JP2005194216A - Composition for ameliorating hepatopathy derived from allium ampeloprasum - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To develop a health food, a medicine or a composition usable for them by finding a new physiological effect in a component abandoned in a processing process of odorless garlic. <P>SOLUTION: The composition for ameliorating hepatopathy comprises a foam component (foamy fraction) recovered from a water-soluble extract of Allium ampeloprasum known as odorless garlic. The hepatopathy includes hepatopathy caused by various causes, for example, hepatopathy caused by hepatitis virus, alcohol, stress, medicine or immunoabnormality. Especially in a preferable embodiment, the composition is used as a prophylactic and/or a therapeutic agent against alcoholic hepatopathy. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a composition for improving liver damage obtained from jumbo leek (Jumbo leek) or, in particular, a foam component recovered from a water-soluble extract thereof. The present invention relates to a composition for improving the above and a method for producing the same.

  Garlic has been known as a spice for which physiological effects are expected since BC, and it is effective for deodorization as garlic spice, odor control and folklore medical uses such as asthma, arthritis, arteriosclerosis, bronchitis, etc. It is said. In addition, the usefulness of garlic, such as its physiological action and antibacterial properties, is mostly described mainly on allyl 2-propenethiosulfinate derived from allylcysteine sulfoxides, which is a causative substance of specific odor. Alliin is an organic sulfur compound contained in leeks and is an odorless substance particularly common in garlic bulbs. The alliin in the cell is crushed and minced to change to the odorous substance allicin by the action of the enzyme. Therefore, it has been considered that the odor and physiological action peculiar to garlic have a two-sided relationship.

  Odorless garlic is known, which contains a large amount of alliin, the causative substance of this odor, and has an odor amount (same threshold concentration) as low as 1/14 compared to ordinary garlic. This odorless garlic is considered a subspecies of garlic, and has a feature that it has a less irritating odor and is very easy to eat compared to ordinary garlic. In addition, it is about 8 times larger than normal garlic, and contains about twice as much scordinin, which is one of the active ingredients of garlic. When the bioactive action was examined using the extract powder extracted from this odorless garlic, it was found that it has biological defense functions such as leukocyte (neutrophil) increasing action, TNF-induced prining action, macrophage proliferation inducing action, etc. (For example, refer nonpatent literature 1).

  Moreover, as a result of examining the extract component extracted from this odorless garlic using the 8-OHdG value in urine as an index, it is also recognized that it has a strong antioxidant activity using tocopherol acetate as a control (for example, non-patented) Reference 2). These results show that odorless garlic, which has less irritating odor than ordinary garlic and is easy to eat, is useful as a health food or food material. For example, Okura Pharmaceutical Co., Ltd. Registered trademark).

  At present, the odorless garlic extract component is crushed odorless garlic, extracted and then freeze-dried and used. However, foam and residue generated in the manufacturing process remain as waste components. doing. However, scordinin, which is an active ingredient, remains in these waste components to some extent, and the effective use of the scordinin remains, and a search for a new medicinal effect is strongly desired for a new composition obtained as a by-product. Yes.

Ayumi Uchida, “Activating action of biological defense mechanism of natural garlic-like plant (odorless garlic)”, FOOD Style 21, July 1998, Vol. 2, No. 7, p. 45-48 Mitsuo Yoshida and three others, "Antioxidant activity of Allium sativum LINNE Shiro" Medicine and Pharmacology, Natural Sciences, September 2001, Vol. 46, No. 3, p. 365-370

  The present invention aims to make effective use of odorless garlic that has less irritating odor and is easier to ingest than `` odorous garlic '', which has been recognized as a folklore effect, especially for components that are discarded in processing steps The object is to find a new physiological action and develop a health food, a drug or a composition usable for them.

  In view of the above problems, the present inventors have studied the physiological effects of the foam components generated in the processing process of odorless garlic, and as a result, have found that they have the effect of remarkably improving various liver disorders. Completed the invention.

  That is, the composition for improving liver damage of the present invention comprises a foam component (foamed fraction) recovered from a water-soluble extract of jumbo leek (Allium ampeloprasum) known as odorless garlic. Features.

  In a preferred embodiment, the foam component is recovered by heating a water-soluble extract of Allium ampeloprasum. The liver disorder includes a liver disorder caused by various causes, for example, a liver disorder caused by hepatitis virus, alcohol, stress, drug or immune abnormality, and in a particularly preferred embodiment, alcoholic liver disorder It can be used as a preventive and / or therapeutic agent. The composition preferably contains saponin as an active ingredient.

  In a different aspect of the present invention, a step of pulverizing and / or squeezing jumbo leek (Allium ampeloprasum), a step of obtaining an extract from the pulverized and / or compressed product with water, a hydrophilic organic solvent or a mixed solvent thereof, There is provided a method for producing a composition for improving liver damage, comprising a step of heating an extract and a step of recovering a foam component from the heated extract.

  The composition for improving liver damage of the present invention can prevent liver damage caused by alcohol, stress, various drugs or the like, or can treat and improve a damaged liver. Although the mechanism of its pharmacological action is not necessarily clear, it is possible to prevent hepatocytes from being damaged by the above-mentioned factors, for example, to suppress the generation of active oxygen by macrophages activated by TNF-α, and to reduce hepatocytes. It is thought that it may be to defend the obstacles.

  The composition for improving liver damage of the present invention (hereinafter referred to as “the composition of the present invention”) is prepared from a food material called so-called odorless garlic. Although some odorless garlic has been low-bromide by an artificial operation, the odorless garlic according to the present invention is a natural odorless garlic, Jumboriki (Allium ampeloprasum), which is considered a subspecies of garlic. This plant is larger than normal garlic in both plant height and bulb, and the scale is closely attached to the flower stem to form a bulb and the small one attached to the edge of the bulb, the number of which is 20 . As a result of chromosomal DNA and isozyme analysis, this plant is very closely related to Leek and can be classified in Allium ampeloprasum L. (J. Japan. Soc. Hort Sci.) 71, 362-369, 2002).

  This jumbo leek (Allium ampeloprasum LINNE Shiro) strain is native to South America and has been cultivated in Nagano more than ten years ago in Japan, and today it is produced in Toyama, Ibaraki, Gifu, and others. It is particularly preferable that the composition of the present invention is produced using Jumboriki “Mushurik (registered trademark)” which is an odorless garlic produced by organic farming in Nagano and Toyama. The scientific name for Jamboreeki may also be called Allium sativum LINNE Shiro.

  The composition of the present invention can be produced from this jumbo leek (Allium ampeloprasum) by various methods.For example, jumbo liqui is used as an extraction raw material, and is added to water, a hydrophilic organic solvent, or a mixed solvent thereof. After extraction using an arbitrary extraction device at room temperature or a temperature lower than the boiling point of the solvent, the foam component can be recovered from the extract, that is, the water-soluble extract. The extraction solvent may be any water or hydrophilic organic solvent, and includes, for example, tap water, ion exchange water, distilled water, physiological saline, phosphate buffer and the like. . Examples of the water-soluble organic solvent include lower alcohols such as methanol, ethanol, propyl alcohol and isopropyl alcohol, lower aliphatic ketones such as acetone and methyl ethyl ketone, 1,3-butylene glycol, propylene glycol, isopropylene glycol and glycerin. Examples thereof include polyhydric alcohols, and a mixed solvent of these hydrophilic organic solvents and water can also be used. The water for extraction includes water in the plant cells, and a squeezed solution obtained by squeezing raw jumbo liquor pieces can be used as it is. Subsequently, the residue is preferably separated and removed from the extract by a method such as filtration or centrifugation. The separated residue may be extracted again with water and mixed with the extract.

  Next, the foam component is recovered from the extract by various methods. In general, it is known that an extract of a certain plant easily foams (foams) when heated. Since the extract of a plant containing saponins such as asparagus, elephant garlic, and soybean is likely to foam, it is considered that the foam component according to the present invention also contains saponins. Saponins are glycosides widely distributed in the plant kingdom, and are a general term for a group of compounds having steroids and triterpenoids as non-sugar parts. As a common property, it is said that the aqueous solution has a remarkable foaming property and exhibits hemolysis. Unlike other foodstuffs, the saponin contained in the foam component according to the present invention has a specific content and composition ratio.

  The recovered foam component can be dried into a powdery composition by any method known to those skilled in the art. For example, methods such as freeze drying, reduced pressure drying, spray drying and the like can be used, but it is preferable to operate at a low temperature so as not to impair the activity of the active ingredient. In the case where the achievement of the object of the present invention is not hindered, a purification step may be added by a method such as activated carbon treatment or adsorption resin treatment.

  The composition of the present invention can be administered or ingested as a form of food or drink or health supplement, for example, tablets (including sugar-coated tablets and film-coated tablets), powders, granules, capsules (including soft capsules). ), And can be safely administered orally as a syrup, liquid or the like. In order to obtain a preparation for oral administration, saponin as an active ingredient is, for example, an excipient (eg, lactose, sucrose, starch, etc.), a disintegrating agent (eg, starch, calcium carbonate, etc.), a binder according to a known method. (Eg, starch, gum arabic, carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropylcellulose, etc.) or lubricant (eg, talc, magnesium stearate, polyethylene glycol 6000, etc.) etc. are added and compression molded, then if necessary, For the purpose of taste masking, enteric properties or persistence, it can be prepared as an orally administered preparation by coating by a known method. Examples of the coating agent include hydroxypropylmethylcellulose, ethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, polyoxyethylene glycol, Tween 80, Pluronic F68, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, hydroxymethylcellulose acetate succinate, Eudragit (Rohm) Company, Germany, methacrylic acid / acrylic acid copolymer) and dyes (eg, bengara, titanium dioxide, etc.) are used. The preparation for oral administration may be either an immediate release preparation or a sustained release preparation. Or it can be ingested as a form of general food and drink, for example, beverages such as soft drinks, nutritional beverages, fruit beverages, lactic acid beverages, confectionery such as jelly, confectionery, jam, cream, kamaboko, ham, sausage, etc. Seafood, processed livestock foods, and other various forms of health, nutritional supplements, and the like are possible, but not limited to these.

  The dosage when the composition of the present invention is used as an agent for preventing or treating liver damage varies depending on the age of the patient, the type of disease, the degree, etc., and cannot be generally defined. In the case of oral administration, the daily dose is 0.1 to 100 g, preferably 1 to 10 g. In the case of parenteral administration, the daily dose is 20 to 1000 mg, preferably 50 to 500 mg, and is preferably divided into 1 to 3 times according to the symptoms.

(Mechanism of liver injury and action mechanism of the composition of the present invention)
The liver is damaged by various factors such as viruses, drugs, and alcohol, and causes liver diseases such as acute hepatitis, chronic hepatitis, fatty liver, jaundice, and cirrhosis. At present, only a few types such as malotilate and prednisolone are clinically used as therapeutic agents for these liver diseases. Even antiviral agents such as interferon have not been able to reliably eliminate hepatitis virus, and side effects such as fever have been reported. As an acute liver injury model similar to human viral hepatitis, D-galactosamine (GalN) -induced liver injury rats are known. Excessive administration of GalN to rats shows fulminant hepatitis (anorexia, nausea, collapse feeling, jaundice, etc.). On the other hand, alcoholic hepatitis is said to easily develop if a regular drinker suddenly increases alcohol intake. In liver cells damaged by these causes, intracellular ALT, AST, γ-GTP, and the like increase because intracellular enzymes flow into the blood. In the following examples of the present invention, the abbreviations of blood markers measured as indicators of liver damage are as follows. AST: aspartate aminotransferase, ALT: alanine aminotransferase, GGT: γ-glutamyl transpeptidase, LDL: lactate dehydrogenase.

  EXAMPLES The present invention will be described more specifically with reference to the following examples, but the present invention is not limited to these examples.

(Production Example 1)
1 L of pure water was added to 1 kg of jumbo liquor raw phosphorus pieces, ground with a mixer, and then filtered with gauze. The obtained filtrate was heated in a pan, and a large amount of the generated foam component was recovered with a handle. After cooling, the filtrate was lyophilized to obtain 15 g of white powder (yield 1.5%).

(Production Example 2)
40 kg of jumbo kiln raw phosphorus pieces were pulverized and pressed to obtain a pressing solution and a residue. Next, twice the amount of water was added to the compressed liquid, and the mixture was applied to a foam recovery apparatus (100 ° C., 2 hours) to recover the foam component as a liquid and powdered with a freeze dryer (FD). The obtained powder was white and hygroscopic, and the yield was 0.14% (55 g). On the other hand, the residue and the foam-recovered extract were mixed, 15 L of water was added, the foam component was re-extracted with a foam recovery device, and freeze-dried. The yield was 0.15% (61 g). As a result of mixing these, a total of 116 g of lyophilized powder was obtained with a yield of 0.29%.

(Test Example 1) Measurement of liver injury improving effect by galactosamine-treated liver injury model rats Seven male SD rats (5 weeks old, body weight 110 to 130 g) were subjected to the test as a group. 700 mg / kg D-galactosamine was injected intraperitoneally to induce liver injury. Production Example 2 three times at 8, 24, and 32 hours after administration of D-galactosamine (Group C), or four times at 15 hours before administration of D-galactosamine, 8, 24, and 32 hours after administration (Group D) Jamboriki foam powder prepared by the above was orally administered to rats using a gastric sonde per 0.06 g / kg body weight. In addition, the non-treatment group (group A) which does not administer any of the said D-galactosamine and jumbo liquor foam powder, and the group (group B) which performed only D-galactosamine administration were made into the control, respectively. Blood was collected at the same time and 48 hours after D-galactosamine administration, and after centrifugation, plasma AST, ALT, total bilirubin, GGT, and LDL were measured. These measurements were performed using the “Spotchem ^TM II Liver Function-2 [Liver-II]” kit (manufactured by ARKRAY, Inc.) according to the instructions in the instruction manual attached to the kit.

  The results are shown in Tables 1 and 2 and FIGS. As can be seen from these results, in rat plasma 48 hours after GalN treatment, extremely high AST, ALT, GGT and LDL activities were observed, and the total bilirubin amount was also significantly increased. It can be seen that these activities are significantly reduced in the groups administered with (C group and D group). In addition, the effects were almost the same in each of the three administrations (Group C) and the four administrations (Group D). As for the dose, if a 50 kg person eats 100 g of raw jumbo liqueur per day, it becomes 2 g / kg, and the content of the foam component is about 3% of the total, so it is 0.06 g / kg. Set.

(Test Example 2) Measurement of liver function improvement effect by alcohol-ingested rat (sample) Jumbo liquor foam powder, jumbo liquor powder (mushulic powder PSII) and turmeric powder prepared in Production Example 2 were each 0.002 g / ml, It melt | dissolved in 40% ethanol and 90% ethanol so that it might become 0.002 g / ml and 0.012 g / ml, respectively.

(Test method) Seven male SD rats (5 weeks old, body weight 110 to 130 g) were subjected to the test as a group. After preliminary breeding for 7 days, a 40% ethanol solution containing each of the above samples was administered at 1 ml per day for 25 days using a stomach tube. On the 26th day from the start of administration, 1 ml of a 90% ethanol solution containing each of the above samples was finally administered, and blood was collected on the 28th day after the start of administration. After the collected blood was centrifuged, plasma AST, ALT, total bilirubin, GGT, and LDL were measured. In addition, the group which administered physiological saline or 40% and 90% ethanol instead of the said sample solution was made into the non-treatment group and the control group, respectively. As in Test Example 1, the measurement method was performed using a “Spotchem ^TM II liver function-2 [Liver-II]” kit (manufactured by ARKRAY, Inc.). The results are shown in Tables 3 and 4 and FIGS. In addition, about the dosage of a sample, it converted so that foam powder and jumbo liquor powder might be 500 mg / day / person, and turmeric powder might be 3 g / day / person.

  As is apparent from the results shown in Tables 3 and 4 and FIGS. 7 to 9, alcohol administration increases blood AST and ALT activities as indicators of liver function, and the total amount of bilirubin in plasma is significantly increased. Although it increases, it turns out that these enzyme activities fall significantly by administering a jumbo liquor foam powder component simultaneously. Moreover, even if it compares with a turmeric powder, it turns out that the effect of the jumbo liquor foam powder component which is a composition of this invention is excellent.

  The composition for improving liver damage according to the present invention is effective in preventing or treating liver damage by suppressing elevation of plasma ALT and AST in rats with experimental liver damage induced by D-galactosamine and alcohol. .

It is a graph showing the effect of jumbo leek foam powder on AST activity of GalN-treated rats. It is a graph showing the effect of jumbo leek foam on the ALT activity of GalN-treated rats. It is a graph showing the effect of jumbo liquor foam powder on the total bilirubin of GalN-treated rats. It is a graph showing the effect of jumbo leek foam powder on GGT activity of GalN-treated rats. It is a graph showing the effect of jumbo liquor foam powder on LDL activity of GalN-treated rats. It is a graph showing the effect of jumbo leek foam powder on the AST activity of alcohol-ingested rats. It is a graph showing the effect of jumbo leek foam powder on the ALT activity of alcohol-ingested rats. It is a graph showing the effect of jumbo liquor foam powder on the total amount of bilirubin in alcohol-ingested rats.

Claims (6)

  A composition for improving liver damage, comprising a foam component recovered from a water-soluble extract of jumbo leek (Allium ampeloprasum).   The composition of claim 1, wherein the foam component is recovered by heating a water-soluble extract of jumbo leek (Allium ampeloprasum).   The composition according to claim 1 or 2, wherein the hepatic disorder is a hepatic disorder caused by hepatitis virus, alcohol, stress, drugs or immune abnormalities.   The composition according to any one of claims 1 to 3, which is a preventive and / or therapeutic agent for alcoholic liver injury.   The composition according to any one of claims 1 to 4, comprising saponin as an active ingredient. Crushing and / or pressing jumbo leek (Allium ampeloprasum),
A step of obtaining an extract from the pulverized and / or pressed product with water, a hydrophilic organic solvent, or a mixed solvent thereof;
A step of heating the extract, and a step of recovering a foam component from the heated extract,
A method for producing a composition for improving liver damage, comprising:

Images