ala 21 to 57 mg/g, Arg 0.8 to 3.6 mg/g, Asp 11 to 40 mg/g, Cystine 4 mg/g or less, Glu 22 to 53 mg/g, Gly 13 to 32 mg/g, His 4 to 14 mg/g , Ile 17-47 mg/g, Leu 32-82 mg/g, Lys 18-54 mg/g, Met 0.4-17 mg/g, Phe 15-38 mg/g, Pro 12-40 mg/g, Ser 15-41 mg/g, Thr 14-38 mg/g, Trp 3.8-11 mg/g, Tyr 1.9-34 mg/g, Val 21-59 mg/g are more preferable, Ala 26-45 mg/g, Arg 1-2.9 mg/g, Asp 14- 32 mg/g, Cystine 3 mg/g or less, Glu 27-42 mg/g, Gly 16-26 mg/g, His 5-11 mg/g, Ile 21-40 mg/g, Leu 40-66 mg/g, Lys 22-43 mg/g g, Met 0.5-14 mg/g, Phe 19-31 mg/g, Pro 15-32 mg/g, Ser 18-33 mg/g, Thr 18-30 mg/g, Trp 4.8-8.4 mg/g, Tyr 2.4-27 mg/g g, Val 27 to 48 mg/g is more preferable.

Although it is known that a liver hydrolyzate improves the liver function in chronic liver disease, and carbon tetrachloride liver disorder, it is not known that it improves the liver function or pancreas function under a high fat diet and alcohol intake.

As shown in the Examples to be described later, the hydrolyzate of the liver has an effect of improving the liver function and the pancreatic function caused by the normal eating habits such as high fat diet and alcohol intake. The effect of this liver hydrolyzate occurs at a lower dose than, for example, the effect on carbon tetrachloride liver disorder in Patent Document 1. That is, about the liver disorder of carbon tetrachloride of patent document 1, it was effective by adding 2% to a diet, but about the liver disorder under a high fat diet and alcohol intake, it was effective by adding 0.031% of low concentration to a diet. Therefore, it is thought that the mechanism of action of the liver function improvement effect under a high fat diet and alcohol intake of a liver hydrolyzate differs from the effect on a carbon tetrachloride liver disorder model.

As a liver function in this invention, AST activity and ALT activity increase inhibitory effect are mentioned. Further, examples of the pancreatic function in the present invention include an effect of improving insulin secretion disorders.

Although the liver function and/or pancreas function improving agent of this invention can be administered by oral administration, transdermal administration, enteral administration, jugular vein administration, etc., oral administration is more preferable. Examples of the preparation for oral administration include liquids, tablets, powders, fine granules, granules, and capsules, but liquids and tablets are preferable, and liquids are more preferable.

In order to prepare these formulations for oral administration, excipients such as lactose, mannitol, corn starch and crystalline cellulose, cellulose derivatives, binders such as gum arabic and gelatin, disintegrants such as carboxymethyl cellulose calcium, lubricants such as talc and magnesium stearate , a solubilizing agent such as a nonionic surfactant, a flavoring agent, a sweetener, a stabilizer, a pH adjuster, water, ethanol, propylene glycol, glycerin, and the like can be used. Moreover, you may use coating materials, such as hydroxymethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, a cellulose acetate phthalate, and a methacrylate copolymer.

In addition, another active ingredient can also be mix|blended with the liver function and/or pancreas function improving agent of this invention. Examples of other active ingredients include vitamin B ₁ ; Thiamine nitrate, thiamine, thiamine hydrochloride, thiamine greener sulfonic, bis Ben thiamine, benpo thiamin, thiamine disulfide, thiamine disabled automatically, thiamine propyl disulfide, and derivatives thereof, vitamin B ₂ and the like; Riboflavin and its derivatives and salts thereof, vitamin B _3, etc .; Niacin, nicotinic acid, nicotinic acid amide, and derivatives and salts thereof, vitamin B ₅ and the like; Panthenol, pantothenic acid and derivatives and salts thereof, vitamin B ₆ and the like; pyridoxine and derivatives and salts thereof, vitamin B ₁₂ ; cyanocobalamin and derivatives and salts thereof, and other vitamins; Vitamin A, vitamin C, vitamin E, vitamin K, vitamin P, dichloroacetate diisopropylamine, taurine, chondroitin sulfate, royal jelly, caffeine, turmeric, milk thistle, dandelion, dandelion, burdock, garlic, chrysanthemum, yarrow , gardenia, sesame, ginseng root, asparagus, onion, chicory, medicinal saruvia, Korean thistle (artichoke), wolfberry, leguminous irises, fern, elba de pasarinho, cetessangria, alba de pasarini, black tea, Resveratrol, catechins, berberine, rosemary, soybean extract, metformin, etc. are mentioned.

In addition, the liver function and/or pancreatic function improving agent of the present invention can be used as a functional food such as a quasi-drug, a food for specific health use, a sports drink, a recycled drink, and a pet food in addition to a pharmaceutical.

Although content of the liver hydrolyzate in the liver function and/or pancreatic function improving agent of this invention also changes with dosage forms, Usually, 0.001-10 mass % is preferable as dry weight, and 0.001-5 mass % is more preferable. do. In addition, the daily dose of the liver hydrolyzate in the liver function and/or pancreatic function improving agent of the present invention is preferably 100 mg to 1076 mg, more preferably 383 mg to 623 mg, further 351 mg to 680 mg by dry weight. desirable.

Example

Next, the present invention will be described in detail with reference to examples, but the present invention is not limited thereto.

Example 1

(Experimental method)

1) use animals

Twenty-four 7-week-old Wistar/Std female rats were used (Nippon S.L.C.). They were individually reared in an animal room (temperature 23±2° C., humidity 50±10%RH) with a light-dark cycle of 12 hours each day and night (light: 08:00-20:00). Before the start of the experiment, they were acclimatized with solid feed for 3 days (Funabashi Farm F-2), and then divided into two experimental groups. That is, as a control, one containing isolate soy protein (Soy protein isolate = SPI) and one containing porcine liver hydrolyzate (PLH) were prepared, and put into an alcohol formula and given for 14 days.

14 hours before slaughter, alcohol was removed and fasted, and deionized water was given instead. Blood was collected in EDTA-2Na-treated blood collection vessels, and plasma was collected by centrifugation, and tissue samples for various analyzes were stored at -25°C. A part of soy sauce was rapidly frozen with liquid nitrogen after extraction, stored at -70°C, and used as a sample for subsequent analysis.

2) Composition of empirical formula by alcohol-containing liquid formula

Preparation of liquid feed was prepared based on the Lieber-DeCarli formula improved in 1989 (Table 1). A blender manufactured by Braun was used for stirring. In addition, with respect to vitamin A, which has been reported to promote alcoholic liver disorder by addition, it was prepared in an amount containing 5 times more than a normal vitamin mixture, and provided to the feed.

3) Experimental group

Control type (Con)

Control alcohol formula (Con-Alc)

・Pork liver hydrolyzate alcohol formula (PLH-Alc)

Table 3 shows the components and amino acid composition contained in the used soy sauce hydrolyzate.

4) Method of measurement of breeding conditions and tissue sampling

Using Wistar rats (Wistar/Std), 7-week-old female, experimental breeding was performed for 14 days under the following conditions. For the experimental group, two groups of the alcohol group and the control group were prepared, and pair feeding was performed. During the breeding period, plasma is collected from the tail vein, and plasma GPT (glutamic acid pyruvate transaminase [=ALT "alanine transaminase"]) activity, GOT (glutamic oxaloacetate transaminase [= AST "aspartic acid" transaminase])) activity and plasma insulin were measured. Ethanol administration conditions, starting with a 3% concentration diet, from the need for acclimatization with alcohol, was raised to a 5% containing diet after the 4th day. The measurement items are summarized below.

Determination of hepatic impairment markers in plasma (ALT, AST):

It was measured using the Transaminase CII kit of Wako Junyaku Kogyo Co., Ltd.

Measurement of Insulin:

It was measured using the insulin measurement kit of Morinagase Chemicals Kenkyusho Corporation.

(result)

As shown in Fig. 1, the liver hydrolyzate prevented liver failure under high fat and alcohol intake.

In addition, as shown in Fig. 2, the liver hydrolyzate prevented insulin secretion disorders under high fat and alcohol intake.

Claims (20)

delete As an agent for improving pancreatic function under high-fat diet and alcohol intake, comprising liver hydrolysate as an active ingredient,
The hydrolyzate of soy sauce is a hydrolyzate of liver, pig, bonito, or whale, 19 to 78% by mass of amino acids, 17 to 73% by mass of peptides and proteins, 1.8 to 11% by mass of saccharides, 0.005 to 0.04% by mass of lipids, 0.7 to 2.5% by mass of nucleic acids, 1.6 to 5.4% by mass of minerals, 0.03 to 0.2% by mass of vitamins, and 0.8% by mass or less of glutathione,
The pancreatic function improvement agent is an increase in insulin secretion. delete The pancreatic function improving agent according to claim 2, which is an insulin secretion disorder improving agent. delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete delete

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