JP2995652B2 - Method for producing tocol derivative-betaine composite powder and composite powder - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a composite powder of betaine and a tocol derivative constituting vitamin E, and to a composite powder produced by the production method. The composite powder of the present invention can be used as pharmaceuticals, foods, cosmetics and the like.

[0002]

2. Description of the Related Art Tocol derivatives are oily, such as tocopherol, and are not easily formulated. Japanese Patent No. 1290022, which is owned by one of the present applicants, discloses a compound obtained by reacting a tocol derivative with betaine in an organic solvent to form an inclusion complex. This compound is a crystal obtained by inclusion of a tocol derivative such as tocopherol with betaine. As shown in the patent, according to the examples, this clathrate compound is prepared by dissolving tocopherol and anhydrous betaine in a large amount of an organic solvent (ethanol in the example), heating, stirring for 1 hour, cooling, and crystallizing. The substance was filtered under reduced pressure,
It is manufactured by drying.

[0003]

However, the manufacturing method according to the patent has many practical problems. That is,
It is necessary that the solvent completely dissolves betaine and tocopherol, so that the amount used is three times or more the total amount of betaine and tocopherol, which is disadvantageous in terms of safety and cost. In particular, when a large amount of a solvent such as ethanol is used in consideration of use in foods, the cost of the solvent in the product price is large. Further, in consideration of practical production on a large scale, the yield is 90% or less. In order to increase the yield, the amount of energy used is large, such as concentrating the filtrate or crystallizing it by cooling.

Further, the content of the solvent in the filtered cake is high, and the energy for drying the solvent is large. Therefore, there is a strong practical demand for the development of a method for producing a complex powder of a tocole derivative and betaine in a simple process and using less energy. The present inventors have conducted research for the purpose of responding to the above demand. As a result, it was confirmed that the specific substance accelerated the composite powder formation reaction between the tocol derivative and betaine. For example, in the above-mentioned Patent No. 1290022, as shown in the example, α-tocopherol and betaine are added to a large amount of ethanol, heated, stirred and dissolved, and then a complex is formed by a complex process. Certain clathrates have been produced. That is, the patent indicates that ethanol has an important function as both solvents. On the other hand, the present inventors added a small amount of ethanol to α-tocopherol and betaine, so that they did not dissolve in ethanol, but reacted rapidly to form a complex, that is, ethanol promoted the reaction of both. It was confirmed that it had an effect. In other words, by reacting the two in the presence of a small amount of a reaction accelerator, a complex of both is formed very rapidly.

[0005]

That is, the present invention provides a method for producing a tocol derivative-betaine composite powder comprising mixing a tocol derivative, betaine and a specific substance reaction accelerator, and a composite powder produced by the method. About.

[0006]

DESCRIPTION OF THE PREFERRED EMBODIMENTS Specific reaction accelerators used in the method of the present invention include phosphoric acid, citric acid, carbonic acid, glycolic acid, malic acid, polylactic acid, oleic acid, lactic acid, glycerin, ethyl alcohol, propylene glycol , Polyglycerin, and cetyl lactate, which are shown to be extremely practical in the examples described below. In the method of the present invention, by mixing the tocol derivative with betaine and the above-described reaction accelerator, the betaine crystals disappear instantaneously or in an extremely short time, and a complex of almost white fluid tocol derivative and betaine is obtained. A powder can be obtained. In the method of the present invention, there is a difference in the state of powder production depending on the mixing order of the three components. For example, according to the method of mixing betaine and a reaction accelerator and adding a tocol derivative to the mixture, it was found that a powdery composite having particularly excellent fluidity was obtained.

[0007] Even if the three are mixed simultaneously, or if the tocole derivative and the reaction accelerator are mixed and then betaine is added, no particular problem occurs. Further, if necessary, a small amount of an organic solvent may be added to the three components, for example, 2 to 10% by weight based on the total amount of the three components. That is, the degree of atomization, whiteness, and the like of the obtained powdery composite are improved.

[0008]

[0009]

[0010]

As the tocol derivative of the present invention, a tocopherol derivative is practically preferable. Specific examples of tocopherol derivatives include d-α-tocopherol, d-β-
Examples include tocopherol, d-γ-tocopherol, d-δ-tocopherol, d, 1-α-tocopherol and mixtures thereof. Particularly preferred are d-α-tocopherol and d, 1-α-tocopherol.

As the tocol derivative, a tocotrienol derivative can also be used, and d-α-tocotrienol,
Examples thereof include d-β-tocotrienol and d-γ-tocotrienol. The amount of the reaction accelerator used in the present invention is not particularly limited, but is preferably 100% or less based on the total weight of the tocol derivative and betaine in consideration of workability, powder state, and the like.

[0013] More preferably, the content is 20% or less based on the total weight of the tocol derivative and betaine. If the amount of the reaction accelerator is too large, the amount of the active ingredient in the composite is small, and the properties of the obtained composite powder are deteriorated. Since the effect is lost if the amount is too small, it is preferable that the amount is at least 0.5% by weight of the total amount of the tocol derivative and betaine. Further, it is considered that the reaction accelerator substantially functions as a catalyst.

The mixing ratio of the tocol derivative and betaine is by weight.
5 is required. If there is too much betaine, the effect as vitamin E per complex unit is small,
If the amount of betaine is too small, it becomes difficult to produce a powder.

Although a very clean white powder can be obtained even when the amount of betaine is about 10% based on the weight of the tocol derivative (the content of the tocol derivative is 90% by weight), the optimum weight ratio of the tocol derivative: betaine: reaction accelerator is obtained. Is 25: 8:
It is one. The composite powder of the present invention is considered to be an inclusion compound. The complex of the present invention can be stably stored for a long period of time.

[0016]

EXAMPLES Hereinafter, the present invention will be described specifically with reference to Examples, but the present invention is not limited to these.

EXAMPLE 1 250 g of d-α-tocopherol and 68 g of betaine were added to 5
It was weighed in a 00 liter stainless beaker and mixed well with a stirrer. While stirring, add 2 citric acid
7 g were added in small portions. When all the citric acid was added, 5 g of water was added and mixed for 10 minutes. At the end of the mixing, a slightly moist, slightly yellowish, free-flowing powder was obtained. This powder was dried at room temperature under reduced pressure to obtain 331 g of a white tocopherol-betaine complex powder. The yield was about 96%.

[0018]

Example 2 60 g of betaine and 30 g of a 10% acetone solution of citric acid
Was charged into a 500 ml glass beaker and mixed well. While stirring, add 12 g of α-tocopherol to this.
0 g was added. The reaction was completed instantaneously, and 177 g of a very fine and smooth powder was obtained. This powder was a complex of tocopherol and betaine, the yield was about 98%, and the content of tocopherol was 64%.

Example 3 100 g of d-α-tocopherol and 100 g of betaine were charged into a 500 ml glass beaker, and 24 g of glycerin was added thereto with stirring. The reaction proceeded slightly more slowly, yielding 220 g of wet powder. The yield was about 98%.

Example 4 100 g of d-α-tocopherol and 100 g of betaine were charged into a 500 ml glass beaker, and 25 g of ethyl alcohol was added thereto with stirring. The reaction proceeded slightly more slowly, yielding 220 g of wet powder. The yield is about 9
9%.

Example 5 1 kg of d-α-tocopherol and 200 g of a 10% acetone solution of lactic acid were charged into a kneader, and 1 kg of betaine was gradually added while mixing. When the addition of tocopherol was started, a white powder began to be formed, and after the addition, a white powder having good fluidity was obtained. When stirring was continued for about 1 hour, acetone was almost completely evaporated, and a smooth white powder was obtained. This white powder was a composite powder of tocopherol and betaine, and the yield was about 99.5%.

Example 6 A mixture of d-α-tocopherol and betaine at a weight ratio of 1: 1 was previously prepared. Various reaction accelerators shown in Table 1 were added to this mixture, and the time and powder state of the composite powder were observed. The amount of the reaction accelerator added was 3 g per 100 g of the mixture. In Table 1, the reaction time is slow for about 30 seconds, fast for 2-3 seconds, and slightly slow for intermediates between the two.

[0024]

[Table 1]

Experimental Example A stability test was conducted using the composite powder produced by the method of the present invention. Table 2 shows the results.

[Table 2]

The composition of the powder used in the test, the stable value after correction, the quantification method, and the conditions of the flame gas chromatography used in the quantification method are shown below. The loss on drying is a numerical value obtained under the conditions of reduced pressure of 50 ° C. and 2 hours. Powder composition Tocopherol 70 g Betain 35 g Lactic acid 31.5 g Quantitative value after correction = (stable value) / (100-loss on drying) Quantitation method: 0.2471 g of standard d-α-tocopherol
Is precisely weighed and dissolved in 100 ml of ethanol.
On the other hand, 0.6429 g of the sample was precisely weighed and 100 ml
Dissolve in ethanol. Since lactose is insoluble in ethanol, it is filtered to obtain a sample for quantification, injected into 3 μL hydrogen flame gas chromatography, and the content of d-α-tocopherol is calculated by the area ratio with the standard. Conditions for hydrogen flame gas chromatography Column: Silicon GE SE-30, 10% was applied to a glass column having an inner diameter of 3.2 mm and a length of 1.1 mm, and a carrier chromosolve WAW DMCS 60 to 80 m.
eshes filling. Column temperature: 260 ° C, injection temperature, 280 ° C Carrier gas: N ₂ gas Detector: FID Injection amount: 3 μL

[0027]

The method of the present invention for producing a tocol derivative-betaine composite powder does not require the use of an organic solvent, and is advantageous in terms of safety and production cost. Since there is no filtration step, product loss is small, and a yield close to 100% can be achieved. Further, when a solid reaction accelerator such as citric acid or carbonic acid is used as the reaction accelerator, a drying step is not required, and the energy consumption is very small. Furthermore, when the complex is liquid, it is encapsulated in a capsule, but the complex produced by the method of the present invention is used as tablets or granules. Further, the complex of the present invention can be stably stored for a long period of time as shown in the experimental examples.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI A61K 9/14 A61K 47/10 47/10 47/12 47/12 47/14 47/14 47/18 47/18 47/24 47/24 47/34 47/34 9/14 (58) Fields investigated (Int.Cl. ⁶ , DB name) A61K 31/355 A23L 1/302 A61K 7/00 A61K 7/48 A61K 9/14 A61K 47 / 10 A61K 47/12 A61K 47/14 A61K 47/18 A61K 47/24 A61K 47/34

Claims (7)

(57) [Claims] 1. Tocol derivative, betaine and phosphoric acid, citric acid, carbonic acid, glycolic acid, malic acid, polylactic acid, oleic acid, lactic acid, glycerin, ethyl alcohol, propylene glycol, polyglycerin, cetyl lactate as a reaction accelerator A method for producing a tocol derivative-betaine complex powder, comprising mixing one of the above. 2. The method for producing a composite powder according to claim 1, wherein the mixing of the tocol derivative, betaine, and the reaction accelerator comprises first mixing betaine and the reaction accelerator, and adding the tocol derivative to the obtained mixture. . 3. The method according to claim 1, wherein the weight ratio of the tocol derivative to betaine is in the range of 10 to 0.5 betaine to 10 tocol derivative. 4. The method according to claim 1, wherein the tocol derivative is a tocopherol derivative. 5. The method according to claim 4, wherein the tocopherol derivative is at least one of d-α-tocopherol and d, 1-α-tocopherol. 6. Tocol derivative, betaine and phosphoric acid, citric acid, carbonic acid, glycolic acid, malic acid, polylactic acid, oleic acid, lactic acid, glycerin, ethyl alcohol, propylene glycol, polyglycerin, cetyl lactate as a reaction accelerator Composite powder obtained by mixing with one of the above. 7. The composite powder according to claim 6, wherein the weight ratio of the tocol derivative to betaine is in the range of 10 to 0.5 betaine to 10 tocol derivative.