JP6117963B2 - Composition for promoting tissue regeneration, comprising polyamine as an active ingredient - Google Patents

Description

  The present invention relates to a composition for promoting tissue regeneration comprising a polyamine as an active ingredient, and for promoting tissue regeneration comprising a polyamine composition obtained by acid extraction of soybean germ as an active ingredient. Relates to the composition.

  Various diseases, trauma, or aging causes abnormal changes such as damage and degeneration. If a composition capable of rapidly regenerating a tissue that has undergone such an abnormal change can be obtained, it is extremely useful in the treatment or prevention of various diseases and traumas, or in so-called anti-aging.

  For example, liver tissue is essential for vital activities, such as metabolism, detoxification, bile synthesis, etc., so it can be used for tissue degeneration or necrosis in liver cirrhosis or liver cancer, or for excision of these disease sites and liver transplantation. For accompanying donor liver resection, the lost liver tissue needs to be regenerated quickly. However, a composition having sufficient activity to promote the regeneration of such tissues has not been developed yet, and the present situation is that it has a recovery by relying only on the regeneration ability of the patient's own tissues.

  In addition, since cell growth is an important factor in tissue regeneration, tissue regeneration with compounds having cell proliferation activity has been attempted. However, tissue regeneration in vivo requires various factors such as the construction of a scaffold that serves as a regeneration site, cell-to-cell coupling, and induction of blood vessels and nerves. Therefore, at present, a compound having only cell proliferation activity has not yet produced a sufficient effect in tissue regeneration. Furthermore, with regard to compounds having cell proliferation activity and the like, side effects such as carcinogenesis are caused by ingestion, and development of a highly safe composition for promoting tissue regeneration is strong. It is desired.

  In addition, for the purpose of promoting regeneration of the liver and the like, attempts have been made to use injections such as Laennec (Laennec, a water-soluble substance of human placental enzyme degradation product) and freeze-dried platelets, and infusion preparations containing valine or glycyrrhetinic acid derivatives. However, since any administration form is invasive, the burden on the administration subject is large. Therefore, there is a strong demand for the development of a composition that can obtain the effect of promoting tissue regeneration by noninvasive administration such as oral administration as well as the effect and safety of tissue regeneration described above.

  Polyamines are bioactive amines that exist universally in living organisms, from prokaryotes to eukaryotes, and typical polyamines present in cells include putrescine (PUT), spermidine (SPD), and spermine (SPM). There are three types.

  Intracellular polyamine concentration is determined by “biosynthesis” by polyamine biosynthetic enzymes such as ornithine decarboxylase (ODC), “degradation” by polyamine degrading enzymes, and uptake into cells and discharge to the outside of cells. It is strictly controlled through “transport”.

  In addition, when polyamines in cells are depleted, cell growth is stopped, so it is considered that polyamines are essential factors for cell growth. Polyamines are believed to promote protein synthesis by interacting with nucleic acids, particularly RNA, and promote cell growth (Non-patent Document 1).

  However, as described above, a compound having only cell proliferation activity has not yet produced a sufficient effect in tissue regeneration. In addition, since the intracellular polyamine concentration is strictly controlled, it is not clear whether taking a large amount of polyamine can promote tissue regeneration in vivo or cell proliferation in the first place. Was not.

Igarashi K, Kashiwagi K, Biochem Biophys Res Commun. May 19, 2000, Vol. 271, No. 3, pages 559-564

  This invention is made | formed in view of the subject which the said prior art has, and aims at providing the composition which has few side effects and can accelerate | stimulate a tissue reproduction | regeneration.

  In order to achieve the above-mentioned object, the present inventors verified the effect of promoting the tissue regeneration by polyamine using a liver-excised rat. As a result, it was revealed that liver regeneration was significantly promoted in rats fed with a polyamine-containing diet compared to rats fed a polyamine-free diet. In addition, in rats fed with a feed mixed with polyamine composition obtained by acid extraction of soybean germ, the liver regeneration promoting effect is higher than rats fed with a polyamine-containing feed having the same polyamine content as the feed Was recognized. Polyamine is a safe substance with few side effects because it is contained not only in soybeans but also in various plants and animals with a rich dietary experience.

  That is, polyamine has an activity to promote tissue regeneration, and furthermore, the polyamine composition obtained by acid extraction of soybean germ has an activity to promote tissue regeneration higher than that of polyamine alone. And the present invention has been completed.

The present invention provides the following.
<1> at least one polyamine selected from the group consisting of spermidine and spermine as an active ingredient, a subject (except those that over-expression of spermidine / spermine N ¹ acetyltransferase is derived) regeneration of liver tissue in Composition to promote.
<2> A composition for eating and drinking for promoting regeneration of liver tissue, comprising putrescine, spermidine and spermine as active ingredients.
<3> A composition for promoting the regeneration of liver tissue, comprising a polyamine composition that is an acid extract derived from soybean germ as an active ingredient.

  In addition, as shown in the below-mentioned Example, it became clear that the rat which ingested the polyamine containing feed raises the whole body ATP density | concentration compared with the rat ingested the polyamine non-containing feed. In addition, in rats fed with a feed mixed with polyamine composition obtained by acid extraction of soybean germ, the ATP concentration increased higher than rats fed with a polyamine-containing feed having the same polyamine content as the feed. Admitted. Therefore, the reason why the regeneration of the tissue is promoted by polyamine is not necessarily clear, but such an increase in ATP concentration is presumed to be one of the causes.

  According to the present invention, tissue regeneration can be promoted with few side effects.

A graph showing the liver regeneration rate in 70% hepatectomized rats fed with test feed containing no polyamine, test feed containing 0.01% by weight polyamine, test feed containing 0.05% by weight polyamine or test feed containing soybean-derived polyamine. is there. In the figure, “*” indicates that the P value is <0.05, which is statistically significant. After administration of luciferin in a rat expressing luciferase throughout the body fed with a test feed containing no polyamine, a test feed containing 0.01% by weight polyamine, a test feed containing 0.1% by weight polyamine, or a test feed containing soy-derived polyamine It is a graph which shows the light emission brightness | luminance.

  The present invention provides a composition containing polyamine as an active ingredient for promoting tissue regeneration.

  The “tissue” whose regeneration is promoted by the composition of the present invention is not particularly limited, and can be appropriately selected depending on the purpose. Examples thereof include liver tissue, epithelial tissue, connective tissue, muscle tissue, and nerve tissue. Further, in the present invention, “tissue” is a concept including cells constituting the tissue and organs constituted by the tissue. Furthermore, in the present invention, the “tissue” may be a tissue existing in a living body or a tissue (for example, a cultured tissue) existing outside the body. The tissue may be derived from any organism and can be appropriately selected according to the purpose, but among them, it can be derived from animals (for example, derived from mammals), and can be derived from humans in particular. .

  In the present invention, tissue regeneration means that a tissue that has undergone changes such as damage or degeneration is brought close to or returned to an original normal state physically and / or functionally.

In the present invention, “polyamine” means an aliphatic carbohydrate containing two or more primary amino groups, and examples thereof include diamine, triamine, tetraamine, pentaamine, and hexaamine. More specifically, putrescine, Cadaverine, ethylenediamine, trimethylenediamine, hexamethylenediamine, spermidine, cardine, homospermidine, aminopropyl cadaverine, spermine, theremin, thermospermine, canabalmin, aminopentylnorspermidine, aminopropyl homospermine, canabalmin, homospermine, cardopentamine , Homocardopentamine, aminopropyl canabalmin, bis (aminopropyl) homospermine, bis (aminopropyl) norspermine, aminobutyl canabalmin, amino B pills homospermine, Homopentamin, cardo hexamine, homo cardo hexamine, CERUMO hexamine include homo CERUMO hexamine. The composition of the present invention may contain one or more of such polyamines. In addition, among these polyamines, the activity of promoting tissue regeneration is high, and since it is a polyamine that is mainly present in cells, the composition of the present invention includes the following because it is easily used in vivo: Putrescine [NH ₂ (CH ₂ ) ₄ NH ₂ ], spermidine [NH ₂ (CH ₂ ) ₃ NH (CH ₂ ) ₄ NH ₂ ], spermine [NH ₂ (CH ₂ ) ₃ NH (CH ₂ ) ₄ NH (CH ₂ ) ₃ NH ₂ ] is preferably contained.

  In the present invention, the “polyamine” may be in the form of a pharmacologically acceptable salt. Examples of such salts include salts of organic acids such as citric acid, acetic acid, trichloroacetic acid, sulfosalicylic acid (organic acid addition salts), salts of inorganic acids such as sulfuric acid, hydrochloric acid, acetic acid, phosphoric acid, perchloric acid (inorganic Acid addition salts).

  Polyamines are universally present in various plants, animal tissues, and cells, so they are extracted from these tissues, particularly salmon from fish such as salmon, sperm from animals such as cows and pigs, in accordance with known techniques. be able to. Polyamines can also be prepared by chemical synthesis or biochemical synthesis using enzymes or microorganisms. Furthermore, a polyamine can also be obtained by purchasing from Wako Pure Chemical Industries, Ltd., SIGMA, or the like. The acid addition salt of polyamine can be prepared by bringing polyamine in a free base form and an appropriate acid into contact with each other by a conventional method.

  As shown in the examples below, in the hepatectomized rat fed with a feed mixed with a polyamine composition obtained by acid extraction of soybean germ, the liver fed with a polyamine-containing feed having the same polyamine content as that feed The effect of promoting liver regeneration was higher than that of resected rats. Accordingly, the present invention provides a composition for promoting tissue regeneration, comprising a polyamine composition obtained by acid extraction of soybean germ as an active ingredient.

  In the present invention, the term “soy germ” refers to the part of soybean that eventually grows to become buds and roots, that is, the part of the soy embryo excluding the cotyledons (hypocotyl, young germ and young root parts). means.

  Further, before the acid extraction described later, from the viewpoint of removing impurities attached to the surface and increasing the extraction efficiency of the polyamine composition, the soybean germ may be washed with water or a weakly basic aqueous solution. There is no restriction | limiting in particular as this weakly basic aqueous solution, For example, sodium hydroxide aqueous solution (pH 10-14) is mentioned. Furthermore, from the viewpoint of damaging the cell wall and increasing the extraction efficiency of the polyamine composition, the soybean germ is crushed with a mixer, blender, homogenizer, mortar, ultrasonic crusher, etc., and then subjected to acid extraction described below. Also good.

  In the present invention, acidic conditions effective for extracting a polyamine composition effective for promoting tissue regeneration from such soybean germ are those having a pH of 5 or less, preferably 4 or less.

  Acids added to the liquid for extracting the polyamine composition so as to be in an acidic condition include inorganic acids such as sulfuric acid, hydrochloric acid, acetic acid, phosphoric acid and perchloric acid, citric acid, acetic acid, trichloroacetic acid, Examples include organic acids such as sulfosalicylic acid. Moreover, although the addition density | concentration of these acids may be suitably adjusted with the kind of acid to be used, it is 0.001-1M normally, Preferably it is 0.05-0.5M. Moreover, there is no restriction | limiting in particular as a liquid for extracting a polyamine composition, For example, water, alcohol, and an organic solvent are mentioned.

  Other conditions for extracting a composition effective for promoting tissue regeneration from soy germ under such acidic conditions include soy germ and a liquid for extracting the polyamine composition to which the acid is added (hereinafter referred to as a “polyamine composition”). The ratio to “acidic solution” is usually 1 to 1000 g / L. Moreover, in order to extract a polyamine composition from soybean germ, although stirring is normally performed, as time of this stirring, it is 0.5 to 10 hours normally, and temperature is 25 to 100 degreeC normally.

  In this way, after sufficiently extracting polyamine and the like contained in soybean germ into an acidic solution (liquid fraction), the residue is separated from the residue by centrifugation or filtration. A polyamine composition obtained by acid extraction "can be prepared.

  Centrifugation conditions are not particularly limited, but a centrifugal force of 100 to 10000 × G can usually be performed over 0.1 to 60 minutes. There is no restriction | limiting in particular as conditions of filtration, Usually, it can carry out using a filter with a hole diameter of 1-5000 micrometers.

  In addition, “polyamine composition obtained by acid extraction of soybean germ” (the liquid fraction) may be an ion exchange method, gel filtration method, membrane fractionation method, electrodialysis method, solvent extraction method, You may concentrate by the vacuum concentration method, the heat processing method, etc.

  Furthermore, the “polyamine composition obtained by acid extraction of soybean germ” may be neutralized as necessary. In this neutralization treatment, for example, a hydroxide or weak acid salt of an alkali metal such as sodium, calcium, potassium, or magnesium is used as a neutralizing agent.

  From the viewpoint of safety, the “polyamine composition obtained by acid extraction of soybean germ” may be sterilized. Examples of such sterilization treatment include heat sterilization, pressure sterilization, radiation sterilization, filter sterilization, and the like.

  Furthermore, the “polyamine composition obtained by acid extraction of soybean germ” may be dried and powdered by performing a treatment such as spray drying or freeze drying, if necessary.

  The polyamine content of the “polyamine composition obtained by acid extraction of soybean germ” according to the present invention is preferably 0.01 to 50% by mass, more preferably 0.05 to 5% by mass. is there. In addition, the content ratio of putresdin, spermidine and spermine in the “polyamine composition obtained by acid extraction of soybean germ” is preferably 0.0005 to 2.5 mass%, 0.008 to 40 mass%, and It is 0.0015-7.5 mass%, More preferably, they are 0.0025-0.25 mass%, 0.04-4 mass%, and 0.0075-0.75 mass%.

  Further, the “polyamine composition obtained by acid extraction of soybean germ” prepared in this way may be used, for example, as it is as a composition for promoting the regeneration of the tissue of the present invention, As described later, it may be used as a composition for promoting regeneration of the tissue of the present invention by combining with other components.

  The polyamine composition obtained by acid extraction of the polyamine or soybean germ has an excellent activity of promoting tissue regeneration as shown in Examples described later. Therefore, the composition for promoting the regeneration of the tissue of the present invention comprising these as active ingredients is used for treatment or prevention of various diseases and traumas accompanied by tissue changes such as damage and degeneration (for example, cirrhosis and liver cancer). It can be used as a pharmaceutical composition, food or drink for treatment or prevention, excision of a diseased site in liver cirrhosis, liver cancer and the like and treatment of liver tissue after excision of donor liver accompanying liver transplantation. It can also be used as a reagent for promoting the regeneration of cultured tissue.

  The composition for promoting tissue regeneration of the present invention can be formulated by a known pharmaceutical method. For example, capsule, tablet, pill, liquid, powder, granule, fine granule, film coating, pellet, troche, sublingual, chewing agent, buccal, paste, syrup, suspension, Use orally or parenterally as elixirs, emulsions, coatings, ointments, plasters, poultices, transdermal preparations, lotions, inhalants, aerosols, injections, suppositories, etc. Can do. However, the composition of the present invention is preferably used as an oral composition from the viewpoint that the burden on the administration subject is small.

  In these preparations, carriers that are acceptable as pharmacological or food and drink, specifically, sterile water and physiological saline, vegetable oils, solvents, bases, emulsifiers, suspending agents, surfactants, stabilizers, Flavoring agent, fragrance, excipient, vehicle, preservative, binder, diluent, tonicity agent, soothing agent, extender, disintegrant, buffering agent, coating agent, lubricant, colorant, sweetness Can be suitably combined with an agent, a thickening agent, a flavoring agent, a solubilizing agent or other additives.

  When the composition for promoting regeneration of the tissue of the present invention is used as a food or drink, the food or drink is, for example, a health food, a functional food, a food for specified health use, a dietary supplement, a food for a sick person, It can be a food additive or animal feed. The food / beverage products of this invention can be ingested as a composition as described above, and can also be ingested as various food / beverage products. Specific examples of food and drink products include edible oils, dressings, mayonnaise, margarine and other oils; soups, milk drinks, soft drinks, tea drinks, alcoholic drinks, drinks, jelly drinks, functional drinks, etc. Liquid foods; Carbohydrate-containing foods such as rice, noodles, breads; Livestock processed foods such as ham and sausages; Fish processed foods such as kamaboko, dried fish, and salted vegetables; Vegetable processed foods such as pickles; Semis such as jelly and yogurt Solid foods; Fermented foods such as miso and fermented beverages; Various confectionery such as Western confectionery, Japanese confectionery, candy, gums, gummi, frozen confectionery, ice confectionery; Retort products such as curry, sauce, Chinese soup; Instant soup, Examples include instant foods such as instant miso soup and foods for microwave ovens. Furthermore, health foods and drinks prepared in the form of powder, granules, tablets, capsules, liquid, paste or jelly are also included.

  As described above, the composition for promoting tissue regeneration of the present invention can be used for any organism, but is particularly suitable for animals including humans. There is no restriction | limiting in particular as an animal other than a human, Various livestock, a poultry, a pet, a laboratory animal, etc. can be made into object. Specific examples include, but are not limited to, pigs, cows, horses, sheep, goats, chickens, ducks, ostriches, ducks, dogs, cats, rabbits, hamsters, mice, rats, and monkeys.

  Manufacture of the food-drinks in this invention can be implemented with a manufacturing technique well-known in the said technical field. In the said food / beverage products, it is good also as multifunctional food / beverage products by combining with another functional food.

  When the composition for promoting the regeneration of the tissue of the present invention is administered or ingested, the dose or intake is the age, weight, symptom, health condition of the subject, the type of composition (pharmaceuticals, food and drink, etc.) The composition for promoting regeneration of the tissue of the present invention containing 0.2 to 200 mg of polyamine once a day is selected once depending on the subject matter. Or, it is preferably administered in several divided doses, and the regeneration of the tissue of the present invention containing 0.01 to 10 mg, 0.16 to 160 mg and 0.03 to 30 mg of putrescine, spermidine and spermine, respectively, is performed on one day. It is preferable to administer the composition for promoting once or several times.

  The product of the composition of the present invention (pharmaceutical product, food / drink product, reagent) or its instructions may be labeled with an indication that it is used to promote tissue regeneration. Here, “labeled product or instructions” means that the product body, container, packaging, etc. are marked, or instructions, package inserts, promotional materials, or other printed materials that disclose product information. It means that the display is attached to.

  Thus, the present invention is intended for the pharmaceutical composition of the present invention (for example, patients with cirrhosis and liver cancer, patients with liver cirrhosis and liver cancer who have excised disease sites, donors with liver excised with liver transplantation) There is also provided a method for treating or preventing a disease accompanied by promotion of tissue regeneration in a subject, characterized in that the method is administered.

  The polyamine, which is an active ingredient of the composition for promoting the regeneration of the tissue of the present invention, is not limited to soybeans, but is contained in various plants and animals with abundant experience. It is a substance. Therefore, the present invention can provide a composition with few side effects as well as promoting tissue regeneration.

  EXAMPLES Hereinafter, although this invention is demonstrated more concretely based on an Example, this invention is not limited to a following example. Moreover, the present Example was performed using the following composition, feed, and experimental animal.

(Polyamine composition obtained by acid extraction of soybean germ)
In order to prepare a polyamine composition by acid extraction from soybean germ, first, soybean (variety name: galaxy, WONDER, etc.) germ was collected. And the obtained germ was wash | cleaned with water or a weakly basic solution (Sodium hydroxide aqueous solution of pH 12-13), and in order to raise the extraction efficiency of a polyamine, the foreign material adhering to this germ was removed.

  Next, the washed germ was added to an acidic solution (pH 0.1M citric acid aqueous solution) having a pH of 2.5 to 3.5, and treated for 1 hour with stirring at 60 ° C. And after passing this processed material through a 100 mesh filter (pore diameter: 150 μm), it was further passed through a filter paper (pore diameter: 5 μm) to remove the sample residue from the acid extract of soybean germ. Then, the collected acid extract was concentrated by concentration under reduced pressure. Next, the resulting concentrate was neutralized by adding sodium hydroxide and powdered by spray drying.

  Table 1 shows the polyamine content in the “polyamine composition obtained by acid extraction of soybean germ” obtained as described above. The polyamine content was measured by high performance liquid chromatography.

(Test feed containing polyamine)
Polyamine-free test feed is corn oil instead of soybean oil (raw material rich in polyamine), which is a component of the feed, in the production of standard rodent feed (produced by Oriental Bio Co., Ltd.). Were prepared by mixing.

  The test feed containing 0.1% by weight of polyamine is composed of synthetic spermine and spermidine (manufactured by Wako Pure Chemical Industries, Ltd.) in the test feed containing no polyamine, and the polyamine content in the feed is 0.02 and 0.08% by weight, respectively. It was prepared by mixing.

  The test feed containing 0.05% by mass of polyamine is composed of synthetic spermine and spermidine (manufactured by Wako Pure Chemical Industries, Ltd.) in the test feed containing no polyamine, and the polyamine content in the feed is 0.01 and 0.04% by mass, respectively. It was prepared by mixing.

  The test feed containing 0.01% by weight of polyamine is synthetic spermine and spermidine (manufactured by Wako Pure Chemical Industries, Ltd.) in the test feed containing no polyamine, and the polyamine content in the feed is 0.002 and 0.008% by weight, respectively. It was prepared by mixing.

  Moreover, the polyamine composition obtained by acid extraction of the soybean germ and the polyamine-free test feed were mixed at a mass ratio of 5 to 95 to prepare a soybean-derived polyamine-containing test feed. The polyamine content in the soybean-derived polyamine-containing test feed is 0.009 to 0.011% by mass.

  These samples were pelleted and given to rats described later.

(Experimental animal)
For the experiment, a firefly luciferase-expressing transgenic Lewis rat (Luc-Tg LEW rat, male, body weight of 260 to 310 g, 10 to 12 weeks of age) previously established by the present inventors was used. In this rat, luciferase is expressed throughout the body under the control of the gene trap ROSA 26 promoter. Luciferase can generate light by oxidizing luciferin, but since adenosine triphosphate (ATP) is essential in this luminescence reaction, the amount of ATP in the rat body can be evaluated through the generated luminescence. (See Hakakata Y, et al., Transplantation, 2006, 81, 1179-1184; Teratani T, et al., Islets, May-June 2011, 3, 3, 3, 111-117). These rats were bred with a standard laboratory feed or the test feed and water constantly in a light / dark cycle every 12 hours under a temperature / humidity controlled environment. In addition, all animal experiments in this example were performed according to Jichi Medical University animal experiment guidelines.

Example 1
The effect of promoting the regeneration of liver tissue by polyamine in living donor liver transplant donors was examined using model animals. That is, a Luc-Tg LEW rat that was allowed to freely ingest a test feed containing no polyamine, a test feed containing 0.01% by weight polyamine, a test feed containing 0.05% by weight polyamine, or a test feed containing soy-derived polyamine for 3 days. 70% hepatectomy was performed. After the operation, the same diet as before the operation was given, and the rats were euthanized 7 days after the operation. The livers were then removed and their weights were measured. The liver regeneration rate (average value ± standard deviation) was calculated from the measured values obtained. The liver regeneration rate was calculated by the following formula.
Liver regeneration rate (%) = classical 70% liver weight (g) removed 7 days after hepatectomy / estimated total liver weight (g) × 100
The “estimated total liver weight (g)” is “a liver weight (g) removed at the time of classic 70% hepatectomy + an estimated residual liver weight (g)”. (Weight of liver removed at the time of classic 70% liver resection (g) /0.667) × 0.333 ”. In addition, Student t-test is applied to continuous data, Mann-Whitney test is applied to discontinuous low data, statistical analysis is performed, and statistical analysis is performed when P value is <0.05. It was judged to be significant. The obtained results are shown in FIG.

  As shown in FIG. 1 and Table 2, in rats fed with 0.05% by weight polyamine-containing test feed or soybean-derived polyamine-containing test feed (sample with a polyamine content of 0.01% by weight), statistically It was revealed that liver regeneration was significantly promoted. In addition, in rats fed with 0.01% by weight polyamine-containing test diet, it was revealed that liver regeneration was promoted although there was no statistically significant difference.

  Therefore, it was revealed that polyamine has an activity of promoting tissue regeneration. The soybean-derived polyamine-containing test feed and the 0.01% by weight polyamine-containing test feed are ingested by 0.01% by weight polyamine-containing test feed in spite of the same 0.01% by weight polyamine content. Compared to the examples, in the intake of the test feed containing soybean-derived polyamine, a remarkable effect of promoting tissue regeneration was observed. Therefore, the polyamine composition obtained by acid extraction of soybean germ is higher than that of polyamine alone. It was also revealed that it has an activity to promote

(Example 2)
Luc-Tg LEW rats were given a test feed containing no polyamine, a test feed containing 0.01% by weight polyamine, a test feed containing 0.1% by weight polyamine, a test feed containing soy-derived polyamine for 4 weeks under conditions of free intake, The whole body ATP metabolism of the rat was observed every other week.

  That is, at the start of each test feed intake, Luc-Tg LEW rats after 1 week intake, 2 weeks intake, 3 weeks intake, or 4 weeks intake were anesthetized by isoflurane aspiration, and then D-luciferin 30 mg / kg body weight The abdominal cavity was administered under conditions, and imaging was performed using an in vivo luminescence imaging system (IVIS (registered trademark), manufactured by Xenogen) 10 minutes after administration until the emission luminance reached a peak. Then, the light emission luminance was digitized from the photographed data. Furthermore, using analysis software (Living Image ver. 2.12a, manufactured by Xenogen), the luminance at the start of intake of the test feed of each group was set to 100%, and relative changes were determined. The obtained results are shown in FIG.

  As is clear from the results shown in FIG. 2, the intake of the test feed containing 0.01% by weight of polyamine is about 1.2 times that of the test feed containing 0.1% by weight of polyamine, compared to the intake of the test feed containing no polyamine. About 1.6 times in the intake of the test feed and about 1.3 times in the intake of the test feed containing soybean-derived polyamine, the luminescence brightness in the whole body, that is, the ATP concentration in the whole body increased. In addition, similarly to the promotion of tissue regeneration evaluated in Example 1, in spite of the same polyamine content of 0.01% by mass, than the intake example of 0.01% polyamine-containing test feed, The intake example of soybean-derived polyamine-containing test feed showed a higher rate of increase in ATP concentration.

  Therefore, it has also been clarified that polyamine has an activity to increase ATP concentration in cells (tissues) throughout the body. In addition, this increase in the ATP concentration in the tissue is considered as one factor for promoting tissue regeneration by polyamine.

  As described above, according to the present invention, tissue regeneration can be promoted. Therefore, since the composition of the present invention has few side effects and can promote tissue regeneration, the treatment or prevention of various diseases and traumas accompanied by tissue changes such as damage and degeneration (for example, treatment of cirrhosis and liver cancer) Or prevention, liver cirrhosis, excision of diseased part in liver cancer, etc. and treatment of liver tissue after excision of donor liver accompanying liver transplantation, reagent for promoting regeneration of food and drink, or cultured tissue, etc. Useful as.

Claims (2)

  A composition for eating and drinking for promoting the regeneration of liver tissue, comprising putrescine, spermidine and spermine as active ingredients.   A composition for promoting liver tissue regeneration, comprising a polyamine composition, which is an acid extract derived from soybean germ, as an active ingredient.