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WO2007046386A1 - Functional material and functional food comprising useful phospholipid composition - Google Patents

Functional material and functional food comprising useful phospholipid composition Download PDF

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Publication number
WO2007046386A1
WO2007046386A1 PCT/JP2006/320670 JP2006320670W WO2007046386A1 WO 2007046386 A1 WO2007046386 A1 WO 2007046386A1 JP 2006320670 W JP2006320670 W JP 2006320670W WO 2007046386 A1 WO2007046386 A1 WO 2007046386A1
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WIPO (PCT)
Prior art keywords
functional
useful
phospholipid composition
phospholipid
useful phospholipid
Prior art date
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Ceased
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PCT/JP2006/320670
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French (fr)
Japanese (ja)
Inventor
Masatoshi Tanouchi
Koretaro Takahashi
Kenji Fukunaga
Kentaro Murakawa
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Cosmo Foods Corp
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Cosmo Foods Corp
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Publication of WO2007046386A1 publication Critical patent/WO2007046386A1/en
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    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23JPROTEIN COMPOSITIONS FOR FOODSTUFFS; WORKING-UP PROTEINS FOR FOODSTUFFS; PHOSPHATIDE COMPOSITIONS FOR FOODSTUFFS
    • A23J7/00Phosphatide compositions for foodstuffs, e.g. lecithin
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23LFOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • A23L33/00Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/115Fatty acids or derivatives thereof; Fats or oils
    • A23L33/12Fatty acids or derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/127Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant

Definitions

  • the present invention relates to a functional material containing a useful phospholipid composition and a functional food to which the functional material is added. More specifically, a functional material containing a useful phospholipid composition and a functional substance as active ingredients, a functional material containing a functional substance in a ribosome formed by the useful phospholipid composition, and the functional material Relates to functional foods.
  • a functional material containing a useful phospholipid composition and a functional substance as active ingredients More specifically, a functional material containing a useful phospholipid composition and a functional substance as active ingredients, a functional material containing a functional substance in a ribosome formed by the useful phospholipid composition, and the functional material Relates to functional foods.
  • Patent Document 1 Non-Patent Document 1
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • lipophilic components are poorly soluble in powerful human body fluids such as water and blood, so the absorption efficiency into the human body is low. There are cases where expensive and valuable materials are always wasted.
  • Various formulation technologies for improving the absorption efficiency of these lipophilic components and hydrophilic components have been proposed and have become important elemental technologies in the food and pharmaceutical fields.
  • Patent Document 1 Japanese Patent Application Laid-Open No. 11 123052
  • Patent Document 2 JP 2002-272493 A
  • Non-Patent Document 1 Yoshie Inoue, Food and Development, 31, 1, p. 49
  • Non-Patent Document 2 Agaritas Internet ⁇ URL: HYPERLINK "http://www.aicplus.com/about http://www.aicplus.com/about agaricus / index, html, August 19, 2005 Search
  • Non-Patent Document 3 Japan Coenzyme Q Association Internet URL: HYPERLINK "http: / / www. Coenzymeq-jp.com/ enterprise. Html # qlO ⁇ http: //www.coenzymeq—jp.com/ ente rprise.html # qlO, searched on August 19, 2005
  • Non-Patent Document 4 Fragrance Journal, No. 15, p. 68-76, 1965
  • the present invention includes a useful phospholipid composition in which a useful phospholipid and a functional substance are used as active ingredients, and the physiological function is effectively utilized to improve physiological activity.
  • the present inventors have conducted intensive research and combined useful phospholipids and functional substances in combination, or useful phospholipids containing functional substances in ribosomes of useful phospholipids. It has been found that the functional material containing the composition can enhance its physiological function as compared with the case where the functional substance is administered alone, and the present invention has been completed.
  • the functional material containing the useful phospholipid composition of the present invention comprises a useful phospholipid composition containing omega-3 highly unsaturated fatty acid-binding phospholipid and a functional substance as active ingredients. It is characterized by that.
  • the functional material containing the useful phospholipid composition of the present invention is omega-3 highly unsaturated. It consists of a ribosome comprising a useful phospholipid composition containing a fatty acid-binding phospholipid and a functional substance, wherein the functional substance is encapsulated in the ribosome.
  • the omega-3 polyunsaturated fatty acid-binding phospholipid is composed of 10% by weight or more, preferably 20% by weight or more, of DHA (docosahexaenoic acid) and Z Or EPA (eicosapentaenoic acid).
  • the omega-3 polyunsaturated fatty acid-binding phospholipid is preferably a useful phospholipid composition in which the content of omega-3 polyunsaturated fatty acid is increased by transesterification.
  • the functional substance is preferably a functional food material or a pharmaceutical material.
  • the functional substance is preferably agaritas or coenzyme Q10.
  • the omega-3 polyunsaturated fatty acid-binding phospholipid is preferably derived from aquatic products, and the aquatic organism is preferably any of fish eggs, aquatic animal gonads, squid, scallops, starfish, seaweeds and microorganisms. .
  • the useful phospholipid is a naturally-derived omega-3 polyunsaturated fatty acid-binding phospholipid, and contains a food material or a pharmaceutical material as a functional substance, or these It is possible to provide a functional material containing a useful phospholipid composition encapsulating the functional substance.
  • the functional substance is agaritas or coenzyme Q10
  • the effect is significantly higher than that of any single unit of omega-3 highly unsaturated fatty acid-binding phospholipid or agaritas. .
  • the functional food of the present invention preferably contains a functional material containing the useful phospholipid composition.
  • the functional food may be a solid food or a beverage.
  • useful phospholipid compositions and functional substances are contained or useful It is possible to provide a functional material that can encapsulate a functional substance in a ribosome having a lipid composition and improve its bioavailability and a food containing the functional material. In particular, when taken as a beverage, the absorption efficiency of functional substances in the body can be improved.
  • FIG. 1 is a diagram schematically showing the structure of another functional material of the present invention.
  • FIG. 2 is a view showing the size of cancer cells inoculated in mice when water containing the compositions of Example 1 and Comparative Examples 1 and 2 was freely ingested.
  • FIG. 3 is a graph showing the weight% of cancer cells on the 21st day relative to the body weight in Example 1 and Comparative Examples 1 and 2.
  • FIG. 4 is a graph showing the weight of cancer cells inoculated in mice when water containing the compositions of Example 2 and Comparative Examples 1 and 2 was freely ingested.
  • the functional material containing the useful phospholipid composition of the present invention comprises a useful phospholipid composition and a functional substance as active ingredients.
  • the phospholipid is, for example, a glycerin phosphate ester represented by the chemical formula (1), including seafood, egg yolk, soybeans, and the like. It is contained in a lot and is used for extraction.
  • an alcoholamine group whose force is selected from (PE), inositol (PI), serine (PS), and glycerol (PG).
  • the group X may be a group in which a polyhydric alcohol is ester-bonded.
  • glycerin phosphates examples include phosphatidylcholine represented by chemical formula (2) and phosphatidylserine represented by chemical formula (3).
  • R COO and R COO are fatty acid residues and are represented by the chemical formula (1)
  • the acid ester X is choline (PC) or serine (PS).
  • PC choline
  • PS serine
  • omega (taenoic acid) group is shown in the following formulas (4) and (5).
  • DHA and EPA are both called omega ( ⁇ ) -3 highly unsaturated fatty acids because the carbon located third from the end has an unsaturated bond.
  • Phospholipids containing unsaturated fatty acids are omega-3 highly unsaturated fatty acid-bound phospholipids.
  • omega-3 polyunsaturated fatty acid-binding phospholipids are called useful phospholipids, or omega-3 phospholipids are called ⁇ -3 phospholipids.
  • Useful phospholipids have a structure having a good balance between a phosphate group as a hydrophilic group and an alkyl group and an alkenyl group as a lipophilic group. It exhibits the property of forming ribosomes, which are emulsified fine particles in human cells, and taking in the lyophilic and lipophilic components therein.
  • the chemical substance that forms an ester bond to the phosphate part of the useful phospholipid is a phospholipid phosphatidylserine that is a phospholipid bound to phosphatidylcholine that is a main component of phosphatidylcholine, which is a choline.
  • a positive charge to the surface it is possible to repel each other electrically in the liquid and to significantly increase the stability of the ribosome in the dispersion.
  • the coexistence concentration is 5% by weight or more and the stability is remarkable, and 60% by weight or less is preferable.
  • fatty acids that are ester-bonded in useful phospholipids include DHA, which is an omega-3 highly unsaturated fatty acid, and ⁇ or ⁇ .
  • DHA which is an omega-3 highly unsaturated fatty acid
  • ⁇ or ⁇ an omega-3 highly unsaturated fatty acid
  • the effect of the present invention can be obtained if omega-3 highly unsaturated fatty acid is contained even in a small amount. The higher the concentration, the more effective. Specifically, a clear effect is exhibited at 10% by weight or more of the fatty acid ester-bonded in the useful phospholipid, and 20% by weight or more is particularly desirable.
  • phosphatidylserine may be produced by extracting phospholipids derived from aquatic products, or by converting phospholipids such as phosphatidylcholine by phosphatidyl group transfer reaction in the presence of L-serine (Patent Literature). 2). Further, it may be extracted by transesterification by an enzymatic method or the like. Furthermore, by adding cholesterol appropriately in the range of 1% by weight to 50% by weight, the strength of the ribosome membrane can be increased and the dispersion stability can be improved.
  • the functional substance 2 can be any functional food material or pharmaceutical material!
  • Such functional food materials include mushroom extract such as Agaritas, Meshimakobu, Hanabiratake, Coenzyme Q10, water-soluble peptide, carotenoids such as carotene, polyphenol, tea catechin, yew leaf extract, various herbs, Flavonoids such as isoflavones, folic acid, vitamins, minerals, amino acids, tocopherol, dalcosamine, hyaluronic acid, chondroitin sulfate, collagen, fucoidan, chitin, chitosan, blueberry, lutein, austaxanthin, etc., DHA, EPA, etc.
  • Coenzyme Q10 is a substance that is also produced in human cells and is called the “genuine element” of the human body, and many products are sold as supplements for health, beauty and physical fitness.
  • the phospholipid useful for the human body Due to the synergistic effect of the physiologically active function of the composition and the functional substance, a functional food having an extremely high physiologically active function can be provided. In particular, when the functional substance is agaritas, the effect can express a higher bioactive function than either the phospholipid composition or the functional substance alone.
  • FIG. 1 schematically shows the structure of a functional material containing another useful phospholipid composition of the present invention.
  • the functional material containing the useful phospholipid composition of the present invention contains functional substance 3 composed of active ingredients of functional food material and pharmaceutical material in ribosome 2 composed of useful phospholipid 1.
  • Ribosome 2 which contains a functional substance, forms fine particles by emulsifying and aggregating useful phospholipids in water.
  • the particle size of ribosome 2 varies depending on the liposome formation conditions, and is usually 10 m or less, more preferably 1 ⁇ m or less.
  • useful phospholipids and functional substances the same materials as the above functional materials can be suitably used.
  • useful phospholipids may be modified or derivatives of phospholipids to which omega binds and have a liposomal effect.
  • Such lipids may be glycolipids such as digalatatosyldiacylglycerol (DGDG)! /.
  • DGDG digalatatosyldiacylglycerol
  • the functional material 1 containing the useful phospholipid composition of the present invention is also referred to as a ribosome preparation 1 containing the functional substance 3 or a ribosome preparation 1 as appropriate.
  • the ribosome is a closed vesicle that forms a bilayer membrane composed of useful phospholipids and has an aqueous phase therein.
  • emulsification which is a system in which one of the two liquids, such as water and oil, that do not mix is finely divided and dispersed in the other phase.
  • the emulsion is stabilized using a surfactant or the like.
  • useful phospholipid itself also has a surfactant action, in the present invention, it is used as a bilayer membrane of ribosome.
  • ribosomes are multilamellar ribosomes (0.1 ⁇ m to several ⁇ m) and single membrane ribosomes (0.01 ⁇ m to number / zm).
  • the former includes multi-layer ribosomes (MLV), multilamellar ribosomes (OLV), and multiphase ribosomes, and the latter includes small single-membrane ribosomes (SUVs) and large single ribosomes.
  • MLV multi-layer ribosomes
  • OSV multilamellar ribosomes
  • SVS small single-membrane ribosomes
  • SAVs small single-membrane ribosomes
  • the mass production method may be a polyhydric alcohol method, a heating method, a spray drying method, a mechanochemical method, or the like.
  • the functional material containing the useful phospholipid composition of the present invention can be produced by encapsulating the functional substance 3 in the ribosome when forming a ribosome having a useful phospholipid power.
  • the functional substance is added in an amount of 1 to 90% by weight, preferably 20 to 70% by weight, inside the ribosome.
  • the ribosome 2 is formed with the useful phospholipid, and the functional substance 3 is encapsulated therein.
  • the functional material 1 that also has a ribosome power of a useful phospholipid encapsulating a functional substance that improves various bioavailability. Therefore, when used as a functional material containing the useful phospholipid composition of the present invention, it is possible to exert more physical functions than the administration of the functional substance alone.
  • useful phospholipids are known to have many physiological activities, and are also good surfactants. Therefore, a functional material in which useful phospholipids themselves are ribosomed and a functional material is encapsulated therein can be dispersed without using other special additives such as surfactants. For this reason, ribosome 2 can be efficiently formed by adding a useful phospholipid to water and applying a treatment to form a lipid bilayer membrane of phospholipid.
  • useful phospholipids have physiological activities such as liver function improvement, blood pressure lowering, anti-allergy, memory function improvement such as memory ability, and anti-cancer. Synergistic effects with physiologically active ingredients in lipids can also improve the overall physiological function.
  • a ribosome preparation containing the functional substance can be prepared by emulsifying a mixture of the useful phospholipid composition and the predetermined functional substance in water. This emulsification can be carried out by vigorously stirring water, the useful phospholipid composition and the functional substance, or by spraying them through micropores.
  • the functional substance is hydrophilic, the functional substance is easily taken up into the phospholipid bilayer membrane of the ribosome and becomes a uniform emulsion (see Fig. 1).
  • the functional substance is lipophilic, a part or all of the functional substance is sandwiched between layers of the phospholipid bilayer inside the liposome, and held or encapsulated inside the phospholipid.
  • the particle size of ribosome formed by emulsification is 10 / z m or less.
  • the particle size distribution can be appropriately adjusted.
  • the particle size and particle size distribution should be designed appropriately according to the application.
  • Useful phospholipids include fish eggs such as salmon roe, demolition power such as bonito and tuna, gonads, squid, starfish, and oils derived from aquatic products such as scallops, starfish, seaweed and microorganisms. Extracted and purified omega-3 polyunsaturated fatty acid binding phospholipids can be used.
  • the functional material containing the useful phospholipid composition in which the useful phospholipid itself of the present invention is ribosomed and the functional material is encapsulated inside or between the phospholipid bilayer membranes. can be manufactured efficiently.
  • Example 1 a functional material containing a useful phospholipid composition containing a useful phospholipid composition and a functional substance as active ingredients was produced. Specifically, omega-3 highly unsaturated fatty acid-binding phospholipid derived from squid meal dissolved in hexane is placed in an eggplant-shaped flask so that the phospholipid forms a thin film on its side wall under a nitrogen gas stream. Then, the mixture was allowed to dry and then left under reduced pressure to completely distill off the solvent to obtain a dried product. 0.4 g of this dried product was dispersed in 10 OOcm 3 of pure water. On the other hand, lgaritas (manufactured by Health Science Co., Ltd., AICPLUS) water extract lyophilized powder 1 g was dissolved in 1000 cm 3 of pure water.
  • omega-3 highly unsaturated fatty acid-binding phospholipid derived from squid meal dissolved in hexane is placed in an eggplant-shaped flask so that the phospholipid forms
  • Example 1 the functional dispersion of Example 1 was prepared by mixing equal amounts of the above aqueous solution of dried solids and an aqueous solution of agaritas.
  • Example 2 a squid liposome-derived phospholipid is used as a raw material for ribosome 2, and Agaritas (AICPLUS, manufactured by Health Science Co., Ltd.) is used as functional substance 3, and a ribosome preparation containing a functional substance 1 was prepared.
  • AICPLUS Agaritas
  • Agarix was encapsulated in ribosomes from squid omega-3 highly unsaturated fatty acid-binding phospholipids by the following procedure.
  • ribosome preparation 1 containing fragritas of Example 2 was prepared.
  • ribosomal formulation 1 containing the Agari task of Example 2 the emulsion lcm 3 per DHA (omega one 3) the phospholipid content is 0. 2 mg / cm 3, Agaritasu content per emulsion lcm 3 The amount was 0.5 mg.
  • PS phosphatidylserine
  • cholesterol may be appropriately added during the preparation of the dried product.
  • Omega 3 highly unsaturated fatty acid-binding phospholipid derived from squid of Comparative Example 1 was prepared in the same manner as in Example 2 except that no agaritas was added.
  • the content of omega-3 highly unsaturated fatty acid-bound phospholipid containing DHA as the main component per lcm 3 of the emulsion is 0.2 mg / cm 3 .
  • composition was mixed with water and allowed to freely ingest as a beverage in mice (BALBZc), and the effect on cancer cells (SP2tumors) inoculated into the mice was examined.
  • the beverage was given daily from day 7 onwards after cancer cell inoculation.
  • Example 1 Comparative Examples 1 and 2
  • FIG. 2 shows the size of cancer cells inoculated in mice when water containing the compositions of Example 1 and Comparative Examples 1 and 2 was freely ingested.
  • the horizontal axis represents the number of days after cancer cell inoculation, and the vertical axis represents the size (mm 3 ) of cancer cells.
  • the figure also shows the data of mice that freely ingested water that did not contain any of the above-mentioned compositions for comparison with Example 1 and Comparative Examples 1 and 2 (Fig. 1). See no treatment).
  • Example 1 As apparent from FIG. 2, the cancer cells of 21 day, Example 1, Comparative Example 1, Comparative Example 2, the case of no administration, respectively, 2mm 3, 4mm 3, 3. 5mm 3, 7mm 3 Thus, in the case of Example 1, only about 30% proliferated compared with the case of no administration. From this, in the case of Example 1, the effect of suppressing the proliferation of cancer cells was remarkably recognized.
  • FIG. 3 shows the weight of the cancer cells on the 21st day relative to the body weight in Example 1 and Comparative Examples 1 and 2. It is the figure which showed quantity%.
  • the vertical axis represents the weight% of cancer cells.
  • the weight percentage of cancer cells is 8% (about 24% without administration), 20%, 17% in Examples Comparative Example 1, Comparative Example 2 and no administration, respectively.
  • the weight percentage of cancer cells was about 24% without administration, and the effect of suppressing the growth of cancer cells was remarkably observed. .
  • FIG. 4 is a graph showing the weight of cancer cells inoculated into mice when water containing the compositions of Example 2 and Comparative Examples 1 and 2 was freely ingested.
  • the horizontal axis indicates the number of days after cancer cell inoculation, and the vertical axis indicates the weight (g) of cancer cells.
  • the figure also shows the data of a mouse that freely ingested water without any of the above-mentioned composition for comparison with Example 2 and Comparative Examples 1 and 2 (FIG. 4). No administration).
  • mice that freely ingested water containing ribosome formulation 1 containing fragritas in Example 2 showed a gradual growth of cancer cells on the 19th day. 27 g of eyes were alive.
  • mice that were given free access to water containing DHA (omega 3) phospholipid ribosome derived from squid in Comparative Example 1 showed growth of cancer cells on day 12 and died on day 19, The weight of the cancer cell at that time was 30 g.
  • mice that were freely ingested with water containing agaritas of Comparative Example 2 showed gradually growing cancer cells from day 13 and reached 40 g on day 35, but survived.
  • Example 2 and Comparative Example the growth of cancer cells was slowed in the order of Comparative Example 2 and Example 2 in comparison with no administration and Comparative Example 1 that died on the 19th day.
  • the cancer cell growth inhibitory effect was observed.
  • the cancer cell growth inhibitory effect is further enhanced than the case of the administration of agaritas alone of Comparative Example 2. Admitted.
  • the growth of cancer cells was slower in the case of the thread and adult product that only the DHA (omega-3) -bound phospholipid ribosome derived from squid in Comparative Example 1 was used. I helped.
  • Example 3 a ribosome preparation 1 containing a functional substance was prepared in the same manner as in Example 2, except that Coenzyme Q10 (manufactured by Nisshin Faluma) was used as the functional substance 3. A total of 25 mg of a drink (100 cm 3 ) in which the functional material of Example 3 was dispersed was given to 3 healthy males.
  • Coenzyme Q10 manufactured by Nisshin Faluma
  • the functional material 1 containing the useful phospholipid of Example 4 was prepared in the same manner as in Example 2 except that the scallop-derived phospholipid described later was used.
  • the scallop-derived phospholipid was prepared as follows.
  • a useful phospholipid composition of Example 4 was produced using scallop as a starting material.
  • the starting material has a scallop mouth weight of 1000kg, which has been drained for a while but not particularly dry (hereinafter referred to as the wet standard).
  • the breakdown is 23% by weight solids and water strength S770kg.
  • the protein in this solid content is about 13.5% in the case of scallop mouth.
  • the starting materials were continuously added, and the first steaming process and the second solid-liquid separation process were continuously performed. Specifically, 2000 liters of water is added to starting material 1 and steam jar is added. It was heated and boiled at a temperature of 95-100 ° C and a residence time of 20 minutes in a continuous heating tube.
  • the extract obtained here was a brown sticky liquid, and its weight was 15.5 kg.
  • the extract was passed through a stainless steel cup-top column having a diameter of 50 cm and a height of 1.5 m.
  • the chromatographic column is packed with silica gel.
  • Silica gel Hishigel, manufactured by Dokai Chemical Co., Ltd.
  • Separation was developed with 95 wt% ethanol.
  • the dark black-brown initial fraction was separated and discarded, and then the effluent phase that became light brown was collected as the target fraction.
  • ethanol was distilled off from the purified solution under the same conditions as in the fourth step to obtain 7.8 kg of an oil phase as a useful phospholipid composition.
  • This useful phospholipid composition had a black-brown appearance and an oily appearance.
  • Example 4 In the same manner as in Examples 1 and 2, a drinking water addition test to mice was performed. As a result, the amount of cancer cells on day 19 was 1.2 g, 30 g, 4 g, and 39 g in Example 4, Comparative Example 1, Comparative Example 2, and no administration, respectively. In the case of Example 4, the amount of cancer cells was as small as 3% with no administration, showing a very high cancer cell suppression effect.

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Abstract

Disclosed is a functional material (1) comprising a useful phospholipid composition. The composition has a useful phospholipid composition comprising an ω-3 highly-unsaturated fatty acid-bound phospholipid and a functional substance as active ingredients. The functional substance (3) may be encapsulated in a liposome (2) formed from the useful phospholipid composition. The useful phospholipid is formed into a liposome in water while mixing the functional substance simultaneously to thereby form a useful phospholipid liposome having a physiologically active ingredient of the functional substance encapsulated therein. The useful phospholipid liposome can improve the systemic adsorption efficiency of the functional substance and therefore exert the physiological function of the functional substance in a small quantity at a satisfactory level.

Description

明 細 書  Specification

有用リン脂質組成物を含む機能性素材及び機能性食品  Functional materials and functional foods containing useful phospholipid compositions

技術分野  Technical field

[0001] 本発明は、有用リン脂質組成物を含む機能性素材とこの機能性素材を添加した機 能性食品に関する。さらに詳しくは、有用リン脂質組成物と機能性物質とを有効成分 とする機能性素材及び有用リン脂質組成物によって形成されるリボソーム中に機能 性物質を内包した機能性素材と、この機能性材料を含む機能性食品に関する。 背景技術  [0001] The present invention relates to a functional material containing a useful phospholipid composition and a functional food to which the functional material is added. More specifically, a functional material containing a useful phospholipid composition and a functional substance as active ingredients, a functional material containing a functional substance in a ribosome formed by the useful phospholipid composition, and the functional material Relates to functional foods. Background art

[0002] 近年、健康志向の高まりに伴って、様々な機能性食品が注目を集めている。それら 多くの中のひとつとして、魚介類から取れる有用リン脂質がある (特許文献 1,非特許 文献 1参照)。これはヒトの健康に有用な EPA (エイコサペンタエン酸)や DHA (ドコ サへキサェン酸)などの高度不飽和脂肪酸エステルを豊富に含むため、これ自体が 機能性食品の素材として注目を集め、商品ィ匕もされている。  [0002] In recent years, various functional foods have attracted attention as health consciousness increases. One of them is a useful phospholipid obtained from seafood (see Patent Document 1, Non-Patent Document 1). It contains a lot of polyunsaturated fatty acid esters such as EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) that are useful for human health.匕 has also been done.

[0003] 人体に有用な様々な機能性物質を構成する成分は種々あるが、例えば、親油性成 分は、水、血液など力 なる人体体液に難溶性であるため、人体への吸収効率は必 ずしも高くなぐ高価な、また貴重な素材を無駄にする場合がある。これらの親油性成 分や親水性成分の吸収効率を向上させるための様々な製剤技術が提案され、食品 、医薬品分野での重要な要素技術となっている。  [0003] There are various components that constitute various functional substances useful for the human body. For example, lipophilic components are poorly soluble in powerful human body fluids such as water and blood, so the absorption efficiency into the human body is low. There are cases where expensive and valuable materials are always wasted. Various formulation technologies for improving the absorption efficiency of these lipophilic components and hydrophilic components have been proposed and have become important elemental technologies in the food and pharmaceutical fields.

[0004] 主として機能性食品の範疇に属する素材として、天然由来の各種機能性食品素材 を経口摂取することにより、生活習慣の乱れに由来する身体の変調 (メタボリックシン ドローム等)の改善に近年広く利用されるようになったものがある。これらの中には原 料入手が難しぐ生産量に限界がある、などの理由力 供給量の少ない高価な素材 が多い。例えば、ァガリタス (非特許文献 2)、コェンザィム Q10 (非特許文献 3)、ブル 一べリー、ルティン、ァスタキサンチン等を挙げることができる。これら高価な、また貴 重な機能性物質の生物学的利用能を向上させる、すなわち、より少量で同等以上の 効能を図ることが望まれて 、る。  [0004] In recent years, as a material mainly belonging to the category of functional foods, by taking various naturally derived functional food materials orally, it has been widely used in recent years to improve body modulation (metabolic syndrome, etc.) resulting from disorder of lifestyle habits. Some have come to be used. Among these, there are many expensive materials with a small supply amount because of the limited production volume that makes it difficult to obtain raw materials. For example, Agaritas (Non-patent document 2), Coenzyme Q10 (Non-patent document 3), Bulletin, Rutin, Wastaxanthin and the like can be mentioned. It is desirable to improve the bioavailability of these expensive and valuable functional substances, that is, to achieve the same or better effect in a smaller amount.

[0005] 特許文献 1 :特開平 11 123052号公報 特許文献 2:特開 2002— 272493号公報 Patent Document 1: Japanese Patent Application Laid-Open No. 11 123052 Patent Document 2: JP 2002-272493 A

非特許文献 1 :井上良計、食品と開発、 31、 1, p. 49  Non-Patent Document 1: Yoshie Inoue, Food and Development, 31, 1, p. 49

非特許文献 2 :ァガリタス インターネット < URL : HYPERLINK "http://www.aicplus. com/ about http://www.aicplus.com/about agaricus /index, html, 2005年 8月 19日 検索  Non-Patent Document 2: Agaritas Internet <URL: HYPERLINK "http://www.aicplus.com/about http://www.aicplus.com/about agaricus / index, html, August 19, 2005 Search

非特許文献 3 :日本コェンザィム Q協会 インターネットく URL : HYPERLINK"http:/ /www. coenzymeq-jp.com/ enterprise. html#qlO〃http://www.coenzymeq— jp.com/ ente rprise.html#qlO, 2005年 8月 19日検索  Non-Patent Document 3: Japan Coenzyme Q Association Internet URL: HYPERLINK "http: / / www. Coenzymeq-jp.com/ enterprise. Html # qlO〃http: //www.coenzymeq—jp.com/ ente rprise.html # qlO, searched on August 19, 2005

非特許文献 4:フレグランスジャーナル、 No. 15、 p. 68- 76, 1965  Non-Patent Document 4: Fragrance Journal, No. 15, p. 68-76, 1965

発明の開示  Disclosure of the invention

発明が解決しょうとする課題  Problems to be solved by the invention

[0006] し力しながら、現在まで、人体に有用で高価な機能性物質を、より効率的に吸収す ることができる機能性食品や製剤などに使用可能な機能性素材が得られていない。 [0006] However, until now, no functional material that can be used for functional foods and preparations that can more efficiently absorb functional substances useful for the human body has been obtained. .

[0007] 本発明は、上記課題に鑑み、有用リン脂質と機能性物質とを有効成分とし、その相 乗機能を有効に活用して、生理活性を向上させた、有用リン脂質組成物を含む機能 性素材とこれを含む機能性食品を提供することを目的として!、る。 [0007] In view of the above problems, the present invention includes a useful phospholipid composition in which a useful phospholipid and a functional substance are used as active ingredients, and the physiological function is effectively utilized to improve physiological activity. For the purpose of providing functional materials and functional foods containing them!

課題を解決するための手段  Means for solving the problem

[0008] 本発明者等は、鋭意研究を行ない、有用リン脂質と機能性物質とを組み合わせて 一緒に投与するか、又は、有用リン脂質のリボソーム内に機能性物質を内包させた 有用リン脂質組成物を含む機能性素材により、機能性物質の単独投与の場合よりも その生理機能を高めることができることを見出し、本発明を完成するに至った。 [0008] The present inventors have conducted intensive research and combined useful phospholipids and functional substances in combination, or useful phospholipids containing functional substances in ribosomes of useful phospholipids. It has been found that the functional material containing the composition can enhance its physiological function as compared with the case where the functional substance is administered alone, and the present invention has been completed.

[0009] 上記目的を達成するため、本発明の有用リン脂質組成物を含む機能性素材は、ォ メガ 3高度不飽和脂肪酸結合リン脂質を含む有用リン脂質組成物と機能性物質と を有効成分としたことを特徴とする。 [0009] In order to achieve the above object, the functional material containing the useful phospholipid composition of the present invention comprises a useful phospholipid composition containing omega-3 highly unsaturated fatty acid-binding phospholipid and a functional substance as active ingredients. It is characterized by that.

上記構成によれば、人体に有用なリン脂質組成物と機能性物質の生理活性機能 の相乗効果により極めて生理活性機能の高い、有用リン脂質組成物を含む機能性 素材を提供することができる。  According to the above configuration, it is possible to provide a functional material containing a useful phospholipid composition having a very high physiological activity function due to a synergistic effect of a physiological activity function of the phospholipid composition useful for the human body and the functional substance.

[0010] また、本発明の有用リン脂質組成物を含む機能性素材は、オメガ— 3高度不飽和 脂肪酸結合リン脂質を含む有用リン脂質組成物からなるリボソームと機能性物質とか ら成り、機能性物質を、リボソーム内に内包したことを特徴とする。 [0010] The functional material containing the useful phospholipid composition of the present invention is omega-3 highly unsaturated. It consists of a ribosome comprising a useful phospholipid composition containing a fatty acid-binding phospholipid and a functional substance, wherein the functional substance is encapsulated in the ribosome.

この構成によれば、人体に有用な機能性物質は乳化性に優れた有用リン脂質から 形成されるリボソームに内包され、体内における生物学的利用能を高めることによつ て、生理活性機能を向上させることができる。  According to this configuration, functional substances useful for the human body are encapsulated in ribosomes formed from useful phospholipids with excellent emulsifying properties, and increase the bioavailability in the body, thereby increasing the bioactive function. Can be improved.

[0011] 上記構成において、オメガ— 3高度不飽和脂肪酸結合リン脂質は、リン脂質中にェ ステル結合する脂肪酸の 10重量%以上、好ましくは 20重量%以上が DHA (ドコサ へキサェン酸)及び Z又は EPA (エイコサペンタエン酸)である。  [0011] In the above configuration, the omega-3 polyunsaturated fatty acid-binding phospholipid is composed of 10% by weight or more, preferably 20% by weight or more, of DHA (docosahexaenoic acid) and Z Or EPA (eicosapentaenoic acid).

上記オメガ 3高度不飽和脂肪酸結合リン脂質は、好ましくは、エステル交換によ つてオメガ— 3高度不飽和脂肪酸含有量を高めた有用リン脂質組成物である。 上記機能性物質は、好ましくは、機能性食品素材または医薬品素材である。この機 能性物質として、ァガリタス又はコェンザィム Q10であることが好ましい。  The omega-3 polyunsaturated fatty acid-binding phospholipid is preferably a useful phospholipid composition in which the content of omega-3 polyunsaturated fatty acid is increased by transesterification. The functional substance is preferably a functional food material or a pharmaceutical material. The functional substance is preferably agaritas or coenzyme Q10.

前記オメガ 3高度不飽和脂肪酸結合リン脂質は水産生物由来であってよぐ水産 生物は、魚卵、水産動物の生殖巣、イカ、ホタテ貝、ヒトデ、海藻、微生物の何れかで あることが好ましい。  The omega-3 polyunsaturated fatty acid-binding phospholipid is preferably derived from aquatic products, and the aquatic organism is preferably any of fish eggs, aquatic animal gonads, squid, scallops, starfish, seaweeds and microorganisms. .

[0012] 上記構成によれば、有用リン脂質が天然由来のオメガ 3高度不飽和脂肪酸結合 リン脂質であり、その内部に機能性物質として、食品素材や医薬品素材を含有する カゝ、又は、これらの機能性物質を内包する有用リン脂質組成物を含む機能性素材を 提供することができる。特に、機能性物質がァガリタスやコェンザィム Q10である場合 、その効果は著しぐオメガ 3高度不飽和脂肪酸結合リン脂質又はァガリタスの何 れの単体よりも、高 、生理活性機能を発現することができる。  [0012] According to the above configuration, the useful phospholipid is a naturally-derived omega-3 polyunsaturated fatty acid-binding phospholipid, and contains a food material or a pharmaceutical material as a functional substance, or these It is possible to provide a functional material containing a useful phospholipid composition encapsulating the functional substance. In particular, when the functional substance is agaritas or coenzyme Q10, the effect is significantly higher than that of any single unit of omega-3 highly unsaturated fatty acid-binding phospholipid or agaritas. .

[0013] 本発明の機能性食品は、好ましくは、上記有用リン脂質組成物を含む機能性素材 を添加している。この場合、機能性食品は固形の食品であるほか、飲料であってもよ い。  [0013] The functional food of the present invention preferably contains a functional material containing the useful phospholipid composition. In this case, the functional food may be a solid food or a beverage.

上記構成によれば、機能性物質を内包する有用リン脂質組成物を含む機能性素 材を、固形の食品や飲料など力も摂取し得る機能性食品を提供することができる。 発明の効果  According to the above configuration, it is possible to provide a functional food that can ingest a force such as a solid food or a beverage with a functional material containing a useful phospholipid composition encapsulating a functional substance. The invention's effect

[0014] 本発明によれば、有用なリン脂質組成物及び機能性物質を含むか、又は有用なリ ン脂質組成物力 なるリボソームに機能性物質を内包し、その生物学的利用能を向 上させることができる機能性素材及び機能性素材を含有した食品を提供することが できる。特に、飲料として飲用した場合は、機能性物質の体内吸収効率を向上させる ことができる。 [0014] According to the present invention, useful phospholipid compositions and functional substances are contained or useful It is possible to provide a functional material that can encapsulate a functional substance in a ribosome having a lipid composition and improve its bioavailability and a food containing the functional material. In particular, when taken as a beverage, the absorption efficiency of functional substances in the body can be improved.

図面の簡単な説明  Brief Description of Drawings

[0015] [図 1]本発明の別の機能性素材の構造を模式的に示す図である。  [0015] FIG. 1 is a diagram schematically showing the structure of another functional material of the present invention.

[図 2]実施例 1及び比較例 1, 2の組成物を含む水を自由摂取させたときの、マウスに 接種したがん細胞の大きさを示す図である。  FIG. 2 is a view showing the size of cancer cells inoculated in mice when water containing the compositions of Example 1 and Comparative Examples 1 and 2 was freely ingested.

[図 3]実施例 1及び比較例 1, 2において、 21日目のがん細胞の体重に対する重量% を示した図である。  FIG. 3 is a graph showing the weight% of cancer cells on the 21st day relative to the body weight in Example 1 and Comparative Examples 1 and 2.

[図 4]実施例 2及び比較例 1, 2の組成物を含む水を自由摂取させたときの、マウスに 接種したがん細胞の重量を示す図である。  FIG. 4 is a graph showing the weight of cancer cells inoculated in mice when water containing the compositions of Example 2 and Comparative Examples 1 and 2 was freely ingested.

符号の説明  Explanation of symbols

[0016] 1:機能性物質を内包するリボソーム製剤 [0016] 1: Ribosome preparation containing functional substance

2:有用リン脂質力 なるリボソーム  2: Ribosome with useful phospholipid power

3 :機能性物質  3: Functional substances

発明を実施するための最良の形態  BEST MODE FOR CARRYING OUT THE INVENTION

[0017] 以下、図面に基づいて本発明の実施の形態を詳細に説明する。 Hereinafter, embodiments of the present invention will be described in detail with reference to the drawings.

最初に、本発明の有用リン脂質組成物を含む機能性素材について説明する。 本発明の有用リン脂質組成物を含む機能性素材は、有用リン脂質組成物と機能性 物質とを有効成分としている。有用リン脂質を主成分とする有用リン脂質組成物にお いて、リン脂質は、一例として、化学式(1)で表されるようなグリセリンリン酸エステル であり、魚介類をはじめ、卵黄、大豆などに多く含まれ、抽出利用されている。  First, a functional material containing the useful phospholipid composition of the present invention will be described. The functional material containing the useful phospholipid composition of the present invention comprises a useful phospholipid composition and a functional substance as active ingredients. In a useful phospholipid composition containing a useful phospholipid as a main component, the phospholipid is, for example, a glycerin phosphate ester represented by the chemical formula (1), including seafood, egg yolk, soybeans, and the like. It is contained in a lot and is used for extraction.

[化 1] H2C— OOCF^ [Chemical 1] H 2 C— OOCF ^

I  I

R2COO— CH O R 2 COO— CH O

I II  I II

H2C— O— P— O— X H 2 C— O— P— O— X

I I

OH ここで、 R COO, R COOは脂肪酸残基であり、 Xはコリン (PC)、エタノールァミン OH where R COO, R COO are fatty acid residues, X is choline (PC), ethanolamine

1 2  1 2

(PE)、イノシトール (PI)、セリン (PS)、及びグリセロール (PG)のうち力も選ばれるァ ルコールアミン基などである。この基 Xとしては、多価アルコールをエステル結合させ た基であってもよい。  For example, an alcoholamine group whose force is selected from (PE), inositol (PI), serine (PS), and glycerol (PG). The group X may be a group in which a polyhydric alcohol is ester-bonded.

このようなグリセリンリン酸エステルの例として、化学式(2)で表されるホスファチジル コリンや、化学式(3)で表されるホスファチジルセリンなどが挙げられる。  Examples of such glycerin phosphates include phosphatidylcholine represented by chemical formula (2) and phosphatidylserine represented by chemical formula (3).

[化 2] [Chemical 2]

H2C— OOCF^ H 2 C— OOCF ^

I  I

R2COO-CH R 2 COO-CH

I II  I II

H2C— O— P— O— CH2— CH2N+ (CH3)3 H 2 C— O— P— O— CH 2 — CH 2 N + (CH 3 ) 3

[化 3] [Chemical 3]

H2C— OOCF^ H 2 C— OOCF ^

R OO-CH O O R OO-CH O O

I II II  I II II

Hフ C一 O— P— O— CHつ一 CH— C—〇H  H-F C-one O- P- O- CH-one CH- C-〇H

i i  i i

OH NH2 ここで、 R COO、R COOは脂肪酸残基であり、化学式(1)で表されるグリセリンリ OH NH 2 where R COO and R COO are fatty acid residues and are represented by the chemical formula (1)

1 2  1 2

ン酸エステルの Xがコリン(PC)またはセリン(PS)である。 [0019] R COOである脂肪酸残基力 DHA (ドコサへキサェン酸)基、 EPA (エイコサペンThe acid ester X is choline (PC) or serine (PS). [0019] Fatty acid residue strength RCOO DHA (docosahexaenoic acid) group, EPA (eicosapen

1 1

タエン酸)基である場合の化学構造式を下記 (4)式及び(5)式に示す。これら DHA , EPAは、何れも末端から 3番目に位置する炭素が不飽和結合を有していることから 、オメガ(ω )— 3高度不飽和脂肪酸と呼ばれており、このようなオメガ 3高度不飽和 脂肪酸を含むリン脂質が、オメガ— 3高度不飽和脂肪酸結合リン脂質である。本発明 においては、オメガ— 3高度不飽和脂肪酸結合リン脂質を、有用リン脂質、又は、単 にオメガ— 3結合リン脂質ある ヽは η— 3系リン脂質と呼ぶ。  The chemical structural formula in the case of (taenoic acid) group is shown in the following formulas (4) and (5). These DHA and EPA are both called omega (ω) -3 highly unsaturated fatty acids because the carbon located third from the end has an unsaturated bond. Phospholipids containing unsaturated fatty acids are omega-3 highly unsaturated fatty acid-bound phospholipids. In the present invention, omega-3 polyunsaturated fatty acid-binding phospholipids are called useful phospholipids, or omega-3 phospholipids are called η-3 phospholipids.

[化 4]  [Chemical 4]

Figure imgf000008_0001
Figure imgf000008_0001

[0020] 有用リン脂質は、親水基としてのリン酸部と親油基としてのアルキル基、アルケニル 基部をバランスよく有する構造であるので、界面活性剤的な機能を持ち、水中、人体 体液中、人体細胞内などで乳化微粒子であるリボソームを形成して、その内部に親 水成分及び親油成分を取り込む性質を示す。 [0020] Useful phospholipids have a structure having a good balance between a phosphate group as a hydrophilic group and an alkyl group and an alkenyl group as a lipophilic group. It exhibits the property of forming ribosomes, which are emulsified fine particles in human cells, and taking in the lyophilic and lipophilic components therein.

[0021] なお、上記有用リン脂質のリン酸部分にエステル結合する化学物質は、コリンであ るホスファチジルコリンが主要成分である力 セリンの結合したリン脂質であるホスファ チジルセリンを共存させることにより、リボソームの表面に正電荷を持たせることで、液 中で相互に電気的に反発させ、分散液中でのリボソームの安定性を著しく高めること ができる。共存濃度は、 5重量%以上で安定性が顕著であり、 60重量%以下が好ま しい。また、有用リン脂質中でエステル結合する脂肪酸には、オメガ— 3高度不飽和 脂肪酸である DHA及び Ζ又は ΕΡΑが含まれて ヽることが必須である。オメガ 3高 度不飽和脂肪酸は、少量でも含まれていれば本発明の効果を得ることができるが、 高濃度であるほど有効である。具体的には、有用リン脂質中にエステル結合する脂 肪酸の 10重量%以上で明瞭な効果を示し、とくに 20重量%以上が望ましい。 [0021] It should be noted that the chemical substance that forms an ester bond to the phosphate part of the useful phospholipid is a phospholipid phosphatidylserine that is a phospholipid bound to phosphatidylcholine that is a main component of phosphatidylcholine, which is a choline. By imparting a positive charge to the surface, it is possible to repel each other electrically in the liquid and to significantly increase the stability of the ribosome in the dispersion. The coexistence concentration is 5% by weight or more and the stability is remarkable, and 60% by weight or less is preferable. In addition, it is essential that fatty acids that are ester-bonded in useful phospholipids include DHA, which is an omega-3 highly unsaturated fatty acid, and Ζ or Ζ. The effect of the present invention can be obtained if omega-3 highly unsaturated fatty acid is contained even in a small amount. The higher the concentration, the more effective. Specifically, a clear effect is exhibited at 10% by weight or more of the fatty acid ester-bonded in the useful phospholipid, and 20% by weight or more is particularly desirable.

ここで、ホスファチジルセリンは、水産生物由来のリン脂質力 抽出製造しても良い し、ホスファチジルコリンなどのリン脂質を L セリン存在下にホスファチジル基転移 反応により変換することで製造することができる (特許文献 2参照)。また、酵素法等に よるエステル交換によって抽出してもよい。さらにコレステロールを 1重量%〜50重量 %の範囲で適宜加えることで、リボソーム膜の強度が増し、分散安定性を高めること ができる。  Here, phosphatidylserine may be produced by extracting phospholipids derived from aquatic products, or by converting phospholipids such as phosphatidylcholine by phosphatidyl group transfer reaction in the presence of L-serine (Patent Literature). 2). Further, it may be extracted by transesterification by an enzymatic method or the like. Furthermore, by adding cholesterol appropriately in the range of 1% by weight to 50% by weight, the strength of the ribosome membrane can be increased and the dispersion stability can be improved.

[0022] 機能性物質 2は、機能性食品素材や医薬品素材であれば何でもよ!/、。このような機 能性食品素材としては、ァガリタス、メシマコブ、ハナビラタケなどのキノコ抽出エキス 類や、コェンザィム Q10、水溶性ペプチド、カロチンなどカロチノイド類、ポリフエノー ル、茶カテキン、イチヨウ葉エキス、各種ハーブ類、イソフラボン等のフラボノイド類、 葉酸、ビタミン類、ミネラル類、アミノ酸類、トコフエロール、ダルコサミン、ヒアルロン酸 、コンドロイチン硫酸、コラーゲン、フコィダン、キチン、キトサン、ブルーベリー、ルテ イン、ァスタキサンチン等、それに DHA, EPAなどのオメガ 3系脂肪酸、共役脂肪 酸 (CLA)などが挙げられる。これらの中で、ァガリタスは顕著な抗がん作用を示すこ とが知られている。また、コェンザィム Q10は、人体細胞中でも生成して人体の"元気 の素"と呼ばれる物質であり、健康、美容、体力増進の補助剤として多くの商品が販 売されている。  [0022] The functional substance 2 can be any functional food material or pharmaceutical material! Such functional food materials include mushroom extract such as Agaritas, Meshimakobu, Hanabiratake, Coenzyme Q10, water-soluble peptide, carotenoids such as carotene, polyphenol, tea catechin, yew leaf extract, various herbs, Flavonoids such as isoflavones, folic acid, vitamins, minerals, amino acids, tocopherol, dalcosamine, hyaluronic acid, chondroitin sulfate, collagen, fucoidan, chitin, chitosan, blueberry, lutein, austaxanthin, etc., DHA, EPA, etc. Omega-3 fatty acids and conjugated fatty acids (CLA). Of these, Agaritas is known to exhibit a marked anticancer effect. Coenzyme Q10 is a substance that is also produced in human cells and is called the “genuine element” of the human body, and many products are sold as supplements for health, beauty and physical fitness.

[0023] 一般に医薬品は、食品と異なり不都合な副作用を伴っている。例えば、アドレアマ イシン、シスブラチン、タキソール等の杭がん剤は、優れた殺がん細胞効果を示すの で広くがんの治療に用いられている。し力しながら、効果を高めるために使用量を増 すと、脱毛、吐き気などの副作用が強くなり、治療の障害となっている。本発明の有 用リン脂質組成物を含む機能性素材により、これら医薬品の効能を高めると、医薬品 の使用量を低下させ、副作用のレベルも大幅に低減ィ匕することができる。その結果、 患者の生活の質 (Quality of Life)を著しく高めることができる点も、本発明の優れた 効果の一つである。  [0023] In general, pharmaceuticals have inconvenient side effects unlike foods. For example, pile cancer drugs such as adriamycin, cisbratin, and taxol are widely used for cancer treatment because they exhibit excellent cancer-killing cell effects. However, increasing the amount of use to increase the effect increases the side effects such as hair loss and nausea, which hinders treatment. When the efficacy of these pharmaceuticals is enhanced by the functional material containing the useful phospholipid composition of the present invention, the amount of the pharmaceuticals used can be reduced and the level of side effects can be greatly reduced. As a result, one of the excellent effects of the present invention is that the quality of life of the patient can be remarkably improved.

[0024] 本発明の有用リン脂質組成物を含む機能性素材によれば、人体に有用なリン脂質 組成物と機能性物質の生理活性機能の相乗効果により、極めて生理活性機能の高 い機能性食品を提供することができる。特に、機能性物質がァガリタスである場合、そ の効果は著しぐリン脂質組成物又は機能性物質の単体のいずれより高い生理活性 機能を発現することができる。 [0024] According to the functional material containing the useful phospholipid composition of the present invention, the phospholipid useful for the human body. Due to the synergistic effect of the physiologically active function of the composition and the functional substance, a functional food having an extremely high physiologically active function can be provided. In particular, when the functional substance is agaritas, the effect can express a higher bioactive function than either the phospholipid composition or the functional substance alone.

[0025] 次に、本発明のさらに別の機能性素材として、オメガ一 3結合リン脂質力もなるリポ ノームに機能性物質を内包させた、有用リン脂質組成物を含む機能性素材について 説明する。  [0025] Next, as another functional material of the present invention, a functional material containing a useful phospholipid composition in which a functional substance is encapsulated in a liposome having omega-13 binding phospholipid power will be described.

図 1は、本発明の別の有用リン脂質組成物を含む機能性素材の構造を模式的に示 すものである。図において、本発明の有用リン脂質組成物を含む機能性素材は、有 用リン脂質 1からなるリボソーム 2内に、機能性食品素材や医薬品素材の有効成分か らなる機能性物質 3が内包されている。機能性物質を内包するリボソーム 2は、有用リ ン脂質が水中で乳化凝集して微粒子を形成している。このリボソーム 2の粒径はリポ ソーム化条件によって異なり、通常 10 m以下であり、より好ましくは 1 μ m以下であ る。  FIG. 1 schematically shows the structure of a functional material containing another useful phospholipid composition of the present invention. In the figure, the functional material containing the useful phospholipid composition of the present invention contains functional substance 3 composed of active ingredients of functional food material and pharmaceutical material in ribosome 2 composed of useful phospholipid 1. ing. Ribosome 2, which contains a functional substance, forms fine particles by emulsifying and aggregating useful phospholipids in water. The particle size of ribosome 2 varies depending on the liposome formation conditions, and is usually 10 m or less, more preferably 1 μm or less.

ここで、有用リン脂質及び機能性物質としては、上記の機能性素材と同様の材料を 好適に用いることができる。さらに、有用リン脂質としては、オメガが結合し、リポソ一 ム効果を有するリン脂質の修飾又は誘導体であってもよ、。このような脂質としては、 ジガラタトシルジァシルグリセロール (DGDG)のような糖脂質であってもよ!/、。  Here, as useful phospholipids and functional substances, the same materials as the above functional materials can be suitably used. Further, useful phospholipids may be modified or derivatives of phospholipids to which omega binds and have a liposomal effect. Such lipids may be glycolipids such as digalatatosyldiacylglycerol (DGDG)! /.

なお、本発明の有用リン脂質組成物を含む機能性素材 1を、適宜、機能性物質 3を 内包するリボソーム製剤 1又は単にリボソーム製剤 1とも呼ぶ。  The functional material 1 containing the useful phospholipid composition of the present invention is also referred to as a ribosome preparation 1 containing the functional substance 3 or a ribosome preparation 1 as appropriate.

[0026] 上記リボソームは、有用リン脂質よりなる二分子膜を形成し、その内部に水相を有 する閉鎖小胞のことである。水と油など混じり合わない二液の一方が細粒となって他 方の相に分散する系、乳化 (ェマルジヨン)とは異なる。通常の乳化は界面活性剤な どを用いてェマルジヨンの安定ィ匕がなされて 、る。有用リン脂質自体も界面活性剤の 作用はあるが、本発明ではリボソームの二分子膜等として使用している。リボソームの 形態としては、多膜リボソーム(0. 1 μ m〜数 μ m)と一枚膜リボソーム(0. 01 μ m〜 数 /z m)が知られている。前者には、多重層リボソーム (MLV)、数枚膜リボソーム (O LV)、多相リボソームがあり、後者には小さな一枚膜リボソーム(SUV)、大きな一枚 膜リボソーム (LUV)、それに巨大一枚膜リボソーム (GUV)がある。内部水相乃至二 重膜相に機能性物質を必要量保持できさえすれば、そのいずれでも良いが、好まし くは一枚膜リボソームである。 [0026] The ribosome is a closed vesicle that forms a bilayer membrane composed of useful phospholipids and has an aqueous phase therein. This is different from emulsification, which is a system in which one of the two liquids, such as water and oil, that do not mix is finely divided and dispersed in the other phase. In normal emulsification, the emulsion is stabilized using a surfactant or the like. Although useful phospholipid itself also has a surfactant action, in the present invention, it is used as a bilayer membrane of ribosome. Known forms of ribosomes are multilamellar ribosomes (0.1 μm to several μm) and single membrane ribosomes (0.01 μm to number / zm). The former includes multi-layer ribosomes (MLV), multilamellar ribosomes (OLV), and multiphase ribosomes, and the latter includes small single-membrane ribosomes (SUVs) and large single ribosomes. There are membrane ribosomes (LUV) and giant single membrane ribosomes (GUV). As long as the required amount of functional substance can be retained in the internal aqueous phase or bilayer membrane phase, any of them may be used, but single membrane ribosome is preferable.

ここで、リボソームの調製'製造方法としては、 vortexing法、 sonication法、 reverse- phase evaporation法、などを用いることができる(非特許文献 4参照)。大量生産法と しては、多価アルコール法、加温法、噴霧乾燥法、メカノケミカル法などでもよい。  Here, vortexing method, sonication method, reverse-phase evaporation method, etc. can be used as the preparation method of ribosomes (see Non-Patent Document 4). The mass production method may be a polyhydric alcohol method, a heating method, a spray drying method, a mechanochemical method, or the like.

[0027] 本発明の有用リン脂質組成物を含む機能性素材においては、有用リン脂質力もな るリボソーム形成の際に、リボソーム内に機能性物質 3を内包させることで製造するこ とができる。この場合、機能性物質は、リボソームの内部に 1〜90重量%、好ましくは 20〜70重量%添加される。  [0027] The functional material containing the useful phospholipid composition of the present invention can be produced by encapsulating the functional substance 3 in the ribosome when forming a ribosome having a useful phospholipid power. In this case, the functional substance is added in an amount of 1 to 90% by weight, preferably 20 to 70% by weight, inside the ribosome.

[0028] 本発明の有用リン脂質組成物を含む機能性素材によれば、図 1に示すように、有用 リン脂質でリボソーム 2を形成し、その内部に機能性物質 3を内包させているので、種 々の生物学的利用能を向上させる機能性物質を内包する有用リン脂質のリボソーム 力もなる機能性素材 1を提供することができる。したがって、本発明の有用リン脂質組 成物を含む機能性素材に用いる場合には、機能性物質を単独で投与する以上の生 理機能を発揮させることができる。  [0028] According to the functional material containing the useful phospholipid composition of the present invention, as shown in Fig. 1, the ribosome 2 is formed with the useful phospholipid, and the functional substance 3 is encapsulated therein. Thus, it is possible to provide a functional material 1 that also has a ribosome power of a useful phospholipid encapsulating a functional substance that improves various bioavailability. Therefore, when used as a functional material containing the useful phospholipid composition of the present invention, it is possible to exert more physical functions than the administration of the functional substance alone.

この場合、有用リン脂質は、単独でも多くの生理活性があることが知られており、良 好な界面活性剤でもある。したがって、有用リン脂質自体をリボソーム化し、その内部 に機能性素材を内包させた機能性素材は、その他の特別な界面活性剤などの添カロ 物を使用せずに分散化できる。このため、有用リン脂質を水に添加して、リン脂質の 脂質二重膜を形成する処理を施すことにより、リボソーム 2を効率良く形成することが できる。  In this case, useful phospholipids are known to have many physiological activities, and are also good surfactants. Therefore, a functional material in which useful phospholipids themselves are ribosomed and a functional material is encapsulated therein can be dispersed without using other special additives such as surfactants. For this reason, ribosome 2 can be efficiently formed by adding a useful phospholipid to water and applying a treatment to form a lipid bilayer membrane of phospholipid.

[0029] さらに、有用リン脂質は、例えば、肝機能改善、血圧降下、抗アレルギー、記憶力な どの学習機能向上、制がんなどの生理活性があるので、機能性物質 3の有効成分と 有用リン脂質中の生理活性成分との相乗効果によっても、全体としての生理機能を 向上させることができる。  [0029] Furthermore, useful phospholipids have physiological activities such as liver function improvement, blood pressure lowering, anti-allergy, memory function improvement such as memory ability, and anti-cancer. Synergistic effects with physiologically active ingredients in lipids can also improve the overall physiological function.

[0030] ここで、生理活性機能を向上させる機構としては、小腸における吸収性を高めたり、 腸内や体内での機能性物質の分解を抑えたり、徐放性による血中濃度の維持、生体 膜と類似構造であることから細胞との相互作用を促進したりすることに起因すると考え られる。また、生体の特定部位 (疾患のターゲット部位)に機能性物質を、濃度高く集 積したりできるものと推定される。さらに、腸管のパイエル板の免疫細胞の活性ィ匕や、 オメガー3高度不飽和脂肪酸結合リン脂質で作成したリボソームが、がん細胞の増殖 抑制効果がある場合や、オメガ 3高度不飽和脂肪酸結合リン脂質そのものの他の 生理機能との相乗効果などのいずれか、又はその複合効果などの種々の要因が考 えられるが、詳細は不明である。 [0030] Here, as a mechanism for improving the physiologically active function, the absorption in the small intestine is increased, the decomposition of the functional substance in the intestine or in the body, the maintenance of blood concentration by sustained release, This is thought to be due to the fact that it has a similar structure to the membrane and promotes interaction with cells. In addition, it is presumed that functional substances can be collected at a high concentration in a specific part of the living body (target part of the disease). In addition, the immune cell activity of Peyer's patches of the intestinal tract and ribosomes made with omega-3 highly unsaturated fatty acid-binding phospholipids are effective in inhibiting the growth of cancer cells. Various factors such as the synergistic effect with other physiological functions of the lipid itself or a combined effect thereof are considered, but details are unknown.

[0031] 次に、本発明の有用リン脂質自体をリボソーム化し、その内部に機能性素材を内包 させた有用リン脂質組成物を含む機能性素材の製造方法を説明する。  [0031] Next, a method for producing a functional material containing a useful phospholipid composition in which the useful phospholipid of the present invention itself is ribosomally encapsulated with the functional material will be described.

有用リン脂質組成物と所定の機能性物質との混合物を、水中で乳化することによつ て、機能性物質を内包するリボソーム製剤を調製することができる。この乳化は、水、 有用リン脂質組成物及び機能性物質を強力に撹拌し、又は、微細孔を通して噴射す ることによって行なうことができる。特に、機能性物質が親水性である場合には、機能 性物質がリボソームのリン脂質二重膜内部に取り込まれて、均一な乳液となり易い( 図 1参照)。さらに、機能性物質が親油性である場合には、その一部又は全部がリポ ソーム内部のリン脂質二重膜の層間に挟まれて、リン脂質の内部に保持、即ち内包 される。乳化により形成されるリボソームの粒径は、 10 /z m以下である。粒径が小さい ほど水性媒体中でリボソームは安定であり、有用リン脂質中のリン酸部分にエステル 結合する化学物質として、 5重量%以上のセリンが含まれる場合、安定性は向上する 。リボソーム化の方法によって、粒径分布は適宜調製されることができる。粒径および 粒径分布は用途に応じて適宜設計すればょ ヽ。  A ribosome preparation containing the functional substance can be prepared by emulsifying a mixture of the useful phospholipid composition and the predetermined functional substance in water. This emulsification can be carried out by vigorously stirring water, the useful phospholipid composition and the functional substance, or by spraying them through micropores. In particular, when the functional substance is hydrophilic, the functional substance is easily taken up into the phospholipid bilayer membrane of the ribosome and becomes a uniform emulsion (see Fig. 1). Further, when the functional substance is lipophilic, a part or all of the functional substance is sandwiched between layers of the phospholipid bilayer inside the liposome, and held or encapsulated inside the phospholipid. The particle size of ribosome formed by emulsification is 10 / z m or less. The smaller the particle size, the more stable the ribosome in the aqueous medium, and the stability is improved when 5% by weight or more of serine is contained as a chemical substance that forms an ester bond to the phosphate moiety in the useful phospholipid. Depending on the method of ribosomeization, the particle size distribution can be appropriately adjusted. The particle size and particle size distribution should be designed appropriately according to the application.

[0032] 有用リン脂質としては、イクラなどの魚卵、カツォ、マグロなどの解体力卩ェ屑や生殖 巣、イカ、ヒトデや、ホタテ貝、ヒトデ、海藻、微生物等の水産生物由来の油分から抽 出し、精製したオメガ 3高度不飽和脂肪酸結合リン脂質を用いることができる。  [0032] Useful phospholipids include fish eggs such as salmon roe, demolition power such as bonito and tuna, gonads, squid, starfish, and oils derived from aquatic products such as scallops, starfish, seaweed and microorganisms. Extracted and purified omega-3 polyunsaturated fatty acid binding phospholipids can be used.

[0033] 上記製造方法によれば、本発明の有用リン脂質自体をリボソーム化し、その内部又 はリン脂質二重膜間に機能性素材を内包させた、有用リン脂質組成物を含む機能性 素材を効率良く製造することができる。  [0033] According to the above production method, the functional material containing the useful phospholipid composition in which the useful phospholipid itself of the present invention is ribosomed and the functional material is encapsulated inside or between the phospholipid bilayer membranes. Can be manufactured efficiently.

実施例 1 [0034] 以下、実施例によって本発明をさらに詳細に説明する。 Example 1 Hereinafter, the present invention will be described in more detail with reference to examples.

実施例 1として、有用リン脂質組成物と機能性物質とを有効成分とする、有用リン脂 質組成物を含む機能性素材を製造した。具体的には、へキサンに溶解したイカミー ル由来のオメガ 3高度不飽和脂肪酸結合リン脂質をナス型フラスコに入れ、窒素ガ ス気流下にて、その側壁にリン脂質が薄膜を形成するようにして乾固させ、さらに、減 圧下で放置して溶媒を完全に留去して乾固物を得た。この乾固物 0. 4gを、純水 10 OOcm3に分散させた。一方、ァガリタス (健康科学株式会社製、 AICPLUS )の水抽 出エキス凍結乾燥粉末 lgを純水 1000cm3に溶解させた。 As Example 1, a functional material containing a useful phospholipid composition containing a useful phospholipid composition and a functional substance as active ingredients was produced. Specifically, omega-3 highly unsaturated fatty acid-binding phospholipid derived from squid meal dissolved in hexane is placed in an eggplant-shaped flask so that the phospholipid forms a thin film on its side wall under a nitrogen gas stream. Then, the mixture was allowed to dry and then left under reduced pressure to completely distill off the solvent to obtain a dried product. 0.4 g of this dried product was dispersed in 10 OOcm 3 of pure water. On the other hand, lgaritas (manufactured by Health Science Co., Ltd., AICPLUS) water extract lyophilized powder 1 g was dissolved in 1000 cm 3 of pure water.

次に、上記乾固物の水分散液とァガリタス水溶液とを等量混合し、実施例 1の機能 性素材を調製した。  Next, the functional dispersion of Example 1 was prepared by mixing equal amounts of the above aqueous solution of dried solids and an aqueous solution of agaritas.

実施例 2  Example 2

[0035] 実施例 2では、リボソーム 2の原料としてイカ由来の DHA結合リン脂質を用い、機 能性物質 3としてァガリタス (健康科学株式会社製、 AICPLUS )を用い、機能性物質 を内包するリボソーム製剤 1を調製した。  [0035] In Example 2, a squid liposome-derived phospholipid is used as a raw material for ribosome 2, and Agaritas (AICPLUS, manufactured by Health Science Co., Ltd.) is used as functional substance 3, and a ribosome preparation containing a functional substance 1 was prepared.

イカ由来のオメガ 3高度不飽和脂肪酸結合リン脂質によるリボソームに、ァガリク スを下記の手順により内包させた。  Agarix was encapsulated in ribosomes from squid omega-3 highly unsaturated fatty acid-binding phospholipids by the following procedure.

最初に、実施例 1と同様の手順で、オメガ— 3高度不飽和脂肪酸結合リン脂質の乾 固物を得た。  First, a dried product of omega-3 polyunsaturated fatty acid-binding phospholipid was obtained by the same procedure as in Example 1.

次に、ァガリタスエキス凍結乾燥粉末 0. 5gを純水 1000cm3に溶かし、さらに、上 記乾固物 0. 2gを加え、ボルテックスミキサーで 20分間攪拌して、リボソーム化を行な つた o Next, 0.5 g of garlicus extract lyophilized powder was dissolved in 1000 cm 3 of pure water, and 0.2 g of the dried product was further added, and the mixture was stirred with a vortex mixer for 20 minutes to effect ribosome formation.

次に、孔径 0. 4 mのメンブランフィルターに 20回通し、サイジング及び除菌を行 ない、実施例 2のァガリタスを内包するリボソーム製剤 1を調製した。実施例 2のァガリ タスを内包するリボソーム製剤 1において、その乳化液 lcm3当りの DHA (オメガ一 3 )リン脂質含有量は、 0. 2mg/cm3であり、乳化液 lcm3当たりのァガリタス含有量 は、 0. 5mgであった。ここで、リボソームに電荷を持たせて安定ィ匕させる場合には、 ホスファチジルセリン (PS)及びコレステロールを乾固物の調製時に適宜加えればよ い。 [0036] 次に、比較例について説明する。 Next, it was passed through a membrane filter having a pore size of 0.4 m 20 times, sizing and sterilization were performed, and a ribosome preparation 1 containing fragritas of Example 2 was prepared. In ribosomal formulation 1 containing the Agari task of Example 2, the emulsion lcm 3 per DHA (omega one 3) the phospholipid content is 0. 2 mg / cm 3, Agaritasu content per emulsion lcm 3 The amount was 0.5 mg. Here, when the ribosome is charged and stabilized, phosphatidylserine (PS) and cholesterol may be appropriately added during the preparation of the dried product. Next, a comparative example will be described.

(比較例 1)  (Comparative Example 1)

ァガリタスを配合しな 、以外は実施例 2と同様の操作で、比較例 1のイカ由来のオメ ガー 3高度不飽和脂肪酸結合リン脂質を調製した。比較例 1のリボソーム製剤 1にお いて、乳化液 lcm3当たりの DHAを主成分とするオメガ— 3高度不飽和脂肪酸結合 リン脂質の含有量は、 0. 2mg/cm3である。 Omega 3 highly unsaturated fatty acid-binding phospholipid derived from squid of Comparative Example 1 was prepared in the same manner as in Example 2 except that no agaritas was added. In the ribosome preparation 1 of Comparative Example 1, the content of omega-3 highly unsaturated fatty acid-bound phospholipid containing DHA as the main component per lcm 3 of the emulsion is 0.2 mg / cm 3 .

[0037] (比較例 2)  [0037] (Comparative Example 2)

ァガリタス単体を比較例 2とした。  Agaritas alone was designated as Comparative Example 2.

[0038] 次に、実施例 1, 2及び比較例 1, 2で調製した各組成物の効果について説明する。 Next, the effects of the compositions prepared in Examples 1 and 2 and Comparative Examples 1 and 2 will be described.

各組成物を水に混ぜてマウス (BALBZc)に飲料として自由摂取させ、マウスに接 種したがん細胞(SP2tumors)に及ぼす影響を調べた。上記飲料は、がん細胞接種 後 7日目以降毎日与えた。  Each composition was mixed with water and allowed to freely ingest as a beverage in mice (BALBZc), and the effect on cancer cells (SP2tumors) inoculated into the mice was examined. The beverage was given daily from day 7 onwards after cancer cell inoculation.

ここで、試験に使用したマウスは、 BALBZcの雄 (nuZnu)、 5週齢で入室馴化飼 育後、 6週齢力 試験を開始した。がん細胞 SP2は、 7頭のマウス (試料数 n= 7)に、 各頭 30万細胞を右脇下に皮下投与した。マウスは、 日本クレア製の飼料 CE2で飼 育した。また、実施例 1, 2及び比較例 1, 2で調製した各組成物の水への添加濃度 は 0. 4mg/cm3とした。 Here, the mouse used for the test was a BALBZc male (nuZnu), bred at 5 weeks of age, and started the 6-week age test. Cancer cells SP2 were administered subcutaneously to the right armpit of 7 million mice (sample number n = 7). Mice were bred with a diet made from CLEA Japan (CE2). The concentration of each composition prepared in Examples 1 and 2 and Comparative Examples 1 and 2 to water was 0.4 mg / cm 3 .

[0039] 最初に、実施例 1と比較例 1, 2との比較について説明する。  First, a comparison between Example 1 and Comparative Examples 1 and 2 will be described.

図 2は、実施例 1及び比較例 1, 2の組成物を含む水を自由摂取させたときの、マウ スに接種したがん細胞の大きさを示す。図 2において、横軸はがん細胞接種以後の 日数を、縦軸はがん細胞の大きさ (mm3 )を示す。図には、実施例 1及び比較例 1, 2 に対して、比較対照のために上記組成物を何も入れない水を自由摂取させたマウス のデータも合わせて示して 、る(図 1の無投与参照)。 FIG. 2 shows the size of cancer cells inoculated in mice when water containing the compositions of Example 1 and Comparative Examples 1 and 2 was freely ingested. In Fig. 2, the horizontal axis represents the number of days after cancer cell inoculation, and the vertical axis represents the size (mm 3 ) of cancer cells. The figure also shows the data of mice that freely ingested water that did not contain any of the above-mentioned compositions for comparison with Example 1 and Comparative Examples 1 and 2 (Fig. 1). See no treatment).

図 2から明らかなように、 21日目のがん細胞量は、実施例 1、比較例 1、比較例 2、 無投与の場合、それぞれ、 2mm3、 4mm3、 3. 5mm3、 7mm3となり、実施例 1の場 合には、無投与の場合と比較して、約 30%しか増殖しな力つた。これから、実施例 1 の場合には、がん細胞の増殖を抑圧している効果が顕著に認められた。 As apparent from FIG. 2, the cancer cells of 21 day, Example 1, Comparative Example 1, Comparative Example 2, the case of no administration, respectively, 2mm 3, 4mm 3, 3. 5mm 3, 7mm 3 Thus, in the case of Example 1, only about 30% proliferated compared with the case of no administration. From this, in the case of Example 1, the effect of suppressing the proliferation of cancer cells was remarkably recognized.

[0040] 図 3は、実施例 1及び比較例 1, 2において、 21日目のがん細胞の体重に対する重 量%を示した図である。図において、縦軸はがん細胞の重量%を示す。 図 3から明らかなように、がん細胞の重量%は、実施例 比較例 1、比較例 2、無投 与の場合、それぞれ、 8% (無投与の約 24%)、 20%、 17%、 33%となり、実施例 1 の組成物の場合には、がん細胞の重量%は無投与の約 24%であり、がん細胞の増 殖を抑圧している効果が顕著に認められた。 [0040] FIG. 3 shows the weight of the cancer cells on the 21st day relative to the body weight in Example 1 and Comparative Examples 1 and 2. It is the figure which showed quantity%. In the figure, the vertical axis represents the weight% of cancer cells. As is clear from FIG. 3, the weight percentage of cancer cells is 8% (about 24% without administration), 20%, 17% in Examples Comparative Example 1, Comparative Example 2 and no administration, respectively. In the case of the composition of Example 1, the weight percentage of cancer cells was about 24% without administration, and the effect of suppressing the growth of cancer cells was remarkably observed. .

[0041] 次に、実施例 2と比較例 1, 2との比較について説明する。 Next, a comparison between Example 2 and Comparative Examples 1 and 2 will be described.

図 4は、実施例 2及び比較例 1, 2の組成物を含む水を自由摂取させたときの、マウ スに接種したがん細胞の重量を示す図である。図において、横軸はがん細胞接種以 後の日数を示し、縦軸はがん細胞の重量 (g)を示す。図には、実施例 2及び比較例 1 , 2に対して、比較対照のために上記組成物を何も入れない水を自由摂取させたマ ウスのデータも合わせて示して 、る(図 4の無投与参照)。  FIG. 4 is a graph showing the weight of cancer cells inoculated into mice when water containing the compositions of Example 2 and Comparative Examples 1 and 2 was freely ingested. In the figure, the horizontal axis indicates the number of days after cancer cell inoculation, and the vertical axis indicates the weight (g) of cancer cells. The figure also shows the data of a mouse that freely ingested water without any of the above-mentioned composition for comparison with Example 2 and Comparative Examples 1 and 2 (FIG. 4). No administration).

19日目のがん細胞量は無投与 20g、リボソームのみ(比較例 1) 15g、ァガリタスの み (比較例 2) 3g、に対して、実施例では lg (無投与の 5%)と抑制効果が認められた 図 4から明らかなように、実施例 2のァガリタスを内包するリボソーム製剤 1を含む水 を自由摂取させたマウスは、 19日目力 がん細胞の成長が徐々に認められ、 35日 目に 27gになった力 生存していた。  On the 19th day, the amount of cancer cells was 20g without administration, ribosome alone (Comparative Example 1) 15g, only agaritas (Comparative Example 2) 3g, and in the Examples, lg (5% without administration), and the suppressive effect As can be seen from FIG. 4, mice that freely ingested water containing ribosome formulation 1 containing fragritas in Example 2 showed a gradual growth of cancer cells on the 19th day. 27 g of eyes were alive.

[0042] 比較例 1のイカ由来の DHA (オメガ 3)リン脂質リボソームを含む水を自由摂取さ せたマウスは、 12日目力もがん細胞の成長が認められ、 19日目で死亡し、そのとき のがん細胞の重量は 30gであった。  [0042] Mice that were given free access to water containing DHA (omega 3) phospholipid ribosome derived from squid in Comparative Example 1 showed growth of cancer cells on day 12 and died on day 19, The weight of the cancer cell at that time was 30 g.

[0043] 比較例 2のァガリタスを含む水を自由摂取させたマウスは、 13日目からがん細胞の 成長が徐々に認められ、 35日目には 40gになったが、生存していた。  [0043] Mice that were freely ingested with water containing agaritas of Comparative Example 2 showed gradually growing cancer cells from day 13 and reached 40 g on day 35, but survived.

[0044] 一方、組成物を何も投与しない無投与の場合には、 12日目からがん細胞の成長が 認められ、 19日目で死亡し、そのときのがん細胞の重量は 38gであった。  [0044] On the other hand, in the case of no administration without administration of any composition, the growth of cancer cells was observed from the 12th day and died on the 19th day, and the weight of the cancer cells at that time was 38g. there were.

[0045] 上記実施例 2及び比較例によれば、 19日目に死亡した無投与や比較例 1に対して 、比較例 2、実施例 2の順に、がん細胞の成長が遅くなり、明瞭にがん細胞成長抑制 効果が認められた。さらに、実施例 2のァガリタスを内包するリボソーム製剤 1の場合 には、比較例 2のァガリタス単独投与の場合よりもさらに、がん細胞成長抑制効果が 認められた。また、比較例 1のイカ由来の DHA (オメガ—3)結合リン脂質リボソーム のみ力もなる糸且成物の場合には、無投与の場合に比較して、がん細胞の成長が遅い ことが分力つた。 [0045] According to the above Example 2 and Comparative Example, the growth of cancer cells was slowed in the order of Comparative Example 2 and Example 2 in comparison with no administration and Comparative Example 1 that died on the 19th day. The cancer cell growth inhibitory effect was observed. Furthermore, in the case of the ribosome preparation 1 encapsulating agaritas of Example 2, the cancer cell growth inhibitory effect is further enhanced than the case of the administration of agaritas alone of Comparative Example 2. Admitted. In addition, it was found that the growth of cancer cells was slower in the case of the thread and adult product that only the DHA (omega-3) -bound phospholipid ribosome derived from squid in Comparative Example 1 was used. I helped.

実施例 3  Example 3

[0046] 実施例 3では、機能性物質 3としてコェンザィム Q10 (日清フアルマ製)を用いた以 外は、実施例 2と同様にして、機能性物質を内包するリボソーム製剤 1を調製した。 全量で 25mgの実施例 3の機能性素材を分散させた飲料(100cm3 )を健常人男 性 3名に飲ませた。 [0046] In Example 3, a ribosome preparation 1 containing a functional substance was prepared in the same manner as in Example 2, except that Coenzyme Q10 (manufactured by Nisshin Faluma) was used as the functional substance 3. A total of 25 mg of a drink (100 cm 3 ) in which the functional material of Example 3 was dispersed was given to 3 healthy males.

比較例として、健常人 3名に、ノィキノン lOmg錠 (エーザィ株式会社製のコェンザ ィム Q 10製剤) 10錠を単回経口投与した。この場合のコェンザィム Q 10の投与量は lOOmgである。両群より経時的に採血して、血漿注のコェンザィム Q10濃度を測定 した。実施例 3群および比較例群とも血漿中のコェンザィム Q10濃度の経時変化力 ーブはほぼ同一であった。両群ともに投与 6時間後に最高血漿中濃度 (0. 55 - 0. 70 μ g/cm )に達し、以後緩やかに減少した。  As a comparative example, 10 healthy tablets were administered orally once with 10 quinone lOmg tablets (Coenzyme Q 10 preparation from Eisai Co., Ltd.). In this case, the dose of Coenzyme Q 10 is lOOmg. Blood was collected from both groups over time, and the Coenzyme Q10 concentration in plasma injections was measured. The time course of the Coenzyme Q10 concentration in plasma was almost the same in the Example 3 group and the Comparative group. In both groups, the maximum plasma concentration (0.55-0.70 μg / cm) was reached 6 hours after administration, and then gradually decreased.

以上により、実施例 3のコェンザィム Q 10を有用リン脂質に内包させた機能性素材 1を含有させた飲料は、巿販コェンザィム Q10製剤(ノィキノン)の 1Z4の量で、効率 良く体内に取り込まれ、コェンザィム Q10の血漿中濃度を高めることができた。 実施例 4  As described above, the beverage containing the functional material 1 in which Coenzyme Q10 of Example 3 is encapsulated in useful phospholipid is efficiently taken into the body in the amount of 1Z4 of the commercial Coenzyme Q10 preparation (Nyquinone), We were able to increase the plasma concentration of Coenzyme Q10. Example 4

[0047] 後述するホタテ由来のリン脂質を用いた以外は実施例 2と同様にして、実施例 4の 有用リン脂質を含む機能性素材 1の調製を行った。  [0047] The functional material 1 containing the useful phospholipid of Example 4 was prepared in the same manner as in Example 2 except that the scallop-derived phospholipid described later was used.

[0048] 上記ホタテ由来のリン脂質は以下のようにして調製した。  [0048] The scallop-derived phospholipid was prepared as follows.

出発原料としてホタテゥロを用い、実施例 4の有用リン脂質組成物を製造した。出発 原料のホタテゥ口の重量は 1000kgであり、一応の水切りはしてあるが特に乾燥して いない状態 (以下、湿潤基準と呼ぶ)である。その内訳は、固形分 23重量%で、水分 力 S770kgである。この固形分中の蛋白質は、ホタテゥ口の場合には約 13. 5%程度 である。  A useful phospholipid composition of Example 4 was produced using scallop as a starting material. The starting material has a scallop mouth weight of 1000kg, which has been drained for a while but not particularly dry (hereinafter referred to as the wet standard). The breakdown is 23% by weight solids and water strength S770kg. The protein in this solid content is about 13.5% in the case of scallop mouth.

最初に、出発原料を連続的に投入し、第 1の蒸煮工程及び第 2の固液分離工程を 連続して行なった。具体的には、出発原料 1に水 2000リットルをカ卩え、スチームジャ ケット加熱式連続蒸煮管で、 95〜100°C、 20分の滞留時間で加熱煮沸した。 First, the starting materials were continuously added, and the first steaming process and the second solid-liquid separation process were continuously performed. Specifically, 2000 liters of water is added to starting material 1 and steam jar is added. It was heated and boiled at a temperature of 95-100 ° C and a residence time of 20 minutes in a continuous heating tube.

[0049] 続いて、第 2の固液分離工程として、連続式遠心分離機に通し、 2000Gの回転を 掛け、固形物及び液相を得た。この液相は廃棄物として回収した。この工程で得た固 形物の重量は 470kgあり、カールフィッシャー測定により含水量は 61. 7重量%であ つた o [0049] Subsequently, as a second solid-liquid separation step, it was passed through a continuous centrifuge and subjected to rotation of 2000G to obtain a solid and a liquid phase. This liquid phase was recovered as waste. The weight of the solid material obtained in this process was 470 kg, and the water content was 61.7% by Karl Fischer measurement.

[0050] 有機溶剤抽出工程として、上記固形物のうち 100kg (乾燥固形分約 38kg)を、ステ ンレススティール製の円筒状抽出装置(直径 0. 5m、高さ 1. 5m、容量 200リットル) に充填し、 95%エタノール 300リットルを流通速度 100リットル Z時で流通して抽出 操作を行なった。最後に、空気で残留液相を押出して、これも有機溶剤抽出液に加 え、約 400リットルの有機溶剤抽出液を得た。このときに得られた抽出残渣固形物は 、 35kgであった。  [0050] As an organic solvent extraction process, 100 kg of the above solids (about 38 kg of dry solids) was extracted from a stainless steel cylindrical extraction device (diameter 0.5 m, height 1.5 m, capacity 200 liters). The extraction operation was performed by circulating 300 liters of 95% ethanol at a circulation rate of 100 liters Z. Finally, the residual liquid phase was extruded with air, and this was added to the organic solvent extract to obtain about 400 liters of the organic solvent extract. The solid residue of the extraction residue obtained at this time was 35 kg.

[0051] 第 4工程として、約 400リットルの有機溶剤抽出液を、 50°C、 650mmHg (約、 8. 7  [0051] As the fourth step, about 400 liters of the organic solvent extract was added to 50 ° C, 650 mmHg (about, 8.7

X 104 Pa)で減圧蒸留して有機溶剤を除去回収した。ここで得られた抽出液は、褐 色粘ちような液体で、その重量は 15. 5kgであった。 X 10 4 Pa) under reduced pressure to remove and recover the organic solvent. The extract obtained here was a brown sticky liquid, and its weight was 15.5 kg.

[0052] 第 5工程として、上記抽出液を直径 50cm、高さ 1. 5mのステンレススティール製ク 口マトカラムに通した。クロマトカラム中には、シリカゲルを充填してある。粒径 250 /z πι〜500 /ζ πιのシリカゲル(ヒシゲル、洞海化学製)を用いた。分離には 95重量%ェ タノールで展開した。流出液相のうち、濃黒褐色の初期画分を分離廃棄し、その後 淡褐色になった流出液相を目的画分として回収した。  [0052] As the fifth step, the extract was passed through a stainless steel cup-top column having a diameter of 50 cm and a height of 1.5 m. The chromatographic column is packed with silica gel. Silica gel (Hishigel, manufactured by Dokai Chemical Co., Ltd.) having a particle size of 250 / z πι to 500 / ζ πι was used. Separation was developed with 95 wt% ethanol. Of the effluent phase, the dark black-brown initial fraction was separated and discarded, and then the effluent phase that became light brown was collected as the target fraction.

[0053] 次に、第 6工程として、上記精製液から、第 4工程と同条件でエタノールを蒸留除去 すると、有用リン脂質組成物として油相 7. 8kgを得た。この有用リン脂質組成物は、 黒褐色の外観とオイル状の性状とを呈して 、た。  [0053] Next, in the sixth step, ethanol was distilled off from the purified solution under the same conditions as in the fourth step to obtain 7.8 kg of an oil phase as a useful phospholipid composition. This useful phospholipid composition had a black-brown appearance and an oily appearance.

[0054] 実施例 1及び 2と同様に、マウスへの飲料水添加試験を行なった。その結果、 19日 目のがん細胞量は、実施例 4、比較例 1、比較例 2、無投与の場合、それぞれ、 1. 2g 、 30g、 4g、 39gとなった。実施例 4の場合には、がん細胞量は無投与の 3%と非常 に小さぐ高いがん細胞抑圧効果を示した。  [0054] In the same manner as in Examples 1 and 2, a drinking water addition test to mice was performed. As a result, the amount of cancer cells on day 19 was 1.2 g, 30 g, 4 g, and 39 g in Example 4, Comparative Example 1, Comparative Example 2, and no administration, respectively. In the case of Example 4, the amount of cancer cells was as small as 3% with no administration, showing a very high cancer cell suppression effect.

[0055] 上記実施例 1〜4及び比較例 1、 2から、本発明の有用リン脂質組成物を含む機能 性素材は、高 、がん細胞抑圧効果を示すことが判明した。 本発明は、上記実施例に限定されることなぐ特許請求の範囲に記載した発明の 範囲内で種々の変形が可能であり、それらも本発明の範囲内に含まれることはいうま でもない。例えば、上記機能性物質を内包するリボソーム製剤の製造工程における p Hや、クロマト法による精製工程のクロマトカラムなどは、適宜に設計でき、また、魚介 類の部位は、上記実施例のホタテやイカ由来に限らな 、ことは 、うまでもな!/、。 [0055] From Examples 1 to 4 and Comparative Examples 1 and 2, it was found that the functional material containing the useful phospholipid composition of the present invention has a high cancer cell suppressing effect. The present invention can be variously modified within the scope of the invention described in the claims without being limited to the above embodiments, and it goes without saying that these are also included in the scope of the present invention. For example, the pH in the production process of the ribosome preparation encapsulating the functional substance, the chromatographic column in the purification process by the chromatographic method, and the like can be designed as appropriate. It ’s not only the origin, but it ’s a natural thing! /.

Claims

請求の範囲 The scope of the claims [1] オメガ— 3高度不飽和脂肪酸結合リン脂質を含む有用リン脂質組成物と機能性物 質とを有効成分としたことを特徴とする、有用リン脂質組成物を含む機能性素材。  [1] A functional material containing a useful phospholipid composition, comprising a useful phospholipid composition containing omega-3 highly unsaturated fatty acid-binding phospholipid and a functional substance as active ingredients. [2] オメガ— 3高度不飽和脂肪酸結合リン脂質を含む有用リン脂質組成物力もなるリポ ノームと、機能性物質と、から成り、 [2] Omega-3, a useful phospholipid composition containing highly unsaturated fatty acid-binding phospholipids, and a functional substance. 上記機能性物質を、上記リボソーム内に内包したことを特徴とする、有用リン脂質組 成物を含む機能性素材。  A functional material containing a useful phospholipid composition, wherein the functional substance is encapsulated in the ribosome. [3] 前記オメガ 3高度不飽和脂肪酸結合リン脂質が、リン脂質中にエステル結合する 脂肪酸の 10重量%以上、好ましくは 20重量%以上が DHA (ドコサへキサェン酸)及 び Z又は EPA (エイコサペンタエン酸)であることを特徴とする、請求項 1又は 2に記 載の有用リン脂質組成物を含む機能性素材。 [3] The omega-3 polyunsaturated fatty acid-binding phospholipid is not less than 10% by weight, preferably not less than 20% by weight, of DHA (docosahexaenoic acid) and Z or EPA A functional material comprising the useful phospholipid composition according to claim 1 or 2, wherein the functional material is icosapentaenoic acid. [4] 前記オメガ— 3高度不飽和脂肪酸結合リン脂質が、エステル交換によってオメガ—[4] The omega-3 highly unsaturated fatty acid-binding phospholipid is converted to omega- 3高度不飽和脂肪酸含有量を高めた有用リン脂質組成物であることを特徴とする、請 求項 3に記載の有用リン脂質組成物を含む機能性素材。 3. A functional material containing the useful phospholipid composition according to claim 3, which is a useful phospholipid composition having a high content of highly unsaturated fatty acids. [5] 前記機能性物質が機能性食品素材であることを特徴とする、請求項 1又は 2に記載 の有用リン脂質組成物を含む機能性素材。 [5] The functional material containing the useful phospholipid composition according to claim 1 or 2, wherein the functional substance is a functional food material. [6] 前記機能性物質が医薬品素材であることを特徴とする、請求項 1又は 2に記載の有 用リン脂質組成物を含む機能性素材。 [6] The functional material comprising the useful phospholipid composition according to claim 1 or 2, wherein the functional substance is a pharmaceutical material. [7] 前記機能性物質が、ァガリタスであることを特徴とする、請求項 1又は 2に記載の有 用リン脂質組成物を含む機能性素材。 [7] The functional material containing a useful phospholipid composition according to claim 1 or 2, wherein the functional substance is Agaritas. [8] 前記機能性物質が、コェンザィム Q 10であることを特徴とする、請求項 1又は 2に記 載の有用リン脂質組成物を含む機能性素材。 [8] The functional material containing the useful phospholipid composition according to claim 1 or 2, wherein the functional substance is Coenzyme Q10. [9] 前記オメガ 3高度不飽和脂肪酸結合リン脂質が水産生物由来であり、該水産生 物力 魚卵、水産動物の生殖巣、イカ、ホタテ貝、ヒトデ、海藻、微生物の何れかであ ることを特徴とする、請求項 1又は 2に記載の有用リン脂質組成物を含む機能性素材 [9] The omega-3 polyunsaturated fatty acid-binding phospholipid is derived from an aquatic product, and is any of the aquatic product, fish egg, marine animal gonad, squid, scallop, starfish, seaweed, or microorganism. A functional material comprising the useful phospholipid composition according to claim 1 or 2, [10] 請求項 1〜9の何れか〖こ記載の有用リン脂質組成物を含む機能性素材を、添加し たことを特徴とする、機能性食品。 [11] 前記機能性食品が、飲料であることを特徴とする、請求項 10に記載の機能性食 [10] A functional food comprising a functional material containing the useful phospholipid composition according to any one of [1] to [9]. [11] The functional food according to claim 10, wherein the functional food is a beverage.
PCT/JP2006/320670 2005-10-17 2006-10-17 Functional material and functional food comprising useful phospholipid composition Ceased WO2007046386A1 (en)

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