Capsules and method for manufacturing capsules

Abstract

To solve the problem in which: in the case where 3-hydroxyisovaleric acid is blended in the content liquid of a capsule, the capsule coating tends to deform, leading to a leak of the content liquid.SOLUTION: A capsule comprises a capsule coating filled with the content liquid, the capsule coating comprising at least pullulan, the content liquid comprising 3-hydroxyisovaleric acid and a sugar alcohol, the sugar alcohol having a DE value of 40-80, the proportion of disaccharides comprised in the sugar alcohol being 25-70%, and the proportion of trisaccharides comprised in the sugar alcohol being 8-40%.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a capsule and a method for producing the capsule. [Background technology]

[0002] In hard capsules and soft capsules, especially those containing liquids (content liquids), their capsule shells can be damaged, causing the content liquid to leak. This is mainly due to the volume change of the content liquid (solution or suspension, etc.) enclosed in the capsule shell caused by environmental changes such as temperature and air pressure. Furthermore, when the capsule shell is deformed due to factors such as dropping the capsule or applying external pressure after being packaged in a supplement, large stress acts locally, causing the capsule shell to crack at that point, making the content liquid more susceptible to leakage.

[0003] In addition, leakage of the contents from the capsule shell is also affected by the components contained in the contents. When soft capsules containing L-carnitine as the main component are manufactured, the high hygroscopicity of L-carnitine can dry out the capsule shell, causing cracks in the capsule shell and making the contents more susceptible to leakage.

[0004] In the past, the inventors of the present invention have proposed a method for manufacturing soft capsules in which an aqueous solution containing sugar or sugar alcohol is filled into the soft capsule shell as the content liquid, and then the sugar or sugar alcohol is supersaturated, in order to solve the problem of leakage of the content liquid from the soft capsule shell (Patent Document 1).

[0005] In recent years, 3-hydroxyisovaleric acid (β-hydroxy-β-methylbutyric acid, HMB) has attracted attention for its effectiveness in maintaining muscle mass and strength, and is used in supplements and functional foods for sports and the elderly. [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2013-173714 Summary of the Invention [Problem to be solved by the invention]

[0007] The HMB commonly used in health foods is in the form of a salt of HMB calcium (HMB-Ca), but there is a growing need for the intake of free HMB due to its rapid absorption in the body.

[0008] However, there have been no reports that have fully verified how the free form of 3-hydroxyisovaleric acid affects the capsule shell when it is added to the content liquid of a capsule. As a result of further investigations by the present inventors, they have newly discovered a problem that when the free form of 3-hydroxyisovaleric acid is added to the content liquid of a capsule, compatibility with the base of the capsule shell has a significant effect, making the capsule shell more likely to deform and leading to leakage of the content liquid. [Means for solving the problem]

[0009] As a result of further investigation, the inventors discovered that it was possible to prevent deformation of the capsule shell and leakage of the content liquid by a means completely different from the technology of Patent Document 1, and thus completed the present invention.

[0010] Specifically, the inventors discovered that by incorporating at least pullulan as a base in the capsule shell and adjusting the sugar alcohol composition in the capsule content liquid, deformation of the capsule shell and leakage of the content liquid can be prevented, leading to the completion of the present invention.

[0011] That is, the present invention provides the capsules described below.

[0012] [1] A capsule in which a capsule shell is filled with a content liquid, the capsule shell containing at least pullulan, The inner liquid contains 3-hydroxyisovaleric acid and a sugar alcohol, The DE value of the sugar alcohol is 40 to 80, The sugar alcohol ratio of disaccharides contained in the sugar alcohol is 25 to 70%, The sugar alcohols contained in the capsules have a trisaccharide sugar alcohol ratio of 8 to 40%.

[0013] [2] The capsule according to [1], wherein the content of the sugar alcohol is 1 to 20% by mass relative to the total amount of the content liquid.

[0014] [3] The capsule according to [1] or [2], wherein the content of the 3-hydroxyisovaleric acid is 98% by mass or less based on the total amount of the content liquid.

[0015] The present invention also provides the following method for producing capsules.

[0016] [4] Contains 3-hydroxyisovaleric acid and sugar alcohols, The DE value of the sugar alcohol is 40 to 80, The sugar alcohol ratio of disaccharides contained in the sugar alcohol is 25 to 70%, preparing a content liquid in which the sugar alcohol ratio of trisaccharides contained in the sugar alcohol is 8 to 40%; preparing a capsule shell composition containing at least pullulan; A method for producing a capsule, comprising the step of preparing a capsule by filling the content liquid in the coating composition. [Effects of the Invention]

[0017] According to the present invention, by incorporating at least pullulan into the capsule shell and adjusting the sugar alcohol composition in the capsule content liquid to one that is difficult to pass through the capsule shell containing pullulan, it is possible to suppress deformation of the capsule shell and improve leakage of the content liquid. DETAILED DESCRIPTION OF THE INVENTION

[0018] One embodiment of the present invention is a capsule having a capsule shell filled with a content liquid, wherein the capsule shell contains at least pullulan, The inner liquid contains 3-hydroxyisovaleric acid and a sugar alcohol, The DE value of the sugar alcohol is 40 to 80, The sugar alcohol ratio of disaccharides contained in the sugar alcohol is 25 to 70%, The capsule is provided in which the sugar alcohol contains trisaccharides at a ratio of 8 to 40%.

[0019] The capsules are not particularly limited as long as they are capsules used in the fields of food and pharmaceuticals, and various dosage forms such as hard capsules and soft capsules (including seamless capsules) can be used.

[0020] (Liquid content of capsule) In the capsule of the present invention, the content liquid contains at least 3-hydroxyisovaleric acid and a sugar alcohol.

[0021] 3-Hydroxyisovaleric acid (3-hydroxy-3-methylbutyrate, β-hydroxy-β-methylbutyrate, hereinafter also referred to as HMB) is a compound represented by the structural formula (CH3)2C(OH)CH2COOH, and HMB is known to have muscle mass-enhancing effects, etc. In the present invention, HMB is the free acid and is also referred to as HMB free form.

[0022] The content of 3-hydroxyisovaleric acid is not limited and may be varied as appropriate depending on the dosage form, the types and amounts of other ingredients, the intended recipient, etc., but may be, for example, 80% by mass or more of the total amount of the liquid content, preferably 82% by mass or more, more preferably 84% by mass or more, even more preferably 86% by mass or more, and particularly preferably 88% by mass or more. The content of 3-hydroxyisovaleric acid can be, for example, 98% by mass or less, 97% by mass or less, 96% by mass or less, 95% by mass or less, 94% by mass or less, etc., relative to the total amount of the content liquid. In addition, the content of 3-hydroxyisovaleric acid is, for example, 80-98% by mass, 82-98% by mass, 84-98% by mass, 86-98% by mass, 88-98% by mass, 80-97% by mass, 82-97% by mass, 84-97% by mass, 86-97% by mass, 88-97% by mass, 80-96% by mass, 8 2-96% by mass, 84-96% by mass, 86-96% by mass, 88-96% by mass, 80-95% by mass, 82-95% by mass, 84-95% by mass, 86-95 % by mass, 88-95% by mass, 80-94% by mass, 82-94% by mass, 84-94% by mass, 86-94% by mass, 88-94% by mass, etc.

[0023] The type of sugar alcohol is not particularly limited as long as it achieves the effects of the present invention. Examples of sugar alcohols include known ingredients that can be used in the food and pharmaceutical fields, such as sorbitol, xylitol, erythritol, mannitol, maltitol, lactitol, and reduced starch syrup. Among sugar alcohols, for example, sorbitol, xylitol, erythritol, and mannitol are monosaccharide alcohols composed of monosaccharides, while lactitol is a disaccharide alcohol composed of disaccharides.

[0024] It is preferable to use multiple types of sugar alcohols in order to achieve the effects of the present invention more significantly. The sugar alcohols may be an appropriate combination of the above sugar alcohols, or the material to be blended with multiple types may be, but is not limited to, reduced starch syrup, for example. Reduced starch syrup is a general term for a sugar alcohol mixture of monosaccharides and polysaccharides produced by reducing the glucose terminals by hydrogenation, using starch syrup obtained by hydrolyzing starch with acid or enzymes as a raw material. Reduced starch syrup is also called reduced starch hydrolysate, reduced starch saccharification product, reduced oligosaccharide, etc.

[0025] Reduced starch syrup is classified according to the sugar content of the raw material starch syrup, and examples include high sugar content reduced starch syrup, medium sugar content reduced starch syrup, and low sugar content reduced starch syrup. The reduced starch syrup is not particularly limited, but medium sugar content reduced starch syrup is preferred from the viewpoint of significantly achieving the effects of the present invention. These reduced starch syrups may be produced by appropriately adjusting the sugar content of the raw material starch syrup, or commercially available products may be used. Commercially available high sugar content reduced starch syrup products include SE 600 (manufactured by Bussan Food Science Co., Ltd.) and PO-60 (manufactured by Mitsubishi Corporation Life Sciences Co., Ltd.). Commercially available medium sugar content reduced starch syrup products include Sweet OL (manufactured by Bussan Food Science Co., Ltd.) and SE 57 (manufactured by Bussan Food Science Co., Ltd.). Commercially available low sugar content reduced starch syrup products include SE 30 (manufactured by Bussan Food Science Co., Ltd.) and PO-30 (manufactured by Mitsubishi Corporation Life Sciences Co., Ltd.).

[0026] From the viewpoint of significantly achieving the effects of the present invention, the DE (Dextrose Equivalent) value of the sugar alcohol is 40 to 80, preferably 40 to 70, more preferably 40 to 65, even more preferably 40 to 60, and particularly preferably 40 to 50. The DE (Dextrose Equivalent) value is an index showing the purity of glucose, and the DE value of crystalline glucose is 100.

[0027] Furthermore, in terms of the sugar composition of the sugar alcohol, from the viewpoint of significantly achieving the effects of the present invention, it is preferable that the ratio of disaccharide alcohols contained in the sugar alcohol is 25 to 70% and the ratio of trisaccharide alcohols contained in the sugar alcohol is 8 to 40%. The ratio of disaccharide alcohols contained in the sugar alcohol is, for example, more preferably 30 to 65%, even more preferably 35 to 60%, and particularly preferably 40 to 55%. The ratio of trisaccharide alcohols contained in the sugar alcohol is, for example, more preferably 15 to 40%, even more preferably 20 to 40%, and particularly preferably 25 to 40%.

[0028] The sugar alcohol content may be varied as appropriate depending on the dosage form, the type and amount of other ingredients, the intended recipient, etc., and is not limited to a specific amount. For example, the sugar alcohol content may be 1% by mass or more of the total volume of the liquid content, preferably 2% by mass or more, more preferably 4% by mass or more, even more preferably 6% by mass or more, and particularly preferably 8% by mass or more. Furthermore, the sugar alcohol content can be, for example, 20% by mass or less, preferably 18% by mass or less, more preferably 16% by mass or less, even more preferably 14% by mass or less, and particularly preferably 12% by mass or less, relative to the total amount of the liquid content.

[0029] (capsule membrane) The capsule shell contains at least pullulan.

[0030] Pullulan is a type of water-soluble polysaccharide, and has a structure in which maltotriose units, each of which is made up of three glucose molecules linked together via an α1-4 bond, are linked together via an α1-6 bond. In the present invention, pullulan is contained as a constituent base material for the capsule shell.

[0031] The pullulan content is not limited and may be varied as appropriate depending on the dosage form, the types and amounts of other ingredients, the intended recipient, etc. For example, in the case of a hard capsule dosage form, the pullulan content can be 85% by mass or more of the total amount of the coating composition, preferably 86% by mass or more, more preferably 87% by mass or more, and particularly preferably 88% by mass or more. The content of pullulan can be, for example, 91% by mass or less, 90% by mass or less, 89% by mass or less, 88% by mass or less, etc. As the hard capsule containing pullulan, commercially available products can also be used, such as Plantcaps capsules (manufactured by Capsugel).

[0032] For example, in the case of a soft capsule dosage form, the pullulan content can be 20% by mass or more, preferably 26% by mass or more, more preferably 28% by mass or more, even more preferably 30% by mass or more, and particularly preferably 32% by mass or more, relative to the total amount of the coating composition. The pullulan content can be, for example, 45% by mass or less, preferably 40% by mass or less, more preferably 38% by mass or less, even more preferably 36% by mass or less, and particularly preferably 35% by mass or less, relative to the total amount of the coating composition.

[0033] In addition to the above, the capsule shell may contain, for example, carrageenan.

[0034] The carrageenan content may be varied as appropriate depending on the dosage form, the type and amount of other ingredients, the intended recipient, etc., and is not limited thereto. For example, in the case of a hard capsule dosage form, the content can be 0.1% by mass or more of the total amount of the coating composition, preferably 0.2% by mass or more, more preferably 0.3% by mass or more, even more preferably 0.4% by mass or more, and particularly preferably 0.5% by mass or more. The content of carrageenan can be, for example, 2% by mass or less, 1.5% by mass or less, 1% by mass or less, 0.7% by mass or less, 0.6% by mass or less, etc., relative to the total amount of the coating composition.

[0035] For example, in the case of a soft capsule dosage form, the carrageenan content can be 5% by mass or more of the total amount of the coating composition, preferably 7% by mass or more, more preferably 9% by mass or more, even more preferably 10% by mass or more, and particularly preferably 12% by mass or more. Furthermore, the carrageenan content can be, for example, 25% by mass or less, preferably 23% by mass or less, more preferably 21% by mass or less, even more preferably 19% by mass or less, and particularly preferably 17% by mass or less, relative to the total amount of the coating composition.

[0036] The method for manufacturing the capsules can be any known method without any particular restrictions. In the case of a hard capsule dosage form, the content liquid is filled into the hard capsule shell, and a band seal is applied to the seam between the body and cap parts that make up the hard capsule, thereby preventing the content liquid from leaking from the seam (band seal method).

[0037] For soft capsule dosage forms, known rotary die or seamless methods can be used. For the rotary die method, for example, a soft capsule can be prepared by molding the capsule while filling the space between two film sheets using a rotary die, and then punching out the contents. For the seamless method, seamless capsules can be prepared, for example, by a dropping method using a double nozzle. [Example]

[0038] Next, the present invention will be specifically explained with reference to examples and test examples, but the present invention is not limited to the following examples and test examples.

[0039] [Test Example 1. Effect of the type of base on HMB-containing capsules] HMB was filled into hard and soft capsules with different bases, and changes over time were observed when stored at room temperature. Plantcaps capsules (manufactured by Capsugel) were used as a hard capsule coating product (commercially available) manufactured from a coating containing at least pullulan. Natural B / C capsules (manufactured by Capsugel) were used as a hard capsule coating product manufactured from a coating containing gelatin but not pullulan. VP Natural B / C capsules (manufactured by Capsugel) were used as a hard capsule coating product manufactured from a coating containing HPMC but not pullulan. For soft capsules, capsule coatings were prepared using the coating compositions listed in Table 1 by conventional methods. These coatings were used to fill HMB as the content liquid, and hard and soft capsules were prepared by conventional methods. Specifically, for hard capsule dosage forms, the content liquid was encapsulated in the hard capsule coating to prepare hard capsules. For soft capsule dosage forms, the content liquid was encapsulated in the following coating composition using a conventional rotary die method to prepare soft capsules.

[0040] [Table 1]

[0041] (Evaluation method) The five capsules were checked for "softening" and "cracks" and evaluated based on the following criteria. The results are shown in Table 2.

[0042] (Softening criteria) 〇: No softened capsules among 5 capsules △: Less than 2 softened capsules out of 5 capsules ×: 3 or more softened capsules out of 5 capsules

[0043] (Crack Judgment Criteria) 〇: No broken capsules among 5 capsules △: 2 or less broken capsules out of 5 capsules ×: 3 or more broken capsules out of 5

[0044] [Table 2]

[0045] As shown in Table 2, when gelatin or HPMC was used as the capsule shell base, the capsules softened and were prone to cracking due to the influence of HMB in the capsule contents. On the other hand, when pullulan was used as the capsule shell base, although it was effective in preventing capsule softening, it did not have a sufficiently satisfactory effect on preventing capsule cracking.

[0046] [Test Example 2. Effect of sugar alcohol composition in HMB-containing capsules 1] As a simple method for evaluating soft capsule formulation, we investigated the effect of HMB-containing liquid on the hard capsule shell when it was filled into a hard capsule. HMB content solutions were prepared so that the sugar alcohol concentrations were 40%, 25%, and 10% by mass, and filled into hard capsules containing pullulan as a base. Changes over time during storage at room temperature were examined. Specifically, hard capsules were produced by conventional methods based on the capsule content composition shown in Table 3, using Plantcaps capsules (manufactured by Capsugel) as a hard capsule shell product (commercially available) manufactured from a shell containing at least pullulan. The composition of the sugar alcohols used is shown in Table 4. The evaluation methods for capsule "softening" and "cracking" were the same as in Test Example 1. The results for sugar alcohol concentrations of 40%, 25%, and 10% by mass are shown in Tables 5 to 7, respectively.

[0047] [Table 3]

[0048] [Table 4]

[0049] [Table 5]

[0050] [Table 6]

[0051] [Table 7]

[0052] As shown in Tables 5 to 7, the effect of changing the sugar alcohol content and composition on the stability over time of HMB-containing capsules using pullulan as the capsule shell base was confirmed. Among the sugar alcohols, sweet OL was confirmed to have high stability against "softening" and "cracking."

[0053] [Test Example 3. Effect of sugar alcohol composition in HMB-containing capsules 2] Based on the results of Test Example 2, the stability against "softening" and "cracking" was confirmed using a commercially available reduced starch syrup (PO-300: manufactured by Mitsubishi Corporation Life Sciences Co., Ltd.) that has a sugar alcohol composition similar to that of Sweet OL. Specifically, HMB content solutions were prepared so that the PO-300 concentrations were 40%, 25%, and 10% by mass, and filled into hard capsules containing pullulan as a base. Changes over time during storage at room temperature were observed. Specifically, Plantcaps capsules (manufactured by Capsugel) were used as a hard capsule shell product (commercially available) manufactured from a shell containing at least pullulan. Hard capsules were manufactured by conventional methods based on the capsule content composition shown in Table 8. Table 9 compares the sugar alcohol compositions of Sweet OL and PO-300. The evaluation methods for capsule "softening" and "cracking" were the same as in Test Example 1. The results are shown in Table 10.

[0054] [Table 8]

[0055] [Table 9]

[0056] [Table 10]

[0057] As shown in Table 10, even in the case of a commercially available reduced starch syrup (PO-300) with a similar sugar alcohol composition to Sweet OL, high stability against "softening" and "cracking" was confirmed in HMB-containing capsules using pullulan as the capsule shell base. Sweet OL and PO-300 are particularly similar in the compositions of disaccharide alcohols and trisaccharide alcohols contained in the sugar alcohols, and it is believed that the blending ratio of these alcohols has a particular impact on the effects of the present invention.

[0058] [Test Example 4. Examination of the effective concentration of sugar alcohol raw materials for HMB] HMB content solutions were prepared with HMB concentrations of 77-82% by mass and 92-98% by mass, and the effects of filling pullulan-derived hard capsules on "softening" and "cracking" over time were examined. Specifically, Plantcaps capsules (manufactured by Capsugel) were used as a hard capsule shell product (commercially available) made from a shell containing at least pullulan, and hard capsules were produced by conventional methods based on the capsule content composition shown in Table 11. The evaluation methods for capsule "softening" and "cracking" were the same as in Test Example 1. The results are shown in Tables 12 and 13.

[0059] [Table 11]

[0060] [Table 12]

[0061] [Table 13]

[0062] As shown in Tables 12 and 13, it was shown that in HMB-containing capsules using pullulan as the base for the capsule shell, stability against "softening" and "cracking" can be achieved by setting the HMB content in the capsule contents to 70% by mass to 98% by mass.

[0063] [Test Example 5. Confirmation of the effects of HMB and sugar alcohols on pullulan-based soft capsule coatings] Capsule contents were prepared containing 10% by mass of each sugar alcohol to achieve an HMB concentration of 90% by mass. Specifically, 20 g of each capsule content was weighed into a 50 ml bottle, sealed with a pullulan-containing soft capsule shell according to the formulation shown in Table 14 below, and stored upside down. This confirmed the effect of contacting the HMB content solution with the pullulan-containing soft capsule shell on the cracking of the shell. The evaluation methods for capsule "softening" and "cracking" were the same as in Test Example 1. The results are shown in Table 15.

[0064] [Table 14]

[0065] [Table 15]

[0066] As shown in Table 15, the test using soft capsule shells also yielded results comparable to those obtained in Example 3 using hard capsules. These results confirmed that, in HMB-containing capsules using pullulan as the capsule shell base, adjusting the sugar alcohol composition examined in Test Examples 2 to 4 above provides high stability against "softening" and "cracking" not only for hard capsule shells but also for soft capsule shells with different shell compositions.

Claims

1. A capsule in which a capsule shell is filled with a content liquid, the capsule shell containing at least pullulan, The inner liquid contains 3-hydroxyisovaleric acid and a sugar alcohol, The sugar alcohol has a DE value of 40 to 80; The ratio of monosaccharide alcohol contained in the sugar alcohol is 2 to 6%, The ratio of disaccharide alcohol contained in the sugar alcohol is 45 to 55%, The ratio of trisaccharide alcohol contained in the sugar alcohol is 25 to 35%, The ratio of tetrasaccharide alcohol contained in the sugar alcohol is 1 to 4%, The ratio of alcohols with five or more sugars contained in the sugar alcohol is 1 to 15%, The content of the 3-hydroxyisovaleric acid is 82 to 92% by mass based on the total amount of the content liquid, The capsule has a sugar alcohol content of 8 to 18% by mass based on the total amount of the content liquid.

2. A capsule having a capsule shell filled with a liquid content, wherein the capsule shell contains at least pullulan, The inner liquid contains 3-hydroxyisovaleric acid and a sugar alcohol, The sugar alcohol has a DE value of 40 to 80; The ratio of monosaccharide alcohol contained in the sugar alcohol is 17 to 25%, The ratio of disaccharide alcohol contained in the sugar alcohol is 25 to 33%, The ratio of trisaccharide alcohol contained in the sugar alcohol is 33 to 39%, the ratio of tetrasaccharides and pentose or higher sugar alcohols contained in the sugar alcohol is 10 to 19%; The content of the 3-hydroxyisovaleric acid is 82 to 92% by mass based on the total amount of the content liquid, The capsule has a sugar alcohol content of 8 to 18% by mass based on the total amount of the content liquid.

3. Contains 3-hydroxyisovaleric acid and a sugar alcohol, The sugar alcohol has a DE value of 40 to 80; The ratio of monosaccharides contained in the sugar alcohol is 2 to 6%, the sugar alcohol contains a disaccharide in an amount of 45 to 55%; the ratio of trisaccharides contained in the sugar alcohol is 25 to 35%, the sugar alcohol contains tetrasaccharides in an amount of 1 to 4%; the ratio of five or more sugars contained in the sugar alcohol is 1 to 15%; The content of the 3-hydroxyisovaleric acid is 82 to 92% by mass based on the total amount, preparing a content liquid having a sugar alcohol content of 8 to 18% by mass relative to the total amount of the content liquid; preparing a capsule shell composition containing at least pullulan; A method for producing a capsule, comprising the step of preparing a capsule by filling the content liquid in the coating composition.

4. A method for producing a soluble fiber comprising: The sugar alcohol has a DE value of 40 to 80; The ratio of monosaccharides contained in the sugar alcohol is 17 to 25%, the ratio of disaccharides contained in the sugar alcohol is 25 to 33%, the ratio of trisaccharides contained in the sugar alcohol is 33 to 39%, the ratio of tetrasaccharides and pentasaccharides or more contained in the sugar alcohol is 10 to 19%; The content of the 3-hydroxyisovaleric acid is 82 to 92% by mass based on the total amount, preparing a content liquid having a sugar alcohol content of 8 to 18% by mass relative to the total amount of the content liquid; preparing a capsule shell composition containing at least pullulan; A method for producing a capsule, comprising the step of preparing a capsule by filling the content liquid in the coating composition.

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