JP4913340B2 - Capsule - Google Patents

Description

  The present invention relates to a capsule in which disintegration delay is prevented, a method for producing the capsule, and a capsule film.

  In the pharmaceutical and food fields, capsules, especially gelatin (hard and soft) capsules, are the most widely used dosage forms. This is because gelatin capsules have such advantages as (1) harmless to the human body and (2) rapid dissolution in the body. However, gelatin capsules have a problem in that decay delay occurs due to insolubilization of the gelatin film by heat denaturation and formation of a crosslinked structure of gelatin molecules by oxidation. In particular, when the filling content contains unsaturated fatty acids such as DHA and EPA, and oil components composed of fats and oils having unsaturated fatty acid residues, herbal medicines, etc., the gelatin film is insolubilized over time, and the formulation There was a problem that the collapse of the was significantly delayed. When such a disintegration delay occurs, the bioavailability of the drug decreases, so that the expected effect cannot be obtained sufficiently.

Several methods have been reported to solve such problems.
Examples of the method for preventing decay delay include a method for preventing insolubilization of gelatin by adding an amino acid or an organic acid to a gelatin film (Patent Documents 1 and 2), and a method for adding pullulan and a polypeptide to the gelatin film (Patent Document 3). ) Is disclosed. However, the collapse delay preventing effect by these methods is not fully satisfactory.
Also disclosed is a method (Patent Document 4) in which modified gelatin obtained by modifying the amino group of gelatin with an organic acid is used as a film. In this method, insolubilization can be improved to some extent, but the effect is not fully satisfactory. Further, this gelatin is inferior in film strength and more expensive than ordinary gelatin. Furthermore, this gelatin has a drawback that its use is limited to pharmaceuticals and it cannot be used for foods.
A method of adding an antioxidant such as tryptophan or tocopherol to the contents (Patent Document 5) has also been reported. However, the effect of preventing decay delay by this method is not fully satisfactory.
Japanese Patent Publication No.57-30088 JP 59-39834 A Japanese Patent Laid-Open No. 05-65222 Japanese Patent Publication No.57-4267 Japanese Patent Laid-Open No. 03-34921

  Accordingly, an object of the present invention is to provide a capsule, a method for producing the capsule, and a capsule film in which the collapse delay is more effectively prevented.

  As a result of intensive studies, the present inventors have effectively prevented the decay delay by blending the phospholipid and / or amino sugar and the organic acid into the capsule filling content and / or capsule film. As a result, the present invention has been completed.

That is, a first aspect of the present invention, the filling contents are viewed contains a lecithin, citric acid or a phytic acid, a further composed of fats with herbal, unsaturated fatty acids, unsaturated fatty acid residues one or more selected from the group consisting of oil and mushrooms is a capsule, characterized in containing Mukoto.

INDUSTRIAL APPLICABILITY According to the present invention, there are provided a capsule, a method for producing the capsule, and a capsule film in which disintegration is prevented.
Further, the capsule, the method for producing a capsule and the capsule film of the present invention can prevent disintegration delay and do not require a special production process, and thus can be widely applied from pharmaceuticals to foods. .

Hereinafter, the present invention will be described in more detail.
<< Capsule of the first aspect >>
The capsule of the first aspect of the present invention is characterized in that the filling content contains phospholipid and / or amino sugar and an organic acid.
The capsule referred to in the present invention indicates a soft capsule and a hard capsule.
Soft capsules include a main ingredient such as pharmaceuticals, or an additive such as an appropriate excipient added to the main ingredient, gelatin or a suitable capsule base listed in the Japanese Pharmacopoeia, such as glycerin or sorbitol Is encapsulated with a capsule base with increased plasticity and molded into a certain shape.
Hard capsules are suitable for capsules that are uniformly mixed with main ingredients such as pharmaceuticals or additives suitable for the main ingredients, or those that are granulated or granulated by an appropriate method. It is the one that has been coated with a coating agent and is filled in the capsule as it is or lightly molded.
The capsule of the present invention is preferably a soft capsule.

<Filled contents>
The phospholipid used in the present invention is not particularly limited, and phosphatidylserine, phosphatidylcholine (lecithin), phosphatidylinositol, phosphatidylethanolamine (kephalin), cardiolipin, phosphatidylglycerol, phosphatidic acid, lysophosphatidylcholine, sphingomyelin and derivatives thereof Etc. Among these, phosphatidylethanolamine and its derivatives are preferable because of the high effect of the present invention. The derivatives of phosphatidylethanolamine include diacyl phosphatidylethanolamine monoacyl type (lyso type), alkenyl type, acyl type, and N-methyl type and N, N-dimethyl type in which the base part is methylated. , N-acyl type and the like.
Moreover, soybean phospholipid (soy lecithin), egg yolk phospholipid (egg yolk lecithin) and the like are commercially available as phospholipid-containing products containing one or more of these phospholipids. Since the effect is also excellent, it is preferably used in the present invention. These may be purified products or crude products. Moreover, those hydrogenated substances etc. can also be used. Moreover, what powdered these may be used.
These phospholipids may be used alone or in combination of two or more.

Examples of amino sugars used in the present invention include sugars having amino groups such as glucosamine, N-acetylglucosamine, galactosamine, N-acetylgalactosamine, N-acetylneuraminic acid, chitosan which is a polymer of glucosamine, and derivatives thereof, poly Compounds having a structure in which a sugar hydroxyl group is substituted with an amino group, such as galactosamine and derivatives thereof, are included.
Examples of chitosan derivatives include chitosan oligosaccharides, deacetylated chitin, and the like, and both low molecular weight and high molecular weight are preferably used.

  In this embodiment, the phospholipid and / or amino sugar in the filling content is 0.005 to 20% by mass, preferably 0.01%, based on the total amount of the filling content, as the total amount of phospholipid and amino sugar. -20% by mass, more preferably 0.1-15% by mass, and still more preferably 0.5-10% by mass.

As the organic acid used in the present invention, a linear or cyclic organic acid having 12 or less carbon atoms, more preferably 1 to 10 carbon atoms, more preferably 2 to 8 carbon atoms, and still more preferably 3 to 6 carbon atoms. Can be mentioned. Examples of such organic acids include amino acids such as tryptophan, aspartic acid, glutamic acid, glycine, phenylalanine, arginine, and lysine, citric acid, succinic acid, fumaric acid, tartaric acid, lactic acid, malic acid, inositol phosphate derivatives, and Examples thereof include a mixture of these, and inositol phosphate derivatives and citric acid are particularly preferable.
The inositol phosphate derivative is a compound represented by the general formula C ₆ H _12-n (H ₂ PO ₄ ) _n (where n = 1 to 6), and includes inositol monophosphate (n = 1) and inositol. 2-phosphate (n = 2), inositol 3-phosphate (n = 3), inositol 4-phosphate (n = 4), inositol 5-phosphate (n = 5) and inositol 6-phosphate (n = 6, phytic acid) ). In the present invention, inositol 6-phosphate (phytic acid) is preferably used.
These organic acids are 0.05 to 20% by mass, preferably 0.1 to 15% by mass, more preferably 0.5 to 10% by mass, and still more preferably 1 to 10%, based on the total amount of the filled contents. It is desirable to be blended by mass%.

In addition to phospholipids and / or amino sugars and organic acids, the filling content of the capsules of this embodiment includes, as main ingredients, pharmaceuticals, quasi drugs, cosmetics, health foods, foods, beverages, seasonings, fragrances, herbal medicines. , Vitamins, and compositions thereof, may include materials that are generally blended into capsules.
Among these, the present invention is particularly effective when the main agent is a crude drug, an unsaturated fatty acid, an oil component composed of fats and oils having an unsaturated fatty acid residue, mushrooms, and compositions thereof.

Here, the herbal medicine as used in the present invention refers to raw materials for pharmaceuticals, cosmetics, etc. that are processed and prepared by cutting, crushing, and drying plants, animals, minerals, etc. as they are or without changing their properties. , Used for herbal medicine, folk medicine, spices, etc.
More specifically, as herbal medicines used in the present invention, Akamegashiwa, Asenyaku, Aloe, Ikarisou, Fennel, Ubai, Uyaku, Uwaurushi, Turmeric, Ages, Ezoukogi, Engosaku, Enmeiso, Ougi, Ogon, Ousei, Oubaku, Ouhi, Ouren, Onji, Kaikujin, Kaiba, Kashu, Gajutsu, Kakon, valerian, Guarana, licorice, Kyodo, Kiseki, Beef bile, Kyonin, Kokushi, Keigai, Keihi, Ketsumeishi, Gentiana, Gennoshoko, Koujin, Koubou, Gobo , Gosh, goshyu, garbage, psycho, saishin, saimu, salvia, sankirai, hawthorn, sanshishi, sanshuyu, salamander, sansonin, san yak, jiou, sibet, peonies, jachoushi Shazensou, Shukuyaku, Shukusha, Shokyo, Shozuk, Jotei, Ziryu, Shinyi, Senega, Senkyu, Zenko, Sembli, Sojutsu, Sakuhaku, Soyo, Daio, Taiso, Takusha, Chouji, Butterflyfish, Chinpi, Pepper, Ginger Tounin, Spruce, Tocon, Toshishi, Toshu, Nantenjitsu, Nambange, Nikujuyou, Garlic, Starfish, Hamaboufu, Hange, Hampi, Byakujutsu, Bukuryu, Bowie, Choshi, Chokoshi, Buttonpi, Hops, Maou, Mukoten Ryo, Mukunin Ryo , Ryugannik, Ryutan, Rotokon, Rokujo, Blueberry, Bilberry, Echinacea, Chrysanthemum, Young Wheat, Kouka, Salacia, Rosemary, Ginseng, ginseng (Ginseng, ginseng, etc.), mugwort, green tea, herbs (eg ginkgo biloba, St. John's wort, chamomile, hippopotamus, saw palmetto, Salacia oblonga, garcinia, rosemary, citrus, citrus periwinkle) Herbal powders such as chondroitin, glucosamine, collagen, extracts, fluid extracts or tinctures, extracts from organs such as animal liver, heart or placenta, or hydrolysis produced using acids, bases or enzymes Animal and plant extracts such as foods, cereals, plants, marine products fermented with koji mold, koji mold, lactic acid bacteria, acetic acid bacteria, natto bacteria, yeast, etc., moromi vinegar, propolis, or combinations of these herbal medicines Herbal medicine, specifically Kakkonto (Kakkon, Taisou, Peonies, Shokyo) , Maou, Keihi, Licorice), Toki remedy (Toki, Senkyo, Peonies, Bukuryu, Soujutsu, Takusha), Hachimi-jio Huang (Ziou, Sanyaku, Bukkyou, Keihi, Sanshuyu, Takusha, Buttonpi, Tsuji), Small blue dragon Hot water (Maou, Syoukyo, Keihi, Goshi, Peonies, Licorice, Saishin, Hange), Mumon Fuyuto (Bakumondou, Koubay, Carrot, Hange, Taiso, Licorice), Kamizo Harukasan (Toki, Sojitsu, Psycho, Sanshi, And the like. Among these, moromi vinegar, garlic, propolis, carrots, rosemary, citrus, citrus periwinkle, blueberry, bilberry, kakkonto, and the like are preferable.

As unsaturated fatty acid used by this invention, C14 or more, More preferably, C14-C22 long-chain unsaturated fatty acid is mentioned. Examples of long-chain unsaturated fatty acids having 14 or more carbon atoms include DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), linoleic acid, arachidonic acid, linolenic acid, oleic acid, pinolenic acid, cyanidic acid, juniperonic acid, and columbic acid. Conjugated linoleic acid, eleostearic acid, octadecenoic acid, octadecadienoic acid, docosenoic acid, ricinoleic acid, alpha-linolenic acid, gamma-linolenic acid, behenic acid and the like, and DHA and EPA are particularly preferable.
Examples of unsaturated fatty acids include unsaturated fatty acids in which DHA, EPA, etc. and phospholipids are combined, such as PC-DHA in which DHA is combined with phosphatidylcholine (PC), PS-DHA in which phosphatidylserine (PS) is combined. It is done.

Moreover, the oil component comprised by the fats and oils which have an unsaturated fatty acid residue means the fats and oils or the mixture of such fats and oils in which at least one of the fatty acid residues which comprise the fats and oils is an unsaturated fatty acid residue. In addition, in this invention, as fats and oils which comprise this oil component, the fats and oils which do not have an unsaturated fatty acid residue other than the fats and oils which have an unsaturated fatty acid residue may be contained.
Examples of oils composed of oils and fats having such unsaturated fatty acid residues include vegetable oils (soybean oil, rapeseed oil, rice bran oil, cottonseed oil, sesame oil, sunflower oil, mustard oil, safflower oil, corn oil, etc. Peanut oil, olive oil, palm oil, coconut oil, etc.) and animal fats (fish oil, whale oil, beef tallow, pork fat, milk fat, etc.). Among these, fish oil is preferable.

  Examples of the mushrooms used in the present invention include Agaricus, Meshimakobu, Mannentake, Enokitake, Suehirotake, Shiitake, Maitake, Chaga (Babaanatake), Mushroom, Hatake-Shimeji, Kawaratake, Chahiratake, Fusarium natto The substance obtained by drying and pulverizing the substance as it is, the extract and extract powder obtained by extracting mushrooms with hot water (which may contain moderately ethanol), and further inoculating mushrooms on grains, bagasse, etc. Examples thereof include an extract and an extract powder obtained by concentrating and drying the obtained solid culture or its hot water extract. In particular, agaricus, medmacob, shiitake, ganoderma and its extract and extract powder are preferred.

  The filled contents of the capsule of the present invention include additives usually used in pharmaceuticals and foods, such as excipients, binders, disintegrants, stabilizers, dispersants, colorants, flavoring agents, and large additives. Surfactant such as vegetable oil such as bean oil, corn oil, olive oil, long chain unsaturated fatty acid such as linoleic acid, oleic acid, medium chain fatty acid monoglyceride, medium chain fatty acid triglyceride, polyethylene glycols, glycerin fatty acid esters, vitamin E, Antioxidants such as astaxanthin and catechin can be arbitrarily blended.

  The capsule of the first aspect can be produced by a generally known method, for example, by the production method of the second aspect described below.

<< Production Method of Second Aspect >>
In the production method of the second aspect, a filling content containing a phospholipid and / or amino sugar and an organic acid is made into a liquid, suspension, paste, powder or granule, and the filling content is converted into a capsule. Or is encapsulated with a capsule film.

As capsules, commercially available capsules can be used. Moreover, you may shape | mold using the following capsule membranes.
As the capsule film, generally known materials are used, and examples thereof include gelatin and the like mentioned in the third embodiment to be described later. A colorant, a preservative, and the like can be added to the capsule film as necessary.

  If an example of the manufacture example of a capsule is given, for example, as an example which encapsulates a filling content with a capsule film, 20-40 mass parts of glycerol or sorbitol and 90 mass parts of water are added to 100 mass parts of gelatin, for example. Heat to 80 ° C., dissolve with stirring to prepare a gelatin solution, add 1 to 5 parts by mass of a dye or titanium oxide for the purpose of further coloring, if necessary, and then use a rotary soft capsule filling machine. The prepared gelatin solution is cooled to a thin film having a thickness of 0.8 to 0.9 mm, and a gelatin sheet is prepared. The gelatin sheet is passed through a roll mold from the left and right and filled with a pump immediately before punching. A soft capsule can be produced by punching the gelatin sheet sprayed with the above solution onto the surface and drying it.

<< capsule film of the third aspect >>
The capsule film of the third aspect of the present invention is characterized in that it contains gelatin, phospholipid and / or amino sugar, and an organic acid.

Examples of the gelatin used for the capsule film include acid-treated gelatin, chemically modified gelatin, amphoteric treated gelatin, and alkali-treated gelatin, but can be used without particular limitation. Among these, acid-treated gelatin and alkali-treated gelatin are preferable.
Here, acid-treated gelatin refers to gelatin obtained by hydrolyzing and extracting collagen with an acid such as hydrochloric acid or sulfuric acid, and chemically modified gelatin refers to reacting the amino group of gelatin with succinic acid or phthalic acid. The alkali-treated gelatin refers to the gelatin obtained by hydrolyzing and extracting collagen with alkali such as lime, and the amphoteric-treated gelatin is extracted by treating the collagen with acid and alkali. Refers to the gelatin obtained.

As the phospholipid and amino sugar, those similar to the phospholipid and amino acid mentioned in the first embodiment can be used.
The blending amount of phospholipid and / or amino sugar in the capsule film is 0.005 to 10% by mass, preferably 0.01 to 10% by mass, more preferably, based on gelatin as the total amount of phospholipid and amino sugar. Is preferably 0.5 to 10% by mass, more preferably 2 to 5% by mass.

As the organic acid, the same organic acids as mentioned in the first embodiment can be used.
The compounding amount of the organic acid in the capsule film is preferably 0.05 to 10% by mass, more preferably 1 to 10% by mass, and further preferably 2 to 5% by mass with respect to gelatin.

  A colorant, a preservative, and the like can be added to the capsule film as necessary.

  The capsule film can be produced by a generally known method, for example, 100 parts by weight of gelatin, 0.005 to 10 parts by weight of phospholipid and / or amino sugar, and 0.05 to 10 parts by weight of organic acid in water. Dissolve. At this time, heat may be applied, and a plasticizer, preservative, amino acid and the like may be added as necessary. The obtained capsule film can be obtained by, for example, drying the obtained solution to a moisture content of 5 to 20%, preferably 7 to 15%.

<< Capsule of Fourth Embodiment >>
The capsule of the fourth aspect of the present invention is characterized in that the capsule film is composed of the capsule film of the third aspect.

In the capsule of this aspect, the filling content filled in the capsule film is not particularly limited, and those listed as the filling content in the first aspect can be used.
In this embodiment, the filling contents do not necessarily include phospholipids and / or amino sugars and organic acids, but the filling contents include phospholipids and / or amino sugars and organic acids. Also good.

  The capsule of the fourth aspect can be produced by a generally known method, for example, by the production method of the following fifth aspect.

<< Production Method of Fifth Aspect >>
According to a fifth aspect of the manufacturing method, the filling content is liquid, suspension, paste, powder or granule, and the filling content is gelatin, phospholipid and / or amino sugar, and organic acid. It is characterized by filling a capsule molded with a capsule film containing or encapsulating with a capsule film.
In this aspect, if an example of the manufacture example of a capsule is given, it can be manufactured by the same procedure as the said 2nd aspect, for example, glycerin or sorbitol 20-40 mass parts, phospholipid, / Or 0.005-10 parts by weight of an amino sugar, 0.05-10 parts by weight of an organic acid and 100 parts by weight of water are added, heated to 80 ° C., stirred and dissolved to prepare a gelatin solution, and if necessary Further, after adding 1 to 5 parts by mass of a pigment or titanium oxide for the purpose of coloring, the prepared gelatin solution is cooled to a thin film having a thickness of 0.8 to 0.9 mm using a rotary soft capsule filling machine. A gelatin sheet is prepared by the following procedure, the gelatin sheet is passed through a roll mold from the left and right, and the gelatin sheet is sprayed onto the surface with a solution of the filling content by a pump immediately before punching. And the mold, it is possible to produce a soft capsule by drying.
The hard capsule is prepared by, for example, dissolving gelatin powder in warm water at 70 ° C. while stirring to prepare a 30% by weight solution of gelatin. In this solution, 4% by weight of organic acid, 1% by weight of gelatin % Phospholipid and / or amino sugar is added to prepare a gelatin mixed solution, then a hard capsule is produced by a conventional method such as a dipping method, and the hard capsule is filled with a filling content.

  EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these.

Comparative Examples 1-5, Examples 1-6
(1) Preparation of filled contents Each component shown in Table 1 was stirred with a homogenizer (10000 rpm, 5 minutes) until uniform, and liquid (solution or suspension) filled contents (M-1) to (M-11) was prepared.
In Table 1,% is mass%, and phytic acid is inositol 6-phosphate.

(2) Manufacture of capsules After dissolving and defoaming a gelatin solution consisting of 45% by weight gelatin, 15% by weight glycerin and 40% by weight water at 80 ° C., the mixture was allowed to stand for about 10 hours, and a rotary soft capsule filling machine (Oval 6 type) was used to prepare a capsule film, and 360 mg of each of the filling contents (M-1) to (M-11) prepared in (1) was filled. After filling, the capsule film was dried to a film moisture of 8% at a temperature of 27 ° C. and a humidity of 50% or less to produce a soft capsule.
The soft capsules of filling contents (M-1) to (M-5) are Comparative Examples 1 to 5, respectively, and the soft capsules of filling contents (M-6) to (M-11) are Examples 1 to 5, respectively. 6.

Test Example 1 [Evaluation of Insolubilization Inhibition Effect of Gelatin Film]
After adding 100 g of gelatin and 35 g of glycerin to 100 g of purified water to swell with water absorption, the mixture was stirred and dissolved at about 80 ° C. and degassed under reduced pressure.
This gelatin solution was poured into a TLC plate, spread uniformly to a thickness of about 1 mm, and dried at 30 ° C. for 24 hours to obtain a gelatin-coated sheet having a water content of about 9%.
Next, 10 g of each of the filling contents (M-1) to (M-11) prepared in (1) of Comparative Examples 1 to 5 and Examples 1 to 6 was taken into a screw tube (capacity 15 mL), A small piece (1 × 1 cm) of the gelatin-coated sheet prepared above was immersed and stored at 50 ° C.
After taking out the gelatin-coated sheet piece over time and wiping off the adhering filling contents, it was placed in 200 ml of warm water at 60 ° C., stirred for 2 minutes with a stirrer, and then allowed to stand to visually check for insoluble matters. The insolubilization inhibitory effect was evaluated by doing. The results are shown in Table 2.
In addition, the insolubilization inhibitory effect was evaluated in the following six stages.
When the gelatin film piece is completely dissolved and no insoluble matter is observed: (-)
Gelatin film piece dissolves but slight insoluble matter is found: (±)
Gelatin film piece dissolves, but a small amount of insoluble film is observed: (+)
Gelatin film piece dissolves but moderate insoluble film is observed: (++)
Gelatin film piece dissolves but a large amount of insoluble film is found: (++++)
When gelatin film pieces do not dissolve at all and become completely insoluble: (++++)
In addition, this test is a severe test performed under storage at 50 ° C., and evaluates the insolubilization phenomenon due to the effect of the filling content of the gelatin film of the soft capsule in storage at room temperature (25 ° C.). The difference of several days required for insolubilization obtained in this test reflects the long-term room temperature storage conditions.

  From the above results, formation of an insoluble film was remarkably suppressed in the filling contents (M-6) to (M11) in which soybean lecithin and citric acid or phytic acid were added to the ganoderma extract mixture.

Comparative Example 6 and Example 7
Gelatin solution consisting of 45% by weight of gelatin, 15% by weight of glycerin and 40% by weight of water was dissolved at 80 ° C., defoamed, and allowed to stand for about 10 hours, then capsules using a rotary soft capsule filling machine (Oval type 6) A film was prepared, and 360 mg of each of the filling contents (A-1) or (A-2) having the formulation shown in Table 3 was filled. After filling, the capsule film was dried to a film moisture of 8% at a temperature of 27 ° C. and a humidity of 50% or less to produce a soft capsule.
In Table 3,% is mass%, and phytic acid is inositol 6-phosphate.
The soft capsule of the filling content (A-1) is Comparative Example 6, and the soft capsule of the filling content (A-2) is Example 7.

Test Example 2 [Confirmation of insolubilization inhibitory effect of soft capsule]
The soft capsules obtained in Comparative Example 6 and Example 7 were each placed in a glass bottle, sealed with a metal cap (packing with a rubber liner), and stored at 40 ° C. and 75% humidity for 1 week to compare disintegration times. The disintegration time was measured using a disintegration tester. The results are shown in Table 4.

  From the above results, remarkable insolubilization of the film was confirmed in (A-1), but good solubility was shown in (A-2).

Comparative Examples 7-8, Examples 8-10
(1) Preparation of Filling Contents Each component shown in Table 5 was stirred with a homogenizer (10000 rpm, 5 minutes) until uniform, and liquid (solution or suspension) filling contents (S-1) to (S-5) was prepared.

(2) Manufacture of capsules After dissolving and defoaming a gelatin solution consisting of 45% by weight gelatin, 15% by weight glycerin and 40% by weight water at 80 ° C., the mixture was allowed to stand for about 10 hours, and a rotary soft capsule filling machine (Oval 6 type) was used to prepare a capsule film, and 360 mg of each of the filling contents (S-1) to (S-5) prepared in (1) above was filled. After filling, the capsule film was dried to a film moisture of 8% at a temperature of 27 ° C. and a humidity of 50% or less to produce a soft capsule.
The soft capsules of the filling contents (S-1) to (S-2) are Comparative Examples 7 to 8, respectively, and the soft capsules of the filling contents (S-3) to (S-5) are Examples 8 to 8, respectively. 10.

Test Example 3 [Evaluation of Insolubilization Inhibition Effect of Gelatin Film]
After adding 100 g of gelatin and 35 g of glycerin to 100 g of purified water to swell with water absorption, the mixture was stirred and dissolved at about 80 ° C. and degassed under reduced pressure. This gelatin solution was poured into a TLC plate, spread uniformly to a thickness of about 1 mm, and dried at 30 ° C. for 24 hours to obtain a gelatin-coated sheet having a water content of about 9%.
Take 10 g of each of the filled contents of (S-1) to (S-5) prepared in (1) of Comparative Examples 7 to 8 and Examples 8 to 10 in a screw tube (capacity 15 mL), A small piece (1 × 1 cm) of the gelatin-coated sheet prepared above was immersed and stored at 50 ° C. After taking out the gelatin-coated sheet piece over time and wiping off the adhering filling contents, it was placed in 200 ml of warm water at 60 ° C., stirred for 2 minutes with a stirrer, and then allowed to stand to visually check for insoluble matters. The insolubilization inhibitory effect was evaluated by doing. The results are shown in Table 6. In addition, the insolubilization inhibitory effect was evaluated in 6 steps as in Test Example 1.

  From the above results, formation of an insoluble film was remarkably suppressed in the filling contents (S-3) to (S-5) in which soybean lecithin and phytic acid were added to DHA.

Production Examples 1 to 10 [Production of capsule film]
To 100 g of purified water, 100 g of gelatin, 3 g of soybean lecithin as phospholipid and / or amino sugar, 5 g of phytic acid as organic acid, and 35 g of glycerin were added and swollen with water absorption, and stirred and dissolved at about 80 ° C. under reduced pressure. Defoamed. This gelatin solution was poured into a TLC plate, spread uniformly to a thickness of about 1 mm, and dried at 30 ° C. for 24 hours to obtain a soft capsule film (B-1).
Further, except that the phospholipid and / or amino sugar and the organic acid are those shown in Table 7, and the additives shown in Table 7 are further added, the same as above, the soft capsule film (B-2) to ( B-10) was obtained. However, in each formulation, the total amount of phospholipid and amino sugar was 3 g, and the amount of organic acid was 5 g.
In Table 7, the numbers in parentheses in the phospholipid / amino sugar indicate the ratio (mass ratio) of the blending amounts.

Examples 11-20
A gelatin solution prepared in the same manner as in Production Examples 1 to 10 was allowed to stand for about 10 hours, and a capsule film was prepared using a rotary soft capsule filling machine (Oval 6 type). 360 mg of the filling content (M-2) prepared in (1) of Example 2 above was filled. After filling, the capsule film was dried to a film moisture of 8% at a temperature of 27 ° C. and a humidity of 50% or less to produce a soft capsule.
The soft capsules of formulas (B-1) to (B-10) are Examples 11 to 20, respectively.

Examples 21-25
A gelatin solution consisting of 45% by weight of gelatin, 15% by weight of glycerin and 40% by weight of water was dissolved at 80 ° C., defoamed, and allowed to stand for about 10 hours, using a rotary soft capsule filling machine (Oval type 6). A capsule film was prepared, and 360 mg each of the filling contents of the formulations (C-1) to (C-5) shown in Table 8 was filled in the capsule film. After filling, the capsule film was dried to a film moisture of 8% at a temperature of 27 ° C. and a humidity of 50% or less to produce a soft capsule.
In Table 8, the numbers in parentheses in various crude drug extracts indicate the ratio (mass ratio) of the blending amounts.
The soft capsules of the filling contents of the formulations (C-1) to (C-5) are Examples 21 to 25, respectively.

Claims (5)

Filling contents is seen containing a lecithin, citric acid or a phytic acid, a further selected herbal, unsaturated fatty acids, from the group consisting of consisting oil and mushrooms in oil with unsaturated fatty acid residues capsules, characterized in including Mukoto the one or more kinds. The filling content further includes at least one selected from the group consisting of moromi vinegar, garlic, propolis, carrots, rosemary, citrus, cinnamon perilla, blueberry, bilberry, kakkonto, DHA, EPA, and mushrooms. The capsule according to claim 1, wherein The capsule according to claim 1 or 2 , wherein lecithin is contained in an amount of 0.005 to 20% by mass based on the total amount of the filled contents. The capsule according to any one of claims 1 to 3 , wherein citric acid or phytic acid is contained in an amount of 0.05 to 20% by mass based on the total amount of the filled contents. It is a soft capsule, The capsule as described in any one of Claims 1-4 characterized by the above-mentioned.