JPH02149598A - Solubilization of gamma-orizanol - Google Patents

Abstract

PURPOSE:To solubilize gamma-orizanol without using ethyl alcohol by dissolving a monoester-containing sucrose fatty ester in purified water, mixing a melt composed of a polyoxyethylene hardened castol oil and gamma-orizanol therewith and fusing the resultant mixture. CONSTITUTION:gamma-Orizanol is uniformly fused and mixed with a polyoxyethylene hardened castol oil of >=3 times the weight thereof and the resultant mixture is blended with an aqueous solution of a >=90% monoester-containing sucrose fatty ester prepared by dissolution thereof in purified water in an amount of >=2 times the weight of gamma-orizanol at >=50 deg.C, thus fusing the objective compound.

Description

[Detailed description of the invention] [Industrial application field]

The present invention relates to a solubilization method for incorporating γ-oryzanol in a pharmaceutical drink.

[Conventional technology]

Attempts have been made to incorporate γ-oryzanol into pharmaceutical drinks aimed at increasing physical strength, recovering from fatigue, increasing vitality, and the like. However, γ-oryzanol is a poorly water-soluble substance and must be solubilized in order to be incorporated into drinks. Commonly known medicinal solubilizers include polysorbate 80 and polyoxyethylene hydrogenated castor oil. Among these, when polysorbate 80 is used for the purpose of solubilization, a large amount is required, so
Polyoxyethylene hydrogenated castor oil (hereinafter referred to as POE-HC)
(abbreviated as O) is commonly used. however,
POE-HCO is difficult to dissolve in water and has a unique odor. The problem is that it has a slightly bitter taste. Regarding the difficulty in dissolving in water, even when heated, a clear liquid cannot be obtained, and the liquid becomes slightly cloudy. Ethyl alcohol is therefore used as a solubilizer for dissolution. The amount of ethyl alcohol added is suppressed as much as possible by the drink, but if you drink a large number of these drinks at once, the amount of ethyl alcohol will inevitably increase. For this reason, there are cases in which drivers, such as long-distance truck drivers, regularly use large amounts of drinkable drugs to recover from fatigue. In this case, even if the driver has not consumed alcoholic beverages, the driver may be judged to be driving under the influence of alcohol or cause an unexpected traffic accident, which is a major social problem. Therefore, the inventor conducted extensive research on a method for solubilizing without using ethyl alcohol, which is a solubilizing agent.
1 stacked. As a food solubilizer with high performance,
Sucrose fatty acid ester with a monoester content of 90% or more (
(hereinafter abbreviated as MSE) is already known (Japanese Patent Publication No. 58-51743). Therefore, this MSE was also highly anticipated as a solubilizing agent for pharmaceutical drinks. However, in most cases the pH of the drink is 3.
0 to 3.5, and when drinking the drink, it is often placed in a low-temperature showcase to cool it.In such cases, the drink using 1M5E as a solubilizer has a low pH of 1 low temperature. Precipitation occurs in
May precipitate. Therefore, it was inappropriate to use it alone as a solubilizer for pharmaceutical drinks.

[Problem to be solved by the invention]

The present invention does not use ethyl alcohol and
The purpose of this invention is to provide a method for solubilizing γ-oryzanol in a pharmaceutical drink that has good storage stability at low temperatures.

[Means and effects for solving the problem] The inventors have discovered that γ
- As a result of extensive research into a method for solubilizing oryzanol into a pharmaceutical drink without using ethyl alcohol, it was discovered that the above problems could be overcome, leading to the present invention. In other words, in the method of solubilizing γ-oryzanol in a pharmaceutical drink, twice the amount of γ-oryzanol (
A sucrose fatty acid ester with a monoester content of 90% or more (by weight) is dissolved in purified water, and then polyoxyethylene hydrogenated castor oil and γ-oryzanol are added in an amount of 3 times or more (by weight) to γ-oryzanol. γ characterized in that the homogeneous melt-mixed product is mixed at a temperature of 50°C or higher.
- A method for solubilizing oryzanol. The object of the present invention is a pharmaceutical drink that is used for the purpose of increasing physical strength, recovering from fatigue, increasing vitality, etc. POE-HCO used in the present invention is a nonionic surfactant obtained by addition polymerizing ethylene oxide to hydrogenated castor oil, and the average number of moles of ethylene oxide added is About 60 is preferred. The molten mixture of γ-oryzanol and POE/HCO is 1
It melts at 45 to 150°C, producing a uniform melt. γ
-The melting point of oryzanol is approximately 140"Cte, squirrel, PO
Among E-HC(M), for example, POE(60)HCO has a melting point of about 40°C. MSE is an esterified product of sucrose and fatty acid, and the number of carbon atoms in the fatty acid is 12 or more and less than 22. From the viewpoint of taste etc., saturated fatty acids are preferably 16 or more and 18 or less. The monoester content is 90% or more, preferably 95% or more, and the diester or higher ester content is less than 10%, preferably less than 5%, and more preferably does not contain triester or higher ester. For the purpose of solubilization, POE-HCO should be used at least 3 times the amount (weight) of γ-oryzanol, and MSE should be used at least 2 times the amount (by weight) of γ-oryzanol.
If the amount is less than this, a transparent solubilized liquid cannot be obtained. Since a melt cannot be obtained, a melt mixture of γ-oryzanol and POE-HCO was prepared and subjected to MSE.
must be dissolved in water. On the other hand, when mixing γ-oryzanol and MSE, a homogeneous melt can be obtained, but in this case it is necessary to dissolve POE/HCO in water, which requires ethyl alcohol, It can't be. Next, the solubilization temperature needs to be 50°C or higher. Below this temperature solubilization takes a very long time. Further, the temperature of the melt is not particularly limited, but is preferably the same temperature as the solubilization temperature.

【Example】

Next, the present invention will be explained in more detail with reference to Examples. In order to evaluate the solubilization state by the solubilization method of the present invention and the storage stability at low temperatures of the prepared solubilized solution, tests were conducted using the following model system. Polyoxyethylene hydrogenated castor oil. The one containing 60 moles of ethylene oxide was used. (Model system) Melted mixture of γ-oryzanol/POE (60) HCO Predetermined amount (100 mg of γ-oryzanol) MSE
Predetermined amount of citric acid 1.000mg
Quenchusu thorium 200mg fructose
30g glucose
20g purified purified water Amount to make the whole 500ml Example 1 γ-Oryzanol/POE (60) HCO2 1/3 (
A melt of (weight) was prepared at 150°C. Next, 200 mg of MSE was dissolved in 300 ml of purified water along with 30 g of fructose and 209 g of glucose, and kept at 60°C. While stirring this with a magnetic stirrer at 1100 rpm, γ-oryzanol/POE (60) HCO
= 1/3 Add 400 mg of the melt and solubilize for 5 minutes, then mix 1.000 mg of citric acid and 200 mg of sodium citrate dissolved in 100 mJ1 of purified water. Finally, the total volume is made up to 500 ml with purified water. The evaluation criteria for solubilization state and storage stability at 5°C were as follows, and the results are shown in Table 1. 0: Transparent solubilized state Δ: Slightly cloudy state Comparative Examples 1 to 5 were conducted and the results are also shown in Table-1. (Left below) From the results in Table 1, good solubilization! For γ-oryzanol, POE
-HCO must be at least 3 times the amount (ffiMt), MSE must be at least 2 times the amount (by weight), and the solubilization temperature must be at least 50°C.

【Effect of the invention】

According to the present invention, it is possible to solubilize γ-oryzanol, which is a poorly water-soluble substance, in a pharmaceutical drink, and the pharmaceutical drink has excellent storage stability at low temperatures. Therefore, it makes a great contribution to the medicinal drink industry. Patent applicant Daiichi Kogyo Seiyaku Co., Ltd.

Claims (1)

[Claims] 1. In a method for solubilizing γ-oryzanol in a pharmaceutical drink, a sucrose fatty acid ester having a monoester content of 90% or more, which is twice the amount (weight) of γ-oryzanol, is purified. Dissolve in water, then homogeneously melt-mix polyoxyethylene hydrogenated castor oil and γ-oryzanol in an amount more than three times the amount (weight) of γ-oryzanol at a temperature of 50°C or higher. Characteristic method for solubilizing γ-oryzanol. 2. A pharmaceutical drink containing γ-oryzanol obtained by the method according to claim 1.