KR20150134828A - Method for preparing astaxanthin monoesters - Google Patents
Method for preparing astaxanthin monoesters Download PDFInfo
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- KR20150134828A KR20150134828A KR1020140062120A KR20140062120A KR20150134828A KR 20150134828 A KR20150134828 A KR 20150134828A KR 1020140062120 A KR1020140062120 A KR 1020140062120A KR 20140062120 A KR20140062120 A KR 20140062120A KR 20150134828 A KR20150134828 A KR 20150134828A
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Abstract
Description
The present invention relates to a process for preparing astaxanthin, and more particularly to a process for preparing astaxanthin monoester.
Astaxanthin is a kind of carotenoid pigment that was isolated from lobster in 1938 and is a pigment that produces red color of fish such as salmon or trout or red color when crustaceans such as shrimp are heated. Astaxanthin is a pigment that exists in animals but can not be synthesized in animals and is transferred from food. It is a nutrient source for red coloring fish muscle such as salmon and rainbow trout. It is mainly used as a feed additive for aquaculture fish. In addition, it has strong antioxidant function, and it has activity to prevent and treat various diseases caused by free radicals generated by oxidation in the body, and thus it is increasingly used as a material for enhancing human health function.
Astaxanthin is an ester form in which one or two esters exist rather than a free form in which the ester is not bonded. It is easily absorbed into fish and easily transferred to muscle when used as a feed, WO-00/62625). Since it is more stable to heat and oxygen than glassy, it is known to produce glassy astaxanthin as a raw material in a diester form (WO-03/066583). It is also known that astaxanthin of the heavy chain fatty acid ester type is superior to astaxanthin of the long chain fatty acid ester type in nature and most excellent in oral absorption of the monoester type of medium chain fatty acid (Korean Patent No. 10 -0941899).
However, the production method of astaxanthin in the above-mentioned ester form has an extremely low production yield, and therefore, a method of producing astaxanthin in a short time and in a high yield is required in order to be widely used industrially.
The present invention has been made to solve the above problems and it is an object of the present invention to provide a process for producing astaxanthin in the form of a monoester which is stable to heat and oxygen and is well absorbed by fishes, do. However, these problems are exemplary and do not limit the scope of the present invention.
According to one aspect of the present invention, there is provided a process for producing a starch, comprising: a first reaction step of reacting free astaxanthin and a heavy chain fatty acid in the presence of an activating agent; A second reaction step of adding the heavy chain fatty acid and the activating agent to the reactant produced by the first reaction step to induce an additional reaction; And a step of separating the astaxanthin monoester from the reactant produced by the secondary reaction step, wherein the astaxanthin monoester is separated from the reactant.
According to one embodiment of the present invention as described above, in the astaxanthin esterification reaction, the fatty acid is divided and added and reacted to selectively react with only one of two hydroxyl groups having similar reactivity to form astaxanthin diester The production of astaxanthin monoester can be suppressed and the production amount of astaxanthin monoester can be increased to realize a high yield in a short time. Of course, the scope of the present invention is not limited by these effects.
1 is a photograph of thin layer chromatography showing astaxanthin free form used in the production of astaxanthin and astaxanthin monodecanoate and astaxanthin didecanoate produced in the reaction solution.
Definition of Terms:
As used herein, " Astaxanthin "has a structure similar to beta carotene, lutein and zeaxanthin and the molecular formula is C 40 H 52 O 4 . Carotenoids carry out the general physiological functions possessed by the carotenoid system but have unique chemical functions based on the molecular structure. Astaxanthin has a hydroxyl group (OH) and a keto group (C = O) at both ends and corresponds to the xanthophyll family. It has a higher polarity than the other carotenoids, is more easily esterified, And exhibits unique characteristics such as activity. Because of these properties, astaxanthin is very unstable and tends to be particularly susceptible to oxidation. Therefore, astaxanthin is present in nature in the form of protein complexes (exoskeleton of salmon muscle or lobster) or ester bonding (monoester or diester) with one or two fatty acids.
As used herein, "astaxanthin esters" are molecules that have two hydroxyl groups (-OH) in a molecule and can have two esters, and can be distinguished by the number of esters. When there is no ester, it is called free form, when there is one, it is called monoester form, and when there are two, it is called diester form. In the natural world, it is mainly present in the form of esters of fatty acids such as palmitic acid, oleic acid and linoleic acid. Glassy astaxanthin is unstable due to temperature and oxygen and is easily decomposed, while ester type is relatively stable. Representative examples of the astaxanthin ester type include astaxanthin eicosapentaenoic acid diester, astaxanthin docosahexaenoic acid diester and astaxanthin acetic acid diester. .
As used herein, the term " astaxanthin mixture "refers to a mixture of astaxanthin monoester and astaxanthin diester produced by ester reaction between free astaxanthin and fatty acid and free astaxanthin unused in the reaction ≪ / RTI > Thus, the number of molecules of free astaxanthin used in the initial reaction and the molecular number of the astaxanthin mixture produced by the reaction are maintained on the basis of astaxanthin.
As used herein, "decanoic acid" is a carboxylic acid of n-decane and is a saturated fatty acid and the formula is CH 3 (CH 2 ) 8 COOH. It does not dissolve in water, but it melts in alcohol and ether. Glyceride, and is widely contained in oils such as palm oil and palm oil, or in animal fat. It is used in organic synthesis and in the manufacture of spices, lubricants, greases, rubbers, dyes, plastics, food additives and pharmaceuticals.
As used herein, "medium-chain fatty acids" refers to fatty acids having 6 to 12 carbon atoms.
As used herein, "long-chain fatty acids" refers to fatty acids having more carbon atoms than heavy chain fatty acids, i.e., fatty acids having 13 or more carbon atoms.
DETAILED DESCRIPTION OF THE INVENTION [
According to one aspect of the present invention, there is provided a process for producing a starch, comprising: a first reaction step of reacting free astaxanthin and a heavy chain fatty acid in the presence of an activating agent; A second reaction step of adding the heavy chain fatty acid and the activating agent to the first astaxanthin mixture produced by the first reaction step to induce an additional reaction; And a step of separating the astaxanthin monoester from the secondary astaxanthin mixture produced by the secondary reaction step, wherein the astaxanthin monoester is separated from the secondary astaxanthin mixture.
In the preparation method, the mole ratio of the free astaxanthin and the heavy chain fatty acid in the first reaction step may be from 2 to 4: 1, and the primary astaxanthin mixture and the The mole fraction of the heavy chain fatty acid may range from 2 to 4: 1.
In the above-mentioned production method, the heavy chain fatty acid and the activating agent are added to the reaction product produced by the second reaction step between the second reaction step and the astaxanthin monoester separation step, A reaction step can be added.
In the above production method, the production yield of astaxanthin monoester can be increased by repeating the step of adding the heavy chain fatty acid and the activator to the reaction product one or more times after the third reaction step, Can be appropriately adjusted in consideration of the yield, time, and cost.
In the above production method, the mole ratio of the secondary astaxanthin mixture and the heavy chain fatty acid in the third reaction step may be 2 to 4: 1.
In the above production method, the reaction or the addition reaction may be carried out in an organic solvent, and the organic solvent may be dichloromethane, chloroform, ethyl acetate or tetrahydrofuran.
Wherein the activating agent is selected from the group consisting of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDCI), 4- (dimethylamino) pyridine, N, N-dicyclohexylcarbodiimide, Lt; / RTI >
The free astaxanthin may be a synthetic product (commercially available from Roche, Sigma, etc.) or may be derived from natural sources. In addition, Phaffia yeast may be cultured and stored in cells and then extracted or purified. Alternatively, genetically engineered microorganisms, yeasts, fungi, or plants may be cultured or grown, and those extracted or purified may be used It is possible. Or astaxanthin fatty acid ester, and then removing the fatty acid through a deesterification reaction, followed by purification. The astaxanthin fatty acid ester may be a fatty acid ester, a monoester, a diester, or a mixture of both. The above-mentioned astaxanthin fatty acid ester can be used regardless of synthetic or natural extract. For example, astaxanthin fatty acid esters extracted from nature, such as crustaceans such as green algae, hematococzas, krill, crustaceans such as shrimp and crabs, and fish eggs, are mixtures of monoester and diastereomer, Fatty acids are also mixtures of various fatty acids, but they can be used without problems.
The reaction conditions may include stirring at 15 to 25 DEG C for 1 to 3 hours.
The heavy chain fatty acid is selected from the group consisting of caproic acid (C6), heptanoic acid (C7), octanoic acid (C8), nonanoic acid (C9), decanoic acid Undecanoic acid, C11), and lauric acid (C12) may be used alone or in combination of two or more.
The heavy chain fatty acid refers to a fatty acid having 6-12 carbon atoms and no double bond. Medium chain fatty acids have no physical, colorless, transparent, no specific taste, no perfume, and low viscosity and present as a 'water-like' liquid at room temperature. In addition, the heavy chain fatty acid has a short carbon length so that it is absorbed fast and has a higher thermal efficiency than the long chain fatty acid and does not accumulate body fat. Due to these characteristics, the heavy chain fatty acid has been used in the gastrointestinal penetration enhancement technology in the medical field related to formulations designed to minimize the adverse effects of existing drugs and to maximize efficacy and efficacy and to efficiently deliver necessary amounts of drugs. In addition, medium-chain fatty acids are used in various fields such as detergents, cosmetic raw materials and food additives.
Hereinafter, the present invention will be described in more detail through reference examples and examples. The present invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, It is provided to fully inform the owner of the scope of the invention.
Comparative Example 1: Preparation of astaxanthin didecanoate
It was confirmed that astaxanthin didecanoate was produced by reacting free astaxanthin and heavy chain fatty acid with an activating agent in an organic solvent in the manner conventionally used in the prior art.
Specifically, 200 mg (0.34 mM) of astaxanthin (commercially available from Sigma Co.) was dissolved in 25 ml of a dichloromethane solution in 5 ml of dry dichloromethane obtained by drying dichloromethane with anhydrous calcium chloride (CaCl 2 ) , And 121.2 mg (0.70 mM) of decanoic acid as a medium chain fatty acid and 160.5 mg (0.84 mM) of 1-ethyl (3- (3-dimethylaminopropyl) -carbodiimide ) And 81.9 mg (0.67 mM) of 4- (dimethylamino) pyridine were successively added thereto, followed by stirring at 20 ° C for 6 hours.
Example 1: Preparation of astaxanthin mono decanoate
In the present invention, the astaxanthin monoester having an absorption effect superior to the diester type was produced at a high yield in a short time by selectively reacting only one of the two hydroxyl groups of astaxanthin.
Specifically, 200 mg (0.34 mM) of free astaxanthin was dissolved in a 25-ml round-bottomed flask using 5 ml of dry dichloromethane obtained by drying dichloromethane with anhydrous calcium chloride (CaCl 2 ) and distilling 20.7 mg (0.12 mM) of decanoic acid as a back-chain fatty acid, 26.7 mg (0.14 mM) of EDCI as an activator and 13.7 mg (0.11 mM) of 4- (dimethylamino) pyridine were successively mixed and stirred at 20 ° C for 2 hours (Primary reaction).
Subsequently, 20.2 mg of decanoic acid, 26.7 mg of EDCI and 13.7 mg of 4- (dimethylamino) pyridine were sequentially added to the reaction mixture, followed by stirring for 2 hours (secondary reaction). Further, 20.2 mg of decanoic acid, and 13.7 mg of 4- (dimethylamino) pyridine were successively added thereto, followed by reaction at 20 ° C for 2 hours (tertiary reaction). The mixture of the final reaction mixture and 50 ml of dichloromethane was washed with 20 ml of a 1 N aqueous hydrochloric acid solution, washed with distilled water, dried over anhydrous sodium sulfate (Na 2 SO 4 ), filtered, The rometane was removed by evaporation.
Experimental Example 1: Confirmation of production of astaxanthin ester
The silica gel thin layer chromatography analysis of the astaxanthin esters produced in Comparative Example 1 and Example 1 was performed using a mixed solvent of acetone and normal hexane 3: 7 (v / v).
As a result, as shown in Fig. 1, the astaxanthin produced by Comparative Example 1 was mostly astaxanthin didecanoate, and only a relatively small amount of astaxanthin monodecanoate was produced. On the other hand, astaxanthin produced according to one embodiment of the present invention obtained 24.3 mg (0.03 mM) of astaxanthin didecanoate as a reddish brown solid and astaxanthin monodecanoate as a reddish brown solid, 130.8 mg (0.17 mM) was obtained more than five times more than didecanoate, and 76.0 mg (0.13 mM) of free astaxanthin free reddish brown solid was recovered. The free foam astaxanthin can be reused as a starting material in the following reaction. The purification conditions and yields are shown in Table 1 below.
In conclusion, in the esterification of astaxanthin, the present inventors have found that, when the free astaxanthin and the heavy chain fatty acid are not reacted at once, but when they are divided and reacted, only one of the two hydroxyl groups of astaxanthin having similar reactivity is selectively , It was confirmed that astaxanthin monoester can be produced by combining fatty acids. Therefore, the astaxanthin monoester excellent in oral absorbability can be produced with a high yield in a short time by the method according to the embodiment of the present invention. Therefore, it is possible to reduce the cost of production of astaxanthin monoester, It can be economically used as a feed for fish farming by using a small amount when used, and can be further enhanced when it is used as a health functional food.
While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed exemplary embodiments, but, on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims. Accordingly, the true scope of the present invention should be determined by the technical idea of the appended claims.
Claims (10)
A second reaction step of adding the heavy chain fatty acid and the activating agent to the first astaxanthin mixture produced by the first reaction step to induce an additional reaction;
And separating the astaxanthin monoester from the secondary astaxanthin mixture produced by the secondary reaction step. ≪ RTI ID = 0.0 > 11. < / RTI >
Wherein the molar ratio of the free astaxanthin and the heavy chain fatty acid in the first reaction step is from 2 to 4: 1.
Wherein the molar ratio of the primary astaxanthin mixture and the heavy chain fatty acid in the second reaction step is from 2 to 4: 1.
Wherein the medium chain fatty acid and the activating agent are added to the secondary astaxanthin mixture produced by the secondary reaction step between the secondary reaction step and the astaxanthin monoester separation step to obtain a tertiary reaction ≪ / RTI > wherein the step is added.
Wherein the molar ratio of the secondary astaxanthin mixture and the heavy chain fatty acid in the third reaction step is from 2 to 4 to 1 day.
Wherein the reaction or the addition reaction is carried out in an organic solvent.
Wherein the organic solvent is methylene chloride, chloroform, ethyl acetate, or tetrahydrofuran. 2. The method of claim 1, wherein the organic solvent is methylene chloride, chloroform, ethyl acetate or tetrahydrofuran.
Wherein the activator is selected from the group consisting of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDCI), 4- (dimethylamino) pyridine, N, N- dicyclohexylcarbodiimide, ≪ / RTI >
Wherein the reaction and the further reaction are carried out by stirring at 15 to 25 DEG C for 1 to 3 hours.
The heavy chain fatty acid is selected from the group consisting of caproic acid (C6), heptanoic acid (C7), octanoic acid (C8), nonanoic acid (C9), decanoic acid Wherein at least one selected from the group consisting of undecanoic acid, C11) and lauric acid (C12) is used.
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| KR20240034947A (en) | 2022-09-07 | 2024-03-15 | 전북대학교산학협력단 | Composite extract containing cryptocapsin and lutein using Maclura tricuspidate fruits and marigold flowers and manufacturing method thereof |
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| KR20240034947A (en) | 2022-09-07 | 2024-03-15 | 전북대학교산학협력단 | Composite extract containing cryptocapsin and lutein using Maclura tricuspidate fruits and marigold flowers and manufacturing method thereof |
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