JP2014015431A - Soft capsule coating and soft capsule - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a novel soft capsule coating which contains no gelatine, is enteric, and can be formed by a rotary die method, and to provide a soft capsule comprising the soft capsule coating.SOLUTION: The soft capsule coating contains a cyclic structure, formed by a glycosidic linkage, in a molecule. A non-cyclic glucan chain containing a branch glucan chain formed by α-1,4 glycosidic linkage and α-1,6 glycosidic linkage bonds to the cyclic structure. Further, the soft capsule coating contains branched cyclic dextrin of which the weight average degree of polymerization is 2000 to 3000 and the number of glucoses constituting the cyclic structure is 16 to 100, iota-carrageenan, and alginate, and does not contain gelatine. A soft capsule is obtained by filling content into the soft capsule coating.

Description

  The present invention relates to a soft capsule film that does not use gelatin and a soft capsule including the soft capsule film.

  Gelatin is a unique substance that combines excellent film-forming ability and reversible sol-gel change with temperature change (gelation ability), and is widely used as a film base for general soft capsules. Yes. In particular, the production of soft capsules using a rotary die requires that the film has a heat-sealing property, so gelatin that changes sol and gel at a temperature close to room temperature is extremely useful as a film forming agent for soft capsules using a rotary die. It is. On the other hand, for the purpose of mad cow disease (bovine spongiform encephalopathy) countermeasures and religious reasons, it is also required to form a soft capsule film from plant-derived raw materials without using gelatin.

  Therefore, various techniques have been proposed for forming a plant-derived soft capsule film that can be substituted for gelatin by burdening different substances with film-forming ability and gelation ability. In the past, the present applicant also used a hydroxypropylated dextrin and oxidized starch as a film-forming agent, a technique for forming a soft capsule film using at least one of processed algae algae and farcellulan as a gelling agent (see Patent Document 1), and A technique for forming a soft capsule film using a modified starch of glutinous corn starch as a film forming agent and iota carrageenan as a gelling agent (see Patent Document 2) is proposed.

  On the other hand, soft capsules may contain components that lose their efficacy due to stomach acid or components that irritate stomach tissue. In such cases, the soft capsule film does not disintegrate or dissolve in the stomach without being dissolved or dissolved in the stomach. It is necessary to impart the property of disintegrating or dissolving (enteric properties) after reaching the point. Conventionally, soft capsule films to which enteric properties are imparted include those in which an outer surface of a formed gelatin film is coated with an enteric substance such as zein or shellac. In addition, a polysaccharide that gels with polyvalent metal ions and exhibits acid resistance is contained in a soft capsule film mainly composed of gelatin, and the formed soft capsule film is immersed in an aqueous solution containing polyvalent metal ions. A technique for forming an acid-resistant outer skin by the use of the above, or a non-water-soluble salt of a polyvalent metal ion (slightly water-soluble salt) is previously contained in a soft capsule film, and the polyvalent metal ion is dissociated in gastric acid to form a polysaccharide. There has been proposed a technique for causing a gelation reaction. However, the soft capsule film according to these proposals has a problem that a transparent and glossy appearance is impaired, and a rotary die type molding cannot be performed due to a decrease in heat sealability.

  On the other hand, the present applicant has proposed a technique in which a low amount of low methoxyl pectin having a degree of esterification in a predetermined range is contained in gelatin in a predetermined amount and a soft capsule film is formed by a rotary die method (Patent Document 3). ). According to this, a soft capsule film having a transparent and glossy appearance and excellent enteric properties can be produced by a rotary die type having a high degree of freedom in shape and size.

  However, the above enteric soft capsule film uses gelatin as a film forming agent. Therefore, there has been a demand for an enteric soft capsule film that does not use gelatin and a soft capsule provided with such a soft capsule film.

  Therefore, the present inventors have proposed the above-described technique, that is, a technique for producing a non-gelatin soft capsule film derived from a plant using starch as a film forming agent and carrageenan as a gelling agent (Patent Document 2), And it tried to give entericity to the soft capsule film | membrane made from a plant and a non-gelatin by applying the technique (patent document 3) which provides enteric property to a soft capsule film | membrane by pectin. However, although we studied diligently under various conditions, the characteristics of the capsule film solution (castability, etc.), the stock solution of the soft capsule film, the moldability of the capsule film (heat sealability, etc.) by the rotary die method, enteric properties In any case, satisfactory soft capsules could not be obtained.

  In addition, a conventional technique for imparting enteric properties to a gelatin film by coating an enteric substance such as zein is applied to a plant-derived non-gelatin soft capsule film proposed by the present inventors (Patent Document 2). I also tried that. However, although the actual amount of coating of zein was variously studied, it was difficult to impart sufficient gastric juice resistance to the non-gelatin soft capsule film by zein.

  For this reason, the present inventors have come to consider solving the above-mentioned problem by a completely different means, not on the extension of the prior art.

  Therefore, in view of the above circumstances, the present invention provides a novel soft capsule film that does not contain gelatin and is enteric and can be molded by a rotary die type, and a soft capsule including the soft capsule film. It is to be an issue.

  In order to solve the above-mentioned problems, the soft capsule film according to the present invention is a "soft capsule film having a seam formed by being molded by a rotary die molding apparatus, and having an annular structure formed by glycosidic bonds. A non-cyclic glucan chain having one in the molecule and including a branched glucan chain formed by an α-1,4 glycoside bond and an α-1,6 glucoside bond is bonded to the cyclic structure, and has a weight average It contains a branched cyclic dextrin having a degree of polymerization of 2000 to 3000 and 16 to 100 glucose constituting the cyclic structure part, iota carrageenan, and alginate, and no gelatin ”.

  “The acyclic glucan chain having one cyclic structure part formed by glycosidic bonds and containing branched glucan chains formed by α-1,4 glycosidic bonds and α-1,6 glucosidic bonds is described above. A branched cyclic dextrin having a weight average polymerization degree of 2000 to 3000 and 16 to 100 glucose constituting the cyclic structure (hereinafter simply referred to as “branched cyclic dextrin”). Is a dextrin obtained by allowing a branching enzyme (branching enzyme) to act on starch. The “cyclic structure part formed by glycosidic bonds” includes a cyclic structure part formed by α-1,4 glycosidic bonds and α-1,6 glucoside bonds. In addition, the “acyclic glucan chain” bonded to the cyclic structure includes an α-1,4 glycoside in addition to a branched glucan chain formed by an α-1,4 glycoside bond and an α-1,6 glucoside bond. Linear glucan chains formed from bonds can be included.

  As the branched cyclic dextrin having the above-described structure, a commercially available branched cyclic dextrin (cluster dextrin (manufactured by Glico Nutrition Foods Co., Ltd.)) manufactured using glutinous corn starch as a raw material and using a branching enzyme derived from Bacillus stearothermophilus ) Can be used.

  As the “alginate”, sodium alginate, potassium alginate, ammonium alginate and the like can be used.

  As a result of the study, the present inventors have studied that the branched cyclic dextrin having the above-described structure is a film-forming agent and contains iota carrageenan and alginate, so that the capsule film can be cast and the capsule film can be formed using a rotary die. And a soft capsule film having enteric properties is obtained, and the present invention has been achieved. Therefore, according to the present invention, it is possible to provide a novel soft capsule film that is manufactured from a raw material not containing gelatin, has enteric properties, and can be molded by a rotary die method.

  Further, in the present invention, in order to impart enteric properties, unlike the prior art, it is not necessary to coat any material on the surface of the soft capsule film. In addition, unlike the conventional technology in which polysaccharides are gelled with polyvalent metal ions to impart acid resistance, the molded soft capsule film is immersed in a solution containing polyvalent metal ions, or the polyvalent metal ions are added to the soft capsule film. It is not necessary to contain a water-insoluble salt. Therefore, the soft capsule film of the present invention exhibits a transparent and glossy appearance. This is a very significant advantage since soft capsules have a high market value for a transparent and glossy appearance. Further, the soft capsule film of the present invention has an advantage that it can be produced very easily without requiring a coating process or a dipping process.

  Furthermore, since the soft capsule film of the present invention can be formed by a rotary die type, heat sealability is not required, but unlike a soft capsule film formed by a dropping method limited to a small-diameter true spherical shape, There is an advantage that the degree of freedom in size is high.

  The soft capsule film according to the present invention has, in addition to the above-described structure, “32 to 36 parts by weight of iota carrageenan with respect to 100 parts by weight of the branched cyclic dextrin, the alginate is sodium alginate, and 100 weights of iota carrageenan. 42.5 parts by weight to 50 parts by weight of sodium alginate ".

  By adopting such a composition, as described later, the capsule film liquid is excellent in castability, and a soft capsule film sufficiently sealed by heat sealing can be molded with excellent moldability and molded. The soft capsule film has excellent enteric properties.

  Next, the soft capsule according to the present invention is “a soft capsule in which the content of the soft capsule film described above is filled”.

  The “content” is not particularly limited, and a substance obtained by dissolving or suspending a target substance such as a pharmaceutical ingredient, a health food ingredient, or a nutritional supplement in an oil or oily substance, or the above target substance itself. That is oily or pasty can be used.

  According to the present invention, it is possible to provide a soft capsule that is easy to be accepted by consumers by not containing gelatin in the soft capsule film and that has excellent enteric properties.

  As described above, as an effect of the present invention, it is possible to provide a novel soft capsule film that does not contain gelatin and is enteric and can be molded by a rotary die type, and a soft capsule including the soft capsule film. it can.

  Hereinafter, a soft capsule film that is an embodiment of the present invention and a soft capsule including the soft capsule film will be described.

  The soft capsule film of the present embodiment is a soft capsule film having a seam formed by being molded by a rotary die type molding apparatus, and has one cyclic structure portion formed by glycosidic bonds in the molecule, and α A non-cyclic glucan chain including a branched glucan chain formed by a -1,4 glycoside bond and an α-1,6 glucoside bond is bonded to the cyclic structure part, and the weight average degree of polymerization is 2000 to 3000, It contains a branched cyclic dextrin having 16 to 100 glucose constituting the cyclic structure, iota carrageenan, and alginate, and does not contain gelatin.

  Further, when sodium alginate is used as the alginate, 32 to 36 parts by weight of iota carrageenan is contained with respect to 100 parts by weight of the branched cyclic dextrin, and 42.5 to 50 parts by weight with respect to 100 parts by weight of iota carrageenan. Contains parts by weight of sodium alginate.

  Such a soft capsule film and a soft capsule comprising the soft capsule film are prepared by dissolving a branched cyclic dextrin, iota carrageenan, and alginate together with a plasticizer in water to prepare a capsule film solution. It can be obtained by molding using a type molding apparatus. As the plasticizer, glycerin, sorbitol, maltitol, polyethylene glycol and the like can be used alone or in combination.

  In general, a rotary die type molding apparatus is composed of a casting drum for forming a capsule coating liquid into a film, a pair of die rolls having a molding mold formed on the outer surface, and a wedge for filling contents placed between the die rolls. And a pump that presses the content into the segment and pushes the content from the tip of the segment.

  In the molding process, first, the capsule coating liquid is cast on the surface of the casting drum and gelled to form a film. Next, two of the formed films are fed along a segment between a pair of die rolls. Then, with the rotation of the pair of die rolls in opposite directions, when the two capsules are heat sealed to form a soft capsule film opened upward, the contents extruded from the segments are filled therein. . At the same time, the two films are heat-sealed at the top to form a soft capsule filled with the contents in a closed internal space.

  In addition, the obtained soft capsule can be dried in a humidity control dryer until a predetermined moisture content is obtained.

  Next, the reason why the soft capsule film of this embodiment is the above composition will be described. First, the examination result about the kind of film forming agent is shown. The following four types of film forming agents were used as film forming agents, and as shown in Table 1, sample S1 containing 32 parts by weight of iota carrageenan and 16 parts by weight of sodium alginate with respect to 100 parts by weight of film forming agent. A soft capsule film of ~ S4 was formed. The capsule film solution, which is a stock solution of the soft capsule film, was prepared by dissolving 60 parts by weight of glycerin in 100 parts by weight of the film forming agent in water together with the film forming agent having the above composition, iota carrageenan, and sodium alginate. . The prepared capsule film solution was molded with a rotary die molding apparatus and filled with vegetable oil as the contents to obtain soft capsules.

<Types of film forming agent>
Sample S1: An acyclic glucan chain having one cyclic structure portion formed by glycosidic bonds in the molecule and including branched glucan chains formed by α-1,4 glycosidic bonds and α-1,6 glucoside bonds Is bonded to the cyclic structure, the weight average degree of polymerization is 2000 to 3000, and the cyclic structure dextrin sample S2 is a glutinous corn starch having a molecular weight of about 2 million)
Sample S3: Pea starch sample S4: dextrin different from sample S1 (molecular weight about 20,000, DE value 10 or less)

  Here, as the branched cyclic dextrin which is the film forming agent of the sample S1, highly branched cyclic dextrin “Cluster Dextrin” (registered trademark) manufactured by Glico Nutrition Foods Co., Ltd. was used. Sample S2 is starch whose viscosity is reduced by heat-treating glutinous corn starch, and sample S3 is starch whose viscosity is reduced by acetyl oxide treatment of pea starch. It is.

<Evaluation of castability>
Whether or not a film having a uniform thickness can be formed by casting as to whether or not the capsule coating liquid, which is a stock solution of the soft capsule film of samples S1 to S4, exhibits castability suitable for film formation in rotary die molding. In addition, “○” (good) was evaluated as having practical castability, and “x” was evaluated otherwise. The evaluation results are shown in Table 1.

  In addition, the molded soft capsule film was subjected to a disintegration test for evaluation of moldability and enteric evaluation by the following methods. The results are also shown in Table 1.

<Evaluation of formability>
Whether the film formed by the rotary die method is easy to handle after molding, such as no stickiness, in the macroscopic observation of the molded soft capsule film, it is sufficiently sealed by heat sealing, and the contents leak out It was judged whether there was no deformation such as crushing, etc., and “◯” (good) was evaluated when it was judged to be normal comprehensively, and “x” (bad) when it was not.

<Disintegration test>
The disintegration test was performed using the first liquid and the second liquid in accordance with the disintegration test method defined in the Japanese Pharmacopoeia. Here, the first solution is a test solution having a pH of 1.2 for evaluating gastric juice resistance, and the soft capsule is moved up and down in the test solution for 120 minutes, and in the subsequent observation, the soft capsule film remains and the content remains. If it is not leaking and does not crush when pressed with a finger, "○", the soft capsule film remains, but if the contents are leaking, it is crushed when pressed with a finger, or the soft capsule film does not remain Cases are indicated by “×”. The second solution is a test solution having a pH of 6.8 for evaluating the resistance to intestinal fluid. The soft capsule is moved up and down in the test solution for 60 minutes, and in the subsequent observation, the soft capsule film does not remain, or the soft capsule The case where the film remains but the contents are leaked is indicated by “◯”, and the case where the soft capsule film remains and the contents are not leaked is indicated by “X”. Therefore, it can be judged that it is excellent as an enteric soft capsule film when both the first liquid and the second liquid are “◯”.

  As shown in Table 1, all of the samples S1 to S4 had good castability in the rotary die molding. Regarding moldability, sample S4 using a dextrin different from sample S1 had poor stickiness after molding and was poor. When samples S1 to S3 having good moldability were subjected to a disintegration test for evaluating enteric properties, sample S2 using glutinous corn starch and sample S3 using pea starch were found to be resistant to gastric juice. The sex was poor. On the other hand, sample S1 using a branched cyclic dextrin was excellent in enteric properties. From the above, it was considered that a branched cyclic dextrin is suitable as a film forming agent for a soft capsule film exhibiting enteric properties.

  Next, the result of having examined the mass ratio with respect to the branched cyclic dextrin of iota carrageenan using a branched cyclic dextrin as a film formation agent is shown. As shown in Table 2, the samples S11 to S20 in which the weight parts of iota carrageenan with respect to 100 parts by weight of branched cyclic dextrin were changed as shown in Table 2 were cast, moldability, and enteric properties in the same manner as described above. Was evaluated. The results are also shown in Table 2. In samples S11 to S20, the mass ratio of sodium alginate to iota carrageenan is 50 parts by weight of sodium alginate with respect to 100 parts by weight of iota carrageenan. Moreover, the capsule membrane | film | coat liquid was prepared by dissolving 60 weight part glycerol with water with respect to 100 weight part of branched cyclic dextrin similarly to the above with branched cyclic dextrin, iota carrageenan, and sodium alginate. The prepared capsule film solution was molded with a rotary die molding apparatus and filled with vegetable oil as the contents to obtain soft capsules.

  As shown in Table 2, Samples S19 and S20 having a high mass ratio of iota carrageenan to branched cyclic dextrin had a high gelation rate and poor castability. On the other hand, Samples S11 to S14 having a small mass ratio of iota carrageenan were insufficiently sealed by heat sealing and had poor moldability. When a disintegration test was performed on samples S15 to S18, which had good castability and moldability, the gastric juice resistance was insufficient for sample S15, but samples S16 to S18 showed excellent enteric properties. . From the above, in the composition of the soft capsule film, by setting the iota carrageenan to 32 parts by weight to 36 parts by weight with respect to 100 parts by weight of the branched cyclic dextrin, the soft capsule film (soft capsule) having excellent moldability and enteric properties can be rotated. It was thought that it could be molded practically with a die type.

  Next, the result of examining the mass ratio of sodium alginate to iota carrageenan is shown. First, as shown in Table 3, the composition of the soft capsule film, iota carrageenan is 32 parts by weight which is the lower limit of the above desirable range (32 parts by weight to 36 parts by weight with respect to 100 parts by weight of branched cyclic dextrin). About the samples S21-S32 which changed the ratio of the sodium alginate with respect to a weight part in the range of 0 weight part-70 weight part, castability, a moldability, and enteric evaluation were performed by the method similar to the above. The results are also shown in Table 3. In addition, the capsule membrane | film | coat liquid was prepared by dissolving 60 weight part glycerol with water with respect to 100 weight part of branched cyclic dextrin similarly to the above with branched cyclic dextrin, iota carrageenan, and sodium alginate. The prepared capsule film solution was molded with a rotary die molding apparatus and filled with vegetable oil as the contents to obtain soft capsules.

  As shown in Table 3, Sample S32 having a high sodium alginate ratio had a high viscosity of the capsule coating solution and had poor castability. As for the other samples S21 to S31, both castability and moldability were good. However, as a result of the disintegration test, sample S21 containing no sodium alginate with respect to 100 parts by weight of iota carrageenan and alginic acid with respect to 100 parts by weight of iota carrageenan Samples S22 to S26 having a sodium ratio of 41.3 parts by weight or less had insufficient gastric juice resistance. On the other hand, samples S27 to S31 in which the ratio of sodium alginate to 100 parts by weight of iota carrageenan was 42.5 parts by weight to 60 parts by weight were excellent in enteric properties. From the above, it is necessary to contain both iota carrageenan and sodium alginate in order to obtain an enteric soft capsule film, and there is a suitable range for the ratio of both, and the weight of the branched cyclic dextrin is 100 wt. When the iota carrageenan was 32 parts by weight with respect to parts, the ratio of sodium alginate to 100 parts by weight of iota carrageenan was considered to be suitable in the range of 42.5 parts by weight to 60 parts by weight.

  Next, as shown in Table 4, the composition of the soft capsule film is such that iota carrageenan is 36 parts by weight which is the upper limit of the above desirable range (32 parts by weight to 36 parts by weight with respect to 100 parts by weight of the branched cyclic dextrin). About the samples S41-S52 which changed the ratio of the sodium alginate with respect to 100 weight part in the range of 0 weight part-70 weight part, castability, a moldability, and enteric evaluation were performed by the method similar to the above. The results are also shown in Table 4. In addition, the capsule membrane | film | coat liquid was prepared by dissolving 60 weight part glycerol with water with respect to 100 weight part of branched cyclic dextrin similarly to the above with branched cyclic dextrin, iota carrageenan, and sodium alginate. The prepared capsule film solution was molded with a rotary die molding apparatus and filled with vegetable oil as the contents to obtain soft capsules.

  As can be seen from Table 4, the same tendency as the results shown in Table 3 is observed, and the sample S52 having a high proportion of sodium alginate has a high viscosity of the capsule coating solution and has poor castability. As for S51, castability and moldability were both good, but as a result of the disintegration test, sample S41 not containing sodium alginate with respect to 100 parts by weight of iota carrageenan and sample S42 to which the ratio of sodium alginate to iota carrageenan was low S45 was insufficient in gastric juice resistance. The range excellent in all of castability, moldability, and enteric properties is such that when the iota carrageenan is 36 parts by weight with respect to 100 parts by weight of the branched cyclic dextrin, the ratio of sodium alginate to 100 parts by weight of iota carrageenan is 42. It was considered to be in the range of 5 to 50 parts by weight.

  Considering together the results shown in Tables 3 and 4, branched cyclic dextrin, 32 to 36 parts by weight of iota carrageenan with respect to 100 parts by weight of branched cyclic dextrin, and 42 with respect to 100 parts by weight of iota carrageenan. It can be said that the soft capsule film containing 5 parts by weight to 50 parts by weight of sodium alginate and containing no gelatin is excellent in all of the castability of the capsule film solution, the moldability of the soft capsule film, and the enteric property. .

  As described above, according to this embodiment, it is possible to provide a novel soft capsule film that does not contain gelatin and has enteric properties, and a soft capsule that includes the soft capsule film.

  Although the present invention has been described with reference to the preferred embodiments, the present invention is not limited to the above-described embodiments, and various improvements and design changes can be made without departing from the scope of the present invention. It is.

JP 2008-088111 A JP 2011-026262 A Japanese Patent No. 4252619

Claims (3)

A soft capsule film having a seam formed by being molded by a rotary die molding device,
An acyclic glucan chain having a cyclic structure part formed by glycosidic bonds and having a branched glucan chain formed by α-1,4 glycosidic bonds and α-1,6 glucosidic bonds in the molecule A branched cyclic dextrin bound to the structure part, having a weight average polymerization degree of 2000 to 3000 and 16 to 100 glucose constituting the cyclic structure part;
With iota carrageenan,
Containing alginate,
A soft capsule film characterized by not containing gelatin. Containing 32 to 36 parts by weight of iota carrageenan with respect to 100 parts by weight of the branched cyclic dextrin,
2. The soft capsule film according to claim 1, wherein the alginate is sodium alginate and contains 42.5 to 50 parts by weight of sodium alginate with respect to 100 parts by weight of iota carrageenan.   The soft capsule which filled the soft capsule membrane | film | coat of Claim 1 or Claim 2 with the content.