JP2016190814A - Calcium permeation promoter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new calcium permeation promoter having excellent calcium permeability.SOLUTION: The present invention provides a calcium permeation promoter comprising plants belonging to Polypodiaceae.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a calcium permeation enhancer that improves calcium permeability.

  Calcium, the main component of bone, is a major mineral component and plays an important role in the living body. Bone is constantly broken and absorbed and reborn. This phenomenon is called remodeling. Healthy individuals generally have a balance between bone resorption and bone formation. However, when the ability to absorb calcium is reduced and the balance is lost, bone mass is reduced, resulting in bone-derived diseases. Therefore, it is very important to improve calcium absorption and permeability.

  There are mainly two known calcium absorption mechanisms in the digestive tract (see Non-Patent Documents 1 to 3 below). The first is calcium absorption by the small intestine calcium transporter TRPV6. TRPV6 has been reported to be upregulated by active vitamin D, and is known to be a factor in enhancing calcium absorption upon vitamin D intake. The second is calcium absorption through the intestinal epithelial cell stroma, and it has been reported that expansion of the intestinal epithelial cell stroma by piperine or short-chain fatty acids enhances absorption of minerals such as calcium.

  For example, casein phosphopeptide (CPP) has been developed as a substance that improves calcium absorption capacity. CPP is a phosphopeptide obtained in the hydrolyzate by allowing trypsin to act on casein, and binds to calcium to form a soluble complex. For this reason, it is considered that calcium is solubilized by suppressing the precipitation of calcium in an aqueous solution and the absorption rate of calcium is increased (see Patent Documents 1 and 2 below).

JP 58-170440 A JP-A-7-241172

Prakash UN et.al., “Enhanced intestinal uptake of iron, zinc and calcium in rats fed pungent spice principles-piperine, capsaicin and ginger (Zingiber officinale), J Trace Elem Med Biol., Vol. 27 (3), pp. 184-190, July, 2013 Hiroko Isoda et. Al., “Effects of capsaicin on human intestinal cell line Caco-2”, Cytotechnology, Vol. 36 (1-3), pp. 155-161, July, 2001 Akiko Fukushima et. Al., “Short-Chain Fatty Acids Induce Intestinal Transient Receptor Potential Vanilloid Type 6 Expression in Rats and Caco-2 Cells”, The Journal of Nutrition, Vol. 139 (1), pp. 20-25, January 2013

  An object of the present invention is to provide a new calcium permeation accelerator having excellent calcium permeability.

  The present inventors have found that dwarf stars have excellent calcium permeation promoting ability.

  It is known that metabolism is promoted by increasing the calcium concentration in fat cells. The promotion of calcium permeation from the intestinal tract by the cometary star of the present case increases the calcium concentration in the adipocytes and increases the activity of the adipocytes, thereby promoting metabolism.

  It is also known that blood pressure decreases as the calcium concentration in the blood increases. The action of promoting the calcium permeation from the intestinal tract by the cometary star in this case leads to a decrease in blood pressure by increasing the calcium concentration in the blood.

  Dwarf stars improve or promote calcium permeability. Therefore, an agent containing dwarf stars is useful for preventing or improving diseases caused by bone due to, for example, calcium deficiency, age or sex, and suffering from or possibly having the disease caused by bone. Useful for some people. In addition, the dwarf stars enhance the activity of adipocytes by increasing the calcium concentration in the adipocytes. Thus, agents containing dwarf stars are useful for promoting metabolism and are useful for those suffering from or possibly having a decrease in metabolism. Furthermore, comet stars cause a drop in blood pressure due to an increase in blood calcium concentration. Accordingly, agents containing dwarf stars are useful for lowering blood pressure and are useful for those suffering from or possibly having high blood pressure.

It is a figure which shows the permeation amount of calcium.

  A dwarf star is a plant belonging to the family Laboraceae. Examples of the use site of the cocoon star used in the present invention include stems, leaves, flowers, and roots. Among the roots, rhizomes are particularly preferable, and those obtained by removing the rhizome scales are more preferable.

  As the dwarf star, a processed product obtained by subjecting a dwarf star plant to one or more processes selected from pulverization, extraction, and drying is preferable. As a preferable processed product, a dried product obtained by drying a plant body, a pulverized plant body obtained by pulverizing the plant body as it is or after processing, or water and / or an organic solvent as it is or after processing the plant body The extract obtained by extracting with can be mentioned. The processing referred to here includes at least one treatment selected from heating, drying, pulverization, and pressing. These workpieces can be used either alone or in combination.

  Water or an organic solvent is selected as a solvent for obtaining an extract of a dwarf star plant. When water is used, warm water or hot water is used. The organic solvent used for the extraction may be a commonly used organic solvent, for example, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butane, acetone, hexane, cyclohexane, propylene. Glycol, water-containing ethanol, water-containing propylene glycol, ethyl methyl ketone, glycerin, methyl acetate, ethyl acetate, diethyl ether, dichloromethane, edible fats and oils, 1,1,1,2-tetrafluoroethane, 1,1,2-trichloroethene Preferably used. These water and organic solvent may be used independently and may be used in combination of 2 or more type. In particular, for example, hot water, water-containing ethanol or water-containing propylene glycol can be preferably used.

  The extraction method for obtaining the extract of the dwarf star plant is not particularly limited, and for example, a warm extraction method or a supercritical fluid extraction method may be 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, for example, carbon dioxide, ethylene, propane, or nitrous oxide (laughing gas) is used, but carbon dioxide can be 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 or an 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. It is a method that drastically increases the solubility of the target extract in the extraction solvent or enhances the separation selectivity by performing supercritical fluid extraction using this fluid. It is a method to obtain a simple 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 a high temperature, the advantage that the extraction fluid does not remain, and the recycling of the solvent is possible. Therefore, the supercritical fluid extraction method has an advantage that, for example, the desolvation step can be omitted, and the process becomes simple.

  Moreover, the extraction method from the plant body for obtaining the extract of the plant body of dwarf stars is, for example, a liquid carbon dioxide batch method, a liquid carbon dioxide reflux method, or a supercritical carbon dioxide reflux method other than the above-described extraction method. You may carry out by the method of.

  A plurality of extraction methods may be combined as an extraction method for obtaining an extract of a dwarf star plant body. By combining a plurality of extraction methods, it is possible to obtain extracts having various compositions.

  Extracts from dwarf star plants should be purified by ultrafiltration or column method or batch method using adsorptive carrier (eg Diaion HP-20, Sephadex-LH20, or chitin). Is preferable from the viewpoint of safety. Further, if necessary, it may be concentrated or dried by a method such as vacuum concentration or freeze-drying to obtain a liquid, paste, powder (extract powder), fine granule, or granule. It is preferable that the processed product of the dwarf star extract is in the form of powder, fine particles, or granules.

  The raw material of the dwarf star is available as a commercial product, for example.

  It does not specifically limit as a form of the calcium-permeation promoter according to this invention, It can be set as arbitrary forms. For example, the oral form includes, for example, forms suitable for oral use, specifically, granular, powder, tablet, chewable, capsule, liquid or syrup forms. It is done.

  The calcium permeation enhancer according to the present invention may optionally contain excipients, binders, disintegrants, lubricants, colorants, flavoring agents, or flavoring agents or combinations thereof commonly used in the art. . The excipient can be, but is not limited to, for example, a saccharide (eg, sucrose, lactose, sugar alcohol), starch, or dextrin, or a combination thereof. The binder can be, for example, honey, rice starch, or tragacanth, or a combination thereof, but is not limited thereto. The disintegrant can be, for example, starch or celluloses or combinations thereof, but is not limited thereto. The lubricant can be, for example, but not limited to, wax (eg, magnesium stearate), or talc or a combination thereof. The colorant can be any colorant of natural or synthetic origin. The corrigent can be, for example, a saccharide (eg, sucrose, lactose, sugar alcohol), but is not limited thereto. The flavoring agent can be, for example, menthol, but is not limited thereto. The content of excipients, binders, disintegrants, lubricants, coloring, flavoring, or flavoring is known to those skilled in the art.

  The calcium permeation enhancer according to the present invention may include a compound or agent having an effect of promoting calcium permeation other than dwarf stars. Such compounds and agents include, for example, fish agents such as fish bones, shells, coral calcium, calcium lactate, calcium carbonate, calcium chloride, difructose anhydride III (DFAIII), fructooligosaccharide (FOS), casein phosphopeptide (CPP), quencher It can be, but is not limited to, acid malic acid (CCM), calcium citrate malate, lactose, vitamin D, vitamin K, soy isoflavone, or collagen or combinations thereof.

  The calcium permeation enhancer according to the present invention comprises cocoon stars, for example, generally 0.01 to 30% by weight, preferably 0.05 to 20% by weight, more preferably 0.1 to 10% by weight, based on the final product. May be included in quantity.

  The calcium permeation enhancer according to the present invention can be taken, for example, 1 to 3 times per day, for example, before meals, after meals or before going to bed, but is not limited thereto.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated more concretely, this invention is not limited to these Examples.

  Calcium permeation promoting effect of dwarf star extract was evaluated by calcium permeability to monolayer CACO-2. The test for the evaluation was performed according to the following method.

(Preparation of dwarf star extract)
The dwarf star extract was prepared according to the following method. Ultra-pure water was added to Samurai Star (obtained from BGG Japan Co., Ltd.) to prepare concentrations of 100 and 30 mg / mL. Further, the comet extract extracted to each concentration was added to HBSS-HEPES-Ca buffer to prepare each comet extract (test substance solution) at a final concentration of 100 and 30 μg / mL. The dwarf star extract was used on the same day after adjustment. As a control, a medium in which ultrapure water was added to HBSS-HEPES-Ca buffer instead of the dwarf star extract was used.

(Test method)
Immediately after obtaining POCA (registered trademark: Point Of Cell Assay) small intestine absorption CACO-2 (hereinafter referred to as single layer CACO-2) (model number DSPOCA001-ZS: DS Pharma Biomedical Co., Ltd.), 5% CO ₂ incubator ( ASTEC). Replace the apical side (100 μL) and multiwell basal side (600 μL) of transwell filter chanber (Corning, pore size 0.4 μm, made of polycarbonate) in which single layer CACO-2 is cultured with HBSS-HEPES buffer, and 20 It was left in a 5% CO ₂ incubator for 5 minutes. The apical side HBSS-HEPES buffer was removed by aspiration, 100 μL of the test substance solution and the control solution were added, and the well plate was allowed to stand in the CO ₂ incubator for 24 hours. The well plate was removed from the 5% CO ₂ incubator, the basal side medium was collected, and the calcium concentration was measured according to the following method.

The calcium concentration of the recovered basal side medium was tested according to the following method.
The recovered basal side medium (600 μL) was dried under reduced pressure at 40 ° C. for 18 hours with a centrifugal concentrator (Tomy Seiko). 30 μL HBSS-HEPES buffer was added to the dried sample and mixed until completely dissolved. 2 μL of the sample dissolved in the HBSS-HEPES buffer was added dropwise to a 96-well plate, 240 μL metalloassay Ca was added, and the mixture was allowed to stand at room temperature for 10 minutes. The absorbance of the sample in each well was measured using VARIOSKAN (Thermoscientific) at an absorbance of 690 nm, and the calcium permeation amount was measured. The result is shown in FIG.

(result)
As shown in FIG. 1, the comet star extract significantly increased calcium permeation compared to the control 24 hours after its addition at any concentration (100 and 30 μg / mL).

  In the following formulation examples 1 to 10, formulation examples of quasi-drugs, cosmetics, or pharmaceuticals containing a dwarf star extract are shown, but the present invention is not limited thereto.

(Formulation example 1: lotion)
Based on 100 parts by mass of the whole, 0.005 parts by mass of dwarf star extract, 10 parts by mass of glycerin, 3 parts by mass of diglycerin, 12 parts by mass of 1,3-butylene glycol, 3 parts by mass of pentylene glycol, sodium hyaluronate 0 0.1 part by mass, citric acid 0.01 part by mass, sodium citrate 0.02 part by mass, xanthan gum 0.1 part by mass, methyl paraben 0.15 part by mass, carbomer 0.2 part by mass, sodium hydroxide 0.03 part by mass The agent of the present invention was prepared in the form of a lotion by mixing the part and the rest of the water.

(Formulation example 2: shampoo)
Based on 100 parts by mass as a whole, 0.001 part by mass of dwarf star extract, 7.5 parts by mass of sodium laureth sulfate, 4.2 parts by mass of cocamidopropyl betaine, 3 parts by mass of cocamide DEA, 1,3-butylene glycol 0 0.1 part by mass, 0.25 part by mass of polyquaternium-10, 0.15 part by mass of citric acid, 0.05 part by mass of sodium citrate, 0.9 part by mass of phenoxyethanol, and the remainder of water are mixed together to form a shampoo. Inventive agents were prepared.

(Formulation example 3: soap)
100 parts by weight as a whole, 1 part by weight of dwarf star powder, 2 parts by weight of glycerin, 1 part by weight of olive oil, 0.1 part by weight of EDTA-4 sodium, 0.2 part by weight of etidronate 4 sodium, and the rest of the soap base The agent of the present invention was prepared in the soap form by mixing and solidifying.

(Formulation example 4: emulsion)
100 parts by weight as a whole, 0.05 parts by weight of dwarf star extract, 3 parts by weight of sucrose fatty acid ester, 12 parts by weight of glycerin, 6 parts by weight of squalane, 24 parts by weight of dimethyl silicone oil, 1 part by weight of polypropylene glycol The agent of the present invention was prepared in the form of an emulsion by mixing 0.06 parts by weight of a viscous agent, 0.2 parts by weight of phenoxyethanol, 5 parts by weight of ethanol, 0.01 parts by weight of sodium hydroxide, and the remainder of purified water.

(Formulation Example 5: Cosmetic cream)
1. 100 parts by mass of the whole, 0.03 parts by mass of dwarf star extract, 15.0 parts by mass of squalane, 4.0 parts by mass of octyldodecyl myristate, 0.2 parts by mass of hydrogenated soybean phospholipid, butyl alcohol 4 parts by mass, 1.5 parts by mass of hardened oil, 1.5 parts by mass of stearic acid, 1.5 parts by mass of lipophilic glyceryl monostearate, 0.5 parts by mass of polyglyceryl monostearate, 0.8 parts by mass of behenyl alcohol, Polyglyceryl monomyristate 0.7 parts by weight, beeswax 0.3 parts by weight, d-δ-tocopherol 0.1 parts by weight, methylparaben 0.3 parts by weight, C10-30 alkyl-modified carboxyvinyl polymer 0.2 parts by weight, Carboxyvinyl polymer 0.1 mass part, 1,3-butanediol 18.0 mass parts, sodium hydroxide 0.1 mass And a mixture of purified water balance, to prepare a preparation of the present invention in the form of cosmetic creams.

(Formulation Example 6: Packing agent)
100 parts by mass as a whole, 0.1 parts by mass of dwarf star extract, 20.0 parts by mass of polyvinyl alcohol, 5.0 parts by mass of glycerin, 20.0 parts by mass of ethanol, 6.0 parts by mass of kaolin, preservative 0 .2 parts by mass, 0.1 part by mass of fragrance, and the remainder of purified water were mixed to prepare the agent of the present invention in the form of a pack agent.

(Formulation Example 7: Tablet)
Mixing 100 parts by weight of the whole, 5 parts by weight of dwarf star powder, 5 parts by weight of vitamin B ₁ , 12 parts by weight of vitamin B ₆ , 4 parts by weight of calcium stearate, 30 parts by weight of maltose and the rest of hydroxypropylcellulose, The agent of the present invention was prepared in the form of a tablet by tableting.

(Formulation Example 8: Granules)
The agent of the present invention in the form of a granule by mixing and granulating 5 parts by mass of dwarf star extract, 10 parts by mass of lactose, 1 part by mass of calcium stearate and the rest of crystalline cellulose, with 100 parts by mass as a whole. Was prepared.

(Formulation example 9: capsule)
In the form of a capsule, the total amount is 100 parts by mass, and the mixture is prepared by mixing 10 parts by mass of dwarf star extract, 8 parts by mass of lecithin, and the remainder of olive oil. The agent of the present invention was prepared.

(Formulation example 10: liquid agent)
100 parts by weight as a whole, 1 part by weight of dwarf star extract, 1 part by weight of vitamin B _1, 10 parts by weight of fructose glucose liquid sugar, 1 part by weight of citric acid, 0.02 part by weight of sodium benzoate, 2 parts by weight of a fragrance preparation Part, 0.05 part by mass of sucralose, 0.03 part by mass of acesulfame potassium, and the remainder of purified water were mixed to prepare the agent of the present invention in the form of a solution.

Claims (2)

  Calcium permeation enhancer containing dwarf stars.   Metabolic promoter containing dwarf stars.