Gelatin capsule

Abstract

To provide a gelatin capsule having disintegration delay suppressed. A capsule having a capsule shell which comprises gelatin as a base material, and malic acid or a salt thereof.

Description

Gelatin capsules

[0001] The present invention relates to a gelatin capsule having suppressed delayed disintegration.

[0002] Capsules with a gelatin coating have advantages such as being harmless to the human body and quickly dissolving in the body, making them the most commonly used dosage form, especially in the food industry. However, gelatin has problems such as delayed disintegration due to insolubilization caused by thermal denaturation and the formation of crosslinked structures of gelatin molecules due to oxidation. In particular, when the filling contains unsaturated fatty acids such as DHA and EPA, oil components composed of oils and fats having unsaturated fatty acid residues, vitamins, polyphenols, etc., the interaction between the gelatin coating molecules and the filling causes the gelatin coating to become insolubilized over time, significantly delaying the disintegration of the formulation. Such delayed disintegration reduces the bioavailability of the drug, preventing the expected effect from being fully achieved.

[0003] As methods for preventing disintegration delay, for example, a method of blending an amino acid into a gelatin coating (Patent Document 1), a method of blending citric acid (Patent Document 2), a method of blending inositol hexaphosphate (phytic acid) (Patent Document 3), a method of blending tartaric acid (Patent Document 4), etc. have been reported. However, the disintegration delay preventing effect of these methods cannot be said to be sufficient, and there has been concern that the addition of an organic acid reduces the viscosity, thereby reducing the strength of the coating, which may affect the appearance and other problems.

[0004] Japanese Patent Publication No. 57-30088 Japanese Patent Laid-Open No. 59-39834 Japanese Patent Laid-Open No. 2006-328044 Japanese Patent No. 5829607

[0005] The present invention relates to providing a gelatin capsule that suppresses delay in disintegration.

[0006] In light of this situation, the inventors have conducted research and found that by adding malic acid or a salt thereof to a capsule shell containing gelatin, the decrease in the solubility of the shell in water can be effectively suppressed without causing a significant decrease in viscosity.

[0007] That is, the present invention relates to the following 1) to 6). 1) A capsule having a gelatin-based capsule shell containing malic acid or a salt thereof. 2) The capsule according to 1), wherein the content of malic acid or a salt thereof in the shell is 0.5 to 12 parts by mass per 100 parts by mass of gelatin. 3) The capsule according to 1) or 2), which is a soft capsule. 4) The capsule according to any one of 1) to 3), which encapsulates one or more selected from a) unsaturated fatty acids, b) oils and fats containing unsaturated fatty acids as constituent fatty acids, c) vitamins, d) polyphenols, e) natural materials containing one or more of a) to d), f) mushrooms, g) fermentation extracts, h) flavors, i) minerals, j) amino acids, k) proteins or peptides, and l) microorganisms or metabolites thereof. 5) A capsule shell composition containing gelatin, malic acid or a salt thereof, and a plasticizer. 6) A method for inhibiting the delay in disintegration of gelatin-based capsules, which comprises blending malic acid or a salt thereof into the capsule shell.

[0008] According to the present invention, it is possible to provide a capsule preparation which is excellent in quality and stability and in which the delay in disintegration in the body is suppressed.

[0009] The capsules of the present invention are gelatin-based capsules (gelatin capsules) and have a capsule shell containing malic acid or a salt thereof. In the present invention, the gelatin used as the base material for the capsule shell is a denatured collagen obtained by treating a collagen-derived raw material, which is the main protein component of the skin, bones, tendons, etc. of cows, sheep, pigs, chickens, fish, etc., with an acid or alkali and then extracting it with warm water. The origin of the collagen and the processing method for the gelatin used in the present invention are not particularly limited.

[0010] The content of gelatin in the capsule shell is not particularly limited, and is preferably 60 to 90% by mass, more preferably 65 to 85% by mass, based on the total mass of the capsule shell.

[0011] Malic acid, also known as 2-hydroxybutanedioic acid, is an organic compound classified as a hydroxy acid. Malic acid or its salts are often used as an acidulant in beverages and foods. In the present invention, malic acid may be in the D-form, L-form, or DL-form (a mixture of the D- and L-forms), but it is preferable to use DL-malic acid. Furthermore, malic acid may be anhydrous or hydrated.

[0012] Examples of salts of malic acid include salts of alkali metals such as sodium and potassium, salts of alkaline earth metals such as calcium, and magnesium salts, and are not particularly limited. However, sodium salts and potassium salts are preferred, and sodium salts are more preferred.

[0013] As shown in the examples below, capsules containing malic acid in their shells effectively inhibit the decrease in capsule solubility in water over time. Therefore, gelatin capsules containing malic acid in their shells are capsules in which disintegration delay is inhibited. Furthermore, malic acid or a salt thereof acts as a disintegration delay inhibitor for gelatin capsules, particularly soft capsules, and by incorporating it into the capsule shell of gelatin-based capsules, disintegration delay of the capsules can be inhibited. The disintegration delay inhibitory effect can be evaluated by measuring the disintegration time of capsules after storage under specified conditions (e.g., 40°C, 75% humidity, 1 to 3 months) in accordance with the disintegration test method of the 17th edition of the Japanese Pharmacopoeia.

[0014] The amount of malic acid or a salt thereof in the capsule shell may be determined as appropriate taking into consideration the expected effects, etc., but is preferably 0.5 to 12 parts by mass, more preferably 1 to 8 parts by mass, and even more preferably 2 to 6 parts by mass of malic acid (free acid) per 100 parts by mass of gelatin.

[0015] A plasticizer can be appropriately blended into the capsule shell to impart flexibility and elasticity. Examples of plasticizers include glycerins (e.g., glycerin, diglycerin, polyglycerin, etc.), sugar alcohols (sorbitol, xylitol, erythritol, maltitol, mannitol, cyclitol, etc.), glycols (propylene glycol, dipropylene glycol, 1,3-butylene glycol, ethylene glycol, polyethylene glycol, etc.), disaccharides, oligosaccharides, etc. The blending ratio of such plasticizers is, for example, 5 to 150 parts by weight, preferably 10 to 80 parts by weight, and more preferably 20 to 50 parts by weight per 100 parts by weight of gelatin.

[0016] Furthermore, the capsule shell may contain, if necessary, pigments, anti-adhesion agents (processed starch, silicon dioxide, etc.), etc., within the range that does not impair the effects of the present invention.

[0017] The capsule of the present invention may be in the form of either a hard capsule in which the contents are filled into a capsule, or a soft capsule in which the contents are encapsulated in a capsule shell, but a soft capsule is preferred.

[0018] In the capsule formulation of the present invention, the capsule contents are not particularly limited, and examples thereof include substances that can generally be filled into capsules, such as ingredients used in pharmaceuticals, quasi-drugs, cosmetics, foods (health foods, foods for specified health uses, foods with functional claims, supplements, etc.), seasonings, flavorings, mushrooms, fermentation extracts, minerals, amino acids, proteins, microorganisms or their metabolites, etc. Among these, the capsule shell of the present invention is particularly effective when encapsulating one or more selected from a) unsaturated fatty acids, b) oils and fats containing unsaturated fatty acids as constituent fatty acids, c) vitamins, d) polyphenols, and e) natural materials containing one or more of the above a) to d), f) mushrooms, g) fermentation extracts, h) flavorings, i) minerals, j) amino acids, k) proteins or peptides, and l) microorganisms or their metabolites.

[0019] Here, examples of unsaturated fatty acids include ω3 polyunsaturated fatty acids such as α-linolenic acid, stearidonic acid, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), ω6 polyunsaturated fatty acids such as linoleic acid, γ-linolenic acid, and arachidonic acid, and ω9 monounsaturated fatty acids such as oleic acid. Examples of fats and oils containing unsaturated fatty acids as constituent fatty acids include vegetable fats and oils such as soybean oil, rapeseed oil, safflower oil, rice oil, corn oil, sunflower oil, cottonseed oil, olive oil, sesame oil, peanut oil, Job's tears oil, wheat germ oil, perilla oil, linseed oil, perilla oil, sacha inchi oil, walnut oil, kiwi seed oil, salvia seed oil, grape seed oil, macadamia nut oil, hazelnut oil, pumpkin seed oil, camellia oil, tea seed oil, borage oil, palm oil, palm olein, palm stearin, coconut oil, palm kernel oil, cocoa butter, monkey fat, shea butter, and algae oil; animal fats and oils such as fish oil, lard, beef tallow, and butterfat; and interesterified, hydrogenated, and fractionated oils thereof. Of these, fish oils containing large amounts of ω3 fatty acids such as DHA and EPA are preferred.

[0020] Examples of polyphenols include flavonols, isoflavones, tannins, catechins, quercetin, anthocyanins, flavangenols, and flavonoids. Of these, anthocyanins contained in bilberry and black currant, and rhodanthenone B contained in mangosteen extract are preferred.

[0021] Examples of mushrooms include powders or extracts thereof obtained by drying and grinding mushrooms such as agaricus, phellinus linteus, Ganoderma lucidum, enokitake, schizophyllum commune, shiitake, maitake, chaga (obscured ob ...

[0022] Examples of fermented extracts include those obtained by fermenting plants such as vegetables, fruits, beans, and grains, seaweed, mushrooms, and sugars using microorganisms such as yeast, lactic acid bacteria, koji mold, red koji mold, acetic acid bacteria, and natto bacteria.

[0023] Examples of minerals include calcium, phosphorus, sodium, potassium, magnesium, zinc, selenium, iron, and copper, which can be used as inorganic or organic salts.

[0024] Examples of amino acids include functional amino acids such as GABA (γ-aminobutyric acid), HMB (3-hydroxyisovaleric acid), theanine, 5-ALA (5-aminolevulinic acid), β-alanine, cystine, ergothioneine, selenoneine, cysteine, ornithine, and citrulline.

[0025] Examples of proteins or peptides include functional proteins or peptides such as elastin, collagen, carnosine, anserine, balenine, and glutathione.

[0026] Examples of microorganisms include lactic acid bacteria belonging to the genus Lactobacillus, Lactococcus, Streptococcus, Enterococcus, and Leuconostoc, which are used in fermented foods, as well as bacteria of the genus Bifidobacterium, Eubacterium, and Propionibacterium, as well as microorganisms of the genus Bacillus and Acetobacter.

[0027] The capsule of the present invention can generally be produced by filling or enclosing the contents in a capsule shell. The capsule shell is formed by adding an appropriate amount of water to the shell composition containing the above-mentioned gelatin, malic acid or a salt thereof, and a plasticizer, mixing and stirring the mixture under heating (70 to 90°C, preferably around 80°C) to prepare a shell liquid (gelatin solution), molding the mixture, and drying the mixture.

[0028] Soft capsules include rotary die-type soft capsules, which are produced by using a rotary die to fill the contents between two film sheets while molding and punching them out, and seamless capsules, which are produced by a dropping method using a double nozzle, and the capsules of the present invention may be in either form. In the production of rotary die-type soft capsules, a film solution is prepared from a film composition and formed into a sheet, which is then punched out by the rotation of two die rolls, and at the same time, the inner solution is enclosed, and the film is compressed by the die rolls to seal.

[0029] The capsule shell can be dried using, for example, a rotary drum dryer, and the drying conditions, such as temperature and time, can be appropriately adjusted depending on the components contained in the contents and the components contained in the capsule shell. For example, the drying temperature can be about 15°C to 35°C, the humidity can be about 10% RH to 50% RH, and the drying time can be about 0.5 to 2 days.

[0030] The capsules of the present invention thus produced are of excellent quality and stability, since the decrease in the solubility of the capsules in water over time is suppressed and the decrease in the viscosity of the gelatin, which is the coating base material, is also suppressed, and the delayed disintegration when ingested is suppressed.

[0031] Example 1 Production of Soft Capsules <1> (1) Soft Capsule A (Vitamin C-Containing Soft Capsule) 1) Preparation of Capsule Shell Solution The components shown in Table 1 were mixed in the prescribed ratios and stirred and dissolved while heating in a water bath at approximately 80°C to prepare gelatin solutions for a malic acid-containing shell and a malic acid-uncontaining shell.

[0032]

[0033] 2) Preparation of Capsule Contents The specified amounts of beeswax, Poem S-100, and sunflower oil shown in Table 2 were mixed and dissolved by heating at approximately 70°C, then cooled to 40°C or below, and vitamin C was added and stirred. The mixture was then wet-pulverized (using a colloid mill), sieved, and degassed to prepare the capsule contents.

[0034]

[0035] 3) Production of soft capsules The gelatin solution prepared in 1) was degassed at 80°C and then left to stand for about 10 hours, after which it was formed into a thin film of 0.8 to 0.9 mm using a rotary die type soft capsule filling machine (Oval No. 5), and cooled to produce a gelatin sheet. The gelatin sheet was passed through a roll mold from both sides, and while heating to about 40°C with a segment to adhere the gelatin sheet, the capsule contents prepared in 2) were filled in with a pump just before punching, and the punched-out molded product was dried to produce soft capsule A.

[0036] (2) Soft Capsule B (Soft Capsule Containing Mangosteen Extract) 1) Preparation of Capsule Shell Solution Gelatin solutions for the malic acid-containing shell and the malic acid-uncontaining shell were prepared in the same manner as in (1) above. 2) Preparation of Capsule Contents Beeswax, Poem S-100, linseed oil, and olive oil shown in Table 3 were dissolved by heating at approximately 70°C, then cooled to 40°C or below, mangosteen extract was added, and the mixture was stirred. The mixture was then wet-pulverized (in a colloid mill), sieved, and degassed to prepare the capsule contents.

[0037]

[0038] A gelatin sheet was prepared in the same manner as in (1). The gelatin sheet was passed through a roll mold from both sides, and while the gelatin sheet was being adhered by heating at about 40°C with a segment, the capsule contents prepared in 2) were filled in with a pump just before punching, and the punched and molded product was dried to produce soft capsule B.

[0039] Test Example 1 Disintegration Test (1) Soft capsules A and B produced in Example 1 were placed in glass bottles, sealed with metal caps (packings with rubber liners), and stored in a constant temperature and humidity chamber at 40°C and 75% RH for one month at a time up to three months, and the disintegration times were compared. The disintegration times were measured using a disintegration tester (ERWEKA Automatic Detection Disintegration Tester ZT720) in accordance with the disintegration test method of the 17th edition of the Japanese Pharmacopoeia.

[0040] (2) Results The results are shown in Table 4. Both soft capsules A and B, which contained malic acid in the coating, disintegrated within 20 minutes, as specified by the Japanese Pharmacopoeia, when stored at 40°C and 3M, whereas capsules without malic acid in the coating either disintegrated after 20 minutes or were completely insoluble when stored at 40°C and 1M.

[0041]

[0042] Test Example 2: Gelatin-coated sheet dissolution test (1) Preparation of gelatin-coated sheet i) 100 g of purified water was placed in a 500 ml glass beaker, and 100 g of gelatin (BCN200S (Nitta Gelatin)) and 35 g of glycerin (food additive glycerin) were added thereto and allowed to absorb water and swell, followed by stirring and dissolving while heating in a water bath at approximately 80° C. to prepare a gelatin solution. The prepared gelatin solution was spread evenly to a thickness of approximately 1 mm and dried at room temperature of 25° C. for 24 hours to prepare a gelatin-coated sheet (Table 5: reference film). ii) 100 g of purified water was placed in a 500 ml glass beaker, and 100 g of gelatin (BCN200S (Nitta Gelatin)) and 35 g of glycerin (food additive glycerin) were added thereto and allowed to absorb water and swell, and then 3 g of an organic acid shown in Table 5 was added and dissolved by stirring while heating in a water bath at about 80°C to prepare a gelatin solution containing an organic acid. Gelatin coating sheets A to F were produced in the same manner as in i).

[0043] In Table 5, glycerin was used as "food additive glycerin," malic acid was used as "Fuso Malic Acid Type S (Fuso Chemical Industries)," phytic acid was used as "50% aqueous solution of food additive phytic acid (Fuso Chemical Industries)," citric acid was used as "anhydrous citric acid," and gluconic acid was used as "gluconic acid solution (50% aqueous solution)."

[0044]

[0045] (2) Dissolution test Capsules containing fish oil as the capsule contents were assumed. 10 g of fish oil (DHA-46G: Nippon Suisan) was placed in a screw tube, and 7 mm x 7 mm pieces of each gelatin coating sheet were immersed in the oil and stored in a constant temperature bath at 50 ° C. Each stored gelatin coating sheet piece was removed over time, the adhering fish oil was wiped off, and then placed in 150 ml of 60 ° C. hot water and stirred with a stirrer (magnetic stirrer, 600 rpm) for 3 minutes. The pieces were then left to stand and visually confirmed for the presence or absence of insoluble matter. The number of days until insolubilization was observed and evaluated according to the following criteria. The results are shown in Table 6.

[0046] <Evaluation criteria> When the film pieces are completely dissolved and no unwanted matter is found: - When the film pieces are dissolved, but a small amount of insoluble matter is found: ± When the film pieces are dissolved, but a small amount of insoluble film is found: + When the film pieces are dissolved, but a moderate amount of insoluble film is found: ++ When the film pieces are dissolved, but a large amount of insoluble film is found: +++ When the film pieces are dissolved, but a large amount of insoluble film is found: ++++ When the film pieces are completely insolubilized

[0047]

[0048] Film sheet D containing gluconic acid and film sheet E containing succinic acid became insolubilized on the same day as the reference film, 5 days later, and no insolubilization prevention effect was observed. Film sheet A containing malic acid, film sheet B containing phytic acid, and film sheet C containing citric acid were found to have an insolubilization suppression effect, with film sheet A containing malic acid being the most effective.

[0049] Test Example 3: Viscosity Decrease of Gelatin Shell Solution During Heated Storage Soft capsules are generally manufactured as follows: 1) Glycerin and purified water are added to gelatin, and the mixture is stirred and dissolved while heated to 70-80°C, followed by vacuum degassing to prepare a gelatin solution (viscosity adjusted to 20,000 mPa s). The gelatin solution is then heated at 60°C for 4-10 hours and stored. 2) The 60°C-heated gelatin shell solution is then supplied to a capsule filling machine, which fills and molds the contents. For this purpose, the gelatin solution is heated to 60°C for approximately 40 hours from preparation to capsule filling and molding. On the other hand, it is known that the viscosity of gelatin solutions decreases over time when stored at 60°C. When the viscosity decreases from the initial value of 20,000 mPa·s to 14,000 mPa·s or less (70% or less of the initial value), the strength of the gelatin shell decreases, causing mechanical problems during filling and fatal defects such as cracking and deformation due to insufficient strength of the molded soft capsules. Adding an organic acid to a gelatin solution is a concern as it may decrease the viscosity. Therefore, the following test was conducted to address this issue.

[0050] 1) Preparation of Gelatin Solution: 112 g of purified water was placed in a 500 ml glass beaker, and 7 g of the weighed organic acid shown in Table 7 was dissolved with stirring. (Tartaric acid and succinic acid were dissolved in the purified water while heating in a water bath at approximately 80°C.) Next, 140 g of gelatin (BCN200S (Nitta Gelatin)) and 49 g of glycerin (food additive glycerin) were added and allowed to absorb water and swell. The mixture was then stirred and dissolved while heating in a water bath at approximately 80°C to prepare a gelatin solution. In Table 7, malic acid was replaced with Fuso Malic Acid Type S (Fuso Chemical Industries), tartaric acid with L-Tartaric Acid S (Fuso Chemical Industries), citric acid with Anhydrous Citric Acid (Iwata Chemical Industries), and succinic acid with Succinic Acid (Fuso Chemical Industries).

[0051]

[0052] 2) Viscosity Measurement The viscosity of the prepared gelatin solutions was measured using a Brookfield viscometer (rotor rotation speed: 12 rpm), and then the solutions were divided into 90 g portions in standard No. 10 glass bottles and stored in a thermostatic bath at 60°C. Each stored gelatin solution was taken out after 48 hours and its viscosity was measured. The results are shown in Table 8.

[0053]

[0054] The viscosity of gelatin solution F containing malic acid decreased to 70% after storage at 60°C for 48 hours, but this was the same viscosity reduction rate as the unblended reference solution and was within the target lower limit of 14,000 mPa s. Gelatin solution G containing tartaric acid, gelatin solution H containing citric acid, and gelatin solution I containing succinic acid all showed viscosity reduction rates of over 30%, below 14,000 mPa s, raising concerns about the impact on capsule molding and capsule strength.

[0055] Example 2 Production of soft capsules <2> (1) Soft capsule C (soft capsules containing mushroom extract) 1) Preparation of capsule shell solution The components shown in Table 9 were mixed in the prescribed ratios and dissolved by stirring while heating in a water bath at approximately 80°C to prepare gelatin solutions for a malic acid-containing shell and a malic acid-uncontaining shell.

[0056]

[0057] 2) Preparation of Capsule Contents The sunflower oil, beeswax, and emulsifiers shown in Table 10 were dissolved by heating at approximately 70°C, cooled to 40°C or below, and reishi mushroom was added and stirred. The mixture was then wet-pulverized (using a colloid mill), sieved, and degassed to prepare the capsule contents.

[0058]

[0059] 3) Production of soft capsules A gelatin sheet was prepared in the same manner as in (1) of Example 1. The gelatin sheet was passed through a roll mold from the left and right, and while the gelatin sheet was adhered by applying heat of about 40°C with a segment, the capsule contents prepared in 2) were filled with a pump just before punching, and the punched and molded product was dried to produce soft capsules C.

[0060] (2) Soft Capsule D (Probiotic-Containing Soft Capsule) 1) Preparation of Capsule Shell Solution Gelatin solutions for the malic acid-containing shell and the malic acid-free shell were prepared in the same manner as in (1) above.

[0061]

[0062] 2) Preparation of Capsule Contents The sunflower oil, beeswax, and emulsifiers shown in Table 12 were dissolved by heating at approximately 70°C, cooled to 40°C or below, and then bifidobacteria and Bacillus subtilis var. natto were added and stirred. The mixture was then wet-pulverized (using a colloid mill), sieved, and degassed to prepare the capsule contents.

[0063]

[0064] A gelatin sheet was prepared in the same manner as in (2). The gelatin sheet was passed through a roll mold from both sides, and while the gelatin sheet was being adhered by heating at about 40°C with a segment, the capsule contents prepared in 2) were filled in with a pump just before punching, and the punched and molded product was dried to produce soft capsule D.

[0065] (3) Soft Capsule Formulation E (Amino Acid-Containing Soft Capsule) 1) Preparation of Capsule Shell Solution Gelatin solutions for the malic acid-containing shell and the malic acid-free shell were prepared in the same manner as in (1) above.

[0066]

[0067] 2) Preparation of Capsule Contents The sunflower oil, beeswax, and emulsifiers shown in Table 14 were dissolved by heating at approximately 70°C, cooled to 40°C or below, and GABA was added and stirred. The mixture was then wet-pulverized (using a colloid mill), sieved, and degassed to prepare the capsule contents.

[0068]

[0069] A gelatin sheet was prepared in the same manner as in (2). The gelatin sheet was passed through a roll mold from both sides, and while the gelatin sheet was being adhered by heating at about 40°C with a segment, the capsule contents prepared in 2) were filled in with a pump just before punching, and the punched and molded product was dried to produce soft capsule E.

[0070] (4) Soft Capsules F, G, and H (Bilberry- and DHA-Containing Soft Capsules) 1) Preparation of Capsule Shell Solution Gelatin solutions for a malic acid-containing shell and a malic acid-free shell were prepared in the same manner as in (1) above.

[0071]

[0072] 2) Preparation of Capsule Contents The DHA, beeswax, and emulsifier shown in Table 16 were dissolved by heating at approximately 70°C, cooled to 40°C or below, and bilberry was added and stirred. The mixture was then wet-pulverized (using a colloid mill), sieved, and degassed to prepare the capsule contents.

[0073]

[0074] 3) Production of soft capsules Gelatin sheets were prepared in the same manner as in (2). The gelatin sheets were passed through a roll mold from the left and right, and heated to about 40°C with a segment to adhere the gelatin sheets. Just before punching, the capsule contents prepared in 2) were filled with the capsule contents using a pump, and the punched and molded pieces were dried to produce soft capsules. Of the malic acid coatings, soft capsule F was used with a gelatin solution containing 3 parts by weight of malic acid, soft capsule G was used with a gelatin solution containing 5 parts by weight of malic acid, soft capsule H was used with a gelatin solution containing 8 parts by weight of malic acid, and soft capsule I was used with a gelatin solution containing no malic acid.

[0075] Test Example 4 Disintegration Test (1) Test Method Soft capsules F, G, and H produced in Example 2 were placed in glass bottles, sealed with metal caps (packings with rubber liners), and stored in a constant temperature and humidity chamber at 40°C and 75% RH for one month at a time up to four months, and the disintegration times were compared. The disintegration times were measured using a disintegration tester (manufactured by ERWEKA, automatic detection type disintegration tester ZT720) in accordance with the disintegration test method of the 17th edition of the Japanese Pharmacopoeia.

[0076] (2) Results The results are shown in Table 17. Soft capsules F, G, and H, each containing malic acid in the shell, all disintegrated within 20 minutes, as specified by the Japanese Pharmacopoeia, when stored at 40°C and 3M. However, soft capsule I, which did not contain malic acid in the shell, disintegrated within 20 minutes or was completely insoluble when stored at 40°C and 2M.

[0077]

Claims

1. A capsule agent having a capsule film containing malic acid or its salt and using gelatin as a base material.

2. The capsule agent according to claim 1, wherein the content of malic acid or its salt in the film is 0.5 to 12 parts by mass with respect to 100 parts by mass of gelatin.

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

4. The capsule agent according to any one of claims 1 to 3, which encapsulates one or more selected from a) unsaturated fatty acids, b) oils and fats containing unsaturated fatty acids as constituent fatty acids, c) vitamins, d) polyphenols, e) natural materials containing any one or more of a) to d) above, f) mushrooms, g) fermentation extracts, h) flavors, i) minerals, j) amino acids, k) proteins or peptides, and l) microorganisms or their metabolites.

5. A capsule film composition containing gelatin, malic acid or its salt, and a plasticizer.

6. A method for suppressing the delay of disintegration of a capsule agent, in which malic acid or its salt is blended in a capsule film in a capsule agent using gelatin as a base material.