WO2015046563A1 - Soft capsule containing dha and epa - Google Patents

Soft capsule containing dha and epa Download PDF

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Publication number
WO2015046563A1
WO2015046563A1 PCT/JP2014/076042 JP2014076042W WO2015046563A1 WO 2015046563 A1 WO2015046563 A1 WO 2015046563A1 JP 2014076042 W JP2014076042 W JP 2014076042W WO 2015046563 A1 WO2015046563 A1 WO 2015046563A1
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WO
WIPO (PCT)
Prior art keywords
oil
fish oil
epa
dha
soft capsule
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PCT/JP2014/076042
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French (fr)
Japanese (ja)
Inventor
秀爾 遠藤
Original Assignee
サントリーホールディングス株式会社
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Filing date
Publication date
Application filed by サントリーホールディングス株式会社 filed Critical サントリーホールディングス株式会社
Priority to JP2015539453A priority Critical patent/JP6450317B2/en
Priority to CN201480065091.5A priority patent/CN105764499A/en
Publication of WO2015046563A1 publication Critical patent/WO2015046563A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A61K31/36—Compounds containing methylenedioxyphenyl groups, e.g. sesamin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/60—Fish, e.g. seahorses; Fish eggs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A61K9/4825—Proteins, e.g. gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the present invention relates to a soft capsule containing docosahexaenoic acid and eicosapentaenoic acid at a high concentration and further containing other health ingredients.
  • Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) contained in fish oil such as blue fish are known to have preventive effects on lifestyle-related diseases such as arteriosclerosis and hyperlipidemia, and improve learning functions. Yes.
  • the preferred daily intake of EPA and DHA for those 18 years and older is 1 g or more.
  • the consumption of Japanese seafood such as blue fish is decreasing, and fewer people are taking the desired amount of EPA and DHA.
  • supplements containing DHA and EPA are commercially available.
  • DHA and EPA supplements are components contained in fish oil that is liquid at room temperature, and may have a peculiar odor of fish oil, and are susceptible to deterioration due to oxidation and are lost at the processing stage. Therefore, a soft capsule form that can contain the DHA / EPA-containing fish oil as it is without a complicated process is preferable.
  • the applicant manufactured a supplement (weighing 415 mg per capsule) containing 4 mg soft capsules, 300 mg DHA, 100 mg EPA, sesamin, a rare health ingredient contained in sesame, and vitamin E having an antioxidant effect, As of the end of February 2012, it has been enjoyed by many customers, including a cumulative total of over 1 million. The applicant has been continually studying to further improve the health function of the above supplement.
  • supplements can be improved daily by daily consumption.
  • it is easy for consumers to take solutions, small granules).
  • Tablets or capsules convenience in carrying and storage (tablets, capsules, etc.), low price, etc. are desirable factors.
  • it is desirable from the viewpoint of ease of daily drinking that a desired amount of health ingredients can be taken in as few grains as possible.
  • some supplement users may take several kinds of supplements a day (for example, 10 or more), but more kinds of health ingredients in one supplement, If there is something that contains a larger amount, it may be possible to reduce the number (type) of supplements and the number of grains taken in a day, which is desirable.
  • the applicant in the above-mentioned supplement (soft capsule), the amount of health ingredients (DHA 300 mg, EPA 100 mg, sesamin, vitamin E per 4 capsules) contained in the supplement is still unchanged, and a new health Consider adding ingredients.
  • DHA 300 mg, EPA 100 mg, sesamin, vitamin E per 4 capsules the amount of health ingredients contained in the supplement is still unchanged, and a new health Consider adding ingredients.
  • DHA and EPA are obtained as liquid oil (refined fish oil) at room temperature and have a certain volume (volume), so in a so-called “container” having a certain capacity such as soft capsules.
  • a so-called “container” having a certain capacity such as soft capsules.
  • the present invention softens other health ingredients (especially those having a certain volume such as oil) while maintaining the amount of DHA and EPA contained in existing products without increasing the size of the capsule.
  • the purpose is to provide a technology that can be encapsulated inside to increase the value as a supplement of soft capsules, or to enhance health functions while maintaining ease of drinking (size, number of grains per day) To do.
  • the present invention includes the following aspects. 1.
  • the total weight of the soft capsule (the total content of the internal volume and the capsule film) is 380 mg to 420 mg. 6).
  • the oil other than fish oil that is liquid at room temperature comprises rice germ oil, linseed oil, sesame oil, olive oil, sesame oil, or a mixture of two or more thereof.
  • the soft capsule contains 20 mg or more of oil other than fish oil that is liquid at normal temperature per capsule. 8).
  • the soft capsule contains 20 to 60 mg of oil other than fish oil that is liquid at normal temperature per capsule. 9.
  • additional health ingredients are further contained in the soft capsule. It can be contained, and the value as a supplement of a soft capsule can be increased. Specifically, since the size per grain is relatively small, it is easy to take, and since additional health ingredients are included in addition to DHA and EPA, further health effects can be expected. In addition, since the content of health ingredients per grain is high, the number of grains taken per day is relatively small (4 as a guide). It is beneficial for health-conscious consumers that the supplement contains many types of health ingredients.
  • the fact that the number of grains taken per day is small, in addition to the advantage that consumers can easily take, in addition to the products (for example, for one month) in supplements that are usually packed and sold in containers in units of one month.
  • the size of the container containing the supplement is not increased, which is advantageous for both consumers and sellers during transportation and storage.
  • the number of soft capsules to be taken per day is small, the corresponding amount It is considered that the daily intake of components other than health components such as the film of this skin is reduced, which is preferable.
  • the present invention contains a fish oil containing a specific amount or more of docosahexaenoic acid and eicosapentaenoic acid, and further contains a liquid oil at room temperature other than the fish oil (ie, a liquid contained in the capsule).
  • the present invention relates to a method for producing soft capsules having an amount of 220 to 260 mg.
  • One of the features of the method of the present invention is to use oil concentrated so that the content of docosahexaenoic acid is 50% or more.
  • Docosahexaenoic acid is an unsaturated fatty acid of the molecular formula C 22 H 32 O 2 .
  • Eicosapentaenoic acid is an unsaturated fatty acid molecular formula C 20 H 30 O 2. All of these are known to be contained in a large amount in fish oil (for example, sardine oil: DHA 12%, EPA 17%, tuna oil: DHA 25%, EPA 7%, skipjack oil: DHA 24%, EPA 5%, salmon oil: DHA14 %, EPA 9%).
  • the contents of DHA and EPA are not only the amounts of DHA and EPA as free fatty acids, but also the amounts of DHA and EPA in the form of triglycerides, diglycerides, or monoglycerides (converted to the amount of free fatty acids). Shall also be included.
  • the respective contents or contents of DHA and EPA in fish oil can be measured using GC (gas chromatography) as shown in detail in the following examples.
  • Examples of the method for concentrating DHA and EPA in fish oil include a method of removing fatty acids other than a desired fatty acid using a lipase having a substrate specificity, and such methods have been reported in various ways (for example, JP-A-8-214891, JP-2002-136298, JP4530311, JP5204776, JP2013-55893).
  • purified fish oil having a desired concentration by any method can be used. Since DHA and EPA are easily oxidized components, it is important to use oil obtained from fresh fish as fish oil.
  • the type of fish is not particularly limited, but oils obtained from tuna, bonito, sardines, mackerel, saury, horse mackerel, squid, cod and the like are preferable because they contain abundant DHA and EPA.
  • EPA refined fish oil with an EPA content of 15% or more is used.
  • fish oil EPA refined concentrated fish oil
  • a purified product or a concentrated refined fish oil can be appropriately used as the EPA refined fish oil.
  • the upper limit value in the EPA concentrated and refined fish oil is not particularly limited, but the content of EPA in the EPA concentrated and refined fish oil purified by the above method is considered to be about 30% at the maximum.
  • DHA DHA concentrated refined fish oil
  • DHA concentration in the DHA-concentrated and refined fish oil has been increased to about 75%.
  • concentration of EPA contained in the DHA-concentrated and refined fish oil decreases, making it difficult to supplement the amount of EPA required in the soft capsule from the DHA-concentrated and refined fish oil.
  • fish oil obtained by concentrating DHA at a high concentration is expensive.
  • the upper limit of the DHA content should be about 70%, preferably up to about 60%.
  • DHA-concentrated and refined fish oil concentrated so that the DHA content is in the range of 50% to 60% EPA with a content of 5% or more, preferably about 5% to 8% remains.
  • EPA from EPA refined fish oil a predetermined amount of EPA to be contained in the soft capsule can be achieved.
  • DHA concentrated refined fish oil having a DHA content of 53% to 58% and / or an EPA content of 6.5% to 7% can be suitably used.
  • DHA concentrated and refined fish oil and EPA refined fish oil may be stirred and mixed while passing through a net of about 100 mesh to 120 mesh as necessary and kept at an appropriate temperature. If the temperature is too high, DHA and EPA may deteriorate. Preferably, it is in the range of 30 to 40 ° C. Further, the stirring should be performed so as not to involve oxygen as much as possible in the fish oil, and is preferably performed while blowing nitrogen.
  • the soft capsule of the present invention 75 mg or more of DHA is contained per grain, and more preferably 25 mg or more of EPA. This is an amount of 4 soft capsules to give 300 mg DHA and 100 mg EPA.
  • the preferred daily intake of EPA and DHA for those over 18 years old is 1 g or more, but the group with the lowest EPA and DHA intake ( (18-29 year old female) has a daily intake of 188 mg, and the most common group (70 year old male) is 775 mg.
  • EPA and DHA currently do not reach the desired amount per day for each generation of men and women.
  • the soft capsule of the present invention plays a role in assisting ingestion of EPA and DHA.
  • the upper limit of daily intake of EPA and DHA is not calculated in the “Japanese dietary intake standard” (2010 edition). However, it is important to keep an appropriate amount of any substance, because an extremely large amount can cause health problems.
  • DHA and EPA By taking DHA and EPA in appropriate amounts every day, it has a wide range of effects such as cardiovascular risk reduction, triglyceride reduction, rheumatoid arthritis symptom reduction, age-related macular degeneration risk reduction, cognitive function reduction suppression It is known to be obtained.
  • the soft capsule of the present invention is further blended with a liquid oil at room temperature other than fish oil, particularly one having a health function.
  • a liquid oil at room temperature other than fish oil particularly one having a health function.
  • DHA-concentrated and refined fish oil condensed to a specific concentration is combined with EPA-purified fish oil, so that a predetermined amount or more of DHA and EPA are contained in a soft capsule having a certain volume, We found that oils with health functions can also be added.
  • the oil at room temperature suitable for blending in the soft capsule of the present invention is not particularly limited as long as it has a health function.
  • rice germ oil linseed oil, sesame sesame oil, olive oil, sesame oil, or The thing etc. which mixed these are mentioned.
  • Rice germ oil is one preferred oil.
  • Rice germ oil is a fatty oil extracted from rice germ and is usually said to contain about 1.0 to 1.5 w / w% of ⁇ -oryzanol.
  • Rice germ oil contains, for example, ORIZA oil S-1 (Ichimaru Falcos Co., Ltd.) containing 1.2 to 1.5 w / w% of ⁇ -oryzanol and 1.0 to 1.5 w / w% of ⁇ -oryzanol.
  • ORIZA oil S-1 Ichimaru Falcos Co., Ltd.
  • rice germ oil PRO-15 Tsukino Food Industry Co., Ltd.
  • ⁇ -oryzanol refers to a generic name of ferulic acid in which triterpene alcohol or sterol is ester-bonded.
  • triterpene alcohol include cycloartol, 2,4-methylenecycloartanol, and cycloartanol.
  • cyclobranol examples of the sterol include campesterol, stigmasterol, and ⁇ -sitosterol.
  • ⁇ -Oryzanol may be a mixture of these compounds or a single compound.
  • ⁇ -Oryzanol has blood neutral lipid lowering action (Geriant. Med.
  • the sample is dissolved in heptane and the absorbance is measured at the maximum wavelength of absorption near 315 nm as described in “Standards for raw materials of quasi drugs” and “Voluntary standards for food additives other than chemically synthesized products”. Can be quantified.
  • ⁇ -oryzanol concentrated may be used as the rice germ oil.
  • the content of ⁇ -oryzanol in the concentrated oil is preferably 2 w / w% or more, and more preferably 30 w / w% or more.
  • Such a concentrated oil of ⁇ -oryzanol can be industrially obtained by extraction with an organic solvent or purification after resin treatment, such as rice germ oil gamma 30 (Tsukino Food Industry Co., Ltd.) , ⁇ -oryzanol, oryzadorim V-50, rice bran oil, brown rice germ oil (Oryza Oil Co., Ltd.).
  • the content of rice germ oil in the soft capsule can be measured by using the sterol content characteristically contained in rice germ oil or rice germ oil concentrate and the content ratio of various sterols as an index.
  • the preferred blending amount of rice germ oil is 1 to 40 mg, more preferably 1 to 20 mg, and most preferably 5 to 10 mg per soft capsule of the present invention.
  • the preferred amount of ⁇ -oryzanol is 0.3 to 12 mg, more preferably 0.3 to 6 mg, and most preferably 1.5 to 3 mg per soft capsule of the present invention.
  • Oils other than fish oil that is liquid at room temperature can be blended preferably in an amount of 20 mg or more per soft capsule of the present invention. More preferably, it is 20 to 60 mg, and more preferably 40 to 60 mg. Such oils can be mixed together when mixing DHA concentrated refined fish oil and EPA refined fish oil.
  • oils-soluble health ingredients such as sesamin, episesamin, sesaminol, episesaminol, sesamorin, ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, tocopherol esters (such as tocopherol acetate), carotenoids such as ⁇ -carotene, canthaxanthin, astaxanthin, flavone derivatives, phyllosilsins, kojic acid, gallic acid derivatives, catechins, fucic acid, gossypol, pyrazine Natural antioxidants such as derivatives, sesamol, guaiaol, guaiacic acid,
  • Sesamin is a kind of lignan compound contained in sesame seeds, blood cholesterol lowering action and blood neutral lipid lowering action, liver function improving action, active oxygen scavenging action, ⁇ 5 desaturase inhibiting action, peroxidation
  • Various physiological activities such as an adipogenesis inhibitory action, an antihypertensive action, a sickness prevention action, and a breast cancer inhibitory action have been reported.
  • sesamin is a general term for a series of compounds including sesamin and its analogs.
  • sesamin for example, the above-mentioned sesamin, episesamin, sesaminol, episesaminol, sesamoline and the like are included, and these stereoisomers or racemates can be used alone or in combination.
  • metabolites of sesamin compounds for example, described in JP-A-2001-139579
  • sesamin compounds can be used as sesamin compounds in the present specification as long as they have an effect.
  • Sesamin is not limited by its form or production method.
  • commercially available sesame oil (liquid) can be used as it is, or sesamin extracted from sesame oil by a known method (for example, the method described in JP-A-4-9931) Sesamin extract or concentrate) can also be used.
  • the sesamin extract may be made tasteless and odorless by known means, for example, activated clay treatment.
  • the degree of concentration in the sesamin concentrate may be appropriately set according to the type of sesamin used, etc., but usually the sesamin concentrate concentrated so that the total amount of sesamin is 1 w / w% or more. Is preferably used.
  • the total sesamin content in the sesamin concentrate is preferably 20 w / w% or more, more preferably 50 w / w% or more, further preferably 70 w / w% or more, and concentrated (purified) to 90 w / w% or more. The one is the best.
  • the content of sesamin can be measured using any known method such as HPLC. Regarding the HPLC method, for example, the method described in JP2009-155531A can be referred to.
  • the applicant has found that the physiological action of sesamin, for example, anti-fatigue action is remarkably increased by using ⁇ -oryzanol (included in rice germ oil) together with sesamin (Japanese Patent Application Laid-Open (JP-A) No. 2009). No. 073749). Furthermore, the applicant has found that combining sesamin with ⁇ -oryzanol (contained in rice germ oil) promotes in vivo absorption of sesamin (Japanese Patent Application No. 2012-135034). (See International Publication No. 2013/187391)). Therefore, it is preferable to add a combination of sesamin and ⁇ -oryzanol (or rice germ oil) in the soft capsule of the present invention.
  • the most preferred example of inclusion in the soft capsule of the present invention includes a combination of purified fish oil containing DHA and EPA, rice germ oil (including ⁇ -oryzanol), sesamin, and vitamin E.
  • the preferred blending amount of sesamin is 0.1 to 10 mg, more preferably 1 to 5 mg per soft capsule of the present invention.
  • the preferred amount of vitamin E is 0.35 to 20 mg, more preferably 7 to 18 mg, and most preferably 7 to 11 mg per soft capsule of the present invention.
  • Sesamin and vitamin E may be added when mixing fish oil and liquid oil other than fish oil and dissolved in these oils, or the oil mixing step It may be dissolved in advance in fish oil and / or oil other than fish oil.
  • vitamin E is commercially available as a vitamin E-containing oil.
  • the preferred amount of the vitamin E-containing oil depends on the content of vitamin E in the oil, but is, for example, 1 to 50 mg, more preferably 20 to 50 mg, most preferably, per soft capsule of the present invention. 30-50 mg.
  • Soft capsules are, as prescribed by the Japanese Pharmacopoeia, “A combination of active ingredients with an appropriate capsule base such as gelatin with increased plasticity by adding glycerin or D-sorbitol, etc. "Encapsulated in the shape of”.
  • the capsule base material (capsule film material) and the encapsulation method are not particularly limited, and ordinary materials and methods may be used.
  • gelatin with increased plasticity by adding glycerin or D-sorbitol may be used as a coating material, and capsule coating using a punching method (rotary die) or the like. May be formed and the contents may be filled.
  • the shape and size of the soft capsule are not particularly limited, and are set in consideration of the amount of capsule contents and ease of swallowing by consumers.
  • Soft capsule shapes include oval (oval), oblong (oblong), spherical (round), slender, special (triangle, heart, rhombus, etc.), but slender (
  • the shape (sometimes referred to as a drop shape) is preferable because it is easy to swallow and is easy to handle for consumers because it is difficult to roll when taken out of the container.
  • the size of the soft capsule is preferably about 17 mm or less for the major axis and about 8 mm or less for the minor axis in consideration of ease of drinking.
  • the lower limit of the soft capsule size (major axis, minor axis) varies depending on the amount of capsule contents.
  • the amount of content (weight other than capsule film) contained in one soft capsule of the present invention is in the range of 220 mg to 260 mg. If the internal volume is small, it will be difficult to take the desired amount of healthy ingredients in 4 capsules per day. If the internal volume is too large, the overall size of the capsule will become too large and consumed. It is not preferable because it becomes difficult for a person to swallow.
  • the total weight per soft capsule is not limited, but considering the desired amount of health ingredients, ease of swallowing, capsule film strength, etc., 380 mg About 420 mg is preferable.
  • the soft capsule of the present invention may be provided with a display regarding the function after being packed in a bottle container or the like.
  • a display regarding the function There are no particular restrictions on the method of displaying the function, but examples include display on food packaging, container surfaces, food instructions, food advertisements, and the like.
  • the functions of the soft capsule of the present invention include cardiovascular risk reduction, neutral fat reduction action, rheumatoid arthritis symptom reduction action, age-related macular degeneration development risk reduction, cognitive function reduction suppression effect, and the like.
  • Table 1 shows the difference in DHA content and EPA content in the DHA-concentrated and refined fish oil depending on the degree of concentration. Fish oil was collected from the tuna head, and DHA was concentrated by a method of removing fatty acids other than DHA using lipase.
  • the amount of DHA and EPA in fish oil was measured according to the following method: A. Pretreatment of sample When fish oil was contained in a soft capsule, the content liquid was taken out with a syringe with an injection needle or the like and subjected to measurement.
  • Example 1 Using the aforementioned fish oil, the contents for soft capsules were prepared by stirring and mixing under heating in accordance with the composition shown in Table 2 below (unit per mg of soft capsule).
  • Commercially available purified concentrated fish oil was used as the EPA concentrated purified fish oil.
  • Commercial products were also used for vitamin E-containing oil and rice germ oil.
  • water was added to 100 parts by weight of gelatin and 30 parts by weight of dietary glycerin and dissolved at 50 to 60 ° C. to prepare a base material for soft capsule film.
  • the weight of the film per one soft capsule obtained was 160 mg (gelatin 123 mg, glycerin 37 mg).
  • the total weight (per capsule) of the soft capsules was 398 mg for the reference product and 395 mg for the product of the present invention, and the sizes were 15 mm for the major axis and 7 mm for the minor axis.
  • Both the reference product and the product of the present invention contained 300 mg or more of DHA, 100 mg or more of EPA, 10 mg or more of sesamin, and 40 mg or more of vitamin E per 4 grains. In addition to these, the product of the present invention further contained 10 mg or more of ⁇ -oryzanol.
  • the fish oil concentrated so that the DHA content is 50% or more is combined with the EPA refined fish oil without increasing the weight per capsule of the reference product.
  • rice germ oil including ⁇ -oryzanol as a health ingredient
  • Example 2 Using the aforementioned fish oil 3, soft capsules having a content weight of 220 to 260 mg and a preparation weight of 380 to 420 mg were produced according to the composition shown in Table 3 below (unit: mg per soft capsule).
  • Commercially available EPA refined fish oil, vitamin E-containing oil and rice germ oil were used. The production method was in accordance with Example 1.
  • Each of the obtained soft capsules contained 300 mg or more of DHA and 100 mg or more of EPA per 4 capsules. In addition, about 20 to 60 mg of oil other than liquid fish oil was contained per capsule, and the size was easy to take.

Abstract

Without increasing the size of an existing capsule product, a further health-promoting component is sealed into the soft capsule while maintaining the DHA and EPA content of the existing product. A fish oil concentrated such that the content of docosahexaenoic acid is greater than or equal to 50% and a fish oil containing greater than or equal to 15% eicosapentaenoic acid are used, and these are mixed with the other health-promoting component, which is an oil that is liquid at room temperature.

Description

ＤＨＡ及びＥＰＡを含む軟カプセルSoft capsule containing DHA and EPA
　本発明は、ドコサヘキサエン酸とエイコサペンタエン酸とを高濃度に含有し、さらに他の健康成分を含有する軟カプセルに関する。 The present invention relates to a soft capsule containing docosahexaenoic acid and eicosapentaenoic acid at a high concentration and further containing other health ingredients.
　青魚などの魚油に含まれるドコサヘキサエン酸（ＤＨＡ）及びエイコサペンタエン酸（ＥＰＡ）は、動脈硬化や高脂血症などの生活習慣病の予防効果や、学習機能の向上効果があることが知られている。厚生労働省による「日本人の食事摂取基準」（２０１０年版）（非特許文献１）によれば、１８歳以上におけるＥＰＡ及びＤＨＡの望ましい１日当たり摂取量は１ｇ以上とされているが、近年の食の欧米化に伴い、日本人の青魚などの魚介類消費量は減少しており、ＥＰＡ及びＤＨＡの望ましい量を摂取している人は少なくなっている。このような状況に鑑み、ＤＨＡやＥＰＡを含有するサプリメントが市販されている。サプリメントには、ドリンク剤、錠剤、顆粒剤、散剤、硬カプセル剤、軟カプセル剤など多様な形態のものがあるが、携帯や保管に便利であり、また一定量の健康成分を簡便に摂取できる錠剤やカプセル剤はサプリメントの主流となっている。ＤＨＡやＥＰＡのサプリメントに関しては、ＤＨＡやＥＰＡが常温で液状の魚油に含まれる成分であり、魚油独特の匂いを発する可能性があること、また、酸化による劣化をうけやすく、加工の段階で失われる可能性があることから、複雑な工程を経ずにＤＨＡ・ＥＰＡ含有魚油をそのまま封じ込めることができる軟カプセルの形態が好適である。出願人は、軟カプセル４粒に、ＤＨＡ３００ｍｇ、ＥＰＡ１００ｍｇと、ゴマに含まれる希少な健康成分であるセサミン及び抗酸化作用のあるビタミンＥとを含むサプリメント（カプセル１粒当たりの重量４１５ｍｇ）を製造、販売しており、２０１２年２月末時点で累計１００万人以上といった多くのお客様にご愛飲いただいている。出願人は、上記のサプリメントのさらなる健康機能の向上にむけて鋭意検討を継続している。 Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) contained in fish oil such as blue fish are known to have preventive effects on lifestyle-related diseases such as arteriosclerosis and hyperlipidemia, and improve learning functions. Yes. According to the “Japanese Food Intake Criteria” by the Ministry of Health, Labor and Welfare (2010 edition) (Non-Patent Document 1), the preferred daily intake of EPA and DHA for those 18 years and older is 1 g or more. With the shift to westernization, the consumption of Japanese seafood such as blue fish is decreasing, and fewer people are taking the desired amount of EPA and DHA. In view of such circumstances, supplements containing DHA and EPA are commercially available. There are various types of supplements such as drinks, tablets, granules, powders, hard capsules, soft capsules, etc., but they are convenient to carry and store and can easily take in a certain amount of health ingredients. Tablets and capsules are the mainstream supplement. Regarding DHA and EPA supplements, DHA and EPA are components contained in fish oil that is liquid at room temperature, and may have a peculiar odor of fish oil, and are susceptible to deterioration due to oxidation and are lost at the processing stage. Therefore, a soft capsule form that can contain the DHA / EPA-containing fish oil as it is without a complicated process is preferable. The applicant manufactured a supplement (weighing 415 mg per capsule) containing 4 mg soft capsules, 300 mg DHA, 100 mg EPA, sesamin, a rare health ingredient contained in sesame, and vitamin E having an antioxidant effect, As of the end of February 2012, it has been enjoyed by many customers, including a cumulative total of over 1 million. The applicant has been continually studying to further improve the health function of the above supplement.
　サプリメントは、一般に、日々継続して摂取することにより、体質等の改善がみられるものであるが、そのように日々継続して摂取するためには、消費者が服用しやすいこと（液剤、小粒の錠剤またはカプセルなど）、持ち運びや保管に便利であること（錠剤、カプセルなど）、価格が高くないことなどは、望ましい要素の１つであるといえる。また、錠剤やカプセルの場合、健康成分の所望の量をできるだけ少ない粒数で摂取できるものは、日々の飲みやすさの観点から望ましいといえる。また、サプリメントの愛用者の中には１日に数種類ものサプリメントを、何粒も（例えば１０粒以上）服用する場合もあるが、１粒のサプリメント中に、より多くの種類の健康成分を、より多くの量含むものがあれば、１日に服用するサプリメントの数（種類）や粒数を減らすことができる場合もあると考えられ、望ましいと考えられる。 In general, supplements can be improved daily by daily consumption. However, in order to continue daily intake of such supplements, it is easy for consumers to take (solutions, small granules). (Tablets or capsules), convenience in carrying and storage (tablets, capsules, etc.), low price, etc. are desirable factors. In the case of tablets and capsules, it is desirable from the viewpoint of ease of daily drinking that a desired amount of health ingredients can be taken in as few grains as possible. In addition, some supplement users may take several kinds of supplements a day (for example, 10 or more), but more kinds of health ingredients in one supplement, If there is something that contains a larger amount, it may be possible to reduce the number (type) of supplements and the number of grains taken in a day, which is desirable.
　このような状況に鑑み、出願人は、上記のサプリメント（軟カプセル）において、現在含まれている健康成分（４粒当たりＤＨＡ３００ｍｇ、ＥＰＡ１００ｍｇ、セサミン、ビタミンＥ）の量はそのままで、さらに新たな健康成分を加えることを検討した。 In view of such a situation, the applicant, in the above-mentioned supplement (soft capsule), the amount of health ingredients (DHA 300 mg, EPA 100 mg, sesamin, vitamin E per 4 capsules) contained in the supplement is still unchanged, and a new health Consider adding ingredients.
　ＤＨＡやＥＰＡは、常温で液状の油（精製魚油）として得られるものであって、一定の容量（体積）を有するものであるから、軟カプセルといったある特定の容量を有するいわば「容器」の中に、既存の製品のＤＨＡ及びＥＰＡの量を維持しつつ、さらに他の健康成分（特に油のような一定の容量を持つもの）を加えることは容易ではない。カプセルのサイズを大きくすれば可能ではあるが、消費者が服用しにくくなるため、好ましくない。 DHA and EPA are obtained as liquid oil (refined fish oil) at room temperature and have a certain volume (volume), so in a so-called “container” having a certain capacity such as soft capsules. In addition, it is not easy to add other health ingredients (especially those with a certain capacity such as oil) while maintaining the amount of DHA and EPA of existing products. Although it is possible to increase the size of the capsule, it is not preferable because it is difficult for consumers to take.
　本発明は、カプセルのサイズを大きくすることなく、既存の製品に含まれるＤＨＡ、ＥＰＡの量は維持しながら、さらに他の健康成分（特に油のような一定の容量を持つもの）を軟カプセル中に封入して、軟カプセルのサプリメントとしての価値を高めること、または、飲みやすさ（大きさ、１日当たり粒数）を維持しつつ健康機能を高めることのできる技術を提供することを目的とする。 The present invention softens other health ingredients (especially those having a certain volume such as oil) while maintaining the amount of DHA and EPA contained in existing products without increasing the size of the capsule. The purpose is to provide a technology that can be encapsulated inside to increase the value as a supplement of soft capsules, or to enhance health functions while maintaining ease of drinking (size, number of grains per day) To do.
　上記目的を達成するために、まず、精製魚油に含まれるＤＨＡ及びＥＰＡの濃縮を試みたが、これらはいずれかを濃縮するともう一方の濃度が低減する傾向があることが判った。そのため、例えば、４粒当たりにＤＨＡ３００ｍｇ、ＥＰＡ１００ｍｇ、さらに他の健康成分を含有する軟カプセルを、カプセルのサイズを現行品より大きくすることなく製造することは困難であった。特にＥＰＡは、最高でも含有率３０％程度の精製魚油が得られるのみであり、所望の量のＥＰＡを含有する魚油を軟カプセル中に封入しようとすると、ＥＰＡ精製魚油のみで軟カプセルの容量の多くを占めることとなり、ＤＨＡや他の健康成分を特定量で封入することが困難であった。しかしながら、鋭意検討を進めた結果、ＤＨＡを特定の濃度にまで濃縮した精製魚油中には、一定量のＥＰＡが含まれることを見出し、このＤＨＡ濃縮精製魚油を、ＥＰＡ精製魚油と組み合わせることで、軟カプセルの形状を大きくすることなく、ＤＨＡとＥＰＡを目標の量（例えば、４粒当たりそれぞれ３００ｍｇ及び１００ｍｇ）で含み、さらに他の健康成分（例えば油のような一定の容量を有する成分）も含む軟カプセルを製造できることを見出した。本発明は、以下の態様を含む。
１．軟カプセル１粒当たりにドコサヘキサエン酸７５ｍｇ以上と、エイコサペンタエン酸とを含有する魚油を含み、さらに、常温で液状の魚油以外の油を含む、カプセル皮膜以外の重量が２２０ｍｇ～２６０ｍｇの軟カプセルの製造方法であって、
ドコサヘキサエン酸の含有率が５０％以上となるように濃縮された魚油と、エイコサペンタエン酸の含有率が１５％以上である魚油と、これら以外の常温で液状の油とを混合すること、
混合した油を軟カプセルの皮膜で包んで、内容量（カプセル皮膜以外の重量）が、２２０ｍｇ～２６０ｍｇの軟カプセルとすること、
を含む、上記方法。
２．前記エイコサペンタエン酸の含有率が１５％以上である魚油として、エイコサペンタエン酸の含有率が２５％以上となるように濃縮された魚油を用いる、上記１の方法。
３．軟カプセルが、１粒当たりにエイコサペンタエン酸を２５ｍｇ以上含有する、上記１または２の方法。
４．ドコサヘキサエン酸の含有率が５０％以上となるように濃縮された魚油が、エイコサペンタエン酸を５％以上の含有率で含む、上記１～３のいずれか１の方法。
５．軟カプセル全体の重量（内容量とカプセル皮膜の重量の合計）が、３８０ｍｇ～４２０ｍｇである、上記１～４のいずれか１の方法。
６．常温で液状の魚油以外の油が、米胚芽油、亜麻仁油、荏胡麻油、オリーブ油、胡麻油またはこれらのうちの２種以上の混合物を含む、上記１～５のいずれか１の方法。
７．軟カプセルが、常温で液状の魚油以外の油を、カプセル１粒当たり２０ｍｇ以上含む、上記１～６のいずれか１の方法。
８．軟カプセルが、常温で液状の魚油以外の油を、カプセル１粒当たり２０～６０ｍｇ含む、上記７の方法。
９．さらに、ビタミンＥを混合することを含む、上記１～８のいずれか１の方法。
１０．さらに、セサミンを混合することを含む、上記１～９のいずれか１の方法。
１１．１粒当たりにドコサヘキサエン酸７５ｍｇ以上、エイコサペンタエン酸２５ｍｇ以上、及びγ－オリザノールを含む、１粒当たりの重量が３８０ｍｇ～４２０ｍｇである軟カプセル。 In order to achieve the above object, first, concentration of DHA and EPA contained in refined fish oil was tried, but it was found that the concentration of either of them tends to decrease the other concentration. Therefore, for example, it has been difficult to produce soft capsules containing DHA 300 mg, EPA 100 mg, and other health ingredients per four grains without making the capsule size larger than the current product. In particular, EPA can only provide purified fish oil with a content rate of about 30% at the maximum. When trying to enclose a fish oil containing a desired amount of EPA in a soft capsule, the volume of the soft capsule can be increased with only EPA purified fish oil. It occupied a lot, and it was difficult to encapsulate DHA and other health ingredients in specific amounts. However, as a result of diligent investigation, it was found that a certain amount of EPA is contained in the refined fish oil obtained by concentrating DHA to a specific concentration, and by combining this DHA enriched refined fish oil with the EPA refined fish oil, Without increasing the size of the soft capsule, DHA and EPA are included in target amounts (eg, 300 mg and 100 mg per 4 tablets, respectively), and other health ingredients (eg, ingredients with a certain volume such as oil) are also available It has been found that soft capsules can be produced. The present invention includes the following aspects.
1. Production of soft capsules containing a fish oil containing 75 mg or more of docosahexaenoic acid and eicosapentaenoic acid per soft capsule, and further containing an oil other than fish oil that is liquid at room temperature and having a weight other than the capsule film of 220 mg to 260 mg A method,
Mixing fish oil concentrated so that the content of docosahexaenoic acid is 50% or more, fish oil having a content of eicosapentaenoic acid of 15% or more, and liquid oil at room temperature other than these,
Wrapping the mixed oil with a soft capsule film to make a soft capsule with an inner volume (weight other than the capsule film) of 220 mg to 260 mg,
Including the above method.
2. The method according to 1 above, wherein the fish oil concentrated so that the content of eicosapentaenoic acid is 25% or more is used as the fish oil having a content of eicosapentaenoic acid of 15% or more.
3. The method of 1 or 2 above, wherein the soft capsule contains 25 mg or more of eicosapentaenoic acid per grain.
4). 4. The method according to any one of 1 to 3 above, wherein the fish oil concentrated so that the content of docosahexaenoic acid is 50% or more contains eicosapentaenoic acid at a content of 5% or more.
5. 5. The method according to any one of 1 to 4 above, wherein the total weight of the soft capsule (the total content of the internal volume and the capsule film) is 380 mg to 420 mg.
6). 6. The method according to any one of 1 to 5 above, wherein the oil other than fish oil that is liquid at room temperature comprises rice germ oil, linseed oil, sesame oil, olive oil, sesame oil, or a mixture of two or more thereof.
7. 7. The method according to any one of 1 to 6 above, wherein the soft capsule contains 20 mg or more of oil other than fish oil that is liquid at normal temperature per capsule.
8). 8. The method according to 7 above, wherein the soft capsule contains 20 to 60 mg of oil other than fish oil that is liquid at normal temperature per capsule.
9. The method according to any one of 1 to 8, further comprising mixing vitamin E.
10. The method according to any one of 1 to 9, further comprising mixing sesamin.
11. A soft capsule containing 75 mg or more of docosahexaenoic acid, 25 mg or more of eicosapentaenoic acid, and γ-oryzanol per grain and having a weight per grain of 380 mg to 420 mg.
　本発明によれば、１粒当たりのサイズ、ならびに１粒に含まれるＤＨＡ及びＥＰＡの量を維持しながら、さらに追加の健康成分（常温で液状の油の形態の健康成分）を軟カプセル中に含有させることができ、軟カプセルのサプリメントとしての価値を高めることができる。具体的には、１粒当たりのサイズが、比較的小さいので服用しやすく、また、ＤＨＡとＥＰＡに加えて追加の健康成分を含むので、さらなる健康効果が期待できる。また、１粒当たりの健康成分の含有量が高いので、１日当たりの服用粒数が、比較的少なくて済む（目安として４粒）。サプリメントが多種類の健康成分を含むことは、健康を志向する消費者にとって利益である。また、１日当たり服用粒数が少なくて済むことは、消費者が手軽に服用できるという利点に加え、通常、１ヶ月単位などで容器に詰められて販売されるサプリメントにおいて、商品（例えば１ヶ月分のサプリメントを入れた容器）の大きさが大きくならずに済み、消費者と販売者の双方にとって運搬や保管の際に利点があるといえる。また、サプリメントしての役割を考えると、サプリメントの摂取による健康成分以外の成分の摂取はできるだけ少ない方が望ましいといえるところ、１日当たりに服用する軟カプセルの粒数が少なければ、その分、カプセルの皮膜などの健康成分以外の成分の１日当たりの摂取量が減ると考えられ、好ましいと考えられる。 According to the present invention, while maintaining the size per grain and the amount of DHA and EPA contained in each grain, additional health ingredients (health ingredients in the form of liquid oil at room temperature) are further contained in the soft capsule. It can be contained, and the value as a supplement of a soft capsule can be increased. Specifically, since the size per grain is relatively small, it is easy to take, and since additional health ingredients are included in addition to DHA and EPA, further health effects can be expected. In addition, since the content of health ingredients per grain is high, the number of grains taken per day is relatively small (4 as a guide). It is beneficial for health-conscious consumers that the supplement contains many types of health ingredients. In addition, the fact that the number of grains taken per day is small, in addition to the advantage that consumers can easily take, in addition to the products (for example, for one month) in supplements that are usually packed and sold in containers in units of one month. The size of the container containing the supplement is not increased, which is advantageous for both consumers and sellers during transportation and storage. In addition, considering the role of supplements, it can be said that it is desirable to consume as little as possible of ingredients other than health ingredients by taking supplements. However, if the number of soft capsules to be taken per day is small, the corresponding amount It is considered that the daily intake of components other than health components such as the film of this skin is reduced, which is preferable.
　本発明は、特定の量以上のドコサヘキサエン酸及びエイコサペンタエン酸を含む魚油を含有し、さらにこの魚油以外の常温で液状の油を含有する、カプセル皮膜以外の重量（すなわち、カプセル中に含まれる液量）が２２０ｍｇ～２６０ｍｇの軟カプセルを製造する方法に関する。本発明の方法は、ドコサヘキサエン酸の含有率が５０％以上となるように濃縮された油を用いることを特徴の１つとする。 The present invention contains a fish oil containing a specific amount or more of docosahexaenoic acid and eicosapentaenoic acid, and further contains a liquid oil at room temperature other than the fish oil (ie, a liquid contained in the capsule). The present invention relates to a method for producing soft capsules having an amount of 220 to 260 mg. One of the features of the method of the present invention is to use oil concentrated so that the content of docosahexaenoic acid is 50% or more.
　（ドコサヘキサエン酸、エイコサペンタエン酸）
　ドコサヘキサエン酸（ＤＨＡ）は、分子式Ｃ２２Ｈ３２Ｏ２の不飽和脂肪酸である。エイコサペンタエン酸（ＥＰＡ）は、分子式Ｃ２０Ｈ３０Ｏ２の不飽和脂肪酸である。これらはいずれも魚油中に多く含まれることが知られている（例えば、イワシ油：ＤＨＡ１２％、ＥＰＡ１７％、マグロ油：ＤＨＡ２５％、ＥＰＡ７％、カツオ油：ＤＨＡ２４％、ＥＰＡ５％、サケ油：ＤＨＡ１４％、ＥＰＡ９％）。本発明では、容量の限定された軟カプセル中に、特定量以上のＤＨＡ及びＥＰＡを配合するために、これらをそれぞれ特定濃度以上とした魚油を組み合わせて用いる。具体的には、ＤＨＡの含有率が５０％以上となるように濃縮された魚油と、ＥＰＡの含有率が１５％以上である魚油とを組み合わせる。なお、本発明において、ＤＨＡ及びＥＰＡの含有量は、遊離脂肪酸としてのＤＨＡ及びＥＰＡの量のみではなく、トリグリセリド、ジグリセリド、またはモノグリセリドの形態にあるＤＨＡ及びＥＰＡの量（遊離脂肪酸量に換算する）も含むものとする。魚油中のＤＨＡ及びＥＰＡのそれぞれの含有率または含有量は、以下の実施例に詳細を示すように、ＧＣ（ガスクロマトグラフィー）を用いて測定することができる。 (Docosahexaenoic acid, eicosapentaenoic acid)
Docosahexaenoic acid (DHA) is an unsaturated fatty acid of the molecular formula C 22 H 32 O 2 . Eicosapentaenoic acid (EPA) is an unsaturated fatty acid molecular formula C 20 H 30 O 2. All of these are known to be contained in a large amount in fish oil (for example, sardine oil: DHA 12%, EPA 17%, tuna oil: DHA 25%, EPA 7%, skipjack oil: DHA 24%, EPA 5%, salmon oil: DHA14 %, EPA 9%). In this invention, in order to mix | blend DHA and EPA more than specific amount in the soft capsule with capacity | capacitance limited, these are used combining the fish oil which made these each more than a specific density | concentration. Specifically, fish oil concentrated so that the DHA content is 50% or more and fish oil having an EPA content of 15% or more are combined. In the present invention, the contents of DHA and EPA are not only the amounts of DHA and EPA as free fatty acids, but also the amounts of DHA and EPA in the form of triglycerides, diglycerides, or monoglycerides (converted to the amount of free fatty acids). Shall also be included. The respective contents or contents of DHA and EPA in fish oil can be measured using GC (gas chromatography) as shown in detail in the following examples.
　魚油中のＤＨＡやＥＰＡを濃縮する方法については例えば、基質特異性のあるリパーゼを用いて、所望の脂肪酸以外の脂肪酸を除去する方法が挙げられ、そのような方法については種々報告されている（例えば、特開平８－２１４８９１号公報、特開２００２－１３６２９８号公報、特許第４５３０３１１号、特許第５２０４７７６号、特開２０１３－５５８９３号公報）。本発明では、いずれかの方法で所望の濃度とした精製魚油を用いることができる。ＤＨＡやＥＰＡは酸化されやすい成分であるから、魚油としては、新鮮な魚から得られた油を用いることが重要である。魚の種類は特に限定されないが、マグロ、カツオ、イワシ、サバ、サンマ、アジ、イカ、タラなどから得られる油は、ＤＨＡやＥＰＡを豊富に含むので好ましい。 Examples of the method for concentrating DHA and EPA in fish oil include a method of removing fatty acids other than a desired fatty acid using a lipase having a substrate specificity, and such methods have been reported in various ways ( For example, JP-A-8-214891, JP-2002-136298, JP4530311, JP5204776, JP2013-55893). In the present invention, purified fish oil having a desired concentration by any method can be used. Since DHA and EPA are easily oxidized components, it is important to use oil obtained from fresh fish as fish oil. The type of fish is not particularly limited, but oils obtained from tuna, bonito, sardines, mackerel, saury, horse mackerel, squid, cod and the like are preferable because they contain abundant DHA and EPA.
　ＥＰＡ精製魚油としては、ＥＰＡの含有率が１５％以上であるものを用いる。好ましくは、ＥＰＡの含有率を２５％以上に濃縮した魚油（ＥＰＡ精製濃縮魚油）を用いる。本発明において、ＥＰＡ精製魚油としては、精製品または濃縮精製魚油を適宜用いることができる。ＥＰＡ濃縮精製魚油中の上限値は特に制限されないが、上記の方法によって精製したＥＰＡ濃縮精製魚油中のＥＰＡの含有率は、最高でも３０％程度であると考えられる。所定の容量の軟カプセル中に、所定量のＥＰＡを含有させるためには、ＤＨＡの濃度を高めるように精製した魚油（ＤＨＡ濃縮精製魚油）中に含まれるＥＰＡも考慮に入れる必要がある。ＤＨＡ濃縮精製魚油中のＤＨＡ含有率は、７５％程度まで高められたものも存在する。しかしながら、ＤＨＡを高濃度に濃縮し過ぎると、ＤＨＡ濃縮精製魚油中に含まれるＥＰＡの濃度が低下して、軟カプセル中に必要な量のＥＰＡをＤＨＡ濃縮精製魚油から補うことが困難となる。また、ＤＨＡを高濃度に濃縮した魚油はコストが高い。ＤＨＡの含有率の上限としては、７０％程度、好ましくは６０％程度までのものがよいであろう。特に、ＤＨＡの含有率が５０％～６０％の範囲となるように濃縮されたＤＨＡ濃縮精製魚油中には、含有率で５％以上、好ましくは５％～８％程度のＥＰＡも残存しており、ＥＰＡ精製魚油からのＥＰＡと組み合わせることで、軟カプセル中に含有させるＥＰＡの所定量を達成することができる。中でも、ＤＨＡの含有率が５３％～５８％の範囲であり、および／または、ＥＰＡの含有率が６．５％～７％の範囲のＤＨＡ濃縮精製魚油を好適に用いることができる。 EPA refined fish oil with an EPA content of 15% or more is used. Preferably, fish oil (EPA refined concentrated fish oil) in which the content of EPA is concentrated to 25% or more is used. In the present invention, as the EPA refined fish oil, a purified product or a concentrated refined fish oil can be appropriately used. The upper limit value in the EPA concentrated and refined fish oil is not particularly limited, but the content of EPA in the EPA concentrated and refined fish oil purified by the above method is considered to be about 30% at the maximum. In order to contain a predetermined amount of EPA in a predetermined volume of soft capsules, it is necessary to take into account EPA contained in fish oil refined to increase the concentration of DHA (DHA concentrated refined fish oil). Some DHA concentration in the DHA-concentrated and refined fish oil has been increased to about 75%. However, if DHA is concentrated to a high concentration too much, the concentration of EPA contained in the DHA-concentrated and refined fish oil decreases, making it difficult to supplement the amount of EPA required in the soft capsule from the DHA-concentrated and refined fish oil. Further, fish oil obtained by concentrating DHA at a high concentration is expensive. The upper limit of the DHA content should be about 70%, preferably up to about 60%. In particular, in DHA-concentrated and refined fish oil concentrated so that the DHA content is in the range of 50% to 60%, EPA with a content of 5% or more, preferably about 5% to 8% remains. In combination with EPA from EPA refined fish oil, a predetermined amount of EPA to be contained in the soft capsule can be achieved. Among them, DHA concentrated refined fish oil having a DHA content of 53% to 58% and / or an EPA content of 6.5% to 7% can be suitably used.
　ＤＨＡ濃縮精製魚油と、ＥＰＡ精製魚油とは、必要に応じて１００メッシュ～１２０メッシュ程度の網を通過させて、適度な温度に保ちながら、撹拌混合すればよい。温度は、高すぎるとＤＨＡ及びＥＰＡが劣化するおそれがある。好ましくは、３０～４０℃の範囲である。また、撹拌は、魚油中にできるだけ酸素を巻き込まないように行うべきであり、窒素を吹き込みながら行うのが好ましい。 DHA concentrated and refined fish oil and EPA refined fish oil may be stirred and mixed while passing through a net of about 100 mesh to 120 mesh as necessary and kept at an appropriate temperature. If the temperature is too high, DHA and EPA may deteriorate. Preferably, it is in the range of 30 to 40 ° C. Further, the stirring should be performed so as not to involve oxygen as much as possible in the fish oil, and is preferably performed while blowing nitrogen.
　本発明の軟カプセル中には、１粒当たり、ＤＨＡ７５ｍｇ以上を含有させ、さらに、好ましくはＥＰＡ２５ｍｇ以上を含有させる。これは、軟カプセル４粒で、ＤＨＡ３００ｍｇ、ＥＰＡ１００ｍｇとなる量である。厚生労働省の「日本人の食事摂取基準」（２０１０年版）によれば、１８歳以上におけるＥＰＡ及びＤＨＡの望ましい１日当たり摂取量は１ｇ以上であるが、ＥＰＡ及びＤＨＡの摂取量の最も少ない群（１８～２９歳の女性）では１日当たり摂取量が１８８ｍｇであり、最も多い群（７０歳以上の男性）でも７７５ｍｇである。ＥＰＡ及びＤＨＡは、現状、各世代の男女において１日当たり所望量に達していない。本発明の軟カプセルは、ＥＰＡ及びＤＨＡの摂取を補助する役割を果たす。なお、ＥＰＡ及びＤＨＡの１日当たりの摂取量の上限値は、「日本人の食事摂取基準」（２０１０年版）では算定されていない。しかしながら、どのような物質であれ、極端な大量摂取は健康障害を引き起こす可能性があるから、適度な量を保って摂取することが大切である。 In the soft capsule of the present invention, 75 mg or more of DHA is contained per grain, and more preferably 25 mg or more of EPA. This is an amount of 4 soft capsules to give 300 mg DHA and 100 mg EPA. According to the Ministry of Health, Labor and Welfare's “Japanese dietary intake standards” (2010 edition), the preferred daily intake of EPA and DHA for those over 18 years old is 1 g or more, but the group with the lowest EPA and DHA intake ( (18-29 year old female) has a daily intake of 188 mg, and the most common group (70 year old male) is 775 mg. EPA and DHA currently do not reach the desired amount per day for each generation of men and women. The soft capsule of the present invention plays a role in assisting ingestion of EPA and DHA. The upper limit of daily intake of EPA and DHA is not calculated in the “Japanese dietary intake standard” (2010 edition). However, it is important to keep an appropriate amount of any substance, because an extremely large amount can cause health problems.
　ＤＨＡ、ＥＰＡを日々適度な量で摂取することにより、心血管リスク低減、中性脂肪低下作用、関節リウマチ症状緩和作用、加齢黄斑変性症発生リスク低減、認知機能低下抑制効果等の幅広い効能が得られることが知られている。 By taking DHA and EPA in appropriate amounts every day, it has a wide range of effects such as cardiovascular risk reduction, triglyceride reduction, rheumatoid arthritis symptom reduction, age-related macular degeneration risk reduction, cognitive function reduction suppression It is known to be obtained.
　（魚油以外に添加する成分）
　本発明の軟カプセルには、上記のＤＨＡ、ＥＰＡを含有する魚油に加えて、魚油以外の常温で液状の油、特に健康機能を有するものをさらに配合する。本発明では、特定の濃度にまで凝縮したＤＨＡ濃縮精製魚油を、ＥＰＡ精製魚油と組み合わせることにより、一定の容量を有する軟カプセル中にＤＨＡとＥＰＡとを所定量以上含有させつつ、さらに、他の健康機能を有する油も追加できることを見出した。 (Ingredients added in addition to fish oil)
In addition to the fish oil containing DHA and EPA, the soft capsule of the present invention is further blended with a liquid oil at room temperature other than fish oil, particularly one having a health function. In the present invention, DHA-concentrated and refined fish oil condensed to a specific concentration is combined with EPA-purified fish oil, so that a predetermined amount or more of DHA and EPA are contained in a soft capsule having a certain volume, We found that oils with health functions can also be added.
　本発明の軟カプセル中に配合するのに適する常温で液状の油としては、健康機能を有するものであれば特に限定されず、例えば、米胚芽油、亜麻仁油、荏胡麻油、オリーブ油、胡麻油、またはこれらを混合したものなどが挙げられる。米胚芽油は、好ましい油の１つである。米胚芽油は、米の胚芽から抽出された脂肪油であり、通常、１．０～１．５ｗ／ｗ％程度のγ－オリザノールを含むと言われている。米胚芽油は、例えば、γ－オリザノールを１．２～１．５ｗ／ｗ％含有するオリザオイルＳ－１（一丸ファルコス株式会社）、γ－オリザノールを１．０～１．５ｗ／ｗ％含有する米胚芽油ＰＲＯ－１５（築野食品工業株式会社）等の名称で市販されている。 The oil at room temperature suitable for blending in the soft capsule of the present invention is not particularly limited as long as it has a health function. For example, rice germ oil, linseed oil, sesame sesame oil, olive oil, sesame oil, or The thing etc. which mixed these are mentioned. Rice germ oil is one preferred oil. Rice germ oil is a fatty oil extracted from rice germ and is usually said to contain about 1.0 to 1.5 w / w% of γ-oryzanol. Rice germ oil contains, for example, ORIZA oil S-1 (Ichimaru Falcos Co., Ltd.) containing 1.2 to 1.5 w / w% of γ-oryzanol and 1.0 to 1.5 w / w% of γ-oryzanol. Such as rice germ oil PRO-15 (Tsukino Food Industry Co., Ltd.).
　本願明細書において、γ－オリザノールとは、フェルラ酸にトリテルペンアルコール又はステロールがエステル結合したものの総称を指し、トリテルペンアルコールとしては、例えば、シクロアルテノール、２，４－メチレンシクロアルタノール、シクロアルタノール、シクロブラノール等を挙げることができ、ステロールとしては、例えば、カンペステロール、スチグマステロール、β－シトステロール等を挙げることができる。γ－オリザノールは、これらの化合物の混合物であってもよいし、単独の化合物であってもよい。γ－オリザノールには、血中中性脂質低下作用（Geriant. Med. 19, 1812-1840, 1981）、内分泌・自律神経調節作用（日薬理誌、75(4)、399-403, 1979）、胃粘膜保護作用（日薬理誌、84(6)、537-542, 1984）などの様々な生理作用が知られており、精製されたものは高脂血症治療剤や心身症（更年期障害、過敏性大腸症候群）治療剤などの医薬品として認可されている。γ－オリザノールの定量法としては、ＵＶ吸光度法やＨＰＬＣ法等の公知の方法を適宜用いることができる。例えば、「医薬部外品原料規格」や「化学的合成品以外の食品添加物自主規格」に記載されている通り、サンプルをヘプタンに溶解し、３１５ｎｍ付近における吸収の極大波長で吸光度を測定することにより定量することができる。 In the specification of the present application, γ-oryzanol refers to a generic name of ferulic acid in which triterpene alcohol or sterol is ester-bonded. Examples of triterpene alcohol include cycloartenol, 2,4-methylenecycloartanol, and cycloartanol. And cyclobranol. Examples of the sterol include campesterol, stigmasterol, and β-sitosterol. γ-Oryzanol may be a mixture of these compounds or a single compound. γ-Oryzanol has blood neutral lipid lowering action (Geriant. Med. 19, 1812-1840, 1981), endocrine / autonomic nerve regulating action (Japanese Pharmacology, 75 (4), 399-403, 1979), Various physiological effects such as gastric mucosal protective effect (Nippon Pharmacological Journal, 84 (6), 537-542, 1984) are known, and purified products are used to treat hyperlipidemia and psychosomatic disorders (menopause, It is approved as a medicine for treating irritable bowel syndrome. As a method for quantifying γ-oryzanol, a known method such as a UV absorbance method or an HPLC method can be appropriately used. For example, the sample is dissolved in heptane and the absorbance is measured at the maximum wavelength of absorption near 315 nm as described in “Standards for raw materials of quasi drugs” and “Voluntary standards for food additives other than chemically synthesized products”. Can be quantified.
　米胚芽油は、γ－オリザノールを濃縮したものを用いても良い。濃縮油中のγ－オリザノールの含有量は、２ｗ／ｗ％以上が好ましく、３０ｗ／ｗ％以上がより好ましい。このようなγ－オリザノールの濃縮油は、工業的には、有機溶剤で抽出するか、または樹脂処理後に精製することにより得ることができ、米胚芽油ガンマ３０（築野食品工業株式会社）や、γ－オリザノール、オリザドリムＶ－５０、コメヌカ油、玄米胚芽油（オリザ油化株式会社）として入手可能である。 As the rice germ oil, γ-oryzanol concentrated may be used. The content of γ-oryzanol in the concentrated oil is preferably 2 w / w% or more, and more preferably 30 w / w% or more. Such a concentrated oil of γ-oryzanol can be industrially obtained by extraction with an organic solvent or purification after resin treatment, such as rice germ oil gamma 30 (Tsukino Food Industry Co., Ltd.) , Γ-oryzanol, oryzadorim V-50, rice bran oil, brown rice germ oil (Oryza Oil Co., Ltd.).
　軟カプセル中の米胚芽油の含有量は、米胚芽油または米胚芽油濃縮物に特徴的に含まれるステロールの含有量、及び各種ステロールの含有比率を指標として測定することができる。 The content of rice germ oil in the soft capsule can be measured by using the sterol content characteristically contained in rice germ oil or rice germ oil concentrate and the content ratio of various sterols as an index.
　米胚芽油の好ましい配合量は、本発明の軟カプセル１粒当たりに、１～４０ｍｇであり、さらに好ましくは１～２０ｍｇ、最も好ましくは５～１０ｍｇである。γ－オリザノールの好ましい配合量は、本発明の軟カプセル１粒当たりに、０．３～１２ｍｇであり、さらに好ましくは０．３～６ｍｇ、最も好ましくは１．５～３ｍｇである。 The preferred blending amount of rice germ oil is 1 to 40 mg, more preferably 1 to 20 mg, and most preferably 5 to 10 mg per soft capsule of the present invention. The preferred amount of γ-oryzanol is 0.3 to 12 mg, more preferably 0.3 to 6 mg, and most preferably 1.5 to 3 mg per soft capsule of the present invention.
　米胚芽油などの、常温で液状の魚油以外の油は、合計で、本発明の軟カプセル１粒当たりに、好ましくは、２０ｍｇ以上配合することができる。さらに好ましくは、２０～６０ｍｇ、さらに好ましくは４０～６０ｍｇである。このような油は、ＤＨＡ濃縮精製魚油とＥＰＡ精製魚油とを混合する際に共に混合することができる。 Oils other than fish oil that is liquid at room temperature, such as rice germ oil, can be blended preferably in an amount of 20 mg or more per soft capsule of the present invention. More preferably, it is 20 to 60 mg, and more preferably 40 to 60 mg. Such oils can be mixed together when mixing DHA concentrated refined fish oil and EPA refined fish oil.
　本発明の軟カプセル中には、ＤＨＡ及びＥＰＡを含有する魚油と、上記の常温で液状の油以外にも、他の油溶性の健康成分や、抗酸化剤などを添加してもよい。このような成分としては、例えば、セサミン、エピセサミン、セサミノール、エピセサミノール、セサモリン等のセサミン類、α－トコフェロール、β－トコフェロール、γ－トコフェロール、δ－トコフェロール、ε－トコフェロール、ξ－トコフェロール、η－トコフェロール、トコフェロールエステル（酢酸トコフェロール等）のトコフェロール類、β－カロチン、カンタキサンチン、アスタキサンチン等のカロテノイド類、フラボン誘導体、フィロズルシン類、コウジ酸、没食子酸誘導体、カテキン類、フキ酸、ゴシポール、ピラジン誘導体、セサモール、グァヤオール、グァヤク酸、ｐ－クマリン酸、ノールジヒドログァヤテッチク酸、ステロール類、テルペン類、核酸塩基類、リグナン類などの天然の抗酸化成分、及びアスコルビン酸パルミチン酸エステル、アスコルビン酸ステアリン酸エステル、ブチルヒドロキシアニソール（ＢＨＡ）、ブチルヒドロキシトルエン（ＢＨＴ）、モノ－ｔ－ブチルヒドロキノン（ＴＢＨＱ）、４－ヒドロキシメチル－２，６－ジ－ｔ－ブチルフェノール（ＨＭＢＰ）に代表されるような合成抗酸化剤が挙げられる。特に、セサミン類は、好ましい化合物の一種である。 In addition to the fish oil containing DHA and EPA and the liquid oil at room temperature, other oil-soluble health ingredients, antioxidants, and the like may be added to the soft capsule of the present invention. Examples of such components include sesamin such as sesamin, episesamin, sesaminol, episesaminol, sesamorin, α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol, ε-tocopherol, ξ-tocopherol, η-tocopherol, tocopherol esters (such as tocopherol acetate), carotenoids such as β-carotene, canthaxanthin, astaxanthin, flavone derivatives, phyllosilsins, kojic acid, gallic acid derivatives, catechins, fucic acid, gossypol, pyrazine Natural antioxidants such as derivatives, sesamol, guaiaol, guaiacic acid, p-coumaric acid, nordihydroguayatic acid, sterols, terpenes, nucleobases, lignans, and ascorbic acid Palmitic acid ester, ascorbic acid stearate, butylhydroxyanisole (BHA), butylhydroxytoluene (BHT), mono-t-butylhydroquinone (TBHQ), 4-hydroxymethyl-2,6-di-t-butylphenol (HMBP) Synthetic antioxidants represented by In particular, sesamin is one of the preferred compounds.
　セサミン類は、ゴマに含有されるリグナン化合物の一種であり、血中コレステロール低下作用及び血中中性脂質低下作用、肝機能改善作用、活性酸素消去作用、Δ５不飽和化酵素阻害作用、過酸化脂質生成抑制作用、抗高血圧作用、悪酔防止作用、乳癌抑制作用等の種々の生理活性が報告されている。本願明細書において、セサミン類とは、セサミン及びその類縁体を含む一連の化合物の総称である。例えば、上記のセサミン、エピセサミン、セサミノール、エピセサミノール、セサモリン等が含まれ、これらの立体異性体又はラセミ体を単独で、または混合して用いることができる。また、セサミン類の代謝体（例えば、特開２００１－１３９５７９号公報に記載）も、効果を有する限り、本願明細書におけるセサミン類として使用することができる。セサミン類は、その形態や製造方法等によって何ら制限されない。例えば、セサミンを選択した場合には、市販の胡麻油（液状）をそのまま用いることもできるし、胡麻油から公知の方法（例えば、特開平４－９９３１号公報に記載された方法）によって抽出したセサミン（セサミン抽出物または濃縮物という）を用いることもできる。後者の方が、必要量をカプセル中に含有させやすく、消費者にとって摂取しやすいので好ましい。セサミン抽出物（またはセサミン濃縮物）は、公知の手段、例えば活性白土処理等により無味無臭としてもよい。セサミン類の濃縮物における濃縮の度合いは、用いるセサミン類の種類などに応じて適宜設定すればよいが、通常、セサミン類が総量で１ｗ／ｗ％以上となるように濃縮されたセサミン類濃縮物を用いるのが好ましい。セサミン類濃縮物中のセサミン類総含量は、２０ｗ／ｗ％以上がより好ましく、さらに５０ｗ／ｗ％以上が好ましく、さらに７０ｗ／ｗ％以上が好ましく、９０ｗ／ｗ％以上まで濃縮（精製）されたものが最適である。セサミン類の含有量は、ＨＰＬＣ法等の公知のいずれかの方法を用いて測定できる。ＨＰＬＣ法に関しては、例えば、特開２００９－１５５３１２号公報に記載の方法等を参考にすることができる。 Sesamin is a kind of lignan compound contained in sesame seeds, blood cholesterol lowering action and blood neutral lipid lowering action, liver function improving action, active oxygen scavenging action, Δ5 desaturase inhibiting action, peroxidation Various physiological activities such as an adipogenesis inhibitory action, an antihypertensive action, a sickness prevention action, and a breast cancer inhibitory action have been reported. In the present specification, sesamin is a general term for a series of compounds including sesamin and its analogs. For example, the above-mentioned sesamin, episesamin, sesaminol, episesaminol, sesamoline and the like are included, and these stereoisomers or racemates can be used alone or in combination. In addition, metabolites of sesamin compounds (for example, described in JP-A-2001-139579) can be used as sesamin compounds in the present specification as long as they have an effect. Sesamin is not limited by its form or production method. For example, when sesamin is selected, commercially available sesame oil (liquid) can be used as it is, or sesamin extracted from sesame oil by a known method (for example, the method described in JP-A-4-9931) Sesamin extract or concentrate) can also be used. The latter is preferable because the necessary amount is easily contained in the capsule and is easily consumed by consumers. The sesamin extract (or sesamin concentrate) may be made tasteless and odorless by known means, for example, activated clay treatment. The degree of concentration in the sesamin concentrate may be appropriately set according to the type of sesamin used, etc., but usually the sesamin concentrate concentrated so that the total amount of sesamin is 1 w / w% or more. Is preferably used. The total sesamin content in the sesamin concentrate is preferably 20 w / w% or more, more preferably 50 w / w% or more, further preferably 70 w / w% or more, and concentrated (purified) to 90 w / w% or more. The one is the best. The content of sesamin can be measured using any known method such as HPLC. Regarding the HPLC method, for example, the method described in JP2009-155531A can be referred to.
　出願人は、セサミン類とビタミンＥ（トコフェロール類）とを組み合わせることにより、相乗的な抗疲労効果が得られることを見出している（国際公開第２００９／０３８０８９号明細書）。したがって、本発明の軟カプセル中に、セサミン類とビタミンＥとの組合せをさらに配合することは好ましい。 The applicant has found that a synergistic anti-fatigue effect can be obtained by combining sesamin and vitamin E (tocopherols) (WO 2009/038089). Therefore, it is preferable to further blend a combination of sesamin and vitamin E into the soft capsule of the present invention.
　また、出願人は、セサミン類とともに、γ－オリザノール（米胚芽油に含まれる）を併用することで、セサミン類の生理作用、例えば、抗疲労作用が顕著に高まることを見出した（特開２００９－０７３７４９号公報）。更に、出願人は、セサミン類を、γ－オリザノール（米胚芽油に含まれる）と組み合わせることにより、セサミン類の体内吸収が促進されることを見出し、出願を行った（特願２０１２－１３５０３４号（国際公開第２０１３／１８７３９１号参照））。したがって、本発明の軟カプセル中に、セサミン類とγ－オリザノール（または米胚芽油）との組合せを配合することは好ましい。 In addition, the applicant has found that the physiological action of sesamin, for example, anti-fatigue action is remarkably increased by using γ-oryzanol (included in rice germ oil) together with sesamin (Japanese Patent Application Laid-Open (JP-A) No. 2009). No. 073749). Furthermore, the applicant has found that combining sesamin with γ-oryzanol (contained in rice germ oil) promotes in vivo absorption of sesamin (Japanese Patent Application No. 2012-135034). (See International Publication No. 2013/187391)). Therefore, it is preferable to add a combination of sesamin and γ-oryzanol (or rice germ oil) in the soft capsule of the present invention.
　したがって、本発明の軟カプセル中に含有させる最も好ましい例としては、ＤＨＡ及びＥＰＡを含有する精製魚油、米胚芽油（γ－オリザノールを含む）、セサミン類、及びビタミンＥの組み合わせが挙げられる。セサミン類の好ましい配合量は、本発明の軟カプセル１粒当たりに、０．１～１０ｍｇであり、さらに好ましくは１～５ｍｇである。ビタミンＥの好ましい配合量は、本発明の軟カプセル１粒当たりに、０．３５～２０ｍｇであり、さらに好ましくは７～１８ｍｇ、最も好ましくは７～１１ｍｇである。 Therefore, the most preferred example of inclusion in the soft capsule of the present invention includes a combination of purified fish oil containing DHA and EPA, rice germ oil (including γ-oryzanol), sesamin, and vitamin E. The preferred blending amount of sesamin is 0.1 to 10 mg, more preferably 1 to 5 mg per soft capsule of the present invention. The preferred amount of vitamin E is 0.35 to 20 mg, more preferably 7 to 18 mg, and most preferably 7 to 11 mg per soft capsule of the present invention.
　セサミン類やビタミンＥは、粉末の状態のものを、魚油と魚油以外の液状の油とを混合する際に添加して、これらの油中に溶解させてもよいし、あるいは、油の混合工程の前に、予め、魚油および／または魚油以外の油中に溶解させておいてもよい。例えば、ビタミンＥは、ビタミンＥ含有オイルとして市販されている。ビタミンＥ含有オイルの好ましい配合量は、オイル中のビタミンＥの含有率にもよるが、例えば、本発明の軟カプセル１粒当たりに１～５０ｍｇであり、さらに好ましくは２０～５０ｍｇ、最も好ましくは３０～５０ｍｇである。 Sesamin and vitamin E may be added when mixing fish oil and liquid oil other than fish oil and dissolved in these oils, or the oil mixing step It may be dissolved in advance in fish oil and / or oil other than fish oil. For example, vitamin E is commercially available as a vitamin E-containing oil. The preferred amount of the vitamin E-containing oil depends on the content of vitamin E in the oil, but is, for example, 1 to 50 mg, more preferably 20 to 50 mg, most preferably, per soft capsule of the present invention. 30-50 mg.
　（軟カプセル）
　軟カプセルは、日本薬局方に規定されるように、「有効成分に添加剤を加えたものを、グリセリン又はＤ－ソルビトールなどを加えて塑性を増したゼラチンなどの適切なカプセル基剤で、一定の形状に被包成形」したものをいう。カプセル基材（カプセル皮膜の材料）や、カプセル化の方法は、特に限定されず、通常の材料及び方法を用いればよい。例えば、日本薬局方に規定されるように「グリセリン又はＤ－ソルビトールなどを加えて塑性を増したゼラチン」を皮膜の材料として用いればよく、また、打ち抜き法（ロータリーダイ）などを用いてカプセル皮膜の成形と内容物の充填とを行えばよい。 (Soft capsule)
Soft capsules are, as prescribed by the Japanese Pharmacopoeia, “A combination of active ingredients with an appropriate capsule base such as gelatin with increased plasticity by adding glycerin or D-sorbitol, etc. "Encapsulated in the shape of". The capsule base material (capsule film material) and the encapsulation method are not particularly limited, and ordinary materials and methods may be used. For example, as specified in the Japanese Pharmacopoeia, “gelatin with increased plasticity by adding glycerin or D-sorbitol” may be used as a coating material, and capsule coating using a punching method (rotary die) or the like. May be formed and the contents may be filled.
　軟カプセルの形状や大きさは特に限定されず、カプセル内容物の量や、消費者の飲み込みやすさを考慮して設定する。軟カプセルの形状には、楕円形（オーバル）、長楕円形（オブロング）、球形（ラウンド）、なみだ形、特殊形（三角形、ハート形、ひし形等）などがあるが、なみだ形（しずく形と呼ばれることもある）の形状は、飲み込みやすく、また、容器から出した際に転がりにくいなど、消費者にとって扱いやすいと考えられるため、好ましい。軟カプセルの大きさは、飲みやすさを考慮すると、長径が１７ｍｍ以下、短径が８ｍｍ以下程度であることが好ましい。軟カプセルの大きさ（長径、短径）の下限値は、カプセル内容物の量によって異なる。 The shape and size of the soft capsule are not particularly limited, and are set in consideration of the amount of capsule contents and ease of swallowing by consumers. Soft capsule shapes include oval (oval), oblong (oblong), spherical (round), slender, special (triangle, heart, rhombus, etc.), but slender ( The shape (sometimes referred to as a drop shape) is preferable because it is easy to swallow and is easy to handle for consumers because it is difficult to roll when taken out of the container. The size of the soft capsule is preferably about 17 mm or less for the major axis and about 8 mm or less for the minor axis in consideration of ease of drinking. The lower limit of the soft capsule size (major axis, minor axis) varies depending on the amount of capsule contents.
　本発明の軟カプセル１粒当たりに含まれる内容物の量（カプセル皮膜以外の重量）は、２２０ｍｇ～２６０ｍｇの範囲内とする。内容量が少なければ、健康成分の所望の量を１日当たりカプセル４粒で摂取する事が困難となるし、また、内容量が多すぎると、カプセルの全体の大きさが大きくなりすぎて、消費者が飲み込みにくくなるから好ましくない。軟カプセル１粒当たりの全体の重さ（内容物の量とカプセル皮膜の重量の合計）は、限定されないが、健康成分の所望量、飲み込みやすさ、及びカプセル皮膜の強度等を考慮すると、３８０ｍｇ～４２０ｍｇ程度がよい。 The amount of content (weight other than capsule film) contained in one soft capsule of the present invention is in the range of 220 mg to 260 mg. If the internal volume is small, it will be difficult to take the desired amount of healthy ingredients in 4 capsules per day. If the internal volume is too large, the overall size of the capsule will become too large and consumed. It is not preferable because it becomes difficult for a person to swallow. The total weight per soft capsule (total amount of contents and capsule film weight) is not limited, but considering the desired amount of health ingredients, ease of swallowing, capsule film strength, etc., 380 mg About 420 mg is preferable.
　本発明の軟カプセルは、ボトル容器などに詰めた後に、機能に関する表示を付して提供してもよい。機能の表示の方法には特別制限はないが、食品の包装、容器の面、食品の説明書、食品の広告等への表示が例示できる。本発明の軟カプセルが有する機能の例は、心血管リスク低減、中性脂肪低下作用、関節リウマチ症状緩和作用、加齢黄斑変性症発生リスク低減、認知機能低下抑制効果等が挙げられる。 The soft capsule of the present invention may be provided with a display regarding the function after being packed in a bottle container or the like. There are no particular restrictions on the method of displaying the function, but examples include display on food packaging, container surfaces, food instructions, food advertisements, and the like. Examples of the functions of the soft capsule of the present invention include cardiovascular risk reduction, neutral fat reduction action, rheumatoid arthritis symptom reduction action, age-related macular degeneration development risk reduction, cognitive function reduction suppression effect, and the like.
　以下に実施例に基づいて本発明の説明をするが、本発明はこれらの実施例に限定されるものではない。 Hereinafter, the present invention will be described based on examples, but the present invention is not limited to these examples.
　（参考例）
　濃縮度合いの違いによるＤＨＡ濃縮精製魚油中のＤＨＡ含有率とＥＰＡ含有率の違いを表１に示す。魚油はマグロの頭部から採取し、リパーゼを用いてＤＨＡ以外の脂肪酸を除去する方法によりＤＨＡを濃縮した。 (Reference example)
Table 1 shows the difference in DHA content and EPA content in the DHA-concentrated and refined fish oil depending on the degree of concentration. Fish oil was collected from the tuna head, and DHA was concentrated by a method of removing fatty acids other than DHA using lipase.
　なお、魚油中のＤＨＡ及びＥＰＡの量は、以下の方法に従って測定した：
　Ａ．試料の前処理
　魚油が軟カプセル中に含まれる場合には、中味液を注射針付きシリンジ等で取り出し、測定に供した。 The amount of DHA and EPA in fish oil was measured according to the following method:
A. Pretreatment of sample When fish oil was contained in a soft capsule, the content liquid was taken out with a syringe with an injection needle or the like and subjected to measurement.
　試料約５０ｍｇを５０ｍｌ共栓付平底フラスコに正しく量り取り、Ｎ／２水酸化ナトリウム－メタノール溶液６ｍｌを加え、還流冷却器を付けて水浴上で３０分間沸騰させた後、三フッ素ホウ素メタノール錯体－メタノール溶液７ｍｌを冷却器上部から加え、５分間沸騰させた後、更にヘキサン５ｍｌを冷却器上部から加え、１分間沸騰させた。加熱を止め、フラスコを冷却器から外し、冷後ヘキサン層がフラスコの首に達するまで塩化ナトリウム飽和水溶液を加えた。約１ｍｌのヘキサン溶液を試験管に移し少量の硫酸ナトリウム（無水）を加え、脱水したものを試料溶液とした。 About 50 mg of a sample is accurately weighed into a 50 ml flat-bottomed flask, added with 6 ml of N / 2 sodium hydroxide-methanol solution, boiled on a water bath for 30 minutes with a reflux condenser, and then trifluoroboron methanol complex- 7 ml of methanol solution was added from the upper part of the condenser and boiled for 5 minutes, and then 5 ml of hexane was further added from the upper part of the condenser and boiled for 1 minute. Heating was stopped, the flask was removed from the condenser, and after cooling, saturated aqueous sodium chloride was added until the hexane layer reached the neck of the flask. About 1 ml of hexane solution was transferred to a test tube, a small amount of sodium sulfate (anhydrous) was added, and the dehydrated sample solution was used.
　Ｂ．ガスクロマトグラフィー条件・カラム：Ｊ＆Ｗ　Ｓｃｉｅｎｔｉｆｉｃ　ＤＢ－ＷＡＸ　３０ｍ×０．２５ｍｍＩ．Ｄ．，０．２５μｍ
・検出器：ＦＩＤ
・キャリアーガス：Ｈｅ（１．５ｍｌ／ｍｉｎ）
・カラム温度：１４０℃（１ｍｉｎ）→３℃／ｍｉｎ→２３０℃（３０ｍｉｎ）
・注入口温度：２７０℃
・検出器温度：２７０℃
・試料溶液注入量：３μｌ
　Ｃ．計算方法および表示
　ピーク面積の総和（溶媒のピーク面積は除く）に対するＤＨＡおよびＥＰＡのそれぞれのピーク面積の百分率をもって、脂肪酸組成中のＤＨＡ含量（％）およびＥＰＡ含量（％）とした。 B. Gas Chromatography Conditions / Column: J & W Scientific DB-WAX 30m × 0.25mmI. D. , 0.25 μm
・ Detector: FID
-Carrier gas: He (1.5 ml / min)
Column temperature: 140 ° C. (1 min) → 3 ° C./min→230° C. (30 min)
・ Inlet temperature: 270 ° C
-Detector temperature: 270 ° C
Sample solution injection volume: 3 μl
C. Calculation method and display DHA content (%) and EPA content (%) in the fatty acid composition were percentages of the peak areas of DHA and EPA with respect to the total peak area (excluding the peak area of the solvent).
Figure JPOXMLDOC01-appb-T000001
 　（実施例１）
　前述の魚油を使い、以下の表２に示す組成（軟カプセル１粒当たり、単位ｍｇ）に従って加温下で撹拌混合し、軟カプセル用の内容物を調製した。ＥＰＡ濃縮精製魚油としては、市販の精製濃縮魚油を用いた。ビタミンＥ含有オイルおよび米胚芽油についても市販品を用いた。
Figure JPOXMLDOC01-appb-T000001
 Example 1
Using the aforementioned fish oil, the contents for soft capsules were prepared by stirring and mixing under heating in accordance with the composition shown in Table 2 below (unit per mg of soft capsule). Commercially available purified concentrated fish oil was used as the EPA concentrated purified fish oil. Commercial products were also used for vitamin E-containing oil and rice germ oil.
Figure JPOXMLDOC01-appb-T000002
 　別に、ゼラチン１００重量部および食添グリセリン３０重量部に水を加え、５０～６０℃で溶解し、軟カプセル皮膜用基材を調製した。
Figure JPOXMLDOC01-appb-T000002
 Separately, water was added to 100 parts by weight of gelatin and 30 parts by weight of dietary glycerin and dissolved at 50 to 60 ° C. to prepare a base material for soft capsule film.
　これらを用いて、ロータリーダイにより、なみだ形の軟カプセルを製造した。得られた軟カプセル１粒当たりの皮膜の重量は、いずれも１６０ｍｇであった（ゼラチン１２３ｍｇ、グリセリン３７ｍｇ）。軟カプセル全体の重量（１粒当たり）は、参考品が３９８ｍｇ、本発明品が３９５ｍｇであり、大きさは、いずれも、長径１５ｍｍ、短径７ｍｍであった。 These were used to produce a slender soft capsule using a rotary die. The weight of the film per one soft capsule obtained was 160 mg (gelatin 123 mg, glycerin 37 mg). The total weight (per capsule) of the soft capsules was 398 mg for the reference product and 395 mg for the product of the present invention, and the sizes were 15 mm for the major axis and 7 mm for the minor axis.
　参考品と本発明品とは、いずれも、４粒当たりにＤＨＡを３００ｍｇ以上、ＥＰＡを１００ｍｇ以上、セサミンを１０ｍｇ以上、ビタミンＥを４０ｍｇ以上含んでいた。これらに加えて、本発明品は、さらにγ－オリザノールを１０ｍｇ以上含んでいた。 Both the reference product and the product of the present invention contained 300 mg or more of DHA, 100 mg or more of EPA, 10 mg or more of sesamin, and 40 mg or more of vitamin E per 4 grains. In addition to these, the product of the present invention further contained 10 mg or more of γ-oryzanol.
　本発明品では、ＤＨＡの含有率が５０％以上となるように濃縮された魚油を、ＥＰＡ精製魚油と組み合わせることにより、参考品に対してカプセル１粒当たりの重量を大きくすることなく、参考品と同程度の量のＤＨＡ、ＥＰＡに加えて、さらに米胚芽油（健康成分であるγ－オリザノールを含む）を軟カプセル中に含有させることができた。 In the product of the present invention, the fish oil concentrated so that the DHA content is 50% or more is combined with the EPA refined fish oil without increasing the weight per capsule of the reference product. In addition to DHA and EPA in the same amount as in the above, rice germ oil (including γ-oryzanol as a health ingredient) could be further contained in the soft capsule.
　（実施例２）
　前述の魚油３を用い、以下の表３に示す組成（軟カプセル１粒当たり、単位ｍｇ）に従って、内容物重量が２２０～２６０ｍｇで、製剤重量が３８０～４２０ｍｇの軟カプセルを製造した。ＥＰＡ精製魚油、ビタミンＥ含有オイルおよび米胚芽油は市販品を用いた。製造方法は、実施例１に準じた。 (Example 2)
Using the aforementioned fish oil 3, soft capsules having a content weight of 220 to 260 mg and a preparation weight of 380 to 420 mg were produced according to the composition shown in Table 3 below (unit: mg per soft capsule). Commercially available EPA refined fish oil, vitamin E-containing oil and rice germ oil were used. The production method was in accordance with Example 1.
　得られた軟カプセルは、いずれも、４粒当たりにＤＨＡを３００ｍｇ以上、ＥＰＡを１００ｍｇ以上含んでいた。また、液状の魚油以外の油を、カプセル１粒当たり約２０～６０ｍｇ程度含んでおり、それでいて、服用しやすい大きさであった。 Each of the obtained soft capsules contained 300 mg or more of DHA and 100 mg or more of EPA per 4 capsules. In addition, about 20 to 60 mg of oil other than liquid fish oil was contained per capsule, and the size was easy to take.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003

Claims (11)

  1. 軟カプセル１粒当たりにドコサヘキサエン酸７５ｍｇ以上と、エイコサペンタエン酸とを含有する魚油を含み、さらに、常温で液状の魚油以外の油を含む、カプセル皮膜以外の重量が２２０ｍｇ～２６０ｍｇの軟カプセルの製造方法であって、
    ドコサヘキサエン酸の含有率が５０％以上となるように濃縮された魚油と、エイコサペンタエン酸の含有率が１５％以上である魚油と、これら以外の常温で液状の油とを混合すること、
    混合した油を軟カプセルの皮膜で包んで、内容量（カプセル皮膜以外の重量）が、２２０ｍｇ～２６０ｍｇの軟カプセルとすること、
    を含む、上記方法。     Production of soft capsules containing a fish oil containing 75 mg or more of docosahexaenoic acid and eicosapentaenoic acid per soft capsule, and further containing an oil other than fish oil that is liquid at room temperature and having a weight other than the capsule film of 220 mg to 260 mg A method,
    Mixing fish oil concentrated so that the content of docosahexaenoic acid is 50% or more, fish oil having a content of eicosapentaenoic acid of 15% or more, and liquid oil at room temperature other than these,
    Wrapping the mixed oil with a soft capsule film to make a soft capsule with an inner volume (weight other than the capsule film) of 220 mg to 260 mg,
    Including the above method.
  2. 前記エイコサペンタエン酸の含有率が１５％以上である魚油として、エイコサペンタエン酸の含有率が２５％以上となるように濃縮された魚油を用いる、請求項１に記載の方法。 The method according to claim 1, wherein a fish oil concentrated so that the content of eicosapentaenoic acid is 25% or more is used as the fish oil having a content of eicosapentaenoic acid of 15% or more.
  3. 軟カプセルが、１粒当たりにエイコサペンタエン酸を２５ｍｇ以上含有する、請求項１または２に記載の方法。 The method according to claim 1 or 2, wherein the soft capsule contains 25 mg or more of eicosapentaenoic acid per grain.
  4. ドコサヘキサエン酸の含有率が５０％以上となるように濃縮された魚油が、エイコサペンタエン酸を５％以上の含有率で含む、請求項１～３のいずれか１項に記載の方法。 The method according to any one of claims 1 to 3, wherein the fish oil concentrated so that the content of docosahexaenoic acid is 50% or more contains eicosapentaenoic acid in a content of 5% or more.
  5. 軟カプセル全体の重量（内容量とカプセル皮膜の重量の合計）が、３８０ｍｇ～４２０ｍｇである、請求項１～４のいずれか１項に記載の方法。 The method according to any one of claims 1 to 4, wherein the total weight of the soft capsule (the total of the content and the weight of the capsule film) is 380 mg to 420 mg.
  6. 常温で液状の魚油以外の油が、米胚芽油、亜麻仁油、荏胡麻油、オリーブ油、胡麻油またはこれらのうちの２種以上の混合物を含む、請求項１～５のいずれか１項に記載の方法。 The method according to any one of claims 1 to 5, wherein the oil other than fish oil that is liquid at room temperature comprises rice germ oil, linseed oil, sesame oil, olive oil, sesame oil, or a mixture of two or more thereof. .
  7. 軟カプセルが、常温で液状の魚油以外の油を、カプセル１粒当たり２０ｍｇ以上含む、請求項１～６のいずれか１項に記載の方法。 The method according to any one of claims 1 to 6, wherein the soft capsule contains 20 mg or more of oil other than fish oil that is liquid at normal temperature per capsule.
  8. 軟カプセルが、常温で液状の魚油以外の油を、カプセル１粒当たり２０～６０ｍｇ含む、請求項７に記載の方法。 The method according to claim 7, wherein the soft capsule contains 20 to 60 mg of oil other than fish oil that is liquid at room temperature per capsule.
  9. さらに、ビタミンＥを混合することを含む、請求項１～８のいずれか１項に記載の方法。 The method according to any one of claims 1 to 8, further comprising mixing vitamin E.
  10. さらに、セサミンを混合することを含む、請求項１～９のいずれか１項に記載の方法。 The method according to any one of claims 1 to 9, further comprising mixing sesamin.
  11. １粒当たりにドコサヘキサエン酸７５ｍｇ以上、エイコサペンタエン酸２５ｍｇ以上、及びγ－オリザノールを含む、１粒当たりの重量が３８０ｍｇ～４２０ｍｇである軟カプセル。 Soft capsules containing docosahexaenoic acid 75 mg or more, eicosapentaenoic acid 25 mg or more, and γ-oryzanol per grain and having a weight per grain of 380 mg to 420 mg.
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JP2017002015A (en) * 2015-06-16 2017-01-05 北海道水産工業株式会社 Supplement and production method thereof
CN112890197A (en) * 2021-03-10 2021-06-04 湖南文理学院 Fish oil product with health promotion effect
WO2023223943A1 (en) * 2022-05-16 2023-11-23 サントリーホールディングス株式会社 Vascular endothelium function-improving composition

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JPH10101550A (en) * 1996-09-25 1998-04-21 Asahi Chem Ind Co Ltd Film for soft capsule
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JPH08134026A (en) * 1994-10-20 1996-05-28 Prospa Bv Salt of aminoalcohol and medicinal prescription containing same
JPH10101550A (en) * 1996-09-25 1998-04-21 Asahi Chem Ind Co Ltd Film for soft capsule
JP2005535733A (en) * 2002-07-08 2005-11-24 アドバンスト ビジョン リサーチ EPA and DHA enriched omega-3 supplements for the treatment of dry eye, meibomian adenitis and xerostomia
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Publication number Priority date Publication date Assignee Title
JP2017002015A (en) * 2015-06-16 2017-01-05 北海道水産工業株式会社 Supplement and production method thereof
CN112890197A (en) * 2021-03-10 2021-06-04 湖南文理学院 Fish oil product with health promotion effect
WO2023223943A1 (en) * 2022-05-16 2023-11-23 サントリーホールディングス株式会社 Vascular endothelium function-improving composition

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