JPH06116171A - Method for purifying natural squalene - Google Patents

Abstract

PURPOSE:To purify a natural squalene useful for medicines, cosmetics, etc., having high purity, high quality and excellent safety free from color, smell and tastes by crystallizing a squalene having a given or higher purity under a specific condition. CONSTITUTION:Squalene having 98% or higher purity purified by distillation is dissolved in acetone 5-10 times as much as that of the squalene, cooled to-10 to-94 deg.C and crystallized and purified to give a natural squalene having 99.5% or higher purity.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a method for providing highly purified, high-quality and safe natural squalene free from color, odor and taste, which can be sufficiently used in the fields of food, cosmetics and pharmaceuticals. .

[0002]

2. Description of the Related Art Natural squalene is an unsaturated natural hydrocarbon compound having a molecular chain structure of 30 carbon atoms consisting of 6 isoprene residues, and is used in fish and shellfish, especially in the deep sea shark liver. Since it is contained in large amounts, it has been widely used as an external medicine for skin and health food since ancient times, and it has been expected to be applied as an additive for cosmetics and medicines. Further, it has been used as a cosmetic and a lubricant after being made into squalane by hydrogenation. The original physiological effects of squalene include the effect of penetrating into cells and activating the function of cells, and by applying it to the skin as a cosmetic or external medicine, it prevents skin aging, and gastric ulcers when taken internally. It has been found to be effective for liver diseases and liver diseases, and along with this, the demand for natural squalene is increasing year by year.

Conventionally, such highly useful natural squalene has been commercialized by saponifying and decomposing crude squalene with oil containing a large amount of squalene such as shark liver oil. .

However, it is impossible to completely remove impurities and returning odor by the conventional method using only vacuum distillation, and coloring and odor remain, so that it is used in applications such as cosmetics where aesthetics are a problem. It was not of sufficient quality. Further, squalene oxide, which adversely affects the skin and the like, cannot be removed to a sufficiently low concentration only by distillation, and there is a problem in terms of safety.

Other methods for purifying natural squalene include:
A method for obtaining a standard sample of squalene through a silica gel column after repeating recrystallization of crude squalene with 1 to 2 times the amount of acetone three times has been reported (KJ Sax and FH Stross., ANAL. CHEM., 29, 1700 (1957)). However, when the present inventor tried this method additionally, it was found that impurities of about 1% could not be removed, and squalene suitable for use in cosmetics and the like could not be obtained. That is, the amount of coloring and odorous components can be reduced or removed by passing through a silica gel column, but squalene has a large number of highly reactive unsaturated bonds, and decomposition products that are peroxidized during purification by a silica gel column are Since it is newly generated, this decomposition product cannot be removed,
High-purity squalene of 99% or more could not be obtained. Further, the purification by silica gel column is not suitable for industrial use, and there is a problem that the recovery rate is low.

Conventionally, purification was performed only by vacuum distillation, because further purification was difficult. Thus, it is not easy to highly purify natural squalene, and in order to meet the demand for large-scale supply of inexpensive squalene at present or in the future, development of a method for simply and highly purifying squalene is a major issue. Has become.

[0007]

DISCLOSURE OF THE INVENTION It is an object of the present invention to provide natural squalene having high purity and high safety which is tasteless, odorless, colorless and has no peroxide.

[0008]

Means for Solving the Problems The inventors of the present invention have conducted extensive studies to solve the above problems, and as a result, recrystallized squalene roughly purified by vacuum distillation at a low temperature in a specific amount of acetone to obtain a high yield. It has been found that pure squalene is easily obtained.

That is, the present invention has a purity of 98 by distillation purification.
% Of squalene is dissolved in 5 to 10 times the amount of acetone of the squalene and cooled to −10 ° C. to −94 ° C. for crystallization to crystallize 99.5% or more of natural squalene. A purification method is provided.

The purity of squalene is the purity determined by gas chromatography using a capillary column. The measurement conditions are shown below.

* Column: Ultra-I (manufactured by Hewlett-Packard Co.) 25 m × 0.2 mm i. d. * Detector: FID detector * Carrier gas: Helium * Flow rate (inlet pressure): 0.8 kg / cm ² * Column temperature: 280 ° C (isothermal analysis) * Injection temperature: 300 ° C Raw material of natural squalene purified by the present invention Examples thereof include shark liver oil, olive oil, yeast fat and other animal and vegetable oils. Particularly, deep-sea shark liver oil is preferable because it has a significantly high squalene content.

Crude squalene having a purity of 98% or more can be obtained by subjecting the raw material to vacuum distillation according to a conventional method. If the purity of the crude squalene used for recrystallization is less than 98%, it is necessary to repeat the recrystallization in order to obtain squalene having a sufficient purity for use in cosmetics and the like by the subsequent recrystallization, and the recovery rate decreases. Therefore, it is not preferable.

The crude squalene obtained is purified by recrystallization from acetone. The amount of acetone used is 5 to 10 times the amount of crude squalene, that is, 5 to 10 parts by weight per 1 part by weight of crude squalene. If the amount of acetone is less than 5 times, the amount of impurities in the crystallized squalene increases, which is not preferable. Even if recrystallization is repeated using less than 5 times the amount of acetone, it is difficult to remove impurities, and the recovery rate is also lowered. Further, if the amount of acetone exceeds 10 times, the recovery rate of squalene decreases, which is not preferable. The crude squalene is dissolved in the above-mentioned amount of acetone at room temperature, filtered if necessary, and then cooled to 2
Leave for about 6 hours. The cooling temperature is -10 ° C to -94.
C, preferably about -30 to -70 ° C, more preferably about -30 to -50 ° C. If the cooling temperature is -10 ° C or higher, it takes a long time for crystallization and the recovery rate is lowered, which is not preferable. If the cooling temperature is lower than -94 ° C, acetone as a recrystallization solvent may be solidified, which is not preferable. When the crude squalene is markedly colored, it may be recrystallized after being decolorized with an adsorbent or the like. The precipitated crystals were collected by filtration, returned to room temperature and dissolved,
By drying under vacuum, purified squalene having a purity of 99.5% or more can be obtained. The recovery rate is 80% or more based on the crude squalene after distillation. As the acetone used for recrystallization, it is preferable to use deoxidized acetone. Deoxygenated acetone is
Examples thereof include blowing an inert gas into acetone, distilling and purifying acetone in an inert gas atmosphere, degassing by ultrasonic irradiation, and separation by gas membrane permeation. Examples of the inert gas include nitrogen, argon, helium, carbon dioxide gas and the like. In addition, recrystallization is preferably performed in an inert gas atmosphere in order to suppress oxide formation.

[0014]

According to the present invention, by selecting a specific amount of a recrystallization solvent and a cooling temperature, squalene, which has hitherto been difficult to highly purify, can be very easily prepared.
It became possible to purify to a purity of 9.5% or more. Moreover, its recovery rate is also very high.

The purified squalene obtained is tasteless, colorless and odorless and contains almost no oxides, and therefore has a wide range of applications as bases and foods for pharmaceuticals and cosmetics, the use of which has been limited in terms of quality and safety. Can be expected.

[0016]

EXAMPLES The present invention will be described in more detail below with reference to examples and comparative examples.

Example 1 Shark liver oil was saponified and decomposed with sodium hydroxide, and then the unsaponifiable matter was distilled under reduced pressure three times to give a boiling point of 252.
As a fraction of ˜254 ° C./5 mmHg, purity 99.0%
Of crude squalene was obtained. 100 g of this crude squalene was dissolved in 700 g of deoxidized acetone at room temperature in an inert gas atmosphere, cooled to about -50 ° C, and allowed to stand for 3 hours for crystallization. The obtained crystals were collected by filtration, returned to room temperature to dissolve the crystals, and acetone was distilled off under reduced pressure while slightly flowing nitrogen using a capillary to obtain pure natural squalene 95
g was obtained. The purity of the obtained purified product by gas chromatography using a capillary column was 99.9%. A gas chromatography chart showing the purity is shown in FIG. In addition, the obtained squalene has no color, taste and odor, and the standard oil and fat analysis test method 2.4.12-7
The peroxide value determined by 1 was 0.2.

Comparative Example 1 Shark liver oil was saponified and decomposed with sodium hydroxide, and then the unsaponifiable matter was distilled twice under reduced pressure to give a boiling point of 250.
As a fraction of ~ 260 ° C / 5mmHg, purity 95.0%
Of crude squalene was obtained. 100 g of crude squalene obtained
Was recrystallized from 700 g of acetone in the same manner as in Example 1 to obtain 80 g of purified squalene. The purity of the obtained purified squalene by gas chromatography is
At 98.0%, there was no color or taste, but a slight odor remained. The peroxide value of this squalene is 0.2.
Met.

Comparative Example 2 100 g of squalene having a purity of 99.0% used in Example 1
Was dissolved in 140 g of acetone and recrystallized three times in the same manner as in Example 1 to obtain 60 g of purified squalene.
The purified squalene obtained has no color, taste or odor, its gas chromatographic purity is 99.5%,
Its peroxide value was 0.2.

Comparative Example 3 100 g of squalene having a purity of 99.0% used in Example 1
Was dissolved in 1500 g of acetone and recrystallized in the same manner as in Example 1 to obtain 60 g of purified squalene. The purified squalene obtained had no color, taste or odor, its gas chromatographic purity was 99.5%, and its peroxide value was 0.2.

Comparative Example 4 100 g of squalene having a purity of 99.0% used in Example 1
Was dissolved in 700 g of acetone and cooled to -5 ° C.
It did not crystallize.

Comparative Example 5 100 g of squalene having a purity of 99.0% used in Example 1
Was purified by passing through a silica gel column (developing solvent: hexane), and 84 g of squalene was recovered. The purity of the obtained purified squalene by gas chromatography is 99.
At 0%, there was coloring and odor, the taste was bad, and the peroxide value was 2.4.

The results of Example 1 and Comparative Examples 1 to 5 are summarized in Table 1 below.

[0024]

[Table 1]

The colors in Table 1 were determined by the APHA method. The taste and smell were evaluated by 5 panelists. The taste and odor were evaluated as follows.

* Taste: 5 to 5 samples before and after recrystallization
The taste was felt when 20 ml was included in the mouth or swallowed.

* Odor: 10 samples each before and after recrystallization
After adding ml to a 20 ml sample bottle and shaking well, the odor immediately after opening the lid was compared. Furthermore, a small amount of sample was applied to the back of the hand, and whether or not there was odor at that time was compared. From the results in Table 1, according to the purification method of the present invention, squalene having no color, odor and taste can be easily obtained. It was revealed that the purification method of the present invention was extremely excellent because of its high recovery rate.

[Brief description of drawings]

1 is a gas chromatograph chart of purified squalene obtained in Example 1. FIG.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification number Office reference number FI technical display location A61K 31/01 ADA 9283-4C

Claims (1)

[Claims] 1. A squalene having a purity of 98% or more obtained by distillation purification is dissolved in 5 to 10 times the amount of acetone of the squalene and cooled to -10 ° C. to -94 ° C. for crystallization. A method for purifying natural squalene having a purity of 99.5% or more.