WO2023008567A1

WO2023008567A1 - Capsule shell composition and capsule obtained using same

Info

Publication number: WO2023008567A1
Application number: PCT/JP2022/029330
Authority: WO
Inventors: 真司矢野; 昌史野津; 雄斗望月; 明広幡野; 憲一小山; 崇典小林; 徹風岡; 広樹小林; 貴広脇田; 裕司藤田
Original assignee: 三生医薬株式会社
Priority date: 2021-07-30
Filing date: 2022-07-29
Publication date: 2023-02-02
Also published as: JPWO2023008567A1

Abstract

Provided is a capsule shell composition and the like having excellent handleability.　The capsule shell composition comprises a starch, iota carrageenan, and a gum, wherein the content of the carrageenan is 2 mass% or higher with respect to the capsule shell composition, which is taken as 100 mass%, and the content of the gum is 0.3-14 mass% with respect to the capsule shell composition, which is taken as 100 mass%.

Description

Capsule shell composition and capsules using the same

The present invention relates to a capsule shell composition and capsules using the same.

Conventionally, gelatin is suitably used for the capsule shell composition used in the production of capsule shells. Gelatin exhibits suitable physical properties such as the viscosity and fluidity of the capsule shell composition, the strength of the formed capsule shell, heat-sealing properties, and resistance to cracking.

However, gelatin is mostly derived from animal collagen, and in recent years, from the viewpoint of religion, vegetarianism, allergies, mad cow disease, etc., there has been a demand for a capsule shell composition that uses a raw material that replaces gelatin as a main component. ing.

As such a capsule shell composition, for example, Patent Document 1 discloses a dry film composition suitable for soft capsules containing a mixture of iota carrageenan and modified starch, water, a plasticizer, and a buffer ( An invention relating to a capsule shell composition) is described.

Patent Document 1 describes that the capsule shell composition forms a film that is mechanically tough and has sufficient elasticity to stretch the film during filling (blow molding). Patent Document 1 describes that a buffer (phosphate buffer) is added for the purpose of preventing destruction (decomposition) of carrageenan.

Japanese Patent Publication No. 2003-504326

However, the capsule shell composition described in Patent Document 1 has high viscosity and is sometimes inferior in handleability. Therefore, there is a demand for a capsule shell composition that is easy to handle.

The present invention includes, for example, the following aspects.

[1] A capsule shell composition comprising starches, iota carrageenan, and gums,
The content of the iota carrageenan is 2% by mass or more with respect to 100% by mass of the capsule shell composition,
A capsule shell composition, wherein the gum content is 0.3 to 14% by mass with respect to 100% by mass of the capsule shell composition.
[2] The capsule shell composition according to [1] above, which does not contain gelatin.
[3] The capsule shell composition according to [1] or [2] above, which does not contain a phosphate buffer.
[4] Any one of [1] to [3] above, wherein the gum is one or more selected from the group consisting of gum arabic, guar gum, locust bean gum, gellan gum, xanthan gum, and tamarind gum. capsule shell composition.
[5] The content ratio of starch to iota carrageenan (starch content (% by mass)/iota carrageenan content (% by mass)) is 1.2 to 10,
The content ratio of starches to gums (starch content (mass%) / gum content (mass%)) is 1 to 50,
Any of the above [1] to [4], wherein the content ratio of iota carrageenan to gums (content of iota carrageenan (% by mass) / content of gums (% by mass)) is 0.5 to 15 2. The capsule shell composition according to 1.
[6] the starch content is 10 to 30% by mass with respect to 100% by mass of the capsule shell composition;
The capsule shell composition according to any one of [1] to [5] above, wherein the iota carrageenan content is 2 to 20% by mass with respect to 100% by mass of the capsule shell composition.
[7] The capsule shell composition according to any one of [1] to [6] above, further comprising alginate.
[8] The capsule shell composition according to any one of [1] to [7] above, further comprising a plasticizer.
[9] The capsule shell composition according to any one of [1] to [8] above, wherein the starch contains at least one selected from the group consisting of natural starch and modified starch.
[10] A capsule containing a content and a capsule shell,
A capsule, wherein the capsule shell is formed using the capsule shell composition according to any one of [1] to [9] above.
[11] The capsule of [10] above, which is a soft capsule.
[12] The content ratio of starch to iota carrageenan in the capsule shell (starch content (% by mass) / iota carrageenan content (% by mass)) is 1.2 to 10,
The content ratio of starches to gums in the capsule shell (starch content (mass%) / gum content (mass%)) is 1 to 50,
[10] or The capsule of [11].
[13] contents;
a capsule shell comprising starches, iota carrageenan, and gums;
including
A capsule having a hardness of 15 kg or more.
[13-1] Contents,
a capsule shell formed using the capsule shell composition according to any one of [1] to [9] above;
including
A capsule having a hardness of 15 kg or more.
[14] The capsule of [13] or [13-1] above, wherein the capsule shell does not contain gelatin.
[15] The capsule of [13], [13-1], or [14] above, wherein the capsule shell does not contain a phosphate buffer.
[16] The capsule of any one of [13] to [15] and [13-1] above, which is a soft capsule.
[17] The content ratio of starch to iota carrageenan in the capsule shell (starch content (mass%) / iota carrageenan content (mass%)) is 1.2 to 10,
The content ratio of starches to gums in the capsule shell (starch content (mass%) / gum content (mass%)) is 1 to 50,
The content ratio of iota carrageenan to gums in the capsule shell (content of iota carrageenan (% by mass) / content of gums (% by mass)) is 0.5 to 15 [13] to [16], and the capsule of any one of [13-1].

According to the present invention, a capsule shell composition and the like with excellent handleability are provided.

Hereinafter, the embodiments for carrying out the present invention will be described in detail.

1 Capsule Shell Composition The capsule shell composition of one aspect of the present invention comprises starches, iota carrageenan, and gums. At this time, the iota-carrageenan content is 2% by mass or more with respect to 100% by mass of the capsule shell composition. Also, the content of the gums is 0.3 to 14% by mass with respect to 100% by mass of the capsule shell composition.

The capsule shell composition has excellent handleability. Specifically, the capsule shell composition has a suitable viscosity. As a result, for example, the obtained capsules are excellent in formability of a film (wet film) that can be formed during production of the capsules, so that filling suitability is high (for example, high-speed filling is possible) and heat-sealability is excellent. At least one of the effects of high blocking resistance, good appearance, and the like can be obtained.
In one embodiment, the capsule shell composition may have jelly strength and flexibility suitable for a film (wet coating) formed during production of the capsule. Therefore, at least one of the effects of high strength of the film formed during production of the capsule and high hardness of the resulting capsule can be achieved.
Furthermore, in one embodiment, since the capsule shell composition contains starches, high disintegrability can be obtained.

In one embodiment, the capsule shell composition of the present invention does not contain gelatin. As a result, even those who cannot take gelatin due to religious reasons, vegetarianism, allergies, etc., can take the capsules. Also, safety issues such as mad cow disease are less likely to occur.

In one embodiment, the capsule shell composition of the present invention does not contain a phosphate buffer. In Patent Document 1, it was necessary to adjust the pH with a phosphate buffer in order to prevent destruction (decomposition) of carrageenan, but the capsule shell composition of the present invention does not require such pH adjustment. can be. As a result, the amount of chemical substances such as phosphate buffers can be reduced, so that even health-conscious people can take the capsules.

Each component of the capsule shell composition will be described in detail below.

[Starches]
Starch has a film-forming property and functions as a base agent for capsule shells. Since the capsule shell composition uses starches as a base agent, the obtained capsules can have excellent disintegration properties.

The starches are not particularly limited, but include natural starch and processed starch.

The natural starch is not particularly limited, but includes potato starch, tapioca starch, glutinous corn starch, glutinous rice starch, sago starch, sweet potato starch, mung bean starch, wheat starch and the like.

The modified starch is obtained by physically, chemically and enzymatically processing natural starch. Said processing includes, for example, esterification, etherification, oxidation, cross-linking, hydrolysis, and combinations thereof.

Specific examples of modified starch include esterified starch such as acetylated starch, phosphated starch and octenyl succinic acid starch; etherified starch such as hydroxypropylated starch and sodium starch glycolate; oxidized starch; Esterified crosslinked starch such as phosphate monoesterified phosphate crosslinked starch and starch phosphate sodium; etherified crosslinked starch such as hydroxypropylated starch for phosphorylation; esterified oxidized starch such as acetylated oxidized starch; glucose, starch syrup , maltodextrin, dextrin, and starch hydrolyzate such as roasted dextrin.

The dextrose equivalent (DE) of the starch hydrolyzate is preferably 20 or less, more preferably 15 or less, even more preferably 10 or less, and particularly preferably 5 or less. , more than 0 and less than or equal to 5. When the starch hydrolyzate has a dextrose equivalent of 20 or less, deterioration over time is less likely to occur, which is preferable. As a result, for example, the physical properties (filling suitability, heat-sealing property, jelly strength, flexibility, etc.) of a film (wet film) formed during the production of capsules and the physical properties of capsules (hardness, blocking resistance, appearance) are high. In addition, it is possible to obtain effects such as prevention of discoloration of the capsule from yellow to brown. In the present specification, "dextrose equivalent (D.E.)" is an index of the degree of starch decomposition, and the amount of reducing sugar in the starch decomposition product is converted to a glucose equivalent, and the glucose equivalent is converted to starch decomposition. It is a value expressed as a percentage (glucose equivalent/total solid content x 100) divided by the total solid content of the product. At this time, the amount of reducing sugars in the starch hydrolyzate is measured by the Reine Einone method, the Willstetter-Schudel method, the Bertrand method, or the HPLC method (for example, "Starch Sugar Related Industrial Analysis Method" (Starch Sugar Technical Committee Ed., published by Shokuhin Kagaku Shimbunsha (published on November 1, 1991))). In addition, pure glucose D.I. E. is 100, the D.O.D. of undegraded starch (native starch). E. becomes 0.

Among these, the starch preferably contains at least one selected from the group consisting of natural starch and modified starch, and at least one selected from the group consisting of natural starch, etherified starch, and starch hydrolyzate. More preferably, it contains at least one selected from the group consisting of native starch and etherified starch, and at least one selected from the group consisting of native starch and hydroxypropylated starch. Especially preferred. In addition, the above-mentioned starches may be used alone or in combination of two or more.

The viscosity of the starch is preferably 200 mPa s or less, more preferably 100 mPa s or less, even more preferably 50 mPa s or less, and particularly preferably 1 to 50 mPa s. Most preferably, it is 20 to 50 mPa·s. It is preferable that the viscosity of the starch is 200 mPa·s or less, since the viscosity of the capsule shell composition can be reduced. In addition, in this specification, the "viscosity of starches" means the average value measured by the method described in the Examples.

The starch content is preferably 3% by mass or more, more preferably 8% by mass or more, and even more preferably 10% by mass or more, relative to the total mass of the capsule shell composition. , is particularly preferably 15% by mass or more, and most preferably 19% by mass or more. The starch content is preferably 40% by mass or less, more preferably 30% by mass or less, and 22% by mass or less, relative to the total mass of the capsule shell composition. More preferably, yes. In one embodiment, the starch content is preferably 3 to 40% by mass, preferably 10 to 30% by mass, and 10 to 25% by mass, based on the total mass of the capsule shell composition. More preferably, 15 to 25% by mass is even more preferable. A starch content of 3% by mass or more is preferable because the capsule shell can be suitably formed. On the other hand, when the starch content is 40% by mass or less, it is preferable because the physical properties can be easily adjusted by adding other components (for example, iota carrageenan) to the capsule shell composition.

[Iota carrageenan]
Iota (ι) carrageenan can form soft, elastic, highly transparent gels with low syneresis. Therefore, iota-carrageenan has the function of improving at least one of jelly strength and flexibility of a film (wet film) formed during production of capsules, hardness and appearance of capsules, and the like.

Iota carrageenan has a main chain with a linear structure represented by the following structural formula.

That is, iota carrageenan has a linear main chain composed of glasstose having one sulfate group and 3,6-anhydrogalactose having one sulfate group. In addition, iota carrageenan may have galactose having two sulfate ester groups, 3,6-anhydrogalactose having no sulfate ester groups, or branched chains in a part of the main chain. may be

The viscosity of iota carrageenan is preferably 5000 mPa s or less, more preferably 4000 mPa s or less, still more preferably 500 to 4000 mPa s, particularly preferably 1000 to 3500 mPa s. . Iota-carrageenan having a viscosity of 5000 mPa·s or less is preferable because the viscosity of the capsule shell composition can be reduced. In the present specification, the "viscosity of iota carrageenan" means the average value measured by the method described in Examples.

The content of iota carrageenan is 2% by mass or more, preferably 3% by mass or more, more preferably 4% by mass or more, and 6% by mass, relative to the total mass of the capsule shell composition. It is particularly preferable that it is above. The content of iota carrageenan is preferably 20% by mass or less, more preferably 15% by mass or less, and preferably 10% by mass or less, relative to the total mass of the capsule shell composition. More preferred. In one embodiment, the content of iota carrageenan is preferably 2 to 20% by mass, more preferably 3 to 20% by mass, more preferably 4 to 20% by mass, based on the total mass of the capsule shell composition. % by mass is more preferred, 4 to 15% by mass is particularly preferred, 4 to 10% by mass is more preferred, and 6 to 10% by mass is most preferred. When the content of iota carrageenan is 2% by mass or more, at least one of the jelly strength and flexibility of the film (wet film) formed during production of the capsule, and the hardness and appearance of the capsule can be improved. preferable. On the other hand, if the content of iota carrageenan is 20% by mass or less, the viscosity of the capsule shell composition can be lowered, which is preferable.

In addition, iota carrageenan can be obtained by extracting Eucheuma Spinosum, etc. For example, Eucheuma Spinosum is washed with water, pulverized, and boiled to extract iota carrageenan, filtered, isolated, purified, dehydrated, dried, pulverized, and if necessary, sugar or the like is used to obtain iota carrageenan. be able to. At this time, isolation, purification and dehydration of iota carrageenan are preferably carried out by a gel press method. The gel press method is a method in which the iota carrageenan extract is cooled to gel the iota carrageenan, and then pressurized and dehydrated. If necessary, a metal salt such as potassium chloride may be added before cooling and gelling. . Compared to the alcohol precipitation method (a method in which the iota carrageenan extract is added to alcohol to precipitate and precipitate the iota carrageenan and recover it), the gel press method does not allow amino acids, proteins, and relatively low-molecular-weight carbohydrates to be extracted during purification. It is difficult for impurities such as Therefore, the gel press method is less likely to cause the Maillard reaction and accompanying pH reduction, and thus less likely to cause the decomposition of iota carrageenan, so that high-quality iota carrageenan can be obtained.

[Gums]
Gums have a function of reducing the viscosity of the capsule shell composition, a function of improving the flexibility of the film (wet film) formed during the manufacture of the capsule, and the like. Gums may exhibit a synergistic effect with the iota carrageenan. For example, gums and iota carrageenan form a double helix structure. The double helix structure is a rigid skeleton having crystalline and amorphous regions, and can stably exist in the wet film and the capsule shell of the capsule. As a result, iota carrageenan enhances the jelly strength and flexibility of the wet film, the hardness and appearance of the capsule, suppresses the increase in viscosity of the capsule shell composition due to the addition of iota carrageenan, and prevents the decomposition of iota carrageenan. At least one effect of performing, etc. can be further exhibited.

The gums are preferably one or more selected from the group consisting of gum arabic, guar gum, locust bean gum, gellan gum, xanthan gum, and tamarind gum, and are selected from the group consisting of gum arabic, guar gum, and gellan gum. It is more preferably one or more, and one or more selected from the group consisting of gum arabic and gellan gum from the viewpoint of improving the jelly strength and flexibility of the resulting wet film and the hardness of the resulting capsule. More preferably, it contains gum arabic. In addition, gums may be used individually or may be used in combination of 2 or more types.

Gum arabic is mainly composed of polysaccharides and includes arabinogalactan, arabinogalactan protein, glycoprotein, and the like.
Guar gum is a polysaccharide having two molecules of mannose linked in a linear chain and one molecule of galactose as a side chain. At this time, the guar gum may be a guar gum derivative, and examples of the guar gum derivative include hydroxypropyl guar gum, cationized guar gum, and guar gum enzymatic decomposition products.
Locust bean gum is a polysaccharide having 4 molecules of mannose linked in a straight chain and a side chain of 1 molecule of galactose.
Gellan gum includes high acyl gellan gum and low acyl gellan gum. The high-acyl gellan gum is also called native gellan gum, and has a structure in which acyl groups are bound to constituent sugars (mainly glucose). The low acyl gellan gum is also called deacylated gellan gum, and is obtained by deacylating high acyl gellan gum. Among these, gellan gum is preferably low acyl gellan gum from the viewpoint of its low gelation temperature and suitability for capsule production.
Xanthan gum has a repeating unit structure of two molecules of glucose, two molecules of mannose, and glucuronic acid.
Tamarind gum is a polysaccharide with a structure called xyloglucan, which contains glucose in the main chain and xylose and galactose in the side chains.

The content of gums is 0.3 to 14% by mass, preferably 0.3 to 7.5% by mass, and 1 to 7.5% by mass, relative to the total mass of the capsule shell composition. %, more preferably 1 to 4% by mass. It is preferable that the content of the gums is within the above range, since the viscosity of the capsule shell composition can be lowered. In addition, at least one of the physical properties of the film (wet film) formed during capsule production (filling suitability, heat-sealing property, jelly strength, flexibility, etc.) and the physical properties of the capsule (hardness, blocking resistance, appearance) It is preferable because it can be improved.

[Contents of starches, iota carrageenan, gums]
In one embodiment, the content ratio of starches to iota carrageenan (content of starches (% by mass)/content of iota carrageenan (% by mass)) is preferably 1 to 20, preferably 1.2 to 10 is more preferred, 1.2 to 5 is even more preferred, and 2 to 5 is particularly preferred.
In one embodiment, the content ratio of starches to gums (starch content (mass%)/gums content (mass%)) is preferably 1 to 75, preferably 1 to 50. It is more preferably 1, more preferably 2 to 50, particularly preferably 2 to 40, and most preferably 5 to 30.
In one embodiment, the content ratio of iota carrageenan to gums (content of iota carrageenan (% by mass)/content of gums (% by mass)) is preferably 0.1 to 30. It is more preferably from 5 to 15, even more preferably from 1 to 25, particularly preferably from 2 to 25, and most preferably from 2 to 12.

In one embodiment, the total content of starches and iota carrageenan is preferably 5 to 40% by mass, more preferably 10 to 40% by mass, based on the total mass of the capsule shell composition. , more preferably 22 to 40% by mass, particularly preferably 26 to 40% by mass.
In one embodiment, the total content of starches and gums is preferably 3.5 to 40% by mass, preferably 5 to 35% by mass, based on the total mass of the capsule shell composition. It is more preferably 15 to 30% by mass, particularly preferably 15 to 25% by mass, and most preferably 21 to 25% by mass.
In one embodiment, the total content of iota carrageenan and gums is preferably 2.5 to 30% by weight, preferably 2.5 to 20% by weight, based on the total weight of the capsule shell composition. is more preferable, 2.5 to 15% by mass is more preferable, and 2.5 to 10% by mass is particularly preferable.

[Alginate ester]
In one embodiment, the capsule shell composition preferably further comprises alginate.

The alginate can improve the jelly strength of the film (wet film) formed during capsule production and the hardness of the physical properties of the capsule while suppressing the increase in the viscosity of the capsule shell composition. Although the reason why such an effect is obtained is not clear, for example, a synergistic effect between alginic acid ester and gums is considered. Specifically, it is conceivable that the action of alginate on proteins, which are constituents of gums, will further improve the effect of suppressing increases in the viscosity of capsule shell compositions due to the addition of iota-carrageenan contained in gums.

Alginic acid ester is a linear polysaccharide polymerized from two types of uronic acid (β-D-mannuronic acid (M) and α-L-guluronic acid (G)). has an ester-bonded structure. Alginate has a surface active effect because it has a hydrophilic alginic acid portion and a lipophilic propylene glycol portion.

The alginate content is 0.001% by mass or more, preferably 0.01% by mass or more, and preferably 0.03% by mass or more, relative to the total mass of the capsule shell composition. More preferably, it is particularly preferably 0.3% by mass or more. The alginate content is preferably 10% by mass or less, more preferably 5% by mass or less, and 0.75% by mass or less, relative to the total mass of the capsule shell composition. is particularly preferred. In one embodiment, the alginate content is preferably 0.001 to 10% by mass, more preferably 0.001 to 5% by mass, relative to the total mass of the capsule shell composition. , more preferably 0.01 to 5% by mass, and particularly preferably 0.03 to 0.75% by mass. When the content of the alginate is within the above range, the jelly strength of the film (wet film) formed during the production of the capsules and the hardness of the physical properties of the capsules are improved while suppressing an increase in the viscosity of the capsule shell composition. can be improved.

The content ratio of gums to alginate (content of gums (% by mass)/content of alginate (% by mass)) is preferably 0.01 to 100, and 0.1 to 50. is more preferred, 0.5 to 20 is even more preferred, and 3 to 20 is particularly preferred.

[Plasticizer]
In one embodiment, the capsule shell composition preferably further comprises a plasticizer.

A plasticizer has the function of imparting flexibility to the film (wet film) formed during the production of capsules.

Plasticizers include, but are not limited to, polyhydric alcohols such as glycerin, sorbitol, maltitol, ethylene glycol, propylene glycol; hydroxymethylcellulose (HPMC), hydroxypropylcellulose (HPC), methylcellulose (MC), carboxymethylcellulose (CMC); ) and other cellulose derivatives. Among these, the plasticizer preferably contains a polyhydric alcohol, and more preferably contains glycerin. These plasticizers may be used alone or in combination of two or more.

The content of the plasticizer is preferably 1 to 50% by mass, more preferably 5 to 30% by mass, and 5 to 25% by mass, relative to the total mass of the capsule shell composition. is more preferred. It is preferable that the content of the plasticizer is within the above range, since the flexibility of the wet film becomes suitable.

[gelatin]
In one embodiment, the capsule shell composition may further comprise gelatin. By including gelatin in the capsule shell composition, it is possible to improve the viscosity and flowability of the capsule shell composition, the strength of the formed capsule shell, the heat-sealing property, the resistance to cracking, and the like.

Examples of gelatin include, but are not limited to, pig gelatin, bovine gelatin, fish gelatin, gelatin derivatives, and the like. Examples of the gelatin derivatives include succinated gelatin, gelatin hydrolysates, and crosslinked gelatin. These gelatins may be used alone or in combination of two or more. For example, by using fish gelatin or a derivative thereof, it may be possible to ingest animal collagen even in cases where it is difficult to ingest animal collagen from the viewpoint of religion, vegetarianism, allergies, or the like.

The gelatin content is preferably 40% by mass or less, more preferably 30% by mass or less, and even more preferably 1 to 20% by mass, relative to the total mass of the capsule shell composition. .

[solvent]
In one embodiment, the capsule shell composition preferably contains a solvent. By including a solvent in the capsule shell composition, the viscosity of the capsule shell composition can be adjusted.

Specific examples of solvents include water and organic solvents.

The organic solvent is not particularly limited, but includes ethanol, isopropyl alcohol, acetone, ethyl butyrate, and the like.

Among these, the solvent preferably contains water. In addition, the above-mentioned solvent may be used independently or may be used in combination of 2 or more types.

The content of the solvent is preferably 20 to 90% by mass, more preferably 30 to 80% by mass, and 40 to 70% by mass, based on the total mass of the capsule shell composition. More preferably, it is particularly preferably 50 to 60% by mass.

[Additive]
In one embodiment, the capsule shell composition may contain additives.

Such additives include other thickeners, pH adjusters, sequestering agents, film coloring agents, corrigents, sweeteners, preservatives, flavoring agents, and the like.

"Other thickeners" means thickeners other than iota carrageenan, gums, gelatin, and alginate. The other thickening agents include, but are not limited to, kappa (κ) carrageenan, lambda (λ) carrageenan, pullulan, agar, alginic acid, sodium alginate, and the like. These other thickening agents may be used alone or in combination of two or more.

Kappa-carrageenan has a linear main chain composed of galactose having one sulfate ester group and 3,6-anhydrogalactose having no sulfate ester group. In addition, kappa carrageenan may have galactose having two sulfate ester groups, 3,6-anhydrogalactose having sulfate ester groups in part of the main chain, or may have a branched chain. good too.

In addition, lambda carrageenan has a main chain with a linear structure composed of galactose with two sulfate ester groups and galactose with one sulfate ester group. Lambda carrageenan may have 3,6-anhydrogalactose having a sulfate ester group, 3,6-anhydrogalactose having no sulfate ester group, or branched It may have chains.

The pH adjuster is not particularly limited, but includes acids such as hydrochloric acid, sulfuric acid, and nitric acid; bases such as sodium hydroxide and potassium hydroxide; buffers such as phosphate buffers and Tris buffers. These pH adjusters may be used alone or in combination of two or more. In one preferred embodiment, the capsule shell composition preferably does not contain a buffering agent, and more preferably does not contain a phosphate buffering agent.

In addition, sequestering agents include citric acid, tartaric acid, lactic acid, phosphoric acid, acetic acid, gluconic acid, ethylenediaminetetraacetic acid, metaphosphoric acid, salts thereof; glycine, and the like.

These additives may be used alone or in combination of two or more.

[Method for producing capsule shell composition]
The method for producing the capsule shell composition is not particularly limited, and it can be produced by a known method. For example, starch, iota carrageenan, gums, and if necessary, alginate, plasticizer, gelatin, and additives are added to a solvent, and the resulting suspension is heated and dissolved to form a capsule shell composition. can manufacture things.

2 Capsules According to one aspect of the present invention, capsules are provided. The capsule includes contents and a capsule shell. At this time, a capsule shell is formed using the capsule shell composition described above.

In addition, according to another aspect of the present invention, there is provided a capsule containing contents and a capsule shell containing starches, iota carrageenan, and gums. At this time, the capsule has a hardness of 15 kg or more. The capsule shell may further contain at least one of alginate, plasticizer, gelatin, solvent and additive.

[Contents]
Contents are not particularly limited, and include active ingredients and additives.

Examples of the active ingredient include, but are not limited to, hypnotics, psychotropic drugs, antiepileptic drugs, antiparkinsonian drugs, analgesics, therapeutic drugs for Alzheimer's disease, antiallergic drugs, cardiotonic drugs, antiarrhythmic drugs, and antianginal drugs. , antihypertensive, antihyperlipidemic, diuretic, expectorant, antiasthmatic, antacid, peptic ulcer, antithrombotic, thrombolytic, anti-inflammatory, antigout, osteoporosis Rheumatoid arthritis therapeutic drugs Diabetes therapeutic drugs Anticancer drugs Antibiotics Antifungal drugs Immunosuppressive drugs; Crude drugs such as senega, clove, angelica gentian, gentian, ryutan, assembly, rhubarb, digitalis, valerian, bellflower, aloe, hange, turmeric, ginger; Herbal medicines such as shakuyakusan and maoto; vitamins, minerals, collagen, coenzyme Q10, DHA, EPA, lutein, blueberry, placenta, soybean isoflavone, lactic acid bacteria, bifidobacteria, and other health-promoting ingredients; caryophyllene, menthol, limonene, Aroma components such as sesquiterpene and vanillin are included. These active ingredients may be used alone or in combination of two or more.

The additives include, but are not particularly limited to, excipients, coloring agents, masking agents, sweeteners, antioxidants, preservatives, lubricants, flavoring agents, and the like. These additives may be used alone or in combination of two or more.

The total mass of the contents is preferably 40-90% by mass, more preferably 50-80% by mass, relative to the total mass of the capsule.

[Capsule membrane]
A capsule shell is formed using a capsule shell composition. In one embodiment, the capsule shell comprises starches, iota carrageenan, and gums. The capsule shell may further contain at least one of alginate, plasticizer, gelatin, solvent, and additives.

In addition, it is preferable that the capsule shell does not contain gelatin. Moreover, it is preferable that the capsule shell does not contain a phosphate buffer.

The film thickness of the capsule shell is preferably 200 μm or more, more preferably 250 to 800 μm, even more preferably 250 to 500 μm. The film thickness of the capsule film can be measured using a digital microscope (for example, trade name VHX-900 manufactured by Keyence Corporation, using a 10 μm calibration scale). can.

The total mass of the capsule shell is preferably 10-60% by mass, more preferably 20-50% by mass, relative to the total mass of the capsule.

In one embodiment, the content ratio of starch to iota carrageenan in the capsule shell (starch content (mass%)/iota carrageenan content (mass%)) is preferably 1 to 20, It is more preferably from 1.2 to 10, even more preferably from 1.2 to 5, and particularly preferably from 2 to 5.
In one embodiment, the content ratio of starches to gums in the capsule shell (starch content (mass%) / gum content (mass%)) is preferably 1 to 75, It is more preferably from 1 to 50, even more preferably from 2 to 50, particularly preferably from 2 to 30, and most preferably from 5 to 30.
In one embodiment, the content ratio of iota-carrageenan to gums in the capsule shell (iota-carrageenan content (% by mass)/gum content (% by mass)) is 0.1 to 30. It is preferably from 0.5 to 15, even more preferably from 1 to 25, particularly preferably from 2 to 25, and most preferably from 2 to 12.
The starch content (% by mass), the iota carrageenan content (% by mass), and the gum content (% by mass) in the capsule shell are the contents of each component with respect to 100% by mass of the capsule shell. means. Moreover, each content ratio can correspond to each content ratio in the capsule shell composition.

[Configuration of Capsule]
The shape of the capsule is not particularly limited, but may be spherical, ellipsoidal, triangular, rhomboidal, rectangular parallelepiped, rectangular parallelepiped, or the like.

In one embodiment, the capsule is preferably a soft capsule. By being a soft capsule, it is possible to obtain effects such as the ability to formulate a liquid active ingredient with a large amount of oil, a high degree of freedom in the shape of the capsule, and the ability to print the product name on the capsule surface.

The hardness of the capsule is preferably 10 kg or more, more preferably 15 kg or more, still more preferably 20 kg or more, particularly preferably 22 kg or more, and preferably 24 kg or more and 25 kg or more. Most preferred. The upper limit of hardness of the capsule is, for example, preferably 40 kg or less, more preferably 35 kg or less, and even more preferably 30 kg or less. Due to the high hardness of the capsule, deformation of the capsule can be suppressed during storage and distribution.

3 Method for producing capsules According to one aspect of the present invention, a method for producing capsules is provided. The method for producing capsules is not particularly limited, but includes a filling step of filling the capsule shell composition described above with a content liquid containing an active ingredient, and a drying step of drying the resulting filling.

[Filling process]
The filling step is a step of filling the capsule shell composition described above with a content liquid containing an active ingredient.

The content liquid contains active ingredients. In addition, additives may be further included. Said active ingredients and additives are as described above.

In addition, the capsule shell composition is as described above.

The filling method is not particularly limited, but it is preferably a random punching method. The stamping process is usually performed using rotary manufacturing equipment. More specifically, the punching method involves sandwiching two skin sheets obtained from a capsule shell composition between a pair of cylindrical molds so as to overlap each other, and injecting the liquid content between the two skin sheets. In this method, pressure cutting and crimping are performed simultaneously using a mold.

In addition, the capsule shell composition according to the present invention has a low viscosity and is excellent in handleability. As a result, for example, at least one of the following: excellent filling suitability (for example, high-speed filling is possible) due to excellent moldability of a film (wet film) that can be formed during the production of capsules; excellent heat sealability; There are two effects.
In addition, the capsule shell composition may have a jelly strength and flexibility suitable for the film formed during production of the capsule. Therefore, it is possible to obtain effects such as high strength of the film formed during production of the capsule.

[Drying process]
A drying process is a process of drying the obtained filling. The resulting filling has a structure in which the content liquid is filled in the wet film. In the drying process, the capsule shell can be obtained by removing mainly the moisture contained in the wet coating.

Although the temperature and relative humidity during drying are not particularly limited, it is performed in an environment with a temperature of 25-45°C and a relative humidity of 30% RH or less.

The drying process is preferably carried out until the water content of the capsule shell falls below 15%.

The present invention will be specifically described below with reference to examples, but the present invention is not limited to these.

[Example 1]
Starch (viscosity: 46 ± 5 mPa s), iota carrageenan (viscosity: 2,600 ± 800 mPa s), gum arabic gum (viscosity: 260 ± 80 mPa s), and glycerin as a plasticizer , was mixed with water at the compounding ratio shown in Table 1, and the resulting suspension was stirred and dissolved under heating at 90°C or higher for 3 hours to prepare a capsule shell composition.

The viscosity of starches, the viscosity of iota carrageenan, and the viscosity of gums were measured by the following methods.

(Viscosity of starches)
No. 15 g of starches and 135 g of purified water were added to a 12 standard bottle and mixed to sufficiently disperse the starches, followed by heating in a hot water bath at 95° C. for 90 minutes. At that time, the mixture was stirred every 10 minutes for the first 30 minutes and then every 30 minutes. A spatula, a glass rod, or the like was used for stirring.
After that, the paste liquid was cooled to 70° C., and the viscosity was measured. The viscosity was measured using the obtained 10% paste liquid with a Brookfield viscometer (DV-E manufactured by Brookfield, liquid temperature 70°C, rotor No. 2, value after rotating at 60 rpm for 1 minute). . In addition, in this example, the viscosity of starches was measured 3 times, and was described as the average ±SD (standard deviation).

(Viscosity of iota carrageenan)
No. After adding 5 g of iota carrageenan and 12 g of glycerin to a 12 standard bottle and mixing well with a spatula, 103 g of purified water was added and mixed well. The prepared mixture was heated in a hot water bath at 95° C. for 90 minutes. At that time, the mixture was stirred every 10 minutes for the first 30 minutes and then every 30 minutes.
After that, the mixed liquid was cooled to 70° C., and the viscosity was measured. The viscosity was measured with a Brookfield viscometer (Brookfield DV-E, liquid temperature 70° C., rotor No. 3, value after rotating at 12 rpm for 1 minute) using the obtained 4% mixed solution. . In this example, the viscosity of iota carrageenan was measured 3 times and expressed as the average ±SD (standard deviation).

(Viscosity of gums)
25 g of gums and 75 g of purified water were placed in a beaker and mixed well with a stirrer. The prepared mixed solution is No. After transferring to a 12 standard bottle and adjusting the mixture to 25° C., the viscosity was measured.
The viscosity was measured with a Brookfield viscometer (Brookfield DV-E, liquid temperature 25° C., rotor No. 2, value after rotating at 60 rpm for 1 minute) using the obtained 25% mixture. . In addition, in this example, the viscosity of gums was measured 3 times, and was described as the average value±SD (standard deviation).

[Examples 2 to 15, Comparative Examples 1 to 6]
A capsule shell composition was produced in the same manner as in Example 1, except that the compounding ratios shown in Tables 1 and 2 were changed.

The raw materials used are as follows.

(starches)
Starch degradation product (dextrose equivalent (DE) = 2 to 5) (viscosity: 15 m ± 5 mPa s)
Starch degradation product (dextrose equivalent (DE) = 10 to 12) (viscosity: 13 m ± 5 mPa s)
Hydroxypropylated starch (viscosity: 34 m±5 mPa s, degree of etherification: 7% or less)
The viscosity of the starches was measured by the same method as the method for measuring the viscosity of the starches in Example 1. In addition, the degree of etherification was measured in accordance with the Japanese Food Code (Hydroxypropylated Starch).

(Gums)
Guar gum was manufactured by Unitech Foods Co., Ltd., and gellan gum was manufactured by Sumitomo Pharma Food & Chemical Co., Ltd., respectively.

(alginic acid ester)
A commercially available product manufactured by Kimika Co., Ltd. was used.

(Additive)
A commercial product manufactured by Hayashibara Co., Ltd. was used as pullulan.
As disodium hydrogen phosphate, a commercially available product manufactured by Taihei Kagaku Sangyo Co., Ltd. was used.

[evaluation]
Viscosity was evaluated for the capsule shell compositions produced in Examples 1-15 and Comparative Examples 1-6.
Also, the wet film formed from the capsule shell composition was evaluated for jelly strength, flexibility, and filling suitability.
Furthermore, hardness, blocking resistance, appearance, and disintegrability were evaluated for soft capsules produced using the capsule shell composition.

1. Capsule composition (viscosity)
The viscosities of the capsule shell compositions produced in Examples 1 to 15 and Comparative Examples 1 to 6 were measured using a Brookfield viscometer (TVB-15 manufactured by Toki Sangyo Co., Ltd., liquid temperature 95° C., rotor No. H7, 12 rpm. value after rotating for 1 minute). In addition, in this example, the viscosity of the capsule shell composition was measured three times, and was described as the mean ± SD (standard deviation).

2. Wet film (jelly strength and flexibility)
150 g of the capsule shell compositions produced in Examples 1 to 15 and Comparative Examples 1 to 6 were applied to No. It was placed in a 12 standard bottle, air-dried overnight, and used as a sample. Using this sample, a rheometer (CR_3000EX_L manufactured by Sun Science Co., Ltd., adapter No. 2, φ10 mm) was used to measure the jelly strength (maximum load N) and flexibility (breaking distance mm) until the sample was broken by applying a load. It was measured. In addition, in this example, the jelly strength and flexibility were measured three times and described as the mean ± SD (standard deviation).

(Proper filling)
The capsule shell compositions produced in Examples 1 to 15 and Comparative Examples 1 to 6 were spread on a smooth metal plate, sealed to prevent drying, and left at room temperature (22±3° C.) for 15 minutes. It was cooled and gelled to give a wet film (thickness: 0.7 mm). Five evaluators evaluated the stickiness of the resulting wet film and the possibility of encapsulation according to the following criteria, and the average was used as the evaluation result.

A: Good B: Slightly bad C: Poor D: No encapsulation

3. Soft capsules (production of soft capsules)
The capsule shell compositions produced in Examples 1 to 15 and Comparative Examples 1 to 6 were filled with medium-chain fatty acid triglycerides using a rotary die capsule filling machine to obtain football-shaped wet capsules. .
The resulting wet capsules were dried in a dryer set at 40±2° C. and a humidity of less than 20% to produce soft capsules. The moisture content of the capsule shell of the soft capsule after drying was set to 10±1% by weight.
Here, the water content was calculated by the following method. That is, based on the loss-on-drying test method of the Japanese Pharmacopoeia, accurately weigh 0.5 g of the capsule shell of the soft capsule prepared in a pre-dried weighing bottle, and dry it at 110 ° C. for 2 hours. Based on this, the water content of the soft capsule was calculated. In addition, it was calculated by the following formula, assuming that all the moisture contained in the soft capsule is evaporated by the drying process.

Loss on drying/weight of sample x 100 = water content (%)

(hardness)
The hardness of the soft capsule prepared above was evaluated using a Monsanto type tablet hardness tester (B type 30 kg) 208-0219-B manufactured by Ohiwa Pharmaceutical Machinery Co., Ltd. Specifically, pressure was applied to the soft capsule using the tablet hardness tester, and the load (hardness) applied when the soft capsule was broken was measured. In this example, the hardness was measured three times, and the average value ± SD (standard deviation) was described.

(blocking resistance)
20 soft capsules prepared above were placed in a No. It was placed in a 6 standard bottle, sealed with a metal cap, and stored in a constant temperature bath at 60°C for 3 days. The bottle was then removed and allowed to return to room temperature (22±3° C.).

　The inner stopper and metal cap of the bottle were removed, and the following conditions A to E were operated in order starting from A, and the evaluation result was the condition when all 20 soft capsules fell out of the bottle. When the soft capsules adhering to the bottle surface fall (peel off) with a low impact, it can be said that the blocking resistance is high, that is, the surface of the soft capsules is less sticky and the soft capsules are less likely to adhere to each other.

A: Place it upside down B: Drop it upside down from 1cm C: Drop it upside down from 3cm D: Drop it upside down from 5cm E: Hit it upside down

(exterior)
The appearance of the soft capsules prepared above was visually observed, and the transparency and luster of the soft capsules were evaluated by five evaluators, and the average was used as the evaluation result. At this time, the evaluation was made on a 10-point scale from 1 to 10, with the external appearance of the soft capsule obtained from the capsule shell composition of Comparative Example 2 being 5.0.

(Collapsible)
The disintegration property of the soft capsule prepared above was performed based on the disintegration test method of the Japanese Pharmacopoeia. At this time, water was used as the test liquid, and whether or not the 6 soft capsules disintegrated within 20 minutes was evaluated. "Disintegration" means that no residue of the sample is found in the glass tube, or that even if it is found, it is in a state of a soft substance that clearly does not retain its original shape, or that it is in a state of fragmentation of the capsule shell. It means when

The above evaluation results are shown in Table 3 below. In Table 3, "-" indicates unevaluated.

From the results in Table 3, it was found that the capsule shell compositions of Examples 1-15 had low viscosities. Also, although the viscosity of the capsule shell composition was low, the jelly strength and flexibility of the wet coating were high. For this reason, it is considered that filling suitability is good and, for example, high-speed filling becomes possible. Also, the hardness of the soft capsule was high. In addition, the soft capsules were found to have high blocking resistance, good appearance, and excellent disintegration properties.

Claims

A capsule shell composition comprising starches, iota carrageenan, and gums,
The content of the iota carrageenan is 2% by mass or more with respect to 100% by mass of the capsule shell composition,
A capsule shell composition, wherein the gum content is 0.3 to 14% by mass with respect to 100% by mass of the capsule shell composition.
The capsule shell composition according to claim 1, which does not contain gelatin.
The capsule shell composition according to claim 1, which does not contain a phosphate buffer.
The capsule shell composition according to claim 1, wherein the gums are one or more selected from the group consisting of gum arabic, guar gum, locust bean gum, gellan gum, xanthan gum, and tamarind gum.
The content ratio of starches to iota carrageenan (starch content (mass%) / iota carrageenan content (mass%)) is 1.2 to 10,
The content ratio of starches to gums (starch content (mass%) / gum content (mass%)) is 1 to 50,
The capsule shell composition according to claim 1, wherein the content ratio of iota-carrageenan to gums (iota-carrageenan content (mass%)/gums content (mass%)) is 0.5 to 15. thing.
The starch content is 10 to 30% by mass with respect to 100% by mass of the capsule shell composition,
2. The capsule shell composition according to claim 1, wherein the content of said iota carrageenan is 2 to 20 mass % with respect to 100 mass % of said capsule shell composition.
The capsule shell composition according to claim 1, further comprising alginate.
The capsule shell composition according to claim 1, further comprising a plasticizer.
The capsule shell composition according to claim 1, wherein the starch contains at least one selected from the group consisting of natural starch and modified starch.
A capsule containing contents and a capsule shell,
A capsule, wherein the capsule shell is formed using the capsule shell composition according to any one of claims 1 to 9.
The capsule according to claim 10, which is a soft capsule.
The content ratio of starch to iota carrageenan in the capsule shell (starch content (mass%) / iota carrageenan content (mass%)) is 1.2 to 10,
The content ratio of starches to gums in the capsule shell (starch content (mass%) / gum content (mass%)) is 1 to 50,
The content ratio of iota-carrageenan to gums in the capsule shell (iota-carrageenan content (% by mass)/gum content (% by mass)) is 0.5 to 15 according to claim 10. capsules.
the contents;
a capsule shell comprising starches, iota carrageenan, and gums;
including
A capsule having a hardness of 15 kg or more.
The capsule according to claim 13, wherein the capsule shell does not contain gelatin.
The capsule according to claim 13, wherein the capsule shell does not contain a phosphate buffer.
The capsule according to claim 13, which is a soft capsule.
The content ratio of starch to iota carrageenan in the capsule shell (starch content (mass%) / iota carrageenan content (mass%)) is 1.2 to 10,
The content ratio of starches to gums in the capsule shell (starch content (mass%) / gum content (mass%)) is 1 to 50,
The content ratio of iota carrageenan to gums in the capsule shell (iota carrageenan content (% by mass)/gum content (% by mass)) is 0.5 to 15 according to claim 13. capsules.