JPS61260097A - Method for separating bile acid - Google Patents

Abstract

PURPOSE:To readily separate bile acid of high purity even in the case where a raw material with a low bile acid content is used, by separating the bile acid from an alcohol obtained by extracting an esterification solution of a raw material containing the bile acid with a supercritical gas or liquefied gas. CONSTITUTION:A raw material containing bile acid, e.g. fish oil, is esterified with a lower alcohol under conditions to form an excess alcohol, and the resultant esterification solution 10 is then introduced into an extraction tank 1 and brought into contact with, for example, a supercritical gaseous carbon dioxide 20 to dissolve preferentially a fatty acid ester, alcohol and bile acid ester in the supercritical gaseous carbon dioxide. The esterification solution 10 and supercritical gaseous carbon dioxide are separated by specific gravity difference to introduce the supercritical gaseous carbon dioxide 20' into the first-stage separation tank 2 and lower the density of the critical gaseous carbon dioxide. Thus, the fatty acid ester 12 is preferantially separated. The alcohol 11 and free bile acid ester 14 are then separated in the secon-stage separation tank 3, and the resultant bile acid ester is separated by crystallization.

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Application of the Invention] The present invention relates to a method and process for separating bile acids with high purity from a raw material containing bile rIR, and particularly to the above-mentioned method using supercritical gas or liquefied gas extraction. Regarding.

[Background of the invention]

Some fish oils contain nicosapentaenoic acid ([F.

There are many valuable substances such as EPA) and decosahexaenoic acid (DMA). EPA and DHA are higher unsaturated fatty acids that have dietary and medicinal effects, and are considered to be precursors of prostaglandins. Fish oil also contains small amounts of bile acids, which have physiological activity to make fats and cholesterol water-soluble.

Various proposals have been made regarding methods for concentrating valuable substances such as EPA and DHA (for example, JP-A-57-187397; JP-A-57-187397;
-149400, etc.) have been made. Generally, fish oil is processed to esterify it with a lower alcohol.

converting glycerides in fish oil into fatty acid esters, and then separating the fatty acid esters from the esterification solution;
A method of fractionating by distillation etc. and concentrating the above EPA and DHA (References, JP-A-57-187397゜JP-A-1I)
There is 8s 8-80373. The detailed steps of the lower alcohol esterification treatment and separation of the produced fatty acid ester from the esterification treatment liquid are shown in Figure 5g5. This process has the following problems.

The esterification reaction is a reversible reaction, and in order to increase the yield of the produced ester, an excess of alcohol is required compared to the theoretical amount of alcohol obtained from one reaction equation.

(81 surplus alcohol and a base as a catalyst (e.g. Na
OH, etc.) and the produced fatty acid esters are highly soluble and difficult to separate from each other. Therefore, as shown in the gs diagram, in addition to the original esterification process, water is introduced to dissolve the excess alcohol in the water. , an extra step is required to separate the fatty acid ester by utilizing the difference in specific gravity between the fatty acid ester and the alcohol aqueous solution. Furthermore, in the lower alcohol esterification process and the separation process of the produced fatty acid ester, separation of alcohol and water by distillation or the like is required in order to recover the alcohol required for esterification.

The inventors have conducted various studies on the application of supercritical gas extraction or liquefied gas extraction to the separation of fatty acid esters and alcohols from fish oil that has been subjected to lower alcohol esterification, and have discovered the following new matter, leading to the present invention.

(1) By supercritical gas extraction or liquefied gas extraction.

Alcohol-free fatty acid esters and 90- or higher alcohols can be separated at yields of 95 or higher, respectively.

(2) Bile acid esters are concentrated in the separated alcohol at a high IA degree of 70 or more (excluding alcohol content).

(3) Bile acid esters always coexist with alcohol.

(4) In the separated alcohol, the bile acids quickly crystallize.

[Purpose of the invention]

An object of the present invention is to provide a method for separating bile acids with high purity from raw materials containing bile acids.

[Summary of the invention]

In the present invention, raw materials containing bile acids are subjected to lower alcohol esterification treatment under conditions that produce surplus alcohol.

The method is characterized in that at least alcohol is separated from the esterification solution by supercritical gas extraction or liquefied gas extraction, and then bile acids are separated from the separated alcohol.

[Embodiments of the invention]

An embodiment of the present invention will be described below using one drawing.

FIG. 1 shows a bile acid separation process according to an embodiment of the present invention. The present invention uses raw materials containing bile acids.

Step (a) of performing a lower alcohol esterification treatment under conditions that produce surplus alcohol, a supercritical carbon dioxide gas extraction step (b) of separating at least alcohol from the esterification treatment liquid 10 obtained from the step (a), and the step ( b
), the bile acid is crystallized from the alcohol 11 separated from the alcohol 11 and separated into solid and liquid (C).

Bile acids are present in the bile of many mammals.

It is also present in trace amounts in fish oil. As a raw material, any material containing bile acid may be used, but hereafter, black oil will be described. In the above process m<a>, the glycerides and bile acids in the fish oil are replaced by KOH,
In the presence of a catalyst such as NaOH, they become lower alcohol esters (hereinafter referred to as fatty acid esters) and bile acid esters, which are mutually soluble with excess alcohol.
Free bile acid esters are extremely soluble in alcohol;
Always coexist with alcohol. Therefore, the key to separating bile acids is to coexist with alcohol.

Furthermore, some bile acids or bile acid esters form complex compounds with cholesterol, alcohol, etc. Process (a
) The composition of the esterification solution obtained in step 2 is as above, fatty acid ester, alcohol, bile acid ester, bile acid complex cholesterol, etc., and glycerin produced as a result of the lower alcohol esterification reaction. , it separates into two phases: glycerin and other substances. What is introduced into the latter step (b) may be the above-mentioned processing/stellation treatment solution, or may be the solution from that pond excluding glycerin.

Other items except glycerin (see below)

Theory BA continues with the esterification treatment liquid and the name J.

Next, the esterification treatment liquid 10 is introduced into step (b). Details of step (b) are shown in FIG.

The esterification treatment liquid 10 is introduced into the extraction tank 1.

Here, it comes into contact with the supercritical carbon dioxide gas 20, and the fatty acid ester, alcohol, and free bile acid ester in the esterification treatment liquid are preferentially dissolved in the supercritical carbon dioxide gas. Next, in the same extraction tank, the esterification treatment liquid and supercritical carbon dioxide are separated based on the difference in specific gravity, and the supercritical carbon dioxide 20' is transferred to the first stage separation tank 2.
Introduced to criticality here! #, reduce the density of m gas and preferentially separate fatty acid ester 12 from supercritical carbon dioxide gas. Next, carbon dioxide gas 21 is taken out from the first stage separation tank 2.

It is introduced into the second stage separation tank 3. Here, the density is further reduced, alcohol 11 and free bile acid ester 14't-
To separate. In the above step (b), the extraction pressure is set to 200
, 150, 1100at, 341[, extraction temperature 55C
1 The first stage separation pressure was 59 atg, the first stage separation temperature was 50C, and the second stage separation pressure was ao atg.

2nd stage separation The 1st stage extract obtained from the 1st stage separation tank and the I obtained from the 2nd stage separation tank 4 when 15G is used once.
The composition of the X2-stage extract is shown in FIGS. 3 and 4, respectively. In both cases, the horizontal axis is the recovery rate of the first-stage extract; the ratio of the outflow of the first-stage extract to the inflow of the esterification solution (in batch processing, the ratio of the amount of the first-stage extract to the amount of esterification ratio of the amount charged in the tank). In the figure, the symbol ■ indicates the extraction pressure of 200 atg.
,, symbol ■di 50 atg, , symbol e is 100
The extraction results for the case of atg are shown, and it can be seen that the composition of the extract does not depend on the extraction pressure but depends on the recovery rate of the extract.

In other words, by turning the recovery rate below the proportion of fatty acid ester present in the esterification solution (8L5T in this example), a 1g single-stage separation tank can yield a fatty acid ester with a tl of 981 or more that does not contain alcohol. At least 90% or more alcohol is obtained from the second stage separation tank with a yield of 95% or more. Approximately 5% of the unrecovered alcohol remains in the extraction tank as a constituent of the bile acid complex, from where it is removed as residue 13. In addition, bile acid esters are included in the concentration of fatty acid esters in analysis, and the black and white symbols indicating fatty acid ester concentrations in Figure 4 indicate that bile acid esters are also included in the concentration. show. In Figure 4, the shaded area is s2
The ratio of fatty acid esters in the perilla extract is shown, and 10% of this is bile acid esters.

Returning to Figure 41, the second stage extract 11 is introduced into step (C). Here, the bile acid ester in the alcohol quickly crystallizes and is separated into solid and liquid from the alcohol. The bile acid ester separated here has one molecule of crystalline alcohol, which can be removed by heating the crystalline alcohol to 130C.

Bile acids of extremely high purity are obtained.

The present invention has been described above with reference to fish oil, but as mentioned above, any raw material containing bile acid may be used.Furthermore, it is possible to use the liver, where bile is produced in the animal's body, the gallbladder, where bile is stored, or the grinding of these materials. It's even better if you use fresh ingredients as raw materials.

〔Effect of the invention〕

The present invention has the following advantages: L: S, high purity bile acids can be easily separated from raw materials containing only trace amounts of bile acids.

If fish oil is used as the raw material, in addition to the above bile acids, alcohol-free fatty acid esters and 90- or higher alcohols can be separated and recovered at a yield of 95% or higher.

In addition, in the present invention, a supercritical gas is a gas at a pressure and temperature that is higher than its critical pressure and a critical temperature, and a liquefied gas is a gas that is at a pressure and temperature that is lower than its critical temperature and higher than its saturated vapor pressure. It is under certain conditions.

[Brief explanation of the drawing]

Figure 1 is a flow diagram showing a bile acid separation process that is an embodiment of the present invention, and Figure 2 is a detailed diagram of the supercritical carbon dioxide extraction step in the bile acid separation process that is an embodiment of the present invention. 7Ci-Fig. ...Extraction tank, 2...1st stage separation monk, 3...2nd stage
Stage separation tank, 10... Esterification treatment liquid, 11... Alcohol, 12... Fatty acid ester, 13... Residue, 14... Bile acid ester, 20... Supercritical carbon dioxide gas, 20'...Supercritical carbon dioxide gas, 21.21'...
·carbon dioxide gas. f330 (A) First blow and i's mouth collection (-)

Claims (1)

[Claims] 1. A raw material containing bile acid is esterified with a lower alcohol under conditions that produce surplus alcohol, and at least alcohol is separated from the esterification solution by supercritical gas extraction or liquefied gas extraction. , and then separating bile acids from the separated alcohol. 2. The method for separating bile acids according to claim 1, which comprises crystallizing the bile acids from the separated alcohol and performing solid-liquid separation. 3. The method for separating bile acids according to claims 1 and 2, wherein the supercritical gas or liquefied gas is supercritical carbon dioxide or liquefied carbon dioxide.