WO2015190573A1

WO2015190573A1 - Composition for preventing and/or improving iron-deficiency anemia, and composition for preventing and/or improving indefinite complaints associated with iron-deficiency anemia

Info

Publication number: WO2015190573A1
Application number: PCT/JP2015/066937
Authority: WO
Inventors: 尚之松永; 泉　可也; 泉堀ノ内; 康博木戸; ゆき子小林; 恵里福田
Original assignee: 株式会社ＢｉｏｍａｔｅｒｉａｌｉｎＴｏｋｙｏ; 京都府公立大学法人
Priority date: 2014-06-11
Filing date: 2015-06-11
Publication date: 2015-12-17
Also published as: JPWO2015190573A1

Abstract

[Problem] To provide a composition for preventing and/or improving iron-deficiency anemia, a composition for preventing and/or improving indefinite complaints associated with iron-deficiency anemia, a pharmacological composition for preventing and/or treating iron-deficiency anemia, a pharmacological composition for preventing and/or treating indefinite complaints associated with iron-deficiency anemia, use as an agent to prevent, improve, and/or treat iron-deficiency anemia, and use as an agent to prevent, improve, and/or treat indefinite complaints associated with iron deficiency anemia. [Solution] A divalent metal salt of cellobionic acid disaccharide is included as an active ingredient.

Description

Composition for preventing and / or improving iron deficiency anemia, composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia

The present invention relates to a composition for preventing and / or improving iron deficiency anemia, and a composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia. Composition for preventing and / or improving iron deficiency anemia comprising a metal salt as an active ingredient, and indefinite complaints associated with iron deficiency anemia comprising a divalent metal salt of cellobionic disaccharide as an active ingredient More particularly, the composition for preventing and / or improving iron deficiency anemia comprising a divalent metal salt of cellobionic acid disaccharide as an active ingredient. A composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia comprising a divalent metal salt as an active ingredient, and a divalent metal salt of cellobionic disaccharide as an active ingredient Pharmaceutical composition for prevention and / or treatment of deficiency anemia, and pharmaceutical composition for prevention and / or treatment of indefinite complaints associated with iron deficiency anemia, comprising a divalent metal salt of cellobionic disaccharide as an active ingredient .

鉄 Iron deficiency anemia is a nutritional disorder that occurs frequently in the world, and it is said that about 10% of Japanese women are affected. Iron deficiency anemia causes a decrease in red blood cells and induces oxygen transport deficiency, reducing the ability of skeletal muscles to produce oxidative energy, resulting in motives and shortness of breath, premature birth in pregnant women, reduced intelligence and developmental disorders in children This is a major problem because it causes serious adverse effects on the body, and effective prevention and countermeasures are required.

Treatment methods for iron deficiency anemia can include oral administration and intravenous administration of iron. However, since iron medication stimulates the gastrointestinal mucosa, side effects such as nausea, nausea, and diarrhea, as well as iron Deficiency anemia often accompanies so-called indefinite complaints such as fatigue, palpitation, shortness of breath, headache, dizziness, tinnitus, fatigue, loss of appetite, nausea, and diarrhea. In addition, while iron is an indispensable trace element in the living body, if it accumulates excessively, it will exhibit toxicity, and it will be extremely dangerous to cause adverse effects such as causing oxidative stress in the living body. There is also.

However, about 60 to 70% of iron in the living body is a component of hemoglobin contained in red blood cells, and is responsible for supplying oxygen to the whole body. Iron is an essential substance for cell division, proliferation, metabolism, etc. throughout the body, and it can be said that life cannot be maintained without iron. Therefore, when administering an iron preparation to the human body, a necessary and sufficient amount of iron should be replenished, and care must be taken so that the amount of iron in the body is never excessive. Since the supply of iron to the living body is mainly made by ingesting the iron contained in the diet, if the iron contained in the food can be efficiently taken into the living body using the interaction with the food component It is preferable because it helps to eliminate iron deficiency anemia and indefinite complaints associated therewith, and it is possible to avoid iron overload by homeostasis.

In recent years, mineral absorption promoters have attracted attention. Among these, sugar carboxylic acids obtained by oxidizing oligosaccharides are considered to have a high mineral-reinforcing effect on living bodies because they exhibit high water solubility. In addition, since sugar hemiacetal hydroxyl groups of oligosaccharides are oxidized, sugar carboxylic acids are less susceptible to degradation by in vivo hydrolases such as β-galactosidase after ingestion, and reach the intestines as they are to induce the growth of bifidobacteria It is thought that it can become a factor to do.

Recently, research results that iron absorption was promoted by ingesting lactobionic acid, which is a sugar carboxylic acid (Non-patent document 1 and Non-patent document 2), have promoted mineral absorption using lactobionic acid as an active ingredient. And mineral absorption promoters containing lactobionic acid and lactose are disclosed (Patent Document 1 and Patent Document 2). On the other hand, a mineral absorption promoter containing maltobionic acid that is an oligosaccharide acid and a salt thereof or maltobiono delta lactone as an active ingredient is disclosed (Patent Document 3). Furthermore, since cellobionic acid shows water solubility when it is in a salt form with calcium, iron or the like, it is considered to be useful as a mineral reinforcing agent (Patent Document 4).

JP-A-7-2777991 JP 2008-303208 A JP 2009-143883 A JP 2014-079185 A1

Cellobionic acid is similar in structure to lactobionic acid, but the functionality related to mineral absorption of cellobionic acid has not been specifically studied so far. In this respect, Patent Document 4 discloses that it can be a mineral reinforcing agent capable of taking in a divalent metal ion bound as a salt into a living body. This is clearly different from a composition that efficiently supplies iron not derived from a divalent metal salt of a saccharide into a living body. In addition, there are reports that the divalent metal salt of cellobionic acid disaccharide is superior in preventing and improving iron deficiency anemia, and indefinite complaints and improving effects associated with iron deficiency anemia. Not even done.

The present invention has been made in order to solve the above-mentioned problems, and is intended to prevent iron deficiency anemia comprising a divalent metal salt of cellobionic disaccharide excluding iron (II) cellobionate as an active ingredient. And / or an improving agent composition, a composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia, comprising as an active ingredient a divalent metal salt of cellobionic disaccharide other than iron (II) cellobionate, A composition for preventing and / or improving iron deficiency anemia comprising iron (II) cellobionate as an active ingredient, which regulates or enhances the absorption of iron contained in the diet, and regulates or enhances the absorption of iron contained in the diet A composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia comprising iron (II) cellobionate as an active ingredient, and a pharmaceutical composition for preventing and / or treating them Use of divalent metal salts of cellobionic acid disaccharides other than iron (II) cellobionate as an agent for the prevention, amelioration and / or treatment of iron deficiency anemia, divalent values of cellobionic acid disaccharides except iron (II) cellobionate Prevention, amelioration and / or treatment of unidentified complaints associated with iron deficiency anemia of metal salts, prevention of iron deficiency anemia of iron (II) cellobionate that regulates or enhances the absorption of iron in the diet, As an agent for improving and / or treating, and as an agent for preventing, ameliorating and / or treating indefinite complaints associated with iron deficiency anemia of iron (II) cellobionate that regulates or enhances the absorption of iron in the diet The purpose is to provide usage.

As a result of diligent research, the present inventors have shown that the divalent metal salt of cellobionic acid disaccharide has an effect of preventing or improving iron deficiency anemia, and further, the effect of preventing or improving indefinite complaints associated with iron deficiency anemia. To have an effect, to regulate or increase the amount of iron in the liver and / or plasma, to promote the absorption of iron in the intestine and to increase the amount of iron in the liver and / or the amount of iron in the plasma Found to suppress the decrease, regulate or enhance the absorption of iron in the intestine, regulate or enhance the absorption of iron in the diet, suppress the production of iron compounds that are insoluble or sparingly soluble in water, Furthermore, the preventive and improving effects of iron deficiency anemia produced by the divalent metal salt of cellobionic acid disaccharide, and the preventive and improving effects of indefinite complaints associated with iron deficiency anemia. Goods, iron deficiency poor Preventive or therapeutic agent The pharmaceutical composition of discomfort caused by and found that can be applied to preventing and improving cosmetic composition of iron deficiency in the skin tissue, and have completed the inventions below.

(1) A composition for preventing and / or improving iron deficiency anemia, comprising as an active ingredient a divalent metal salt of cellobiate disaccharide except iron (II) cellobionate.

(2) A composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia, comprising as an active ingredient a divalent metal salt of cellobionic acid disaccharide excluding iron (II) cellobionate.

(3) The preventive and / or ameliorating agent composition according to (1) or (2), which regulates or enhances the absorption of iron contained in a diet.

(4) The prevention and the prevention according to any one of (1) to (3), wherein the divalent metal salt is one or more salts selected from the group consisting of calcium, magnesium, copper and zinc salts. / Or an improving agent composition.

(5) The preventive and / or ameliorating agent composition according to any one of (1) to (3), wherein the divalent metal salt is calcium.

(6) A composition for preventing and / or improving iron deficiency anemia comprising iron (II) cellobionate as an active ingredient that regulates or enhances absorption of iron contained in a diet.

(7) A composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia, comprising iron (II) cellobionate as an active ingredient, which regulates or enhances absorption of iron contained in a diet.

(8) The preventive and / or ameliorating agent composition according to any one of (1) to (7), which regulates or increases the amount of iron in the liver and / or the amount of iron in plasma.

(9) The prevention and / or the suppression according to any one of (1) to (8), wherein iron absorption in the intestine is promoted to suppress a decrease in the amount of iron in the liver and / or plasma. Improver composition.

(10) The preventive and / or ameliorating agent composition according to any one of (1) to (9), which regulates or enhances iron absorption in the intestine.

(11) The preventive and / or ameliorating agent composition according to any one of (1) to (10), which suppresses the production of an iron compound that is insoluble or hardly soluble in water.

(12) The preventive and / or improving agent composition according to any one of (1) to (11), wherein the composition is a food composition.

(13) The prophylactic and / or ameliorating agent composition according to any one of (1) to (11), wherein the prophylactic and / or ameliorating agent composition is a preventive and / or therapeutic agent pharmaceutical composition.

(14) Use of a divalent metal salt of cellobionic disaccharide other than iron (II) cellobionate as an agent for preventing, improving and / or treating iron deficiency anemia.

(15) Use of a divalent metal salt of cellobiate disaccharide except iron (II) cellobionate as a preventive, ameliorating and / or therapeutic agent for indefinite complaints associated with iron deficiency anemia.

(16) Use of iron (II) cellobionate as a preventive, ameliorating and / or therapeutic agent for iron deficiency anemia, which regulates or enhances absorption of iron contained in the diet.

(17) Use of iron (II) cellobiate, which regulates or enhances the absorption of iron contained in a diet, as an agent for preventing, improving and / or treating indefinite complaints associated with iron deficiency anemia.

(18) A method for suppressing a decrease in the amount of iron in the liver and / or the amount of iron in plasma, comprising a step of orally ingesting a food or drink containing a divalent metal salt of cellobionic disaccharide (excluding medical practice) .)

A composition for preventing and / or improving iron deficiency anemia comprising a divalent metal salt of cellobionic acid disaccharide excluding iron (II) cellobionate according to the present invention as an active ingredient, excluding iron (II) cellobionate A composition for preventing and / or ameliorating indefinite complaints associated with iron deficiency anemia comprising a divalent metal salt of cellobionic disaccharide as an active ingredient, iron cellobionate that regulates or enhances the absorption of iron contained in the diet ( Composition for preventing and / or improving iron deficiency anemia comprising II) as an active ingredient, iron deficiency comprising iron (II) cellobionate as an active ingredient for regulating or enhancing absorption of iron contained in diet Composition for preventing and / or improving indefinite complaints associated with sexual anemia, pharmaceutical composition for preventing and / or treating them, and cellobiate disaccharides other than iron (II) cellobionate Prevention, amelioration and / or treatment of iron deficiency anemia with divalent metal salts, prevention of indefinite complaints associated with iron deficiency anemia of divalent metal salts of cellobionic disaccharides other than iron (II) cellobionate, Use as an ameliorating and / or treating agent, use of iron (II) cellobionate as an agent to prevent or ameliorate and / or treat iron deficiency anemia, which regulates or enhances the absorption of iron in the diet, and According to the use of iron (II) cellobionate, which regulates or enhances the absorption of iron contained, as a preventive, ameliorating and / or therapeutic agent for indefinite complaints associated with iron deficiency anemia, prevention / improvement of iron deficiency anemia Treatment, prevention, improvement and treatment of indefinite complaints associated with iron deficiency anemia, prevention, improvement and treatment of iron deficiency anemia without causing side effects such as nausea, nausea and diarrhea due to treatment of iron deficiency anemia Preparative it is, fatigue, palpitations, shortness of breath, headaches, dizziness, tinnitus, fatigue, anorexia, it is possible to avoid the discomfort caused by iron deficiency anemia, such as nausea. Moreover, since iron contained in food can be efficiently taken into the living body, the amount of iron in the living body can be prevented from becoming excessive while supplementing a necessary and sufficient amount of iron.

It is a figure which shows the structural formula of cellobiose, cellobionic acid, and calcium cellobionate, and its manufacturing process. It is a figure which shows the average body weight gain, average food intake, and average food efficiency from the start of the breeding period to the end of the breeding period of the test animals in each group. In the figure, the value is shown as an average value ± standard error. It is a figure which shows a time-dependent change of the red blood cell count (RBC) from the breeding period start by the test meal of the test animal in each group to the end of the breeding period. In the figure, the value is shown as an average value ± standard error. It is a figure which shows the time-dependent change of the hemoglobin density | concentration (Hb) from the breeding period start by the test meal of the test animal in each group to the end of the breeding period. In the figure, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). It is a figure which shows a time-dependent change of the hematocrit value (Ht) from the breeding period start by the test meal of the test animal in each group to the end of the breeding period. In the figure, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). It is a figure which shows the time-dependent change of the mean erythrocyte volume (MCV) from the breeding period start by the test meal of the test animal in each group to the end of the breeding period. In the figure, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). It is a figure which shows the time-dependent change of the amount of mean erythrocyte hemoglobin (MCH) from the breeding period start by the test meal of the test animal in each group to the end of the breeding period. In the figure, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). It is a figure which shows the time-dependent change of the mean erythrocyte hemoglobin concentration (MCHC) from the breeding period start by the test meal of the test animal in each group to the end of the breeding period. In the figure, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). It is a figure which shows the time-dependent change of plasma iron concentration (PI) from the breeding period start by the test meal of the test animal in each group to the end of the breeding period. In the figure, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). It is a figure which shows a time-dependent change of unsaturated iron binding ability (UIBC) from the breeding period start by the test meal of the test animal in each group to the end of the breeding period. In the figure, the value is shown as an average value ± standard error. It is a figure which shows the time-dependent change of the total iron binding ability (TIBC) from the breeding period start by the test meal of the test animal in each group to the end of the breeding period. In the figure, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). It is a figure which shows the time-dependent change of Tfs from the breeding period start by the test meal of the test animal in each group to the end of the breeding period. In the figure, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). It is a figure which shows the liver weight after the rearing (after dissection) of the test animal in each group by the test meal, spleen weight, and heart weight. In the figure, the value is shown as an average value ± standard error. It is a figure which shows the cecal content weight after breeding | raising by the test meal of the test animal in each group (after dissection). In the figure, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). It is a figure which shows the iron amount per 1g of liver after rearing by the test meal of the test animal in each group (after dissection). In the figure, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). It is a figure which shows the result of the iron hydroxide formation inhibition test by calcium cellobionate.

Hereinafter, a composition for preventing and / or improving iron deficiency anemia comprising, as an active ingredient, a divalent metal salt of cellobionic acid disaccharide other than iron (II) cellobionate according to the present invention, iron (II) cellobionate A composition for preventing and / or ameliorating indefinite complaints associated with iron deficiency anemia comprising a divalent metal salt of cellobionic disaccharide as an active ingredient except for cellobionic acid, which regulates or enhances the absorption of iron contained in diet A composition for preventing and / or improving iron deficiency anemia comprising iron (II) as an active ingredient, and iron (II) cellobionate as an active ingredient for regulating or enhancing absorption of iron contained in a diet Composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia, pharmaceutical composition for preventing and / or treating them, and cellobionic acid except iron (II) cellobionate Of divalent metal salts of iron as an agent for the prevention, amelioration and / or treatment of iron deficiency anemia, indefinite complaints associated with iron deficiency anemia of divalent metal salts of cellobionic disaccharides other than iron (II) cellobionate Use as an agent for the prevention, amelioration and / or treatment of iron, the use of iron (II) cellobionate as an agent for the prevention, amelioration and / or treatment of iron deficiency anemia which modulates or enhances the absorption of iron in the diet, and The use of iron (II) cellobionate as a preventive, ameliorating and / or therapeutic agent for iron deficiency anemia that regulates or enhances the absorption of iron contained in the diet will be described in detail.

A composition for preventing and / or improving iron deficiency anemia comprising a divalent metal salt of cellobionic acid disaccharide excluding iron (II) cellobionate according to the present invention as an active ingredient, excluding iron (II) cellobionate A composition for preventing and / or ameliorating indefinite complaints associated with iron deficiency anemia comprising a divalent metal salt of cellobionic disaccharide as an active ingredient, iron cellobionate that regulates or enhances the absorption of iron contained in the diet ( Composition for preventing and / or improving iron deficiency anemia comprising II) as an active ingredient, iron deficiency comprising iron (II) cellobionate as an active ingredient for regulating or enhancing absorption of iron contained in diet A composition for preventing and / or improving indefinite complaints associated with congenital anemia, and a pharmaceutical composition for the prevention and / or treatment of these are effective preparations of divalent metal salts of cellobionic disaccharides. It included as made.

Iron contained in the diet is converted to divalent iron and taken up into small intestinal epithelial cells. Iron pumped into the blood from epithelial cells binds transferrin and is transported throughout the body for use. Excess iron that has not been used in the living body is stored in the liver as ferritin or hemosiderin, but is released into the blood when iron in the body is insufficient. Moreover, when iron shortage continues in the living body and the amount of stored iron becomes small, absorption of iron contained in the diet is promoted in the intestine. If iron deficiency continues in the body, stored iron for use in hematopoiesis is cut out in order to maintain plasma iron concentration. Such a state is an iron deficiency state without anemia, that is, a state where stored iron is depleted but anemia does not occur, and the total iron binding ability increases and the transferrin saturation rate decreases. Furthermore, as iron deficiency progresses, anemia appears and iron deficiency anemia characterized by microcytic hypochromic anemia develops. The above is an overview up to iron deficiency anemia.

One of the causes of the development of iron deficiency anemia is that the absorption rate of iron contained in the diet is lower than the absorption rate of other nutrients. However, the absorption rate of iron varies widely depending on the amount of iron in the living body and other food ingredients, so that by taking in food ingredients that have an iron absorption promoting effect together with iron, the iron contained in the diet Therefore, the composition for preventing and / or improving iron deficiency anemia according to the present invention is effective for iron deficiency anemia.

In addition, it is known that onset of iron deficiency anemia often involves so-called indefinite complaints. “Indefinite complaints” refers to fatigue, palpitation, shortness of breath, headache, dizziness, tinnitus, fatigue, loss of appetite. , Nausea, diarrhea, and other physical complaints that are strongly related to the autonomic nervous system, characterized by instability, proneness, and poor objective findings (diagnosis and treatment of indefinite complaints, history of medicine) , 181, 12: 1009-1028, 1977).

Examples of the “divalent metal salt” in the present invention include one or more salts selected from the group consisting of calcium, magnesium, iron (II), copper and zinc salts. That is, in the present invention, the “divalent metal salt of cellobionic disaccharide” is, for example, selected from the group consisting of calcium cellobionate, magnesium cellobionate, iron (II) cellobionate, copper cellobionate and zinc cellobionate. One or more substances may be mentioned.

As an example, FIG. 1 shows the structural formulas of cellobiose, cellobionic acid, and calcium cellobionate and their manufacturing steps. As shown in FIG. 1, cellobionic acid is produced by the cell reaction method from the disaccharide cellobiose or after the production of calcium cellobionate from the disaccharide cellobiose by the cell reaction method, followed by cation exchange from the produced calcium cellobionate. Each can be manufactured by the method.

Calcium cellobionate dissolves iron contained in the diet, dissolves iron compounds that are insoluble or sparingly soluble in water, or suppresses the formation of iron compounds that are insoluble or sparingly soluble in water, resulting in a trivalent state of iron The present inventors have recently promoted the so-called mild chelation reaction to the bivalent state and maintain the bivalent state of iron even in the intestinal tract which is in an alkaline condition by pancreatic juice. It became clear by these studies. By such actions, the amount of iron in the liver and / or the amount of iron in plasma can be adjusted or increased, and iron absorption in the intestine is promoted to increase the amount of iron in the liver and iron in plasma. It is possible to suppress the decrease in the amount, and to regulate and enhance the absorption of iron in the intestine, or to regulate and enhance the absorption of iron contained in the diet. The performance is not limited to calcium cellobionate, and examples include magnesium cellobionate, iron (II) cellobionate, copper cellobionate, and zinc cellobionate. Accordingly, in the present invention, not only calcium cellobionate but also magnesium cellobionate, iron (II) cellobionate, copper cellobionate, and zinc cellobionate can be used.

Therefore, a composition for preventing and / or improving iron deficiency anemia comprising a divalent metal salt of cellobionic disaccharide other than iron (II) cellobionate as an active ingredient according to the present invention, iron (II) cellobionate A composition for preventing and / or ameliorating indefinite complaints associated with iron deficiency anemia comprising a divalent metal salt of cellobionic disaccharide as an active ingredient except for cellobionic acid, which regulates or enhances the absorption of iron contained in diet A composition for preventing and / or improving iron deficiency anemia comprising iron (II) as an active ingredient, and iron (II) cellobionate as an active ingredient for regulating or enhancing absorption of iron contained in a diet Composition for preventing and / or ameliorating indefinite complaints associated with iron deficiency anemia, and pharmaceutical composition for preventing and / or treating the same is a divalent metal salt of cellobionic disaccharide By containing as an active ingredient, the amount of iron in the liver and / or the amount of iron in the plasma is adjusted or increased, and iron absorption in the intestine is promoted to increase the amount of iron in the liver and the amount of iron in the plasma. Control the increase of iron absorption in the intestine, control and increase the absorption of iron in the diet, dissolve iron in the diet, dissolve iron compounds that are insoluble or sparingly soluble in water Or the formation of iron compounds that are insoluble or sparingly soluble in water, and the divalent metal salt of cellobionic disaccharide is associated with the prevention, improvement and / or treatment of iron deficiency anemia or iron deficiency anemia It can be used as a preventive, ameliorating and / or therapeutic agent for indefinite complaints.

In the present invention, the “iron compound that is insoluble or hardly soluble in water” is not particularly limited, and examples thereof include ferric hydroxide (Fe (OH) ₃ ; trivalent iron ion) and ferric phosphate (FePO 4). A trivalent iron ion).

In the present invention, “prevention of iron deficiency anemia” means to suppress the state of iron deficiency anemia, to delay the state of iron deficiency anemia, or the boundary area thereof. It is a concept that includes suppressing or delaying the state of the disease, specifically, iron deficiency anemia, acting on the pathogenesis of iron deficiency, and suppressing or delaying the state of iron deficiency anemia , Or preventing or delaying their boundary state.

In the present invention, “improvement of iron deficiency anemia” means that the state of iron deficiency anemia or the boundary region thereof is brought close to the state defined as a normal region, and the state of iron deficiency anemia is recovered. To reduce the state of iron deficiency anemia.

In the present invention, "treatment of iron deficiency anemia" is a concept that includes the prevention of progression of iron deficiency anemia and improvement of the state of iron deficiency anemia, and further, maintenance of remission, prevention of relapse, recurrence It is a concept that includes prevention.

In the present invention, when used as a food composition, the form thereof can be appropriately selected within a range not impairing the characteristics of the present invention. For example, the composition for preventing and / or improving iron deficiency anemia according to the present invention. Examples include those prepared as foods as they are, those added to other foods, or any form commonly used for foods or health foods such as capsules and tablets. In addition, when ingested or administered in the form of food, excipients, extenders, binders, thickeners, emulsifiers, colorants, fragrances, food additives, as long as the characteristics of the present invention are not impaired. It can be mixed with products, seasonings, etc., and shaped into powders, granules, tablets, etc. depending on the application. Furthermore, it can be ingested by preparing a food by mixing it with a food material and commercializing it as a functional food.

When used as a therapeutic agent pharmaceutical composition, formulation and administration forms can be selected as appropriate by methods known to those skilled in the art within a range not impairing the characteristics of the present invention. For example, the dosage form in the case of preparation as an oral administration preparation can include tablet, granule, powder, capsule, coating agent, solution, suspension, etc. Examples of the dosage form include gels, inhalants, injections, drops, suppositories, coatings, sprays, patches, ointments, creams and the like. In addition, the dosage can be appropriately set depending on the formulation form of the pharmaceutical composition, the administration method, the purpose of use, and the age, weight and symptom of the administration subject applied thereto.

Next, the method (except medical practice) for suppressing the decrease in the amount of iron in the liver and / or the amount of iron in plasma according to the present invention has the following step (I).
(I) A step of orally ingesting a food or drink containing a divalent metal salt of cellobionic acid disaccharide (oral ingestion step).

The method of ingesting orally in the oral ingestion step (I) is not particularly limited, and can be performed based on methods that can be appropriately selected by those skilled in the art. Moreover, foodstuffs mentioned above can be mentioned as food and drink containing a divalent metal salt of cellobionic acid disaccharide.

Furthermore, in the method for suppressing the decrease in the amount of iron in the liver and / or the amount of iron in plasma according to the present invention (excluding medical practice), as long as the characteristics of the method are not impaired, the method other than the above (I) You may have the process of.

Hereinafter, a composition for preventing and / or improving iron deficiency anemia comprising, as an active ingredient, a divalent metal salt of cellobionic acid disaccharide other than iron (II) cellobionate according to the present invention, iron (II) cellobionate A composition for preventing and / or ameliorating indefinite complaints associated with iron deficiency anemia comprising a divalent metal salt of cellobionic disaccharide as an active ingredient except for cellobionic acid, which regulates or enhances the absorption of iron contained in diet A composition for preventing and / or improving iron deficiency anemia comprising iron (II) as an active ingredient, and iron (II) cellobionate as an active ingredient for regulating or enhancing absorption of iron contained in a diet Composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia, pharmaceutical composition for preventing and / or treating them, and cellobionic acid except iron (II) cellobionate Of divalent metal salts of iron as an agent for the prevention, amelioration and / or treatment of iron deficiency anemia, indefinite complaints associated with iron deficiency anemia of divalent metal salts of cellobionic disaccharides other than iron (II) cellobionate Use as an agent for the prevention, amelioration and / or treatment of iron, the use of iron (II) cellobionate as an agent for the prevention, amelioration and / or treatment of iron deficiency anemia which modulates or enhances the absorption of iron in the diet, and The use of iron (II) cellobionate as a preventive, ameliorating and / or therapeutic agent for iron deficiency anemia, which regulates or enhances the absorption of iron contained in the diet, will be described based on examples. Note that the technical scope of the present invention is not limited to the features shown by these examples.

<Example 1> Content and result of test (1) Preparation of test animal, preparation of test food and rearing by test food Prevention of iron deficiency anemia when bivalent metal salt of cellobionic disaccharide was administered and Various data necessary for confirming the effect of treatment was obtained using test animals and test meals.

[1-1] Preparation of test animals 30 18-week-old SD female rats (Japan SLC) were prepared as test animals, adjusted to a temperature of 23 ± 2 ° C. and a humidity of 50 ± 2%, and light and dark for 12 hours. Preliminary breeding was carried out by feeding a 20% casein diet for 6 to 7 days in a breeding room set for a cycle (lighting from 8:00 to 20:00). During the pre-breeding period, the 20% casein diet and distilled water were ad libitum.

[1-2] Preparation of test meal As shown in Table 1 below, as a test meal for the control group (hereinafter referred to as “Group C”), a low iron diet group (hereinafter referred to as “LI group”). For the cellobionic acid diet group (hereinafter referred to as “CA group”), for the calcium cellobiate diet group (hereinafter referred to as “CAC group”) and for the cellobiose diet group (hereinafter referred to as “CL group”). Each was prepared. In addition, as the “mineral mixture”, a mixture containing no iron and a salad oil in which rapeseed oil and soybean oil were mixed so that the weight ratio was 7: 3 were used. In addition, as shown in Table 2 below, for the C group, use was made of iron citrate added so that the total iron content was 4.0 mg / 100 g, and for the LI group 5% (5% (w / w) α-corn starch for CA group, CAC group, and CL group were exchanged for 5% (w / w) α-corn starch, respectively, without using iron citrate. w / w) to which cellobionic acid, calcium cellobionate and cellobiose were added was used. The total iron content for the LI group is 0.4 mg / 100 g, the total iron content for the CA group, the CAC group and the CL group is 0.37 mg / 100 g, and the total iron content is C group. It became 1/10 or less of for.

Furthermore, the cellobiose used was manufactured in-house, the calcium cellobiate was manufactured in-house by the cell reaction method using 10% cellobiose solution, and the cellobionic acid was cation exchange method using calcium cellobiate. Each of those manufactured in-house by

In addition, the procurement source of each raw material used for the preparation of the test meal is as follows.
Casein: Oriental Yeast Co., Ltd. α-Corn Starch: Matsutani Chemical Cellobionic Acid: Biomaterial in Tokyo (in-house)
Calcium cellobionate: Biomaterial in Tokyo (in-house)
Cellobiose: Biomaterial in Tokyo (in-house)
Sucrose: Itochu Sugar Seed Oil: Nissin Oilio Soybean Oil: Wako Pure Chemical Industries Vitamin Mix: Oriental Yeast Co., Ltd. (AIN-76 Vitamin Mix)
Mineral mixing: Oriental Yeast Co., Ltd. (iron removal AIN-76 mineral mixing)
* AIN-76 is a standard purified feed for nutritional research using mice and rats, published in 1977 by the National Institute of Nutrition (AIN).
Iron citrate: Wako Pure Chemical Industries, Ltd. (Iron (III) Citrate n-Hydrate)
Cellulose: Oriental Yeast Co., Ltd.

[1-3] Breeding with test food Thirty rats preliminarily raised in Example 1 (1) [1-1] were divided into C group, LI group, CA group, CAC group and CL group based on body weight. Each test meal prepared in Example 1 (1) [1-2] was given for 28 days, divided into 5 groups (n = 6 in any group). The breeding was carried out using a stainless cage in the breeding room of Example 1 (1) [1-1].

(2) Measurement or calculation for various test items Rat body weight and food intake were measured at the same time every day from the start of the rearing period to the end of the rearing period. In addition, the number of red blood cells (RBC), hemoglobin concentration (Hb), hematocrit value (Ht), average red blood cell volume (MCV), average red blood cell hemoglobin amount (MCH), average red blood cell hemoglobin concentration, which are test items for judging anemia status (MCHC), plasma iron concentration (PI), unsaturated iron binding ability (UIBC), total iron binding ability (TIBC) and plasma transferrin iron saturation rate (Tfs) every 3 days from the start of the study Blood was collected from the tail vein of rats. At the end of the breeding period, each rat was laparotomized under ether anesthesia, blood was collected from the inferior vena cava, and then euthanized, and then the liver, heart, spleen, and cecum were collected from each rat. Based on the collected blood, liver, heart, spleen, and cecum, the following test items were measured or calculated.

[2-1] Calculation of average body weight gain, average food intake and average food efficiency As described above, from the start of the breeding period to the end of the breeding period in each group based on the body weight and food intake measured at the same time every day during the breeding period Average body weight gain, average food intake, and average food efficiency were calculated. The result is shown in FIG.

In Fig. 2, the values are shown as mean ± standard error. As shown in FIG. 2, regarding the average weight gain, the average food intake and the average food efficiency value from the start of the breeding period to the end of the breeding period in each group, the average weight gain and the average food efficiency value of the CAC group are C Although there was no significant difference compared with the group value, the LI group value, the CA group value, and the CL group value, the values were low.

[2-2] Measurement of Red Blood Cell Count (RBC) The red blood cell count (RBC) was measured for blood treated with EDTA using a multi-item automatic blood cell counter (KX-21NV, Sysmex). The measurement results are shown as mean ± standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 3, the values are shown as mean ± standard error. As shown in FIG. 3, there was no significant difference in the RBC values from the start of the breeding period to the end of the breeding period in each group.

[2-3] Measurement of hemoglobin concentration (Hb) As with the RBC in Example 1 (2) [2-2], the hemoglobin concentration (Hb) was determined for multi-item automatic blood cell counts for blood treated with EDTA. Measurement was performed using an apparatus (KX-21NV, Sysmex Corporation). The measurement results are shown as mean ± standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 4, the values are shown as mean values ± standard errors, and the case where different alphabets are attached is considered significant (p <0.05). As shown in FIG. 4, there was no significant difference between the values of the C group and the LI group for the Hb values from the start of the breeding period to the end of the breeding period in each group. The value of tended to be lower than that of Group C. The CA group value, the CAC group value, and the CL group value were not significantly different from the LI group value, and the CAC group value was not significantly different from the C group value. There wasn't. On the other hand, the CL group value was significantly lower on the 12th day than the CAC group value, and was significantly lower on the 15th and 21st to 27th days than the C group value. Met. Further, the value of CA group was significantly lower on the 27th day than the value of Group C.

[2-4] Measurement of hematocrit value (Ht) Similar to the RBC of Example 1 (2) [2-2], the hematocrit value (Ht) was also determined for multi-item automatic blood cell counts for blood treated with EDTA. Measurement was performed using an apparatus (KX-21NV, Sysmex Corporation). The measurement results are shown as mean ± standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 5, the value is expressed as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). As shown in FIG. 5, there was no significant difference between the value of the C group and the value of the LI group for the Ht value from the start of the breeding period to the end of the breeding period in each group. The value of tended to be lower than that of Group C. The CA group value, the CAC group value, and the CL group value were not significantly different from the LI group value, and the CAC group value was not significantly different from the C group value. There wasn't. On the other hand, the value of the CL group is significantly lower on the 15th to 21st and 27th days than the value of the C group, and the value of the CA group is 15th and 27th compared with the value of the C group. Significantly low on day.

[2-5] Calculation of mean erythrocyte volume (MCV) The mean erythrocyte volume (MCV) was calculated by using a multi-item automatic blood cell counter (KX-21NV, Sysmex) for blood treated with EDTA. The calculation results are shown as mean ± standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 6, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). As shown in FIG. 6, regarding the value of MCV from the start of the breeding period to the end of the breeding period in each group, the value of the LI group is significantly lower on the 21st and 27th days than the value of the C group. However, there was no significant difference compared to the CA group value, the CAC group value, and the CL group value. On the other hand, the CAC group value was not significantly different from the C group value. Further, the value of the CL group was significantly lower on the 15th to 27th days than the value of the C group, and was significantly lower on the 18th to 27th days than the value of the CAC group. Furthermore, the value of the CA group was significantly lower on the 21st and 27th days than the value of the C group.

[2-6] Calculation of mean erythrocyte hemoglobin amount (MCH) The mean erythrocyte hemoglobin amount (MCH) is the same as that of MCV in Example 1 (2) [2-5] for blood treated with EDTA. Calculation was performed using an automatic blood cell counter (KX-21NV, Sysmex). The calculation results are shown as mean ± standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 7, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). As shown in FIG. 7, regarding the MCH value from the start of the breeding period to the end of the breeding period in each group, the value of the LI group is significantly lower on the 24th and 27th days than the value of the C group. However, there was no significant difference compared to the CA group value, the CAC group value, and the CL group value. On the other hand, the CAC group value was not significantly different from the C group value, and the CA group value was significantly lower on the 24th and 27th days than the C group value. It was. The CL group value was significantly lower on the 24th and 27th days than the C group value, and was significantly lower on the 24th day than the CAC group value.

[2-7] Calculation of mean erythrocyte hemoglobin concentration (MCHC) As with the MCV of Example 1 (2) [2-5], the mean erythrocyte hemoglobin concentration (MCHC) is also high for blood treated with EDTA. Calculation was performed using an automatic blood cell counter (KX-21NV, Sysmex). The calculation results are shown as mean ± standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 8, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). As shown in FIG. 8, regarding the value of MCHC from the start of the breeding period to the end of the breeding period in each group, the value of the LI group is compared with the value of the C group, the value of the CA group and the value of the CAC group on the 24th day. The value was significantly higher. On the other hand, the CL group value was significantly higher on the 24th and 27th days than the CAC group value, and was significantly higher on the 27th day than the LI group value.

[2-8] Measurement of Plasma Iron Concentration (PI) Plasma iron concentration (PI) can be measured for separated plasma using SI measurement reagent (Determiner L Fe, Kyowa Medix) and automatic biochemical analyzer (CL-8000, Shimadzu). (Manufactured by Seisakusho). The measurement results are shown as mean ± standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 9, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). As shown in FIG. 9, regarding the value of PI from the start of the breeding period to the end of the breeding period in each group, the value of the LI group shows a downward trend immediately after the start of the test as compared to the value of the C group, and The value was significantly low on the 27th day. In addition, the value of the LI group was not significantly different from the value of the CA group and the value of the CL group, but was significantly lower on the 9th day than the value of the CAC group. On the other hand, the value of the CAC group showed the same transition as the value of the C group, and was significantly lower on the 24th to 27th days than the value of the C group. The CA group value was significantly lower on the 9th day than the CAC group value, and was significantly lower on the 15th to 27th days than the C group value. Furthermore, the CL group value was significantly lower on the 9th and 12th days compared to the CAC group value, and was significantly lower on the 9th to 27th days compared to the C group value. It was.

[2-9] Measurement of Unsaturated Iron Binding Capacity (UIBC) Unsaturated iron binding capacity (UIBC) is measured using a reagent for measuring UIBC (Determiner L UIBC, Kyowa Medix) and a biochemical automatic analyzer (CL) for separated plasma. -8000, Shimadzu Corporation). The measurement results are shown as mean ± standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 10, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). As shown in FIG. 10, regarding the value of UIBC from the start of the breeding period to the end of the breeding period in each group, the value of the LI group shows an increasing tendency compared to the value of the C group, and the 18th and 24th days The CAC group value was significantly higher than that of the LI group compared with the CA group value and the CL group value. Significantly low on day. On the other hand, the value of the CL group was significantly higher on the 15th day and the 21st to 27th days than the value of the C group, and was significantly higher on the 21st day than the CAC group. In addition, the value of CA group was significantly higher than that of Group C on the 24th to 27th days. Furthermore, the value of the CAC group was significantly higher on the 24th day than the value of the C group.

[2-10] Calculation of Total Iron Binding Capacity (TIBC) The total iron binding capacity (TIBC) was calculated using the PI value measured in Example 1 (2) [2-8] and the Example 1 (2) [2] Based on the UIBC value measured in [-9], the following formula was used.
(Formula) TIBC (μg / dL) = PI + UIBC
The obtained numerical value was shown by the average +/- standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 11, the values are shown as an average value ± standard error. As shown in FIG. 11, there was no significant difference in the TIBC values from the start of the breeding period to the end of the breeding period in each group.

[2-11] Calculation of Plasma Transferrin Iron Saturation Rate (Tfs) The plasma transferrin iron saturation rate (Tfs) is determined according to the PI value measured in Example 1 (2) and [2-8] and Example 1 (2). Based on the UIBC value measured in [2-9], it was calculated by the following formula.
(Formula) Tfs (%) = PI / UIBC × 100
The obtained numerical value was shown by the average +/- standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 12, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). As shown in FIG. 12, regarding the value of Tfs from the start of the breeding period to the end of the breeding period in each group, the value of the LI group shows a tendency to decrease immediately after the start of the test, compared with the value of the C group, and 15 to The value was significantly low on the 27th day. In addition, the value of the LI group was not significantly different from the value of the CA group and the value of the CL group, but was significantly lower on the 9th and 18th days than the value of the CAC group. Met. On the other hand, the value of the CAC group showed the same transition as the value of the C group, and was significantly lower on the 24th to 27th days than the value of the C group. Further, the value of the CA group was significantly lower on the 18th day than the value of the CAC group, and was significantly lower on the 15th to 27th days than the value of the C group. Furthermore, the CL group value is significantly lower on the 9th to 12th, 18th and 24th days compared to the CAC group value, and 15 to 27 days compared to the C group value. It was significantly low in the eyes.

[2-12] Measurement of liver weight, spleen weight and heart weight The collected liver, heart and spleen were washed with physiological saline, and the respective weights were measured. The result is shown in FIG.

In FIG. 13, the values are shown as an average value ± standard error. As shown in FIG. 13, the liver weight, spleen weight and heart weight of the CAC group were compared with those of the C group, the LI group, the CA group and the CL group with respect to the values of the liver weight, spleen weight and heart weight after the test in each group. There was no significant difference and no trend was shown.

[2-13] Measurement of cecal content weight The collected cecum was washed with physiological saline, and the weight of the whole cecum except the content was measured, and the difference between the weights was taken as the content weight. The result is shown in FIG.

In FIG. 14, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). As shown in FIG. 14, regarding the value of the cecal content weight after the test in each group, between the value of the C group, the value of the LI group and the value of the CL group, and the value of the CA group and the value of the CAC group There was no significant difference between them, but the CA group value and the CAC group value were significantly higher than the C group value, the LI group value, and the CL group value.

[2-14] Measurement of the amount of iron per gram of liver The amount of iron per gram of liver was determined by wet ashing the weighed liver using a microwave sample pretreatment system (ETHOS 1000, Milestone General) and evaporating to dryness. After solidifying, it was dissolved in dilute hydrochloric acid and measured using a Nitroso-PSAP direct method (Determiner LFe, Kyowa Medix) and a biochemical automatic analyzer (CL-8000, Shimadzu Corporation). The measurement results are shown as mean ± standard error. In addition, comparison between the (food) groups was analyzed by one-way analysis of variance and then a significant difference test was performed using the Tukey-Kramer method, and a case where p <0.05 was considered significant. The result is shown in FIG.

In FIG. 15, the value is shown as an average value ± standard error, and a case where a different alphabet is attached is considered significant (p <0.05). As shown in FIG. 15, regarding the value of the iron amount per 1 g of liver after the test in each group, the value of the LI group and the value of the CL group were significantly lower than those of the C group. The LI group value was not significantly different from the CA group value, the CAC group value and the CL group value, but was clearly lower than the CAC group value. . On the other hand, although the CA group value and the CAC group value were not significantly different from the C group value, the CAC group value was particularly high compared to the C group value. .

(3) Results As shown in FIG. 3, no significant difference was observed in the RBC values from the start of the breeding period to the end of the breeding period in each group from the start of the breeding period to the end of the breeding period. As shown in FIG. 9 and FIG. 12, at the end of the experiment, the LI group taking the low iron diet had significantly lower PI values and Tfs values than the C group. Further, as shown in FIGS. 4 to 7, the LI group showed a tendency to decrease in the Hb value, the Ht value, the MCV value, and the MCH value as compared with the C group. Furthermore, as shown in FIG. 15, the value of the amount of iron in the liver was significantly reduced in the LI group compared to the C group. Therefore, it was shown that the LI group fed with a low iron diet was in an iron deficient state at the end of the experiment and was in a state of falling into microcytic hypochromic anemia, a characteristic of iron deficient anemia.

On the other hand, in the CAC group that received a diet in which calcium serobionate was mixed with a low iron diet, as shown in FIGS. 9 and 12, the PI value and Tfs were compared with the LI group that received only the low iron diet. The value did not decrease, and even when compared with the C group, it was revealed that the change was similar to that of the C group until the 12th day from the start of the experimental meal, and thereafter it remained relatively high. Further, as shown in FIG. 6 and FIG. 7, it was clarified that the MCV value and the MCH value did not decrease as compared with the LI group. Furthermore, as shown in FIG. 15, the value of the iron content in the liver of the CAC group was clearly higher than that of the LI group, and the value was as high as the value of the C group. From these results, it was shown that the hematopoietic ability was maintained as a result of suppressing the decrease in the amount of stored iron and the decrease in the amount of plasma iron in the CAC group, and that anemia and iron deficiency were avoided. It was.

From these results, it is shown that calcium cellobionate maintains the supply of iron to the living body and suppresses the reduction of stored iron by promoting the absorption of iron contained in the diet even in situations where iron intake is low. It was done. In other words, calcium cellobionate is useful for preventing or improving iron deficiency anemia, especially by regulating or increasing the amount of iron in the liver or plasma, or regulating the absorption of iron in the diet. Or it has been shown to prevent or ameliorate iron deficiency anemia by augmentation.

Example 2 Iron Hydroxide Formation Inhibition Test Using Calcium Cellobionate Iron is taken into the body through small intestinal epithelial cells, but a divalent metal ion transporter, Divalent, is present in the apical membrane of small intestinal epithelial cells. It is known that Metal Transporter 1 (DMT1) is expressed (Ayako Hashimoto et al., Micronutrient Research, 28; 89-94, 2011), and iron contained in the diet is usually included as “trivalent iron” Therefore, in order for DMT1 to transport iron, it is necessary to reduce “trivalent iron” to “divalent iron” (Hiromi Gunjin, Molecular Digestive Diseases, 5, 73-80, 2008). From this, calcium cellobionate dissolved the iron contained in the diet in the intestinal tract of rats and promoted the reaction from trivalent iron to divalent iron form, or in the intestinal tract made alkaline by pancreatic juice It is presumed that the iron contained in the diet was efficiently supplied into the living body by maintaining the iron contained in the diet in the state of “divalent iron”. Therefore, in order to confirm whether calcium cellobionate suppresses the formation of iron hydroxide, the following test was performed.

(1) Contents of test Iron chloride was dissolved in various pH solvents, and the formation of iron hydroxide precipitates was observed. The acidic conditions were set to the same level as the HCl concentration of stomach acid. Subsequently, calcium cellobiate (CAC) to be added was added so that the final concentration was 1%. The reaction conditions are as follows.
≪Reaction conditions≫
Scale: 25 mL
Fe: 0.1%
CAC: 1.0%
The result is shown in FIG.

(2) Results As shown in FIG. 16, in the case where 0.4% NaOH CAC was not added, a clear precipitate was formed. In addition, turbidity was formed in the case where 0.04% NaOH CAC was not added. These indicate that calcium cellobionate suppresses the formation of iron hydroxide, which in particular promotes iron absorption in the intestine, thereby increasing the amount of iron in the liver and / or iron in plasma. It has been shown that iron deficiency anemia can be prevented or ameliorated by suppressing dose reduction or by regulating or enhancing iron absorption in the intestine.

Claims

A composition for preventing and / or improving iron deficiency anemia comprising, as an active ingredient, a divalent metal salt of cellobionic acid disaccharide excluding iron (II) cellobionate.
A composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia, comprising as an active ingredient a divalent metal salt of cellobionic acid disaccharide except iron (II) cellobionate.
The preventive and / or ameliorating agent composition according to claim 1 or 2, which regulates or enhances absorption of iron contained in a diet.
The prevention and / or improvement according to any one of claims 1 to 3, wherein the divalent metal salt is one or more salts selected from the group consisting of calcium, magnesium, copper and zinc salts. Agent composition.
The preventive and / or ameliorating agent composition according to any one of claims 1 to 3, wherein the divalent metal salt is calcium.
A composition for preventing and / or improving iron deficiency anemia comprising iron (II) cellobionate as an active ingredient that regulates or enhances absorption of iron contained in a diet.
A composition for preventing and / or improving indefinite complaints associated with iron deficiency anemia comprising iron (II) cellobionate as an active ingredient, which regulates or enhances the absorption of iron contained in the diet.
The preventive and / or ameliorating agent composition according to any one of claims 1 to 7, which regulates or increases the amount of iron in the liver and / or the amount of iron in plasma.
The prophylactic and / or ameliorating agent composition according to any one of claims 1 to 8, which promotes iron absorption in the intestine to suppress a decrease in the amount of iron in the liver and / or the amount of iron in plasma. object.
The preventive and / or ameliorating agent composition according to any one of claims 1 to 9, which regulates or enhances iron absorption in the intestine.
The preventive and / or improver composition according to any one of claims 1 to 10, which suppresses the formation of an iron compound that is insoluble or hardly soluble in water.
The preventive and / or improver composition according to any one of claims 1 to 11, wherein the composition is a food composition.
The prophylactic and / or ameliorating agent composition according to any one of claims 1 to 11, wherein the prophylactic and / or ameliorating agent composition is a preventive and / or therapeutic agent pharmaceutical composition.