WO2018179199A1 - Seamless capsule and production method therefor - Google Patents

Seamless capsule and production method therefor Download PDF

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Publication number
WO2018179199A1
WO2018179199A1 PCT/JP2017/013177 JP2017013177W WO2018179199A1 WO 2018179199 A1 WO2018179199 A1 WO 2018179199A1 JP 2017013177 W JP2017013177 W JP 2017013177W WO 2018179199 A1 WO2018179199 A1 WO 2018179199A1
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WIPO (PCT)
Prior art keywords
capsule
aqueous solution
seamless
galactose
polyphenol
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PCT/JP2017/013177
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French (fr)
Japanese (ja)
Inventor
陽平 馬場
彰 田渕
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Dsp五協フード&ケミカル株式会社
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Priority to PCT/JP2017/013177 priority Critical patent/WO2018179199A1/en
Priority to JP2018511786A priority patent/JP6347006B1/en
Publication of WO2018179199A1 publication Critical patent/WO2018179199A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate

Definitions

  • the present invention relates to a seamless capsule and a method for producing the same.
  • capsules have been used as orally used products such as various pharmaceuticals and foods.
  • Seamless capsules are used as such capsules.
  • Such a seamless capsule is provided with a capsule film, and the capsule film functions as a container for containing contents such as active ingredients in the inside or the film itself.
  • Japanese Unexamined Patent Publication No. 1-331421 Japanese Unexamined Patent Publication No. 2006-232760 Japanese Unexamined Patent Publication No. 2000-354460
  • a calcium salt that is, a metal ion is required to form a capsule film. Therefore, it becomes difficult to add a component that reacts with metal ions as the content, and as a result, the type of the content may be limited. In addition, if the content contains metal ions, the capsule film is insolubilized accordingly, and as a result, the capsule film may be unnecessarily delayed in dissolution or elution.
  • Patent Document 1 it is necessary to form a sodium alginate in a capsule shape and then cross-link the surface with calcium. Therefore, high technical ability and special equipment are required, and the production is complicated. There is a risk. Further, in the technique of Patent Document 2, it is necessary to form a plurality of constituent films, and accordingly, high technical ability and special equipment are required, and the production may be complicated.
  • Patent Document 3 does not disclose that a capsule film of a seamless capsule can be formed by using a galactose partial decomposition product of galactoxyloglucan and polyphenol.
  • an object of the present invention is to provide a seamless capsule that can be filled with a wider range of contents than before and that can be easily manufactured, and a method for manufacturing the same.
  • galactose partial degradation product of galactoxyloglucan (hereinafter sometimes simply referred to as “galactose partial degradation product”) with polyphenol.
  • galactose partial degradation product a galactose partial degradation product of galactoxyloglucan
  • the surface of the droplet of the aqueous solution of partial decomposition product of galactose reacts instantaneously with polyphenol, resulting in gelation, which causes Was found to be covered with a film. That is, it has been found that a capsule film of a seamless capsule can be easily formed.
  • the thickness of the capsule film changes depending on the time for holding the droplet of the aqueous solution of partially decomposed galactose solution in the polyphenol aqueous solution and the concentration of the polyphenol aqueous solution. Further, the present invention is completed by finding that the polyphenol penetrates more into the inside of the droplet depending on the time and concentration, and that the entire droplet can finally be gelled. It came.
  • the seamless capsule according to the present invention is A seamless capsule with a capsule coating
  • the capsule film contains a galactose partial decomposition product of galactoxyloglucan and polyphenol.
  • the capsule film contains a galactose partial decomposition product and polyphenol, so that a wide range of contents can be filled as compared with the conventional one, and a seamless capsule can be easily produced.
  • the partial decomposition product of galactose is preferably obtained by decomposing 30 to 55% of galactose.
  • the galactose partial decomposition product is obtained by decomposing 30 to 55% of galactose, the reactivity with polyphenol is improved, so that a relatively uniform film can be formed in a relatively short time. Therefore, a seamless capsule having a capsule film with higher strength can be produced in a shorter time.
  • the polyphenol is a tea extract.
  • the polyphenol is a tea extract
  • the reactivity with the partially decomposed product of galactose is improved, so that a seamless capsule having a higher strength capsule film can be produced in a shorter time.
  • the method for producing a seamless capsule according to the present invention includes: Capsules containing the galactose partial decomposed product and the polyphenol by dropping a first aqueous solution containing a galactose partial decomposed product of galactoxyloglucan and water into a second aqueous solution containing polyphenol and water. It is a method provided with the process of forming the seamless capsule which has a membrane
  • a capsule capsule can be formed simply by dropping the first aqueous solution into the second aqueous solution, so that seamless capsules can be easily produced.
  • the obtained seamless capsule can accommodate a wider range of contents than before. Therefore, a seamless capsule that can be filled with a wider range of contents than before can be easily produced.
  • the concentration of the partially decomposed galactose in the first aqueous solution is preferably 0.5 to 3.0% by mass.
  • the concentration of the galactose partial decomposition product in the first aqueous solution to 0.5 to 3.0% by mass, the first aqueous solution has a viscosity suitable for dropping, and the galactose partial decomposition product. Therefore, a seamless capsule with higher strength can be easily produced in a shorter time.
  • the concentration of the polyphenol in the second aqueous solution is preferably 0.25 to 10% by mass.
  • the photograph of the seamless capsule which has each shape of one embodiment of the present invention Photograph showing an example of the maximum diameter of each shape seamless capsule of this embodiment
  • the seamless capsule of the present embodiment is a seamless capsule having a capsule film, and the capsule film contains a galactose partial decomposition product of galactoxyloglucan and polyphenol.
  • the galactoxyloglucan is a constituent component of the cell wall (primary wall) of higher plants such as dicotyledonous and monocotyledonous plants, and is a nonionic polymer polysaccharide that exists as a storage polysaccharide for some plant seeds. is there.
  • This galactoxyloglucan has glucose, xylose and galactose as constituent sugars, has ⁇ -1,4 linked glucose as the main chain, has xylose as the side chain, and further binds to the xylose Galactose.
  • the galactoxyloglucan may be any plant-derived galactoxyloglucan, and can be obtained from, for example, tamarind, jatoba, nastathium seed, soybean, mung bean, kidney bean, rice, barley, or other fruit epidermis. Considering that it is most easily available and has a large content, galactoxyloglucan derived from legume tamarind seeds is preferable. As such galactoxyloglucan, a commercially available product can be adopted. Examples of commercially available products include Griloid (registered trademark, manufactured by DSP Gokyo Food & Chemical Co., Ltd.).
  • the galactose partial degradation product of galactoxyloglucan is a substance obtained by partially decomposing and removing the side chain galactose of galactoxyloglucan.
  • galactoxyloglucan means galactoxyloglucan (complete galactoxyloglucan) from which side chain galactose has not been removed by partial decomposition by enzyme treatment described later. Such complete galactoxyloglucan may also be referred to as native galactoxyloglucan.
  • An enzyme is used for the partial decomposition. Examples of the enzyme include ⁇ -galactosidase.
  • the ⁇ -galactosidase is an enzyme that releases galactose by hydrolyzing the bond between galactose and xylose contained in galactoxyloglucan.
  • ⁇ -galactosidase may be either plant-derived or microorganism-derived, but an enzyme derived from the microorganism Aspergillus oryzae or Bacillus circulans or an enzyme in seeds containing galactoxyloglucan is preferable.
  • ⁇ -galactosidase a commercially available product can be adopted.
  • the galactose partial decomposition product obtained by partial decomposition of galactose by 30 to 55%.
  • the galactose partial degradation product is partially decomposed by 30 to 55% of galactose, and reacts with polyphenol, a relatively uniform film can be formed in a relatively short time. Therefore, a seamless capsule having a capsule film with higher strength can be produced in a shorter time.
  • Galactoxyloglucan usually contains about 37% side chain xylose and about 17% side chain galactose (see Gidley et al., Carbohydrate Research, 214 (1991) 219-314). Therefore, a galactose partial degradation product obtained by partial degradation of 30 to 55% of galactose is calculated to contain 39 to 41% of side chain xylose and 8 to 12% of side chain galactose.
  • the partial decomposition rate of galactose (that is, the removal rate of galactose) is determined by measuring the amount of galactoxyloglucan oligosaccharide produced by cellulase decomposition of the obtained partial decomposition product using high performance liquid chromatography (hereinafter referred to as HPLC). It can be calculated by measuring with (amino column).
  • polyphenols examples include chemically synthesized polyphenols and plant-derived polyphenols (plant polyphenols).
  • plant polyphenols are preferred.
  • Plant polyphenols are green tea (such as matcha green tea), black tea, oolong tea, puer tea (black tea), mate tea and other tea leaves, white vegetables, citrus peels and seeds, grape skins and seeds (red wine, red grape juice, etc.) , Apples, strawberries, peaches, none, onion peels, chestnuts, burdock, coffee beans, cacao beans, and the like (including solid and liquid extracts). This extract is rich in monomeric polyphenols and polymer polyphenols.
  • Examples of the monomer polyphenol include flavonoids, chlorogenic acid, gallic acid, and ellagic acid.
  • flavonoids include catechins, quercetin, rutin, and anthocyanins.
  • Examples of the catechins include (+)-catechin, (+)-gallocatechin, ( ⁇ )-epicatechin, ( ⁇ )-epigallocatechin, and gallic esters thereof. Of these, as the catechins, gallic acid ester (epigallocatechin gallate) of ( ⁇ )-epigallocatechin is preferable.
  • Examples of the polymer polyphenol include condensed and hydrolyzed tannins.
  • Examples of the condensed tannin include proanthocyanidins and the like, and examples of the proanthocyanidins include thealvidin and prodelphinidin.
  • Examples of the hydrolyzable tannin include tannic acid, gallotannin, and ellagitannin.
  • the above-mentioned extract itself may be used, or a polyphenol which is an active ingredient may be concentrated (extracted) from the extract, and further the extract
  • the active ingredient polyphenols may be purified (separated).
  • tea extract which is an extract extracted from tea leaves, is preferable.
  • the said plant polyphenol is not specifically limited to said thing, As long as it is obtained from the plant containing polyphenol, any may be sufficient.
  • polyphenol may be used as a 1 type, or multiple types of mixture.
  • the capsule film contains a galactose partial decomposition product, polyphenol, and water.
  • a capsule film may be in the form of a gel or a film.
  • a gel-like capsule film is obtained by mixing a partially decomposed galactose product, polyphenol, and water, and a film-like capsule film is obtained by reducing the water content of the obtained mixture by drying or the like.
  • the content of the galactose partial degradation product in the capsule film may be set as appropriate according to the strength of the desired capsule film, and is not particularly limited.
  • the content of polyphenol in the capsule film is appropriately set according to the degree to which the galactose partial degradation product can gel and the degree of gelation in the thickness direction of the capsule film, that is, according to the desired capsule film thickness. There is no particular limitation as long as it is sufficient.
  • the size of the seamless capsule (that is, the size of the capsule film) is not particularly limited.
  • the seamless capsule passes through the center of the seamless capsule, and both ends of the seamless capsule (virtual straight lines passing through the center are seamless capsules.
  • the maximum length (maximum diameter) connecting the two intersection points intersecting the surface of the substrate 2 to 10 mm may be 2 to 10 mm.
  • the maximum diameter corresponds to the diameter when the seamless capsule is spherical. In the case of a teardrop shape, this corresponds to the maximum diameter of the spherical portion.
  • the thickness of the capsule film is not particularly limited, but is preferably about 3 to 40% of the maximum diameter, for example.
  • the thickness ratio can be measured as a coating rate by the method described in Examples described later.
  • the thickness of the capsule film is 3% or more, the film has a sufficient strength, and when it is 40% or less, a volume capable of accommodating other components inside the film can be secured.
  • coat may be in the solid state from which the whole surface is gelatinized from the surface of a membrane
  • an aqueous solution of a partially decomposed galactose solution is usually present on the inside.
  • the capsule film of this embodiment may contain various additives that are usually added to the capsule film as necessary.
  • additives include plasticizers, preservatives, water activity lowering agents, pH adjusters and the like.
  • plasticizer include glycerin, sorbitol, propylene glycol, polyethylene glycol and the like.
  • additives for coating include excipients such as various polysaccharides such as various starches (including modified starch, modified starch, starch, starch degradation products, etc.). Is mentioned.
  • the contents can be accommodated in the capsule film (that is, in the aqueous solution of a partially decomposed galactose product) or in the capsule film (its own).
  • the contents are not particularly limited. Examples of the contents include oil agents such as olive oil and canola oil. Moreover, the thing etc. by which the active ingredient was disperse
  • the said oil agent may be mixed and emulsified with the galactose partial decomposition product, and may be dripped at the polyphenol aqueous solution with the galactose partial decomposition product in this state.
  • the oil agent is contained in the capsule film and the capsule film in an emulsified state with the aqueous solution of a partially decomposed galactose solution.
  • the ratio of the content volume to the total volume of the seamless capsule is preferably 20 to 93% by volume. In this case, it is preferable that the coating rate of the capsule coating is 3 to 40%.
  • the manufacturing method of the seamless capsule of this embodiment is as follows: Capsules containing the galactose partial decomposed product and the polyphenol by dropping a first aqueous solution containing a galactose partial decomposed product of galactoxyloglucan and water into a second aqueous solution containing polyphenol and water. It is a method provided with the process of forming the seamless capsule which has a membrane
  • a first aqueous solution is prepared by dissolving a galactose partial decomposition product in water
  • a second aqueous solution is prepared by dissolving polyphenol in water
  • the aqueous solution of 1 is dropped into the second aqueous solution.
  • the droplet of the first aqueous solution comes into contact with the second aqueous solution, it gels from the surface side of the droplet from the moment of dropping, and the second aqueous solution penetrates into the droplet as time passes, Gelation proceeds from the surface side toward the center. As a result, a capsule film is formed.
  • concentration of the galactose partial decomposition product in 1st aqueous solution is not specifically limited, It can set suitably so that a capsule film
  • concentration of the galactose partial decomposition product in the first aqueous solution is preferably 0.25 to 5.0% by mass, and preferably 0.5 to 3.0% by mass. Is more preferable.
  • the concentration of the galactose partial decomposition product in the first aqueous solution By setting the concentration of the galactose partial decomposition product in the first aqueous solution to 0.25 to 5.0% by mass, the first aqueous solution has a viscosity suitable for dripping, and the reactivity between the galactose partial decomposition product and polyphenols. Therefore, a seamless capsule with higher strength can be easily produced in a shorter time.
  • the concentration of polyphenol in the second aqueous solution is not particularly limited, and can be appropriately set so that a capsule film can be formed.
  • the concentration of the polyphenol in the second aqueous solution is preferably 0.1 to 20% by mass, and more preferably 0.25 to 10% by mass.
  • the temperature of the 1st aqueous solution at the time of dripping and the 2nd aqueous solution is not specifically limited, It can set suitably.
  • the temperature of these aqueous solutions is high at the time of dripping, it tends to be difficult to form a capsule film. Therefore, for example, considering this viewpoint, the temperature of the first aqueous solution and the second aqueous solution at the time of dropping is preferably 5 to 25 ° C.
  • the holding time of the 1st aqueous solution in the 2nd solution after dripping is not specifically limited, It can set suitably. For example, as the holding time becomes longer, polyphenol penetrates into the droplets and gels, and as a result, the coating tends to be thicker. Moreover, when holding time becomes still longer, the whole capsule film tends to be in a gelled state. Therefore, for example, considering such a viewpoint, it is preferable that the retention time after dropping is 10 seconds to 2 hours. The supply of the second aqueous solution to the droplet is stopped by removing the droplet from the second aqueous solution.
  • the method of dropping the first liquid into the second liquid is not particularly limited, and a conventionally known dropping method can be adopted.
  • the dropping method include a method using a cylindrical member having an opening at the tip.
  • Examples of such a cylindrical member include a nozzle and a pipette.
  • a method in which a third liquid different from the first liquid and the second liquid is contained in the first liquid and dropped into the second liquid is also included.
  • a method for example, by using a double nozzle in which an inner nozzle is arranged inside an outer nozzle, the first liquid from the outer nozzle, the third liquid from the inner nozzle, Dropping into the second liquid may be mentioned so that the third liquid droplet is accommodated in the liquid droplet.
  • the first liquid droplet is discharged from the one nozzle.
  • the third liquid droplet may be dropped into the second liquid so that the third liquid droplet is accommodated in the first liquid droplet.
  • Two or more types of droplets may be accommodated in the first droplet.
  • a capsule that is smaller than the droplets is dispersed in the first liquid, and this dispersion is dropped into the second liquid to produce a seamless capsule in which the capsule is accommodated inside the capsule film. Good.
  • the size (maximum diameter) of the seamless capsule can be changed, for example, by changing the diameter (diameter) of the tip of the cylindrical member.
  • the seamless capsule of this embodiment is A seamless capsule with a capsule coating
  • the capsule film contains a galactose partial decomposition product of galactoxyloglucan and polyphenol.
  • the capsule film contains a galactose partial decomposition product and polyphenol, so that it becomes a seamless capsule that can be filled with a wider range of contents than ever and can be easily manufactured.
  • the seamless capsule of this embodiment has acid resistance because the capsule film contains a galactose partial decomposition product and polyphenol.
  • the seamless capsule of this embodiment can be decomposed by cellulase (cellulase degradability) because the capsule film contains a galactose partial decomposition product and polyphenol. Therefore, the seamless capsule of this embodiment is suitable for applications where acid resistance is required and applications where cellulase degradability is required.
  • the seamless capsule of this embodiment is useful as an enteric seamless capsule.
  • the seamless capsule of this embodiment can also exhibit the effect derived from polyphenol by having polyphenol. For example, it can exhibit antibacterial properties.
  • the partial decomposition product of galactose is preferably obtained by decomposing 30 to 55% of galactose. According to such a configuration, since the galactose partial decomposition product is obtained by decomposing 30 to 55% of galactose, the reactivity with polyphenol is improved, so that a relatively uniform film can be formed in a relatively short time. Therefore, a seamless capsule having a capsule film with higher strength can be produced in a shorter time.
  • the polyphenol is a tea extract. According to this configuration, since the polyphenol is a tea extract, the reactivity with the partially decomposed product of galactose is improved, so that a seamless capsule having a capsule film with higher strength can be produced in a shorter time.
  • the manufacturing method of the seamless capsule of this embodiment is as follows: Capsules containing the galactose partial decomposed product and the polyphenol by dropping a first aqueous solution containing a galactose partial decomposed product of galactoxyloglucan and water into a second aqueous solution containing polyphenol and water. It is a method provided with the process of forming the seamless capsule which has a membrane
  • a capsule film can be formed simply by dropping the first aqueous solution into the second aqueous solution, so that the seamless capsule can be produced easily.
  • the obtained seamless capsule can accommodate a wider range of contents than before. Therefore, a seamless capsule that can be filled with a wider range of contents than before can be easily produced.
  • the concentration of the partially decomposed galactose in the first aqueous solution is preferably 0.5 to 3.0% by mass. According to such a configuration, by setting the concentration of the galactose partial decomposition product in the first aqueous solution to 0.5 to 3.0% by mass, the first aqueous solution has a viscosity suitable for dropping, and the galactose partial decomposition product. Therefore, a seamless capsule with higher strength can be easily produced in a shorter time.
  • the concentration of the polyphenol in the second aqueous solution is preferably 0.25 to 10% by mass. According to such a configuration, by setting the polyphenol concentration in the second aqueous solution to 0.25 to 10% by mass, the reactivity between the partially decomposed galactose and the polyphenol can be improved, so that a higher strength seamless Capsules can be manufactured in a shorter time.
  • a tea extract as the polyphenol. According to such a configuration, by using the tea extract as the polyphenol, the reactivity between the partially decomposed galactose and the polyphenol is improved, so that a seamless capsule with higher strength can be produced in a shorter time.
  • a seamless capsule that can be filled with a wider range of contents than before and can be easily manufactured and a method for manufacturing the same are provided.
  • the seamless capsule of the present embodiment has excellent acid resistance and is decomposed by cellulase derived from intestinal bacteria. Therefore, the seamless capsule can be widely used in foods, pharmaceuticals, cosmetics, industrial applications, and particularly used in foods. It is useful. Furthermore, when encapsulating lactic acid bacteria in a capsule, the lactic acid bacteria are protected from the gastric juice by the capsule film showing acid resistance, and after moving into the intestine, the capsules are decomposed by the enzyme, and the lactic acid bacteria are released. Is useful in that it can be used as an enteric capsule that is delivered to the intestine without being killed and then dissolved in the intestine.
  • a pretreatment cartridge manufactured by Tosoh Corporation, IC-SP
  • the amount of galactose per unit (7 sugars) was calculated by (8 sugar area + (9 sugar area ⁇ 2)) / (7 sugar area + 8 sugar area + 9 sugar area).
  • the reduction rate from the galactose amount calculated for the control galactoxyloglucan was further calculated as the galactose removal rate (%) of the galactose amount calculated for the gel composition using the above formula, it was about 45%. there were.
  • the gel-like composition obtained above was blown and dried, then pulverized and sieved to obtain a powdered galactose partial decomposition product.
  • the obtained 2.50 mass% aqueous solution of the partially decomposed galactose was diluted with deionized water to obtain 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00.
  • a 2.50 mass% aqueous solution of a partially decomposed galactose product was prepared.
  • the obtained seamless capsule is collected, washed with water, and its strength (breaking stress) is measured with a creep meter (model: RE2-30005S, manufactured by Yamaden Co., Ltd.). And measured. (40 mm plunger, 1 mm / sec speed, unit: Pa). The measurement was performed three times, and the average value of the obtained measurement values was defined as the strength of the seamless capsule.
  • the results are shown in Table 1.
  • the shape of the seamless capsule is shown in FIG.
  • the concentration of the partially decomposed galactose product is a relatively low concentration of about 0.75% by mass
  • the aqueous solution of the partially decomposed galactose solution is dropped, liquid droplets are dropped when falling into the polyphenol aqueous solution. Due to the impact force applied to the capsule film, the shape of the capsule film tends to be flat or distorted as described above.
  • the concentration is 1.00 to 1.50% by mass
  • the shape of the droplet tends to be maintained even when the impact force is applied due to sufficient viscosity (surface tension) and tends to be spherical. It was.
  • the concentration is higher than 2.00% by mass, the viscosity becomes too high, and the droplet is dropped while pulling and is fixed as it is, so that it tends to be a tear-shaped seamless capsule.
  • aqueous solution of theabigo (contains 94% or more of epigallocatechin gallate, manufactured by Taiyo Kagaku Co., Ltd.) was also used as the polyphenol aqueous solution.
  • 0.25, 0.50, 1.00, 1.50 mass% aqueous solution of tannic acid (manufactured by Nacalai Tesque) was also used as the polyphenol aqueous solution.
  • Teavigo epigallocatechin gallate
  • spherical seamless capsules having such strength that can be scooped up with a spoonful even with a low concentration solution of 0.25% by mass are formed. I knew I would get it.
  • tannic acid was used, spherical seamless capsules tended to be easily formed although the strength of the film was slightly weaker than that of Teabigo.
  • Test Example 3 ⁇ Gelization rate of capsule film> A 1.25% by mass aqueous solution of the partially decomposed galactose prepared in Test Example 1 was dropped into a 1.25% by mass aqueous solution of Sanphenon 90-S with a dropper (1 mm in diameter). After dripping, confirm the state of the capsule film when it is allowed to stand for 10 minutes, 30 seconds, 1 minute, 5 minutes, 10 minutes, 30 minutes, 60 minutes, 120 minutes. The coating rate and strength were measured. The results are shown in Table 3.
  • Criteria for determining the capsule film state A film is formed, and when pressed with a finger, it is crushed and comes out with liquid from the inside. B: Although a film is formed, it is not easily crushed even when pressed with a finger (has high strength), and a small amount of liquid comes out from the inside. C: A film is formed, gels up to the center, hardly crushes even when pressed with a finger (has higher strength), and no liquid comes out from the inside.
  • a capsule film was formed only by holding droplets of the partially decomposed galactose in an aqueous polyphenol solution for about 10 seconds. Since this capsule film is not crushed even when taken out from the polyphenol aqueous solution, it was found that it can be taken out and handled for various uses. In addition, the longer the holding time, the thicker the film and the stronger the film. Furthermore, it was found that when held for 60 to 120 minutes, gelation can occur up to the center of the droplet. In addition, after dripping the galactose partial decomposition product aqueous solution to the polyphenol aqueous solution, each seamless capsule obtained by being immersed for 1 minute and 5 minutes was taken out and immersed in deionized water. Became almost 100%. From this, even after taking out from the polyphenol aqueous solution, it is presumed that the polyphenol remaining in the film permeated gradually toward the inside to form a gel, thereby thickening the film.
  • seamless capsules obtained As shown in Table 4, although the size of seamless capsules obtained varies depending on the equipment used, seamless capsules can be produced with a maximum diameter of about 2.0 to 9.0 mm, regardless of which equipment is used. It turns out that can be done.
  • the obtained seamless capsules are put into an aqueous solution having each pH (hydrochloric acid on the acidic side and sodium hydroxide added to deionized water on the alkaline side), 1, 5, 10, 30, 60, The state after 120, 180, 240 minutes and 1 day was visually observed, and the acid resistance was evaluated according to the following criteria.
  • the obtained seamless capsule maintained its shape and did not dissolve even when exposed to a strong acid having a pH of 1.0. On the other hand, it was dissolved in an alkaline solution having a pH of 11.0 or higher. As a result, it was found that the seamless capsule of this embodiment is excellent in acid resistance.
  • the obtained seamless capsule is put in a hydrochloric acid aqueous solution of pH 1.0 and tap water of pH 7.3, and 1, 5, 10, 30, 60, 120, 180, 240 minutes, the state after one day is visually observed. Observed. As a result, in tap water, the seamless capsule maintained its shape and did not dissolve even after 1 day. On the other hand, in an aqueous solution of a strong acid having a pH of 1.0, when trying to scoop up with a spoon after 10 minutes, the seamless capsule was broken, and it was found that the seamless capsule was dissolved. As a result, it was found that the seamless capsule containing the galactose partial degradation product and polyphenol in the capsule film had better acid resistance than the seamless capsule containing gelatin in the capsule film.
  • Gelatin is an animal raw material and its use may be restricted due to BSE and religious problems, whereas galactose partial degradation products and polyphenols are plant raw materials, and such use restrictions are limited. Can be avoided.
  • it is necessary to heat the gelatin in order to dissolve it in water. Therefore, it is difficult to accommodate contents with low thermal stability, and the selection range of contents is narrowed.
  • partially decomposed products and polyphenols it is not necessary to heat them, so it is possible to accommodate contents with low thermal stability, and the range of selection of contents is wider than when gelatin is used. .
  • seamless capsules were dissolved by cellulase. Moreover, it melt
  • cellulase is known to be produced in the intestine by intestinal bacteria. Therefore, as a result of the above, when a seamless capsule is taken, it is expected that the seamless capsule will be disintegrated and dissolved in the intestine by cellulase produced by intestinal bacteria.
  • Reference A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes, Nature. 2014 February 27; 506 (7489): 498-502 shows that human intestinal bacteria assimilate xyloglucans. ing. Since the film of the seamless capsule of the present embodiment is formed by galactoxyloglucan derived from tamarind, that is, xyloglucans, it is sufficiently conceivable that the seamless capsule disintegrates and dissolves in human intestinal bacteria.
  • the obtained seamless capsule was strong enough to be scooped up with a spoon, but when pressed with a finger, the capsule film was crushed and liquid came out from the inside.
  • the film ratio of the obtained seamless capsule was measured by the above-described measuring method, it was 18%.
  • gelation occurred to the center 4 hours after the addition.
  • the part other than the part where the Keldent aqueous solution exists (the outer part where the galactose partial degradation product exists) gels, and the Keldent aqueous solution is in a sol state It was found that the capsule film was retained inside.
  • the viscosity of a 2.0 mass% aqueous solution of Keldent was measured with a B-type viscometer (model: TVB-25L, manufactured by Toki Sangyo Co., Ltd.) and found to be 3192 mPa ⁇ s (25 ° C., 30 rpm).
  • the 2.0 mass% aqueous solution of was a liquid with a viscosity higher than water.
  • Test Example 9 ⁇ Seamless capsules containing glycerin in the capsule film>
  • concentrated glycerin for cosmetics glycerin, manufactured by Kao Corporation
  • the capsule film was crushed and liquid came out from the inside.
  • the film rate of the obtained seamless capsules was measured by the above measurement method and found to be 37%.
  • Test Example 10 ⁇ Seamless capsules containing olive oil inside capsule film>
  • the galactose partial decomposition product aqueous solution was dropped with a dropper (4 mm diameter) instead of a pipette (caliber 8 mm), and a 2.0 mass% aqueous solution of Keldent was dropped into the droplets of the galactose partial decomposition product (1 mm diameter).
  • the olive oil refined (manufactured by DSP Gokyo Food & Chemical Co., Ltd.) was injected with a Pasteur pipette (caliber 1 mm). Otherwise, seamless capsules were obtained in the same manner as in Test Example 8.
  • the obtained seamless capsule was strong enough to be scooped up with a spoon, but when pressed with a finger, the capsule film was crushed and liquid came out from the inside.
  • the film rate of the obtained seamless capsules was 30% when measured by the above measuring method. As a result, it was found that olive oil was retained inside the capsule film in a sol state as in the case of the Keldent aqueous solution of Test Example 8 and the glycerin of Test Example 9.
  • the dropped product After dropping, the dropped product was recovered after 3 hours, washed with deionized water, and then accommodated in deionized water to obtain seamless capsules.
  • the obtained seamless capsules were strong enough to be scooped with a spoon. Moreover, even if it pressed with the finger
  • the film ratio of the obtained seamless capsule was measured by the above measuring method, it was 100%. As a result, it is considered that the entire droplet gels while the olive oil is uniformly dispersed, and the olive oil is held in the entire capsule film.
  • the obtained seamless capsule was strong enough to be scooped up with a spoon, but when pressed with a finger, the capsule film was crushed and liquid came out from the inside.
  • This capsule film was film-like.
  • the film ratio of the obtained seamless capsule was measured by the above-described measuring method, it was 13%.
  • Test Examples 8 to 13 it is possible to add a solution having a higher viscosity than water, a solution having a higher specific gravity, an oil agent, a water-insoluble powder, or the like as a content to the seamless capsule of this embodiment. all right. Further, as shown in Tables 5 and 6 described above, when the seamless capsules of Test Examples 8 to 13 are decomposed by cellulase, it is assumed that each content is released to the outside. Even when the partially decomposed galactose obtained in Production Example 1 was used as the partially decomposed galactose, the same results as in Test Examples 1 to 5 and 7 to 13 were obtained. Does not affect the results.
  • the seamless capsule and the method for producing the same of the present embodiment are effective for a seamless capsule that delivers lactic acid bacteria to the intestine while alive, a pharmaceutical, an animal drug, a supplement, and the like in which an active ingredient is released and exhibited in the intestine.
  • the capsule film does not require the metal ions contained in conventional enteric seamless capsules, it is possible to encapsulate drugs and active ingredients that react with metal ions, and the range of choice of contents is expanded. There is expected.
  • the inclusion of polyphenol in the capsule film is expected to have antibacterial and antioxidative effects, and the capsule can be stored for a longer period of time.
  • the seamless capsule of the present embodiment is useful in a wide range of fields such as food, cosmetics, and pharmaceuticals, and more particularly useful in the food and pharmaceutical fields.

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Abstract

This seamless capsule is provided with a capsule film, wherein the capsule film contains a galactose partial decomposition product of galactoxyloglucan and contains a polyphenol.

Description

シームレスカプセル及びその製造方法Seamless capsule and method for producing the same
 本発明は、シームレスカプセルおよびその製造方法に関する。 The present invention relates to a seamless capsule and a method for producing the same.
 従来、種々の医薬品、食品といった経口的に使用される製品として、カプセルが用いられている。
 このようなカプセルとして、シームレスカプセルが用いられている。かかるシームレスカプセルは、カプセル皮膜を備え、該カプセル皮膜が、その内部または皮膜自身に有効成分などの内容物を収容する容器として機能するように構成されている。
Conventionally, capsules have been used as orally used products such as various pharmaceuticals and foods.
Seamless capsules are used as such capsules. Such a seamless capsule is provided with a capsule film, and the capsule film functions as a container for containing contents such as active ingredients in the inside or the film itself.
 この種のシームレスカプセルとして、カプセル皮膜がアルギン酸ナトリウムとカルシウム塩とを含有してなるシームレスカプセルが提案されている(特許文献1参照)。
 また、カプセル皮膜が、多層の構成皮膜を有するシームレスカプセルが提案されている(特許文献2参照)。
As this type of seamless capsule, a seamless capsule in which the capsule film contains sodium alginate and a calcium salt has been proposed (see Patent Document 1).
In addition, a seamless capsule in which the capsule film has a multi-layered structure film has been proposed (see Patent Document 2).
 一方、ガラクトキシログルカンのガラクトース部分的分解物と、ポリフェノールとを含有することによって、増粘、ゲル化作用を発揮し得る組成物が提案されている(特許文献3参照)。 On the other hand, a composition capable of exerting a thickening and gelling action by containing a galactose partial degradation product of galactoxyloglucan and polyphenol has been proposed (see Patent Document 3).
日本国特開平1-313421号公報Japanese Unexamined Patent Publication No. 1-331421 日本国特開2006-232760号公報Japanese Unexamined Patent Publication No. 2006-232760 日本国特開2000-354460号公報Japanese Unexamined Patent Publication No. 2000-354460
 しかし、特許文献1の技術では、カプセル皮膜を形成するために、カルシウム塩、すなわち金属イオンが必要とされる。よって、内容物として、金属イオンと反応するような成分を添加することが困難となり、その結果、内容物の種類が限定されるおそれがある。しかも、内容物が金属イオンを含んでいると、その分、カプセル皮膜が不溶化され、その結果、カプセル皮膜の崩壊や溶出が不要に遅延するおそれもある。 However, in the technique of Patent Document 1, a calcium salt, that is, a metal ion is required to form a capsule film. Therefore, it becomes difficult to add a component that reacts with metal ions as the content, and as a result, the type of the content may be limited. In addition, if the content contains metal ions, the capsule film is insolubilized accordingly, and as a result, the capsule film may be unnecessarily delayed in dissolution or elution.
 また、特許文献1の技術では、アルギン酸ナトリウムをカプセル状に形成した後、さらにカルシウムでその表面を架橋する必要があるため、その分、高い技術力や特別な機器が必要となり、製造が煩雑になるおそれがある。
 また、特許文献2の技術でも、複数の構成皮膜を形成する必要があるため、その分、高い技術力や特別な機器が必要となり、製造が煩雑になるおそれがある。
In addition, in the technique of Patent Document 1, it is necessary to form a sodium alginate in a capsule shape and then cross-link the surface with calcium. Therefore, high technical ability and special equipment are required, and the production is complicated. There is a risk.
Further, in the technique of Patent Document 2, it is necessary to form a plurality of constituent films, and accordingly, high technical ability and special equipment are required, and the production may be complicated.
 一方、特許文献3では、ガラクトキシログルカンのガラクトース部分分解物とポリフェノールとを用いることによってシームレスカプセルのカプセル皮膜を形成し得ることは、何ら開示されていない。 On the other hand, Patent Document 3 does not disclose that a capsule film of a seamless capsule can be formed by using a galactose partial decomposition product of galactoxyloglucan and polyphenol.
 上記事情に鑑み、本発明は、従来よりも幅広い内容物を充填でき、しかも簡便に製造可能なシームレスカプセル及びその製造方法を提供することを課題とする。 In view of the above circumstances, an object of the present invention is to provide a seamless capsule that can be filled with a wider range of contents than before and that can be easily manufactured, and a method for manufacturing the same.
 本発明者らは、ガラクトキシログルカンのガラクトース部分分解物(以下、単に「ガラクトース部分分解物」という場合がある。)とポリフェノールとの反応性について鋭意研究した。
 すると、驚くべきことに、ガラクトース部分分解物の水溶液をポリフェノールの水溶液に滴下すると、ガラクトース部分分解物水溶液の液滴の表面がポリフェノールと瞬時に反応してゲル化が生じ、これによって液滴の表面が皮膜で覆われることを見出した。すなわち、シームレスカプセルのカプセル皮膜が簡便に形成されることを見出した。
The present inventors diligently studied the reactivity of a galactose partial degradation product of galactoxyloglucan (hereinafter sometimes simply referred to as “galactose partial degradation product”) with polyphenol.
Surprisingly, when an aqueous solution of a partial decomposition product of galactose is dropped into an aqueous solution of polyphenol, the surface of the droplet of the aqueous solution of partial decomposition product of galactose reacts instantaneously with polyphenol, resulting in gelation, which causes Was found to be covered with a film. That is, it has been found that a capsule film of a seamless capsule can be easily formed.
 また、ガラクトース部分分解物水溶液の液滴をポリフェノール水溶液中に保持する時間や、ポリフェノール水溶液の濃度に応じて、カプセル皮膜の厚みが変化することを見出した。さらに、上記時間や濃度に応じてポリフェノールがより液滴の内部に浸透することで、最終的には液滴全体をもゲル化することも可能であることを見出して、本発明を完成するに至った。 Further, it was found that the thickness of the capsule film changes depending on the time for holding the droplet of the aqueous solution of partially decomposed galactose solution in the polyphenol aqueous solution and the concentration of the polyphenol aqueous solution. Further, the present invention is completed by finding that the polyphenol penetrates more into the inside of the droplet depending on the time and concentration, and that the entire droplet can finally be gelled. It came.
 すなわち、本発明に係るシームレスカプセルは、
 カプセル皮膜を備えたシームレスカプセルであって、
 前記カプセル皮膜は、ガラクトキシログルカンのガラクトース部分分解物とポリフェノールとを含有する。
That is, the seamless capsule according to the present invention is
A seamless capsule with a capsule coating,
The capsule film contains a galactose partial decomposition product of galactoxyloglucan and polyphenol.
 かかる構成によれば、カプセル皮膜がガラクトース部分分解物とポリフェノールとを含有することによって、従来よりも幅広い内容物を充填でき、しかも簡便に製造可能なシームレスカプセルとなる。 According to such a configuration, the capsule film contains a galactose partial decomposition product and polyphenol, so that a wide range of contents can be filled as compared with the conventional one, and a seamless capsule can be easily produced.
 上記構成のシームレスカプセルにおいては、
 前記ガラクトース部分分解物は、ガラクトースが30~55%分解されてなることが好ましい。
In the seamless capsule of the above configuration,
The partial decomposition product of galactose is preferably obtained by decomposing 30 to 55% of galactose.
 かかる構成によれば、ガラクトース部分分解物が、ガラクトースが30~55%分解されてなることによって、ポリフェノールとの反応性が向上するため、比較的短時間で比較的均一な皮膜が形成され得る。
 よって、より強度の高いカプセル皮膜を有するシームレスカプセルが、より短時間で製造され得る。
According to such a configuration, since the galactose partial decomposition product is obtained by decomposing 30 to 55% of galactose, the reactivity with polyphenol is improved, so that a relatively uniform film can be formed in a relatively short time.
Therefore, a seamless capsule having a capsule film with higher strength can be produced in a shorter time.
 上記構成のシームレスカプセルにおいては、
 前記ポリフェノールが、茶抽出物であることが好ましい。
In the seamless capsule of the above configuration,
It is preferable that the polyphenol is a tea extract.
 かかる構成によれば、ポリフェノールが茶抽出物であることによって、ガラクトース部分分解物との反応性が向上するため、より強度の高いカプセル皮膜を有するシームレスカプセルが、より短時間で製造され得る。 According to this configuration, since the polyphenol is a tea extract, the reactivity with the partially decomposed product of galactose is improved, so that a seamless capsule having a higher strength capsule film can be produced in a shorter time.
 本発明に係るシームレスカプセルの製造方法は、
 ガラクトキシログルカンのガラクトース部分分解物と水とを含有する第1の水溶液を、ポリフェノールと水とを含有する第2の水溶液に滴下することによって、前記ガラクトース部分分解物と前記ポリフェノールとを含有するカプセル皮膜を有するシームレスカプセルを形成する工程を備えた方法である。
The method for producing a seamless capsule according to the present invention includes:
Capsules containing the galactose partial decomposed product and the polyphenol by dropping a first aqueous solution containing a galactose partial decomposed product of galactoxyloglucan and water into a second aqueous solution containing polyphenol and water. It is a method provided with the process of forming the seamless capsule which has a membrane | film | coat.
 かかる構成によれば、第1の水溶液を第2の水溶液中に滴下するだけでカプセル皮膜が形成されるため、簡便にシームレスカプセルを製造し得る。
 また、上記の通り、得られたシームレスカプセルは、従来よりも幅広い内容物を収容できる。
 従って、従来よりも幅広い内容物を充填できるシームレスカプセルを、簡便に製造し得る。
According to this configuration, a capsule capsule can be formed simply by dropping the first aqueous solution into the second aqueous solution, so that seamless capsules can be easily produced.
In addition, as described above, the obtained seamless capsule can accommodate a wider range of contents than before.
Therefore, a seamless capsule that can be filled with a wider range of contents than before can be easily produced.
 上記構成のシームレスカプセルの製造方法においては、
 前記第1の水溶液における前記ガラクトース部分分解物の濃度を、0.5~3.0質量%とすることが好ましい。
In the method for producing a seamless capsule having the above-described configuration,
The concentration of the partially decomposed galactose in the first aqueous solution is preferably 0.5 to 3.0% by mass.
 かかる構成によれば、第1の水溶液におけるガラクトース部分分解物の濃度を0.5~3.0質量%とすることによって、第1の水溶液が滴下に適した粘度となり、また、ガラクトース部分分解物とポリフェノールとの反応性を向上させることができるため、より強度の高いシームレスカプセルを、簡便に、より短時間で製造し得る。 According to such a configuration, by setting the concentration of the galactose partial decomposition product in the first aqueous solution to 0.5 to 3.0% by mass, the first aqueous solution has a viscosity suitable for dropping, and the galactose partial decomposition product. Therefore, a seamless capsule with higher strength can be easily produced in a shorter time.
 上記構成のシームレスカプセルの製造方法においては、
 前記第2の水溶液における前記ポリフェノールの濃度を、0.25~10質量%とすることが好ましい。
In the method for producing a seamless capsule having the above-described configuration,
The concentration of the polyphenol in the second aqueous solution is preferably 0.25 to 10% by mass.
 かかる構成によれば、第2の水溶液におけるポリフェノールの濃度を0.25~10質量%とすることによって、ガラクトース部分分解物とポリフェノールとの反応性を向上させることができるため、より強度の高いシームレスカプセルを、より短時間で製造し得る。 According to such a configuration, by setting the polyphenol concentration in the second aqueous solution to 0.25 to 10% by mass, the reactivity between the partially decomposed galactose and the polyphenol can be improved, so that a higher strength seamless Capsules can be manufactured in a shorter time.
 上記構成のシームレスカプセルの製造方法においては、
 前記ポリフェノールとして、茶抽出物を用いることが好ましい。
In the method for producing a seamless capsule having the above-described configuration,
It is preferable to use a tea extract as the polyphenol.
 かかる構成によれば、ポリフェノールとして茶抽出物を用いることによって、ガラクトース部分分解物とポリフェノールとの反応性が向上するため、より強度の高いシームレスカプセルを、より短時間で製造し得る。 According to such a configuration, by using a tea extract as the polyphenol, the reactivity between the partially decomposed galactose and the polyphenol is improved, so that a stronger seamless capsule can be produced in a shorter time.
本発明の一実施形態の、各形状を有するシームレスカプセルの写真The photograph of the seamless capsule which has each shape of one embodiment of the present invention 本実施形態の各形状のシームレスカプセルの最大径の一例を示す写真Photograph showing an example of the maximum diameter of each shape seamless capsule of this embodiment
 以下に、本発明に係るシームレスカプセル及びその製造方法の実施形態について、説明する。 Hereinafter, embodiments of the seamless capsule and the manufacturing method thereof according to the present invention will be described.
 本実施形態のシームレスカプセルは、カプセル皮膜を備えたシームレスカプセルであって、前記カプセル皮膜は、ガラクトキシログルカンのガラクトース部分分解物とポリフェノールとを含有する。 The seamless capsule of the present embodiment is a seamless capsule having a capsule film, and the capsule film contains a galactose partial decomposition product of galactoxyloglucan and polyphenol.
 前記ガラクトキシログルカンは、双子葉、単子葉植物など高等植物の細胞壁(一次壁)の構成成分であり、また、一部の植物種子の貯蔵多糖類として存在する非イオン性の高分子多糖類である。
 このガラクトキシログルカンは、グルコース、キシロースおよびガラクトースを構成糖として有しており、主鎖としてβ-1,4結合してなるグルコースを有し、側鎖としてキシロースを有し、そのキシロースにさらに結合されたガラクトースを有する。
 ガラクトキシログルカンは、いかなる植物由来のガラクトキシログルカンでもよく、例えばタマリンド、ジャトバ、ナスタチウムの種子、大豆、緑豆、インゲンマメ、イネ、オオムギなどの穀物またはリンゴなどの果実の表皮から入手できる。最も入手し易く、含有量も多いことを考慮すると、好ましくは、豆科植物タマリンド種子由来のガラクトキシログルカンである。かかるガラクトキシログルカンとしては、市販のものを採用し得る。市販品としては、例えば、グリロイド(登録商標、DSP五協フード&ケミカル(株)製)等が挙げられる。
The galactoxyloglucan is a constituent component of the cell wall (primary wall) of higher plants such as dicotyledonous and monocotyledonous plants, and is a nonionic polymer polysaccharide that exists as a storage polysaccharide for some plant seeds. is there.
This galactoxyloglucan has glucose, xylose and galactose as constituent sugars, has β-1,4 linked glucose as the main chain, has xylose as the side chain, and further binds to the xylose Galactose.
The galactoxyloglucan may be any plant-derived galactoxyloglucan, and can be obtained from, for example, tamarind, jatoba, nastathium seed, soybean, mung bean, kidney bean, rice, barley, or other fruit epidermis. Considering that it is most easily available and has a large content, galactoxyloglucan derived from legume tamarind seeds is preferable. As such galactoxyloglucan, a commercially available product can be adopted. Examples of commercially available products include Griloid (registered trademark, manufactured by DSP Gokyo Food & Chemical Co., Ltd.).
 前記ガラクトキシログルカンのガラクトース部分分解物は、ガラクトキシログルカンの側鎖ガラクトースが、部分分解されて除去されてなる物質である。
 なお、本実施形態においてガラクトキシログルカンとは、側鎖ガラクトースが後述する酵素処理による部分分解によって除去されていないガラクトキシログルカン(完全ガラクトキシログルカン)を意味する。また、かかる完全ガラクトキシログルカンは、ネイティブガラクトキシログルカンとも称される場合がある。
 上記部分分解には酵素が用いられる。酵素としては、例えば、β-ガラクトシダーゼが挙げられる。
The galactose partial degradation product of galactoxyloglucan is a substance obtained by partially decomposing and removing the side chain galactose of galactoxyloglucan.
In addition, in this embodiment, galactoxyloglucan means galactoxyloglucan (complete galactoxyloglucan) from which side chain galactose has not been removed by partial decomposition by enzyme treatment described later. Such complete galactoxyloglucan may also be referred to as native galactoxyloglucan.
An enzyme is used for the partial decomposition. Examples of the enzyme include β-galactosidase.
 前記β-ガラクトシダーゼは、ガラクトキシログルカンに含まれるガラクトースとキシロースの結合を加水分解してガラクトースを遊離する酵素である。β-ガラクトシダーゼとしては、植物由来のものおよび微生物由来のもののいずれでもよいが、微生物Aspergillus oryzaeまたはBacillus circulans由来の酵素、または、ガラクトキシログルカン含有種子中の酵素が好ましい。かかるβ-ガラクトシダーゼとしては、市販のものを採用し得る。 The β-galactosidase is an enzyme that releases galactose by hydrolyzing the bond between galactose and xylose contained in galactoxyloglucan. β-galactosidase may be either plant-derived or microorganism-derived, but an enzyme derived from the microorganism Aspergillus oryzae or Bacillus circulans or an enzyme in seeds containing galactoxyloglucan is preferable. As such β-galactosidase, a commercially available product can be adopted.
 このβ-ガラクトシダーゼによる酵素反応では、反応の進行につれて側鎖ガラクトースが部分的に除去され、その除去率が30%付近になると反応液は急激に増粘しゲル化する。ガラクトースの除去率が30~55%の範囲では、加熱によってゲル化し冷却によってゾル化する可逆的熱応答ゲル化性を有するものとなる。ガラクトース除去率が30%未満ではポリフェノールとの反応性が低下し、また、55%を越えるとガラクトース部分分解物の水への溶解性が低下し、均一なガラクトース部分分解物水溶液を調製しにくく、不均一な皮膜が形成される傾向にある。 In this enzymatic reaction with β-galactosidase, side chain galactose is partially removed as the reaction proceeds, and when the removal rate reaches around 30%, the reaction solution rapidly thickens and gels. When the galactose removal rate is in the range of 30 to 55%, the gel has a reversible thermal response gelation property that gels by heating and sols by cooling. If the galactose removal rate is less than 30%, the reactivity with polyphenol is reduced, and if it exceeds 55%, the solubility of the galactose partial degradation product in water is reduced, making it difficult to prepare a uniform aqueous solution of galactose partial degradation product, It tends to form a non-uniform film.
 この点を考慮すれば、ガラクトースが30~55%部分分解されてなる上記ガラクトース部分分解物を用いることが好ましい。ガラクトース部分分解物が、ガラクトースが30~55%部分分解されてなることによって、ポリフェノールと反応させると、比較的短時間で比較的均一な皮膜が形成され得る。よって、より強度の高いカプセル皮膜を有するシームレスカプセルが、より短時間で製造され得る。 Considering this point, it is preferable to use the galactose partial decomposition product obtained by partial decomposition of galactose by 30 to 55%. When the galactose partial degradation product is partially decomposed by 30 to 55% of galactose, and reacts with polyphenol, a relatively uniform film can be formed in a relatively short time. Therefore, a seamless capsule having a capsule film with higher strength can be produced in a shorter time.
 ガラクトキシログルカンは、通常、側鎖キシロースを約37%、側鎖ガラクトースを約17%含有している(Gidleyら、カーボハイドレート リサーチ(Carbohydrate Research)、214(1991)219-314頁参照)。よって、ガラクトースが30~55%部分分解されてなるガラクトース部分分解物は、側鎖キシロースを39~41%、側鎖ガラクトースを8~12%含有していると算出される。
 なお、ガラクトースの部分分解率(すなわち、ガラクトースの除去率)は、得られた部分分解物がセルラーゼ分解されることによって生成されるガラクトキシログルカンオリゴ糖量を、高速液体クロマトグラフィー(以下、HPLCと称する。)(アミノカラム)で測定することにより算出することができる。
Galactoxyloglucan usually contains about 37% side chain xylose and about 17% side chain galactose (see Gidley et al., Carbohydrate Research, 214 (1991) 219-314). Therefore, a galactose partial degradation product obtained by partial degradation of 30 to 55% of galactose is calculated to contain 39 to 41% of side chain xylose and 8 to 12% of side chain galactose.
In addition, the partial decomposition rate of galactose (that is, the removal rate of galactose) is determined by measuring the amount of galactoxyloglucan oligosaccharide produced by cellulase decomposition of the obtained partial decomposition product using high performance liquid chromatography (hereinafter referred to as HPLC). It can be calculated by measuring with (amino column).
 前記ポリフェノールとしては、化学合成品であるポリフェノール、植物由来のポリフェノール(植物ポリフェノール)が挙げられ、これらのうち、好ましくは植物ポリフェノールである。
 植物ポリフェノールは、緑茶(抹茶煎茶など)、紅茶、ウーロン茶、プーアル茶(黒茶)、マテ茶等の茶葉、白色野菜、柑橘類の果皮や種子、ブドウの果皮や種子(赤ワイン、赤ブドウ果汁など)、リンゴ、柿、桃、なし、タマネギの皮、栗、ゴボウ、コーヒー豆、カカオ豆等から、温水等で抽出される抽出物(固体状及び液状状の抽出物を含む)である。この抽出物には、モノマーポリフェノールやポリマーポリフェノールが多く含まれている。
Examples of the polyphenol include chemically synthesized polyphenols and plant-derived polyphenols (plant polyphenols). Among these, plant polyphenols are preferred.
Plant polyphenols are green tea (such as matcha green tea), black tea, oolong tea, puer tea (black tea), mate tea and other tea leaves, white vegetables, citrus peels and seeds, grape skins and seeds (red wine, red grape juice, etc.) , Apples, strawberries, peaches, none, onion peels, chestnuts, burdock, coffee beans, cacao beans, and the like (including solid and liquid extracts). This extract is rich in monomeric polyphenols and polymer polyphenols.
 上記モノマーポリフェノールとしては、フラボノイド類、クロロゲン酸、没食子酸や、エラグ酸等が挙げられる。
 上記フラボノイド類としては、カテキン類、ケルセチン、ルチン、アントシアニン等が挙げられる。
 上記カテキン類としては、(+)-カテキン、(+)-ガロカテキン、(-)-エピカテキン、(-)-エピガロカテキン、及び、これらの没食子酸エステル等が挙げられる。これらのうち、カテキン類としては、(-)-エピガロカテキンの没食子酸エステル(エピガロカテキンガレート)が好ましい。
Examples of the monomer polyphenol include flavonoids, chlorogenic acid, gallic acid, and ellagic acid.
Examples of the flavonoids include catechins, quercetin, rutin, and anthocyanins.
Examples of the catechins include (+)-catechin, (+)-gallocatechin, (−)-epicatechin, (−)-epigallocatechin, and gallic esters thereof. Of these, as the catechins, gallic acid ester (epigallocatechin gallate) of (−)-epigallocatechin is preferable.
 上記ポリマーポリフェノールとしては、縮合型及び加水分解型のタンニン等が挙げられる。
 上記縮合型のタンニンとしては、プロアントシアニジン類等が挙げられ、該プロアントシアニジン類としては、テアルビジンやプロデルフィニジン等が挙げられる。
 上記加水分解型のタンニンとしては、タンニン酸、ガロタンニンや、エラグタンニン等が挙げられる。
Examples of the polymer polyphenol include condensed and hydrolyzed tannins.
Examples of the condensed tannin include proanthocyanidins and the like, and examples of the proanthocyanidins include thealvidin and prodelphinidin.
Examples of the hydrolyzable tannin include tannic acid, gallotannin, and ellagitannin.
 上記植物ポリフェノールが使用される場合、上述の抽出物それ自体が使用されてもよいし、また、その抽出物から有効成分であるポリフェノールを濃縮(抽出)したものでもよいし、さらに、その抽出物から有効成分のポリフェノールを精製(分離)したものでもよい。これらの抽出物のうち、茶葉から抽出された抽出物である茶抽出物が、好ましい。
 なお、上記植物ポリフェノールは、上記のものに特に限定されるものではなく、ポリフェノールを含有する植物から得られるものであれば、いずれでもよい。
 なお、ポリフェノールは、1種又は複数種の混合物として用いられてもよい。
When the above-mentioned plant polyphenol is used, the above-mentioned extract itself may be used, or a polyphenol which is an active ingredient may be concentrated (extracted) from the extract, and further the extract The active ingredient polyphenols may be purified (separated). Of these extracts, tea extract, which is an extract extracted from tea leaves, is preferable.
In addition, the said plant polyphenol is not specifically limited to said thing, As long as it is obtained from the plant containing polyphenol, any may be sufficient.
In addition, polyphenol may be used as a 1 type, or multiple types of mixture.
 前記カプセル皮膜は、ガラクトース部分分解物と、ポリフェノールと、さらに水を含有する。
 かかるカプセル皮膜は、ゲル状であっても、フィルム状であってもよい。ガラクトース部分分解物と、ポリフェノールと、水とを混合することによってゲル状のカプセル皮膜が得られ、得られた混合物の水分量を乾燥等によって低減させることによって、フィルム状のカプセル皮膜が得られる。
The capsule film contains a galactose partial decomposition product, polyphenol, and water.
Such a capsule film may be in the form of a gel or a film. A gel-like capsule film is obtained by mixing a partially decomposed galactose product, polyphenol, and water, and a film-like capsule film is obtained by reducing the water content of the obtained mixture by drying or the like.
 カプセル皮膜中のガラクトース部分分解物の含有量は、所望のカプセル皮膜の強度に応じて適宜設定されればよく、特に限定されない。 The content of the galactose partial degradation product in the capsule film may be set as appropriate according to the strength of the desired capsule film, and is not particularly limited.
 カプセル皮膜中のポリフェノールの含有量は、ガラクトース部分分解物がゲル化し得る程度、及び、カプセル皮膜の厚み方向におけるゲル化の程度に応じて、すなわち、所望のカプセル皮膜の厚みに応じて適宜設定されればよく、特に限定されない。 The content of polyphenol in the capsule film is appropriately set according to the degree to which the galactose partial degradation product can gel and the degree of gelation in the thickness direction of the capsule film, that is, according to the desired capsule film thickness. There is no particular limitation as long as it is sufficient.
 シームレスカプセルの大きさ(すなわちカプセル皮膜の大きさ)は、特に限定されないが、例えば、図2に示すように、シームレスカプセルの中心を通り、該シームレスカプセルの両端(中心を通る仮想直線がシームレスカプセルの表面と交わる2つの交点)を結ぶ最大の長さ(最大径)が2~10mmとされ得る。なお、最大径は、シームレスカプセルが球状の場合には、直径に相当する。また、涙形の場合には、その球状部分の最大径に相当する。 The size of the seamless capsule (that is, the size of the capsule film) is not particularly limited. For example, as shown in FIG. 2, the seamless capsule passes through the center of the seamless capsule, and both ends of the seamless capsule (virtual straight lines passing through the center are seamless capsules. The maximum length (maximum diameter) connecting the two intersection points intersecting the surface of the substrate 2 to 10 mm may be 2 to 10 mm. The maximum diameter corresponds to the diameter when the seamless capsule is spherical. In the case of a teardrop shape, this corresponds to the maximum diameter of the spherical portion.
 カプセル皮膜の厚みは、特に限定されないが、例えば、その最大径に対して3~40%程度の値であることが好ましい。かかる厚みの比率は、後述する実施例に記載された方法によって、皮膜率として測定され得る。
 カプセル皮膜の厚みが3%以上であることによって、皮膜の強度がより十分なものとなり、40%以下であることによって、皮膜の内部に他の成分を収容し得る体積を確保することができる。
 なお、カプセル皮膜は、皮膜の内側にゲル化されていない部分を有していても、皮膜の表面から中心まで全てゲル化されている中実の状態であってもよい。カプセル皮膜が内側にゲル化されていない部分を有する場合には、その内側には、通常、ガラクトース部分分解物水溶液が存在している。
The thickness of the capsule film is not particularly limited, but is preferably about 3 to 40% of the maximum diameter, for example. The thickness ratio can be measured as a coating rate by the method described in Examples described later.
When the thickness of the capsule film is 3% or more, the film has a sufficient strength, and when it is 40% or less, a volume capable of accommodating other components inside the film can be secured.
In addition, even if it has the part which is not gelatinized inside a membrane | film | coat, the capsule membrane | film | coat may be in the solid state from which the whole surface is gelatinized from the surface of a membrane | film | coat. When the capsule film has a portion not gelled on the inside, an aqueous solution of a partially decomposed galactose solution is usually present on the inside.
 本実施形態のカプセル皮膜は、必要に応じて、通常、カプセル皮膜に添加される各種添加剤を含有してもよい。かかる添加剤としては、例えば、可塑剤、防腐剤、水分活性低下剤、pH調整剤等が挙げられる。可塑剤としては、例えば、グリセリン、ソルビトール、プロピレングリコール、ポリエチレングリコール等が挙げられる。上記の他、添加剤として、皮膜用賦形剤が挙げられ、該賦形剤としては、例えば、各種デンプン類(修飾デンプン、加工デンプン、デンプン、デンプン分解物等を含む)等の各種多糖類が挙げられる。 The capsule film of this embodiment may contain various additives that are usually added to the capsule film as necessary. Examples of such additives include plasticizers, preservatives, water activity lowering agents, pH adjusters and the like. Examples of the plasticizer include glycerin, sorbitol, propylene glycol, polyethylene glycol and the like. In addition to the above, additives for coating include excipients such as various polysaccharides such as various starches (including modified starch, modified starch, starch, starch degradation products, etc.). Is mentioned.
 本実施形態のシームレスカプセルには、カプセル皮膜の内部(すなわちガラクトース部分分解物水溶液内)、または、カプセル皮膜(自身の)内に、内容物が収容され得る。
 内容物は、特に限定されない。内容物としては、例えば、オリーブ油やキャノーラ油などの油剤が挙げられる。また、かかる油剤に有効成分が分散又は溶解されたもの等も挙げられる。なお、上記油剤は、ポリフェノール水溶液に滴下される前に、ガラクトース部分分解物と混合され、乳化され、この状態で、ガラクトース部分分解物と共にポリフェノール水溶液に滴下されてもよい。この場合には、油剤は、ガラクトース部分分解物水溶液と乳化された状態で、カプセル皮膜及びカプセル皮膜内部に収容される。
 シームレスカプセル全体の体積に対する内容物の体積の比は、20~93体積%であることが好ましい。なお、この場合において、カプセル皮膜の上記皮膜率が、3~40%であることが好ましい。
In the seamless capsule of the present embodiment, the contents can be accommodated in the capsule film (that is, in the aqueous solution of a partially decomposed galactose product) or in the capsule film (its own).
The contents are not particularly limited. Examples of the contents include oil agents such as olive oil and canola oil. Moreover, the thing etc. by which the active ingredient was disperse | distributed or melt | dissolved in this oil agent are mentioned. In addition, before dripping at the polyphenol aqueous solution, the said oil agent may be mixed and emulsified with the galactose partial decomposition product, and may be dripped at the polyphenol aqueous solution with the galactose partial decomposition product in this state. In this case, the oil agent is contained in the capsule film and the capsule film in an emulsified state with the aqueous solution of a partially decomposed galactose solution.
The ratio of the content volume to the total volume of the seamless capsule is preferably 20 to 93% by volume. In this case, it is preferable that the coating rate of the capsule coating is 3 to 40%.
 次いで、本実施形態のシームレスカプセルの製造方法について、説明する。 Next, a method for manufacturing the seamless capsule of this embodiment will be described.
 本実施形態のシームレスカプセルの製造方法は、
 ガラクトキシログルカンのガラクトース部分分解物と水とを含有する第1の水溶液を、ポリフェノールと水とを含有する第2の水溶液に滴下することによって、前記ガラクトース部分分解物と前記ポリフェノールとを含有するカプセル皮膜を有するシームレスカプセルを形成する工程を備えた方法である。
The manufacturing method of the seamless capsule of this embodiment is as follows:
Capsules containing the galactose partial decomposed product and the polyphenol by dropping a first aqueous solution containing a galactose partial decomposed product of galactoxyloglucan and water into a second aqueous solution containing polyphenol and water. It is a method provided with the process of forming the seamless capsule which has a membrane | film | coat.
 具体的には、本実施形態のシームレスカプセルの製造方法では、ガラクトース部分分解物を水に溶解させて第1の水溶液を調製し、ポリフェノールを水に溶解させて第2の水溶液を調製し、第1の水溶液を第2の水溶液に滴下させる。第1の水溶液の液滴が第2の水溶液と接触すると、滴下した瞬間から液滴の表面側からゲル化し、時間の経過に伴って第2の水溶液が液滴内に浸透し、液滴の表面側から中心に向かってゲル化が進む。これによって、カプセル皮膜が形成される。 Specifically, in the method for producing a seamless capsule of the present embodiment, a first aqueous solution is prepared by dissolving a galactose partial decomposition product in water, a second aqueous solution is prepared by dissolving polyphenol in water, The aqueous solution of 1 is dropped into the second aqueous solution. When the droplet of the first aqueous solution comes into contact with the second aqueous solution, it gels from the surface side of the droplet from the moment of dropping, and the second aqueous solution penetrates into the droplet as time passes, Gelation proceeds from the surface side toward the center. As a result, a capsule film is formed.
 第1の水溶液におけるガラクトース部分分解物の濃度は、特に限定されず、カプセル皮膜が形成され得るように適宜設定され得る。例えば、ガラクトース部分分解物の濃度が高い程、ポリフェノールとの反応性が高くなる一方、濃度が高くなり過ぎると、粘度が過度に高くなって滴下が困難になる傾向にある。
 従って、例えば、かかる観点を考慮して、第1の水溶液におけるガラクトース部分分解物の濃度を0.25~5.0質量%とすることが好ましく、0.5~3.0質量%とすることがより好ましい。
 第1の水溶液におけるガラクトース部分分解物の濃度を0.25~5.0質量%とすることによって、第1の水溶液が滴下に適した粘度となり、また、ガラクトース部分分解物とポリフェノールとの反応性を向上させることができるため、より強度の高いシームレスカプセルを、簡便に、より短時間で製造し得る。
The density | concentration of the galactose partial decomposition product in 1st aqueous solution is not specifically limited, It can set suitably so that a capsule film | membrane may be formed. For example, the higher the concentration of the partially decomposed galactose, the higher the reactivity with polyphenol. On the other hand, if the concentration is too high, the viscosity tends to be excessively high and dripping tends to be difficult.
Therefore, for example, considering this viewpoint, the concentration of the galactose partial decomposition product in the first aqueous solution is preferably 0.25 to 5.0% by mass, and preferably 0.5 to 3.0% by mass. Is more preferable.
By setting the concentration of the galactose partial decomposition product in the first aqueous solution to 0.25 to 5.0% by mass, the first aqueous solution has a viscosity suitable for dripping, and the reactivity between the galactose partial decomposition product and polyphenols. Therefore, a seamless capsule with higher strength can be easily produced in a shorter time.
 第2の水溶液におけるポリフェノールの濃度は、特に限定されず、カプセル皮膜が形成され得るように適宜設定され得る。例えば、ポリフェノールの濃度が高い程、ガラクトース部分分解物との反応性が高くなる一方、濃度が高くなり過ぎると、形成されたシームレスカプセルが口腔内に含まれた際、苦味が感じられる傾向にある。
 従って、例えば、かかる観点を考慮して、第2の水溶液におけるポリフェノールの濃度は、0.1~20質量%が好ましく、0.25~10質量%であることがより好ましい。
 第2の水溶液におけるポリフェノールの濃度を0.25~10質量%とすることによって、ガラクトース部分分解物とポリフェノールとの反応性を向上させることができるため、より強度の高いシームレスカプセルを、より短時間で製造し得る。また、服用された際の苦みの発生が抑制され得る。
The concentration of polyphenol in the second aqueous solution is not particularly limited, and can be appropriately set so that a capsule film can be formed. For example, the higher the concentration of polyphenol, the higher the reactivity with the partially decomposed product of galactose. On the other hand, when the concentration is too high, bitterness tends to be felt when the formed seamless capsule is contained in the oral cavity. .
Therefore, for example, considering such a viewpoint, the concentration of the polyphenol in the second aqueous solution is preferably 0.1 to 20% by mass, and more preferably 0.25 to 10% by mass.
By setting the polyphenol concentration in the second aqueous solution to 0.25 to 10% by mass, the reactivity between the partially decomposed galactose and the polyphenol can be improved. Can be manufactured. Moreover, the occurrence of bitterness when taken can be suppressed.
 滴下時の第1の水溶液及び第2の水溶液の温度は、特に限定されず、適宜設定され得る。例えば、滴下時にこれら水溶液の温度が高いと、カプセル皮膜を形成し難くなる傾向にある。
 従って、例えば、かかる観点を考慮すれば、滴下時の第1の水溶液及び第2の水溶液の温度は、5~25℃が好ましい。
The temperature of the 1st aqueous solution at the time of dripping and the 2nd aqueous solution is not specifically limited, It can set suitably. For example, when the temperature of these aqueous solutions is high at the time of dripping, it tends to be difficult to form a capsule film.
Therefore, for example, considering this viewpoint, the temperature of the first aqueous solution and the second aqueous solution at the time of dropping is preferably 5 to 25 ° C.
 滴下後における第2の溶液中での第1の水溶液の保持時間は、特に限定されず、適宜設定され得る。例えば、保持時間が長くなる程、ポリフェノールが液滴の内部に浸透してゲル化し、その結果、皮膜が厚くなる傾向にある。また、保持時間がさらに長くなると、最終的に、カプセル皮膜全体がゲル化された状態となる傾向にある。
 従って、例えば、かかる観点を考慮して、滴下後の保持時間を10秒~2時間とすることが好ましい。
 なお、液滴を第2の水溶液から取り出すことによって、液滴への第2の水溶液の供給が停止される。液滴中で未反応の(未だゲル化に関与していない)第2の水溶液が残っている場合には、取り出し後においても、その分だけ、内部へのポリフェノールの拡散、及び、ゲル化が進行し、一方、第2の水溶液が反応に関与できなくなると、ゲル化が停止する。
The holding time of the 1st aqueous solution in the 2nd solution after dripping is not specifically limited, It can set suitably. For example, as the holding time becomes longer, polyphenol penetrates into the droplets and gels, and as a result, the coating tends to be thicker. Moreover, when holding time becomes still longer, the whole capsule film tends to be in a gelled state.
Therefore, for example, considering such a viewpoint, it is preferable that the retention time after dropping is 10 seconds to 2 hours.
The supply of the second aqueous solution to the droplet is stopped by removing the droplet from the second aqueous solution. When the second aqueous solution that has not reacted (not yet involved in gelation) remains in the droplets, even after removal, the polyphenol diffuses into the interior, and gelation occurs. On the other hand, if the second aqueous solution can no longer participate in the reaction, gelation stops.
 第2の液中に第1の液を滴下する方法は、特に限定されるものではなく、従来公知の滴下方法が採用され得る。かかる滴下方法としては、例えば、先端に開口を有する筒状部材を用いた方法が挙げられる。このような筒状部材としては、ノズル、ピペット等が挙げられる。 The method of dropping the first liquid into the second liquid is not particularly limited, and a conventionally known dropping method can be adopted. Examples of the dropping method include a method using a cylindrical member having an opening at the tip. Examples of such a cylindrical member include a nozzle and a pipette.
 また、第1の液の内部に、該第1の液及び第2の液とは異なる第3の液を収容しながら、第2の液中に滴下する方法も挙げられる。このような方法として、例えば、外側のノズルの内部に内側のノズルが配された二重ノズルを用いて、外側のノズルから第1の液、内側のノズルから第3の液を、第1の液滴内に第3の液滴が収容されるように、第2の液に滴下することが挙げられる。この他、一方のノズルの外側に、該一方のノズルよりも口径が小さい他方のノズルが配されてなる2つのノズルを用いて、上記一方のノズルから第1の液滴を、上記他方のノズルから第3の液滴を、第1の液滴内に第3の液滴が収容されるように、第2の液に滴下することも挙げられる。 In addition, a method in which a third liquid different from the first liquid and the second liquid is contained in the first liquid and dropped into the second liquid is also included. As such a method, for example, by using a double nozzle in which an inner nozzle is arranged inside an outer nozzle, the first liquid from the outer nozzle, the third liquid from the inner nozzle, Dropping into the second liquid may be mentioned so that the third liquid droplet is accommodated in the liquid droplet. In addition, by using two nozzles in which the other nozzle having a smaller diameter than the one nozzle is arranged outside the one nozzle, the first liquid droplet is discharged from the one nozzle. The third liquid droplet may be dropped into the second liquid so that the third liquid droplet is accommodated in the first liquid droplet.
 なお、第1の液滴の内部に、2種類以上の液滴を収容してもよい。
 また、第1の液に、液滴よりもさらに小さいカプセル等を分散し、この分散液を第2の液に滴下してカプセル皮膜の内部に上記カプセルが収容されたシームレスカプセルを製造してもよい。
Two or more types of droplets may be accommodated in the first droplet.
Alternatively, a capsule that is smaller than the droplets is dispersed in the first liquid, and this dispersion is dropped into the second liquid to produce a seamless capsule in which the capsule is accommodated inside the capsule film. Good.
 シームレスカプセルの大きさ(最大径)は、例えば、上記筒状部材の先端の口径(直径)を変化させることによって、変化させ得る。 The size (maximum diameter) of the seamless capsule can be changed, for example, by changing the diameter (diameter) of the tip of the cylindrical member.
 以上の通り、本実施形態のシームレスカプセルは、
 カプセル皮膜を備えたシームレスカプセルであって、
 前記カプセル皮膜は、ガラクトキシログルカンのガラクトース部分分解物とポリフェノールとを含有する。
As described above, the seamless capsule of this embodiment is
A seamless capsule with a capsule coating,
The capsule film contains a galactose partial decomposition product of galactoxyloglucan and polyphenol.
 本実施形態のシームレスカプセルによれば、カプセル皮膜がガラクトース部分分解物とポリフェノールとを含有することによって、従来よりも幅広い内容物を充填でき、しかも簡便に製造可能なシームレスカプセルとなる。 According to the seamless capsule of the present embodiment, the capsule film contains a galactose partial decomposition product and polyphenol, so that it becomes a seamless capsule that can be filled with a wider range of contents than ever and can be easily manufactured.
 加えて、本実施形態のシームレスカプセルは、カプセル皮膜がガラクトース部分分解物とポリフェノールとを含有することによって、耐酸性を有する。
 さらに、本実施形態のシームレスカプセルは、カプセル皮膜がガラクトース部分分解物とポリフェノールとを含有することによって、セルラーゼによって分解され得る(セルラーゼ分解性)。
 よって、本実施形態のシームレスカプセルは、耐酸性が要望される用途や、セルラーゼ分解性が要望される用途に好適である。
 特に、耐酸性とセルラーゼ分解性との双方を有することから、本実施形態のシームレスカプセルは、腸溶性のシームレスカプセルとして有用である。
 また、本実施形態のシームレスカプセルは、ポリフェノールを有することによって、ポリフェノールに由来する作用効果も発揮し得る。例えば、抗菌性を発揮し得る。
In addition, the seamless capsule of this embodiment has acid resistance because the capsule film contains a galactose partial decomposition product and polyphenol.
Furthermore, the seamless capsule of this embodiment can be decomposed by cellulase (cellulase degradability) because the capsule film contains a galactose partial decomposition product and polyphenol.
Therefore, the seamless capsule of this embodiment is suitable for applications where acid resistance is required and applications where cellulase degradability is required.
In particular, since it has both acid resistance and cellulase degradability, the seamless capsule of this embodiment is useful as an enteric seamless capsule.
Moreover, the seamless capsule of this embodiment can also exhibit the effect derived from polyphenol by having polyphenol. For example, it can exhibit antibacterial properties.
 本実施形態のシームレスカプセルにおいては、
 前記ガラクトース部分分解物は、ガラクトースが30~55%分解されてなることが好ましい。
 かかる構成によれば、ガラクトース部分分解物が、ガラクトースが30~55%分解されてなることによって、ポリフェノールとの反応性が向上するため、比較的短時間で比較的均一な皮膜が形成され得る。
 よって、より強度の高いカプセル皮膜を有するシームレスカプセルが、より短時間で製造され得る。
In the seamless capsule of this embodiment,
The partial decomposition product of galactose is preferably obtained by decomposing 30 to 55% of galactose.
According to such a configuration, since the galactose partial decomposition product is obtained by decomposing 30 to 55% of galactose, the reactivity with polyphenol is improved, so that a relatively uniform film can be formed in a relatively short time.
Therefore, a seamless capsule having a capsule film with higher strength can be produced in a shorter time.
 本実施形態のシームレスカプセルにおいては、
 前記ポリフェノールが、茶抽出物であることが好ましい。
 かかる構成によれば、ポリフェノールが茶抽出物であることによって、ガラクトース部分分解物との反応性が向上するため、より強度の高いカプセル皮膜を有するシームレスカプセルが、より短時間で製造され得る。
In the seamless capsule of this embodiment,
It is preferable that the polyphenol is a tea extract.
According to this configuration, since the polyphenol is a tea extract, the reactivity with the partially decomposed product of galactose is improved, so that a seamless capsule having a capsule film with higher strength can be produced in a shorter time.
 本実施形態のシームレスカプセルの製造方法は、
 ガラクトキシログルカンのガラクトース部分分解物と水とを含有する第1の水溶液を、ポリフェノールと水とを含有する第2の水溶液に滴下することによって、前記ガラクトース部分分解物と前記ポリフェノールとを含有するカプセル皮膜を有するシームレスカプセルを形成する工程を備えた方法である。
The manufacturing method of the seamless capsule of this embodiment is as follows:
Capsules containing the galactose partial decomposed product and the polyphenol by dropping a first aqueous solution containing a galactose partial decomposed product of galactoxyloglucan and water into a second aqueous solution containing polyphenol and water. It is a method provided with the process of forming the seamless capsule which has a membrane | film | coat.
 本実施形態のシームレスカプセルの製造方法によれば、第1の水溶液を第2の水溶液中に滴下するだけでカプセル皮膜が形成されるため、簡便にシームレスカプセルを製造し得る。
 また、上記の通り、得られたシームレスカプセルは、従来よりも幅広い内容物を収容できる。
 従って、従来よりも幅広い内容物を充填できるシームレスカプセルを、簡便に製造し得る。
According to the method for producing a seamless capsule of the present embodiment, a capsule film can be formed simply by dropping the first aqueous solution into the second aqueous solution, so that the seamless capsule can be produced easily.
In addition, as described above, the obtained seamless capsule can accommodate a wider range of contents than before.
Therefore, a seamless capsule that can be filled with a wider range of contents than before can be easily produced.
 本実施形態のシームレスカプセルの製造方法においては、
 前記第1の水溶液における前記ガラクトース部分分解物の濃度を、0.5~3.0質量%とすることが好ましい。
 かかる構成によれば、第1の水溶液におけるガラクトース部分分解物の濃度を0.5~3.0質量%とすることによって、第1の水溶液が滴下に適した粘度となり、また、ガラクトース部分分解物とポリフェノールとの反応性を向上させることができるため、より強度の高いシームレスカプセルを、簡便に、より短時間で製造し得る。
In the manufacturing method of the seamless capsule of this embodiment,
The concentration of the partially decomposed galactose in the first aqueous solution is preferably 0.5 to 3.0% by mass.
According to such a configuration, by setting the concentration of the galactose partial decomposition product in the first aqueous solution to 0.5 to 3.0% by mass, the first aqueous solution has a viscosity suitable for dropping, and the galactose partial decomposition product. Therefore, a seamless capsule with higher strength can be easily produced in a shorter time.
 本実施形態のシームレスカプセルの製造方法においては、
 前記第2の水溶液における前記ポリフェノールの濃度を、0.25~10質量%とすることが好ましい。
 かかる構成によれば、第2の水溶液におけるポリフェノールの濃度を0.25~10質量%とすることによって、ガラクトース部分分解物とポリフェノールとの反応性を向上させることができるため、より強度の高いシームレスカプセルを、より短時間で製造し得る。
In the manufacturing method of the seamless capsule of this embodiment,
The concentration of the polyphenol in the second aqueous solution is preferably 0.25 to 10% by mass.
According to such a configuration, by setting the polyphenol concentration in the second aqueous solution to 0.25 to 10% by mass, the reactivity between the partially decomposed galactose and the polyphenol can be improved, so that a higher strength seamless Capsules can be manufactured in a shorter time.
 本実施形態のシームレスカプセルの製造方法においては、
 前記ポリフェノールとして、茶抽出物を用いることが好ましい。
 かかる構成によれば、ポリフェノールとして茶抽出物を用いることによって、ガラクトース部分分解物とポリフェノールとの反応性が向上するため、より強度の高いシームレスカプセルを、より短時間で製造し得る。
In the manufacturing method of the seamless capsule of this embodiment,
It is preferable to use a tea extract as the polyphenol.
According to such a configuration, by using the tea extract as the polyphenol, the reactivity between the partially decomposed galactose and the polyphenol is improved, so that a seamless capsule with higher strength can be produced in a shorter time.
 以上の通り、本実施形態によれば、従来よりも幅広い内容物を充填でき、しかも簡便に製造可能なシームレスカプセル及びその製造方法が提供される。 As described above, according to the present embodiment, a seamless capsule that can be filled with a wider range of contents than before and can be easily manufactured and a method for manufacturing the same are provided.
 なお、本実施形態のシームレスカプセルは、耐酸性に優れ、腸内細菌由来のセルラーゼによって分解されることから、食品、医薬品、化粧品、工業用途に幅広く使用することができ、特に食品に使用されることが有用である。さらに、乳酸菌をカプセル中に内包させた場合等においては、耐酸性を示すカプセル皮膜によって胃液から乳酸菌を保護し、腸内に移動した後に酵素によってカプセルが分解され、乳酸菌が放出されるため、乳酸菌を死滅させずに腸内まで送達させ、その後、腸内で溶解させる腸溶性カプセルとして使用できるという点で有用である。 The seamless capsule of the present embodiment has excellent acid resistance and is decomposed by cellulase derived from intestinal bacteria. Therefore, the seamless capsule can be widely used in foods, pharmaceuticals, cosmetics, industrial applications, and particularly used in foods. It is useful. Furthermore, when encapsulating lactic acid bacteria in a capsule, the lactic acid bacteria are protected from the gastric juice by the capsule film showing acid resistance, and after moving into the intestine, the capsules are decomposed by the enzyme, and the lactic acid bacteria are released. Is useful in that it can be used as an enteric capsule that is delivered to the intestine without being killed and then dissolved in the intestine.
 以上、本実施形態について説明したが、本発明は、上記実施形態に特に限定されるものではなく、本発明の意図する範囲内において適宜設計変更可能である。 As mentioned above, although this embodiment was described, this invention is not specifically limited to the said embodiment, A design change is possible suitably in the range which this invention intends.
 以下、本発明について、実施例を参照しながらより詳細に説明するが、本発明はこれらの実施例に限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.
(製造例1)ガラクトース部分分解物の製造
 ガラクトキシログルカン(DSP五協フード&ケミカル(株)製、グリロイド(登録商標))1gを水99gに添加し、75℃で15分撹拌し、基質を1質量%含有する1質量%ガラクトキシログルカン水溶液を得た。精製酵素β-ガラクトシダーゼを用い、1質量%ガラクトキシログルカン水溶液を、酵素濃度2.4×10-5質量%、pH5.6、50℃で反応させた後、100℃で20分間加熱することにより、反応を停止させた。反応溶液は、反応開始後約15時間でゲル化し、これにより、ゲル状の組成物を得た。得られたゲル状の組成物におけるガラクトース除去率を、以下の方法で算出した。
(Production Example 1) Production of partial decomposition product of galactose 1 g of galactoxyloglucan (manufactured by DSP Gokyo Food & Chemical Co., Ltd., Griloid (registered trademark)) is added to 99 g of water, and stirred at 75 ° C. for 15 minutes. A 1% by mass galactoxyloglucan aqueous solution containing 1% by mass was obtained. Using the purified enzyme β-galactosidase, a 1% by mass galactoxyloglucan aqueous solution was reacted at an enzyme concentration of 2.4 × 10 −5 % by mass, pH 5.6, 50 ° C. and then heated at 100 ° C. for 20 minutes. The reaction was stopped. The reaction solution gelled about 15 hours after the start of the reaction, thereby obtaining a gel-like composition. The galactose removal rate in the obtained gel composition was calculated by the following method.
 ゲル状の組成物(1質量%水溶液)7gにセルラーゼオノズカRS(ヤクルト薬品工業(株))0.15質量%溶液(50mM酢酸緩衝液、pH4.0)を1mL加え、50℃、オーバーナイトで反応させた。前述で調製した1質量%ガラクトキシログルカン水溶液も同様の方法で反応させ、対照とした。反応後、反応液を98℃で30分間加熱することによって酵素を失活させて、試料を得た。その後、得られた試料を前処理カートリッジ(東ソー(株)製、IC-SP)および0.45μmのセルロースアセテート製メンブレンフィルターにかけ、得られたろ液10μLを、アセトニトリル:水=60:40(v/v)を0.6mL/分で流しているHPLCのアミノカラムにアプライし、ガラクトキシログルカンのオリゴ糖(7糖(ガラクトース0個)、8糖(ガラクトース1個)、9糖(ガラクトース2個))の溶出面積を示差屈折率計で検出した。次いで、1ユニット(7糖)あたりのガラクトース量を、(8糖の面積+(9糖の面積×2))/(7糖の面積+8糖の面積+9糖の面積)により算出した。上記式を用いてゲル状の組成物について算出されたガラクトース量の、対照のガラクトキシログルカンについて算出されたガラクトース量からの減少率をガラクトース除去率(%)としてさらに算出したところ、約45%であった。 1 mL of a cellulase Onozuka RS (Yakult Pharmaceutical Co., Ltd.) 0.15% by weight (50 mM acetate buffer, pH 4.0) was added to 7 g of a gel-like composition (1% by weight aqueous solution) at 50 ° C. overnight. It was made to react with. The 1 mass% galactoxyloglucan aqueous solution prepared above was reacted in the same manner as a control. After the reaction, the reaction solution was heated at 98 ° C. for 30 minutes to inactivate the enzyme to obtain a sample. Thereafter, the obtained sample was applied to a pretreatment cartridge (manufactured by Tosoh Corporation, IC-SP) and a 0.45 μm cellulose acetate membrane filter, and 10 μL of the obtained filtrate was acetonitrile: water = 60: 40 (v / v) was applied to an HPLC amino column flowing at 0.6 mL / min, and oligosaccharides of galactoxyloglucan (7 sugars (0 galactose), 8 sugars (1 galactose), 9 sugars (2 galactoses) ) Was detected with a differential refractometer. Next, the amount of galactose per unit (7 sugars) was calculated by (8 sugar area + (9 sugar area × 2)) / (7 sugar area + 8 sugar area + 9 sugar area). When the reduction rate from the galactose amount calculated for the control galactoxyloglucan was further calculated as the galactose removal rate (%) of the galactose amount calculated for the gel composition using the above formula, it was about 45%. there were.
 そして、前述で得られたゲル状の組成物を送風乾燥した後、粉砕し、篩過して、粉状のガラクトース部分分解物を得た。 The gel-like composition obtained above was blown and dried, then pulverized and sieved to obtain a powdered galactose partial decomposition product.
(試験例1)
<ガラクトース部分分解物の濃度とポリフェノールの濃度との関係>
(Test Example 1)
<Relationship between the concentration of galactose partial degradation products and the concentration of polyphenol>
(ガラクトース部分分解物水溶液(第1の水溶液)の調製)
 容量300mLのステンレスビーカーに脱イオン水195.0gを入れ、製造例1で得られたガラクトース部分分解物5.0gを加えて室温で混合し、ガラクトース部分分解物の2.50質量%分散液を調製した。分散液を-20℃に2時間静置した後、室温で30分間静置して解凍し、その後、解凍物を攪拌機で1時間撹拌して均一化した。得られたガラクトース部分分解物の2.50質量%水溶液を脱イオン水で希釈して、0.25、0.50、0.75、1.00、1.25、1.50、2.00、2.50質量%のガラクトース部分分解物水溶液を調製した。
(Preparation of galactose partial decomposition product aqueous solution (first aqueous solution))
Add 195.0 g of deionized water to a 300 mL stainless beaker, add 5.0 g of the partially decomposed galactose obtained in Production Example 1 and mix at room temperature to obtain a 2.50 mass% dispersion of the partially decomposed galactose. Prepared. The dispersion was allowed to stand at −20 ° C. for 2 hours, and then allowed to stand at room temperature for 30 minutes to thaw, and then the thawed material was stirred with a stirrer for 1 hour to homogenize. The obtained 2.50 mass% aqueous solution of the partially decomposed galactose was diluted with deionized water to obtain 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00. A 2.50 mass% aqueous solution of a partially decomposed galactose product was prepared.
(ガラクトキシログルカン水溶液(比較例)の調製)
 比較例として、容量300mLのステンレスビーカーに脱イオン水197.5gを入れ、ガラクトキシログルカン(ガラクトースが部分分解されていないガラクトキシログルカン)を2.5g加えて室温で1時間攪拌することによって、ガラクトキシログルカンの1.25質量%水溶液を調製した。
(Preparation of galactoxyloglucan aqueous solution (comparative example))
As a comparative example, 197.5 g of deionized water was placed in a 300 mL stainless beaker, and 2.5 g of galactoxyloglucan (galactoxyloglucan in which galactose was not partially decomposed) was added and stirred at room temperature for 1 hour. A 1.25% by mass aqueous solution of xyloglucan was prepared.
(ポリフェノール水溶液(第2の水溶液)の調製)
 容量200mLのガラスビーカーに脱イオン水97.5gを入れ、ポリフェノールとしてサンフェノン90-S(茶抽出物、カテキン類70%以上含有、太陽化学(株)製)2.5gを加えて混合し、サンフェノン90-Sの2.50質量%水溶液を調製した。得られたサンフェノン90-S2.50質量%水溶液を脱イオン水で希釈し、0.25、0.50、0.75、1.00、1.25、1.50、2.00、2.50質量%水溶液を調製した。
(Preparation of polyphenol aqueous solution (second aqueous solution))
Add 97.5 g of deionized water to a 200 mL glass beaker, add 2.5 g of Sunphenon 90-S (tea extract, containing over 70% catechins, manufactured by Taiyo Kagaku Co., Ltd.) as a polyphenol, and mix. A 2.50 mass% aqueous solution of 90-S was prepared. The resulting Sanphenon 90-S 2.50 mass% aqueous solution was diluted with deionized water to give 0.25, 0.50, 0.75, 1.00, 1.25, 1.50, 2.00, 2. A 50 mass% aqueous solution was prepared.
 容量10mLのガラスビーカーに各濃度のサンフェノン90-S水溶液を10g入れ、各濃度のガラクトース部分分解物水溶液およびガラクトキシログルカン水溶液をスポイト(口径1mm)で滴下した。滴下してから1~2分後に、滴下したガラクトース部分分解物水溶液及びガラクトキシログルカン水溶液の様子を肉眼で観察し、シームレスカプセルが形成されるか否かを評価し、形成された場合にはその形状を、下記の判定基準によって評価した。
 また、シームレスカプセルが形成された場合には、得られたシームレスカプセルを回収し、水洗した後に、その強度(破断応力)をクリープメーター(型式:RE2-33005S、(株)山電社製)を用いて測定した。(40mmプランジャー、1mm/secの速度、単位:Pa)。3回の測定を行い、得られた測定値の平均値を、シームレスカプセルの強度とした。
 結果を表1に示す。また、シームレスカプセルの形状を、図1に示す。
10 g of each concentration of sanphenone 90-S aqueous solution was put into a glass beaker having a capacity of 10 mL, and each concentration of galactose partial decomposition product aqueous solution and galactoxyloglucan aqueous solution was added dropwise with a dropper (caliber 1 mm). One to two minutes after dropping, the state of the dropped galactose partial degradation product aqueous solution and galactoxyloglucan aqueous solution is observed with the naked eye to evaluate whether or not a seamless capsule is formed. The shape was evaluated according to the following criteria.
In the case where a seamless capsule is formed, the obtained seamless capsule is collected, washed with water, and its strength (breaking stress) is measured with a creep meter (model: RE2-30005S, manufactured by Yamaden Co., Ltd.). And measured. (40 mm plunger, 1 mm / sec speed, unit: Pa). The measurement was performed three times, and the average value of the obtained measurement values was defined as the strength of the seamless capsule.
The results are shown in Table 1. The shape of the seamless capsule is shown in FIG.
(判定基準)
・シームレスカプセルが形成されるか否か(形成性)の判定基準
○:シームレスカプセルが形成され、その強度は、薬さじで掬い上げて上記クリープメーターによる強度の測定に供することが可能な程度に高かった。
△:シームレスカプセルは形成されたが、薬さじで掬い上げると皮膜が破れた。すなわち、その強度は、上記クリープメーターによる強度の測定に供することが不可能な程度に低かった。
×:シームレスカプセルが形成されなかった。
(Criteria)
-Judgment criteria for whether or not seamless capsules are formed (formability) ○: Seamless capsules are formed, and the strength of the capsules can be crushed with a spoonful and used for the measurement of strength by the creep meter. it was high.
Δ: A seamless capsule was formed, but the film was broken when scooped up with a spoon. That is, the strength was so low that it could not be used for measuring the strength by the creep meter.
X: Seamless capsules were not formed.
・シームレスカプセルの形状の判定基準
  球:球状のシームレスカプセル
  涙:涙形のシームレスカプセル
  歪球:球状だが歪んだ形状のシームレスカプセル
  扁平:扁平な形状のシームレスカプセル
・ Criteria for seamless capsule shape Sphere: Spherical seamless capsule Tear: Tears-shaped seamless capsule Strain sphere: Spherical but distorted seamless capsule Flat: Seamless capsule with flat shape
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
 表1に示したように、ガラクトース部分分解物の濃度が0.50質量%以上であれば、シームレスカプセルが形成され得ることがわかった。また、該濃度が0.75質量%以上であれば、薬さじで掬い上げることができる程度の強度を有するシームレスカプセルが形成され、1.00~1.50質量%以上であれば、薬さじで掬い上げることができる程度の強度を有する球状のシームレスカプセルが形成され得ることがわかった。
 一方、ポリフェノールの濃度が0.25質量%以上であれば、シームレスカプセルが形成され得ることがわかった。また、該濃度が0.50質量%以上であれば、薬さじで掬い上げることができる程度の強度を有する球状のシームレスカプセルが形成され得ることがわかった。
 シームレスカプセルの形状については、ガラクトース部分分解物の濃度が0.75質量%程度の比較的低濃度であると、ガラクトース部分分解物水溶液を滴下したときに、ポリフェノール水溶液中に落下する際に液滴に加えられる衝撃力によってカプセル皮膜の形状が上記した扁平または歪球になり易い傾向にあった。一方、該濃度が1.00~1.50質量%の場合には、十分な粘度(表面張力)によって上記衝撃力が加えられても液滴の形状が維持され、球状になり易い傾向にあった。さらに、2.00質量%以上の高濃度になると、粘度が高くなり過ぎて、滴下時に糸を引きながら滴下され、そのまま固定されるため、涙形のシームレスカプセルとなる傾向にあった。
As shown in Table 1, it was found that seamless capsules could be formed when the concentration of the partially decomposed galactose was 0.50% by mass or more. When the concentration is 0.75% by mass or more, a seamless capsule having a strength that can be scooped up with a spoon is formed, and when the concentration is 1.00 to 1.50% by mass or more, It was found that spherical seamless capsules having such a strength that can be scooped up can be formed.
On the other hand, it was found that if the polyphenol concentration is 0.25% by mass or more, seamless capsules can be formed. In addition, it was found that when the concentration is 0.50% by mass or more, spherical seamless capsules having such strength that can be scooped up with a spoonful can be formed.
As for the shape of the seamless capsule, when the concentration of the partially decomposed galactose product is a relatively low concentration of about 0.75% by mass, when the aqueous solution of the partially decomposed galactose solution is dropped, liquid droplets are dropped when falling into the polyphenol aqueous solution. Due to the impact force applied to the capsule film, the shape of the capsule film tends to be flat or distorted as described above. On the other hand, when the concentration is 1.00 to 1.50% by mass, the shape of the droplet tends to be maintained even when the impact force is applied due to sufficient viscosity (surface tension) and tends to be spherical. It was. Furthermore, when the concentration is higher than 2.00% by mass, the viscosity becomes too high, and the droplet is dropped while pulling and is fixed as it is, so that it tends to be a tear-shaped seamless capsule.
(試験例2)
<その他のポリフェノール水溶液の影響>
(Test Example 2)
<Influence of other polyphenol aqueous solution>
(ポリフェノール水溶液(第2の水溶液)の調製)
 ポリフェノール水溶液として、下記のポリフェノール含有飲料水を用いた。
 すなわち、煎茶(商品名:「おーいお茶」(株)伊藤園製)、煎茶(濃)(商品名:「おーいお茶濃い茶」(株)伊藤園製)、ウーロン茶(商品名:「烏龍茶」サントリー(株)製)、紅茶(商品名:「午後の紅茶(クリアストレート)」キリンビバレッジ(株)製)及びコーヒー(商品名:「プレミアムボスブラック」サントリー(株)製)、グレープジュース(商品名:「ウェルチグレープ100」アサヒ飲料(株)製)を用いた。
 また、ポリフェノール水溶液として、テアビゴ(エピガロカテキンガレート94%以上含有、太陽化学(株)製)の0.25、0.50、1.00、1.50質量%水溶液も用いた。
 さらに、ポリフェノール水溶液として、タンニン酸(ナカライテスク(株)製)の0.25、0.50、1.00、1.50質量%水溶液も用いた。
(Preparation of polyphenol aqueous solution (second aqueous solution))
The following polyphenol-containing drinking water was used as the polyphenol aqueous solution.
In other words, Sencha (trade name: “Oi Ocha” manufactured by ITO EN), Sencha (dark) (Product name: “OI Ocha Dark Tea” manufactured by ITO EN), Oolong Tea (trade name: “Oolong Tea” Suntory Ltd.) ), Black tea (trade name: “Afternoon Tea (Clear Straight)” Kirin Beverage Co., Ltd.) and coffee (trade name: “Premium Boss Black” Suntory Co., Ltd.), grape juice (trade name: “Welch”) Grape 100 "Asahi Beverage Co., Ltd.) was used.
Moreover, 0.25, 0.50, 1.00, 1.50 mass% aqueous solution of theabigo (contains 94% or more of epigallocatechin gallate, manufactured by Taiyo Kagaku Co., Ltd.) was also used as the polyphenol aqueous solution.
Furthermore, 0.25, 0.50, 1.00, 1.50 mass% aqueous solution of tannic acid (manufactured by Nacalai Tesque) was also used as the polyphenol aqueous solution.
 容量10mLのガラスビーカーに、ポリフェノール水溶液を10g入れ、該ポリフェノール水溶液に、試験例1で調製した各濃度のガラクトース部分分解物水溶液及びガラクトキシログルカン水溶液をスポイト(口径1mm)で滴下した。滴下してから1~2分後に、滴下したガラクトース部分分解物水溶液及びガラクトキシログルカン水溶液の様子を肉眼で観察し、前述した判定基準を用いて、シームレスカプセルが形成される否かを評価し、形成された場合にはその形状を、前述した判定基準で評価した。
 また、シームレスカプセルが形成された場合には、前述した測定方法で、その強度(単位:Pa)を評価した。
 結果を表2に示す。
10 g of polyphenol aqueous solution was put into a glass beaker having a capacity of 10 mL, and the galactose partial decomposition product aqueous solution and galactoxyloglucan aqueous solution of each concentration prepared in Test Example 1 were dropped into the polyphenol aqueous solution with a dropper (1 mm in diameter). One to two minutes after dropping, the state of the dropped galactose partial degradation product aqueous solution and the galactoxyloglucan aqueous solution is observed with the naked eye, and using the above-mentioned criteria, whether or not seamless capsules are formed is evaluated, When formed, the shape was evaluated according to the aforementioned criteria.
When seamless capsules were formed, their strength (unit: Pa) was evaluated by the measurement method described above.
The results are shown in Table 2.
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
 表2に示すように、ポリフェノール含有飲料では、滴下してから1~2分後に、シームレスカプセルが形成されなかった。この原因は、ポリフェノールの濃度が低いことによるものと推察される。
 ただし、煎茶(濃)、紅茶、グレープジュースにガラクトース部分分解物水溶液を滴下し、液滴を1時間保持すると、シームレスカプセルが形成されていた。
 このことから、ガラクトース部分分解物水溶液の液滴をポリフェノール含有飲料(比較的濃度が低いポリフェノール水溶液)に滴下した場合であっても、長時間保持することによってシームレスカプセルを作製し得ることがわかった。
 また、テアビゴ(エピガロカテキンガレート)を用いた場合には、0.25質量%の低濃度溶液であっても、薬さじで掬い上げることができる程度の強度を有する球状のシームレスカプセルが形成され得ることがわかった。
 さらに、タンニン酸を用いた場合には、皮膜の強度がテアビゴよりもやや弱いものの球状のシームレスカプセルが形成され易い傾向にあった。
As shown in Table 2, with the polyphenol-containing beverage, seamless capsules were not formed 1 to 2 minutes after the dripping. This is presumably due to the low concentration of polyphenols.
However, when galactose partial decomposition product aqueous solution was dropped into Sencha (dark), black tea, and grape juice, and the droplets were held for 1 hour, seamless capsules were formed.
From this, it was found that seamless capsules can be produced by holding for a long time even when droplets of a partially decomposed galactose aqueous solution are dropped on a polyphenol-containing beverage (polyphenol aqueous solution having a relatively low concentration). .
In addition, when Teavigo (epigallocatechin gallate) is used, spherical seamless capsules having such strength that can be scooped up with a spoonful even with a low concentration solution of 0.25% by mass are formed. I knew I would get it.
Furthermore, when tannic acid was used, spherical seamless capsules tended to be easily formed although the strength of the film was slightly weaker than that of Teabigo.
(試験例3)
<カプセル皮膜のゲル化速度>
 試験例1で調製したガラクトース部分分解物の1.25質量%水溶液を、サンフェノン90-Sの1.25質量%水溶液にスポイト(口径1mm)で滴下した。滴下してから、10秒、30秒、1分、5分、10分、30分、60分、120分間静置したときのカプセル皮膜の状態を目視及び触感で確認し、また、カプセル皮膜の皮膜率及び強度を測定した。
 結果を表3に示す。
(Test Example 3)
<Gelization rate of capsule film>
A 1.25% by mass aqueous solution of the partially decomposed galactose prepared in Test Example 1 was dropped into a 1.25% by mass aqueous solution of Sanphenon 90-S with a dropper (1 mm in diameter). After dripping, confirm the state of the capsule film when it is allowed to stand for 10 minutes, 30 seconds, 1 minute, 5 minutes, 10 minutes, 30 minutes, 60 minutes, 120 minutes. The coating rate and strength were measured.
The results are shown in Table 3.
・カプセル皮膜の状態の判定基準
A:皮膜が形成され、指で押圧すると潰れて内部から液で出てくる。
B:皮膜が形成されるが、指で押圧しても潰れ難く(高い強度を有する)、内部から液が少量出てくる。
C:皮膜が形成され、中心部分までゲル化し、指で押圧しても潰れ難く(より高い強度を有する)、内部から液が出てこない。
Criteria for determining the capsule film state A: A film is formed, and when pressed with a finger, it is crushed and comes out with liquid from the inside.
B: Although a film is formed, it is not easily crushed even when pressed with a finger (has high strength), and a small amount of liquid comes out from the inside.
C: A film is formed, gels up to the center, hardly crushes even when pressed with a finger (has higher strength), and no liquid comes out from the inside.
・カプセルの皮膜率(厚みの指標)の測定方法
 ガラクトース部分分解物水溶液をポリフェノール水溶液に滴下した後、そのまま、10秒、30秒、1、5、10、30、60、120分間浸漬させたシームレスカプセルを回収し、ハサミを用いて中央で二等分し、皮膜をポリエチレン/ナイロン製のフィルム上に優しく押し広げ、フィルムと共に皮膜の厚み(フィルムの厚み+皮膜の厚み)を、デジタル外側マイクロメータ(型式:MCD130-25、新潟精機(株)製)で測定した。各浸漬時間ごとに3回測定し、平均値を算出し、平均値からフィルムの厚み(3回測定値の平均値)を差し引いて、皮膜の厚みを算出した。
 さらに、上記のように滴下し、10分間経過した(そのまま10分間浸漬させた)後、シームレスカプセルを取り出し、その10個の最も大きな厚みを、デジタル外側マイクロメータを用いて測定し、その平均値を算出し、この平均値をシームレスカプセルの最大径とした。
 そして、皮膜の厚みとシームレスカプセルの最大径とから、以下の式により皮膜率を算出した。
  皮膜率(%)={(皮膜の厚み)×2/(シームレスカプセルの最大径)}×100
 本試験例では、上記した皮膜率の測定において、10分経過後のカプセル皮膜は球形であり、その最大径(直径)は、4.0mmであった。よって、この最大径を用いて皮膜率を算出した。
・ Measurement method of capsule film ratio (thickness index) Seamlessly immersed for 10 seconds, 30 seconds, 1, 5, 10, 30, 60, 120 minutes after dropping a partially decomposed galactose aqueous solution into a polyphenol aqueous solution Capsule is collected and bisected in the center with scissors, and the film is gently spread on a polyethylene / nylon film, and the film thickness (film thickness + film thickness) is measured with the digital outer micrometer. (Model: MCD130-25, manufactured by Niigata Seiki Co., Ltd.) Measurement was performed three times for each immersion time, an average value was calculated, and the thickness of the film was calculated by subtracting the film thickness (average value of the three times measurement value) from the average value.
Furthermore, after dripping as mentioned above and having passed for 10 minutes (it was immersed as it is for 10 minutes), a seamless capsule was taken out, the 10 largest thickness was measured using a digital outside micrometer, and the average value This average value was taken as the maximum diameter of the seamless capsule.
And the film rate was computed by the following formula | equation from the thickness of a film | membrane, and the maximum diameter of a seamless capsule.
Film rate (%) = {(film thickness) × 2 / (maximum diameter of seamless capsule)} × 100
In this test example, in the above-described measurement of the coating rate, the capsule coating after 10 minutes was spherical, and the maximum diameter (diameter) was 4.0 mm. Therefore, the coating rate was calculated using this maximum diameter.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
 表3に示すように、ガラクトース部分分解物の液滴をポリフェノール水溶液に10秒程度の短時間保持しただけでも、カプセル皮膜が形成された。このカプセル皮膜は、ポリフェノール水溶液から取り出しても潰れないことから、取り出して種々の用途に向けて取り扱うことが可能であることがわかった。
 また、保持時間が長くなるほど皮膜の厚みが増し、皮膜が強固になった。
 さらに、60~120分間保持した場合、液滴の中心部までゲル化し得ることがわかった。
 なお、ガラクトース部分分解物水溶液をポリフェノール水溶液に滴下した後、1分間、及び、5分間浸漬させて得られた各シームレスカプセルを取り出し、脱イオン水に浸漬させたところ、24時間経過後に、皮膜率がほぼ100%になった。このことから、ポリフェノール水溶液から取り出した後においても、皮膜に残存するポリフェノールが少しずつ内部に向かって浸透してゲルを形成し、これによって皮膜が厚くなっていったものと推察される。
As shown in Table 3, a capsule film was formed only by holding droplets of the partially decomposed galactose in an aqueous polyphenol solution for about 10 seconds. Since this capsule film is not crushed even when taken out from the polyphenol aqueous solution, it was found that it can be taken out and handled for various uses.
In addition, the longer the holding time, the thicker the film and the stronger the film.
Furthermore, it was found that when held for 60 to 120 minutes, gelation can occur up to the center of the droplet.
In addition, after dripping the galactose partial decomposition product aqueous solution to the polyphenol aqueous solution, each seamless capsule obtained by being immersed for 1 minute and 5 minutes was taken out and immersed in deionized water. Became almost 100%. From this, even after taking out from the polyphenol aqueous solution, it is presumed that the polyphenol remaining in the film permeated gradually toward the inside to form a gel, thereby thickening the film.
(試験例4)
<シームレスカプセルの大きさ>
 ガラクトキシログルカンのガラクトース部分分解物の1.25質量%水溶液を、サンフェノン90-Sの1.25質量%水溶液に、下記表4に示す各種器具で各10回ずつ滴下し、滴下してから1分後に各液滴を回収し、脱イオン水で洗った後、脱イオン水内に収容して、各10個のシームレスカプセルを得た。得られたシームレスカプセルは、いずれも球状であった。用いた器具ごとに、得られたシームレスカプセル(カプセル皮膜)の最大径を上記デジタル外側マイクロメータによって測定し、10個のシームレスカプセルの平均値を算出した。なお、図2に示すように、シームレスカプセルの最大径として、図2の各形状において矢印で示す長さを、上記デジタル外側マイクロメータで測定した。
 結果を表4に示す。
(Test Example 4)
<Seamless capsule size>
A 1.25% by mass aqueous solution of a galactose partial decomposition product of galactoxyloglucan was added dropwise to a 1.25% by mass aqueous solution of Sanphenon 90-S 10 times each with various instruments shown in Table 4 below. After each minute, each droplet was collected, washed with deionized water, and then accommodated in deionized water to obtain 10 seamless capsules each. The obtained seamless capsules were all spherical. For each instrument used, the maximum diameter of the obtained seamless capsule (capsule film) was measured by the digital outer micrometer, and the average value of 10 seamless capsules was calculated. As shown in FIG. 2, as the maximum diameter of the seamless capsule, the length indicated by the arrow in each shape of FIG. 2 was measured with the digital outer micrometer.
The results are shown in Table 4.
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
 表4に示すように、使用器具によって得られるシームレスカプセルの大きさが異なる傾向にあるものの、いずれの器具を使用しても、最大径2.0~9.0mm程度の範囲でシームレスカプセルが製造され得ることがわかった。 As shown in Table 4, although the size of seamless capsules obtained varies depending on the equipment used, seamless capsules can be produced with a maximum diameter of about 2.0 to 9.0 mm, regardless of which equipment is used. It turns out that can be done.
(試験例5)
<シームレスカプセルの耐酸性>
 ガラクトキシログルカンのガラクトース部分分解物の1.25質量%水溶液をサンフェノン90-Sの1.25質量%水溶液にスポイト(口径1mm)で滴下し、滴下から1分後に回収、脱イオン水で洗った後、脱イオン水内に収容して、シームレスカプセルを得た。
 各pHを有する水溶液(酸性側は塩酸、アルカリ性側は水酸化ナトリウムを脱イオン水に添加して水溶液を調製した)に、得られたシームレスカプセルを入れ、1、5、10、30、60、120、180、240分、1日後の様子を、目視で観察し、下記の判定基準で耐酸性を評価した。
(Test Example 5)
<Acid resistance of seamless capsules>
A 1.25% by mass aqueous solution of a galactose partial decomposition product of galactoxyloglucan was dropped into a 1.25% by mass aqueous solution of Sanphenon 90-S with a dropper (1 mm in diameter), collected 1 minute after the addition, and washed with deionized water. Then, it was accommodated in deionized water to obtain a seamless capsule.
The obtained seamless capsules are put into an aqueous solution having each pH (hydrochloric acid on the acidic side and sodium hydroxide added to deionized water on the alkaline side), 1, 5, 10, 30, 60, The state after 120, 180, 240 minutes and 1 day was visually observed, and the acid resistance was evaluated according to the following criteria.
・耐酸性の判断基準
○:シームレスカプセルに変化なし。
△:シームレスカプセルが溶解しつつあって、小さくなる。
×:シームレスカプセルが溶解し、消失する。
・ Criteria for acid resistance ○: No change to seamless capsules.
Δ: The seamless capsule is dissolved and becomes smaller.
X: The seamless capsule dissolves and disappears.
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
 表5に示したように、得られたシームレスカプセルはpH1.0の強酸に晒されてもその形状を維持し、溶解することはなかった。一方、pH11.0以上のアルカリ溶液には溶解した。この結果、本実施形態のシームレスカプセルは耐酸性に優れていることが判明した。 As shown in Table 5, the obtained seamless capsule maintained its shape and did not dissolve even when exposed to a strong acid having a pH of 1.0. On the other hand, it was dissolved in an alkaline solution having a pH of 11.0 or higher. As a result, it was found that the seamless capsule of this embodiment is excellent in acid resistance.
(試験例6)
<ゼラチンをカプセル皮膜に含有するシームレスカプセルの耐酸性>
 ゼラチン(森永製菓(株)製)0.3gを脱イオン水9.7gに添加し、95℃で1分間加熱しながら撹拌して、ゼラチンを脱イオン水に溶解させて、3.0質量%ゼラチン水溶液を得た。得られたゼラチン水溶液を40℃以上に保ちながら、氷水で5℃以下に冷却したシリコーンオイル(KF-96-10CS、信越化学(株)製)に滴下した。滴下してから10分間経過した後に滴下物を回収し、表面に付着している余剰のシリコーンオイルをキムワイプで軽く拭き取ることによって、ゼラチンをカプセル皮膜に含有するシームレスカプセルを得た。
(Test Example 6)
<Acid resistance of seamless capsules containing gelatin in capsule film>
Gelatin (manufactured by Morinaga & Co., Ltd.) (0.3 g) was added to 9.7 g of deionized water and stirred while heating at 95 ° C. for 1 minute to dissolve the gelatin in deionized water. An aqueous gelatin solution was obtained. The obtained gelatin aqueous solution was added dropwise to silicone oil (KF-96-10CS, manufactured by Shin-Etsu Chemical Co., Ltd.) cooled to 5 ° C. or less with ice water while keeping the gelatin aqueous solution at 40 ° C. or more. Ten minutes after dropping, the drop was collected, and excess silicone oil adhering to the surface was gently wiped off with a Kim wipe to obtain a seamless capsule containing gelatin in the capsule film.
 pH1.0の塩酸水溶液、及び、pH7.3の水道水に、得られたシームレスカプセルを入れ、1、5、10、30、60、120、180、240分、1日後の様子を、目視で観察した。
 その結果、水道水中では、1日経過した後においてもシームレスカプセルはその形状を維持し、溶解することはなかった。一方、pH1.0という強酸の水溶液中では、10分経過後に、薬さじで掬い上げようとするとシームレスカプセルが壊れ、このことから、シームレスカプセルが溶解したことがわかった。
 これらの結果、ガラクトース部分分解物とポリフェノールとをカプセル皮膜に含有するシームレスカプセルは、ゼラチンをカプセル皮膜に含有するシームレスカプセルよりも、耐酸性に優れていることが判明した。
The obtained seamless capsule is put in a hydrochloric acid aqueous solution of pH 1.0 and tap water of pH 7.3, and 1, 5, 10, 30, 60, 120, 180, 240 minutes, the state after one day is visually observed. Observed.
As a result, in tap water, the seamless capsule maintained its shape and did not dissolve even after 1 day. On the other hand, in an aqueous solution of a strong acid having a pH of 1.0, when trying to scoop up with a spoon after 10 minutes, the seamless capsule was broken, and it was found that the seamless capsule was dissolved.
As a result, it was found that the seamless capsule containing the galactose partial degradation product and polyphenol in the capsule film had better acid resistance than the seamless capsule containing gelatin in the capsule film.
 なお、ゼラチンは、動物性原料であり、BSEや宗教上の問題から利用が制限されるおそれがあるのに対し、ガラクトース部分分解物及びポリフェノールは、植物性原料であり、このような利用制限が回避され得る。また、ゼラチンを用いた場合には、ゼラチンを水に溶解させるために加熱する必要があるため、熱安定性の低い内容物を収容し難く、内容物の選択の幅が狭まるのに対し、ガラクトース部分分解物及びポリフェノールを用いた場合には、加熱する必要がないため、熱安定性の低い内容物を収容することが可能となり、ゼラチンを用いた場合よりも、内容物の選択の幅が広がる。 Gelatin is an animal raw material and its use may be restricted due to BSE and religious problems, whereas galactose partial degradation products and polyphenols are plant raw materials, and such use restrictions are limited. Can be avoided. In addition, when gelatin is used, it is necessary to heat the gelatin in order to dissolve it in water. Therefore, it is difficult to accommodate contents with low thermal stability, and the selection range of contents is narrowed. When partially decomposed products and polyphenols are used, it is not necessary to heat them, so it is possible to accommodate contents with low thermal stability, and the range of selection of contents is wider than when gelatin is used. .
(試験例7)
<セルラーゼによるシームレスカプセルの溶解>
 ガラクトキシログルカンのガラクトース部分分解物の1.25質量%水溶液を、サンフェノン90-Sの1.25質量%水溶液にスポイト(口径1mm)で滴下し、滴下から1分間経過後に回収、脱イオン水で洗った後、脱イオン水内に収容して、シームレスカプセルを得た。
 セルラーゼオノズカRS(ヤクルト薬品工業(株)製)0.015質量%水溶液(pH4.0)に、得られたシームレスカプセルを入れ、室温もしくは40℃の水浴に静置し、静置から1、5、10、30、60、120、180、240分、1日後の様子を目視で観察し、下記の判定基準で、セルラーゼによる溶解性を評価した。
 結果を表6に示す。
(Test Example 7)
<Dissolution of seamless capsules with cellulase>
A 1.25% by mass aqueous solution of the galactose partial decomposition product of galactoxyloglucan was dropped into a 1.25% by mass aqueous solution of Sanphenon 90-S with a dropper (caliber: 1 mm), and recovered after 1 minute from dropping, with deionized water. After washing, the capsules were accommodated in deionized water to obtain seamless capsules.
Cellulase Onozuka RS (manufactured by Yakult Pharmaceutical Co., Ltd.) 0.015% by mass aqueous solution (pH 4.0), the obtained seamless capsules are put into a water bath at room temperature or 40 ° C. The appearance after 5, 10, 30, 60, 120, 180, 240 minutes and 1 day was visually observed, and the solubility by cellulase was evaluated according to the following criteria.
The results are shown in Table 6.
・セルラーゼによる溶解性の判断基準
○:シームレスカプセルに変化なし。
△:シームレスカプセルが溶解しつつあって、小さくなる。
×:シームレスカプセルが溶解し、消失する。
-Criteria for solubility by cellulase ○: No change to seamless capsules.
Δ: The seamless capsule is dissolved and becomes smaller.
X: The seamless capsule dissolves and disappears.
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
 表6に示すように、シームレスカプセルはセルラーゼによって溶解した。また、40℃の温度では、室温よりも早く溶解した。
 ここで、セルラーゼは、腸内細菌によって腸内で産生されることが知られている。
 従って、上記の結果、シームレスカプセルが服用されると、腸内細菌が産生するセルラーゼによって、シームレスカプセルが腸内で崩壊・溶解することが期待される。
 なお、文献A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes、Nature. 2014 February 27; 506(7489): 498-502 には、ヒトの腸内細菌がキシログルカン類を資化することが示されている。
 本実施形態のシームレスカプセルの皮膜は、タマリンド由来のガラクトキシログルカン、すなわち、キシログルカン類によって形成されていることから、ヒトの腸内細菌でシームレスカプセルが崩壊・溶解することは十分に考えられる。
As shown in Table 6, seamless capsules were dissolved by cellulase. Moreover, it melt | dissolved faster than the room temperature at the temperature of 40 degreeC.
Here, cellulase is known to be produced in the intestine by intestinal bacteria.
Therefore, as a result of the above, when a seamless capsule is taken, it is expected that the seamless capsule will be disintegrated and dissolved in the intestine by cellulase produced by intestinal bacteria.
Reference A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes, Nature. 2014 February 27; 506 (7489): 498-502 shows that human intestinal bacteria assimilate xyloglucans. ing.
Since the film of the seamless capsule of the present embodiment is formed by galactoxyloglucan derived from tamarind, that is, xyloglucans, it is sufficiently conceivable that the seamless capsule disintegrates and dissolves in human intestinal bacteria.
 上記の結果から明らかなように、ガラクトース部分分解物水溶液をポリフェノール水溶液に滴下するという簡便な方法によって、耐酸性を有し、さらに腸内で崩壊・溶解するシームレスカプセルが得られ得ることがわかった。よって、腸溶性カプセルに有用であることがわかった。 As is clear from the above results, it was found that a seamless capsule that has acid resistance and that disintegrates and dissolves in the intestine can be obtained by a simple method of dropping a galactose partial decomposition product aqueous solution into a polyphenol aqueous solution. . Thus, it was found useful for enteric capsules.
(試験例8)
<キサンタンガム水溶液をカプセル皮膜の内部に包含したシームレスカプセル>
 ガラクトキシログルカンのガラクトース部分分解物の1.5質量%水溶液、サンフェノン90-Sの1.25質量%水溶液、及び、ケルデント(キサンタンガム、DSP五協フード&ケミカル(株)製)2.0質量%水溶液を用いた。
 ガラクトース部分分解物水溶液をピペット(口径8mm)でサンフェノン90-S水溶液に滴下する際に、ガラクトース部分分解物水溶液の液滴の内部にケルデント水溶液をスポイト(口径1mm)で注入しながら滴下した。滴下した後、4時間経過後に滴下物を回収し、脱イオン水で洗った後、脱イオン水内に収容して、シームレスカプセルを得た。
(Test Example 8)
<Seamless capsule containing xanthan gum aqueous solution inside capsule film>
1.5% by weight aqueous solution of galactose partial decomposition product of galactoxyloglucan, 1.25% by weight aqueous solution of Sanphenon 90-S, and Keldent (xanthan gum, manufactured by DSP Gokyo Food & Chemical Co., Ltd.) 2.0% by weight An aqueous solution was used.
When the galactose partial decomposition product aqueous solution was dropped into the Sanphenon 90-S aqueous solution with a pipette (8 mm in diameter), the Keldent aqueous solution was dropped into the droplets of the galactose partial decomposition product aqueous solution with a dropper (1 mm in diameter). After dropping, the drop was collected after 4 hours, washed with deionized water, and then accommodated in deionized water to obtain seamless capsules.
 得られたシームレスカプセルは、薬さじで掬い上げることができる程度の強度を有していたが、指で押圧するとカプセル皮膜が潰れ、内部から液が出てきた。得られたシームレスカプセルの皮膜率を上記の測定方法で測定すると、18%であった。
 ここで、ガラクトース部分分解物の1.5質量%水溶液のみをサンフェノン90-Sの1.25質量%水溶液に滴下した場合には、滴下から4時間経過後に中心までゲル化していた。このことを考慮すると、ケルデント水溶液を内包したシームレスカプセルでは、ケルデント水溶液が存在している部分以外の部分(ガラクトース部分分解物が存在している外側の部分)がゲル化し、ケルデント水溶液はゾルの状態のままカプセル皮膜の内部に保持されることがわかった。
 なお、ケルデントの2.0質量%水溶液の粘度をB形粘度計(型式:TVB-25L、東機産業(株)製)で測定したところ、3192mPa・s(25℃、30rpm)であり、ケルデントの2.0質量%水溶液は、水よりも粘度が高い液であった。
The obtained seamless capsule was strong enough to be scooped up with a spoon, but when pressed with a finger, the capsule film was crushed and liquid came out from the inside. When the film ratio of the obtained seamless capsule was measured by the above-described measuring method, it was 18%.
Here, when only a 1.5% by mass aqueous solution of a partial decomposition product of galactose was added dropwise to a 1.25% by mass aqueous solution of Sanphenon 90-S, gelation occurred to the center 4 hours after the addition. Considering this, in the seamless capsule containing the Keldent aqueous solution, the part other than the part where the Keldent aqueous solution exists (the outer part where the galactose partial degradation product exists) gels, and the Keldent aqueous solution is in a sol state It was found that the capsule film was retained inside.
The viscosity of a 2.0 mass% aqueous solution of Keldent was measured with a B-type viscometer (model: TVB-25L, manufactured by Toki Sangyo Co., Ltd.) and found to be 3192 mPa · s (25 ° C., 30 rpm). The 2.0 mass% aqueous solution of was a liquid with a viscosity higher than water.
(試験例9)
<グリセリンをカプセル皮膜の内部に包含したシームレスカプセル>
 試験例8において、ケルデント2.0質量%水溶液に代えて化粧品用濃グリセリン(グリセリン、花王(株)製)を用いた。それ以外は、試験例8と同様にして、シームレスカプセルを得た。
 得られたシームレスカプセルは、薬さじで掬い上げることができる程度の強度を有していたが、指で押圧するとカプセル皮膜が潰れ、内部から液が出てきた。得られたシームレスカプセルの皮膜率を上記の測定方法で測定すると、37%であった。
 この結果、試験例8のケルデント水溶液の場合と同様、グリセリン(水よりも比重が大きい)はゾルの状態のままカプセル皮膜の内部に保持されることがわかった。
(Test Example 9)
<Seamless capsules containing glycerin in the capsule film>
In Test Example 8, concentrated glycerin for cosmetics (glycerin, manufactured by Kao Corporation) was used in place of the Keldent 2.0% by mass aqueous solution. Otherwise, seamless capsules were obtained in the same manner as in Test Example 8.
The obtained seamless capsule was strong enough to be scooped up with a spoon, but when pressed with a finger, the capsule film was crushed and liquid came out from the inside. The film rate of the obtained seamless capsules was measured by the above measurement method and found to be 37%.
As a result, as in the case of the Keldent aqueous solution of Test Example 8, it was found that glycerin (having a specific gravity greater than that of water) was retained inside the capsule film in a sol state.
(試験例10)
<オリーブ油をカプセル皮膜の内部に包含したシームレスカプセル>
 試験例8において、ガラクトース部分分解物水溶液を、ピペット(口径8mm)に代えてスポイト(口径4mm)で滴下し、ガラクトース部分分解物の液滴にケルデント2.0質量%水溶液をスポイト(口径1mm)で注入することに代えてオリーブ油リファインド(DSP五協フード&ケミカル(株)製)をパスツールピペット(口径1mm)で注入した。それ以外は、試験例8と同様にして、シームレスカプセルを得た。
 得られたシームレスカプセルは、薬さじで掬い上げることができる程度の強度を有していたが、指で押圧するとカプセル皮膜が潰れ、内部から液が出てきた。得られたシームレスカプセルの皮膜率を上記の測定方法で測定すると、30%であった。
 この結果、試験例8のケルデント水溶液、及び、試験例9のグリセリンの場合と同様、オリーブ油はゾルの状態のままカプセル皮膜の内部に保持されることがわかった。
(Test Example 10)
<Seamless capsules containing olive oil inside capsule film>
In Test Example 8, the galactose partial decomposition product aqueous solution was dropped with a dropper (4 mm diameter) instead of a pipette (caliber 8 mm), and a 2.0 mass% aqueous solution of Keldent was dropped into the droplets of the galactose partial decomposition product (1 mm diameter). The olive oil refined (manufactured by DSP Gokyo Food & Chemical Co., Ltd.) was injected with a Pasteur pipette (caliber 1 mm). Otherwise, seamless capsules were obtained in the same manner as in Test Example 8.
The obtained seamless capsule was strong enough to be scooped up with a spoon, but when pressed with a finger, the capsule film was crushed and liquid came out from the inside. The film rate of the obtained seamless capsules was 30% when measured by the above measuring method.
As a result, it was found that olive oil was retained inside the capsule film in a sol state as in the case of the Keldent aqueous solution of Test Example 8 and the glycerin of Test Example 9.
(試験例11)
<乳化されたオリーブ油をカプセル皮膜の内部に包含したシームレスカプセル>
 ガラクトキシログルカンのガラクトース部分分解物の2.5質量%水溶液25gにオリーブ油リファインド(DSP五協フード&ケミカル(株)製)15g、脱イオン水10gを加え、ホモジナイザー(型式:M2-f、プライミクス(株)製)を用いて5000rpmで30分撹拌して混合し、乳液を調製した。
 得られた乳液をスポイト(口径1mm)でサンフェノン90-Sの1.25質量%水溶液に滴下した。滴下した後、3時間経過後に滴下物を回収し、脱イオン水で洗った後、脱イオン水内に収容して、シームレスカプセルを得た。
 得られたシームレスカプセルは、薬さじで掬い上げることができる程度の強度を有していた。また、指で押圧してもカプセル皮膜が潰れず、内部から液が出てこなかった。得られたシームレスカプセルの皮膜率を上記の測定方法で測定すると、100%であった。
 この結果、オリーブ油が均一に分散されたまま液滴全体がゲル化し、オリーブ油がカプセル皮膜全体に保持されると考えられる。
(Test Example 11)
<Seamless capsules containing emulsified olive oil inside capsule film>
15 g of olive oil refined (DSP Gokyo Food & Chemical Co., Ltd.) and 10 g of deionized water are added to 25 g of a 2.5% by mass aqueous solution of a galactose partial decomposition product of galactoxyloglucan, and a homogenizer (model: M2-f, Primix) is added. The mixture was stirred at 5000 rpm for 30 minutes and mixed to prepare an emulsion.
The obtained emulsion was dropped into a 1.25% by mass aqueous solution of Sanphenon 90-S with a dropper (1 mm in diameter). After dropping, the dropped product was recovered after 3 hours, washed with deionized water, and then accommodated in deionized water to obtain seamless capsules.
The obtained seamless capsules were strong enough to be scooped with a spoon. Moreover, even if it pressed with the finger | toe, the capsule membrane | film | coat was not crushed and the liquid did not come out from the inside. When the film ratio of the obtained seamless capsule was measured by the above measuring method, it was 100%.
As a result, it is considered that the entire droplet gels while the olive oil is uniformly dispersed, and the olive oil is held in the entire capsule film.
(試験例12)
<ルチンをカプセル皮膜の内部に包含したシームレスカプセル>
 ガラクトキシログルカンのガラクトース部分分解物の2.5質量%水溶液12.5gにルチン(ナカライテスク(株)製)2.5g、脱イオン水10gを加え、撹拌棒で撹拌して混合し、ガラクトース部分分解物水溶液にルチンが分散されてなる分散液を得た。
 得られた分散液をスポイト(口径1mm)でサンフェノン90-Sの1.25質量%水溶液に滴下した。滴下した後、3時間経過後に回収し、脱イオン水で洗った後、脱イオン水内に収容して、シームレスカプセルを得た。
 得られたシームレスカプセルは、薬さじで掬い上げることができる程度の強度を有していた。また、指で押圧してもカプセル皮膜が潰れず、内部から液が出てこなかった。得られたシームレスカプセルの皮膜率を上記の測定方法で測定すると、100%であった。
 この結果、固体のルチンが均一に分散されたまま液滴全体がゲル化し、ルチンがカプセル皮膜全体に保持されると考えられる。
(Test Example 12)
<Seamless capsules containing rutin in the capsule film>
Add 2.5 g of rutin (manufactured by Nacalai Tesque Co., Ltd.) and 10 g of deionized water to 12.5 g of a 2.5% by weight aqueous solution of galactoxyloglucan galactose partial decomposition product, and stir with a stir bar to mix. A dispersion in which rutin was dispersed in the decomposition product aqueous solution was obtained.
The obtained dispersion was dropped into a 1.25% by mass aqueous solution of Sanphenon 90-S with a dropper (1 mm in diameter). After dripping, it collect | recovered after progress for 3 hours, and after washing | cleaning with deionized water, it accommodated in deionized water and obtained the seamless capsule.
The obtained seamless capsules were strong enough to be scooped with a spoon. Moreover, even if it pressed with the finger | toe, the capsule membrane | film | coat was not crushed and the liquid did not come out from the inside. When the film ratio of the obtained seamless capsule was measured by the above measuring method, it was 100%.
As a result, it is considered that the entire droplet is gelled while the solid rutin is uniformly dispersed, and the rutin is held in the entire capsule film.
(試験例13)
<オリーブ油をカプセル皮膜の内部に包含した状態で乾燥されたシームレスカプセル>
 ガラクトキシログルカンのガラクトース部分分解物の2.5質量%水溶液12.5gに濃グリセリン0.25g、脱イオン水12.25gを加え、撹拌棒で撹拌して混合し、ガラクトース部分分解物1.25質量%とグリセリン1.0質量%との混合水溶液を得た。
 得られた混合水溶液をスポイト(口径4mm)でサンフェノン90-Sの1.25質量%水溶液に滴下する際に、混合水溶液の液滴の内部にオリーブ油リファインド(DSP五協フード&ケミカル(株)製)をパスツールピペット(口径1mm)で注入しながら滴下した。滴下した後、1時間経過後に滴下物を回収し、送風乾燥機(型式:SPH-201、エスペック社製)内に静置して50℃で2時間乾燥し、シームレスカプセルを得た。
(Test Example 13)
<Seamless capsules dried with olive oil contained inside the capsule membrane>
Concentrated glycerol 0.25 g and deionized water 12.25 g are added to 12.5 g of a 2.5% by mass aqueous solution of a galactoxyloglucan galactose partial decomposition product, and the mixture is stirred and mixed with a stir bar to obtain a galactose partial decomposition product 1.25. A mixed aqueous solution of mass% and glycerin 1.0 mass% was obtained.
When the obtained mixed aqueous solution was dropped into a 1.25% by mass aqueous solution of Sanphenon 90-S with a dropper (4 mm in diameter), olive oil refined (DSP Gokyo Food & Chemical Co., Ltd.) was placed inside the droplet of the mixed aqueous solution. The product was added dropwise with a Pasteur pipette (1 mm in diameter). After dropping, the drop was collected after 1 hour, and was left in an air dryer (model: SPH-201, manufactured by Espec Corp.) and dried at 50 ° C. for 2 hours to obtain a seamless capsule.
 得られたシームレスカプセルは、薬さじで掬い上げることができる程度の強度を有していたが、指で押圧するとカプセル皮膜が潰れ、内部から液が出てきた。かかるカプセル皮膜は、フィルム状であった。得られたシームレスカプセルの皮膜率を上記の測定方法で測定すると、13%であった。
 この結果、カプセル皮膜がフィルム状であっても、試験例10、11と同様、オリーブ油はゾルの状態のままカプセル皮膜の内部に保持されることがわかった。
The obtained seamless capsule was strong enough to be scooped up with a spoon, but when pressed with a finger, the capsule film was crushed and liquid came out from the inside. This capsule film was film-like. When the film ratio of the obtained seamless capsule was measured by the above-described measuring method, it was 13%.
As a result, it was found that olive oil was retained inside the capsule film in the sol state as in Test Examples 10 and 11, even if the capsule film was in the form of a film.
 試験例8~13の結果、本実施形態のシームレスカプセルには、水よりも粘性の高い溶液や比重の大きい溶液、油剤、水不溶性の粉末等を内容物として添加することが可能であることがわかった。
 また、前述した表5、表6に示すように、試験例8~13のシームレスカプセルは、セルラーゼによって分解されると、各内容物が外部に放出されると推察される。
 なお、ガラクトース部分分解物として、製造例1で得られたガラクトース部分分解物をさらに精製したものを用いた場合であっても、上記試験例1~5、7~13と同様の結果が得られ、結果に影響を及ぼさない。
As a result of Test Examples 8 to 13, it is possible to add a solution having a higher viscosity than water, a solution having a higher specific gravity, an oil agent, a water-insoluble powder, or the like as a content to the seamless capsule of this embodiment. all right.
Further, as shown in Tables 5 and 6 described above, when the seamless capsules of Test Examples 8 to 13 are decomposed by cellulase, it is assumed that each content is released to the outside.
Even when the partially decomposed galactose obtained in Production Example 1 was used as the partially decomposed galactose, the same results as in Test Examples 1 to 5 and 7 to 13 were obtained. Does not affect the results.
 よって、本実施形態のシームレスカプセル及びその製造方法は、乳酸菌を生きたまま腸内まで届けるシームレスカプセルや、腸内で有効成分が放出、発揮される医薬品や動物薬、サプリメント等に有効である。
 また、そのカプセル皮膜には従来の腸溶性シームレスカプセルに含まれる金属イオンが必要ないため、金属イオンに反応する薬剤や有効成分を内包させることが可能であり、内容物の選択の幅が広がることが期待される。
Therefore, the seamless capsule and the method for producing the same of the present embodiment are effective for a seamless capsule that delivers lactic acid bacteria to the intestine while alive, a pharmaceutical, an animal drug, a supplement, and the like in which an active ingredient is released and exhibited in the intestine.
In addition, since the capsule film does not require the metal ions contained in conventional enteric seamless capsules, it is possible to encapsulate drugs and active ingredients that react with metal ions, and the range of choice of contents is expanded. There is expected.
 さらに、カプセル皮膜にポリフェノールが含まれることにより、その抗菌作用や抗酸化作用が期待され、より長期間のカプセルの保存が可能になると考えられる。
 以上のことより、本実施形態のシームレスカプセルは食品、化粧品、医薬品等の幅広い分野で有用であり、特に食品、医薬品分野でより有用である。
Furthermore, the inclusion of polyphenol in the capsule film is expected to have antibacterial and antioxidative effects, and the capsule can be stored for a longer period of time.
From the above, the seamless capsule of the present embodiment is useful in a wide range of fields such as food, cosmetics, and pharmaceuticals, and more particularly useful in the food and pharmaceutical fields.

Claims (7)

  1.  カプセル皮膜を備えたシームレスカプセルであって、
     前記カプセル皮膜は、ガラクトキシログルカンのガラクトース部分分解物とポリフェノールとを含有する、シームレスカプセル。
    A seamless capsule with a capsule coating,
    The capsule film is a seamless capsule containing a galactose partial degradation product of galactoxyloglucan and polyphenol.
  2.  前記ガラクトース部分分解物は、ガラクトースが30~55%分解されてなる、請求項1に記載のシームレスカプセル。 The seamless capsule according to claim 1, wherein the galactose partial degradation product is obtained by decomposing 30 to 55% of galactose.
  3.  前記ポリフェノールが、茶抽出物である、請求項1または2に記載のシームレスカプセル。 The seamless capsule according to claim 1 or 2, wherein the polyphenol is a tea extract.
  4.  ガラクトキシログルカンのガラクトース部分分解物と水とを含有する第1の水溶液を、ポリフェノールと水とを含有する第2の水溶液に滴下することによって、前記ガラクトース部分分解物と前記ポリフェノールとを含有するカプセル皮膜を有するシームレスカプセルを形成する工程を備えた、シームレスカプセルの製造方法。 Capsules containing the galactose partial decomposed product and the polyphenol by dropping a first aqueous solution containing a galactose partial decomposed product of galactoxyloglucan and water into a second aqueous solution containing polyphenol and water. A method for producing a seamless capsule, comprising a step of forming a seamless capsule having a film.
  5.  前記第1の水溶液における前記ガラクトース部分分解物の濃度を、0.5~3.0質量%とする、請求項4に記載のシームレスカプセルの製造方法。 The method for producing a seamless capsule according to claim 4, wherein the concentration of the partially decomposed galactose in the first aqueous solution is 0.5 to 3.0 mass%.
  6.  前記第2の水溶液における前記ポリフェノールの濃度を、0.25~10質量%とする、請求項4または5に記載のシームレスカプセルの製造方法。 The method for producing a seamless capsule according to claim 4 or 5, wherein the concentration of the polyphenol in the second aqueous solution is 0.25 to 10% by mass.
  7.  前記ポリフェノールとして、茶抽出物を用いる、請求項4~6のいずれかに記載のシームレスカプセルの製造方法。 The method for producing a seamless capsule according to any one of claims 4 to 6, wherein a tea extract is used as the polyphenol.
PCT/JP2017/013177 2017-03-30 2017-03-30 Seamless capsule and production method therefor WO2018179199A1 (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019172626A (en) * 2018-03-29 2019-10-10 Dsp五協フード&ケミカル株式会社 Film and production method thereof

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62262993A (en) * 1986-05-03 1987-11-16 ヘキスト・アクチエンゲゼルシヤフト Encapsulation of biologically active substance
JP2000354460A (en) * 1999-06-15 2000-12-26 Dainippon Pharmaceut Co Ltd Thickening and/or gelation of galactoxyloglucan
WO2010050541A1 (en) * 2008-10-31 2010-05-06 大日本住友製薬株式会社 Food for people having difficulty chewing and/or swallowing
JP2011045820A (en) * 2009-08-26 2011-03-10 Niigata Univ Method of manufacturing oily component-containing microcapsule
JP2015199698A (en) * 2014-03-31 2015-11-12 株式会社ファンケル seamless capsule

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS62262993A (en) * 1986-05-03 1987-11-16 ヘキスト・アクチエンゲゼルシヤフト Encapsulation of biologically active substance
JP2000354460A (en) * 1999-06-15 2000-12-26 Dainippon Pharmaceut Co Ltd Thickening and/or gelation of galactoxyloglucan
WO2010050541A1 (en) * 2008-10-31 2010-05-06 大日本住友製薬株式会社 Food for people having difficulty chewing and/or swallowing
JP2011045820A (en) * 2009-08-26 2011-03-10 Niigata Univ Method of manufacturing oily component-containing microcapsule
JP2015199698A (en) * 2014-03-31 2015-11-12 株式会社ファンケル seamless capsule

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2019172626A (en) * 2018-03-29 2019-10-10 Dsp五協フード&ケミカル株式会社 Film and production method thereof
JP7022635B2 (en) 2018-03-29 2022-02-18 Dsp五協フード&ケミカル株式会社 Film and its manufacturing method

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