JPS60116643A - Fat-soluble vitamin-cyclic(1[2)-beta-d-glucan inclusion compound and its preparation - Google Patents

Abstract

PURPOSE:The titled inclusion compound useful as vitamin A, D, E, or K as a drug, having stability to heat, light rays, and oxidation, and water solubility, obtained by reacting a fat-soluble vitamin with cyclic (1 2)-beta-D-glucan. CONSTITUTION:1-100wt% aqueous solution of cyclic(1 2)-beta-D-glucan having 17-24 polymerization degree is reacted directly with a fat-soluble vitamin such as vitamin A, D, E or K, or a solution of it in a small amount of an organic solvent with stirring for 4-48hr. Then the reaction solution is allowed to stand for 1-24hr, only the water layer of lower layer is taken out, dried by through flow drying, drying under reduced pressure, etc., to give fat-soluble vitamin- cyclic(1 2)-beta-D-glucan inclusion compound powder. EFFECT:Useful as a solid drug such as tablet, capsule, granule, powder, etc. and injection.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides fat-soluble vitamin-cyclic (1→2)-β-D-
The present invention relates to a glucan (hereinafter referred to as CG) clathrate compound and its production method.

Vitamins A, D, E, or K are widely used not only as medicines but also as food additives.

However, since these vitamins are insoluble in water, if they are to be used as solutions such as oral solutions or injections, or as drinks, they must be solubilized using surfactants that are harmful to the human body. There are drawbacks.

In addition, these vitamins are unstable to heat and light and easily oxidized, so they should be frozen, protected from light, or
Measures such as replacement with inert gas may be unnecessary. However, in actual preparation operations, it is difficult to avoid the effects of heat, light, and oxidation, which significantly affect the storage stability of the preparation.

Therefore, water solubilization and stabilization of these fat-soluble vitamins is extremely useful.

In order to make these fat-soluble vitamins water-soluble and stabilized, the present inventors have discovered that when they are reacted with CG, the resulting fat-soluble vitamin-CG clathrate compound is water-soluble and They discovered that it is stable against heat, light, oxidation, etc., and completed the present invention.

The fat-soluble vitamins and their derivatives used in the present invention include, for example, vitamin A, vitamin D 2% vitamin D 3.1a-hydroxycholecalciferol, 2
4-hydroxycholecalciferol, 25-hydroxyflecalciferol, 1α,24-dihydroxycholecalciferol, 1a,25-dihydroxycholecalciferol, vitamin E1, vitamin 5, vitamin 2, vitamin 3, etc. However, these are merely illustrative compounds and are not limited thereto.

As CG, those having a degree of polymerization of 17 to 24 are known. (J, CI+romatogr, + 2
65, 89 (1983)). Even if CG is used as a mixture of these (types I-IV, see Table 1), or isolated and used with each degree of polymerization, the clathrate compound in the present invention can be prepared.

Table 1 Composition (%) of CG produced by various microorganisms As a method for obtaining fat-soluble vitamin-○G clathrate compounds, for example, a fat-soluble vitamin Vitamins can be added as is or in a small amount of a suitable organic solvent (
For example, a solution dissolved in an alcohol such as methanol, ethanol, propatool, or a ketone such as acetone or methyl ethyl ketone is added and stirred for 4 to 48 hours. Thereafter, the mixture is allowed to stand for 1 to 24 hours, and only the lower aqueous layer is removed. This is dried by an appropriate drying method such as air drying, reduced pressure drying, or freeze drying to obtain a powder of the clathrate compound.

To quantify the fat-soluble vitamins in the fat-soluble vitamin-CG clathrate compound, add chloroform to an aqueous solution of the fat-soluble vitamin-CG clathrate compound, stir vigorously, remove the chloroform layer, distill off the chloroform, and then This can be done by dissolving each vitamin in an organic solvent (for example, methanol or ethanol) and measuring the characteristic absorption value of the ultraviolet absorption spectrum of each vitamin.

The fat-soluble vitamin-CG clathrate compound obtained as described above is stable against heat, light, and oxidation, and is water-soluble, and can be used in solid forms such as tablets, capsules, granules, and powders. It can be effectively used as a drug and injection.

EXAMPLES The present invention will be explained in more detail with reference to Examples below.

Example 1 100 mg of retinal (vitamin A) was added to 12 mj2 of Type IV CG 5% (w/v) aqueous solution and stirred at 30°C for 48 hours. After standing still for 24 hours, lower layer 10III
! , lyophilized, retinal-CG clathrate'
525 mg of 1llJ was obtained. The retinal content of this was 4.76% by weight.

Examples 2 to 5 Example 1 was repeated except that various fat-soluble vitamins were used instead of retinal to obtain various clathrate compounds.

Table 2 shows the fat-soluble vitamin types, clathrate compound weights, and fat-soluble vitamin contents in the clathrate compounds in Examples 2 to 5.

Claims (1)

[Claims] 1. Fat-soluble vitamins or derivatives thereof in a cyclic form (1→2)
-Fat-soluble vitamins clathrated in β-D-glucan-
Cyclic (1→2)-β-D-glucan clathrate. 2. The clathrate compound according to claim 1, wherein the fat-soluble vitamin is vitamin A, vitamin D, vitamin E, or vitamin A. 3. Cyclic (1→2) fat-soluble vitamins or their derivatives
- A method for producing a fat-soluble vitamin-cyclic (1→2)-β-D-glucan clathrate, which comprises reacting it with β-D-glucan.