JP2013203693A - Composition including ginkgolide and seafood oil - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition for oral or external use having useful functions of DHA, EPA and the like contained in a seafood oil by reducing odor peculiar to the seafood oil, or by reducing the odor to make the seafood oil widely applicable to pharmaceuticals, food, cosmetics or the like.SOLUTION: A composition is prepared by blending 1 pts.wt. of a seafood oil and at least 0.005 pts.wt. of ginkgolide together. As a material including ginkgolide, a ginkgo leaf extract is blended.

Description

  The present invention relates to a composition containing ginkgolide and seafood oil, specifically, an oral or external composition such as pharmaceuticals, cosmetics and foods.

  It is known that seafood oil contains a lot of omega-3 fatty acids such as DHA and EPA. Conventionally, life-style related diseases such as myocardial infarction, cerebral infarction, diabetes and obesity, and brain diseases such as depression, schizophrenia, autism, hyperactivity disorder and Alzheimer's disease have deficiencies in DHA and EPA. It is known that they are related, and it has also been demonstrated that there is a causal relationship between them (Non-Patent Document 5). In addition, effects such as improvement of eye fatigue, improvement of dementia, and reduction of neutral fat have been reported (Non-patent Document 5). Furthermore, it has been reported that DHA has an effect of activating brain function and improving stress coping behavior (stress mitigating action, improvement of stress adaptation disorder) (Non-patent Document 6).

  As described above, DHA and EPA, which are abundant in seafood oil, have an excellent effect, and the Ministry of Health, Labor and Welfare has set the target amount of ω3 fatty acids to be taken as “1.0 g or more of EPA or DHA per day. However, because seafood oil has a peculiar smell of fish, the demand is not necessarily growing.

  On the other hand, ginkgolide is a component contained in ginkgo biloba, which has been used as a raw material for traditional Chinese medicines (Non-patent Document 1), and induces platelet aggregation, release of allergens, and release of active oxygen, resulting in thrombus. It has been confirmed that it suppresses the action of platelet activating factor (PAF), which is known as an information transmitter causing formation, allergic reaction, inflammation, bronchoconstriction, and cerebral circulatory dysfunction (Non-patent Document 2). And 3). For this reason, it is thought that it is effective in prevention of cerebral infarction and arteriosclerosis (nonpatent literature 4), and suppression of inflammation and allergic reaction.

  However, ginkgolide itself has a peculiar taste and bitterness, and also has a smell peculiar to ginkgolide, so it is not necessarily a substance that is easy to take.

Nakanishi, K. “The ginkgolides”, Pure and Applied Chemistry 14 (1), pp.89-113, 1967 Lamant V, et al., Biochem. Pharmacol., 36: 2749-2752, 1987 Braquet P, et al., J. Ethnopharmacol., 32: 135-139, 1991 Yan LJ, et al., Biochem. Biophys. Res. Commun., 212: 360-366, 1995 Michio Hashimoto, “Maintaining Brain / Nerve Functions with DHA and Medical Applications”, Food and Development Vol.45, No.1, pp.14-17, 2010 Meiji Watanabe et al., "Intracranial mechanism of stress adaptation by docosahexaenoic acid (DHA) ingestion-from the viewpoint of pathophysiology", Journal of Japanese Society of Pathophysiology 11 (3): 217-235, 2008

  An object of the present invention is to reduce the odor peculiar to the seafood oil for the seafood oil containing a large amount of ω3 fatty acids such as DHA and EPA having the above-described action. In addition, the present invention reduces the odor of seafood oil so that the seafood oil can be widely applied to pharmaceuticals (including oral and external use), food, cosmetics, etc., and the DHA, EPA, etc. An object of the present invention is to provide an oral or external composition having an effective function of an ω3 fatty acid.

  The present inventor has been diligently studying to achieve the above object, and has found that the smell unique to seafood oil can be suppressed by adding ginkgolide to the seafood oil in a specific ratio.

  In addition, as described above, ginkgolide also has peculiar taste, bitterness, and odor, but by adding ginkgolide to seafood oil at a specific ratio as described above, the taste of ginkgolide (puffy taste, It was also confirmed that bitterness and odor were reduced.

  The present invention has been completed based on these findings, and includes the following embodiments.

(1) Composition of the present invention (1-1) A composition containing ginkgolide in a proportion of at least 0.005 parts by weight per 1 part by weight of seafood oil.
(1-2) The composition according to (1-1), wherein the ratio of ginkgolide to 0.001 part by weight of fish oil is 1 part by weight.
(1-3) The composition according to (1-1) or (1-2), which contains a ginkgo biloba extract.
(1-4) The composition according to any one of (1-1) to (1-3), which is an oral composition or an external composition.
(1-5) The composition according to (1-4), wherein the oral composition is a pharmaceutical composition or a food composition, and the external composition is a pharmaceutical composition or a cosmetic composition.

(2) Method for suppressing seafood oil odor (2-1) Inhibiting odor peculiar to seafood oil, characterized in that ginkgolide is blended at a ratio of at least 0.005 parts by weight with respect to 1 part by weight of seafood oil. Method.
(2-2) The method according to (2-1), wherein the ratio of ginkgolide to 1 part by weight of seafood oil is 0.005 to 0.1 parts by weight.
(2-3) The method according to (2-1) or (2-2), wherein Ginkgo biloba leaf extract is blended as a composition containing ginkgolide.
(2-4) The method according to any one of (2-1) to (2-3), which is a method for suppressing seafood oil odor to a composition containing seafood oil.
(2-5) The method according to (2-4), wherein the composition is an oral composition or an external composition.

  The composition of the present invention is characterized in that the odor peculiar to fishery oil (fishery oil odor) is reduced by containing fishery oil and ginkgolide at a specific ratio. In addition, the composition of the present invention is characterized in that the taste (gummy taste, bitterness, odor) of ginkgolide is also reduced. For this reason, the composition of the present invention is an oral composition (pharmaceuticals, pharmaceutical department) having various actions of ω3 fatty acids such as DHA and EPA and ginkgolide contained in seafood oil, without much concern about seafood oil odor. It can be widely provided as an external product, food) or an external composition (pharmaceutical, quasi-drug, cosmetic).

  In particular, instead of ginkgolide alone (or in combination with ginkgolide alone), the composition of the present invention containing ginkgo biloba extract has various beneficial effects (antioxidant action, blood coagulation) as well as seafood oil action. (Non-patent document 6) because it has inhibitory action, improvement of dementia, improvement of memory, improvement of cerebral dysfunction, improvement of peripheral circulatory disorder, etc. It is useful as a sex food.

  Furthermore, according to the method for suppressing the smell of seafood oil according to the present invention, it is possible to suppress or reduce the off-flavor peculiar to seafood oil. Therefore, a composition that has been conventionally limited by the seafood oil odor (oral medicine, topical medicine, cosmetics, Including foods) can be widely mixed. As a result, it becomes possible to add the function of ω3 fatty acids such as DHA and EPA to many products used orally or externally.

(1) Composition of the present invention The composition of the present invention (the composition of the present invention) is characterized by containing ginkgolide and fishery oil in a specific ratio.

(1-1) Ginkgolide Ginkgolide is a type of terpenoid known to be contained in ginkgo biloba leaves, and there are five types of ginkgolides A, B, C, J and M depending on the difference in substituents. This has been confirmed (see Non-Patent Document 1).

  In the present invention, the ginkgolide can be any of the ginkgolides A, B, C, J, and M regardless of the type. In addition, ginkgolides A and B are known to have an action of suppressing platelet clotting action, inflammation, allergic reaction and the like of PAF by inhibiting platelet activating factor (PAF). Ginkgolide C is known to have an action of improving blood viscosity and smoothing, and Ginkgolide J has an action of removing blood flow injury.

  In the present invention, the ginkgolide may be not only one kind but also any combination of two or more kinds. Ginkgolide is preferably ginkgolide A, B, C and / or J, more preferably ginkgolide A, B and / or C.

  In the present specification and claims, the term “ginkgolide” is used as a collective term for ginkgolides A, B, C, J and M. In addition, in the present specification and claims, the content (blending amount) of ginkgolide such as the content of ginkgolide contained in the composition of the present invention (the composition of the present invention) or the ratio of ginkgolide to 1 part by weight of seafood oil. Unless otherwise stated, the description regarding shall mean the value calculated from the total amount or total amount of various ginkgolides contained in the composition of the present invention.

  The ginkgolide may be commercially available regardless of its origin or degree of purification, or may be prepared by extraction and purification from a plant containing ginkgolides such as ginkgo biloba leaves. Good (see Non-Patent Document 1).

  Moreover, it is not always necessary to use a purified product as ginkgolide, and a composition containing ginkgolide can also be used. Here, as the ginkgolide-containing composition, for example, a crude product (ginkgolide-containing plant extract) containing ginkgolide, which is extracted from a plant body containing ginkgolide and prepared by purification as necessary, can also be used.

  Here, as a plant body containing ginkgolide, preferably, ginkgo (Ginkgo biloba) can be mentioned. As a ginkgo plant, whole grass may be used, or a part thereof may be used. Examples of the ginkgo plant include ginkgo leaves or roots, preferably leaves.

  The method for preparing a ginkgolide-containing plant extract is not particularly limited as long as it can extract ginkgolide in the extract.For example, when using ginkgo leaves as a raw material, the ginkgo leaves are dried, and if necessary The mixture is subjected to an extraction treatment using a lower alcohol, acetone, or a mixed solvent of at least one of these organic solvents and water as an extraction solvent, and a fraction containing ginkgolide is extracted and obtained. A method can be mentioned.

  The extraction solvent is preferably lower alcohol or a mixture of lower alcohol and water (hydrous alcohol). The alcohol content in the case of using a hydrous alcohol is not particularly limited, but can be exemplified by about 30 to 90% by volume, preferably about 40 to 90% by volume, more preferably about 50 to 80% by volume. . Moreover, as a lower alcohol, C1-C3 alcohols, such as methanol, ethanol, propanol, or isopropanol, can be mentioned here. Ethanol is preferable.

  The extraction method is not particularly limited, and can be performed according to a conventional method. For example, an apparatus such as a cold immersion method in which the target plant body is extracted by being immersed in an extraction solvent at a temperature below room temperature, an immersion method in which extraction is performed by being immersed in a heated extraction solvent, or a Soxhlet extraction device is used. The extraction method used can be appropriately selected and used.

  The extract thus obtained is usually subjected to a solid-liquid separation step to remove the solid phase fraction and obtain a liquid phase fraction containing ginkgolide. Such a liquid phase fraction is usually used after distilling off the solvent according to a conventional method and concentrating or drying. The concentrated or dried product can be used as a ginkgolide-containing composition (ginkgolide-containing plant extract) as it is or dissolved in another solvent, and further can be used as a conventional purification method (for example, extraction treatment, column chromatography, etc.) ), And can be used as a crude product (ginkgolide-containing plant extract) in which the purity of ginkgolide is increased.

  Ginkgo biloba contains ginkgolic acid, which causes contact dermatitis and allergies. For this reason, when using a ginkgo leaf as a raw material of a plant body, it is necessary to refine | purify so that the said ginkgolic acid may not be included in a ginkgo leaf extract exceeding 5 ppm. In order to use ginkgo biloba extract as a health food in Japan, it is necessary to satisfy the standard of “containing 24% by weight or more of flavonoids, 6% by weight or more of terpenoid, and containing 5% or less of ginkgolic acid”. There is. Therefore, the ginkgo biloba extract used in the present invention is preferably prepared so as to conform to the standard.

  As described later, the proportion of ginkgolide in the composition of the present invention is 0.005 parts by weight or more, preferably 0.005 to 0.1 parts by weight, based on 1 part by weight of seafood oil contained in the composition of the present invention. More preferably 0.005 to 0.05 parts by weight, still more preferably 0.005 to 0.03 parts by weight, and particularly preferably 0.0075 to 0.025 parts by weight. Not. For example, within this limit, the proportion of ginkgolide in the composition of the present invention is appropriately set from the range of 0.01 to 3% by weight, preferably 0.1 to 3% by weight, more preferably 0.1 to 1% by weight. can do.

  The content of ginkgolide in the composition of the present invention can be analyzed and quantified by a known method. Specifically, for example, analysis and quantification can be performed by the following method.

(Ginkgolide analysis and quantification method)
100 mg of a sample is put in a beaker, 1 ml of water is added thereto, and after mixing well, 1 ml of ethanol is added. After dissolution by warming, add 8 ml of water to make it uniform. Further, 1 ml of water is added and dissolved, and the product filtered through a 0.45 μm membrane filter is used as an analysis sample. These samples are measured for ginkgolides A, B, C, J and M by high performance liquid chromatography. Note that the amount of the sample varies depending on the size of the measurement peak.
The operating conditions for the high performance liquid chromatograph analysis are as follows.
Detector: differential refractometer column: ODS-2 5 μm 4.6 × 15 cm
Mobile phase: water: methanol mixture (7: 3)
Flow rate: 1.0 ml / min
Column temperature: 40 ° C
Detection limit: 0.5 mg / 100 g.

(1-2) Seafood oil Seafood oil, which is a component of the composition according to the present invention, refers to fish such as horse mackerel, sardine, mackerel, shark, saury, cod, herring, tuna, etc .; marine mollusks such as squid; Oil obtained from seafood such as shellfish. Fish liver oil obtained from cod, shark, squid and the like is also included in the seafood oil that is a constituent of the composition according to the present invention.

  The seafood oil contains a significant amount of fatty acids. Specifically, myristic acid, myristoleic acid, pentadecanoic acid, palmitic acid, palmitoleic acid, heptadecanoic acid, heptadecenoic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, octadecatetraenoic acid, arachidic acid, eicosenoic acid , Eicosadienoic acid, eicosatrienoic acid, eicosatetraenoic acid, arachidonic acid, eicosapentaenoic acid, docosenic acid, docosadienoic acid, docosatetraenoic acid, docosapentaenoic acid, docosahexaenoic acid, tetracosenoic acid, behenic acid, hexadecadiene Acids, hexadecatrienoic acid, hexadecatetraenoic acid and the like; fatty acids obtained by subjecting these fatty acids to hydrogenation treatment, and the like.

  The seafood oil is not limited to one containing only one kind of the above-mentioned fatty acids, and two or more kinds may be contained.

  The fishery oil may contain acylglycerol in which at least one of the above fatty acids is ester-linked with mono-, di-, or tri-glycerol. Further, the seafood oil may contain hydrocarbons such as squalane and squalene.

  Among the above-described fatty acids, the fishery oil preferably contains a large amount of omega-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapetaenoic acid (EPA). Specifically, fish oil containing about 12 to 70% by weight of docosahexaenoic acid and about 3 to 45% by weight of eicosapetaenoic acid based on the total amount of fatty acids contained in the seafood oil is preferable as a component of the composition of the present invention. . In addition, the seafood oil contains about 80 to 95% by weight of fatty acids and docosahexaenoic acid and eicosapentaenoic acid in a total amount of 40 to 75% by weight, so that docosahexaenoic acid and eicosapentaenoic acid are included. Is analyzed and quantified by a known method such as a gas chromatographic method, whereby the content of seafood oil in the composition can be grasped. Specifically, for example, analysis and quantification can be performed by the following method.

(Analytical and quantitative analysis of seafood oil)
To 10 mg of the sample, 2 mg of tricosanoic acid as an internal standard and 15 ml of 1N potassium hydroxide-95% ethanol solution are added and heated to reflux at 95 ° C. for 1 hour. This is washed 3 times with 20 ml of petroleum ether to remove unsaponifiable matter. To the aqueous layer, 3 ml of 6N hydrochloric acid is added and extracted three times with 20 ml of diethyl ether. The diethyl ether layer is collected, washed three times with an equal amount of water, dehydrated with anhydrous sodium sulfate, and then dried under reduced pressure. 200 μl of N, N-dimethylformamide is added to this, and the mixture is methylated at 80 ° C. for 1 hour and measured by gas chromatography. Note that the amount of the sample varies depending on the size of the measurement peak.
The operating conditions for gas chromatographic analysis are as follows.
Column: CP-SU88 50 m × 0.25 mm, film thickness 0.2 μm
Detector: FID detector Temperature 240 ° C
Carrier gas: He 1.0ml / min
Injection method: Split method Split ratio 50: 1 Temperature 240 ° C
Column temperature: Initial temperature 180 ° C. Time 2 min
Temperature increase rate 4 ° C / min
Final temperature 235 ° C Time 10min
EPA detected in about 15 minutes, DHA detected in about 19 minutes.

  Although the said fish and shellfish oil is not restrict | limited, After subjecting the above-mentioned raw material to a steaming process as needed and pressing oil collection, it can obtain by removing to a solid-liquid separation process and removing a solid fraction. Furthermore, it may be subjected to purification as appropriate by subjecting it to steps such as acid treatment, alkali treatment, water washing treatment, decolorization treatment, dehydration treatment, enzyme treatment, distillation and the like as necessary.

  The blending ratio of the seafood oil in the composition of the present invention is determined in relation to the ginkgolide to be blended as described above. Further, the ratio of the seafood oil in the composition of the present invention is not particularly limited, but can be appropriately set within the range of 5 to 80% by weight, preferably 20 to 70% by weight.

(1-3) Composition of the Present Invention The composition of the present invention contains the aforementioned ginkgolide and fishery oil. Further, the composition of the present invention may contain a plant extract containing ginkgolide, specifically a ginkgo biloba extract, instead of ginkgolide (or together with a single ginkgolide).

  What is necessary is just to let the compounding ratio of the ginkgolide in this invention composition be 0.005 weight part or more with respect to 1 weight part of fishery oil. Preferably it is 0.005-0.1 weight part, More preferably, it is 0.005-0.05 weight part, More preferably, it is 0.005-0.03 weight part, Most preferably, it is 0.0075-0.025 weight part. It is.

  Further, in place of ginkgolide or together with single ginkgolide, the proportion of the ginkgolide-containing plant extract in the case of using the ginkgolide-containing plant extract is also converted to the amount of ginkgolide to be blended in the composition of the present invention. Can be set to a range.

  Examples of the method for measuring the contents of ginkgolide and seafood oil contained in the composition of the present invention include the methods described above.

  The composition of the present invention is based on the action of omega-3 fatty acids such as DHA and EPA contained in seafood oil, and lifestyle-related diseases such as myocardial infarction, cerebral infarction, diabetes and obesity; depression, schizophrenia, autism It is expected to have an effect of preventing or improving brain diseases such as hyperactivity disorder and Alzheimer's disease.

  In addition, the composition of the present invention has the effect of improving blood flow by making blood smooth based on the action of ginkgolide, the action of preventing cerebral infarction and arteriosclerosis, and the action of suppressing inflammation and allergic reaction. Be expected. In addition, when ginkgo biloba extract contains ginkgo biloba extract, based on the action of ginkgo biloba extract, it also has an antioxidant effect (removal of active oxygen and free radicals, inhibition of platelet aggregation, suppression of active oxygen production from inflammatory cells) Action), blood coagulation inhibitory action (PAF inhibitory action), cerebral infarction and arteriosclerosis preventive action), blood circulation improving action, blood pressure rise inhibiting action, blood sugar rise inhibiting action, dementia (Alzheimer type, cerebral vascular type) prevention Alternatively, it is expected to have an improving action, a memory improving action, a brain function disorder preventing or improving action, or a peripheral circulation disorder preventing or improving action (see Non-Patent Document 7 above).

  And although this invention composition contains fishery oil, the smell specific to fishery oil is suppressed and reduced by mix | blending a specific amount of ginkgolide with this. For this reason, the composition of the present invention can be used in various fields where the above-mentioned action can be used effectively, for example, in many fields applied to humans such as pharmaceuticals, quasi drugs, foods, and cosmetics. Is possible. Uses and application methods are not limited, and can be an oral composition or an external composition depending on various fields.

  Hereinafter, the oral composition and the composition for external use will be described.

(1-3-1) Oral Composition The oral composition targeted by the present invention includes a food composition and an oral pharmaceutical composition or quasi-drug described below.

(A) Food composition When the composition of the present invention is used as a food composition, the above-described composition of the present invention may be used as it is as a food composition, or a carrier or additive acceptable in the field of foods, or others. These food ingredients may be added and mixed, and any of them can be prepared in various food forms.

  Although it does not specifically limit as food, For example, various foods, such as confectionery, breads, soup, etc. are mentioned. A solid or semi-solid form is preferred. Also preferred are foods eaten at room temperature or lower.

  The food composition of the present invention, in addition to the food having the above-mentioned form, is a health food (nutrient functional food, for specific health use) intended for the action of ω3 fatty acids such as DHA and EPA and / or the action of ginkgolide and ginkgo biloba extract. Foods, etc.), supplements, functional foods such as foods for the sick, and the like. When preparing as such foods, for example, granules, films, tablets, capsules (hard capsules, soft capsules), tablets (including chewables), beverages (drinks) It is desirable to prepare in a form such as capsules, tablets, and granules, although these are preferable from the viewpoint of ease of ingestion, but are not particularly limited thereto.

  The food composition prepared in the above-mentioned preparation form can also be appropriately prepared according to a conventional method using the above-mentioned carrier acceptable in the field of food. Moreover, even when preparing in other forms, conventional methods may be followed, and the production method is not particularly limited as long as it does not impair the effects of the present invention, and is used by those skilled in the art for each application. It is sufficient to follow the method.

  In preparing the above-mentioned foods, functional foods and the like, they can be added together with auxiliary materials and additives usually used.

  The daily intake amount of the food composition of the present invention is not particularly limited, but it may be usually about 100 to 1000 mg in terms of the amount of seafood oil. Such an intake can be 1 to several intakes per day.

(B) Oral pharmaceutical composition, quasi-drug When the composition of the present invention is used as an oral pharmaceutical composition, the above-described composition of the present invention may be used as it is as an oral pharmaceutical composition, or is acceptable in the field of pharmaceuticals. Carriers and additives or other pharmaceutical ingredients may be added and mixed, and any of them can be prepared in various dosage forms.

  The oral pharmaceutical composition of the present invention is based on the action of omega-3 fatty acids such as DHA and EPA contained in seafood oil, and lifestyle-related diseases such as myocardial infarction, cerebral infarction, diabetes and obesity; depression, schizophrenia, It is expected to have an effect of preventing or ameliorating brain diseases such as autism, hyperactivity disorder and Alzheimer's disease. The oral composition of the present invention has the effect of improving blood flow by smoothing blood based on the action of ginkgolide, the action of preventing cerebral infarction and arteriosclerosis, and the action of suppressing inflammation and allergic reaction. It is expected. In addition, when ginkgo biloba extract contains ginkgo biloba extract, based on the action of ginkgo biloba extract, it also has an antioxidant effect (removal of active oxygen and free radicals, inhibition of platelet aggregation, suppression of active oxygen production from inflammatory cells) Action), blood coagulation inhibitory action (PAF inhibitory action), cerebral infarction and arteriosclerosis preventive action), blood circulation improving action, blood pressure rise inhibiting action, blood sugar rise inhibiting action, dementia (Alzheimer type, cerebral vascular type) prevention Alternatively, it is expected to have an improving action, a memory improving action, a brain function disorder preventing or improving action, or a peripheral circulation disorder preventing or improving action (see Non-Patent Document 7 above).

  Here, prevention means preventing the onset of the disease, specifically, preventing the onset of such a disease by acting on the onset mechanism of the disease in advance, It can be understood that a function higher than that at the time of normal or remission is acquired, and physiological damage of a lesion caused after the onset of the disease is reduced.

  The dosage form of the oral pharmaceutical composition of the present invention is not particularly limited, and examples thereof include powders, tablets, granules, pills, capsules (soft capsules or hard capsules), troches, chewable tablets, and dry syrups. Can be mentioned. Moreover, you may have a formulation form which controlled the release | release property of the medicinal component (for example, immediate release formulation, sustained release formulation, etc.). Also preferred are tablets, granules, pills, and capsules (soft capsules or hard capsules). Formulations having such dosage forms can be prepared according to conventional methods in the art.

  The oral pharmaceutical composition may be formulated with various carriers and additives that are pharmaceutically acceptable for oral administration in order to formulate the oral dosage form described above and to stabilize the oral dosage form (for example, Japan). (Refer to Pharmacopoeia, “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo)).

  In addition to the above components, as long as the effect of the present invention is not diminished, stabilizers, dispersants, fluidizing agents, buffering agents, wetting agents, thickening agents, preservatives, and the like, which are usually acceptable as additives for pharmaceuticals, Optional components such as a pH adjuster, a solvent, a solubilizing agent and the like can be added as desired.

  In addition to the above, other components such as amino acids, vitamins, and inorganic salts may be included.

  The above-mentioned oral pharmaceutical composition can be prepared and administered as the above-mentioned solid, semi-solid or liquid oral preparation (internal preparation), and the dosage depends on the patient's age, sex, degree of symptoms to be treated, And it can set suitably according to the administration method. For example, in terms of the ratio of seafood oil contained in the oral pharmaceutical composition, the daily dose for adults is usually about 100 to 1000 mg, preferably about 100 to 600 mg. Administration can be divided into several times a day as well as once a day.

  The oral pharmaceutical composition of the present invention can be used in combination with pharmaceuticals for known diseases in order to provide a better preventive or therapeutic effect.

(1-3-2) External Composition The external composition targeted by the present invention includes an external pharmaceutical composition, cosmetic composition or quasi-drug described below.

  The composition for external use of the present invention contains fishery oil as a constituent component. The seafood oil contains hydrocarbons such as squalane in addition to the ω3 fatty acid described above. Since such hydrocarbons are components that are easily taken into the body from the skin, the composition of the present invention can be effectively used as an external preparation composition.

(A) Externally used pharmaceutical composition When the composition of the present invention is used as an externally applied pharmaceutical composition, the composition of the present invention described above may be used as it is as an externally applied pharmaceutical composition, You may prepare in the form of various external pharmaceutical compositions with an additive.

  The dosage form of the external pharmaceutical composition is not particularly limited, and examples thereof include liquid preparations such as liquids, emulsions and suspensions; semisolid preparations such as ointments, gels and creams. Formulations having such dosage forms can be prepared according to conventional methods in the art.

  In order to formulate the external pharmaceutical composition into the above-mentioned external dosage form and to stabilize the pharmaceutical composition, various carriers and additives that are pharmaceutically acceptable for external administration can be blended (for example, Japan). (Refer to Pharmacopoeia, “Pharmaceutical Additives Encyclopedia” (published by Yakuji Nippo)).

  The pharmaceutical composition for external use of the present invention is expected to have an antioxidant action based on the action of ω3 fatty acids such as DHA and EPA contained in fishery oil. The composition for external use of the present invention is expected to have an action of suppressing inflammation and allergic reaction based on the action of ginkgolide. In addition, when ginkgo biloba extract contains ginkgo biloba extract, based on the action of ginkgo biloba extract, it also has an antioxidant effect (removal of active oxygen and free radicals, inhibition of platelet aggregation, suppression of active oxygen production from inflammatory cells) Action), blood coagulation inhibitory action (PAF inhibitory action), blood circulation improving action, or preventing or improving peripheral circulatory disturbance (see Non-Patent Document 7 above). Here, prevention is as described above.

  In addition to the above components, the pharmaceutical composition for external use of the present invention is generally a stabilizer, dispersant, fluidizing agent, buffering agent, wetting agent that is acceptable as an additive for pharmaceuticals, as long as the effects of the present invention are not diminished. Further, optional components such as thickeners, preservatives, pH adjusters, solvents and solubilizing agents can be added as desired.

  In addition to the above, other components such as amino acids, vitamins, and inorganic salts may be included.

  The above-mentioned external pharmaceutical composition can be prepared and administered as the above-mentioned preparation, and its dosage should be set appropriately according to the patient's age, sex, degree of symptoms to be treated, and administration method. Can do. For example, the daily dose of seafood oil contained in a pharmaceutical composition for external use is usually about 10 to 100 mg, preferably about 10 to 60 mg. If it is this administration range, it can also administer in 1 to several times a day.

(B) Cosmetic composition, quasi-drug for external use When the composition of the present invention is used as a cosmetic composition or quasi-drug for external use, the composition of the present invention described above is used as it is as a cosmetic composition or for external use. It may be a quasi-drug, or may be prepared in various dosage forms together with carriers and additives that are acceptable in the cosmetics field.

  If the composition of the present invention is used as a cosmetic composition, it can be expected to exhibit an antioxidant effect in vivo by being applied to skin, hair and the like. When the antioxidant action is exerted in the living body, it is possible to prevent the attack on the cells and the nucleic acid in the living body due to the action of the active oxygen, and the skin and hair tissues and cells caused by such an attack etc. It is expected to prevent aging. In particular, it is expected to have an effect as an anti-aging cosmetic which shows an effect of slowing or improving skin abnormalities such as skin wrinkles, atrophy, skin tissue loss, skin discoloration and the like due to aging. Moreover, since it is also expected to reduce the stress of participating in hair root cells in the scalp, an improvement effect on thinning hair is also expected.

  The shape of the cosmetic composition is not particularly limited, but for example, paste, lotion, mousse, gel, jelly, liquid, emulsion, suspension, cream, ointment, sheet, aerosol And spray form. Further, the form of the cosmetic composition is not limited. For example, makeup cosmetics such as foundation, blusher, and white powder; basic makeup such as lotion, emulsion, cream, lotion, oil, and pack Skin cleansing agents such as facial cleansers, cleansings, body cleansing agents, massage agents, wiping agents, detergents, bathing agents, and the like.

(2) Method of reducing off-flavor derived from seafood oil Although seafood oil exhibits various excellent actions based on the functions of ω3 fatty acids such as DHA and EPA, as described above, it has an off-flavor peculiar to seafood oil. There's a problem.

  The method of the present invention is a method for suppressing or reducing the odor (fishery oil odor) peculiar to the fishery oil by adding ginkgolide to the fishery oil at a specific ratio.

  The amount of ginkgolide to be mixed with seafood oil may be at least 0.005 parts by weight with respect to 1 part by weight of seafood oil. Preferably it is 0.005-0.1 weight part, More preferably, it is 0.005-0.05 weight part, More preferably, it is 0.005-0.03 weight part, Most preferably, it is 0.0075-0.025 weight part. It is.

  Here, the ginkgolide does not need to be purified, and may be a composition containing ginkgolide, specifically a plant extract containing ginkgolide. As such a ginkgolide-containing plant extract, a ginkgo leaf extract can be preferably mentioned. When using a ginkgolide-containing plant extract instead of ginkgolide (or together with a single ginkgolide), the ratio of mixing with seafood oil can be set in the above range in terms of the amount of ginkgolide.

  According to the method for suppressing seafood oil odor of the present invention, by suppressing or reducing the seafood oil odor, a composition containing a seafood oil odor (pharmaceutical composition (oral and external pharmaceutical composition), food composition, cosmetics). With regard to compositions and quasi-drug compositions (oral and topical pharmaceutical compositions), it is possible to suppress or reduce the smell of seafood oil. Therefore, the present invention can be rephrased as a method for suppressing or reducing the odor caused by seafood oil for a composition containing seafood oil.

  The method for measuring the content of seafood oil and the content of ginkgolide in the composition is as described above.

  Hereinafter, the configuration of the present invention and the effects thereof will be described using experimental examples. However, this invention is not restrict | limited at all by this Example.

Experimental Example 1 Deodorant effect of ginkgolide on seafood oil odor
1. material
1-1. Fish oil “Fish oil DHA / EPA (product name: DHA-46)” (Nihon Suisan Co., Ltd.) was used as fish oil. The seafood oil had a DHA content of 46% by weight and an EPA content of 5% by weight.

1-2. Preparation of Ginkgolide Ginkgo biloba extract was prepared by the method shown below, and this was used as a ginkgolide preparation in the following experiments.

  300 g of ginkgo biloba was extracted with 1000 ml of hydrous dimethyl ether at 25 ° C. for 30 minutes, and then the obtained extract was centrifuged, and the supernatant was dried at 40 ° C. for 1 hour to be powdered. It was 6.0 weight% when the ginkgolide content of the obtained ginkgo biloba extract (dry powder product) was measured by the following method.

<Measurement method of ginkgolide>
100 mg of a sample was placed in a beaker, 1 ml of water was added thereto, and after mixing well, 1 ml of ethanol was added. After dissolution by heating, 8 ml of water was added to make it uniform. Further, 1 ml of water was added and dissolved, and the product was filtered through a 0.45 μm membrane filter as an analysis sample. These samples were measured for ginkgolides A, B, C, J and M by high performance liquid chromatography.
The operating conditions for the high performance liquid chromatograph analysis were as follows.
Detector: differential refractometer column: ODS-2 5 μm 4.6 × 15 cm
Mobile phase: water: methanol mixture (7: 3)
Flow rate: 1.0 ml / min
Column temperature: 40 ° C
Detection limit: 0.5 mg / 100 g.

2. Experimental Method 800 mg of a mixed solution prepared by mixing the ginkgolide preparation and fishery oil prepared above in the ratio (weight ratio) shown in Table 1 was placed in a 10 ml glass screw vial and mixed and suspended with 5 ml of water. A test sample was obtained. In addition, the ratio of ginkgolide described in Table 1 is a value converted from the ratio of ginkgolide (6.0% by weight) contained in the ginkgolide preparation prepared above.

  About each test sample, the "smell peculiar to seafood oil (seafood oil scent)" and taste (total evaluation of ginkgoride peculiar taste, bitterness, and odor) were evaluated according to the following methods.

2-1. Evaluation of seafood oil odor At the room temperature, 10 monitors (5 men, 5 women) sniff the odor of each test sample, and the presence and extent of odor (fishery oil odor) peculiar to seafood oil A questionnaire survey was conducted. The questionnaire survey was conducted by answering the questionnaire with a 10-point evaluation based on the Visual Analogue Scale (hereinafter referred to as “VAS”), where “1” indicates a seafood oil odor and “10” indicates no seafood oil odor. We carried out by having.

  The evaluation results were averaged by the number of monitors, and the first decimal place was rounded off. Further, from the obtained seafood oil odor suppression effect, the fishery oil odor suppression effect per unit weight of ginkgolide was calculated by the following formula.

2-2. Evaluation of taste The above monitor was asked to include each of the above test samples in the mouth, and the taste was evaluated (total evaluation of ginkgolide peculiar taste, bitterness and odor). Specifically, the questionnaire was conducted by answering the questionnaire with a 10-level evaluation by VAS where “1” was a poor taste and “10” was a good taste. The evaluation results were averaged by the number of monitors, and the first decimal place was rounded off.

3. Experimental Results Table 1 shows the "fishery oil odor suppression effect" and the "fishery oil odor suppression effect per unit weight of ginkgolide" together with the ratio of seafood oil and ginkgolide in each test sample.

  As can be seen from the “fishery oil odor suppression effect” shown in Table 1, the seafood oil odor could be suppressed by blending ginkgolide in a proportion of 0.005 parts by weight or more with respect to 1 part by weight of the seafood oil. In addition, it was confirmed that the effect of suppressing the smell of seafood oil by ginkgolide depends on the blending ratio of ginkgolide, and the effect of suppression is increased by increasing the proportion of ginkgolide. Moreover, as can be seen from the “fish seafood oil odor suppressing effect per unit weight of ginkgolide” shown in the table, 0.005 to 0.025 parts by weight of ginkgolide, preferably 0.0075 to 0.005 parts per 1 part by weight of seafood oil. It was confirmed that by adding 025 parts by weight, preferably 0.0075 to 0.02 parts by weight, the seafood oil odor can be efficiently suppressed by a small amount of ginkgolide.

  In addition, from the questionnaire results on taste, by adding ginkgolide in a ratio of 0.005 to 0.03 parts by weight to the range of the above experiment, that is, 1 part by weight of seafood oil, the unique taste, bitterness and odor of ginkgolides It was confirmed that the suppression was also improved.

  For these reasons, using ginkgolide in combination with seafood oil not only suppresses the odor peculiar to seafood oil, but also suppresses the peculiar taste, bitterness and odor peculiar to ginkgolide, improving the overall taste of the oral composition. It was confirmed that it was possible.

Formulation Examples 1-28
Tablets were prepared in accordance with the formulation shown in Table 2, and capsules were prepared in accordance with the formulation shown in Table 3, respectively. In each case, the unique odor derived from the seafood oil was suppressed and the taste was also improved as in the Examples. In addition, the taste (gummy taste, bitterness, odor) of ginkgoride was also reduced.

Formulation examples 29-42
According to the formulation shown in Table 4, a composition for external use was prepared according to a conventional method. In each case, the unique odor derived from the seafood oil was suppressed as in the example. In addition, the taste (gummy taste, bitterness, odor) of ginkgoride was also reduced.

Claims (5)

  A composition containing ginkgolide in a proportion of at least 0.005 parts by weight with respect to 1 part by weight of seafood oil.   The composition of Claim 1 whose ratio of the ginkgolide with respect to 1 weight part of fishery oil is 0.005-0.1 weight part.   The composition according to claim 1 or 2, which contains a ginkgo biloba extract. The composition according to any one of claims 1 to 3, which is an oral composition or an external composition.   A method for suppressing or reducing the smell of seafood oil, wherein ginkgolide is blended at a ratio of at least 0.005 part by weight with respect to 1 part by weight of seafood oil.