JP7850962B2 - Soft capsule coating and soft capsule - Google Patents

Description

This invention relates to a soft capsule coating and a soft capsule comprising the soft capsule coating.

Soft capsule coatings require flexibility and elasticity. This is primarily because the contents enclosed within the soft capsule are typically liquids (solutions or suspensions), and their volume changes significantly with ambient temperature fluctuations. If the soft capsule coating lacks flexibility and elasticity, the volume changes of the contents can cause cracking, potentially leading to leakage. Therefore, plasticizers are commonly added to soft capsule coatings to enhance their flexibility and elasticity, and glycerin has traditionally been widely used as such.

In contrast, the present applicant proposes a technology that can impart flexibility and elasticity to the soft capsule coating without using glycerin (see Patent Documents 1 and 2).

The technology described in Patent Document 1 involves a soft capsule shell using gelatin as the film base, containing high-saccharification reduced starch syrup and erythritol without containing glycerin. The technology described in Patent Document 2 involves a soft capsule shell using gelatin as the film base, containing monoacetylmonocylglycerin without containing glycerin.

The applicant has continued to search for novel plasticizers that can replace glycerin and impart flexibility and elasticity to soft capsule coatings. This invention was developed in that process.

Patent No. 5873367 Japanese Patent Publication No. 2015-231955

The present invention aims to provide a soft capsule coating that possesses flexibility and elasticity without containing glycerin, and a soft capsule equipped with said soft capsule coating.

To solve the above problems, the soft capsule coating according to the present invention is
It contains gelatin and the sodium salt of 3-hydroxybutyrate, but does not contain glycerin.

In this invention, the soft capsule shell, which uses gelatin as a film base, contains the sodium salt of 3-hydroxybutyric acid (β-hydroxybutyric acid) without containing glycerin. ₃ -hydroxybutyric acid is a substance represented by the molecular formula _{C₄H ₸ O₃} or _{CH₃CHOHCH₂COOH} , and is produced in the human body by breaking down fat as an alternative energy source when glucose concentration is insufficient. In recent years, 3-hydroxybutyric acid has also been artificially produced by fermenting sugars from natural food materials. Due to the presence of a chiral carbon atom, D-type and L-type optical isomers exist.

In the process of searching for a novel plasticizer that could replace glycerin, the applicant focused on the high hygroscopicity and low volatility of 3-hydroxybutyric acid and hypothesized that it might act as a plasticizer. As a result of the detailed investigation described later, it was discovered that the sodium salt of 3-hydroxybutyric acid can serve as a plasticizer to replace glycerin, leading to the present invention.

Therefore, by incorporating 3-hydroxybutyric acid into a soft capsule coating using gelatin as the coating base, it is possible to provide a soft capsule coating that possesses flexibility and elasticity without containing glycerin.

The soft capsule coating according to the present invention has the above configuration,
The product may contain "35 to 55 parts by weight of sodium salt of 3-hydroxybutyric acid per 100 parts by weight of gelatin."

By setting the ratio of sodium 3-hydroxybutyric acid to gelatin within the above range, as detailed later, it is possible to provide a soft capsule coating that exhibits excellent film-forming properties as well as superior flexibility and elasticity, without containing glycerin.

Next, the soft capsule according to the present invention is
"The contents are filled into the soft capsule shell described above."

The "contents" can include any pharmaceutical ingredients, herbal ingredients, health food ingredients, and nutritional supplements without any particular limitations. These ingredients (the substances intended for intake) can be dissolved or suspended in oil or a fatty substance, or the substance itself may be in an oily or paste form.

This configuration makes it possible to provide soft capsules equipped with a flexible and elastic soft capsule coating.

Furthermore, 3-hydroxybutyrate is said to have effects beyond its role as an energy source that can replace glucose, including inhibiting oxidation and inflammation. Therefore, it is possible to provide soft capsules in which the capsule shell itself, containing the health-beneficial sodium salt of 3-hydroxybutyrate, is also present.

As described above, the present invention provides a soft capsule coating that is flexible and elastic without containing glycerin, and a soft capsule equipped with the soft capsule coating.

The following describes a soft capsule coating, which is one embodiment of the present invention, and a soft capsule equipped with the soft capsule coating.

The soft capsule coating of this embodiment contains gelatin and the sodium salt of 3-hydroxybutyric acid (hereinafter sometimes abbreviated as "3HB"), but does not contain glycerin.

Soft capsules with such a soft capsule coating can be manufactured using a rotary die molding apparatus. The process involves a coating solution preparation step to prepare the coating solution, a molding and filling step to simultaneously mold the soft capsule coating and fill it with contents, and a drying step to dry the soft capsules after the molding and filling process.

In the film base preparation process, gelatin, which is the film base, is dissolved in water while being heated. Sodium salt (powder) of 3HB is then added and heated until dissolved, and the mixture is thoroughly stirred and mixed to prepare the film base.

The molding and filling process is carried out using a rotary die molding apparatus. A rotary die molding apparatus generally comprises a casting drum for forming the film solution into a film, a pair of die rolls with molding molds formed on their outer surfaces, wedge-shaped segments positioned between the die rolls, and a pump that pressurizes the contents into the segments and pushes them out from the tips of the segments.

In the molding and filling process, the film concentrate is first poured onto the surface of the casting drum and gelled to form a film. Next, two of the formed films are fed between a pair of die rolls along the segments. As the pair of die rolls rotate in opposite directions, the two films are heat-sealed, forming a capsule with an open space at the top. The contents extruded from the segments are then filled into this capsule. Simultaneously, the two films are heat-sealed at the top, forming a soft capsule with a closed internal space filled with the contents. Soft capsules molded in a rotary die molding machine have seams, which are the marks left by the heat seals.

In the drying process, the soft capsule coating is dried in a humidity-controlled dryer until it reaches a predetermined moisture content.

Next, we will explain the research that led to the inclusion of sodium 3HB instead of glycerin in the soft capsule coating, which uses gelatin as the coating base.

Using gelatin as the film-forming base, film-forming stock solutions for samples S1 to S4 were prepared, each containing a 40% by mass aqueous solution of 3HB, sodium salt of 3HB (3HB content 81.8% by mass), magnesium salt of 3HB (3HB content 89.6% by mass), and calcium salt of 3HB (3HB content 83.8% by mass), respectively. For the 40% by mass aqueous solution of 3HB, sodium salt of 3HB (powder), magnesium salt of HB (powder), and calcium salt of 3HB (powder), the D-type 3HB and its salts, "OKETOA®," manufactured by Osaka Gas Chemical Co., Ltd., were used.

The proportions of these 3HB and its salts relative to 100 parts by weight of gelatin were set to 40 parts by weight in terms of 3HB equivalent. This was determined by referring to the typical composition of soft capsule coatings, which use gelatin as the coating base and glycerin as the plasticizer, where glycerin is used in proportions of 40 parts by weight per 100 parts by weight of gelatin.

Furthermore, in the sodium salt of 3HB, the hydrogen atoms in the -COOH group of each molecule of 3HB are replaced with sodium atoms, whereas in the magnesium salt and calcium salt of 3HB, the hydrogen atoms in the -COOH group of each of two molecules of 3HB are replaced with one atom of magnesium or calcium.

The undiluted coating solutions of samples S1 to S4 were each cast onto a smooth surface, and their film-forming properties and flexibility/elasticity after drying were evaluated as follows. Hereafter, the soft capsule coating may simply be referred to as "the coating."

<Film-forming properties>
When the undried coating was peeled off the smooth surface of the casting target, if the coating could be peeled off in a sheet and stretched without breaking when pulled by hand, it was evaluated as a "○" indicating that a coating with appropriate strength was formed well. If the coating could not be peeled off in a sheet or broke when pulled, it was evaluated as a "×" indicating poor coating formation.

<Flexibility and elasticity>
After drying the sheet-like coating until its moisture content reached 8% by mass, it was folded in half. If no cracks or fissures were observed with the naked eye, it was evaluated as having good flexibility and elasticity ("○"). If even slight cracks or fissures were observed, it was evaluated as having poor flexibility and elasticity ("×"). In cases where the coating formation was poor, the evaluation of flexibility and elasticity was not performed.

Table 1 shows the evaluation results for film formation and flexibility/elasticity after drying for each film obtained from samples S1 to S4, along with the composition of the film concentrate.

When using a 40% by mass aqueous solution of 3HB for sample S1, no film was formed from the undiluted solution, suggesting that the gelatin's inherent film-forming ability was impaired. This was thought to be due to the low pH of the 40% by mass aqueous solution of 3HB affecting the gelatin's film-forming ability.

Furthermore, regarding the samples using 3HB salts, sample S2, which used the sodium salt, showed good film formation and flexibility/elasticity after drying. However, samples S3 and S4, which used the magnesium salt and calcium salt respectively, showed good film formation but poor flexibility/elasticity after drying. This is thought to be because the sodium salt of 3HB has higher solubility in water and superior hygroscopicity (moisture retention) compared to the magnesium and calcium salts of 3HB, allowing the soft capsule coating to easily retain moisture, and the retained moisture enhances the flexibility and elasticity of the coating.

Based on the above results, it was found that the sodium salt of 3HB acts as a plasticizer that imparts flexibility and elasticity to the soft capsule coating using gelatin as the coating base. Therefore, the desirable ratio of sodium salt of 3HB to gelatin was investigated. Specifically, the coating solutions of samples S11 to S19, each with a different ratio of sodium salt of 3HB to 100 parts by weight of gelatin, were cast onto a smooth surface in the same manner as described above, and the film-forming ability and the flexibility and elasticity after drying were evaluated using the same method as described above. The results, along with the composition of the coating solutions, are shown in Table 2.

As shown in Table 2, the film-forming solutions of samples S12 to S16, where the ratio of 3HB sodium salt to 100 parts by weight of gelatin was 35 parts by weight or more and 55 parts by weight or less, showed good film-forming properties, and the flexibility and elasticity of the film after drying were also good. In contrast, the film-forming solutions of samples S17 to S19, where the ratio of 3HB sodium salt to 100 parts by weight of gelatin was 30 parts by weight or less, showed good film-forming properties, but the flexibility and elasticity of the film after drying were poor, suggesting that there was insufficient 3HB sodium salt as a plasticizer. On the other hand, the film-forming solution of sample S11, where the ratio of 3HB sodium salt to 100 parts by weight of gelatin was 60 parts by weight, showed poor film-forming properties, suggesting that too much 3HB sodium salt inhibits the film-forming ability of gelatin.

For sample S15, which exhibits good film-forming properties and good flexibility and elasticity after drying, the non-adhesion (difficulty of adhesion) and disintegration properties of the dried soft capsule film were confirmed using the following method. For comparison, sample R, a conventional film base solution using gelatin as the film base and glycerin as the plasticizer, was also evaluated in the same manner.

<Non-adhesive>
After casting the undiluted coating solution onto a smooth surface to form a film, the film was dried in the same manner as described above and cut into 1 cm x 1 cm sheet pieces. Fifty of these sheet pieces were placed in a standard No. 9 glass bottle and stored for 100 hours under three different conditions. After 100 hours, when the sheet pieces were removed from the bottle, if there was no adhesion between the sheet pieces and each piece was completely separated, it was evaluated as having very good non-adhesion ("◎"). If some sheet pieces were adhered but could be easily peeled off by hand, it was evaluated as having good non-adhesion ("○"). If any adhesion occurred that could not be peeled off by hand, even if only partially, it was evaluated as having poor non-adhesion ("×").

The three types of preservation conditions are as follows:
• Room temperature environment (normal storage conditions)
Condition A: Temperature 40°C, relative humidity 75% (more severe conditions than normal storage conditions)
Condition B: Temperature 50°C (even more severe conditions than Condition A)

<Collapse-like>
0.5 grams of the dried sheet-like coating was immersed in 100 grams of water maintained at 37°C. If the coating completely disintegrated within 20 minutes, it was evaluated as having good disintegration properties ("○"). If the coating remained intact after 20 minutes, it was evaluated as having poor disintegration properties ("×"). The evaluation results, along with the composition of the coating solution, are shown in Table 3.

As shown in Table 3, the soft capsule coating using sodium 3HB as a plasticizer exhibited non-adhesion properties comparable to conventional soft capsule coatings using glycerin as a plasticizer, and also showed excellent disintegration properties similar to conventional soft capsule coatings using glycerin as a plasticizer.

As described above, by incorporating 3HB sodium salt as a plasticizer into a soft capsule coating using gelatin as the coating base, without including glycerin, we were able to create a soft capsule coating with excellent flexibility and elasticity. In particular, by setting the proportion of 3HB sodium salt to 35 parts by weight or more and 55 parts by weight or less per 100 parts by weight of gelatin, good coating formation was achieved, along with excellent flexibility and elasticity of the soft capsule coating. Furthermore, the non-adhesion of the soft capsule coatings and their disintegration in water at a temperature similar to body temperature were comparable to conventional soft capsule coatings containing glycerin as a plasticizer. Therefore, 3HB sodium salt can be used as a novel plasticizer to replace glycerin.

In addition, 3HB is said to have effects that suppress oxidation reactions and inflammatory reactions, as well as acting as an energy source that can replace glucose. While typical soft capsules contain pharmaceutical or nutritional supplements that contribute to human health, the soft capsules of this embodiment are novel soft capsules in which health-contributing components are contained not only in the contents but also in the soft capsule shell itself.

Although preferred embodiments of the present invention have been described above, the present invention is not limited to the above embodiments. Various improvements and design modifications are possible without departing from the spirit of the invention, as described below.

For example, other additives such as colorants and fragrances can be added to the soft capsule coating produced by this invention.

Claims (3)

A soft capsule coating characterized by containing gelatin and the sodium salt of 3-hydroxybutyric acid, but not containing glycerin. The soft capsule coating according to claim 1, characterized in that it contains 35 to 55 parts by weight of sodium salt of 3-hydroxybutyric acid per 100 parts by weight of gelatin. A soft capsule characterized in that the soft capsule coating described in claim 1 or claim 2 is filled with contents.