KR102623444B1 - Shell composition for soft capsule - Google Patents

Abstract

This specification describes a coating composition for soft capsules. The composition contains an ingredient to prevent film migration, solving the problem of content loss due to film migration of the contents, and can provide safe and highly desirable soft capsules using plant-based materials.

Description

Shell composition for soft capsule}

This specification describes a coating composition for soft capsules.

Gelatin is widely used to form the shell of soft capsules. Because gelatin is an animal ingredient, there are issues where it cannot be used or is avoided due to health concerns such as allergies, religion or personal beliefs, etc.

Furthermore, in the case of soft capsules using conventional gelatin, there is a migration issue in which the content is transferred to a film containing gelatin and the content is reduced. Due to this problem, there are problems such as the content being lowered below the prescribed or designed content, shortening the shelf life, or the content being manufactured in excess of the prescribed content considering the transition phenomenon.

In relation to this, a technology to prevent film transfer of contents using silicon dioxide has been proposed, but silicon dioxide has the problem of being an additive that consumers do not prefer due to concerns about skin side effects.

Accordingly, there is a need for technology to prevent film migration using plant-based materials without concerns about side effects.

European Patent Publication No. 0655241

From one perspective, the problem to be solved by the present invention is to provide a coating composition for soft capsules using plant materials.

From another perspective, the problem to be solved by the present invention is to provide a safe coating composition for soft capsules without fear of side effects.

From another perspective, the problem to be solved by the present invention is to provide a shell composition for soft capsules that can prevent the contents from moving or penetrating into the shell.

From another perspective, the problem to be solved by the present invention is to provide a shell composition for vegetable soft capsules that can exclude animal ingredients.

From another perspective, the problem to be solved by the present invention is to provide a shell composition for soft capsules that can increase the shelf life of soft capsules by minimizing the phenomenon of contents transferring to the shell.

In one embodiment, the present invention provides a shell composition for soft capsules containing one or more of ginseng fruit polysaccharide and green tea powder as a film migration prevention ingredient.

From one perspective, the present invention can provide a shell composition for soft capsules using vegetable materials.

From another perspective, the present invention can provide a safe shell composition for soft capsules without fear of side effects.

From another perspective, the present invention can provide a shell composition for soft capsules that can prevent the contents from moving or penetrating into the shell.

From another perspective, the present invention can prevent the content from transferring or penetrating into the film by including a material having a macromolecular structure.

From another perspective, the present invention can provide a shell composition for vegetable soft capsules that can exclude animal ingredients.

From another perspective, the present invention can provide a shell composition for soft capsules that can increase the shelf life of soft capsules by minimizing the phenomenon of contents moving into the shell.

Figure 1 schematically shows the reaction for detecting arabinogalactan using the β-glucosyl yarib reagent.
Figure 2 is a graph showing the fraction of water-soluble substances in ginseng fruit.
Figure 3 is a graph showing the chromatography results of ginseng fruit polysaccharide.
Figure 4 is a photograph showing precipitation of standard substances, ginseng fruit polysaccharide and red ginseng root polysaccharide by treatment with β-glucosyl yarib reagent.
Figure 5 is a graph showing a comparison of the precipitation areas of standard material, ginseng fruit polysaccharide, and red ginseng root polysaccharide by treatment with β-glucosyl Yariv reagent.
Figure 6 is a photograph of the sample used in Test Example 2.
Figure 7 is a schematic diagram showing an example of the content transfer mechanism of a conventional gelatin film and a film according to an embodiment of the present invention.

Hereinafter, embodiments of the present application will be described in more detail with reference to the attached drawings. However, the technology disclosed in this application is not limited to the embodiments described herein and may be embodied in other forms. However, the embodiments introduced here are provided to ensure that the disclosed content is thorough and complete and that the spirit of the present application can be sufficiently conveyed to those skilled in the art. In order to clearly express each component in the drawing, the size of the component, such as width or thickness, is shown somewhat enlarged. Additionally, for convenience of explanation, only some of the components are shown, but those skilled in the art will be able to easily understand the remaining components. Additionally, a person skilled in the art will be able to implement the ideas of this application in various other forms without departing from the technical spirit of this application.

In this specification, “soft capsule” may refer to a dosage form encapsulated by dissolving or suspending the contents in a liquid or semi-solid excipient and filling the soft shell in a liquid or paste-like form. If the content (functional ingredient) has sufficient solubility or dispersibility in a fat-soluble solution, the most appropriate form for ingesting the functional ingredient as a solid preparation is a soft capsule. In addition, by sealing it with a film, it has the advantages of convenience of ingestion, masking odor and taste, and blocking the ingredients it contains from oxygen and light.

In one embodiment, the present invention can provide a film composition for soft capsules containing a film migration prevention ingredient. In one example, the film migration prevention component may include one or more of ginseng fruit polysaccharide and green tea powder.

Ginseng fruit polysaccharide may be a polysaccharide component derived from the fruit part of the aerial part of ginseng ( Panax ginseng CA Meyer). In one example, the ginseng fruit may be a portion containing ginseng fruit pulp, pericarp, or both pulp and pericarp.

The ginseng fruit polysaccharide can be obtained from the extracted insoluble components that do not dissolve in ethanol after extracting the ginseng fruit using ethanol. For example, the ethanol-extractable insoluble component can be extracted using water to separate only the water-soluble component, and the ginseng fruit polysaccharide contained in this water-soluble component can be used as an active ingredient. For example, ginseng fruit polysaccharide can be obtained by concentrating the water-soluble component, precipitating it with ethanol, and then removing the low molecular weight component.

For example, ginseng fruit with the seeds removed is extracted using 50-100% ethanol, and then the insoluble components are heated and extracted with 3-10 times the volume of water to obtain a water-soluble extract. The water-soluble extract is concentrated to a solid content of 10-50% by weight, precipitated with 2-5 times the volume of ethanol, and then separated with a molecular weight cut off of 10,000-30,000 to remove low molecular weight components. Thus, ginseng fruit polysaccharide can be obtained. Removal of the low molecular weight components can be performed by filtration such as ultrafiltration using an ultrafiltration membrane, dialysis, or repeated dissolution treatment with 2-10 times the volume of 50-100% ethanol 1-10 times. In one example, drying may be performed after removing the low molecular weight component. The drying may be done by freezing, hot air, spraying, or vacuum treatment.

In one example, enzyme treatment may be further included before water-extracting the water-soluble components of the ginseng fruit. The enzyme may be used without limitation as long as it is an enzyme used in food, but may be selected from, for example, amylase, protease, pectinase, lipase, cellulase, xylase, beta-glucanase, or pullulanase. . The enzyme treatment may be performed, for example, by reacting with the enzyme at 40 to 60°C for 10 to 60 minutes.

The ginseng fruit polysaccharide may include arabinose, galactose, galacturonic acid, and glucuronic acid.

In one example, the total amount of galacturonic acid and glucuronic acid based on the total weight of the polysaccharide is 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, 0.6% by weight or more, 0.7% by weight or more, 0.8% by weight or more, 0.9% by weight or more, 1% by weight or more, 2% by weight or more, 3% by weight or more, 4% by weight or more, 5% by weight or more, 6% by weight or more, 7% by weight or more, 8 wt% or more, 9 wt% or more, or 10 wt% or more, and 25 wt% or less, 24 wt% or less, 23 wt% or less, 22 wt% or less, 21 wt% or less, 20 wt% or less, 19 wt% or less. or less, 18 weight% or less, 17 weight% or less, 16 weight% or less, 15 weight% or less, 14 weight% or less, 13 weight% or less, 12 weight% or less, 11 weight% or less, 10 weight% or less, 9 weight% or less Hereinafter, it may be included in 8 weight% or less, 7 weight% or less, 6 weight% or less, 5 weight% or less, or 4 weight% or less. For example, the content may be 0.1% by weight to 25% by weight, or 0.5% by weight to 20% by weight.

The galacturonic acid is present in an amount of more than 0.1% by weight, more than 0.2% by weight, more than 0.3% by weight, more than 0.4% by weight, more than 0.5% by weight, more than 0.6% by weight, more than 0.7% by weight, more than 0.8% by weight, 0.9% by weight or more, 1% by weight or more, 2% by weight or more, 3% by weight or more, 4% by weight or more, 5% by weight or more, 6% by weight or more, 7% by weight or more, 8% by weight or more, 9% by weight or more, or 10% by weight or more, 20% by weight or less, 19% by weight or less, 18% by weight or less, 17% by weight or less, 16% by weight or less, 15% by weight or less, 14% by weight or less, 13% by weight or less, 12% by weight. Hereinafter, it may be included in 11 weight% or less, 10 weight% or less, 9 weight% or less, 8 weight% or less, 7 weight% or less, 6 weight% or less, 5 weight% or less, or 4 weight% or less. The content may be, for example, 0.1% to 20% by weight, 0.1% to 15% by weight, 1% to 5% by weight, 5% to 15% by weight, or 0.5% to 5% by weight.

The glucuronic acid is present in an amount of at least 0.1% by weight, at least 0.2% by weight, at least 0.3% by weight, at least 0.4% by weight, at least 0.5% by weight, at least 0.6% by weight, at least 0.7% by weight, at least 0.8% by weight, At least 0.9% by weight, at least 1% by weight, at least 2% by weight, at least 3% by weight, at least 4% by weight, at least 5% by weight, at least 6% by weight, or at least 7% by weight, and at least 10% by weight, at least 9% by weight. Hereinafter, it may be included in 8 weight% or less, 7 weight% or less, 6 weight% or less, 5 weight% or less, or 4 weight% or less. The content may be, for example, 0.1% to 10% by weight, 0.5% to 5% by weight, or 0.1% to 5% by weight.

In one example, the arabinose may be included in an amount of 2% to 30% by weight based on the total weight of the polysaccharide.

In one example, the galactose may be included in an amount of 5% to 50% by weight based on the total weight of the polysaccharide.

The ginseng fruit polysaccharide contains a high proportion of arabinogalactan structures. Detection of the arabinogalactan structure can be done using β-glucosyl Yariv reagent. Figure 1 schematically shows the reaction for detecting arabinogalactan using the β-glucosyl yarib reagent. The β-glucosyl yarib reagent is 1,3,5-tri-(4-β-glucopyranosyl-oxyphenylazo)-2,4,6-trihydroxybenzene (1,3,5-tri-( 4-β-oxyphenylazo)-2,4,6-trihydroxybenzene), which reacts specifically with type II arabino-β-3,6-galactan among arabinogalactans. This forms a red precipitate. The area of the red precipitate produced by treatment with the β-glucosyl yarib reagent and the concentration of the arabinogalactan structure are proportional in a concentration-dependent manner. The ginseng fruit polysaccharide is 40% or more, 50% or more, 60% or more when the precipitation size produced from standard arabino-β-3,6-galactan (arabino-β,6-galactan) at the same concentration is 100%. % or more, 70% or more, or 80% or more, and may indicate a needle conversion area of 90% or less, 80% or less, 70% or less, or 60% or less. For example, the sediment conversion area may be 50% to 90% or 50% to 80%.

The weight average molecular weight of the ginseng fruit polysaccharide may be 10 kDa or more. The ginseng fruit polysaccharide may have a main peak at a molecular weight of 70 kDa to 80 kDa.

The ginseng fruit polysaccharide is a total of various polysaccharide components, and can exhibit a significant film migration prevention effect through the synergistic effect of the combination of specific components included.

Green tea powder is made by drying and grinding the leaves of camellia sinensis, for example, matcha can be used. In one example, green tea powder includes green tea leaves processed into granulated powder using a grinder, etc., or processed into fine powder using an air mill or jet mill.

According to one embodiment of the present invention, a material having a macromolecular structure can be included as a film transfer prevention component to prevent the contents from transferring to the film due to their macromolecular structure.

Figure 7 is a schematic diagram showing an example of the content film transition mechanism of a conventional gelatin film and a film according to an embodiment of the present invention. In the case of a conventional gelatin shell, the content may be transferred to the film, causing a problem of content reduction. However, according to the shell composition for soft capsules according to an embodiment of the present invention, the shell contains a material having a macromolecular structure, and the macromolecular structure thereof This can prevent the contents from moving into the film.

The film migration prevention component may be included in an amount of 0.1% to 10% by weight based on the total weight of the composition. For example, the film migration prevention component is present in an amount of 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, 0.6% by weight or more, 0.7% by weight or more, 0.8% by weight or more. % or more, 0.9 % or more, 1.0 % or more, 1.5 % or more, 2.0 % or more, 2.5 % or more, or 3.0 % or more by weight, and 10 % or less, 9.5 % or less, 9.0 % by weight or less. , 8.5 wt% or less, 8.0 wt% or less, 7.5 wt% or less, 7.0 wt% or less, 6.5 wt% or less, 6.0 wt% or less, 5.5 wt% or less, 5.0 wt% or less, 4.5 wt% or less, or 4.0 wt% or less. You can. Within the above range, the effect of preventing film migration may be excellent.

In one embodiment, the composition may further include starch. The starch may be raw starch; It may include one or more modified starches selected from acid-treated starch, hydroxypropylated starch, alpha starch, cross-linked starch, and starch decomposition products. Starch raw materials may include grains such as corn and wheat, potatoes, sweet potatoes, tapioca, etc., but are not limited thereto.

The starch may be included in an amount of 10% to 40% by weight based on the total weight of the composition. For example, the starch may be at least 10% by weight, at least 15% by weight, at least 20% by weight, or at least 25% by weight, and at most 40% by weight, at most 35% by weight, or at most 30% by weight, based on the total weight of the composition. . Within the above range, the contents may have excellent efficacy in preventing film migration.

In one embodiment, the composition may include glycerin. The glycerin may be included in an amount of 5% to 20% by weight based on the total weight of the composition. For example, the glycerin is present in an amount of at least 5% by weight, at least 6% by weight, at least 7% by weight, at least 8% by weight, at least 9% by weight, at least 10% by weight, at least 11% by weight, or at least 12% by weight, based on the total weight of the composition. or more, and may be 20 wt% or less, 19 wt% or less, 18 wt% or less, 17 wt% or less, 16 wt% or less, 15 wt% or less, 14 wt% or less, or 13 wt% or less. Within the above range, the effect of preventing film migration of the contents may be excellent.

In one embodiment, the composition may further include a gelling agent, a buffering agent, etc., but is not limited thereto. For example, the gelling agent may be one or more selected from pullulan, agar, carrageenan, cellulose, gum arabic, guar gum, mannan gum, and xanthan gum, but is not limited thereto. For example, the buffering agent may be one or more selected from trisodium citrate, sodium phosphate dibasic, and potassium phosphate dibasic, but is not limited thereto. In addition, additives such as disintegration aids, antioxidants, and film softeners may be further included within the range that do not impair the effects according to the embodiments of the present invention, but are not limited thereto. The gelling agent, buffer, and additive may be included in an amount of 3% to 30% by weight based on the total weight of the composition, but is not limited thereto.

In one embodiment, the contents of the soft capsule may include pharmacologically active ingredients or functional ingredients of functional health foods. The content is not particularly limited as long as it can be filled in a soft capsule, and for example, fat-soluble ingredients can be used.

The shell composition for soft capsules according to embodiments of the present invention excludes animal ingredients by using plant-derived ingredients, and at the same time, it can suppress the transfer of contents into the shell by evenly including a film migration prevention ingredient in the film. When the content transfers to a film, the content decreases over time. In this case, the shelf life may be shortened as the content falls below the prescription or design content, but the shelf life can be sufficiently secured due to the migration prevention effect of the composition according to an embodiment of the present invention. For example, when the soft capsule according to this embodiment is for health functional food, the contents can maintain the prescribed or designed content for 18 to 36 months, which is a typical expiration date. In addition, considering the phenomenon of content migration, the problem of having to manufacture the content in excess of the prescribed content can be solved.

A soft capsule coating composition according to an embodiment of the present invention can be used to produce a soft capsule coating composition using a method commonly used in the technical field. For example, the film composition for soft capsules can be prepared and then aged and dried to form a film.

In another embodiment of the present invention, a soft capsule composition including the soft capsule coating composition and contents can be provided. Since the shell composition and contents for soft capsules are the same as described above, description thereof will be omitted.

The soft capsule can be manufactured by a method commonly used in the technical field.

The soft capsule may be a health functional food formulation containing a medicine containing a pharmacologically effective ingredient or a health functional substance.

Hereinafter, the present invention will be described in detail with reference to examples, comparative examples, and test examples. These are only presented as examples to explain the present invention in more detail, and it is clear to those skilled in the art that the scope of the present invention is not limited by these Examples, Comparative Examples, and Test Examples. It will be self-explanatory.

[Preparation Example 1] Preparation of ginseng fruit polysaccharide

Ginseng fruits with seeds removed are extracted with 10 times the volume of 90% ethanol, water-soluble components are precipitated, and the supernatant is removed. The precipitated insoluble components are extracted with 20 times the volume of water at 90°C for 5 hours. The extract is concentrated to a solid content of 30% by weight and precipitated by adding 90% ethanol twice the volume of the concentrate. High-performance liquid chromatography (HPLC) results of the precipitated water-soluble components are shown in Figure 2. The precipitate was separated through ultrafiltration with a molecular weight cut off of 20,000 to remove low molecular weight components and freeze-dried to obtain a ginseng fruit polysaccharide with a molecular weight of 10 kDa or more, with a main molecular peak of 70 to 80 kDa. High-performance liquid chromatography (HPLC) results of the prepared ginseng fruit polysaccharide are shown in Figure 3.

[Preparation Example 2] Preparation of red ginseng polysaccharide

Red ginseng polysaccharide was prepared in the same manner as Preparation Example 1, except that red ginseng root was used instead of ginseng fruit.

[Test Example 1] Detection of Arabinogalactan

Reactivity with β-glucosyl Yariv reagent (Biosupplies, Parkville, Australia) to confirm the presence of arabino-β-3,6-galactan was tested using the method of Holst and Clarke (Van Holst GJ , Clarke AE. Quantification of arabinogalactan-protein in plant extracts by single radial gel diffusion. Anal. Chem. 148: 446-450 (1985)).

Prepare a 0.15M NaCl agarose plate containing 10㎍/㎖ of β-glucosyl yarib reagent, create wells with a diameter of 2.5mm, and add a solution containing 5㎍ of sample and gum Arabic, a standard substance diluted by concentration. It was injected into each well. The plate was allowed to react in a wet state for 15 hours, and the presence or absence of arabino-β-3,6-galactan was observed by observing the red precipitate formed, and the sample, β-glucosyl yarib reagent, and The reactivity was compared by calculating the area of the sedimentation produced. As shown in Figure 4, the samples were used at concentrations of 62.5, 125, 250, 500, and 1000 ㎍/㎖ as the standard material, and the polysaccharide of Preparation Example 1 and Preparation Example 2 at concentrations of 100, 500, and 1000 ㎍/㎖, respectively.

The area of the resulting red precipitate was measured, and the relative content of arabino-β-3,6-galactan is shown in Figure 5. The results in Figure 5 compare the area of each sample treated at a concentration of 1000 μg/ml with the standard substance treated at a concentration of 1000 μg/ml.

From the results in Figure 5, it can be seen that the ginseng fruit polysaccharide contains an arabinogalactan structure at a content more than twice that of the red ginseng polysaccharide.

[Comparative Example 1] Preparation of general gelatin film

A composition containing 48.8% gelatin, 37.9% glycerin, 11% vegetable starch, and 2.3% processed oil powder based on dry weight was prepared, aged, and dried to prepare a gelatin shell used as a conventional soft capsule shell.

[Example 1] Preparation of a film containing green tea powder

By weight, the composition is 26.55% modified starch (corn starch; hydroxypropyl starch, Neocap, Samyang Corporation), 12.3% glycerin, 7.7% pullulan, 1% green tea powder (matcha), 1% trisodium citrate, and 51.45% purified water. The shell composition for soft capsules containing the green tea powder of Example 1 was prepared by manufacturing, maturing and drying the shell composition according to the manufacturing process.

[Example 2] Preparation of a film containing ginseng fruit polysaccharide

Composition by weight: 26.55% modified starch (corn starch; hydroxypropyl starch, Neocap, Samyang Corporation), 12.3% glycerin, 7.7% pullulan, 1% ginseng fruit polysaccharide (preparation example 1), 1% trisodium citrate, 51.45% purified water. A shell for soft capsules containing the ginseng fruit polysaccharide of Example 2 was prepared by preparing, maturing and drying the shell composition according to a typical film manufacturing process.

[Test Example 2] Evaluation of fulfillment of contents

Using the soft capsule films prepared in Comparative Example 1, Example 1, and Example 2, the film transfer of the contents was evaluated. A Haematococcus extract containing 6.59 mg/g astaxanthin was used as the content.

The films of Comparative Example 1, Example 1, and Example 2 were each immersed in the content of the Haematococcus extract dissolved at a concentration of 10% by weight using edible oil (avocado oil) as a solvent, sealed, and stored. Storage was performed at 40°C for 2 weeks, and the astaxanthin concentration in the film was measured and shown in Table 1 below. Astaxanthin concentration is determined by obtaining the film according to Test Method 4 of the Health Functional Food Code of the Ministry of Food and Drug Safety. It was measured based on the 3-46 astaxanthin test method.

film sample Astaxanthin content (mg/g) Comparative Example 1 0.63 Example 1 Not detected Example 2 Not detected

From the results in Table 1, in the case of the gelatin film of Comparative Example 1, transfer of about 10% of astaxanthin into the film was observed, whereas in the case of Examples 1 and 2, no transferred astaxanthin was detected, resulting in the film of the contents. It can be seen that the implementation effect is excellent. The above experiment was conducted for two weeks, but since it was conducted under accelerated conditions of 40°C, when compared to actual use conditions, trials 1 and 2 can be interpreted as showing the effect of no transfer of contents for about 6 months.

Claims (10)

A shell composition for soft capsules containing at least one of ginseng fruit polysaccharide and green tea powder as an ingredient to prevent film migration. According to paragraph 1,
A composition wherein the ginseng fruit polysaccharide includes arabinose, galactose, galacturonic acid, and glucuronic acid. According to paragraph 2,
A composition comprising 0.1% by weight to 25% by weight of galacturonic acid and glucuronic acid based on the total weight of the ginseng fruit polysaccharide. According to paragraph 1,
The ginseng fruit polysaccharide is 100% of the standard arabino-β-3,6-galactan when treated with β-glucosyl Yariv reagent. , a composition that exhibits a response of at least 40%. According to paragraph 1,
The composition, wherein the ginseng fruit polysaccharide is derived from a water-soluble component of the ethanol-insoluble fraction of ginseng fruit. According to paragraph 1,
The composition further includes starch. According to paragraph 1,
The composition further includes glycerin. According to paragraph 1,
A composition comprising 0.1% to 10% by weight of the film migration prevention component based on the total weight of the composition. According to clause 6,
A composition comprising 10% to 40% by weight of the starch based on the total weight of the composition. In clause 7,
A composition comprising 5% to 20% by weight of glycerin based on the total weight of the composition.