JPH0762039B2 - Powdered vitamin E-albumin complex - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a powdered vitamin E-albumin complex.

Vitamin E is widely used as a therapeutic and preventive drug for habitual miscarriage, peripheral vascular disease and heart disease. However, since Vitamin E is a pale yellow viscous oil by itself and is extremely unstable against oxidation, it has been difficult to formulate it when used in medicines and foods. Therefore, various methods have been used to powder vitamin E and improve the stability over time. For example, JP-B-45-38348 discloses that an emulsion containing fat-soluble vitamins is mixed with reducing sugars and amino acids,
A method of obtaining a powder of a fat-soluble vitamin by producing a reaction product of the saccharide and an amino acid at the same time as heating and drying, and JP-B-54-21403 discloses that vitamin E is mixed with soybean milk treated with lactic acid bacteria, and then dried. To obtain a powdered vitamin E formulation. However, since these preparations have hygroscopicity, it was necessary to add dextrin or starch as a moisture absorption inhibitor during production or to add a desiccant during storage. On the other hand, recently, it has been known to use human serum albumin to solubilize a drug which is insoluble or sparingly soluble in water (see JP-A-58-216126).

As a result of studying the powdering of vitamin E, which is superior to the conventional method, the present inventors have combined vitamin E with an albumin complex, and the amount of vitamin E bound to albumin in water is 5 to 250%. The present invention has been completed by finding that the insoluble powdery vitamin E-albumin complex has very excellent properties and is extremely easy to formulate. Human serum albumin described in JP-A-58-216126 facilitates the dissolution of a water-insoluble or sparingly soluble drug in water, whereas the complex obtained by the present invention is water-insoluble. It also has no hygroscopicity and is excellent in storage stability. Moreover, JP-A-58-21612
No. 6 publication does not suggest or describe vitamin E.

Vitamin E used in the present invention is a naturally occurring α
-, Β-, γ- and δ-tocopherol are mentioned.
Further, any of these d, l and dl optical isomers can be used. Furthermore, synthetic vitamin E esters such as acetic acid ester or nicotinic acid ester can also be used. As albumin,
Examples thereof include ovalbumin, serum albumin, placalbumin, α-lactalbumin, leucosine, phaserin and levmeline. Particularly, the complex obtained by the present invention is applied to the field of pharmaceuticals where antigenicity is a problem. It is preferable to use human-derived albumin.

The vitamin E-albumin complex of the present invention can be easily produced by first dissolving albumin in an aqueous solution and adding vitamin E to the solution and bringing them into contact with each other.

The concentration of the aqueous albumin solution at the time of producing this complex is not particularly limited, but it can be used at a concentration of at least 1% (W / V), preferably 5 to 25% (W / V). The ratio of vitamin E to albumin is 100 albumin.
5 to 250 parts per part.

As the aqueous solution, any solution can be used as long as it dissolves albumin without denaturing it, but water is most preferable. However, a part of the water can be replaced with a water-soluble solvent such as ethanol, propylene glycol or glycerin.

The reaction temperature and reaction time are not critical and may vary depending on the albumin used, but generally it is advantageous to react both with stirring at a temperature at which albumin does not undergo thermal denaturation, preferably at room temperature for about 1 to 30 hours. Is.

Vitamin E and albumin react almost 100% regardless of the ratio of addition of both, and depending on the ratio of addition of both, a precipitate in which about 5 to 250% of vitamin E is bound to albumin can be obtained.

The precipitate thus obtained is air dried, vacuum dried, drum dried,
The target powdery vitamin E-albumin complex can be obtained by removing the solvent using a means such as spray drying.

The above-described vitamin E-albumin complex of the present invention has no hygroscopicity and is insoluble in water, and is a natural vitamin E.
However, it has the characteristic of being stable over time. Therefore, it is easy to process the obtained complex into various forms, for example, excipients commonly used for drugs,
It can be processed into tablets or sheets together with binders, disintegrants, lubricants and the like. Further, it becomes possible to mix it uniformly with other powders, and it can be used for foods, cosmetics, medicines, beverages and the like.

The powdery vitamin E-albumin complex obtained in the present invention has extremely excellent stability over time.

The powdered vitamin E-albumin complex prepared in Example 1 below is placed in a brown bottle and sealed, and the mixture is stored at room temperature for 1 month, 6 months, 12 months.
The residual rate of vitamin E after storage for 18 months and 18 months was measured. As a control, untreated dl-α-tocopherol was used.

The results are shown in Table 1.

The binding strength between vitamin E and albumin of the complex of the present invention is very strong, and it is impossible to completely extract vitamin E by the chloroform-methanol extraction method which is a usual analysis method. Therefore, the residual rate of vitamin E and the binding rate of the complex of the present invention were measured by the methods described below.

Vitamin E Quantitative Method Vitamin E-albumin complex 2-10 g was precisely weighed in a 200 ml eggplant-shaped flask and added with water 10-50 ml.
-Bioprase corresponding to 1% by weight of albumin complex was added and stirred at 40 ° C for 1-2 hours. Then add 30-100 ml of chloroform-methanol (2: 1) solution and add vitamin E.
Was extracted, the chloroform-methanol layer was washed with water, magnesium sulfate was added for dehydration, and the solvent was distilled off under reduced pressure in a nitrogen gas atmosphere. Dissolve the residue in methanol to make exactly 50 ml, and perform liquid chromatography (column; Zorbax
ODS (trade name), 4.6 mm ID x 250 mm, moving bed; methanol:
Water (95: 5), room temperature, moving bed speed; 1.0 ml / min, detector UV254
nm).

Example 1 5 g of ovalbumin was dissolved in 100 ml of water, and dl was added to the solution.
1 g of -α-tocopherol was added, and the mixture was stirred at room temperature for 24 hours.
After the stirring was completed, it was dried using a spray dryer to obtain 4.3 g of white powdery dl-α-tocopherol-ovalbumin complex (bonding ratio 1: 5).

Example 2 5 g of ovalbumin was dissolved in 100 ml of water, and dl was added to the solution.
10 g of -α-tocopherol was added, and the mixture was stirred at room temperature for 24 hours. After stirring, add 100 ml of ethanol to the reaction solution,
3.5g of white powdery dl-α-tocopherol-ovalbumin complex by drying under reduced pressure (binding ratio 1: 0.5)
Got

 ─────────────────────────────────────────────────── --Continued from the front page (56) References JP-A-48-33013 (JP, A) JP-A-58-216126 (JP, A) JP-A-58-162517 (JP, A)

Claims (3)

[Claims] 1. A combination of vitamin E and albumin, wherein the amount of vitamin E bound to albumin is 5 to 250.
% Water-insoluble powdered vitamin E-albumin complex. 2. The complex according to claim 1, wherein the albumin is ovalbumin. 3. The complex according to claim 1, wherein the vitamin E is dl-α-tocopherol.