JP2017178934A - Vitamin d3-stabilizing composition - Google Patents
Vitamin d3-stabilizing composition Download PDFInfo
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Abstract
Description
本発明は、ビタミンD3安定化組成物に関する。 The present invention relates to a vitamin D3 stabilizing composition.
ビタミンD(vitamin D)は、ビタミンの一種であり、脂溶性ビタミンに分類される。ビタミンDはさらにビタミンD2(エルゴカルシフェロール、Ergocalciferol)とビタミンD3(コレカルシフェロール、Cholecalciferol)に分けられる。ビタミンD2は植物に、ビタミンD3は動物に多く含まれ、ヒトではビタミンD3が重要な働きを果たしている。
ビタミンD3(コレカルシフェロール)は、肝臓においてC25の位置でヒドロキシ化の代謝を受け、25−ヒドロキシコレカルシフェロール(別名:25(OH)D3、カルシフェジオール)へと変化し肝細胞に貯えられ、必要なときにα−グロブリンと結合しリンパ液中に放出される。この代謝物を含めてビタミンD3として利用されている。
近年、このビタミンD3の代謝物である25−ヒドロキシコレカルシフェロールの作用が注目を集めている。例えば筋肉の発達促進(特許文献1)、高血糖の改善(特許文献2)、生殖能力の改善(特許文献3)、エオタキシンの増加に伴って発症するアレルギー疾患の改善(特許文献4)などが代表的である。
また、その他の新たな用途開発も始まっている。
Vitamin D (vitamin D) is a kind of vitamin and is classified as a fat-soluble vitamin. Vitamin D is further divided into vitamin D2 (Ergocalciferol, Ergocalciferol) and Vitamin D3 (Cholecalciferol). Vitamin D2 is abundant in plants and vitamin D3 is abundant in animals, and vitamin D3 plays an important role in humans.
Vitamin D3 (cholecalciferol) undergoes hydroxylation metabolism at the C25 position in the liver, changes to 25-hydroxycholecalciferol (also known as 25 (OH) D3, calciferdiol) and is stored in hepatocytes. When necessary, it binds to α-globulin and is released into the lymph. This metabolite is used as vitamin D3.
In recent years, the action of 25-hydroxycholecalciferol, which is a metabolite of vitamin D3, has attracted attention. For example, promotion of muscle development (Patent Document 1), improvement of hyperglycemia (Patent Document 2), improvement of fertility (Patent Document 3), improvement of allergic diseases that develop with an increase in eotaxin (Patent Document 4), etc. Representative.
Other new application developments have also begun.
一方、25−ヒドロキシコレカルシフェロールやコレカルシフェロールは、化学的に極めて不安定なことが知られている。特に酸化による影響が大きい。通常、空気中で酸化されてその活性を速やかに消失することが知られている。特許文献5には、ビタミンDと油成分、ポリグリセリン脂肪酸エステル多価アルコールを含む安定なマイクロエマルジョンの技術が開示されている。特許文献6には、活性型ビタミンD類を塩基性高分子物質中に分散してなる安定化組成物が記載されている。 On the other hand, 25-hydroxycholecalciferol and cholecalciferol are known to be extremely unstable chemically. The influence by oxidation is particularly large. It is generally known that it is oxidized in the air and its activity disappears quickly. Patent Document 5 discloses a technique of a stable microemulsion containing vitamin D, an oil component, and a polyglycerol fatty acid ester polyhydric alcohol. Patent Document 6 describes a stabilized composition obtained by dispersing active vitamin Ds in a basic polymer substance.
本発明者らは、活性型である25−ヒドロキシコレカルシフェロールの安定化を研究しているが、25−ヒドロキシコレカルシフェロールやビタミンD3(コレカルシフェロール)が特定の乳化剤成分を共存させることで安定性が増加する現象を見いだし、本発明を
完成させた。
The present inventors are studying stabilization of the active form of 25-hydroxycholecalciferol, but 25-hydroxycholecalciferol and vitamin D3 (cholecalciferol) are allowed to coexist with a specific emulsifier component. The phenomenon of increased stability was found and the present invention was completed.
すなわち、本発明は、ビタミンD3が安定化された組成物を提供することを課題とする。 That is, an object of the present invention is to provide a composition in which vitamin D3 is stabilized.
本発明の主な構成は以下の通りである。
1.ビタミンD3と、大豆レシチン、酵素分解大豆レシチン、ライスレシチンオイル、ヒマワリレシチンから選択される1以上のレシチンからなる組成物。
2.ビタミンD3がコレカルシフェロール及び/又は活性型ビタミンD3である1に記載の組成物。
3.活性型ビタミンD3が25−ヒドロキシコレカルシフェロールである2に記載の組成物。
4.大豆レシチン、酵素分解大豆レシチン、ライスレシチンオイル、ヒマワリレシチンから選択される1以上のレシチン1000質量部当たりビタミンD3を0.1〜10質量部含む1〜3のいずれかに記載の組成物。
5.大豆レシチン、酵素分解大豆レシチン、ライスレシチンオイル、ヒマワリレシチンから選択される1以上のレシチンとビタミンD3のエタノール溶液を混合し、ついでエタノールを含む混合溶液を減圧乾燥することを特徴とするビタミンD3の安定化組成物を製造する方法。
The main configuration of the present invention is as follows.
1. A composition comprising vitamin D3 and at least one lecithin selected from soybean lecithin, enzyme-degraded soybean lecithin, rice lecithin oil, and sunflower lecithin.
2. 2. The composition according to 1, wherein the vitamin D3 is cholecalciferol and / or active vitamin D3.
3. 3. The composition according to 2, wherein the active vitamin D3 is 25-hydroxycholecalciferol.
4). The composition in any one of 1-3 which contains 0.1-10 mass parts of vitamin D3 per 1000 mass parts of 1 or more lecithin selected from soybean lecithin, enzyme-degraded soybean lecithin, rice lecithin oil, and sunflower lecithin.
5). One or more lecithins selected from soybean lecithin, enzyme-degraded soybean lecithin, rice lecithin oil and sunflower lecithin are mixed with an ethanol solution of vitamin D3, and then the ethanol-containing mixed solution is dried under reduced pressure. A method for producing a stabilizing composition.
本発明によりビタミンD3が安定化された組成物を提供できる。本発明により得られた組成物は、ビタミンD3が長時間安定である。また本発明の組成物は、水にも油にも溶解又は分散するため、食品や医薬品の原料として極めて有用である。 According to the present invention, a composition in which vitamin D3 is stabilized can be provided. In the composition obtained according to the present invention, vitamin D3 is stable for a long time. Moreover, since the composition of the present invention dissolves or disperses in water and oil, it is extremely useful as a raw material for foods and pharmaceuticals.
本発明は、ビタミンD3と、レシチンからなる組成物に係る発明である。
本発明に用いられるビタミンD3は、コレカルシフェロール及び/又は活性型ビタミンD3類である。
活性型ビタミンD3類としては1α,25−(OH)2−D3(25−ヒドロキシコレカルシフェロール)、1α−ヒドロキシビタミンD3(1α−OH−D3)、1α,25−ジヒドロキシビタミンD3(1α,25−(OH)2−D3)、1α,24−ジヒドロキシビタミンD3(1α,24−(OH)2−D3)、1α,24,25−トリヒドロキシビタミンD3(1α,24,25−(OH)3−D3)、1α−ヒドロキシ−24−オキソビタミンD3、1α,25−ジヒドロキシ−24−オキソビタミンD3、1α,25−ジヒドロキシビタミンD3−26,23−ラクトン、1α,25−ジヒドロキシビタミンD3−26,23−パーオキシラクトン、26,26,26,27,27,27−ヘキサフルオロ−1α,25−ジヒドロキシビタミンD3などの1α位に水酸基を有する活性型ビタミンD3類、あるいは25−ヒドロキシビタミンD3(25−OH−D3)、24−ヒドロキシビタミンD3(24−OH−D3)、24−オキソビタミンD3、24,25−ジヒドロキシビタミンD3(24,25−(OH)2−D3)、25−ヒドロキシ−24−オキソビタミンD3、25−ヒドロキシビタミンD3−26,23−ラクトン、25−ヒドロキシビタミンD3−26,23−パーオキシラクトンなどの1α位に水酸基を有しない活性型ビタミンD3類などが挙げられる。
The present invention relates to a composition comprising vitamin D3 and lecithin.
Vitamin D3 used in the present invention is cholecalciferol and / or active vitamin D3.
The active vitamin D3s are 1α, 25- (OH) 2-D3 (25-hydroxycholecalciferol), 1α-hydroxyvitamin D3 (1α-OH-D3), 1α, 25-dihydroxyvitamin D3 (1α, 25 -(OH) 2-D3), 1α, 24-dihydroxyvitamin D3 (1α, 24- (OH) 2-D3), 1α, 24,25-trihydroxyvitamin D3 (1α, 24,25- (OH) 3 -D3), 1α-hydroxy-24-oxovitamin D3, 1α, 25-dihydroxy-24-oxovitamin D3, 1α, 25-dihydroxyvitamin D3-26,23-lactone, 1α, 25-dihydroxyvitamin D3-26, 23-peroxylactone, 26,26,26,27,27,27-hexafluoro-1α, 25-dihydroxybi Active vitamin D3 having a hydroxyl group at the 1α position such as Tamine D3, or 25-hydroxyvitamin D3 (25-OH-D3), 24-hydroxyvitamin D3 (24-OH-D3), 24-oxovitamin D3, 24 , 25-dihydroxyvitamin D3 (24,25- (OH) 2-D3), 25-hydroxy-24-oxovitamin D3, 25-hydroxyvitamin D3-26,23-lactone, 25-hydroxyvitamin D3-26,23 -Active vitamin D3 having no hydroxyl group at the 1α position, such as peroxylactone.
これらの活性型ビタミンD3類の中でも1α,25−(OH)2−D3(25−ヒドロキシコレカルシフェロール又は「25(OH)D3」)が好ましい。 Among these active vitamins D3, 1α, 25- (OH) 2-D3 (25-hydroxycholecalciferol or “25 (OH) D3”) is preferable.
本発明で用いる大豆レシチンとは、大豆油を得る工程で、脱ガム工程によって得られる水和物であり、レシチンとその他リン脂質を含む。本発明においては食品や医薬品の乳化剤として利用可能な程度に脱色、精製されたものであれば使用可能である。
酵素分解大豆レシチンとは、リゾレシチンとも呼ばれ、大豆レシチンを酵素処理したものである。大豆レシチンと同様に食品や医薬品の乳化剤として利用可能な程度に脱色、精製されたものであれば使用可能である。
ライスレシチンオイルとは、米油精製工程において、大豆レシチンと同様に脱ガム工程によって得られる水和物であり、レシチンとその他リン脂質を含む。本発明においては食品や医薬品の乳化剤として利用可能な程度に脱色、精製されたものであれば使用可能である。
ヒマワリレシチンは、ヒマワリ油精製工程において、大豆レシチンと同様に脱ガム工程によって得られる水和物であり、レシチンとその他リン脂質を含む。本発明においては食品や医薬品の乳化剤として利用可能な程度に脱色、精製されたものであれば使用可能である。
The soy lecithin used in the present invention is a hydrate obtained by a degumming step in the step of obtaining soybean oil, and includes lecithin and other phospholipids. In the present invention, any material that has been decolorized and purified to the extent that it can be used as an emulsifier for foods and pharmaceuticals can be used.
Enzyme-degraded soybean lecithin is also called lysolecithin and is obtained by enzymatic treatment of soybean lecithin. Similar to soybean lecithin, any product that has been decolorized and purified to the extent that it can be used as an emulsifier for foods and pharmaceuticals can be used.
Rice lecithin oil is a hydrate obtained by a degumming process in the same manner as soybean lecithin in the rice oil refining process, and contains lecithin and other phospholipids. In the present invention, any material that has been decolorized and purified to the extent that it can be used as an emulsifier for foods and pharmaceuticals can be used.
Sunflower lecithin is a hydrate obtained by a degumming step in the same manner as soybean lecithin in the sunflower oil refining step, and contains lecithin and other phospholipids. In the present invention, any material that has been decolorized and purified to the extent that it can be used as an emulsifier for foods and pharmaceuticals can be used.
本発明の組成物を得るためには、ビタミンD3をエタノールなどの溶媒に溶解させる。溶媒としては水又はエタノールが好ましい。この溶解液を大豆レシチン、酵素分解大豆レシチン、ライスレシチンオイル、ヒマワリレシチンから選択される1以上のレシチン(以
下「レシチン類」)と均質に混合し、混合終了後ビタミンD3を含むレシチン類を乾燥装置で乾燥させて溶媒を除去することで得ることができる。混合に当たっては、ビタミンD3が可能な限り小粒子として分散されるように混合する。必要に応じて高圧ホモジナイザーを用いることもできる。乾燥にあたっては、できるだけ低温で行うことが好ましく、真空凍結乾燥や減圧乾燥などの方法を採用することがより好ましい。
To obtain the composition of the present invention, vitamin D3 is dissolved in a solvent such as ethanol. As the solvent, water or ethanol is preferable. This solution is homogeneously mixed with one or more lecithins selected from soybean lecithin, enzyme-degraded soybean lecithin, rice lecithin oil, and sunflower lecithin (hereinafter referred to as “lecithins”). It can obtain by drying with an apparatus and removing a solvent. In mixing, vitamin D3 is mixed so that it is dispersed as small particles as possible. A high-pressure homogenizer can also be used as necessary. Drying is preferably performed at a temperature as low as possible, and it is more preferable to employ a method such as vacuum freeze drying or reduced pressure drying.
レシチン類とビタミンD3は、レシチン類1000質量部当たりコレカルシフェロール及び/又は25−ヒドロキシコレカルシフェロール(25(OH)D3)を0.1〜10質量部の比率となるようにすることが好ましい。
かくして得られる組成物は、レシチン中にビタミンがD3が分散した状態であって、レシチン類が溶解分散可能な水や油に速やかに溶解する。
またこの組成物は、澱粉や糖を加えて粉末とすることも可能である。
It is preferable that the lecithins and vitamin D3 have a ratio of 0.1 to 10 parts by mass of cholecalciferol and / or 25-hydroxycholecalciferol (25 (OH) D3) per 1000 parts by mass of the lecithin. .
In the composition thus obtained, vitamin D3 is dispersed in lecithin, and lecithins dissolve rapidly in water or oil that can be dissolved and dispersed.
The composition can also be powdered by adding starch or sugar.
以下に試験例を示し、本発明を説明する。
レシチン類によるビタミンD3の安定性試験
(1)ビタミンD3
下記の表1に示すビタミンD3を用いて試験をおこなった。
Test examples are shown below to explain the present invention.
Vitamin D3 stability test with lecithins (1) Vitamin D3
A test was conducted using vitamin D3 shown in Table 1 below.
(2)使用レシチン類
市販の下記の表2に示すレシチン類を試験に用いた。
(2) Used lecithins Commercially available lecithins shown in Table 2 below were used in the test.
(3)試験方法
<試料の調製>
1)コレカルシフェロールの調製
市販のコレカルシフェロール結晶175μgを無水エタノール1750mgに溶解させ溶液とした。
この溶液1.75gを、バイアル瓶に予め秤量してあった各レシチン類1gに加え、ボルテックスミキサーを用いて3分間撹拌混合した。その後、エタノールを減圧乾燥して除去し試料を得た。
(3) Test method <Sample preparation>
1) Preparation of cholecalciferol 175 μg of commercially available cholecalciferol crystals were dissolved in 1750 mg of absolute ethanol to obtain a solution.
1.75 g of this solution was added to 1 g of each lecithin previously weighed in a vial and stirred and mixed for 3 minutes using a vortex mixer. Thereafter, ethanol was removed by drying under reduced pressure to obtain a sample.
2)25(OH)D3の調製
(25(OH)D3)10.205mgを無水エタノール500gに溶解させ溶液とした。この溶液2.5gをバイアル瓶に予め秤量してあった各レシチン類1gに加え、ボルテックスミキサーを用いて3分間撹拌混合した。その後、エタノールを減圧乾燥し試料を得た。
2) Preparation of 25 (OH) D3 10.205 mg of (25 (OH) D3) was dissolved in 500 g of absolute ethanol to obtain a solution. 2.5 g of this solution was added to 1 g of each lecithin previously weighed in a vial and stirred and mixed for 3 minutes using a vortex mixer. Thereafter, ethanol was dried under reduced pressure to obtain a sample.
3)安定性試験
上記試料を60℃の恒温槽で2週間保存し、ビタミンD3の残存率を測定した。
<コレカルシフェロールの分析方法>
1.コレカルシフェロール含有試料約0.01gを精密に量り、20mL程度の容器に入れ、10mLのホールピペットにてエタノールを加え撹拌し、5分間超音波にかけ撹拌後約1mLをエッペンチューブに採取し、15000prm 5分間遠心する。上清を試料溶液とする。
2.コレカルシフェロール標準品を1mg/mLとなるようエタノールにて調整後、0.1、0.5、1.0、5.0、10.0μg/mLとなるようエタノール溶液にて適宜希釈し、標準溶液とする。
試料溶液及び標準溶液それぞれ10μLを以下の条件の高速液体クロマトグラフィーに注入し、コレカルシフェロールのピーク面積を求め、標準溶液のコレカルシフェロールのピーク面積から検量線(y=bx+a:a=切片、b=傾き)を求め、下記に示した計算法に従って試料のコレカルシフェロールの含量を求める。
3.測定条件
検出器 : 紫外吸光光度計(測定波長 265nm)
カラム : 内径4.6mm、長さ250mmのステンレス管に粒径5μmのオクタデシル化シリカゲルを充填したもの(Capcellpak C−18 UG−120 株式会社資生堂製)
カラム温度: 40℃
移動相 : 80%アセトニトリル水溶液
流速 : 1mL/分
4.計算法
コレカルシフェロール含量(μg/g)=(試料溶液のコレカルシフェロール面積−切片)/傾き×定容量/試料採取量×純度
3) Stability test The said sample was preserve | saved for two weeks in a 60 degreeC thermostat, and the residual rate of vitamin D3 was measured.
<Method of analyzing cholecalciferol>
1. About 0.01 g of cholecalciferol-containing sample is precisely weighed, placed in a container of about 20 mL, added with ethanol with a 10 mL hole pipette, stirred, subjected to ultrasonic wave for 5 minutes, and after stirring, about 1 mL was collected in an Eppendorf tube, and 15000 prm Centrifuge for 5 minutes. Use the supernatant as the sample solution.
2. After adjusting the cholecalciferol standard product to 1 mg / mL with ethanol, appropriately dilute with ethanol solution to 0.1, 0.5, 1.0, 5.0, 10.0 μg / mL, Use standard solution.
10 μL each of the sample solution and the standard solution was injected into high performance liquid chromatography under the following conditions, the peak area of cholecalciferol was determined, and a calibration curve (y = bx + a: a = intercept, from the peak area of cholecalciferol in the standard solution) b = slope), and the cholecalciferol content of the sample is determined according to the calculation method shown below.
3. Measurement condition detector: UV absorption photometer (measurement wavelength: 265 nm)
Column: A stainless steel tube with an inner diameter of 4.6 mm and a length of 250 mm filled with octadecylated silica gel having a particle size of 5 μm (Capcellpak C-18 UG-120, manufactured by Shiseido Co., Ltd.)
Column temperature: 40 ° C
Mobile phase: 80% aqueous acetonitrile flow rate: 1 mL / min Calculation method Cholecalciferol content (μg / g) = (cholecalciferol area of sample solution−intercept) / slope × constant volume / sample amount × purity
<25(OH)D3の分析方法>
1.25(OH)D3含有試料約0.1gを20mL程度の容器に精密に量り、10mLのホールピペットにてエタノールを加え撹拌し、10分間超音波にかけ撹拌後約1mLをエッペンチューブに移し、15000prm 5分間遠心する。上清を試料溶液とする。
2.25(OH)D3標準品を1mg/mLとなるようエタノールにて調整後、0.1、0.2、0.5、1.0、2.0μg/mLとなるようエタノール溶液にて適宜希釈し、標準溶液とする。試料溶液及び標準溶液それぞれ10μLを以下の条件の高速液体クロマトグラフィーに注入し、25(OH)D3のピーク面積を求め、標準溶液の25(OH)D3のピーク面積から検量線(y=bx+a:a=切片、b=傾き)を求め、下記に示した計算法に従って試料の25(OH)D3含量を求める。
3.測定条件
検出器 : 紫外吸光光度計(測定波長 265nm)
カラム : 内径4.6mm、長さ250mmのステンレス管に粒径5μmのオクタデシル化シリカゲルを充填したもの(Capcellpak C−18 UG−120 株式会社資生堂製)
カラム温度: 40℃
移動相 : 80%アセトニトリル水溶液
流速 : 1mL/分
4.計算法
25(OH)D3含量(μg/g)=(試料溶液の25(OH)D3面積−切片)/傾き×定容量/試料採取量×純度
<25 (OH) D3 Analysis Method>
About 0.1 g of 1.25 (OH) D3-containing sample is precisely weighed into a container of about 20 mL, ethanol is added with a 10 mL hole pipette, stirred, and ultrasonically stirred for 10 minutes, and then about 1 mL is transferred to an Eppendorf tube. Centrifuge at 15000 prm for 5 minutes. Use the supernatant as the sample solution.
2.25 (OH) D3 standard product is adjusted with ethanol to 1 mg / mL, and then with ethanol solution to 0.1, 0.2, 0.5, 1.0, 2.0 μg / mL. Dilute appropriately to make a standard solution. 10 μL each of the sample solution and the standard solution is injected into high performance liquid chromatography under the following conditions, the peak area of 25 (OH) D3 is obtained, and a calibration curve (y = bx + a: a = intercept, b = slope), and the 25 (OH) D3 content of the sample is determined according to the calculation method shown below.
3. Measurement condition detector: UV absorption photometer (measurement wavelength: 265 nm)
Column: A stainless steel tube with an inner diameter of 4.6 mm and a length of 250 mm filled with octadecylated silica gel having a particle size of 5 μm (Capcellpak C-18 UG-120, manufactured by Shiseido Co., Ltd.)
Column temperature: 40 ° C
Mobile phase: 80% aqueous acetonitrile flow rate: 1 mL / min Calculation method 25 (OH) D3 content (μg / g) = (25 (OH) D3 area of sample solution−intercept) / slope × constant volume / sampled amount × purity
(4)結果
各試料の安定性試験結果を表3及び図1に示す。なお結果は、保存期間経過後の残存率で表している。
(4) Results Table 3 and FIG. 1 show the stability test results of each sample. The results are expressed as the remaining rate after the storage period.
コレカルシフェロールは大豆レシチン及び酵素分解大豆レシチンにより安定化する。一方25(OH)D3は、コレカルシフェロールとは異なり、酵素分解大豆レシチン、ヒマワリレシチン、ライスレシチンオイルによって安定化することが確認できた。
Cholecalciferol is stabilized by soy lecithin and enzymatically degraded soy lecithin. On the other hand, it was confirmed that 25 (OH) D3 was stabilized by enzymatically decomposed soybean lecithin, sunflower lecithin and rice lecithin oil, unlike cholecalciferol.
Claims (5)
One or more lecithins selected from soybean lecithin, enzyme-degraded soybean lecithin, rice lecithin oil and sunflower lecithin are mixed with an ethanol solution of vitamin D3, and then the ethanol-containing mixed solution is dried under reduced pressure. A method for producing a stabilizing composition.
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