JP2009007346A - Prophylactic for diabetes-combined disease - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide prophylactics for diabetes-combined diseases and prophylactic foods and drinks for diabetes-combined diseases, preventing diabetes-combined diseases. <P>SOLUTION: The prophylactics for diabetes-combined diseases contain pine bark extracts and astaxanthin. The pine bark extracts are preferably extracts containing ≥5 wt.% catechins and ≥20 wt.% oligomeric proanthocyanidin. As the astaxanthin, a free form, monoesters and diesters of the astaxanthin are each usable, and the Haematococcus alga extracts derived from natural products are preferable. The diabetes-superinducing disease preventives can be in a state of tablets, pills, capsules, granules, powders, powdered drugs or liquids, and may be solid foods, gel foods or drinks, each containing the diabetes-combined disease preventives. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  TECHNICAL FIELD The present invention relates to a preventive agent for diabetes complications useful for diabetic patients, and a food and drink for preventing diabetes complications, comprising pine bark extract and astaxanthin.

  Diabetes has a risk of causing not only complications such as diabetic neuropathy, diabetic kidney and diabetic retinopathy, but also diseases associated with diabetes such as arteriosclerosis (hereinafter referred to as “diabetes complications”). There are concerns. In order to prevent such complications of diabetes, intake of antioxidants is desired for the purpose of preventing fat-soluble peroxidation. Antioxidants include water-soluble substances and fat-soluble substances.

  One water-soluble substance is pine bark extract proanthocyanidins. Proanthocyanidins are a kind of water-soluble polyphenols contained in plants, and are known to have various activities such as antioxidant activity (Patent Document 1). Proanthocyanidins are known to have superoxide radical scavenging activity as an action, and synergistic action with vitamin C having an antioxidant action has been reported (Non-patent Document 1).

  One of the fat-soluble substances is astaxanthin in algae. Astaxanthin is a kind of fat-soluble carotenoid, widely distributed in nature, especially the ocean, such as shrimp, crab and other crustaceans, salmon, fish such as Thailand, algae such as green alga Hematococcus, yeasts such as red yeast Phaffia, It is used as a red pigment and has been found to have an antioxidant action about 1000 times that of vitamin E and about 40 times that of β-carotene. Astaxanthin is known as its action to suppress cataracts in diabetes (Patent Document 2), the therapeutic effect of insulin-dependent diabetes mellitus (Patent Document 3), and the improvement effect of metabolic syndrome (Patent Document 4).

On the other hand, since proanthocyanidins are water-soluble substances, there is a problem that the radical scavenging activity is low compared to other radicals with respect to alkoxy radicals and the like generated from fatty acids by the intervention of transition metal ions and the like. Astaxanthin is fat-soluble, so it has excellent scavenging effects on lipophilic active oxygen species such as singlet oxygen and lipid peroxidation suppression effect, but it has excellent scavenging effects on hydrophilic water-soluble active oxygen species. Not. The applicant combines a pine bark containing proanthocyanidins, a water-soluble antioxidant, obtained from natural products, and an astaxanthin, a fat-soluble antioxidant, and is extremely useful in terms of safety and synergistic. A patent application has been filed for an antioxidant-enhanced food that has an effect (Patent Document 5). However, the synergistic effect of a water-soluble substance and a fat-soluble substance for prevention of diabetes complications is not known.
Japanese Patent Publication No. 3-7232 Japanese Unexamined Patent Publication No. 10-276721 Japanese National Table 2004-534800 International Publication WO2006 / 59730 Pamphlet Japanese Unexamined Patent Publication No. 2005-21098 Bagchi D. et al., Toxicology, 2000, Vol. 148

  An object of the present invention is to provide a preventive agent for comorbidity with diabetes and a food and drink for preventing complications of diabetes, which have a synergistic effect of a water-soluble substance and a fat-soluble substance and can prevent a complication of diabetes.

As a result of intensive studies to achieve the above object, the present inventors have found an effect of preventing diabetes-complicated diseases by a synergistic effect of a pine bark extract and astaxanthin.
That is, the present invention
[1] An agent for preventing complications of diabetes, comprising pine bark extract and astaxanthin,
[2] The anti-diabetes agent according to the above [1], wherein the pine bark extract contains 5% by weight or more of catechins and 20% by weight or more of OPC,
[3] The agent for preventing diabetes associated with diabetes according to any one of [1] to [2], wherein astaxanthin is contained in an extract derived from Haematococcus algae.
[4] The agent for preventing complications of diabetes according to any one of [1] to [3], which is in the form of a tablet, pill, capsule, granule, powder, powder or liquid,
[5] A food or drink comprising the agent for preventing complications of diabetes according to any one of [1] to [4],
[6] The food or drink according to any one of [1] to [5], which is a solid food, a gel food, or a beverage, and
[7] The food or drink according to any one of [1] to [6], which is a soft drink.

  ADVANTAGE OF THE INVENTION According to this invention, the diabetes combined disease preventive agent and the diabetes combined disease prevention food-drinks which are useful for diabetes combined disease prevention can be provided.

  Hereinafter, embodiments of the present invention will be described. In addition, this invention should not be limited and interpreted by description of the following embodiment, A various change is possible within the range of description in a claim.

(Pine bark extract)
As the pine bark extract of the present invention, French coastal pine (Pinus
Martima), larch, black pine, Japanese red pine, Japanese pine, Korean pine, Korean pine, Japanese pine, Ryukyu pine, Utsukushima pine, Japanese pine, white pine, and Canada's Quebec aneda bark extract are preferably used. Among these, a bark extract of French coastal pine is preferably used.

French coastal pine is a marine pine that grows on the Atlantic coast of southern France. The bark of French coastal pine contains proanthocyanidin, which is a flavonoid, as a main component, and also contains an organic acid and other physiologically active components. This main component, proanthocyanidins, is known to have a strong antioxidant action to remove active oxygen.
The pine bark extract is obtained by extracting the pine bark with water or an organic solvent. When water is used, warm water or hot water is used. As an organic solvent used for extraction, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butane, acetone, hexane, cyclohexane, propylene glycol, hydrous ethanol, hydrous propylene glycol, ethyl methyl ketone, Organic solvents that are acceptable for the production of food or drugs such as glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible oils and fats, 1,1,1,2-tetrafluoroethane, 1,1,2-trichloroethene Preferably used. These water and organic solvents may be used alone or in combination. In particular, hot water, hydrous ethanol, hydrous propylene glycol and the like are preferably used.

  The extraction method from pine bark is not particularly limited, and for example, a warm extraction method, a supercritical fluid extraction method, or the like is used.

  The supercritical fluid extraction method is a method of performing extraction using a supercritical fluid that is a fluid that exceeds the critical point (critical temperature, critical pressure) of a gas-liquid substance. As the supercritical fluid, carbon dioxide, ethylene, propane, nitrous oxide (laughing gas) or the like is used, and carbon dioxide is preferably used.

  In the supercritical fluid extraction method, an extraction process for extracting a target component with a supercritical fluid and a separation process for separating the target component and the supercritical fluid are performed. In the separation step, any one of extraction separation by pressure change, extraction separation by temperature change, and extraction separation using an adsorbent / absorbent may be performed.

  Moreover, you may perform supercritical fluid extraction by the entrainer addition method. In this method, for example, ethanol, propanol, n-hexane, acetone, toluene, other aliphatic lower alcohols, aliphatic hydrocarbons, aromatic hydrocarbons, and ketones are added to the extraction fluid in an amount of 2 to 20 W / V. Add about% and perform supercritical fluid extraction using this fluid to dramatically increase the solubility of the target extract, such as OPC and catechins, in the extraction solvent, or enhance the selectivity of the separation. This is a method for obtaining an efficient pine bark extract.

  Since the supercritical fluid extraction method can be operated at a relatively low temperature, it can be applied to substances that are altered or decomposed at high temperatures, the advantage that the extraction fluid does not remain, and the solvent can be recycled, so the desolvation process There is an advantage that the process can be simplified.

  Extraction from pine bark may be performed by a liquid carbon dioxide batch method, a liquid carbon dioxide reflux method, a supercritical carbon dioxide reflux method, or the like other than the above extraction method.

  For extraction from pine bark, a plurality of extraction methods may be combined. By combining a plurality of extraction methods, it becomes possible to obtain pine bark extracts having various compositions.

  The pine bark extract obtained by the above extraction is safe to be purified by ultrafiltration or a column method or a batch method using an adsorptive carrier (Diaion HP-20, Sephadex-LH20, chitin, etc.). From the viewpoint of

  Specifically, the pine bark extract used for the preventive agent for complications of diabetes according to the present invention is prepared by the following method, but this is illustrative and is not limited to this method.

  1 kg of French coastal pine bark is placed in 3 L of a saturated aqueous solution of sodium chloride and extracted at 100 ° C. for 30 minutes to obtain an extract (extraction process). Thereafter, the extract is filtered, and the resulting insoluble matter is washed with 500 mL of a saturated solution of sodium chloride to obtain a washing solution (washing step). The extract and washing solution are combined to obtain a crude extract of pine bark.

  Next, 250 mL of ethyl acetate is added to the crude extract and the phases are separated, and the process of recovering the ethyl acetate layer is repeated 5 times. The collected ethyl acetate solutions are combined and added directly to 200 g of anhydrous sodium sulfate for dehydration. Thereafter, the ethyl acetate solution is filtered, and the filtrate is concentrated under reduced pressure until the original volume is reduced to 1/5. The concentrated ethyl acetate solution is poured into 2 L of chloroform, and the resulting precipitate is collected by filtration. Thereafter, the precipitate is dissolved in 100 mL of ethyl acetate, and then added again to 1 L of chloroform and precipitated for washing twice. By this method, for example, about 5 g of pine bark extract containing 20% by mass or more of proanthocyanidins having a degree of polymerization of 2 to 4 and 5% by mass or more of catechins is obtained. Here, the content of the specific component in the extract is a value based on the dry mass of the extract. The same applies hereinafter.

(Composition of pine bark extract)
The pine bark extract used in the present invention contains proanthocyanidins as one of the main active ingredients. Proanthocyanidins refer to a group of compounds consisting of a condensation polymer having a degree of polymerization of 2 or more, with flavan-3-ol and / or flavan-3,4-diol as a structural unit. It is a powerful antioxidant produced by plants and is intensively contained in the leaves, bark, fruit peel and seeds of plants. This proanthocyanidin is a substance that cannot be produced in the human body.

  When a pine bark extract containing this proanthocyanidin is ingested, an excellent effect of improving lipid metabolism is obtained. The pine bark extract contains a condensed polymer having a polymerization degree of 2 or more as proanthocyanidins, and further contains catechin and the like. In particular, proanthocyanidins containing a large amount of a condensation polymer having a low degree of polymerization are preferably used. The condensation polymer having a low polymerization degree is preferably a condensation polymer having a polymerization degree of 2 to 30 (2 to 30 mer), more preferably a condensation polymer having a polymerization degree of 2 to 10 (2 to 10 mer). Further, a condensation polymer (2 to 4 mer) having a polymerization degree of 2 to 4 is more preferable. Proanthocyanidins that are condensation polymers having a degree of polymerization of 2 to 4 (2 to 4 mer) are particularly easily absorbed into the body. In the present specification, the polymer having a degree of polymerization of 2 to 4 is referred to as oligomeric proanthocyanidin (hereinafter referred to as “OPC”).

  Moreover, as a pine bark extract, 15% by mass, preferably 20% by mass or more, and more preferably 30% by mass of a condensation polymer having a degree of polymerization of 2 to 4 (2 to 4 mer; that is, OPC). An extract containing a pentamer or more proanthocyanidins in a proportion of 10% by mass or more, preferably 15% by mass or more is preferable.

  The pine bark extract may further contain catechins, and these catechins are preferably contained in a proportion of 5% by mass or more, more preferably 10% by mass or more. Catechin can be extracted together with proanthocyanidins (OPC) by the above extraction method. Catechin is a general term for polyhydroxyflavan-3-ol. As catechins, (+)-catechin (referred to as catechin in a narrow sense), (−)-epicatechin, (+)-gallocatechin, (−)-epigallocatechin, epigallocatechin gallate, epicatechin gallate, and afzelechin Etc. are known. From the above pine bark extract, in addition to the above (+)-catechin, gallocatechin, afzelekin, and (+)-catechin or 3-galloyl derivatives of gallocatechin have been isolated. Catechins are known to have a carcinogenic inhibitory effect, an active oxygen or free radical scavenging effect, an antioxidant effect, and the like. In addition, catechins are known to have an antidiabetic effect that suppresses an increase in blood sugar. Catechins are poor in water solubility by themselves and have low physiological activity, but in the presence of OPC, catechins have the property of being activated at the same time as water solubility increases. Therefore, catechins work effectively when ingested with OPC.

  The catechins are preferably contained in the pine bark extract in an amount of 5% by mass or more. More preferably, the pine bark extract containing 20% by mass or more of OPC and 10% by mass or more of a pentamer or more of proanthocyanidins preferably contains 5% by mass or more of catechins. For example, when the catechin content of the pine bark extract is less than 5% by mass, the catechins may be added so that the content is 5% by mass or more. It is most preferable to use a pine bark extract containing 5% by mass or more of catechins, 20% by mass or more of OPC, and 10% by mass or more of proanthocyanidins of 5 or more.

(Astaxanthin)
Astaxanthin used in the present invention includes astaxanthin and / or an ester thereof unless otherwise specified. Furthermore, the ester of astaxanthin includes a monoester form and / or a diester form. Moreover, the natural product containing astaxanthin is included.

  As the astaxanthin of the present invention, at least one of astaxanthin free form, monoester form and diester form can be used. Diesters are chemically and physically more stable than free and monoesters because two hydroxyl groups are protected by ester bonds, and are less susceptible to oxidative degradation in the composition of the present invention. However, it is considered that when it is taken into the intestine by an enzyme or into a living body, it is rapidly hydrolyzed to astaxanthin by the in vivo enzyme and exhibits an effect.

  Examples of astaxanthin monoesters include esters esterified with lower or higher saturated fatty acids or lower or higher unsaturated fatty acids. Specific examples of the lower or higher saturated fatty acid or the lower or higher unsaturated fatty acid include acetic acid, lauric acid, myristic acid, pentadecanoic acid, palmitic acid, palmitooleic acid, hebutadecanoic acid, elaidic acid, ricinoleic acid, and betrothelin. Acid, vaccenic acid, eleostearic acid, punicic acid, ricinic acid, parinaric acid, gadoric acid, 5-eicosenoic acid, 5-docosenoic acid, cetoleic acid, erucic acid, 5,13-docosadienoic acid, ceracholic acid, decenoic acid , Stering acid, dodecenoic acid, oleic acid, stearic acid, eicosaopentaenoic acid, docosahexaenoic acid, linoleic acid, linolenic acid, arachidonic acid and the like. Examples of carotenoid diesters include diesters esterified with the same or different fatty acids selected from the group consisting of the above fatty acids.

  Furthermore, astaxanthin monoesters include amino acids such as glycine and alanine; mono- or polyvalent carboxylic acids such as acetic acid and citric acid; inorganic acids such as phosphoric acid and sulfuric acid; sugars such as glucoside; glycerosugar fatty acids and sphingosaccharides. Examples thereof include sugar esters such as fatty acids; fatty acids such as glycero fatty acids; monoesters esterified with glycerophosphoric acid and the like. In addition, the salt of the said monoester is also included when it can be considered. Examples of fatty acid derivatives include phospholipid type, alcohol type, ether type, sucrose ester type and polyglycerin ester type of the above fatty acids.

  Astaxanthin diester, the group consisting of the lower saturated fatty acid, higher saturated fatty acid, lower unsaturated fatty acid, higher unsaturated fatty acid, amino acid, mono- or polyvalent carboxylic acid, inorganic acid, sugar, sugar fatty acid, fatty acid and glycerophosphoric acid And diesters esterified with the same or different acids selected from In addition, the salt of the said diester is also included when it can be considered. Examples of the diester of glycerophosphoric acid include saturated fatty acid esters of glycerophosphoric acid, or glycerophosphoric acid esters containing fatty acids selected from higher unsaturated fatty acids, unsaturated fatty acids or saturated fatty acids.

Astaxanthin means a product derived from a natural product or obtained by synthesis. Examples of those derived from natural products include microalgae such as the green alga Hematococcus, yeasts such as the red yeast Phaffia, crustacean shells such as shrimp, krill and crabs, craniopod viscera such as squid and octopus, various Seafood skins and fins, petals of the genus Adonis, such as Natsuzaki Fukujusou, Paracoccus
Production of α-proteobacteria such as sp. N81106, Brevundimonas sp. SD212, Erythrobacter sp. PC6, actinomycetes such as Gordonia sp. Examples include those obtained from genetically modified organisms. Natural extracts and chemically synthesized products are commercially available and are readily available.

  Astaxanthin is 3,3′-dihydroxy-β, β-carotene-4,4′-dione and has stereoisomers. Specifically, three stereoisomers of (3R, 3′R) -astaxanthin, (3R, 3 ′S) -astaxanthin and (3S, 3 ′S) -astaxanthin are known. Any of these can be used. The present invention includes monoesters and diesters of these astaxanthin isomers.

  In the present invention, the fatty acid ester of astaxanthin may be any of those derived from natural products or those obtained by synthesis, but those derived from natural products in which astaxanthin esters are dissolved in various oils and fats are preferred from absorption in the body. Natural sources include, for example, a krill extract, a faffia yeast extract, and a hematococcus alga extract. Particularly preferred is a hematococcus alga extract depending on the stability of astaxanthin and the type of ester of astaxanthin.

  Fatty acid esters of astaxanthin have not been observed to be mutagenic, are known to be highly safe compounds, and are widely used as food additives (Jiro Takahashi et al .: Toxicity test of hematococcus alga astaxanthin-Ames Test, rat single dose toxicity test, rat 90 day repeated oral dose toxicity test-, clinical medicine, 20: 867-881, 2004).

  Haematococcus algae is a green algae belonging to the Volboxic Chlamydomonas family, and since it is a green algae, it has a high chlorophyll content and is green, and it swims in the water with two flagella, but it lacks nutrient sources, changes in temperature, etc. Under starvation conditions, dormant spores are formed, the astaxanthin content is increased, and red spheres are formed. In the present invention, hematococcus in any state can be used, but it is preferable to use hematococcus that has become dormant spores containing a large amount of astaxanthin. In addition, among green algae belonging to the genus Haematococcus, for example, Haematococcus pluvialis is preferable.

  As a method for culturing Haematococcus green algae, a hermetically sealed culture method is preferred in which no foreign microorganisms are mixed and propagated and other contaminants are not mixed. For example, a partially open-type dome shape, conical shape or cylindrical shape is preferable. A culture method using a culture medium having a culture apparatus and a gas discharge device movable within the apparatus (International Publication No. 99/50384), or culturing by irradiating light from inside a sealed culture apparatus And a method using a flat culture tank or a tube-type culture layer are suitable.

  The method for obtaining an extract from Haematococcus algae according to the present invention includes a method in which Haematococcus algae is dried and pulverized and then extracted with an organic solvent such as acetone or alcohol, and the Haematococcus algae is suspended in an organic solvent and pulverized and extracted simultaneously. Or a supercritical extraction method using carbon dioxide or the like.

  The method for obtaining an extract from Haematococcus algae according to the present invention includes a method in which Haematococcus algae is dried and pulverized and then extracted with an organic solvent such as acetone or alcohol, and the Haematococcus algae is suspended in an organic solvent and pulverized and extracted simultaneously. Or a supercritical extraction method using carbon dioxide or the like.

The supercritical extraction method can be performed by a conventional method. For example, the extraction method from pine bark described above, or Hirose (Ind Eng Chem Res, 2006, 45 (10), 3652-3657, Extraction of
Astaxanthin from Haematococcus pluvialis Using Supercritical CO2 and Ethanol as
Entrainer) et al.

  Various methods are known for extracting and purifying the culture or the crustacean using an organic solvent. For example, since astaxanthin and its esters are oil-soluble substances, astaxanthin-containing components can be extracted from natural products containing astaxanthin with an oil-soluble organic solvent such as acetone, alcohol, ethyl acetate, benzene, and chloroform. Also, supercritical extraction can be performed using carbon dioxide, water, or the like. After extraction, the solvent is removed according to a conventional method to obtain a mixed concentrate of monoester type astaxanthin and diester type astaxanthin. The obtained concentrate can be further purified by separation column or lipase decomposition, if desired.

  A method of drying Haematococcus algae cultured in the above-mentioned dome type culture apparatus or closed type culture apparatus, extracting with acetone after pulverization, or performing pulverization and extraction in acetone at the same time, and then removing acetone to extract astaxanthin However, since there is almost no oxidation of astaxanthin because it does not come into contact with air, there are few impurities, that is, there are few substances that inhibit the effects of the present invention, and astaxanthin and triglyceride can be contained in high purity, which is preferable.

  In the present invention, when astaxanthin is used, synthetic astaxanthin or naturally-derived astaxanthin can be used, but astaxanthin derived from natural products, particularly extracted from Haematococcus algae, includes astaxanthin as a component other than astaxanthin. It is preferable because it contains a substance that promotes stability and absorbability to the living body.

  The preventive agent for comorbidity of diabetes according to the present invention is effective in preventing a complication of diabetes associated with a high blood glucose level even before diabetes. Further, by administering / ingesting the preventive agent for comorbidity of diabetes according to the present invention, in addition to prevention, it has improvement, treatment, and suppression effects. In addition to the three major diabetic complications of diabetic neuropathy, diabetic kidney, diabetic retinopathy, diabetic nephropathy, diabetic foot lesion, diabetic gangrene, arteriosclerosis It is effective for concurrent diseases such as hyperlipidemia, myocardial infarction, cerebral infarction, stroke, chronic infection, cholelithiasis, and dementia. In addition, by improving and preventing these comorbidities of diabetes, there is also an effect of improving diabetes in diabetes itself in which symptoms have worsened.

  The preventive agent for comorbidity with diabetes according to the present invention has an unprecedented effect due to the synergistic effect of a water-soluble antioxidant substance and a pine bark extract, which is a fat-soluble antioxidant substance, and astaxanthin. There are hydrophilic and lipophilic reactive oxygen species in the living body, and for the elimination of these, the existence of antioxidants effective for each elimination is effective. The effect of suppressing oxidative damage in two stages is remarkable. Substances that are ingested and both present in the body at about the same time are preferred, and pine bark extract and astaxanthin are particularly effective. Furthermore, pine bark extract and astaxanthin have been proven to be safe for long-term intake, and are suitable for drugs that require long-term intake such as diabetes. The compound of pine bark extract and astaxanthin, which is a preventive agent for complications of diabetes according to the present invention, may be formulated according to a conventional method and does not need to be in a special form.

  The pine bark extract and astaxanthin contained in the agent for preventing diabetes complications of the present invention are highly absorbable in the living body and can be easily added to foods and drinks while maintaining their functions. In addition, an effect can be expected in a short period after the start of intake, and a sufficient effect can be obtained even with a small amount of intake. Therefore, it is highly useful as a meal material for elderly people, diabetics, etc., whose intake allowance and intake form as food and drink are limited. The food / beverage products of the present invention may be food / beverage products that can be sold for the purpose of efficacy, such as health foods (special health foods, nutritional foods).

(Diabetic disease preventive agent of the present invention)
The agent for preventing diabetes according to the present invention contains pine bark extract and astaxanthin, and the ratio thereof is arbitrary. Preferably, astaxanthin is contained in an amount of 0.1 to 1000 parts by weight, preferably 1 to 200 parts by weight, more preferably 2 to 50 parts by weight, based on 100 parts by weight of the pine bark extract.

  The amount of pine bark extract and astaxanthin in the preparation of the present invention is not particularly limited, but when the purpose is to obtain an excellent effect of pine bark extract and astaxanthin, Usually, it is 0.01 to 80% by weight, preferably 0.1 to 50% by weight.

  The agent for preventing diabetes complications of the present invention can be appropriately prepared by known methods in the form of solids or solutions such as tablets, pills, capsules, granules, powders, powders, softeners, gels, and liquids. That is, the solid preparation or liquid preparation useful as the preparation of the present invention is produced by mixing a pine bark extract and astaxanthin and, if desired, an additive and using a well-known preparation method that has been well established. . Examples of additives include excipients, pH adjusting agents, cooling agents, suspending agents, diluents, antifoaming agents, thickeners, solubilizers, disintegrating agents, binders, lubricants, antioxidants. Agents, coating agents, colorants, flavoring agents, surfactants, plasticizers or fragrances.

  Examples of the excipient include sugar alcohols such as D-sorbitol, D-mannitol or xylitol, sugars such as glucose, sucrose, lactose or fructose, crystalline cellulose, carmellose sodium, calcium hydrogen phosphate, wheat starch, rice Examples thereof include starch, corn starch, potato starch, dextrin, β-cyclodextrin, light anhydrous silicic acid, titanium oxide, and magnesium aluminate metasilicate.

  Examples of the pH adjuster include citric acid, malic acid, sodium hydrogen phosphate, and dipotassium phosphate.

  Examples of the refreshing agent include l-menthol or mint water.

  Examples of the suspending agent include kaolin, carmellose sodium, xanthan gum, methylcellulose, and tragacanth.

  Examples of the diluent include purified water, ethanol, vegetable oil, and emulsifier.

  Examples of the antifoaming agent include dimethylpolysiloxane or silicon antifoaming agent.

  Examples of the thickener include xanthan gum, tragacanth, methylcellulose, and dextrin.

  Examples of the solubilizer include ethanol, sucrose fatty acid ester, and macrogol.

  Examples of the disintegrant include low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium, croscarmellose sodium, hydroxypropyl starch, or partially pregelatinized starch.

  Examples of the binder include methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, gelatin, gum arabic, ethylcellulose, polyvinyl alcohol, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, or propylene glycol alginate. Can be mentioned.

  Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, and white beeswax.

  Examples of the antioxidant include ascorbic acid, dibutylhydroxytoluene (BHT), propyl gallate, butylhydroxyanisole (BHA), and citric acid.

  Examples of the coating agent include hydroxypropylmethylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer. , Hydroxypropylmethylcellulose acetate succinate, methacrylic acid copolymer, polyvinyl acetate diethylaminoacetate or shellac.

  Examples of the colorant include turmeric extract, riboflavin, and titanium oxide.

  Examples of the flavoring agent include citric acid, adipic acid, fructose, D-sorbitol, glucose, sodium saccharin, simple syrup, sucrose, honey, amacha, licorice, citric acid, adipic acid, orange oil, spruce tincture, fennel oil, mint Or menthol etc. are mentioned.

  Examples of the surfactant include polyoxyethylene hydrogenated castor oil, glyceryl monostearate, sorbitan monostearate, sorbitan monolaurate, polyoxyethylene polyoxypropylene, polysorbates, sodium lauryl sulfate, macrogol or sucrose. Examples include fatty acid esters.

  Examples of the plasticizer include triethyl citrate, polyethylene glycol, triacetin, and cetanol.

  As said fragrance | flavor, synthetic fragrance | flavors, such as natural fragrance | flavors, such as an animal fragrance | flavor or a vegetable fragrance | flavor, or an isolated fragrance | flavor, a pure synthetic fragrance | flavor, etc. are mentioned, for example.

(Diabetic disease-preventing food or drink of the present invention)
The food / beverage products of this invention are manufactured by mix | blending a pine bark extract and an astaxanthin or the said diabetes disease preventive agent with food-drinks material at the time of food-drinks manufacture. For example, solid foods such as bread, chewing gum, cookies, chocolate, cereals, jams, ice creams, yoghurts, jellys, jams, creams or gels, juices, coffee, cocoa, green tea, oolong teas, teas, etc. Any food form can be used. Moreover, it can also mix | blend with a seasoning, a food additive, etc. The blending amount of the pine bark extract and astaxanthin or the above-mentioned diabetes disease preventive agent into the food or drink material is not particularly limited, but is usually about 0.00001 to 80% by weight, preferably about 0.00005 to 50% by weight. . Moreover, especially in the case of a soft drink, it is 1 mg / L-20 g / L, Preferably it is 2 mg / L-10 g / L.

  ADVANTAGE OF THE INVENTION According to this invention, the diabetes combined disease preventive agent containing a pine bark extract and astaxanthin and the diabetes combined disease preventive food are obtained. When a diabetic patient takes this food, the effect on prevention of comorbid diseases is enhanced.

Hereinafter, the present invention will be described with reference to examples. The present invention should not be construed as being limited to the following examples, and various modifications can be made within the scope of the claims.

(Test 1)
In order to evaluate the effect of the preparation according to the present invention for preventing diabetes-associated disease, the following experiment was conducted using a diabetes model rat.
Diabetic model rats were prepared such that streptozotocin-containing physiological saline (STZ: Wako Pure Chemical Industries, Ltd.) was intraperitoneally administered at a rate of 50 mg / kg, and the urine volume became 100 mL / day or more after 7 to 10 days. .
As the feed, a solid feed (CF-2: Nippon Claire Co., Ltd.) was used and each test substance was contained. These diets were freely consumed by diabetic model rats throughout the test period. Table 1 shows the composition of the feed.
In this test, a pine bark extract (Toyo Shinyaku Co., Ltd .: containing 5% by mass or more of catechins and 20% by mass or more of OPC) was used.
In this test, astaxanthin (Fuji Chemical Industry Co., Ltd .: Haematococcus alga extract, containing 5% by mass of astaxanthin in terms of free astaxanthin) was used.

各値は質量％である。

Each value is mass%.

  Seven-week-old male diabetic model rats were used in the test with 8 animals in each group (32 animals in total). Diabetes model rats that had been fed for 16 weeks and were fasted for 16 hours or more on the last day of the study were dissected under Nembutal (Dainippon Pharmaceutical Co., Ltd.) anesthesia, and blood, liver and kidney Elephants were collected.

  Blood glucose level of collected blood, one of the risk factors of arteriosclerosis, serum TBARS, liver chemirmi, kidney chemirmi, which is generally used as an index of lipid peroxide production, which is one of the risk factors of arteriosclerosis Neutral fat was measured. The average value of the obtained numerical values was calculated. The test results are shown in Table 2 below and FIGS.

  As shown in Table 2, when blood glucose level and neutral fat were compared, Example 1 and Comparative Example 1 showed significantly lower values than Comparative Example 3. When comparing kidney chemirmi, Example 1 and Comparative Example 2 showed significantly lower values than Comparative Example 3. Moreover, when liver chemirmi and serum TBARS were compared, Example 1 showed a significantly lower value than Comparative Examples 1-3. It was confirmed that the prophylactic agent has a synergistic effect on lipid peroxide production and neutral fat suppression. From the above results, it was confirmed that the preventive agent for comorbidity with diabetes according to the present invention using a combination of pine bark extract and astaxanthin synergistically exhibits the effect of preventing complications of diabetes.

[Production Example 1] Tablet According to a conventional method, the following ingredients were uniformly mixed and tableted at the following composition ratio to give a tablet of 300 mg per tablet.
Asteryl powder 20F 50 parts by weight Pine bark extract 20 parts by weight Potato starch 20 parts by weight Crystalline cellulose 10 parts by weight Polyvinyl alcohol 2 parts by weight Magnesium stearate 1 part by weight Asteryl powder 20F [manufactured by Fuji Chemical Co., Ltd.] is free It is a powder produced from Haematococcus alga extract oil containing 2% by weight of astaxanthin in terms of body. The pine bark extract used here contains 20% by mass and 5% by mass of catechin as OPC [manufactured by Toyo Shinyaku Co., Ltd.].

[Production Example 2] Capsules According to a conventional method, 100 mg of soft capsule skin (70 parts by weight of gelatin, 25 parts by weight of glycerin) was kneaded with the following components in the following composition ratio and filled with 300 mg to obtain soft capsules of 400 mg per capsule. .
Contents Asteryl oil 50F 20 parts by weight Pine bark extract 7 parts by weight Medium chain fatty acid triglyceride 73 parts by weight Asteryl oil 50F [manufactured by Fuji Chemical Industry Co., Ltd.] is a hematococcus containing 5% by weight of astaxanthin in terms of free form Algae extract oil.

  According to the present invention, it is possible to provide a preventive agent for comorbidity with diabetes, and a food and drink for preventing complications of diabetes, which contain a pine bark extract and astaxanthin, which can provide a synergistic effect between a water-soluble substance and a fat-soluble substance. it can.

It is a graph which shows the blood glucose level at the time of completion | finish of a test of a male diabetes model rat. It is a graph which shows the neutral fat at the time of completion | finish of a test of a male diabetic model rat. It is a graph which shows the liver chemirmi at the time of completion | finish of a test of a male diabetic model rat. It is a graph which shows a renal chemirmi at the time of completion | finish of a test of a male diabetes model rat. It is a graph which shows the serum TBARS at the time of completion | finish of a test of a male diabetic model rat.

Claims (7)

  A preventive agent for complications of diabetes, comprising pine bark extract and astaxanthin.   The agent for preventing complications of diabetes according to claim 1, wherein the pine bark extract contains 5% by weight or more of catechins and 20% by weight or more of OPC.   The agent for preventing diabetes associated with diabetes according to claim 1 or 2, wherein astaxanthin is contained in an extract derived from Haematococcus algae.   It is a tablet, pill, capsule, granule, powder, powder or liquid form, The diabetes combined disease prevention agent in any one of Claims 1-3.   A food and drink comprising the preventive agent for comorbidity with diabetes according to any one of claims 1 to 4.   The food or drink according to any one of claims 1 to 5, which is a solid food, a gel food or a beverage. It is a soft drink, The food-drinks in any one of Claims 1-6.

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