JP4679687B2 - Liver function improving agent - Google Patents

Description

【００２２】
肝機能障害モデルラットは、常法に従って、四塩化炭素を用いて作成した。すなわち、 4週齢SD系雄ラットを 1群 8匹に分け、24時間絶食後、1ml/kg用量で10％四塩化炭素溶液（v/v,パナセート 800）を腹腔内投与して作成した。
このモデルラットに、表１に組成を示した動物用飼料を与え、４週間飼育した後、血清中のグルタミン酸-オキザロ酢酸トランスアミナーゼ（GOT）活性及びグルタミン酸-ピルビン酸トランスアミナーゼ（GPT）活性を測定することで、肝機能改善作用を評価した。
その結果を表２に示す。
【００２３】
【表２】

【００２４】
これによると、血清中のGOT活性及びGPT活性は、対照食群に比べ、LPO食群、LF食群及びLPO・LF食群で有意に低下していることが認められ、肝機能改善作用を有することがわかった。
【００２５】
【発明の効果】
本発明に使用するラクトパーオキシダーゼ及びラクトフェリンは、四塩化炭素による急性の肝機能障害に対して肝機能改善作用を有するだけでなく、安全性が高いので、それらを配合した本発明の肝機能改善剤及び肝機能改善作用を付与した飲食品は、長期的摂取が可能で、肝機能の改善に有用である。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a liver function improving agent containing lactoperoxidase or lactoferrin as active ingredients. Moreover, this invention relates to the food-drinks which mix | blended lactoperoxidase and lactoferrin and provided the liver function improvement effect | action.
[0002]
[Prior art]
In recent years, with the westernization of dietary habits, the intake of fat, particularly animal fat, and the accompanying increase in cholesterol intake are remarkable. In addition, the burden on the liver responsible for metabolism is increasing due to an uneven nutritional balance and alcohol consumption. The liver has circulatory function, excretion function, metabolic function, protection / detoxification function, and hematological function. If any of these functions is impaired, fatigue, malaise, loss of appetite, jaundice, and slight fever Symptoms peculiar to hepatic dysfunction, such as.
[0003]
On the other hand, lactoperoxidase is a glycoprotein with a molecular weight of about 80,000 that exists in milk and contains heme iron, but its detailed structure has not yet been clarified. Regarding the use of lactoperoxidase, an anti-aging agent (JP-A-5-124980), a low caries nutrition composition (JP-A-9-107917), an animal skin disease treatment (JP-A-7-233086) However, it has not yet been clarified to have an effect of improving liver function, and has not been used for the purpose of improving liver function.
Lactoferrin is a glycoprotein having a molecular weight of about 80,000 present in milk, has two regions (N rope and C rope), and each has a property of chelating iron of one atom. Regarding the use of lactoferrin, a pharmaceutical composition for the treatment and prevention of periodontal disease (Japanese Patent Laid-Open No. 5-279266), a bioprotective agent activator (Japanese Patent Laid-Open No. 6-14068), an infection protective agent (Japanese Patent Laid-Open No. No. 259137) is known, however, it has not yet been clarified to have an effect of improving liver function, and it has not been used for the purpose of improving liver function.
[0004]
[Problems to be solved by the invention]
This invention makes it a subject to provide the chemical | medical agent and food / beverage products which are safe and can be ingested on a daily basis from a viewpoint of improvement of liver dysfunction.
[0005]
[Means for Solving the Problems]
The present inventors have found that lactoperoxidase and lactoferrin have an effective action for improving liver function in the process of searching for substances effective for improving liver function disorder and preventing liver function decline. It came to complete.
That is, as a result of searching for substances having liver function improving action by using carbon tetrachloride to cause liver dysfunction in rats and using the biochemical marker value in the serum as an indicator of improvement, lactoperoxidase and lactoferrin It was confirmed that there is the effect.
[0006]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, the present invention will be described in detail.
The lactoperoxidase and lactoferrin used in the present invention are derived from mammalian milk such as cow's milk, human milk, goat milk, and sheep milk. Lactoperoxidase and lactoferrin contain many basic amino acids such as lysine and arginine, and are sometimes collectively referred to as basic proteins. This basic protein can be obtained by purifying milk raw materials such as skim milk and whey using a cation exchange resin. After separating and purifying lactoperoxidase and lactoferrin from milk, each can also be blended according to the required amount, but in particular contains lactoperoxidase and lactoferrin obtained from skim milk and whey of milk Use of the basic protein fraction is preferable from the viewpoint of economy.
[0007]
As a method for obtaining this basic protein fraction, milk or a milk-derived raw material is brought into contact with a cation exchanger to adsorb a basic protein, and then the basic protein fraction adsorbed on the cation exchanger is obtained. , A method obtained by elution with an eluent exceeding pH 5 and an ionic strength exceeding 0.5 (Japanese Patent Laid-Open No. 5-202098), a method obtained using an alginate gel (Japanese Patent Laid-Open No. 61-246198), inorganic porosity A method of obtaining from whey using particles (Japanese Patent Laid-Open No. 1-86839), a method of obtaining from milk using a sulfated ester compound (Japanese Patent Laid-Open No. 63-255300), and the like are known. The basic protein fraction obtained by such a method can be used.
[0008]
Lactoperoxidase and lactoferrin are more preferably combined in combination in the liver function-improving agent, not in combination with each other, and exhibit a stronger liver function-improving effect when used in combination. Can do.
[0009]
The present inventors have confirmed that it is desirable for adults to take lactoperoxidase at 0.1 mg / day or more in terms of solids and at least 0.1 g / day of lactoferrin in terms of solids. Therefore, with regard to lactoperoxidase and lactoferrin, it is possible to blend lactoperoxidase 0.1 mg / 100 g or more in terms of solids and lactoferrin 0.1 g / 100 g or more in terms of solids to foods and beverages that have been given liver function improving action. desirable.
[0010]
In the liver function improving agent of the present invention, lactoperoxidase or lactoferrin may be used alone, or may be used together with other components, depending on the purpose and method of use, powdered, liquid, What is necessary is just to formulate in shapes, such as a tablet form.
[0011]
Moreover, about the liver function improving agent of this invention, protein, saccharide | sugar, a lipid, vitamins, minerals, etc. can also be comprised as a main component as a form of a nutrition composition.
[0012]
Examples of proteins include casein, whey protein concentrate (WPC), whey protein isolate (WPI), αs-casein, β-casein, α-lactalbumin and β-lactoglobulin and other milk protein fractions, soybean Plant proteins such as protein and wheat protein can be mentioned, and these proteins may be treated with acid or enzyme and used in the form of peptides or free amino acids. In addition to the nitrogen source, the free amino acid can also be used for imparting a specific physiological action. Examples of these amino acids include taurine, cystine, cysteine, arginine, and glutamine. These proteins, peptides, or free amino acids are preferably blended in an amount of 5 to 30% by weight based on the solid content of the nutritional composition.
[0013]
Examples of the saccharide include starch, soluble polysaccharides, dextrin, sucrose, lactose, maltose, and glucose, oligosaccharides such as galactosyl lactose, fructooligosaccharide, and lactulose, and artificial sweeteners. It is preferable to mix 40-80 weight% of saccharide | sugar with respect to solid content of a nutritional composition.
[0014]
Examples of lipids include animal fats such as milk fat, lard, beef tallow and fish oil, soybean oil, rapeseed oil, corn oil, evening primrose oil, medium chain fatty acid triglyceride (MCT) and vegetable oil such as cottonseed oil, and fractionation thereof. And oil, hydrogenated oil, transesterified oil, and the like. The lipid is preferably blended in an amount of 40% by weight or less based on the solid content of the nutritional composition.
[0015]
About vitamins and minerals, vitamins and minerals of designated additives based on the Food Sanitation Law (additives listed in Appendix 2 of the Enforcement Regulations) and existing additives (additives listed in the existing additive list) Use it.
Specific examples of vitamins include vitamin A, vitamin B, vitamin C, vitamin D, vitamin E, vitamin K, folic acid, pantothenic acid, β-carotene, nicotinamide, biotin, inositol, choline, etc. It is preferable to blend 0.01 to 5% by weight with respect to the solid content of the nutritional composition.
Specific examples of minerals include calcium, magnesium, potassium, sodium, phosphorus, chlorine, iron, copper, zinc, iodine, manganese, selenium, fluorine, chromium, molybdenum and the like. It is preferable to blend 0.001 to 5% by weight per solid content.
[0016]
Furthermore, as foods and drinks imparted with the liver function improving action of the present invention, milk foods such as cheese, butter and fermented milk, milk drinks, drink yogurt, coffee drinks and fruit juice drinks, jelly, pudding, cookies, biscuits and Examples include confectionery such as wafers, and various foods and beverages such as frozen foods.
Next, an Example is shown and this invention is demonstrated in detail.
[0017]
[Example 1]
(Manufacture of liver function improving agents)
After adding milk-derived lactoperoxidase (Sigma) 0.1 mg, and milk-derived lactoferrin (Sigma) 100 mg, water-containing crystalline glucose 93.4 g, calcium carbonate 5 g, sugar ester 1 g, flavor 0.5 g The tablet was tableted to produce a liver function improving agent.
[0018]
[Example 2]
(Milk drink with liver function improving effect)
Basic protein fraction obtained by contacting skim milk with CM Sepharose (Pharmacia), eluting the adsorbed fraction with 1M saline, desalting by electrodialysis, concentrating and freeze-drying. The milk was added to raw milk so as to be 1 g per liter, homogenized at a pressure of 120 kg / cm ² , and then heat sterilized at 120 ° C. for 4 seconds to produce a milk beverage imparted with an action for improving liver function.
This milk beverage contained 12 mg of lactoperoxidase and 12 mg of lactoferrin per 100 ml.
[0019]
[Example 3]
(Yogurt with liver function improving effect)
The skim milk powder is dissolved in water to a solid content of 12%, sterilized by heating at 90 ° C for 20 minutes, cooled to 25 ° C, Lactobacillus acidophilus ( L. acidophilus) and Streptococcus thermophilus ( S.thermophilus ) was inoculated. When the lactic acid acidity reached 1.0% and the pH reached 4.3, it was cooled to 5 ° C. Further, the cheese whey was brought into contact with CM Sepharose (Pharmacia), the adsorbed fraction was eluted with 1M saline, desalted by electrodialysis, then concentrated and freeze-dried to obtain a basic protein. Fraction 1.5g was added. The starter culture prepared in this way is inoculated with 5% by weight of 3.5% fat milk that has been sterilized by heating at 115 ° C for 2 seconds, followed by fermentation and cooling in accordance with conventional methods to produce yogurt with an action to improve liver function. did.
The yogurt contained 12 mg of lactoperoxidase and 12 mg of lactoferrin per 100 g.
Next, test examples whose effects were confirmed by animal experiments are shown.
[0020]
[Test Example 1]
Four types of test meals shown in Table 1 were prepared as animal feeds. Lactoperoxidase was indicated as LPO, and lactoferrin was indicated as LF.
[0021]
[Table 1]

[0022]
Liver dysfunction model rats were prepared using carbon tetrachloride according to a conventional method. Specifically, 4-week-old SD male rats were divided into 8 groups, and after fasting for 24 hours, 10% carbon tetrachloride solution (v / v, panacet 800) was intraperitoneally administered at a dose of 1 ml / kg.
This model rat is fed with an animal feed having the composition shown in Table 1, and after breeding for 4 weeks, serum glutamate-oxaloacetate transaminase (GOT) activity and glutamate-pyruvate transaminase (GPT) activity are measured. Thus, the liver function improving effect was evaluated.
The results are shown in Table 2.
[0023]
[Table 2]

[0024]
According to this, serum GOT activity and GPT activity were significantly decreased in the LPO diet group, LF diet group, and LPO / LF diet group compared to the control diet group, and improved liver function. I found it.
[0025]
【The invention's effect】
The lactoperoxidase and lactoferrin used in the present invention not only have liver function improving action against acute liver dysfunction due to carbon tetrachloride, but also have high safety. The food and drink provided with the agent and the liver function improving action can be taken for a long time and are useful for improving the liver function.

Claims (3)

  A liver function improving agent comprising lactoperoxidase as an active ingredient.   A liver function improving agent comprising lactoperoxidase and lactoferrin as active ingredients. The liver function improving agent according to claim 1 or 2, which is for oral use.