JP4252619B1 - Method for producing enteric soft capsule and enteric soft capsule - Google Patents

Abstract

Provided is a method for producing enteric soft capsules that can apply a rotary die method capable of forming capsules of various shapes and sizes, and can produce capsules having excellent enteric properties and beautiful appearance in a simple process. To do.
The method for producing an enteric soft capsule contains gelatin, water, a plasticizer, and 10 to 30 parts by weight of low methoxyl pectin with a degree of esterification of 20 to 40% and 100 parts by weight of gelatin. And a forming step of forming a soft capsule in which the capsule coating formed from the capsule coating solution is filled with the content by a rotary die type molding apparatus. In this production method, the salt containing polyvalent metal ions that gel low methoxyl pectin is not added to the capsule film solution, and the step of immersing the molded soft capsule in the gelling solution containing polyvalent metal ions is provided. Not done.
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Description

  The present invention relates to a method for producing an enteric soft capsule and an enteric soft capsule, and more particularly, to a method for producing an enteric soft capsule by a rotary die method, and an enteric soft capsule produced by the production method.

  Gelatin, which is generally used as a film base for soft capsules, reversibly changes to sol and gel with changes in temperature, has excellent film-forming ability and high mechanical strength, and disintegrates in the body. Alternatively, it has many advantages as a film base, such as being easily dissolved and having itself nutritional value and being easily absorbed into the body. However, since gelatin is readily soluble in gastric acid, it does not disintegrate or dissolve in the stomach in order to make the contents of soft capsules contain components that lose their efficacy by gastric acid, or that irritate stomach tissue. It is necessary to impart a gelatin film with a property of disintegrating or dissolving after reaching the intestine (enteric solubility).

  Conventionally, as a capsule in which entericity is imparted to a gelatin film, a capsule in which an outer surface of a formed capsule is coated with an enteric substance such as zein or shellac has been implemented (for example, see Patent Document 1).

  Technology that makes capsule film enteric by adding polysaccharides that show acid resistance by gelling with polyvalent metal ions such as calcium ion and magnesium ion, such as alginate, low methoxyl pectin, gellan gum, etc. Is disclosed. In this technique, a polysaccharide is gelled by immersing it in an aqueous solution containing polyvalent metal ions after the capsule is formed, and an acid-resistant outer skin is formed on the surface of the capsule film (for example, see Patent Document 2), A technique in which a water-insoluble salt of a polyvalent metal ion (slightly water-soluble salt) is previously contained in a capsule film, and the polyvalent metal ion is dissociated in gastric acid to cause a gelling reaction to a polysaccharide (for example, a patent) (Refer to Reference 3).

JP 2004-18443 A JP 61-151127 A JP-A-4-27352

  However, in the conventional capsule in which shellac or the like is coated on the outer surface, there is a problem that a uniform coating layer is difficult to be formed and the appearance is impaired due to the roughness of the surface. Here, since soft capsules have high market value for transparency and unique gloss, the problem that the beautiful appearance is impaired is serious. Further, since a coating process is required in addition to the capsule forming process, the equipment is required, the process becomes complicated, and the manufacturing cost increases. In addition, peeling of the coating layer may impair the enteric properties of the capsule.

  On the other hand, in the conventional technique in which a capsule containing the above polysaccharide is formed in a film and then the capsule is gelled by immersing the capsule in an aqueous solution containing polyvalent metal ions, moisture is transferred from the immersion liquid to the capsule film. In addition, there is a risk that moisture may reach the contents. Moreover, since the process for immersion is required in addition to the capsule forming process, the equipment is required, the process becomes complicated, and the production cost increases. Furthermore, there is a problem in that the capsule surface is partially dissolved by the immersion liquid and the smoothness and gloss are lost, and the appearance of the capsule is impaired.

  In addition, in the above polysaccharides, alginate and low methoxyl pectin do not have a sol-gel change property depending on temperature unlike gelatin, and gellan gum is far from gelatin which changes sol-gel at a temperature close to normal temperature. Since the sol-gel changes with temperature, the heat-sealability when soft capsules are formed by the rotary die method must be mainly secured by gelatin. Therefore, when the blending ratio of the polysaccharide in the coating liquid is increased, the adhesiveness is lowered with the decrease in the ratio of gelatin, and there is a possibility that the capsule cannot be formed. Therefore, in the conventional technology represented by Patent Document 2, the soft capsule molding method is performed by a dropping method (seamless capsule method) that does not require heat sealing. In addition, since the above polysaccharides are also called thickening polysaccharides and the viscosity of the aqueous solution is high, the rotary die method in which a sheet is formed from a coating solution and capsules are formed by heat-sealing two sheets, capsules are formed. In view of this, capsules have been molded by the dropping method.

  Here, since the dropping method is a method of forming a capsule using the surface tension of the coating liquid, the shape of the capsule to be formed is limited to a true sphere. Therefore, unlike the rotary die method, which can be variously shaped according to the shape of the mold, such as drop type, triangular type, heart type, etc., in addition to the oval type, round type, support type, oblong type, tube type, etc., the dropping method However, there is a disadvantage that there is no room for selection in the capsule shape. Moreover, since the size of the capsule is limited to a small one by the dropping method, there is a problem that a large number of capsules must be taken in order to take a necessary amount of the active ingredient of the contents.

  On the other hand, Patent Document 3 discloses a technique for forming a capsule by a rotary die method by suppressing an increase in the viscosity of a coating liquid containing a polysaccharide by adding a pH adjusting agent and a chelating agent. . However, in this technique, since a water-insoluble calcium salt is previously contained in the capsule film, there is a problem that the film becomes white and cloudy, the transparency is lost, and the appearance of the capsule is impaired.

  Therefore, in view of the above circumstances, the present invention can apply a rotary die method capable of forming capsules of various shapes and sizes, and can produce capsules that have excellent enteric properties and have a beautiful appearance in a simple process. An object of the present invention is to provide a method for producing enteric soft capsules that can be produced, and to provide enteric soft capsules produced by the production method.

  In order to solve the above-mentioned problems, the method for producing an enteric soft capsule according to the present invention includes: “gelatin, water, plasticizer, and 10 parts by weight per 100 parts by weight of gelatin with a degree of esterification of 20% to 40%. A preparation process for preparing a capsule film liquid containing -30 parts by weight of low methoxyl pectin, and a molding for forming a soft capsule in which the capsule film formed from the capsule film liquid is filled with the contents by a rotary die type molding apparatus A salt containing polyvalent metal ions that gels low methoxyl pectin is not added to the capsule coating solution, and the molded soft capsule is immersed in the gelled solution containing the polyvalent metal ions. Is not included ".

  “Pectin” is a polysaccharide in which galacturonic acid and its methyl ester are polymerized, and “DE (Degree of Esterification)” is the proportion of galacturonic acid present in the form of methyl ester in the total galacturonic acid. Say. A pectin having an esterification degree of 50% or more is called “high methoxyl pectin (HM pectin)”, whereas a pectin having a lower esterification degree is called “low methoxyl pectin (LM pectin)”. ing.

  The mechanism of gelation is greatly different between low methoxyl pectin and high methoxyl pectin, whereas high methoxyl pectin forms a gel due to hydrogen bonding in the presence of sugar of pH 3.5 or less and about 55% or more, whereas low methoxyl pectin. Pectin gels in the presence of multivalent metal ions. The gelation mechanism is based on the concept that polyvalent metal ions cross-link between the carboxyl groups of galacturonic acid by ionic bonds, and the concept based on coordinate bonds between lone pairs of galacturonic acid and polyvalent metal ions (egg Box model). Here, examples of the “polyvalent metal ion” include metal ions such as calcium, magnesium, aluminum, iron, copper, zinc, strontium, barium and nickel.

  As the “plasticizer”, glycerin, sorbitol, maltitol, polyethylene glycol and the like can be used alone or in combination. The “capsule film solution” of the present invention may contain a colorant such as caramel and tar pigment, a light hiding agent such as titanium oxide, and a preservative such as paraben in addition to gelatin, water and a plasticizer. I do not care.

  Examples of the “contents” to be filled in the capsule film include those obtained by dissolving or suspending pharmaceutical ingredients, health food ingredients, and nutritional supplement ingredients in oils, but are not particularly limited, such as lactic acid bacteria Components that easily lose their activity due to stomach acid and components that easily irritate the cell wall of the stomach such as iron are highly significant as the contents of the present invention.

  As a result of investigation, the present inventors have added 10 to 30 parts by weight of low methoxyl pectin having a degree of esterification of 20 to 40% to 100 parts by weight of gelatin in a capsule film solution based on gelatin. As a result, it was found that soft capsules having excellent enteric properties can be produced with good moldability by the same production method as other methods for producing soft capsules that are not enteric using a rotary die molding apparatus. Therefore, in the past, when low methoxyl pectin having no sol-gel changing property with temperature was used, it was difficult to form enteric soft capsules by the rotary die method. Enteric soft capsules of various sizes and shapes can be produced.

  Here, when the degree of esterification of low methoxyl pectin is outside the range of 20 to 40%, and when the ratio of low methoxyl pectin to 100 parts by weight of gelatin is less than 10 parts by weight, gelation of low methoxyl pectin The resistance to the added gastric acid is insufficient. On the other hand, when the ratio of low methoxyl pectin to 100 parts by weight of gelatin exceeds 30 parts by weight, the viscosity of the capsule film increases and the heat sealability of the capsule film decreases, thereby forming a soft capsule by the rotary die method. Sex is reduced. In addition, if the ratio of the low methoxyl pectin to 100 parts by weight of gelatin is 10 to 20 parts by weight, it is possible to achieve harmonization of the above-mentioned conflicting actions, which is more desirable.

  Further, unlike the above-described conventional technology, it is not necessary to previously add a water-insoluble salt of a polyvalent metal ion to the capsule film in order to gel low methoxyl pectin, so the capsule film may become cloudy white. And a beautiful enteric soft capsule with a clear feeling can be produced.

  Furthermore, unlike the above-mentioned conventional technology, there is no need for a step of immersing the formed capsule in a gelling liquid containing polyvalent metal ions, so there is no need for additional equipment or equipment, and the cost is reduced with a simple process. Enteric soft capsules can be produced.

  In addition, unlike the above-described prior art, there is no need for a process for coating an enteric substance such as shellac on the surface of the molded capsule, so there is no need for additional equipment or equipment, and the cost is reduced with a simple process. Reduced to produce enteric soft capsules.

Next, the enteric soft capsule according to the present invention is “a soft capsule having a seam formed by being molded by a rotary die molding apparatus, and the capsule film has gelatin, a plasticizer, and a degree of esterification. 20% to 40% containing 10 parts by weight to 30 parts by weight of low methoxyl pectin with respect to 100 parts by weight of gelatin and containing a salt containing a polyvalent metal ion that gels low methoxyl pectin. It does not have a coating skin gelled by the polyvalent metal ions .

  A "seam" is formed when two sheets formed from a capsule coating solution are fed between a pair of die rolls when being molded by a rotary die molding apparatus, and both sheets are heat sealed together with filling of contents. It is a joining line. Such a seam is a configuration unique to soft capsules molded by a rotary die method and does not exist in soft capsules (seamless capsules) molded by a dropping method.

  The enteric soft capsule having the above-described configuration is produced by the above-described method for producing an enteric soft capsule and has excellent enteric properties. Moreover, since it is a soft capsule shape | molded with a rotary die type manufacturing apparatus, it has an advantage with a high freedom degree of a size and a shape. In addition, the enteric soft capsule of the present invention produced by the above-described method for producing enteric soft capsules does not contain a salt of polyvalent metal ions such as calcium carbonate and calcium hydrogen phosphate in the capsule film. Since it does not have a coating skin that has been gelated by being immersed in an aqueous solution containing a valent metal ion, and has no coating layer of an enteric substance on the outer surface, it has a beautiful appearance with transparency. .

  As described above, as an effect of the present invention, a rotary die method capable of forming capsules of various shapes and sizes can be applied, and capsules having excellent enteric properties and beautiful appearance can be produced by a simple process. A method for producing an enteric soft capsule and an enteric soft capsule produced by the production method can be provided.

  Hereinafter, the manufacturing method of the enteric soft capsule which is the best embodiment of this invention, and the enteric soft capsule manufactured by this manufacturing method are demonstrated.

  The method for producing an enteric soft capsule of the present embodiment includes gelatin, water, a plasticizer, and a capsule containing 10 to 30 parts by weight of low methoxyl pectin with a degree of esterification of 20 to 40% and 100 parts by weight of gelatin. A preparation step of preparing a coating solution, and a forming step of forming a soft capsule in which the capsule coating formed from the capsule coating solution is filled with a content by a rotary die type molding apparatus. And in the manufacturing method of the enteric soft capsule of this embodiment, while the salt containing the polyvalent metal ion which gelatinizes low methoxyl pectin is not added to a capsule membrane | film | coat liquid, the shape | molded soft capsule is made into a polyvalent metal ion. There is also no step of immersing in a gelling solution containing. Further, the enteric soft capsule produced by the method for producing the enteric soft capsule of the present embodiment is a soft capsule having a seam formed by being molded by a rotary die type molding apparatus, and the capsule film includes gelatin, and The esterification degree is 20% to 40%, and 10 parts by weight to 30 parts by weight of low methoxyl pectin is contained with respect to 100 parts by weight of gelatin.

  More specifically, in the preparation step, first, low methoxyl pectin, a plasticizer, and water are dissolved by heating. Further, gelatin is added, mixed and dissolved by heating to prepare a mixed solution having a desired viscosity. At this time, additives such as a colorant, a light hiding agent, and a preservative can be blended as necessary. Thereafter, the capsule liquid can be obtained by defoaming the mixed liquid.

  The molding process is performed by using a rotary die type molding device. In a general rotary die type molding device, a casting drum for molding a capsule film solution into a sheet shape, and a molding mold is formed on the outer surface. It mainly includes a pair of die rolls, a wedge-shaped segment disposed between the die rolls, and a pump that presses the contents into the segments and pushes the contents from the tip of the segments.

  In the molding step, first, a capsule film solution that is maintained at 60 to 100 ° C. and is in a sol state is cast on the surface of the casting drum, cooled, and gelled to form a sheet. Next, two of the formed sheets are fed between a pair of die rolls along the segment. Then, as the pair of die rolls rotate in opposite directions, the two sheets are heat-sealed to form a capsule opened upward, and the contents extruded from the segments are filled therein. At the same time, the two sheets are heat-sealed at the top, forming a soft capsule filled with the contents in a closed internal space. In addition, the capsule shape | molded by the shaping | molding process can be dried in a humidity control dryer until it becomes a predetermined | prescribed moisture content.

  Next, the basis for the above-described configuration of the enteric soft capsule manufacturing method of the present embodiment will be described. First, the results of studies on materials that impart enteric properties to gelatin-based capsule films are shown. In the study, glycerin was used as a plasticizer, and gellan gum, sodium alginate, carrageenan, low methoxyl pectin, and high methoxyl pectin were used alone or in combination to prepare capsule film solutions of film compositions A to H shown in Table 1, respectively. . Using each capsule film solution, soft capsules were molded in the same manner as described above using a rotary die molding apparatus. In addition, including Table 1, below, the film composition is displayed in parts by weight with respect to 100 parts by weight of gelatin.

  About the soft capsule of each film | membrane composition, the enteric evaluation was performed according to the disintegration test method prescribed | regulated to the Japanese Pharmacopoeia. The results are also shown in Table 1. Here, the first solution is a test solution having a pH of 1.2 for evaluating gastric juice resistance. The soft capsule is moved up and down in the test solution for 120 minutes, and in the subsequent observation, the capsule film remains and the contents leak out. “◯” indicates that the capsule film remains, but “△” indicates that the contents are leaked but “x” indicates that the capsule film does not remain. The second solution is a test solution having a pH of 6.8 for evaluating the resistance to intestinal juice. The soft capsule is moved up and down in the test solution for 60 minutes, and in the subsequent observation, the capsule film shape does not remain. ”,“ △ ”indicates that the capsule film remains but the contents are leaked, and“ × ”indicates that the capsule film remains and the contents are not leaked. Therefore, it can be judged that it is excellent as an enteric capsule when it is “◯” with respect to both the first liquid and the second liquid.

  As is apparent from Table 1, when low methoxyl pectin (LM pectin) was added to a capsule film based on gelatin, excellent enteric properties were exhibited. In addition, when low methoxyl pectin is added alone (film composition D), it is more enteric than when low methoxyl pectin is used in combination with sodium alginate (film composition F), and when low methoxyl pectin is used in combination with carrageenan. (Coating composition G) did not show enteric properties. And even if it was the same pectin, high methoxyl pectin (HM pectin) did not show enteric property (film composition H). The film composition using gellan gum, sodium alginate, and carrageenan (film composition A, film composition B, and film composition C, respectively) is less added than when low methoxyl pectin is added alone (film composition D). However, when the addition amount is increased more than that, the viscosity of the capsule coating liquid increases and capsule molding becomes difficult. Based on the above, it was considered that it is preferable to add low methoxyl pectin alone to the capsule film solution in order to impart enteric properties to the capsule film based on gelatin.

  Next, the result of examining the relationship between the degree of esterification (DE) of low methoxyl pectin and enteric properties is shown. As shown in Table 2, capsule film solutions of film compositions I to M were prepared by adding 20 parts by weight of low methoxyl pectin having different degrees of esterification to 100 parts by weight of gelatin, and soft capsules using a rotary die molding apparatus Was molded. The molded soft capsule was subjected to the same disintegration test as described above. The results are also shown in Table 2.

  As shown in Table 2, when a low methoxyl pectin having a degree of esterification of 20 to 40% was used, a soft capsule excellent in enteric properties could be obtained. In the film composition I having a degree of esterification smaller than this, it was observed that the capsule film was hard and brittle, so that the film collapsed in the first liquid and the contents leaked out. This was thought to be due to the fact that when the degree of esterification is small, the proportion of galacturonic acid responsible for the gelation is large, so that gelation proceeds rapidly and the degree of gelation is high.

  On the other hand, in the case of the film composition M having a degree of esterification larger than the above range, it was observed that the gel strength of the capsule film was weak, so that the film was crushed in the first liquid and the contents leaked out. This is because, when the degree of esterification is large, the ratio of galacturonic acid responsible for gelation is small, contrary to the above, so the number of bond points for gelation is small and the progress of gelation is slow. This was thought to be due to the low degree of gelation.

  In addition, in the disintegration test, it was observed that the shape of the capsule film remained firmly in the first liquid. Therefore, it was considered that the esterification degree was more preferably 20 to 30%. .

  A low methoxyl pectin with a degree of esterification of 27% was used as a low methoxyl pectin within a more preferable range of esterification (20-30%), and the relationship between the amount of low methoxyl pectin added and enteric properties was examined. The results are shown below. As shown in Table 3, capsule film solutions were prepared for film compositions NT having different mixing ratios of low methoxyl pectin to 100 parts by weight of gelatin, and the viscosity of the prepared capsule film solution was measured. Here, the viscosity was measured using a B-type viscometer (rotor No. 4, rotation speed 6 rpm) at a measurement temperature of 75 ° C. Furthermore, soft capsules were molded with a rotary die molding apparatus using the prepared capsule coating solution, and the same disintegration test as described above was performed on the molded soft capsules. Table 3 shows the results of the viscosity measurement and the results of the disintegration test.

  As shown in Table 3, when 10 to 30 parts by weight of low methoxyl pectin was added to 100 parts by weight of gelatin, excellent enteric properties were exhibited. In the film compositions N and O in which the ratio of low methoxyl pectin was less than 10 parts by weight, it was considered that the gastric juice resistance imparted to the gelatin film by gelation of low methoxyl pectin was insufficient. On the other hand, in the film composition T in which the low methoxyl pectin exceeds 30 parts by weight, the capsule film solution has a very high viscosity. For this reason, handling is difficult in molding using a rotary die molding apparatus, and heat sealability is poor, and soft capsules cannot be molded. In consideration of ease of handling during molding by a rotary die molding apparatus, it is desirable that the capsule coating solution has a viscosity not exceeding 60000 mPa · s. Therefore, the amount of low methoxyl pectin added is gelatin 100 It was thought that it was more suitable when it was 10-20 weight part with respect to the weight part.

  Table 4 summarizes the results of the disintegration test for the soft capsules of the film compositions P, Q, R (J), K, L, and S (soft capsules of the examples) having the constituent requirements of this embodiment, and is a control. Table 4 shows the results of a similar disintegration test performed on commercially available products. Moreover, the observation result of an external appearance is combined with Table 4 about an Example and a commercial item. Here, the commercial product is a type in which entericity is imparted by coating the surface of the soft capsule with shellac zein.

  As shown in Table 4, the enteric soft capsules of this example were superior in enteric properties to commercial products. In addition, the enteric soft capsules of the present example were glossy and exhibited a beautiful appearance excellent in transparency as opposed to a commercial product in which the capsules were dull.

  As described above, according to the method for producing an enteric soft capsule of the present embodiment, a capsule film is formed by adding 10 to 30% of low methoxyl pectin having a degree of esterification of 20 to 40% to 100 parts by weight of gelatin. By forming the same, the other conditions are the same as those for producing an ordinary soft capsule having no enteric properties, and a soft capsule having excellent enteric properties can be produced without requiring any special process.

  Conventionally, it has been difficult to form enteric soft capsules by the rotary die method using a low methoxyl pectin that does not have the property of changing sol and gel depending on temperature. By applying the method, enteric soft capsules of various sizes and shapes can be produced with good moldability.

  As for gelatin, even if any of cattle bone-derived gelatin, cattle skin-derived gelatin, pig skin-derived gelatin, pork bone-derived gelatin, and fish skin-derived gelatin is used, the production method according to the present embodiment makes it enteric. A soft capsule having excellent moldability and a beautiful appearance could be produced with good moldability.

  In the present embodiment, since it is not necessary to coat an enteric substance such as shellac on the soft capsule surface in order to impart enteric properties, the manufacturing process is very simple, the manufacturing cost can be reduced, and the transparent without dullness. Enteric soft capsules with a feeling can be produced.

  Furthermore, unlike conventional technology, it is not necessary to add a water-insoluble salt of polyvalent metal ions to the capsule film solution in order to gel low methoxyl pectin, so that enteric soft capsules with transparency are produced. Can do.

  In addition, unlike the prior art, there is no need for a step of immersing the molded capsule in a gelling solution containing polyvalent metal ions, so the manufacturing process is extremely simple and the manufacturing cost can be reduced. It is possible to produce enteric soft capsules that do not have an outer skin hardened by a gelling solution and have a smooth surface and a transparent feeling.

  The present invention has been described with reference to the preferred embodiments. However, the present invention is not limited to the above-described embodiments, and various improvements can be made without departing from the scope of the present invention as described below. And design changes are possible.

  For example, in the above, the case where 50 parts by weight of glycerin is added to 100 parts by weight of gelatin as a plasticizer is exemplified, but the present invention is not limited thereto, and the content of glycerin is 20 to 60 parts by weight with respect to 100 parts by weight of gelatin. It can be a weight part. Also, the type of plasticizer is not limited to glycerin.

Claims (2)

A preparation step of preparing a capsule film solution containing gelatin, water, a plasticizer, and 10 to 30 parts by weight of low methoxyl pectin with a degree of esterification of 20 to 40% and 100 parts by weight of gelatin;
Forming a soft capsule in which the capsule film formed from the capsule film liquid is filled with the contents by a rotary die type molding apparatus,
A salt containing a polyvalent metal ion that gels low methoxyl pectin is not added to the capsule film solution, and does not include a step of immersing the molded soft capsule in the gelling solution containing the polyvalent metal ion. A method for producing an enteric soft capsule. A soft capsule having a seam formed by being molded by a rotary die molding device,
Capsule shell include gelatin, plasticizer, and, together with the degree of esterification is containing low methoxyl pectin of 10 parts by weight to 30 parts by weight per 100 parts by weight of gelatin with 20% to 40%, the low methoxyl pectin An enteric soft capsule characterized in that it does not contain a salt containing a polyvalent metal ion to be gelled, and does not have a skin coat that is gelled by the polyvalent metal ion .