Encapsulated formulation

Abstract

The present disclosure addresses the problem of providing a technology for suppressing insolubilization due to storage of a coating film in an encapsulated formulation in which a content including a medium-chain fatty acid triglyceride is encapsulated in the coating film including gelatin.　This encapsulated formulation comprises a content including a medium-chain fatty acid triglyceride, neotame, and sucralose, wherein the content is encapsulated in a coating film including gelatin.

Description

Capsules

[0001] The present disclosure relates to a capsule in which a content containing a medium-chain fatty acid triglyceride is encapsulated in a shell containing gelatin, and in which insolubilization of the shell during storage can be suppressed.

[0002] Gelatin is non-toxic to the human body, inexpensive, and has excellent jelly-forming and thickening properties, and is therefore widely used as a capsule coating component in the pharmaceutical and food industries. However, when gelatin is used as a capsule coating component, the coating tends to become insoluble (decreased in solubility) over time due to crosslinking reactions with the contents filled in the capsule. Such insolubilization of the capsule coating can cause inconveniences such as inappropriate release of active ingredients after ingestion. Therefore, insolubilization of the capsule coating can lead to serious problems such as a decrease in the quality of the capsule.

[0003] Various techniques for suppressing the insolubilization of capsule shells have been investigated. For example, Patent Document 1 reports that the insolubilization of shells can be suppressed by using a shell containing gelatin and inositol having 1 to 6 phosphates ester-bonded thereto. Furthermore, Patent Document 2 reports that the insolubilization of shells can be suppressed by encapsulating a content containing at least one oil selected from the group consisting of peppermint oil, parsley seed oil, and menthone oil in a shell containing porcine-derived gelatin and / or fish-derived gelatin.

[0004] JP 2006-328038 A JP 2020-105140 A

[0005] As mentioned above, techniques for suppressing the insolubilization of capsule shells have been reported in the past, but a technique for suppressing the insolubilization of capsule shells is needed in view of the diversification of manufacturing techniques, etc. Furthermore, in capsules used in the food industry, medium-chain fatty acid triglycerides are sometimes used as the base material for the contents, but when contents containing medium-chain fatty acid triglycerides are encapsulated in a shell containing gelatin, the shell is likely to become insolubilized during storage.

[0006] Therefore, an object of the present disclosure is to provide a technology for suppressing insolubilization of a capsule shell containing gelatin during storage, in which a content containing a medium-chain fatty acid triglyceride is encapsulated in the shell.

[0007] The present inventors have conducted extensive research to solve the above-mentioned problems and have found that a capsule having a gelatin-containing shell encapsulating a content containing a medium-chain fatty acid triglyceride, neotame, and sucralose can effectively prevent the shell from becoming insolubilized during storage. The present disclosure has been completed through further research based on this finding.

[0008] That is, the present disclosure provides capsules according to the following aspects. Item 1. A capsule comprising a fill containing a medium-chain fatty acid triglyceride, neotame, and sucralose encapsulated in a shell containing gelatin. Item 2. The capsule according to Item 1, wherein the fill further contains a monoterpene. Item 3. The capsule according to Item 2, wherein the monoterpene is menthol. Item 4. The capsule according to any one of Items 1 to 3, comprising 0.0005 to 1 part by weight of neotame and 0.001 to 1 part by weight of sucralose per 100 parts by weight of the total fill. Item 5. The capsule according to any one of Items 1 to 4, which is a soft capsule.

[0009] According to the present disclosure, in a capsule in which a content containing a medium-chain fatty acid triglyceride is encapsulated in a shell containing gelatin, insolubilization of the shell during storage can be effectively suppressed.

[0010] In the present disclosure, the expression "X to Y" regarding a numerical range refers to a numerical range of not less than X but not more than Y. Furthermore, in the present disclosure, "insolubilization of the coating" refers to a phenomenon in which the coating becomes difficult to dissolve in an aqueous solution. A capsule with an insolubilized coating may have a problem in that the coating becomes difficult to disintegrate after ingestion, preventing proper release of the contents.

[0011] The capsule of the present disclosure is characterized in that the contents containing medium-chain fatty acid triglyceride, neotame, and sucralose are encapsulated in a shell containing gelatin. The capsule of the present disclosure will be described in detail below.

[0012] [Capsule Contents] Medium-chain fatty acid triglyceride The capsule contents of the present disclosure include medium-chain fatty acid triglyceride, which is also commonly known as MCT (Medium Chain Triglyceride) and is a glycerin triester of fatty acids having 6 to 12 carbon atoms.

[0013] The medium-chain fatty acids constituting the medium-chain fatty acid triglycerides may be either saturated or unsaturated fatty acids, but are preferably saturated fatty acids. The carbon number of the medium-chain fatty acids constituting the medium-chain fatty acid triglycerides may be 6 to 12, but is preferably 8 to 10. Specific examples of the medium-chain fatty acids constituting the medium-chain fatty acid triglycerides include caproic acid, caprylic acid, capric acid, and lauric acid. Preferred examples of the medium-chain fatty acids constituting the medium-chain fatty acid triglycerides include caprylic acid and capric acid.

[0014] In a medium-chain fatty acid triglyceride, the three medium-chain fatty acids contained in one molecule may be the same medium-chain fatty acid, or may be a combination of two or three types of medium-chain fatty acids.

[0015] In the present disclosure, the medium-chain fatty acid triglyceride may be an oil or fat containing a medium-chain fatty acid triglyceride, such as palm oil or coconut oil.

[0016] The content of medium-chain fatty acid triglycerides contained in the contents of the capsules of the present disclosure is not particularly limited, but examples thereof include 50 to 98 parts by weight, preferably 60 to 97 parts by weight, more preferably 70 to 96 parts by weight, even more preferably 80 to 96 parts by weight, and particularly preferably 83 to 95 parts by weight of medium-chain fatty acid triglycerides per 100 parts by weight of the total amount of the contents. When an oil or fat containing medium-chain fatty acid triglycerides is used, the value of the content of medium-chain fatty acid triglycerides described here is the value converted into the amount of medium-chain fatty acid triglycerides contained in the oil or fat.

[0017] Neotame and sucralose The contents of the capsule of the present disclosure include neotame and sucralose in addition to medium-chain triglycerides. In conventional technology, when a content containing medium-chain triglycerides is encapsulated in a shell containing gelatin, there is a drawback in that the shell is prone to insolubilization during storage. However, in the capsule of the present disclosure, by including neotame and sucralose in the contents in addition to medium-chain triglycerides, the synergistic effect of these ingredients can effectively prevent the shell from becoming insolubilized during storage.

[0018] Neotame, whose IUPAC name is N-"N-(3,3-dimethylbutyl)-L-α-aspartyl"-L-phenylalanine 1-methyl ester, is a dipeptide methyl ester derivative obtained by reductive N-alkylation of aspartame. Sucralose, whose IUPAC name is 1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl-4-chloro-4-deoxy-α-D-galactopyranoside, is a derivative of sucrose.

[0019] The content of neotame contained in the contents of the capsule of the present disclosure may be, for example, 0.0005 to 1 part by weight, preferably 0.001 to 0.5 parts by weight, more preferably 0.001 to 0.3 parts by weight, even more preferably 0.005 to 0.1 parts by weight, and particularly preferably 0.01 to 0.1 parts by weight or 0.01 to 0.05 parts by weight, per 100 parts by weight of the total amount of the contents.

[0020] The content of sucralose in the contents of the capsules of the present disclosure may be, for example, 0.001 to 1 part by weight, preferably 0.005 to 0.5 parts by weight, more preferably 0.01 to 0.3 parts by weight, even more preferably 0.05 to 0.15 parts by weight or 0.05 to 0.2 parts by weight, and particularly preferably 0.1 to 0.15 parts by weight or 0.1 to 0.2 parts by weight, per 100 parts by weight of the total amount of the contents.

[0021] Furthermore, the ratio of neotame to sucralose in the contents of the capsule of the present disclosure is, for example, 0.01 to 100 parts by weight, preferably 0.1 to 50 parts by weight, and more preferably 1 to 10 parts by weight of sucralose per 1 part by weight of neotame.

[0022] Monoterpenes The contents of the capsules of the present disclosure may optionally contain monoterpenes, which are compounds having a structure containing two isoprene units in the molecule.

[0023] The type of monoterpene used in the present disclosure is not particularly limited, as long as it is edible. Examples include alcohol-based monoterpenes such as menthol, thymol, geraniol, linalool, borneol, cineole, and terpineol; aldehyde-based monoterpenes such as citral, citronellal, perillaldehyde, and safranal; and ketone-based monoterpenes such as camphor, menthone, carbomenthone, and ionone. When optical isomers exist, these monoterpenes may be d-, l-, or dl-isomers. These monoterpenes may be used alone or in combination of two or more.

[0024] Furthermore, as the monoterpene, an essential oil containing a monoterpene may be used. The essential oil containing a monoterpene may be appropriately selected from known essential oils, and examples of essential oils containing menthol include peppermint oil, peppermint oil, and spearmint oil.

[0025] Of these monoterpenes, menthol and essential oils containing menthol are preferred.

[0026] When a monoterpene is contained in the contents of the capsule of the present disclosure, the content is not particularly limited, but may be, for example, 0.1 to 20 parts by weight, preferably 1 to 18 parts by weight, and more preferably 5 to 15 parts by weight of monoterpene per 100 parts by weight of the total amount of the contents. When an essential oil containing a monoterpene is used, the value of the monoterpene content described here is the value converted into the amount of monoterpene contained in the essential oil.

[0027] Other fats and oils The contents of the capsule of the present disclosure may contain fats and oils other than medium-chain fatty acid triglycerides. The type of fats and oils other than medium-chain fatty acid triglycerides is not particularly limited, and examples include vegetable oils such as black cumin seed oil, sunflower seed oil, jojoba seed oil, olive oil, coconut oil, palm oil, palm kernel oil, safflower oil, castor oil, avocado oil, sesame oil, tea oil, evening primrose oil, wheat germ oil, macadamia nut oil, hazelnut oil, kukui nut oil, rosehip oil, meadowfoam oil, persic oil, tea tree oil, corn oil, rapeseed oil, wheat germ oil, linseed oil, cottonseed oil, soybean oil, peanut oil, rice bran oil, and jojoba oil; and animal oils such as fish oil, whale oil, beef tallow, lard, and milk fat. These fats and oils may be used alone or in combination of two or more.

[0028] Among these oils and fats, vegetable oils are preferred, and black cumin seed oil is more preferred.

[0029] When fats and oils (other than medium-chain fatty acid triglycerides) are contained in the contents of the capsule of the present disclosure, the amount of the fats and oils (other than medium-chain fatty acid triglycerides) is not particularly limited, but may be, for example, 0.001 to 5 parts by weight, preferably 0.005 to 2 parts by weight, and more preferably 0.01 to 1 part by weight per 100 parts by weight of the total amount of the contents.

[0030] Other Components In addition to the components described above, the capsule contents of the present disclosure may contain other edible components that can be incorporated into the capsule contents. Examples of such edible components include water, plasticizers, colorants, amino acids, vitamins, enzymes, sweeteners, flavorings, excipients, disintegrants, fluidizing agents, surfactants, flavorings, odorants, suspending agents, humectants, emulsifiers, solubilizers, dispersants, buffers, binders, penetration enhancers, stabilizers, bulking agents, preservatives, thickeners, pH adjusters, coating agents, absorption enhancers, antioxidants, anti-inflammatory agents, waxes, etc. These edible components may be used alone or in combination of two or more.

[0031] The contents of the capsule of the present disclosure are produced by mixing the above-mentioned components. A suitable example of the contents of the capsule of the present disclosure is a mixture of medium-chain fatty acid triglyceride and other fat-soluble components (monoterpenes, oils, and the like, which are contained as needed), followed by adding and mixing neotame, sucralose, and water-soluble components, which are contained as needed, while heating as needed.

[0032] [Capsule Coating] Gelatin The capsule coating of the present disclosure contains gelatin. The gelatin used in the present disclosure may be edible, and its origin is not particularly limited, but examples include skin, bone, tendon, ligament, scales, etc., of pigs, cows, fish, etc. Furthermore, the gelatin used in the present disclosure may be any of acid- and / or alkali-treated gelatin, chemically modified gelatin such as acylated gelatin, gelatin hydrolysate, etc., as long as it can form a coating.

[0033] The content of gelatin contained in the shell of the capsule of the present disclosure is, for example, 15 to 85 parts by weight, preferably 20 to 80 parts by weight, more preferably 25 to 75 parts by weight, even more preferably 30 to 70 parts by weight, and particularly preferably 50 to 70 parts by weight, per 100 parts by weight of the total amount of the shell in terms of dry weight.

[0034] Plasticizer The capsule shell of the present disclosure may contain a plasticizer. The type of plasticizer is not particularly limited, and any plasticizer that is commonly used as a capsule shell component may be used. Examples include glycerin; sugar alcohols such as erythritol, xylitol, sorbitol, and mannitol; monosaccharides or disaccharides such as fructose and sucrose; and water-insoluble celluloses such as crystalline cellulose, low-substituted hydroxypropyl cellulose, and ethyl cellulose. These plasticizers may be used alone or in combination of two or more.

[0035] Among these plasticizers, preferred examples include at least one of glycerin and sugar alcohol, and more preferably a combination of glycerin and sugar alcohol.

[0036] When glycerin and a sugar alcohol are used in combination as a plasticizer, the ratio thereof is not particularly limited, but examples thereof include 1 to 500 parts by weight, preferably 10 to 150 parts by weight, more preferably 20 to 80 parts by weight, and even more preferably 30 to 50 parts by weight of the sugar alcohol per 100 parts by weight of glycerin.

[0037] When a plasticizer is contained in the shell of the capsule of the present disclosure, the content thereof is not particularly limited, but for example, the content of the plasticizer may be 1 to 50 parts by weight, preferably 10 to 50 parts by weight, and more preferably 20 to 42 parts by weight or 20 to 40 parts by weight per 100 parts by weight of the total amount of the shell in terms of dry weight.

[0038] Other Components In addition to the components described above, the capsule shell of the present disclosure may contain other components that can be incorporated into the capsule shell. Examples of such edible components include water, excipients, disintegrants, fluidizing agents, surfactants, lubricants, flavorings, colorings, sweeteners, flavorings, odorants, suspending agents, humectants, emulsifiers, solubilizers, dispersants, buffers, binders, penetration enhancers, stabilizers, bulking agents, preservatives, thickeners, oily bases, pH adjusters, coating agents, absorption enhancers, antioxidants, anti-inflammatory agents, cooling agents, amino acids, vitamins, enzymes, etc.

[0039] - Production of the Coating The coating of the capsule of the present disclosure can be produced by a method depending on the type of capsule.

[0040] [Capsules] The capsules of the present disclosure are obtained by encapsulating the contents in the shell. In the capsules of the present disclosure, the ratio of the contents to the shell is not particularly limited, but may be 85 to 97 parts by weight, preferably 87 to 97 parts by weight, and more preferably 88 to 95 parts by weight of the contents per 100 parts by weight of the total amount of the capsules (total amount of the contents and the shell) in terms of dry weight.

[0041] The capsule of the present disclosure may be either a soft capsule or a hard capsule, and a suitable example is a soft capsule.

[0042] The shape of the capsule of the present disclosure is not particularly limited, and may be, for example, oval (football)-shaped, oblong (long elliptical), round (spherical), teardrop-shaped, triangular, etc. The weight per capsule of the present disclosure is also not particularly limited, and may be, for example, 0.3 to 2.5 g, preferably 0.4 to 1.6 g, and more preferably 0.6 to 1.0 g.

[0043] The capsules of the present disclosure can be used as foods, medicines, etc. When the capsules of the present disclosure are used as foods, they can be provided as foods for specified health uses, foods with nutrient functions, foods with functional claims, supplements, etc. Furthermore, the capsules of the present disclosure may be, for example, swallowed immediately or may be left in the oral cavity for a certain period of time and then swallowed.

[0044] The capsules of the present disclosure can be produced by known methods depending on the type of capsule. For example, when the capsules of the present disclosure are soft capsules, they can be produced by, for example, a rotary soft encapsulation method, a seamless encapsulation method, or the like.

[0045] The invention of the present disclosure will be explained in more detail below by showing examples, but the invention of the present disclosure is not limited to these examples.

[0046] Test Example 1: Evaluation of the degree of insolubilization of a gelatin-containing coating (1) 1. Preparation of contents and coating pieces Contents with the compositions shown in Table 1 were prepared. Specifically, first, predetermined amounts of flavoring, black cumin seed oil, and L-menthol were added to a predetermined amount of medium-chain fatty acid triglyceride, and the mixture was heated and stirred to dissolve. Next, predetermined amounts of neotame and sucralose were added to the resulting solution, and the mixture was heated and stirred to dissolve, thereby preparing the contents.

[0047] Separately, film pieces were prepared with the composition shown in Table 1. A predetermined amount of gelatin was mixed with twice the amount of water, and the gelatin was heated and dissolved at 80°C. The remaining ingredients were mixed with the gelatin solution, and then cooled to 25°C to gelatinize it. The cooled product was cut into sheets measuring 1.5 cm x 1.5 cm (weight 80 mg) each, to obtain film pieces containing gelatin (gelatin film pieces).

[0048] 2. Method for evaluating the degree of insolubilization of gelatin coating pieces One gelatin coating piece was completely immersed in 2.3 g of each content heated to 50°C and left to stand for one week. After that, the gelatin coating piece was removed from the content, washed with hexane, and the weight of the gelatin coating piece (weight A) was measured. At this point, all of the gelatin coating pieces maintained the shape they had before being immersed in the content.

[0049] Next, 50 mL of water at 60° C. was placed in a 50 mL beaker, and the washed gelatin coating pieces were further placed therein, and stirred for 5 minutes (670 rpm) using a stirrer while maintaining the water temperature at 60° C. After that, if any gelatin coating pieces remained, the remaining matter (insoluble matter) was recovered and washed with hexane, and the weight of the remaining matter (weight B) was measured.

[0050] The remaining rate of gelatin film pieces was calculated according to the following formula.

[0051] 3. Evaluation Results The results are shown in Table 1. The gelatin-coated pieces immersed in a content containing a medium-chain fatty acid triglyceride (Comparative Example 1) showed a significant decrease in solubility in water, with 80% remaining gelatin-coated pieces. Furthermore, the gelatin-coated pieces immersed in a content containing a medium-chain fatty acid triglyceride and neotame, sucralose, aspartame, or sucrose (Comparative Examples 2 to 6) did not improve the decrease in solubility in water. In contrast, the gelatin-coated pieces immersed in a content containing a medium-chain fatty acid triglyceride, neotame, and sucralose (Examples 1 to 4) showed significantly better solubility in water, with 0% or 5% remaining gelatin-coated pieces.

[0052] These results confirmed that when a medium-chain triglyceride-containing content is coated with a gelatin-containing film, the insolubilization of the gelatin-containing film can be effectively suppressed by adding neotame and sucralose to the content together with the medium-chain triglyceride. It also became clear that the inhibitory effect of the gelatin-containing film on insolubilization is brought about by the synergistic action of neotame and sucralose.

[0053]

[0054] Test Example 2: Evaluation of the degree of insolubilization of a gelatin-containing shell (2) 1. Production of soft capsules Soft capsules were prepared consisting of the contents and shell shown in Table 2. The specific production procedure is as follows.

[0055] The contents were prepared as follows: First, predetermined amounts of flavoring, black cumin seed oil, and L-menthol were added to a predetermined amount of medium-chain fatty acid triglyceride, and the mixture was heated and stirred to dissolve. Next, predetermined amounts of neotame and sucralose were added to the resulting solution, and the mixture was heated and stirred to dissolve, thereby obtaining the contents.

[0056] The coating composition for forming a coating was prepared as follows: First, predetermined amounts of glycerin, erythritol, xylitol, acesulfame potassium, and synthetic coloring agents were added to purified water and dissolved by stirring. Next, a predetermined amount of gelatin was added to the resulting solution to swell it, and the solution was heated to 50°C to dissolve the gelatin, thereby obtaining a coating composition (water content 60% by weight).

[0057] The obtained contents and the coating composition were used to encapsulate the contents with the coating composition by a seamless encapsulation method, thereby obtaining soft capsules (total weight per capsule: 0.1 to 0.12 g).

[0058]

[0059] 2. Evaluation Method for the Degree of Insolubilization of the Shell After Storage The obtained soft capsules were stored at 40°C for 30 or 70 days. The degree of insolubilization of the shell of each soft capsule before storage (immediately after production) and after storage was evaluated using a disintegration tester. The evaluation of the degree of insolubilization of the shell using a disintegration tester was performed using the following procedure. One soft capsule was gently placed into the basket of the disintegration tester while tilting it diagonally, and an auxiliary plate disk was gently placed on top of it so as not to impact the soft capsule. Next, with the basket entirely immersed in purified water at 37-38°C, the disintegration tester was turned on, and the basket was vibrated up and down at an amplitude speed of 30 times / min / 55 mm, and the instantaneous time until the shell of the soft capsule broke and the contents were ejected was measured. The measurement was performed six times on the same sample, and the average time until the shell broke was calculated.

[0060] 3. Evaluation Results The results are shown in Table 3. The average time until the shell of the soft capsule before storage was similar in Example 1 and Comparative Example 1. On the other hand, for the soft capsules stored at 40°C for 30 or 70 days, the average time until the shell broke was significantly shorter in Example 5 than in Comparative Example 8, indicating that insolubilization of the shell was suppressed. In other words, the results also confirmed that when a content containing a medium-chain fatty acid triglyceride is coated with a shell containing gelatin, insolubilization of the shell can be effectively suppressed by including neotame and sucralose in the content together with the medium-chain fatty acid triglyceride.

[0061]

[0062] Formulation Example Soft capsules (total weight per capsule: 0.1 to 0.12 g) were prepared consisting of the contents and coating shown in Table 4. The specific manufacturing procedure was basically the same as in the above Test Example, except that the raw materials used were changed. The obtained soft capsules were evaluated under the same conditions as in Test Example 1, and it was found that insolubilization of the coating was suppressed.

[0063]

Claims

1. A capsule comprising an ingredient containing medium-chain triglyceride, neotame, and sucralose encapsulated in a shell containing gelatin.

2. The capsule of claim 1, wherein the contents further comprise a monoterpene.

3. The capsule of claim 2, wherein the monoterpene is menthol.

4. The capsule according to claim 1 or 2, which contains 0.0005 to 1 part by weight of neotame and 0.001 to 1 part by weight of sucralose per 100 parts by weight of the total content.

5. The capsule according to claim 1 or 2, which is a soft capsule.

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