Gelatin capsules

Abstract

Provided is a gelatin capsule agent having a suppressed disintegration delay.　The capsule agent contains gelatin as a base material and has a capsule film containing malic acid or a salt thereof.

Description

[Technical Field]

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

[0002] Gelatin-coated capsules are the most commonly used dosage form, especially in the food industry, due to their advantages of being harmless to the human body and rapidly dissolving in the body. However, gelatin has problems such as delayed disintegration due to insolubilization caused by thermal denaturation and the formation of cross-linked 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 with unsaturated fatty acid residues, vitamins, polyphenols, etc., the interaction between the gelatin coating 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 effects from being fully achieved.

[0003] As methods for preventing delayed disintegration, for example, a method of incorporating an amino acid into a gelatin coating (Patent Document 1), a method of incorporating citric acid (Patent Document 2), a method of incorporating inositol hexaphosphate (phytic acid) (Patent Document 3), a method of incorporating tartaric acid (Patent Document 4), etc. have been reported. However, it cannot be said that these methods are necessarily effective in preventing the delay in disintegration, and there are concerns that the addition of organic acids may reduce the viscosity and therefore the strength of the coating, which may affect the appearance and other problems. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Special Publication No. 57-30088 [Patent Document 2] Japanese Patent Application Publication No. 59-39834 [Patent Document 3] Japanese Patent Application Laid-Open No. 2006-328044 [Patent Document 4] Patent No. 5829607 Summary of the Invention [Problem to be solved by the invention]

[0005] The present invention relates to providing a gelatin capsule that suppresses delay in disintegration. [Means for solving the problem]

[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 base and a capsule shell containing malic acid or a salt thereof. 2) A 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) A capsule according to any one of 1) to 3), which contains one or more selected from a) unsaturated fatty acids, b) fats and oils 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) fermented extracts, h) flavorings, 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 incorporating malic acid or a salt thereof into the capsule shell. [Effects of the Invention]

[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. DETAILED DESCRIPTION OF THE INVENTION

[0009] The capsule of the present invention is a capsule based on gelatin (gelatin capsule) and has 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. There are no particular limitations on the origin of collagen or the processing method for the gelatin used in the present invention.

[0010] The content of gelatin in the capsule shell is not particularly limited, and is preferably 60 to 90% by mass, and 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 and its salts are widely used as an acidulant in beverages and foods. In the present invention, malic acid may be any of D-, L-, or DL-isomers (a mixture of D- and L-isomers), but DL-malic acid is preferably used. 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 capsules based on gelatin, disintegration delay of the capsules can be inhibited. The disintegration delay suppression effect can be evaluated by measuring the disintegration time after storing the capsule 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 can be determined appropriately taking into consideration the expected effect, etc., but it is suitable to use 0.5 to 12 parts by mass of malic acid (free acid) per 100 parts by mass of gelatin, preferably 1 to 8 parts by mass, and more preferably 2 to 6 parts by mass.

[0015] The capsule shell can be appropriately blended with a plasticizer to impart flexibility and elasticity, such as 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, and oligosaccharides. The blending ratio of such a plasticizer is, for example, 5 to 150 parts by mass, preferably 10 to 80 parts by mass, and more preferably 20 to 50 parts by mass, relative to 100 parts by mass 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 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 rich in omega-3 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 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] The 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 the 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 under heating (70 to 90°C, preferably around 80°C) to prepare a shell liquid (gelatin solution), which is then molded and dried.

[0028] Soft capsules include rotary die 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 soft capsules using a rotary die, a coating liquid is prepared from a coating composition and formed into a sheet. The sheet is then punched out by the rotation of two die rolls, and at the same time, the inner solution is enclosed and the coating is compressed by the die rolls to seal the capsule.

[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 adjusted appropriately depending on the components contained in the contents and the components contained in the capsule shell. For example, the drying temperature is about 15°C to 35°C, the humidity is about 10% RH to 50% RH, and the drying time is 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. [Example]

[0031] Example 1: Preparation of soft capsules <1> (1) Soft capsule A (soft capsule containing vitamin C) 1) Preparation of capsule coating solution The components shown in Table 1 were mixed in the prescribed proportions and stirred and dissolved while heating in a water bath at approximately 80°C to prepare gelatin solutions for coatings containing malic acid and coatings not containing malic acid.

[0032] [Table 1]

[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 below 40°C, 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] [Table 2]

[0035] 3) Manufacturing of soft capsules The gelatin solution prepared in 1) was degassed at 80°C and then allowed to stand for approximately 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 the gelatin sheet was adhered by applying heat of approximately 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 A.

[0036] (2) Soft capsule B (soft capsule containing mangosteen extract) 1) Preparation of capsule coating solution Gelatin solutions for coatings containing malic acid and coatings not containing malic acid 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 below 40°C, and mangosteen extract was added and stirred. The mixture was then wet-pulverized (using a colloid mill), sieved, and degassed to prepare the capsule contents.

[0037] [Table 3]

[0038] 3) Manufacturing of soft capsules 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 heat was applied to about 40°C with the segments to adhere the gelatin sheet. Just before punching, the capsule contents prepared in (2) were filled in with a pump, 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 prepared 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 contain malic acid in the coating, disintegrated within the 20 minutes required by the Japanese Pharmacopoeia standard when stored at 40°C and 3M. However, capsules without malic acid in the coating disintegrated after more than 20 minutes or became completely insoluble when stored at 40°C and 1M.

[0041] [Table 4]

[0042] Test Example 2: Gelatin film sheet dissolution test (1) Preparation of gelatin film sheets 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 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 (25°C) for 24 hours to prepare a gelatin film 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 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 approximately 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 Industry)," phytic acid was used as "50% aqueous solution of food additive phytic acid (Fuso Chemical Industry)," citric acid was used as "anhydrous citric acid," and gluconic acid was used as "gluconic acid solution (50% aqueous solution)."

[0044] [Table 5]

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

[0046] <Evaluation criteria> If the film is completely dissolved and no unwanted material is found: If the film pieces dissolve but a small amount of insoluble matter is found: ± If the film pieces dissolve but a small amount of insoluble film remains:+ If the film fragments dissolve but a moderate amount of insoluble film remains: ++ If the film pieces dissolve but a large amount of insoluble film is found: +++ Complete insolubilization of membrane fragments:++++

[0047] [Table 6]

[0048] Film sheet D containing gluconic acid and film sheet E containing succinic acid became insolubilized on the same day as the reference film, five 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 inhibitory effect, with film sheet A containing malic acid being the most effective.

[0049] Test Example 3: Decrease in viscosity of gelatin film 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. The resulting gelatin solution (viscosity adjusted to 20,000 mPa·s) is then vacuum-degassed and stored at 60°C for 4–10 hours. 2) The 60°C-heated gelatin shell solution is then fed into a capsule filling machine, where the contents are filled and molded. For this purpose, the gelatin solution is heated to 60°C for approximately 40 hours, from preparation to capsule filling and molding. However, it is known that the viscosity of gelatin solutions decreases over time when stored at 60°C. A decrease in viscosity from the initial value of 20,000 mPa·s to 14,000 mPa·s or less (70% or less of the initial value) reduces the strength of the gelatin shell, resulting in 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 may decrease the viscosity, so the following test was carried out to investigate this issue.

[0050] 1) Preparation of gelatin solution A 500 ml glass beaker was charged with 112 g of purified water, and 7 g of the weighed organic acid shown in Table 7 was dissolved by 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. After that, the gelatin solution was prepared by stirring and dissolving while heating in a water bath at approximately 80 °C. In Table 7, malic acid was "Malic Acid Fuso Type S (Fuso Chemical Industries)," tartaric acid was "L-Tartaric Acid S (Fuso Chemical Industries)," citric acid was "Anhydrous Citric Acid" (Iwata Chemical Industries), and succinic acid was "Succinic Acid (Fuso Chemical Industries)."

[0051] [Table 7]

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

[0053] [Table 8]

[0054] The viscosity of gelatin solution F containing malic acid decreased to 70% after 48 hours of storage at 60°C, but this was the same rate of viscosity decrease 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 decreased in viscosity by more than 30%, below 14,000 mPa·s, raising concerns about the impact on capsule molding and capsule strength.

[0055] Example 2: Preparation of soft capsules <2> (1) Soft capsule C (soft capsule containing mushroom extract) 1) Preparation of capsule coating solution The components shown in Table 9 were mixed in the prescribed proportions and stirred and dissolved while heating in a water bath at approximately 80°C to prepare gelatin solutions for coatings containing malic acid and coatings not containing malic acid.

[0056] [Table 9]

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

[0058] [Table 10]

[0059] 3) Manufacturing 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 both sides, and heat of about 40°C was applied with a segment to adhere the gelatin sheet. Just before punching, the capsule contents prepared in 2) were filled in with a pump, and the punched and molded product was dried to produce soft capsule C.

[0060] (2) Soft capsule D (soft capsule containing live bacteria) 1) Preparation of capsule coating solution Gelatin solutions for coatings containing malic acid and coatings not containing malic acid were prepared in the same manner as in (1) above.

[0061] [Table 11]

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

[0063] [Table 12]

[0064] 3) Manufacturing of soft capsules 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 heat was applied to about 40°C with the segments to adhere the gelatin sheet. Just before punching, the capsule contents prepared in (2) were filled in with a pump, and the punched and molded product was dried to produce soft capsule D.

[0065] (3) Soft capsule E (soft capsule containing amino acids) 1) Preparation of capsule coating solution Gelatin solutions for coatings containing malic acid and coatings not containing malic acid were prepared in the same manner as in (1) above.

[0066] [Table 13]

[0067] 2) Preparation of capsule contents The sunflower oil, beeswax, and emulsifier shown in Table 14 were heated and dissolved at approximately 70°C, then cooled to below 40°C, 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] [Table 14]

[0069] 3) Manufacturing of soft capsules 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 heat was applied to about 40°C with a segment to adhere the gelatin sheet. Just before punching, the capsule contents prepared in (2) were filled in with a pump, and the punched and molded product was dried to produce soft capsule E.

[0070] (4) Soft capsules F, G, and H (soft capsules containing bilberry and DHA) 1) Preparation of capsule coating solution Gelatin solutions for coatings containing malic acid and coatings not containing malic acid were prepared in the same manner as in (1) above.

[0071] [Table 15]

[0072] 2) Adjustment of capsule contents The DHA, beeswax, and emulsifier shown in Table 16 were dissolved by heating at approximately 70°C, then 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] [Table 16]

[0074] 3) Manufacturing of soft capsules 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 heated to about 40°C with a segment to adhere the gelatin sheet. Just before punching, the capsule contents prepared in 2) were filled with the capsule contents using a pump, and the punched and molded product was 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 (ERWEKA, automatic detection 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, which contain malic acid in the coating, all disintegrated within the 20 minutes required by the Japanese Pharmacopoeia standard when stored at 40°C and 3M. However, soft capsule I, which does not contain malic acid in the coating, disintegrated after more than 20 minutes or became completely insoluble when stored at 40°C and 2M.

[0077] [Table 17]

Claims

1. A method for inhibiting the delay in disintegration of gelatin-based capsules, comprising incorporating malic acid or a salt thereof into the capsule shell.

2. 2. The method according to claim 1, wherein the amount of malic acid or a salt thereof in the coating is 0.5 to 12 parts by mass per 100 parts by mass of gelatin.

3. The method according to claim 1 or 2, wherein the composition is a soft capsule.

4. The method according to any one of claims 1 to 3, wherein the capsule contains 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) fermented extracts, h) flavorings, i) minerals, j) amino acids, k) proteins or peptides, and l) microorganisms or metabolites thereof.

5. An inhibitor for retarding disintegration of gelatin-based capsules, the active ingredient of which is malic acid or a salt thereof.

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