JP2015030690A - Composition with improved bioabsorbability of pteridine derivative and bioabsorbency promoter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve bioabsorbability of a pteridine derivative.SOLUTION: This invention provides a composition with improved bioabsorbability of a pteridine derivative, comprising enzyme-treated rutin and the pteridine derivative; and a bioabsorbency promoter for a pteridine derivative comprising enzyme-treated rutin.

Description

  The present invention relates to a composition having improved bioabsorbability of a pteridine derivative and a bioabsorption enhancer of a pteridine derivative. Moreover, this invention relates to the use of the said composition or bioabsorption promoter.

  Folic acid, which is classified as a pteridine derivative, is known as a vitamin required for normal fetal development and red blood cell formation. For example, according to Komyo No. 72, Kenji No. 78, it is recommended that women planning to become pregnant or pregnant should take 0.4 mg of folic acid from outside the diet. Giant erythroblastic anemia is known as a deficiency of folic acid.

  In addition, folic acid is allowed to indicate that it contributes to reducing disease risk among foods for specified health use, and based on the intake from normal foods, the recommended intake per day for food for specified health use is 400- It is set to 1,000 μg.

  Patent Document 1 discloses that a specific pteridine derivative exhibits an effect of inhibiting adipocyte differentiation, an anti-obesity effect, an effect of improving glucose tolerance abnormality, and an effect of promoting adiponectin production. Further, in Patent Documents 2 and 3, certain pteridine derivatives are used for the treatment of autoimmune disorders, the treatment of transplant rejection and the treatment of inflammatory diseases, cardiovascular diseases, allergic conditions, diseases of the central nervous system, TNF- It is also disclosed that it is useful in the prevention or treatment of α-related diseases, viral diseases and cell proliferation diseases.

  However, some of the pteridine derivatives have poor bioabsorbability, for example, absorbability into the human or animal body. Therefore, even if it is a food, pharmaceutical, cosmetic and feed containing a pteridine derivative, and the pteridine derivative is added to food, pharmaceutical, cosmetic and feed, the human body or animal can efficiently absorb the pteridine derivative into the body. May not be possible.

International Publication No. 2008/136173 Pamphlet Special table 2007-508355 gazette JP 2002-533464 A

  The present invention is to solve the problems associated with the prior art as described above, and an object thereof is to improve the bioabsorbability of the pteridine derivative.

  The present inventors have intensively studied to solve the above problems. As a result, it was found that the bioabsorbability of the pteridine derivative is improved by using the enzyme-treated rutin and the pteridine derivative in combination rather than using the pteridine derivative alone, and the present invention has been completed.

The present invention relates to the following [1] to [12], for example.
[1] A composition comprising an enzyme-treated rutin and a pteridine derivative and having improved bioabsorbability of the pteridine derivative.

[2] The composition according to [1], wherein the pteridine derivative is folic acid.
[3] The composition according to [1] or [2], wherein the content of the pteridine derivative is 0.1 to 99% by mass with respect to the entire composition.

  [4] The enzyme-treated rutin is an α-glucosylrutin-containing product obtained by adding a sugar donor to rutin and transferring a sugar from the sugar donor to rutin by acting a glucose residue transferase. The composition according to any one of [1] to [3].

[5] The composition according to any one of [1] to [4], wherein the rutin conversion amount in the enzyme-treated rutin is 10 to 85% by mass.
[6] The composition according to any one of [1] to [5], wherein the content of the enzyme-treated rutin is 0.1 to 1,000 parts by mass with respect to 1 part by mass of the pteridine derivative.

[7] A food, pharmaceutical, cosmetic or feed comprising the composition according to any one of [1] to [6].
[8] Use of the composition according to any one of [1] to [6] for food, medicine, cosmetics or feed.

[9] A bioabsorption enhancer of a pteridine derivative containing enzyme-treated rutin.
[10] Use of enzyme-treated rutin as a bioabsorption promoter for pteridine derivatives.
[11] Bioabsorbability is improved, comprising a step of blending the composition according to any one of [1] to [6] above with at least one article selected from foods, pharmaceuticals, cosmetics, and feeds. A method for producing the article comprising the prepared pteridine derivative.

  [12] At least one kind of article selected from foods, pharmaceuticals, cosmetics and feeds containing a pteridine derivative has an enzyme-treated rutin content of 0.1 to 1 with respect to 1 part by mass of the pteridine derivative contained in the article. A method for improving the bioabsorbability of a pteridine derivative contained in the article, comprising the step of adding the bioabsorption enhancer according to [9] at a ratio of 1,000 parts by mass.

  According to the present invention, the bioabsorbability of a pteridine derivative can be improved. According to the present invention, in particular, the bioabsorbability of folic acid, specifically, the absorbability into the human body or animal body can be improved.

FIG. 1 is a graph showing changes in blood folic acid concentration over time after the folic acid-containing composition obtained in Examples and the folic acid-containing composition obtained in Comparative Examples were applied to the human body (oral intake). .

Hereinafter, the form for implementing this invention including a suitable aspect is demonstrated in detail.
[Composition with improved bioabsorbability of pteridine derivatives]
The composition of the present invention contains an enzyme-treated rutin and a pteridine derivative. In the composition, the bioabsorbability of the pteridine derivative is improved. That is, the pteridine derivative can be efficiently absorbed into the body by applying the composition to a human body or an animal (eg, ingestion, application to the outer surface of the skin, injection). In addition, due to the action of the enzyme-treated rutin, for example, photolysis of the pteridine derivative during storage or transportation of the composition can also be suppressed.

<Pteridine derivative>
As the pteridine derivative, for example, a compound represented by the formula (A1) is preferable.

Details of each symbol in the formula (A1) are as follows.

R ¹ is —OH, ═O or —NH ₂ . R ² , R ⁴ and R ⁵ are each independently a hydrogen atom or an alkyl group having 1 to 5 carbon atoms. R ³ , R ⁶ and R ⁷ are each independently a hydrogen atom, halogen atom, alkyl group, hydroxy group, alkoxy group, alkoxyalkyl group, aldehyde group, alkyl ester group, amino group, alkylamino group, cyano group or nitro group It is a group. a to d are each independently 0 or 1. e is an integer of 0-10.

The bonds of (1) to (5) in formula (A1) are single bonds except in the following cases.
The bond of (1) is a double bond when R ¹ is a group other than ═O and a is 0.
The bond (2) is a double bond when the bond (1) is a single bond and a is 0.
The bond of (3) is a double bond when the bond of (2) is a single bond and b is 0.
The bond of (4) is a double bond when c is 0,
The bond of (5) is a double bond when d is 0.

In R ³ , R ⁶ and R ⁷ in formula (A1), examples of the alkyl group include straight-chain or branched hydrocarbon groups having 1 to 20 carbon atoms, such as methyl group, ethyl group, propyl group. Group, isopropyl group, butyl group and pentyl group; examples of the alkoxy group include methoxy group and ethoxy group; examples of the alkoxyalkyl group include diethoxymethyl group; Examples include a methyl ester group and an ethyl ester group; examples of the alkylamino group include a methylamino group and a dimethylamino group.

The alkyl group of 1 to 5 carbon atoms for R ^2, R ⁴ and R ⁵ in the formula (A1), for example, a methyl group, an ethyl group, a propyl group, an isopropyl group and a butyl group.
R ³ in formula (A1) is preferably a hydrogen atom, an alkyl group, a hydroxy group, an alkoxy group, an alkoxyalkyl group or an amino group, more preferably an amino group, and R ⁶ is a hydrogen atom or an aldehyde group. R ⁷ is preferably a hydrogen atom, an alkyl group, a hydroxy group, an alkoxy group, an alkoxyalkyl group, an amino group or an alkylamino group, more preferably a hydrogen atom or an alkyl group, e Is preferably 1 or 2.

Specific examples of pteridine derivatives include pteroyl monoglutamic acid (folic acid), pteroyldi-γ-glutamic acid, pteroyltriglutamic acid, pteroylheptaglutamic acid, formyltetrahydrofolic acid, xantopterin, 10-formylpteroic acid, folinic acid, Methotrexate is mentioned. Among these, folic acid is preferable from the viewpoint of significantly improving the bioabsorbability by the enzyme-treated rutin and from the viewpoint of usefulness for uses such as food. Folic acid, which is one of pteridine derivatives, has an action as a nutrient enhancer, an anemia, an action to promote growth, an action to normalize the function of the gastrointestinal mucosa, and the like.
A pteridine derivative may be used individually by 1 type, and may use 2 or more types together.

<Enzyme-treated rutin>
The enzyme-treated rutin is not particularly limited as long as sugar is added to rutin by an enzyme. For example, a glucose residue transferase such as amylase, glycosidase or transglycosidase is allowed to act on a composition obtained by adding a sugar donor such as starch or a partial hydrolyzate thereof (eg, dextrin or maltose) to rutin, Or a composition (α-glucosylrutin-containing product) containing α-glucosylrutin obtained by transferring (adding) sugar (glucose) from a sugar donor such as a partial hydrolyzate thereof to rutin. preferable.

  By using enzyme-treated rutin, the bioabsorbability of pteridine derivatives, particularly folic acid, is significantly improved. For example, the absorption efficiency when folic acid is orally ingested in the human body is 2 times or more, for example, 2 to 3 times the blood concentration of folic acid when enzyme-treated rutin is used in combination, compared with the case where enzyme-treated rutin is not used together. (See FIG. 1).

In addition, enzyme-treated rutin itself has acid / high temperature stability, stability to light, long-term storage, safety, prevention of fading / discoloration of natural pigments, prevention of photodegradation of vitamins, Maillard reaction It is a compound that has effects such as inhibition, oxidation prevention, and aroma retention, and is excellent in water solubility. Therefore, the composition of the present invention containing the enzyme-treated rutin together with the pteridine derivative can not only improve the bioabsorbability of the pteridine derivative when taken orally, but for example during storage or transportation, Acidity / high temperature stability of the composition, stability to light, long-term storage, safety, prevention of fading / discoloration of natural pigments blended in foods, cosmetics, etc., if necessary, suppression of food Maillard reaction Further, it is possible to improve the antioxidant and the retention of aroma such as food and cosmetics.
α-Glucosyl rutin is represented by the formula (A2).

In formula (A2), G is a glucose residue, R is a rhamnose residue, and G ′ is a glucose residue at the α-position. The α-position glucose residue number m is usually 1 to 15. If m is 1 or more, there is no problem in solubility, but the addition number may be large in order to maintain stable solubility.

  As a method for producing α-glucosyl rutin, various conventionally known methods can be employed. For example, the method described in JP-B-54-32073 or JP-B-58-54799 can be employed.

  The rutin conversion amount in the enzyme-treated rutin is preferably 10 to 85% by mass, more preferably 40 to 85% by mass, and still more preferably 70 to 85% by mass. Thus, the enzyme-treated rutin obtained as described above may contain, for example, a small amount of unreacted rutin or quercetin which is a degradation product of rutin together with α-glucosylrutin. Further, isoquercitrin having a structure in which the rhamnose residue (R in formula (A2)) is removed from rutin may be included. It is preferable that the rutin conversion amount in the enzyme-treated rutin is in the above range because the bioabsorbability of the pteridine derivative is improved.

Although it does not restrict | limit especially as such an enzyme process rutin, Specifically, (alpha) G rutin PS (A brand name, rutin conversion amount 80-82 mass%, the Toyo Seika Co., Ltd. product), (alpha) G rutin P (A brand name, rutin) Conversion amount 40-46 mass%, manufactured by Toyo Seika Co., Ltd.), αG rutin H (trade name, rutin conversion amount 22-26 mass%, manufactured by Toyo Seika Co., Ltd.).
Enzyme-treated rutin may be used alone or in combination of two or more.

<Other ingredients>
The composition of this invention may contain another component according to the usage form. For example, a binder for preparing the composition in a solid state, specifically cyclodextrin, dextrin, water-soluble dietary fiber, starch, etc .; a solvent for preparing the composition in a liquid state, specifically water, alcohol (Example: ethyl alcohol, glycerin, propylene glycol) and the like.
In the composition of the present invention, additives such as glycerin fatty acid ester and sucrose fatty acid ester may be appropriately added according to the desired purpose and application within the range not impairing the effects of the present invention.

<Content of each component>
In the composition of the present invention, the content of the enzyme-treated rutin is usually 0.1 to 1,000 parts by weight, preferably 1 to 100 parts by weight, more preferably 5 to 50 parts by weight with respect to 1 part by weight of the pteridine derivative. Part. When the content is within the above range, the solubility is excellent, and therefore, it is preferable in terms of bioabsorbability when taken orally and the (light) stability during storage, storage, and transportation of the composition.

  In the composition of the present invention, the content of the pteridine derivative is usually 0.1 to 90% by mass, preferably 0.5 to 60% by mass, more preferably 1 to 40% by mass with respect to the entire composition. . When the content of the pteridine derivative is within the above range, the daily required amount can be easily ingested, and since the combined use of the enzyme-treated rutin is easy, it is preferable in that the medicinal effect of the pteridine derivative is remarkably exhibited.

<Preparation of composition>
The composition of the present invention can be prepared by mixing the enzyme-treated rutin and the pteridine derivative, and the preparation method is not particularly limited. The composition of the present invention can be prepared by simply mixing the enzyme-treated rutin and the pteridine derivative by a simple method without using a special apparatus such as a spray drying method. The preparation of such a composition is usually performed at room temperature, but may be performed under heating as necessary.
The shape of the composition is not particularly limited, and may be liquid or solid.

<Use of composition>
The composition of the present invention can be taken orally as it is, and can be used for at least one application selected from foods, pharmaceuticals (including quasi-drugs, the same shall apply hereinafter), cosmetics and feeds, For example, in anticipation of the ingestion effect of the pteridine derivative or the above-mentioned combined effect of the pteridine derivative and the enzyme-treated rutin, it can also be used by mixing with raw materials such as foods, pharmaceuticals, cosmetics and feeds.

  The enzyme-treated rutin concentration derived from the composition according to the present invention in foods, pharmaceuticals, feeds or cosmetics is, for example, preferably from 1 to 2,000 mass ppm, more preferably from 10 to 1,000 from the viewpoint of solubilization. Mass ppm. Since the composition of the present invention is also excellent in solubility in water at room temperature, it is suitable for producing not only solid products but also liquid food products, pharmaceutical products, cosmetics and feeds.

  The composition of the present invention may be added at the beginning of the production process of foods, pharmaceuticals, cosmetics and feeds, or may be added at the middle stage or the final stage of the production process. What is necessary is just to select an appropriate thing from immersion, dispersion | spreading, spraying, application | coating, etc. according to the aspect of a product.

  For the use, the composition of the present invention and catechin, vitamin C, vitamin E, vitamin D, vitamin B2, hyaluronic acid, theanine, collagen, citric acid, saw palmetto, L-carnitine, α lipoic acid, turmeric, beta carotene , Capsaicin, zinc (Zn), champignon extract, chitosan, mushroom chitosan, chondroitin, lecithin, oyster extract, glucosamine, pycnogenol, proanthocyanidins, coenzyme Q10, supplements such as enzyme-treated stevia, lacanca, glycyrrhizin, sucralose, acesulfame K, Saccharin, sodium saccharin, aspartame, sugar, fructose, glucose fructose liquid sugar, reduced starch syrup, fructooligosaccharide, galactooligosaccharide, xylo-oligosaccharide, emulsified oligosaccharide, soybean oligosaccharide, isomalteo Gore sugar, raffinose, trehalose, lactose, xylitol, erythritol, sorbitol, maltitol, mannitol, palatinose, a combination of one or two or more such reducing palatinose can be used.

《Food》
Examples of foods include fermented foods, breads, pickles, dried foods, paste products, flours, canned foods, frozen foods, retort foods, instant foods (instant noodles, dry foods, powdered beverages, etc.), dairy products (processed milk, Non-fat dry milk, processed foods such as processed fish products, processed livestock products; taste foods such as confectionery; cooking and seasoning materials such as fats, sweeteners, seasonings and spices; health foods such as supplements (functionality) Food); special-purpose food (food for the sick, food for the elderly, food for childcare); food for specified health use; processed materials such as gelling agent and swelling agent; preservative food; emergency food; space food; water, refreshing Drinks such as drinking water, alcoholic beverages, tea and coffee are listed.

《Pharmaceuticals》
The medicine may be any of internal medicine, external medicine, injection, etc. Specifically, tablets, powders (fine granules, granules, etc.), capsules, drinks, syrups, troches, gargles Medicines, toothpastes, mouth fresheners, bad breath odors, Kampo soaps, detergents, shampoos, rinses, hair products, hair restorers.

"Cosmetics"
Examples of cosmetics include powders, emulsions, liquids, creamy foundations, sunscreens, skin lotions, creams, lipsticks, and fragrances.

"feed"
Examples of the feed include various cat foods, dog foods, food for ornamental fish, and food for cultured fish.

[Bioabsorption enhancer of pteridine derivatives]
The pteridine derivative bioabsorption enhancer according to the present invention contains the above-mentioned enzyme-treated rutin. By adding the accelerator to an article containing a pteridine derivative, for example, at least one article selected from foods, pharmaceuticals, cosmetics, and feeds, the action of the enzyme-treated rutin allows the use of the pteridine derivative contained in the article. Absorption into the body is promoted.

  The content of the enzyme-treated rutin is preferably 1 to 100% by mass and more preferably 10 to 50% by mass with respect to 100% by mass of the bioabsorption accelerator of the present invention. By using an absorption promoter containing the enzyme-treated rutin in the above amount, the bioabsorbability of the pteridine derivative can be improved.

  In the above accelerator, the enzyme-treated rutin is usually 0.1 to 1,000 parts by weight, preferably 1 to 100 parts by weight, more preferably 5 to 1 part by weight of the pteridine derivative contained in the article to which it is added. It can be added to the article in an amount of ˜50 parts by mass. Moreover, you may add enzyme-treated rutin itself as a bioabsorption promoter.

  EXAMPLES Hereinafter, although this invention is demonstrated further more concretely based on an Example, this invention is not limited to these Examples. In the following description of Examples and the like, “part” means “part by mass” unless otherwise specified.

〔reagent〕
Enzyme-treated rutin: αG rutin PS (rutin equivalent = 80% by mass, manufactured by Toyo Seika Co., Ltd.
αG rutin PS includes a compound represented by the following formula)

・ Dextrin: Paindex # 1 (Matsuya Chemical Co., Ltd.)
・ Folic acid: Folic acid (deer grade) (manufactured by Kanto Chemical Co., Inc.)

[Example 1]
1 mg of folic acid, 9 mg of “αG rutin PS”, and 90 mg of “Paindex # 1” are thoroughly mixed at normal temperature (25 ° C.) and normal pressure (1 atm) to obtain a folic acid concentration of 1% by mass. A containing composition was obtained. The following folic acid absorption test was performed using the obtained folic acid-containing composition.

[Comparative Example 1]
1 mg of folic acid and 99 mg of “Paindex # 1” were mixed at normal temperature (25 ° C.) and normal pressure (1 atm) to obtain a folic acid-containing composition having a folic acid concentration of 1 mass%. The following folic acid absorption test was performed using the obtained folic acid-containing composition.

[Folate absorption test]
The folic acid absorption test was performed under the following conditions.
In this test, the subject (healthy person) is a food containing a lot of folic acid on the day before and on the day of the test (for example, a food having a water content of 40% by mass or more is 120 μg / 100 g or more, and a food having a water content of less than 40% by mass is 260 μg / 100 g. Ingestion of food containing folic acid in the above range was restricted. The test subjects were 5 adult men and women (4 men, 1 woman, age 30 to 39 years, weight 52 to 65 kg; average age 33.8 years, average weight 57 kg).

  The subjects had a light meal avoiding foods rich in folic acid 3 hours before the test day, and orally ingested 100 mg of the folic acid-containing composition obtained in Comparative Example 1 at 12:30. received. Blood was collected (5 ml) immediately before ingestion, and blood was collected (5 ml) 30 minutes, 1 hour, 2 hours and 4 hours after ingestion. The subject's diet was restricted between the first and last blood draw.

  Five days after ingesting the above composition, the five subjects took 100 mg of the folic acid-containing composition obtained in Example 1 orally. Blood was collected (5 ml) immediately before ingestion, and blood was collected (5 ml) 30 minutes, 1 hour, 2 hours and 4 hours after ingestion. The subject's diet was restricted between the first and last blood draw.

  The blood concentration of folic acid in each subject was measured by the CLIA method. Changes in blood concentration of folic acid over time (average value of 5 subjects) are shown in Table 1 and FIG. In addition, Table 2 shows the area under the folic acid blood concentration-time curve 2 hours and 4 hours after ingestion (AUC, average value of 5 subjects).

  Compared to the intake of the folic acid-containing composition obtained in Comparative Example 1 (containing 1 mg of folic acid and 99 mg of “Paindex # 1” and not containing αG rutin PS), it was obtained in Example 1 (1 mg of folic acid). Folic acid-containing composition (including 9 mg of αG rutin PS and 90 mg of “Paindex # 1”) significantly improved blood folic acid concentration. Therefore, it can be seen that the amount of folic acid absorbed into the human body is improved by adding αG rutin PS to folic acid. In other words, according to the present invention, a high effect of folic acid can be efficiently expected with a smaller amount of folic acid intake.

Claims (12)

A composition containing an enzyme-treated rutin and a pteridine derivative and having improved bioabsorbability of the pteridine derivative.   The composition according to claim 1, wherein the pteridine derivative is folic acid.   The composition according to claim 1 or 2, wherein the content of the pteridine derivative is 0.1 to 99 mass% with respect to the entire composition.   The enzyme-treated rutin is an α-glucosylrutin-containing product obtained by adding a sugar donor to rutin and allowing a glucose residue transferase to act to transfer sugar from the sugar donor to rutin. The composition according to any one of the above.   The composition according to any one of claims 1 to 4, wherein the rutin-converted amount in the enzyme-treated rutin is 10 to 85% by mass.   The composition according to any one of claims 1 to 5, wherein the content of the enzyme-treated rutin is 0.1 to 1,000 parts by mass with respect to 1 part by mass of the pteridine derivative.   A food, medicine, cosmetic or feed comprising the composition according to any one of claims 1 to 6.   Use of the composition according to any one of claims 1 to 6 for food, medicine, cosmetics or feed.   A bioabsorption enhancer of a pteridine derivative containing an enzyme-treated rutin.   Use of enzyme-treated rutin as a bioabsorption enhancer of pteridine derivatives.   The said containing the pteridine derivative with which the bioabsorbability improved which has the process of mix | blending the composition of any one of Claims 1-6 with the at least 1 sort (s) of articles chosen from a foodstuff, a pharmaceutical, cosmetics, and feed. Article manufacturing method.   The enzyme-treated rutin is 0.1 to 1,000 masses per 1 part by mass of the pteridine derivative contained in at least one article selected from foods, pharmaceuticals, cosmetics and feeds containing the pteridine derivative. A method for improving the bioabsorbability of a pteridine derivative contained in the article, comprising the step of adding the bioabsorption enhancer according to claim 9 at a ratio of parts.