JP2009107952A - Anti-osteoporosis agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an anti-osteoporosis agent which has high safety and excellent anti-osteoporosis effect, because the outbreak of the osteoporosis, that lowers the density of bone to weaken the bone, accompanies symptoms such as bone curvature, ache and bone fracture, and requests an effective therapeutic method, is cited as an important problem of the ageing society in recent years, and to provide a food or drink using the anti-osteoporosis agent. <P>SOLUTION: This anti-osteoporosis agent is characterized by containing proanthocyanidin originated from a pine bark extract as an active ingredient. The food or drink is characterized by containing the anti-osteoporosis agent. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to an anti-osteoporosis agent and a food or drink containing the same.

An important problem of the aging society in recent years is the occurrence of osteoporosis in which bone density decreases and bones become brittle. Osteoporosis is accompanied by symptoms such as bone curvature, pain, and fracture, and an effective treatment method is required.
Examples of therapeutic agents for osteoporosis include active vitamin D ₃ , female hormone (estrogen), calcitonin, ipriflavone, bisphosphonate, vitamin K, and the like, but a great effect cannot be expected. It is important to prevent osteoporosis by paying attention to proper exercise and foods taken daily. Concerning the above foods, intake of dairy products and fish containing a large amount of calcium is recommended. Furthermore, the use of health foods including calcium, magnesium, vitamin D, casein phosphopeptide (which is said to have an action of promoting calcium absorption from the intestinal tract) and the like is also recommended.
Patent Document 1 listed below proposes an anti-osteoporosis agent containing vitamin K and soy soflavone as active ingredients, having a vitamin K concentration in a dry weight of 100 ppm or more and a soy isoflavone concentration of 5000 ppm or more. .

On the other hand, proanthocyanidins are a kind of polyphenols contained in plants, and are known to have various activities such as antioxidant action (Patent Document 2) and anti-obesity action (Patent Document 3).
Japanese Patent No. 3250071 Japanese Patent Publication No. 3-7232 JP 2006-16330 A

  An object of the present invention is to provide an anti-osteoporosis agent having high safety and an excellent anti-osteoporosis effect, and a food and drink using the same.

The invention according to claim 1 is an anti-osteoporosis agent characterized by containing proanthocyanidins as an active ingredient.
The invention according to claim 2 is the anti-osteoporosis agent according to claim 1, wherein the proanthocyanidins are pine bark-derived extracts.
The invention according to claim 3 is the anti-osteoporosis agent according to claim 1 or 2, wherein the proanthocyanidins are oligomeric proanthocyanidins.
Invention of Claim 4 contains the anti-osteoporosis agent in any one of Claims 1-3, It is food-drinks characterized by the above-mentioned.

  ADVANTAGE OF THE INVENTION According to this invention, the anti-osteoporosis agent which has high safety | security and the outstanding anti-osteoporosis effect, and food-drinks using this can be provided.

Hereinafter, the present invention will be described in more detail.
The proanthocyanidins used as the active ingredient of the present invention have a degree of polymerization of 2 or more, preferably 2 to 10 monomers, more preferably flavan-3-ol and / or flavan-3,4-diol as a structural unit. The compound group which consists of a 2-4 mer condensation polymer, a derivative | guide_body, and those stereoisomers are designated. Among the proanthocyanidins, a polycondensation polymer having a polymerization degree of 2 to 4 having flavan-3-ol and / or flavan-3,4-diol as a structural unit is referred to as OPC (oligomeric proanthocyanidin). OPC is a powerful antioxidant and is abundant in plant leaves, bark, fruit peel or seed parts. Specifically, it is contained in grapes, pine bark, peanut skin, ginkgo, false acacia fruit, cowberry, blueberry, strawberry, avocado, barley, wheat, soybean, black soybean, cacao and the like. It is also known that OPC is contained in the roots of cola nuts in West Africa and Latania in Peru. OPC is a substance that cannot be produced in the human body.

  With regard to proanthocyanidins used as the active ingredient of the present invention, the origin of the raw material or the utilization part of the raw material, the production method, and the purification method are not limited at all, but the bark, fruit or seed pulverized product, or the extract of these extracts Such food ingredients can be used. In particular, it is preferable to use an extract of pine bark, more preferably French coast pine bark rich in OPC. French coastal pine bark is preferably used as a raw material for proanthocyanidins.

  Proanthocyanidins can be obtained by a known method [for example, the method described in Patent Document 1 or an extraction method from pine bark; RW Hemingway et al., Physochemistry, 1983, Volume 22, p. 275-281] or a method based thereon can be easily obtained from the above-mentioned various plants.

  Hereinafter, a method for preparing proanthocyanidins will be described by taking an extract of pine bark rich in OPC as an example.

  The pine bark extract is obtained by extracting pine bark with water or an organic solvent. When water is used, warm water or hot water is used. As the organic solvent used for extraction, an organic solvent that is acceptable for food or pharmaceutical production is used, for example, methanol, ethanol, propanol, butanol, butane, acetone, hexane, cyclohexane, propylene glycol, hydrous ethanol, hydrous propylene glycol, Examples include ethyl methyl ketone, glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible oils and fats, 1,1,1,2-tetrafluoroethane, 1,2-trichloroethene and the like. These water and organic solvent may be used alone or in combination. In particular, hot water, hydrous ethanol, and hydrous propylene glycol are preferably used.

  A method for extracting proanthocyanidins 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 particularly preferably used.

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

  Moreover, you may perform supercritical fluid extraction by the entrainer addition method. In this method, for example, about 2 to 20% of ethanol, propanol, n-hexane, acetone, toluene, or the like is added to the supercritical fluid, and supercritical fluid extraction is performed with the obtained extraction fluid, so that OPC or the like is performed. This is a method for dramatically increasing the solubility of the extract in the extraction fluid, or for enhancing the separation selectivity, and for efficiently obtaining a pine bark extract.

  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, in addition to the above method.

  The proanthocyanidins obtained as described above can be obtained in a liquid or semi-solid form. If the extraction solvent is removed from this product by a known method such as distillation under reduced pressure, spray drying, freeze drying, or the like, it remains as it is. It can be used as a proanthocyanidin-containing concentrate or dried product. For further purification, a known purification means such as column chromatography or countercurrent distribution method can be employed to achieve the object.

  The proanthocyanidins of the present invention dissolve well in water and have high absorbability to living bodies. It is highly stable in any of acidic, neutral and alkaline conditions, and can be easily blended with food and drink while maintaining its function. In addition, the effect can be expected in a short period after the start of ingestion, and a sufficient effect can be obtained even with a small amount of ingestion, so it can be used as a food material for infants and the elderly who have limited intake allowance and intake form as food and drink High value. Therefore, the food and drink of the present invention may be, for example, health foods, health function foods (specific health foods, nutrient function foods), and the like.

  The anti-osteoporosis agent of the present invention can be appropriately prepared by a known method in the form of a solid or solution (hereinafter also referred to as a preparation) such as a tablet, pill, capsule, granule, powder, powder, or liquid. That is, the solid preparation or liquid preparation useful in the present invention is produced by mixing proanthocyanidins and, if desired, additives 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, coloring agents, 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), tocopherol, ascorbic acid, 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, hydroxypropyl methylcellulose acetate succinate, methacrylic acid copolymer, polyvinyl acetate diethylaminoacetate or shellac.
Examples of the colorant include turmeric extract, riboflavin, titanium oxide, or carotene solution.

Examples of the flavoring agents include citric acid, adipic acid, ascorbic acid, fructose, D-sorbitol, glucose, sodium saccharin, simple syrup, sucrose, honey, amacha, licorice, citric acid, adipic acid, ascorbic acid, orange oil, Spruce tincture, fennel oil, mint or menthol.
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 etc. are mentioned, for example.

In the various preparation forms, the amount of proanthocyanidins is usually about 1 to 80% by weight, preferably about 2 to 50% by weight, based on the whole preparation.
The administration method of the preparation of the present invention may be oral or parenteral. The dose of proanthocyanidins, which are the active ingredients of the present invention, varies depending on the type, dosage form, patient age, body weight, indication symptoms, and the like. Several doses may be administered at a dose of about 1 to 500 mg, preferably about 3 to 300 mg.

  The food / beverage products of this invention are manufactured by mix | blending proanthocyanidin or the said proanthocyanidin containing formulation with food / beverage-drink material at the time of food-drinks manufacture. For example, solid foods such as bread, chewing gum, cookies, chocolate, cereals, jams, ice cream, yogurt, jelly and other jams, creams or gels, juices, coffee, cocoa, green tea, oolong tea, tea and other beverages Any food form can be used. Moreover, it can also mix | blend with a seasoning, a food additive, etc. The blending amount of the proanthocyanidins or the proanthocyanidin-containing preparations in the food and drink material is not particularly limited, but is usually about 0.0001 to 80% by weight, preferably about 0.005 to 50% by weight. Moreover, especially in the case of a drink, it is 1 mg / L-20 g / L, Preferably it is 2 mg / L-10 g / L.

  In addition, the intake of proanthocyanidins when the present invention is a food or drink may be an amount equivalent to the dose of the internal medicine because there is no concern about side effects.

  Hereinafter, the present invention will be described in detail by way of examples using a pine bark extract rich in OPC as an example, but the present invention is not limited thereto.

Example 1
To 900 g of pine bark, 7.2 L of purified water was added, crushed with a blender (Waring Blender), and then extracted by heating at 100 ° C. for 10 minutes. Then, it filtered immediately and obtained the filtrate. The residue after filtration was washed with 1.8 L of purified water, and the filtrate and the washing solution were combined to obtain 9 L of a crude hot water extract of pine bark. When 1 mL of this extract was freeze-dried, the dry weight was 8 mg.

  1 L of the above crude extract (powder dry weight 8 g) was allowed to cool to 25 ° C., sodium chloride was added to 100% saturation concentration and stirred well, and then allowed to stand at 4 ° C. for 24 hours. After standing, this solution was filtered to obtain 910 mL of filtrate. This filtrate was further purified by the steps shown below. First, the filtrate was passed through a 30 × 300 mm column packed with 100 mL of an aromatic synthetic resin swollen with water (Diaion HP-20: manufactured by Mitsubishi Chemical Corporation), and further washed with 1 L of purified water. . Next, the column was eluted with a 15% (V / V) ethanol-water mixed solvent to obtain 200 mL of a pine bark hot water extraction purified product (hereinafter referred to as pine bark hot water extract 1). The obtained purified product was freeze-dried and powdered. This operation was repeated to obtain 7.51 g of dry powder of hot water extract 1 of pine bark from 9 L of hot water extract of pine bark.

  As a result of measuring the content of proanthocyanidins and OPC in the dry powder by the method described in JP-A-2005-23032, 40% by weight of proanthocyanidins was contained in the dry powder. Further, OPC was contained as a 2 to 4 mer in 20% by weight in the dry powder.

The following animal experiment was conducted to examine the anti-osteoporosis effect of the dry powder of hot water extract 1 of pine bark.
Osteoporosis Improvement Effect Test SD rat (22 weeks old) Female ovaries were surgically removed to create osteoporosis model rats. The ovariectomized rats were divided into 6 groups of 7 animals, and every other day (total 17 times) during the 35-day test period, the dry powder intake of the hot water extract 1 was 1 mg / kg. 2 ml of physiological saline-dissolved liquid was orally administered. The feed was the solid feed CRF-1 for mice, rats and hamsters from Oriental Yeast Co., Ltd. There was no difference in food intake between groups during the study period. On the 35th day after the start of the test, the weight of the rat was measured, and then the femur was removed. The femur was used for analysis with the adhesive tissue and muscle removed. After measuring the volume of the femur, it was washed three times with ethanol, then washed three times with acetone, dried overnight, and then weighed to determine the dry weight of the femur. From the volume and dry weight, the bone density (dry weight g / volume mm ³ ) was measured. In addition, as a control experiment, Table 1 shows the results together with an example (comparative example) in which the above experiment was repeated except that physiological saline containing no dry powder of the hot water extract 1 was administered to rats. .

  When Example 1 was compared with the comparative example, a significant difference was found in Example 1 with a risk factor of p <0.05.

Example 2
In Example 1, Example 1 was repeated except that the intake amount of the dry powder of the hot water extract 1 was 0.5 mg / kg. As a result, the bone density of Example 2 was 1.056 ± 0.004 mg / mm ³ .

Example 3
Deionized water was added so that the tea leaf usage rate was 0.8% by weight with respect to the extract of oolong tea, black tea, green tea, hoji tea and jasmine tea extracted with hot water at 85 ° C. At that time, ascorbic acid was added so that it might become 0.025 weight%, and then it adjusted to pH which was easy to drink using baking soda. Furthermore, after adding so that the dry powder of the said hot-water extract 1 might be set to 5 mg with respect to the said preparation liquid 100g, UHT sterilization was performed as usual, and it filled into the 350 ml volume PET bottle, and various drinks were obtained.

Example 4
Juice was prepared according to the following formulation.
Frozen concentrated orange juice 5.0 parts by weight Fructose glucose liquid sugar 1.0 part by weight Citric acid 0.10 parts by weight L-ascorbic acid 0.09 parts by weight Dry powder of the hot water extract 1 0.05 parts by weight

Claims (4)

  An anti-osteoporosis agent comprising proanthocyanidins as an active ingredient.   The anti-osteoporosis agent according to claim 1, wherein the proanthocyanidins are pine bark-derived extracts.   The anti-osteoporosis agent according to claim 1 or 2, wherein the proanthocyanidins are oligomeric proanthocyanidins.   Food-drinks characterized by including the anti-osteoporosis agent in any one of Claims 1-3.