JP2006124488A - Aqueous dispersion of highly unsaturated fatty acid-containing phospholipid - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an aqueous dispersion excellent in the long term preservation stability of a phospholipid composition containing highly unsaturated fatty acids useful for a human body, as its constituting fatty acids. <P>SOLUTION: This aqueous dispersion of the phospholipid composition having highly unsaturated fatty acids as its constituting fatty acids is characterized with that the phospholipid is dispersed by 0.001-5.0 mass% concentration with 0.1-10 μm mean dispersion diameter in water. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to an aqueous dispersion of a highly unsaturated fatty acid-containing phospholipid composition.

  Polyunsaturated fatty acids such as arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), especially ω-3 system in which the first double bond is at the third carbon from the methyl end (ω end) Polyunsaturated fatty acids are substances that have attracted much attention in recent years due to their various physiological activities. Among them, docosahexaenoic acid (hereinafter referred to as DHA) is said to have a learning ability / memory improvement action, a retinal reflex improvement action, a blood pressure lowering action, a cholesterol lowering action, and the like. Conventionally, DHA is mainly supplied with a triglyceride type extracted from fish oil, and the market as a health food has been established.

  A phospholipid having DHA as a constituent fatty acid (referred to as phospholipid type DHA) has higher physiological activity than that of triglyceride type DHA when administered orally, and therefore, it is desired to supply phospholipid type DHA. In addition, in DHA-containing phospholipids, it is known that those in which DHA is bound to the sn-2 position that exists in a natural form in fish and shellfish and the like greatly contributes to physiological activity.

  Since triglyceride type DHA is not soluble in water, in order to use it in an aqueous system, it must be emulsified with a surfactant or the like. In addition, highly unsaturated fatty acids have a problem in long-term stability because of their extremely poor oxidation stability.

  Glycerophospholipids, where the triglyceride sn-3 position is not a fatty acid ester but a phosphate ester, have a hydrophilic group, as represented by phosphadylcholine and phosphadylethanolamine, and therefore generally have a higher affinity for water than the triglyceride type. good. For this reason, it is possible to disperse in water, but as with the triglyceride type, phospholipids containing polyunsaturated fatty acids that have long-term storage stability such as acid value stability problems and destruction of emulsions caused by long-term storage. No emulsion has yet been reported.

  As a similar technique, a liposome preparation using a phospholipid having DHA, which is a highly unsaturated fatty acid, as a constituent fatty acid has been reported. (Patent Literature 1-Patent 2911550, Patent Literature 2-Japanese Patent Laid-Open No. 8-151334, Patent Literature 3-Japanese Patent Laid-Open No. 10-265388) However, all have poor oxidation stability. For example, Patent Document 1 is characterized by the fact that the drug is released by using rather poor oxidative stability. In Patent Document 2, the amount of DHA is clearly reduced when FIG. It is thought that it is oxidized. In addition, the reverse phase evaporation method, the fat thin film method (vortexing method), the surfactant dialysis method and the like are used to form liposomes, and the operation is complicated. Moreover, liposomes are produced for the purpose of transporting the underlying drug to the site of action.

  On the other hand, the present invention relates to an aqueous dispersion (emulsion) for the purpose of supplying a stable aqueous composition of a highly unsaturated fatty acid useful for the human body. Emulsions and liposomes with completely different purposes and production methods should not be compared in general, and stable aqueous dispersions (emulsions) for the purpose of supplying highly unsaturated fatty acids have not yet been reported.

Moreover, although it is not a polyunsaturated fatty acid containing phospholipid, the report regarding the aqueous dispersion of phospholipids, such as a soybean, is made (patent document 4-Unexamined-Japanese-Patent No. 8-311086). However, in the case of phospholipids such as soybeans, a stable aqueous suspension is obtained only after the dispersion diameter is uniform, and according to the examples, the aqueous dispersion having a particle diameter in the range of 0.2 to 10 μm is obtained. Separate into an aqueous phase and a precipitate in as little as 10 days. Therefore, long-term stability is obtained only when the particle size is uniform.
As described above, there are various problems in the conventional technology, and it is not necessary to strictly control the particle size, and it is difficult to oxidize, that is, supply a stable aqueous composition of a highly unsaturated fatty acid having long-term storage stability. Was strongly desired.
Japanese Patent No. 2911550 JP-A-8-151334 JP-A-10-265388 JP-A-8-311086

  An object of the present invention is to provide an aqueous dispersion excellent in long-term storage stability of a phospholipid composition having a highly unsaturated fatty acid useful for the human body as a constituent fatty acid.

  As a result of intensive studies to solve the above problems, the inventors of the present invention do not separate a water phase and a precipitate from a phospholipid having a highly unsaturated fatty acid as a constituent component even if the particle size is not strictly controlled. In addition, it was surprisingly found that by dispersing in a certain concentration range with an average dispersion diameter in a specific range, an aqueous dispersion having excellent long-term stability in which oxidation is unlikely to occur is obtained, and the present invention has been achieved. It was. That is, the present invention is as follows.

(1) A phospholipid composition having a highly unsaturated fatty acid as a constituent fatty acid, wherein the phospholipid is dispersed in water at a concentration of 0.001 to 5.0% by mass and an average dispersion diameter of 0.1 to 10 μm. Water dispersion.
(2) The aqueous dispersion according to (1), wherein the phospholipid is extracted from a fish and shellfish tissue.
(3) The aqueous dispersion according to any one of (1) and (2), which contains 100 ppm or more of vitamin E relative to the phospholipid composition.
(4) A food comprising the aqueous dispersion according to any one of (1) to (3).

  The aqueous dispersion of the present invention is a phospholipid composition having a highly unsaturated fatty acid useful for the human body as a constituent fatty acid, and can be suitably used in the field of health foods because of its excellent long-term storage stability.

  The preferred embodiments of the present invention will be specifically described below. In the present invention, a highly unsaturated fatty acid means a polyunsaturated fatty acid having 4 or more double bonds. The phospholipid composition having a highly unsaturated fatty acid as a constituent fatty acid according to the present invention (referred to as a highly unsaturated fatty acid-containing phospholipid composition) is mainly obtained by extraction from a fish and shellfish tissue. The seafood tissue may be a part of the internal organs or skin of the seafood as long as it contains a highly unsaturated fatty acid-containing phospholipid composition, or it may be an individual itself that is an aggregate thereof. Eggs are also acceptable. These can be used alone or in combination.

  In particular, among the seafood tissues, those having a relatively high content of highly unsaturated fatty acid-containing phospholipids are preferred. Examples include internal organs such as squid skin, squid, scallops, tuna, sardines, bonito, mackerel, cod, salmon, Thai, flounder, shark, trout, and fish eggs such as octopus and salmon.

  In particular, the internal organs of scallops are commonly called uro and are discarded in large quantities. The term uro is called uro in the broad sense when the whole part of the scallop soft body other than the scallops (mid-gut line, gonads, string) is called uro in the narrow sense. Absent. In the present invention, uro in a narrow sense, uro in a broad sense, or a mixture thereof may be used. Uro is preferred as a raw material because it is available at low cost. The extraction of the phospholipid composition from the seafood tissue may be performed according to a known method. For example, there are methods such as JP-A-06-321970, JP-A-07-162757, and JP-A-2004-026767. There is also a method of obtaining phospholipid fatty acids such as soybean lecithin and egg yolk lecithin by converting them into highly unsaturated fatty acids using enzymes.

  The highly unsaturated fatty acid-containing phospholipid composition refers to a phospholipid composition containing a phospholipid in which one or two of the two fatty acid residues of the glycerophospholipid are highly unsaturated fatty acid residues. Examples of the glycerophospholipid include phosphadyl choline, phosphadyl serine, phosphadyl inositol, phosphadyl ethanolamine, phosphadyl glycerol, and phosphadic acid. These may be used alone or as a mixture. Of course, other types of phospholipids and glycolipids originally held by natural products, such as sphingophospholipids, plasmalogen-type phospholipids, and lyso forms of each phospholipid, may be contained. Examples of highly unsaturated fatty acids include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (AA).

  The fatty acid composition in the phospholipid composition is preferably such that the content of highly unsaturated fatty acid is 20% by mass or more of the total fatty acid. More preferably, it is 40 mass% or more. In addition, the phospholipid composition contains one or more tocopherols and tocotrienols (vitamin E), carotenoid pigments such as ascorbic acid (vitamin C) and astaxanthin, and antioxidant substances such as tea catechins. It is preferable because more antioxidant properties can be expected. In particular, vitamin E is contained in an amount of 100 ppm or more, preferably 0.01 to 0.5% by mass, based on the phospholipid composition. Vitamin E may be a natural extract or a synthetic product, and among them, d-σ-tocopherol having a strong antioxidant power is preferable. Further, the neutral lipid is preferably 10% by mass or less with respect to the phospholipid composition because the stability of the emulsion is further enhanced. More preferably, it is 5 mass% or less.

  The aqueous dispersion of the phospholipid composition of the present invention can be obtained by dispersing highly unsaturated fatty acid-containing phospholipids with a specific average particle size in a specific concentration range. The average particle size can be adjusted by adding the phospholipid composition to water to a specific concentration and mixing with a stirrer or homogenizer. Depending on the state of the phospholipid composition, it can also be prepared by shaking vigorously by hand. At that time, the concentration of the phospholipid composition is preferably 0.001 to 5% by mass. More preferably, it is 0.01-1 mass%. Further, the average dispersion diameter is preferably 0.1 to 10 μm, more preferably 0.2 to 6.0 μm. The pH of the liquid is preferably 4.0 to 9.0. More preferably, it is 4.6-8.0. The aqueous dispersion of the present invention is preferably stored in a cool and dark place.

  Since the aqueous dispersion of the present invention is a water-based fluid, it is easy to handle and can be used for pharmaceuticals, foods, cosmetics and the like. For example, it can be used in the form of drugs such as liquids and injections. Among the foods, green tea drinks, black tea drinks, semi-fermented tea drinks (oolong tea, etc.), coffee drinks, milk drinks, soy milk, soft drinks, sports drinks, fruit juice drinks, lactic acid bacteria drinks, vegetable juices, drinks, alcoholic drinks Ideal for use in beverages such as

  Also, jelly-like foods, soups, dressings, sprinkles, bread, ramen, udon, soba, pudding, jelly, snacks, cakes, buns, mutton, eel, rice balls, gum, candy, chocolate, cookies, caramel, ice cream, soft It can also be used for dairy products such as cream, mayonnaise, margarine, seasonings, and yogurt.

  Furthermore, since the component of the present invention is a very useful component for the human body, it can be added as a dietary supplement for lipid components, such as addition to liquid foods for people with dysphagia, and addition to space foods. Polyunsaturated fatty acid-containing phospholipids are said to have a whitening effect and can be incorporated into cosmetics. For example, it may be incorporated into a whitening agent, moisturizing agent, sunscreen, foundation, lipstick, lip balm, makeup remover, shampoo, rinse, hair color, gray hair dye, soap and the like.

  In the methods of formulating, formulating foods, and blending into cosmetics, other components such as diluents acceptable in the production of each form may be contained as one or a mixture containing a plurality thereof. Other components include, for example, antioxidants such as vitamin E, vitamin C, catechin, and astaxanthin, extenders, surfactants, buffers, flavoring agents, flavoring agents, fragrances, preservatives, etc. It is not limited to.

Examples of the present invention will be described below, but the present invention is not limited to the following examples. The methods related to the physical property evaluation described in the examples and comparative examples are as follows.
[Measurement of Average Particle Size] The average particle size was measured using a laser diffraction / scattering particle size distribution analyzer (HORIBA LA-910). The measurement was performed at room temperature, and the measurement was performed by degassing with ultrasonic waves for 30 seconds before the measurement.
[Acid value and peroxide value] The acid value and the peroxide value were measured based on the standard oil analysis test method 4.2.1 and the standard oil analysis method 2.5.2, respectively.
[Fatty acid composition (DHA, EPA)] Methyl esterification was performed according to the standard oil analysis method and analyzed by gas chromatography.

[Examples 1 and 2, Comparative Examples 1 and 2]
10 kg of scallops were dried with a vacuum dryer to obtain 2.5 kg of dried uros. After extracting 3 times with 7.5 L of 90 mass% ethanol from this dry scale, the solvent was distilled off and 503 g of extraction crude oil was obtained. The crude extracted oil was dissolved in 1 L of hexane, and the organic phase was washed with 2 L of 50 mass% acetone aqueous solution. The organic phase hexane was distilled off, the residue was washed 3 times with 2.5 L of cold acetone to remove neutral lipids, and the washed residue was dissolved in hexane. 0.3 g of vitamin E was added and stirred well, and the solvent was distilled off to obtain 107 g of a highly unsaturated fatty acid-containing phospholipid composition.

  In Example 1, the phospholipid composition obtained by the above operation was placed in a sample bottle so as to be 0.1% by mass, covered, and shaken vigorously by hand to disperse the sample bottle. The average dispersion diameter immediately after dispersion was 5.2 μm. This dispersion was allowed to stand in a refrigerator at 2 ° C. for 4 months, but the average particle size was hardly changed without separation into an aqueous phase and a precipitate. Further, oxidation, peroxide value, EPA, and DHA were measured at 2 and 4 months. The results are shown in Table 1. In the table, AV means acid value, and POV means peroxide value. It can be seen that there is no significant change in any value, and the long-term storage stability is excellent.

  In Example 2, the phospholipid composition obtained by the same operation as in Example 1 was placed in a sample bottle so as to be 0.05% by mass and stirred with a homogenizer. The average particle size immediately after dispersion was 0.26 μm. This dispersion was allowed to stand at 2 ° C. for 4 months in a refrigerator, but did not separate into an aqueous phase and a precipitate. In addition, oxidation, peroxide value, EPA, and DHA were measured at 2 and 4 months. The results are shown in Table 1. It can be seen that there is no significant change in any value, and the long-term storage stability is excellent.

  In Comparative Example 1, the phospholipid composition obtained by the same operation as in Example 1 was placed in a sample bottle so as to be 10% by mass and stirred with a homogenizer. The average particle size immediately after dispersion was 1.1 μm. However, when it was also left at 2 ° C., precipitation occurred after one month. Moreover, the average particle diameter at that time was 11.6 μm. Long-term stability was poor because the concentration was too high.

  In Comparative Example 2, the phospholipid composition obtained by the same operation as in Example 1 was placed in a sample bottle so as to be 3.0% by mass, covered, and shaken vigorously by hand to disperse the sample bottle. The average particle size was 12.4 μm. When left at 2 ° C. for 4 months, it was not separated into an aqueous phase and a precipitate. Therefore, oxidation, peroxide value, EPA, and DHA were measured at 2 and 4 months. The results are shown in Table 1. Since the average particle size was too large, the peroxide value and acid value increased with time, and the long-term stability was poor.

[Example 3, Comparative Example 3]
10 kg of squid skin was vacuum-dried to obtain 3.2 kg of dried skin. The phospholipid composition was extracted twice from this dried skin with 6 L of a mixed solvent of ethanol and hexane in a 1: 1 volume ratio, and the solvent was distilled off. The crude extracted oil was dissolved in 1 L of hexane, and the organic phase was washed with 2 L of 50 mass% acetone aqueous solution. The organic phase was separated and hexane was distilled off. The residue was washed twice with 3 L of cold acetone to remove neutral lipid, and residual acetone was distilled off from the washed residue to obtain 132 g of an extracted oil containing highly unsaturated fatty acid-containing phospholipid.

  In Example 3, the phospholipid composition obtained by the above operation was placed in a sample bottle so as to be 1.5% by mass and dispersed by stirring with a paddle blade. The average dispersion diameter immediately after dispersion was 6.3 μm. This dispersion was allowed to stand at 2 ° C. for 4 months, but the average particle size was hardly changed without separation into an aqueous phase and a precipitate. In addition, oxidation, peroxide value, EPA, and DHA were measured at 2 and 4 months. The results are shown in Table 2. It can be seen that there is no significant change in any value, and the long-term storage stability is excellent.

  On the other hand, in Comparative Example 3, commercially available soy lecithin (reagent, manufactured by Wako Pure Chemical Industries, Ltd.) was placed in a sample bottle so as to be 1.5% by mass and dispersed by stirring with a paddle blade. The average dispersion immediately after dispersion was 4.2 μm. When the dispersion was stored at 2 ° C., it separated into an aqueous phase and an oil phase in one week. This soy lecithin was poor in long-term stability because it contained almost no highly unsaturated fatty acids in the constituent fatty acids.

  Since the aqueous dispersion of the present invention is excellent in long-term storage stability of a phospholipid composition having a highly unsaturated fatty acid useful as a constituent fatty acid for the human body, it can be suitably used in the field of health food.

Claims (4)

An aqueous dispersion of a phospholipid composition having a highly unsaturated fatty acid as a constituent fatty acid, wherein the phospholipid is dispersed in water at a concentration of 0.001 to 5.0 mass% and an average dispersion diameter of 0.1 to 10 μm. . The aqueous dispersion according to claim 1, wherein the phospholipid is extracted from a fish and shellfish tissue. The aqueous dispersion according to claim 1, comprising 100 ppm or more of vitamin E based on the phospholipid composition. The foodstuff characterized by adding the water dispersion liquid in any one of Claims 1-3.