JP2013213000A - Soft capsule - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a soft capsule which controls the oxidation in contents of the soft capsule, controls collapse retardation, controls blocking, and improves preservability such as browning prevention and deterioration prevention.SOLUTION: A soft capsule prepared by covering a content containing at least an unsaturated fatty acid or an unsaturated fatty acid ester with a coating film is characterized in that the content and/or the coating film contain the following components (A), (B) and (C). (A): a content of a Zingiberaceae plant. (B): a saccharide or a sugar alcohol having a melting point of ≤150°C and a solubility of ≥60 g/100 mL in 100 mL of water at 25°C. (C): a saccharide or a sugar alcohol having a melting point of ≥160°C and a solubility of ≤30 g/100 mL in 100 mL of water at 25°C.

Description

  The present invention relates to a soft capsule characterized by the component composition of the content and / or film, and more specifically, the content containing at least an unsaturated fatty acid or an unsaturated fatty acid ester, the content of a specific component composition, and / or The present invention relates to a soft capsule whose storage stability and blocking resistance of various performances are greatly improved by covering with a film.

Soft capsules are obtained by encapsulating active ingredients such as pharmaceuticals, health materials, and functional materials in a film prepared using a solution such as a protein such as gelatin; a polysaccharide such as starch;
In particular, when the active ingredient, or in some cases, the dispersion medium or solvent thereof is a liquid, there is a risk of gap leakage from between the lid portion and the body portion in the case of a hard capsule. The feature is that there is no possibility of leakage.
In addition, tablets cannot contain such a liquid as it is, but soft capsules have the advantage that they can be filled as they are.
In addition, since the oxygen permeability is generally low, the contents are not easily oxidized.

However, although the soft capsule is a dosage form in which the content is relatively difficult to oxidize, the content may oxidize due to a decrease in oxygen barrier property due to an increase in the moisture content of the film. There was also a problem that it was necessary to suppress oxidation.
In particular, material components such as pharmaceuticals, health foods, foods, animal feeds, etc. include “components that are easily altered” such as components that are easily oxidized and browned, but oxides react with film materials such as gelatin. This may cause a phenomenon of insolubilization (insolubilization of gelatin, delay of disintegration), and in particular, soft capsules using gelatin as a film may cause health damage.

Further, the soft capsule has a problem that the soft capsule is likely to cause a blocking problem due to an increase in temperature and humidity.
In addition to the above, in soft capsules, there is also deterioration in preservability such as browning and alteration of the contents due to the interaction between the contents and the film, etc., and there is a decay delay due to the interaction between the contents and the film. There was also a problem that it was easy to occur.

  Regarding the decay delay caused by the interaction between the “contents or oxide of the contents” and the film component, a method of containing citric acid in the film (Patent Document 5) and a method of containing tocopherol (Patent Document 6) A method of containing phytic acid (Patent Document 7), a method of containing a specific starch degradation product (Patent Document 8), and the like are known.

  Further, regarding the suppression of oxidation of the contents, there are Patent Document 9 and the like in addition to Patent Document 6, and Patent Document 10 and the like are particularly intended to improve browning prevention, alteration prevention and the like. is there.

  In order to prevent blocking of soft capsules, for example, xylitol (melting point: 92 ° C. to 96 ° C., solubility in 100 mL of water at 25 ° C. is 10 g / 100 mL) is contained in the film. A method of precipitating (Patent Document 1), a method of containing a silicon dioxide fine powder in a film (Patent Document 2), a method of allowing a crystalline fine powder to deposit on the surface by standing (aging) in a high-humidity atmosphere ( Patent Document 3), a method of spraying fine powder onto a capsule surface in a capsule film drying step (Patent Document 4), and the like are known.

  However, in order to sufficiently suppress blocking, the above-mentioned “fine powder” and “substance that becomes a fine powder as a result of deposition on the capsule surface” must be used in large quantities, and the number of processes increases. There was a problem.

  In recent years, demands for solving the above-described problems with respect to soft capsules are increasing, and such known techniques are insufficient and there is room for further improvement.

International Publication WO2005 / 011402 Japanese Patent Laid-Open No. 2003-070880 JP 2001-089362 A JP 2001-178376 A JP 59-039834 A Japanese Patent Laid-Open No. 10-101550 JP 2006-328038 A JP 2010-090080 A JP 2001-262180 A JP 2001-178383 A

  The present invention has been made in view of the above-mentioned background art, and its problem is to suppress deterioration due to auto-oxidation or the like of “unsaturated fatty acid or unsaturated fatty acid ester” which is the content of the soft capsule, and to preserve the soft capsule To suppress the phenomenon of soft capsule disintegration in the body (hereinafter sometimes abbreviated as “delay delay”), and soft capsules by storing multiple soft capsules adjacent to each other Another object of the present invention is to provide a soft capsule that suppresses the adhesion between each other (hereinafter sometimes abbreviated as “blocking”) and has improved storage stability such as prevention of browning and alteration.

  As a result of intensive studies to solve the above problems, the present inventor has (A) ginger plant content, (B) a relatively low melting point in the contents of the soft capsule and / or the soft capsule film, By including at least three kinds of components of “saccharides or sugar alcohols” having a relatively high solubility in water, (C) “saccharides or sugar alcohols” having a relatively high melting point and a relatively low solubility in water, The inventors have found that the above problems can be solved and have completed the present invention.

That is, the present invention is a soft capsule in which a content containing at least an unsaturated fatty acid or an unsaturated fatty acid ester is covered with a film, and the content and / or the film includes the following components (A) and (B): And component (C)
(A) Ginger plant inclusions (B) Sugars or sugar alcohols having a melting point of 150 ° C. or lower and solubility in 100 mL of water at 25 ° C. of 60 g / 100 mL or higher (C) Melting point of 160 ° C. or higher And a soft capsule characterized by containing a saccharide or sugar alcohol having a solubility in 100 mL of water at 25 ° C. of 30 g / 100 mL or less.

According to the present invention, there can be provided a soft capsule that solves the problems and problems described above and suppresses deterioration of components that are susceptible to auto-oxidation such as unsaturated fatty acid and unsaturated fatty acid ester contained in the contents of the soft capsule.
That is, for example, unsaturated fatty acids such as docosahexaenoic acid and eicosapentaenoic acid having physiological activity, or fats and oils obtained by the reaction thereof are easily oxidized by oxygen in the air, but if the soft capsule of the present invention is used, , Such oxidation can be suppressed.
Furthermore, due to recent advances in purification technology, it has become possible to contain various higher unsaturated fatty acids having a high content (for example, 70% by mass or more), or esters thereof in soft capsules. Such functional components are more susceptible to oxidation. However, if the soft capsule of the present invention is used, for example, the above-mentioned “component with a high content of unsaturated fatty acids” that is easily affected by oxidation can sufficiently suppress such oxidation.

  In particular, when the contents of the soft capsule include “unsaturated fatty acid or unsaturated fatty acid ester” (hereinafter, the parentheses may be simply abbreviated as “unsaturated fatty acids”), When stored and aged, the unsaturated fatty acids and the “component of the soft capsule film” interact with each other. For example, a reaction at the interface between the contents and the film may cause a delay in decay. According to this, it is possible to provide a soft capsule in which the decay delay is suppressed.

Pharmaceutical materials containing "unsaturated fatty acids"; functional materials such as health foods; foods; animal feeds; etc., which are susceptible to oxidation, but oxides produced by oxidation react with film materials such as gelatin As a result, it may cause a phenomenon of insolubility (insolubilization of gelatin, delay of disintegration). According to the present invention, such a phenomenon can be suppressed.
In particular, even when the content of the higher unsaturated fatty acid is particularly high in the contents of the soft capsule, if the soft capsule of the present invention is used, the delay of the disintegration time of the film over time can be extremely reduced.

  Moreover, the reaction between contents, or the Maillard reaction (reaction of saccharides and an amine compound) in the interface of a content and a film | membrane can be suppressed. Therefore, even when the soft capsules are stored and aged, decay delay, browning, etc. can be suppressed. In particular, when the main component of the film is gelatin, the reaction between the amino group of the gelatin and saccharides can be suppressed, and as a result, disintegration delay and browning can be suppressed. Gelatin has an amino group in a lysine residue or the like, which is a constituent component of gelatin, and the reactivity of the amino group sometimes becomes a problem.

In general, when an oily drug, oily food, or the like is softly encapsulated, gelatin is suitably used for the film. The required properties of the gelatin coating are: (1) it is easy to prevent the contents from deteriorating by blocking the contact between the contents and external oxygen, and (2) the contents are easily disintegrated in the digestive organs of the human body. Two things must be fulfilled: the ability to release objects.
However, when using highly fatty substances such as unsaturated fatty acids and fats and oils having unsaturated fatty acids as the contents, the disintegration time is delayed over time in the normal gelatin film after production. The contents may deteriorate.
Such a problem can be solved by using the soft capsule of the present invention.

Moreover, according to this invention, the soft capsule in which blocking which is adhesion of soft capsules was suppressed can be provided. That is, when a plurality of soft capsules are stored in a container or the like, the soft capsules may adhere to each other, and even if the soft capsules can be taken (separated) immediately, it becomes uncomfortable for the user.
However, in the soft capsule of the present invention, when the later-described component (C) is contained in the film, the component (C) can easily form a layer on the surface of the soft capsule film during the preparation of the soft capsule. (Hereinafter, the property that blocking is difficult to occur is abbreviated as “blocking resistance”).
Furthermore, when the component (B) is contained in the coating, the component (C) moves to the surface of the coating of the soft capsule and easily forms a layer, so that blocking is less likely to occur.

  In addition, some known techniques require that the fine powder be deposited on the surface by leaving it in a high humidity environment in order to improve the blocking resistance. Even if it is not left in the environment, a soft capsule excellent in blocking resistance can be prepared, so that the number of steps is reduced and the cost can be reduced.

  Further, according to the present invention, the anti-blocking property may be improved by depositing the fine powder of the component (C) on the surface of the film, but the layer of the component (C) is formed on the surface of the film and the anti-resistance In some cases, the blocking property may be improved, and in this case, a soft capsule excellent in blocking resistance can be produced despite its gloss.

Further, according to the present invention, if the contents of the soft capsule contain components (A), (B) and (C) described later, various contents including deterioration due to oxidation of unsaturated fatty acids are deteriorated. Can be suppressed. Further surprisingly, even when the components (A), (B), and (C) are contained only in the soft capsule film, deterioration due to oxidation of unsaturated fatty acids as contents can be suppressed.
According to the present invention, it is possible to provide a soft capsule capable of maintaining its physiological effectiveness and safety for a long period of time even when the content of a saturated fatty acid is high and easily oxidized.

  Hereinafter, the present invention will be described, but the present invention is not limited to the following specific embodiments, and can be arbitrarily modified within the scope of the technical idea.

The “unsaturated fatty acid” in the present invention refers to a fatty acid having a carbon-carbon double bond or triple bond, whether it exists in nature or not, even if it is a natural product, it is a modified natural product. There may be. Further, the number of carbon-carbon double bonds or triple bonds is not limited, and may be one or two or more. The “unsaturated fatty acid” in the present invention may have a branch in the molecule, or may have an organic group such as a hydroxyl group.
The “unsaturated fatty acid” in the present invention may be a higher fatty acid or a higher fatty acid, but is preferably a higher fatty acid. The “higher fatty acid” in the present invention refers to a fatty acid having 12 or more carbon atoms including carbon of a carboxyl group.

  The “unsaturated fatty acid ester” in the present invention refers to a compound in which the carboxyl group of an unsaturated fatty acid and the hydroxyl group of a compound having a hydroxyl group form an ester bond. Although there is no particular limitation, the “compound having a hydroxyl group” is preferably glycerin. Hereinafter, the “unsaturated fatty acid ester” may be simply abbreviated as “oil or fat”.

In the present invention, the term “saccharide” refers to a “cyclic compound having an aldehyde group or a ketone group” (hereinafter abbreviated as “monosaccharide”) existing inside a living organism, or a plurality of them bonded by glycosidic bonds. A compound (hereinafter referred to as “polysaccharide”). “Polysaccharides” include “disaccharides” and may or may not be reducible.
The “saccharide” in the present invention may be digested in the human body, not digested or difficult to digest, and it does not matter whether it is sweet or not.

  The “sugar alcohols” in the present invention refers to a compound having a hydroxyl group derived from a saccharide. It may be derived from saccharides by naturally occurring microorganisms in nature, may be artificially fermented from saccharides, or may be artificially synthesized from saccharides. The “sugar alcohols” in the present invention may be digested in the human body or may not be digested or difficult to digest.

  The “saccharides” and “sugar alcohols” in the present invention may overlap. That is, from the above definition, a compound belonging to both may or may exist.

The present invention relates to a soft capsule in which a content containing at least an unsaturated fatty acid or an unsaturated fatty acid ester is covered with a film.
The “unsaturated fatty acid” in the present invention is not specifically limited. For example, crotonic acid, myristoleic acid, palmitoleic acid, oleic acid, elaidic acid, vaccenic acid, gadoleic acid, eicosenoic acid, erucic acid, Monounsaturated fatty acids such as nervonic acid; diunsaturated fatty acids such as linoleic acid, eicosadienoic acid, docosadienoic acid; linolenic acid, pinolenic acid, eleostearic acid, mead acid, dihomo-γ-linolenic acid, eicosatrienoic acid, etc. Triunsaturated fatty acids; tetraunsaturated fatty acids such as stearidonic acid, arachidonic acid, eicosatetraenoic acid, adrenic acid; boseopentaenoic acid, eicosapentaenoic acid (hereinafter sometimes abbreviated as “EPA”), docosapentaene Pentaunsaturated fatty acids such as acid, ozbond acid, sardine acid, tetracosapentaenoic acid; Kosahekisaen acid (hereinafter sometimes abbreviated as "DHA"), hexamethylene unsaturated fatty acids such as herring acid, and the like.

In the present invention, the number of carbon-carbon double bonds of the “unsaturated fatty acid” is preferably 2 or more, more preferably 3 or more, particularly preferably 4 to 7, and further preferably 5 or 6.
If the number of carbon-carbon double bonds is too small, the degree of alteration due to oxidation is reduced, so that the effect of suppressing oxidation of the present invention may not be sufficiently exhibited.
Higher unsaturated fatty acids having 12 or more carbon atoms are preferred, 14 or more carbon atoms are more preferred, 16 to 24 carbon atoms are particularly preferred, and 18 to 22 carbon atoms are still more preferred. When the carbon number is within this range, the effect of suppressing oxidation of the present invention can be sufficiently exhibited.

The “unsaturated fatty acid ester” in the present invention refers to a compound in which the carboxyl group of the unsaturated fatty acid and the hydroxyl group of the “compound having a hydroxyl group” are ester-bonded. As the “compound having a hydroxyl group”, A monohydric alcohol, a dihydric alcohol, or a trihydric alcohol is mentioned. In addition to the alcohol, sugars, amino acids, phosphoric acid and the like can be mentioned as those to which unsaturated fatty acids are bonded.
The trihydric alcohol is not particularly limited, but glycerin is preferable. That is, the “unsaturated fatty acid ester” is preferably “oil or fat” which is a glycerin ester. This is because there are many types of oils and fats as naturally occurring functional substances.

  Specifically, for example, “monoglyceride, diglyceride or triglyceride” formed by binding EPA and / or DHA; “EPA or DHA monovalent alkyl” such as EPA ethyl ester, DHA ethyl ester, EPA methyl ester, DHA methyl ester, etc. Phospholipids containing EPA and / or DHA; and the like.

  When the content is an unsaturated fatty acid or an unsaturated fatty acid ester, the soft capsule of the present invention easily exhibits an effect of suppressing oxidation by oxygen in the air. And especially when the content rate of a higher unsaturated fatty acid is high, an effect is exhibited. Specifically, it is particularly effective when the content of the higher unsaturated fatty acid is preferably 60% by mass or more, more preferably 70% by mass or more, and particularly preferably 80% by mass or more, based on the entire contents. To do.

The “oxidation inhibiting effect” in the present invention is evaluated by measuring the transition (change) of the peroxide value (POV) and the change width from the initial, and the “oxidation inhibiting effect” in the present invention is thus Defined as evaluated.
Specifically, for example, from the transition (change) or initial value of the peroxide value (POV) from 3 days to 3 months at 60 ° C. or from 2 months to 1 year at 40 ° C. and 75% relative humidity. Evaluation is made by measuring the width of change.

The peroxide value represents the amount of hydroperoxide generated by auto-oxidation of an object in milliequivalents per 1 kg of the object, and is measured according to an iodometric titration method according to the Japanese Agricultural Standards Measurement Method.
Specifically, potassium iodide is allowed to act on an object, and the liberated iodine is obtained by a titration method using a sodium thiosulfate solution and converted to milliequivalents of hydroperoxide.
Note that a correlation with values measured by other methods such as a colorimetric method may be obtained in advance and may be obtained by interpolation. Further, “POV analysis kit” manufactured by Shibata Scientific Instruments Co., Ltd. may be used.

The soft capsule of the present invention must contain the following component (A), component (B) and component (C) in the contents and / or the film.
(A) Ginger plant inclusions (B) Sugars or sugar alcohols having a melting point of 150 ° C. or lower and solubility in 100 mL of water at 25 ° C. of 60 g / 100 mL or higher (C) Melting point of 160 ° C. or higher And sugars or sugar alcohols having a solubility in 100 mL of water at 25 ° C. of 30 g / 100 mL or less

The “content of ginger family plant” which is the component (A) in the present invention refers to a component contained in a plant belonging to Zingiberaceae family. The ginger family plant is preferably a plant belonging to the genus Zingiber, particularly preferably Zingiber officinale. If it is a ginger, the kind, production center, etc. will not ask | require.
Although the containing site is not particularly limited, a rhizome is preferable.
Ingredients (A), “contents of ginger family plants” include ginger family plants (preferably ginger family rhizomes) powdered, ground, ginger family plants (preferably ginger family plants) And those obtained by drying the extract.
Here, the “extract” includes both those extracted by squeezing and those extracted with a solvent.

The component (A) in the present invention is particularly preferably ethanol or a single compound or “mixture of a plurality of compounds” extracted with “a mixed solvent of ethanol and water”.
In particular, the type of solvent actually extracted is not particularly limited as long as it is the same as that extracted with ethanol or a mixed solvent of ethanol and water. Moreover, there is no limitation about the ratio of ethanol and water, and what is extracted by arbitrary ratios is included.
The “content of ginger family plant” is more preferably extracted from a rhizome of ginger (preferably dried one) with a solvent.

  As extracts from ginger rhizomes, 6-gingerol and 6-shogaol are known, but instead of “content of ginger family plant”, 6-gingerol and / or 6-shogaol are used. As a result of evaluation, none of the effects of the present invention was exhibited. Therefore, the inclusion of 6-gingerol and / or 6-shogaol is not excluded in the “content of ginger plant” in the present invention, but the “content of ginger plant” in the present invention is 6- Those that are neither Gingerol nor 6-Shogaol are considered effective.

In the case where the “ginger plant content” in the present invention is not dissolved in water, and the film of the soft capsule is prepared from the aqueous solution in order to contain the component (A), the component (B) and the component (C) in the film. In order to disperse the ginger plant content in water, it is preferable to contain an emulsifying dispersant in the aqueous solution.
In addition, in the case where the “content of ginger family plant” in the present invention is not dissolved in the contents of the soft capsule, and the ingredients (A), (B) and (C) are contained in the contents, In order to disperse the content of the ginger family plant in the contents, it is preferable to contain an emulsifying dispersant.

  Such an emulsifying dispersant is not particularly limited, but fatty acid esters such as sucrose fatty acid ester and polyol fatty acid ester (for example, glycerin ester of fatty acid); saponins such as soybean saponin; lecithin such as egg yolk lecithin as a main component And lysolecithin obtained by hydrolyzing the ester bond of phospholipid and lecithin with an enzyme.

When the content of the component (A) ginger plant is included in the film of the soft capsule, it is extremely effective not only for suppressing the oxidation of the contents but also for suppressing the decay delay.
Furthermore, when the content of ginger plant is present in the film of the soft capsule, the rate at which the component (C) forms a layer on the film surface increases when the solvent of the film component (for example, water) is diffused during the preparation of the soft capsule. As a result, there is no need to leave it in a high-humidity environment as described in, for example, Patent Document 1 and Patent Document 3 (for example, “(4) Drying” which is an example of the manufacturing method described later. However, soft capsules with excellent blocking resistance can be prepared.
For example, compared with the soft capsules described in Patent Document 1 and Patent Document 3, soft capsules having extremely excellent blocking resistance can be prepared.

Component (B) in the present invention is “a saccharide or sugar alcohol having a melting point of 150 ° C. or lower and a solubility in 100 mL of water of 25 ° C. of 60 g / 100 mL or higher”.
Hereinafter, the solubility in 100 mL of water at 25 ° C. may be simply abbreviated as “solubility”.

The melting point of component (B) is essential to be 150 ° C. or lower, preferably 130 ° C. or lower, more preferably 110 ° C. or lower, and particularly preferably 100 ° C. or lower. The lower limit is not particularly limited, but is preferably 60 ° C or higher, particularly preferably 70 ° C or higher.
If the melting point is too high or too low, it may affect the layer formation of the coating surface of the component (C), and the above effect of the present invention may not be exhibited.

The solubility of the component (B) in water at 25 ° C. is essential to be 60 g / 100 mL or more, preferably 62 g / 100 mL or more, more preferably 64 g / 100 mL or more, and particularly preferably 66 g / 100 mL or more. The upper limit is not particularly limited, but is preferably 90 g / 100 mL or less, and particularly preferably 80 g / 100 mL or less.
The component (B) functions as a plasticizer, but if the solubility of the component (B) is too low, a sufficient amount as a plasticizer, that is, a sufficient amount for maintaining the strength of the film may not be blended. .

  Specific examples of the component (B) include trehalose (melting point 97 ° C., solubility 69 g / 100 mL), maltose (melting point 102 to 108 ° C., solubility 72 g / 100 mL), erythritol (melting point 121 to 123 ° C., solubility 60 g). / 100 mL), maltitol (melting point 145 ° C., solubility 114 g / 100 mL) and the like.

  The component (B) is particularly preferably a disaccharide or higher saccharide having no reducing property. When the contents contain saccharides or sugar alcohols with reducing properties and gelatin is used for the film, the contents and the film may interact with each other at the interface, resulting in decay delay or browning. .

Component (C) in the present invention is “a saccharide or sugar alcohol having a melting point of 160 ° C. or higher and a solubility in 100 mL of water of 25 ° C. of 30 g / 100 mL or lower”.
The melting point of component (C) is essential to be 160 ° C. or higher, but is preferably 180 ° C. or higher, more preferably 190 ° C. or higher, and particularly preferably 210 ° C. or higher. Although an upper limit does not have limitation in particular, 290 degrees C or less is preferable and 270 degrees C or less is especially preferable.
If the melting point is too low, the blocking resistance may be inferior even if the component (C) forms a layer on the surface of the soft capsule film or precipitates as a fine powder during soft capsule preparation.
On the other hand, when the melting point of the component (C) is too high, the above effect of the present invention may not be exhibited.

The solubility of the component (C) in water at 25 ° C. is essentially 30 g / 100 mL or less, preferably 25 g / 100 mL or less, more preferably 20 g / 100 mL or less, and particularly preferably 15 g / 100 mL or less. The lower limit is not particularly limited, but is preferably 0.1 g / 100 mL or more, more preferably 1 g / 100 mL or more, and particularly preferably 10 g / 100 mL or more.
If the solubility is too high, when preparing the soft capsule, component (C) may not form a layer on the surface of the soft capsule film or may not form a layer, may not precipitate as a fine powder, or may not easily precipitate, As a result, only soft capsules with poor blocking resistance may be produced.
On the other hand, when the solubility is too low, the above effect of the present invention may not be exhibited.

  Specifically, as the component (C), for example, inositol (melting point: 225 to 227 ° C., solubility: 14 g / 100 mL), lactose (melting point: 202 to 223 ° C., solubility: 22 g / 100 mL), mannitol (melting point: 166 to 168 ° C., Solubility 18 g / 100 mL), pentaerythritol (melting point 260 ° C., solubility 5.5 g / 100 mL) and the like.

Moreover, it is preferable that a component (C) is cyclitols. The term “cyclitols” refers to a compound in which one hydroxyl group is bonded to each of three or more carbon atoms constituting a cycloalkane ring.
When the component (C) is a cyclitol, at the time of soft capsule preparation, it is easy to deposit as a fine powder or a layer on the surface of the soft capsule film, and a soft capsule excellent in blocking resistance is easily obtained.

  As the cyclitols, inositol is particularly preferable in that a soft capsule excellent in blocking resistance can be obtained by forming a layer on the surface of the film or depositing it as a fine powder.

  The contents of the soft capsule of the present invention must contain at least an unsaturated fatty acid or an unsaturated fatty acid ester, and the components (A), (B) and (C) are contents when they are not contained in the film. In addition to these, various medicinal ingredients, health ingredient ingredients, functional ingredient ingredients, extenders, dispersants, etc., which are usually encapsulated in soft capsules (ie, in normal contents) In the present invention can also be included and contained.

  In addition, when the content of the soft capsule of the present invention contains citric acid, ascorbic acid, tocopherol, rosemary extract and the like, oxidation of unsaturated fatty acid or unsaturated fatty acid ester can be further suppressed.

There are no particular limitations on the type and manufacturing method of soft capsules, but soft capsules usually contain a base polymer such as gelatin or starch and a plasticizer such as glycerin or sorbitol added to the plate to prepare the contents. These are compression-molded, and their specific production methods are roughly classified into two methods: a flat plate method and a rotary die method.
A manufacturing method using gelatin will be described below using the rotary die method which is the mainstream of the current manufacturing method as an example, but the manufacturing method of the soft capsule of the present invention is not limited to the following.

(1) Preparation of contents If the contents are liquid, put them directly into the medicine tank, or if pretreatment such as emulsion or suspension is necessary, put them into the medicine tank after the treatment, for example, unsaturated fatty acid Alternatively, when the components (A), (B) and (C) are contained in the contents in addition to the unsaturated fatty acid ester, they are mixed here and set in a predetermined position of the filling machine.

(2) Preparation of coating solution When gelatin, plasticizer, colorant, purified water, etc. are added to a gelatin melting tank and components (A), (B) and (C) are contained in the coating, These are blended, heated and dissolved at about 80 ° C., and then defoamed in the same tank to adjust the viscosity to obtain a film stock solution. This stock solution is transferred to a small tank (50 to 55 ° C.) while being filtered, and is set at a predetermined position of the filling machine.

(3) Capsule filling The prepared film and contents are set at a predetermined position of a filling machine, and a soft capsule is molded by a filling machine in which a target die roll is set. The temperature of the filling chamber is usually maintained at 20 to 30 ° C. and the relative humidity is maintained at 30 to 50%. The soft capsule immediately after molding is fed into a tumbler dryer connected to a filling machine, and while rotating, clean fixation similar to the indoor conditions is performed, and the shape is temporarily fixed and the moisture in the film is temporarily dried in about 1 to 4 hours.

(4) Drying Soft capsules that have been molded and temporarily dried are transferred to a tumbler dryer, and the moisture content is 30 to 40% at the time of filling at a temperature of 20 to 30 ° C. and a relative humidity of 30 to 50% over 24 to 48 hours. Drop to 6-8%.

(5) Polishing If necessary, the soft capsules after drying can be polished with a tumbler for 2 minutes to 1 hour to finish the soft capsules.

The base polymer of the soft capsule film of the present invention is not particularly limited, but gelatin is preferable.
The present invention exerts effects such as suppression of decay delay, suppression of browning, suppression of "reaction occurring at the interface between the contents and the inner surface of the film", etc. The effect of the present invention is particularly exerted on gelatin that is prone to “reaction in”.

  EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples (experimental examples). However, the present invention is not limited to these unless it exceeds the gist.

Experimental example 1
As "unsaturated fatty acid or unsaturated fatty acid ester", DHA is 50 parts by mass, and as "component (A) ginger plant inclusion", ginger extract powder HI (manufactured by Nippon Powder Chemical Co., Ltd.) 2.5 parts by mass As component (B), 22 parts by mass of trehalose (manufactured by Hayashibara Co., Ltd.), as component (C), 10 parts by mass of inositol, 11.5 parts by mass of safflower oil, and as an emulsifying dispersant, “Poem J-0381V” 4 parts by mass (produced by Riken Vitamin Co., Ltd., glycerin fatty acid ester) were stirred and dissolved or dispersed to obtain soft capsule contents. The content is referred to as “content 01”.
Ginger extract powder HI (manufactured by Nippon Powder Chemical Co., Ltd.) is obtained by extracting from a rhizome of ginger (Zingiber officinales R.) with a water / ethanol mixed solvent and then pulverizing the solvent.

  The above contents were put into a sample bottle and stored in a constant temperature bath at 60 ° C. for 7 days, and then the change in peroxide value was measured to evaluate the oxidation resistance.

Experimental example 2
In Experimental Example 1, the contents 02 to 12 were obtained in the same manner as in Experimental Example 1 except that the presence or absence or amount of each component was changed as described in Table 1, and the change in the peroxide value with time was similarly obtained. Measurements were made to evaluate oxidation resistance. The numerical values in Table 1 are parts by mass.
As described above, the “peroxide value (POV)” was measured according to the iodometric titration method according to the Japanese Agricultural Standards Measurement Method, and evaluated according to the following “Evaluation Criteria in Actual Survey of Oil Confections by Consumer Groups”.
The results are summarized in Table 2.

Peroxide value (POV)
(Mg equivalent / kg)
0 or more and less than 10: Almost no oxidation 10 or more and less than 30: Oxidation is starting to proceed 30 or more and less than 40: Start to feel an oxidative odor 40 or more and less than 50: It is better not to eat 50 or more: Oxidation is severe. There is a risk of poisoning.

  Content No. containing all components (A), (B) and (C). In 01, 02 and 03, the peroxide value (POV) after 7 days at 60 ° C. was as small as less than 10 (mg equivalent / kg). Among components (A), (B) and (C) 1 (content No. 05-09) and one lacking (content No. 10-12), the peroxide value (POV) after 7 days at 60 ° C. Oxidation proceeded greatly at 10 (mg equivalent / kg) or more.

  From this, it was found that when all of the components (A), (B) and (C) were contained, the oxidation of DHA was synergistically suppressed.

Experimental example 3
The content excluding any one of the components (A), (B), and (C) was prepared. The sum of the component amounts of the components (A), (B) and (C) is determined as the content No. The content ratio of each component is 34.5 parts by mass in accordance with 01 and 02, and only the components contained excluding components that are not contained. The contents were prepared according to the ratio of each component of 01. In all the contents, DHA was blended at 50 parts by mass and safflower oil was blended at 11.5 parts by mass.

  When evaluated in the same manner as in Experimental Example 1, it was found that the same results as in Experimental Examples 1 and 2 were obtained, and in particular, even when the amount was increased, the oxidation inhibitory effect did not appear significantly. Moreover, when all the components (A), (B), and (C) were contained, it turned out that the oxidation of DHA is suppressed synergistically.

Experimental Example 4
<Preparation of contents F>
184.5 parts by mass of DHA as unsaturated fatty acid or unsaturated fatty acid ester, 7.5 parts by mass of ginger extract powder HI (manufactured by Nippon Powder Chemical Co., Ltd.) as “component (A) ginger plant inclusion” (B) 66.0 parts by mass of trehalose (manufactured by Hayashibara Co., Ltd.), 30.0 parts by mass of inositol as the component (C), and “Poem J-0381V” (manufactured by Riken Vitamin Co., Ltd., glycerin) Fatty acid ester) 12.0 parts by mass was stirred and dissolved and dispersed to obtain the contents of a soft capsule. The content is referred to as “content P”.

<Preparation of contents f>
The content of soft capsules was obtained using 300.0 parts by mass of DHA and no other components. The content is referred to as “content f”.

<Preparation of solution for forming coating G>
100 parts by weight of gelatin (manufactured by Nitta Gelatin Co., Ltd., GAR), 1 part by weight of ginger extract powder HI (manufactured by Nippon Powdery Chemical Co., Ltd.) as “component (A) ginger plant inclusions”, as component (B) 6 parts by mass of trehalose (manufactured by Hayashibara Co., Ltd.), 4 parts by mass of inositol as the component (C), 2 parts by mass of “Poem J-0381V” (manufactured by Riken Vitamin Co., Ltd., glycerin fatty acid ester), 35 parts by mass of glycerin Part and 75 parts by mass of water were stirred and dissolved and dispersed to obtain a solution for forming the film G.

<Preparation of solution for forming coating g>
100 parts by weight of gelatin, 35 parts by weight of glycerin, and 80 parts by weight of water were stirred and dissolved and dispersed to obtain a solution for forming a coating g.

  Using these as materials, an OVAL NO4 type soft capsule filled with a coating sheet thickness of 0.8 mm and a content solution of 300 mg was produced by a normal rotary die method. The room environment was 22 to 26 ° C. and the relative humidity was 30 to 45% from the time of molding to the end of drying.

Cover the contents f with the coating G and set the soft capsule No. 1 was produced. Soft capsule No. 1 contains components (A), (B) and (C) only in the film.
Cover the contents F with the coating G and set the soft capsule No. 2 was produced. Soft capsule No. 2 contains components (A), (B) and (C) in both the contents and the film.
Cover the contents f with the coating g and apply the soft capsule No. 3 was produced. Soft capsule No. 3 does not contain any of the components (A), (B) and (C) in the contents and the film.

<Evaluation method of blocking resistance>
Put the soft capsule in the sample bottle up to the eighth minute, put it in a thermostatic bath at 50 ° C, take it out from the thermostatic bath after 3 hours, 1 day, 7 days, return to room temperature, whether the capsule is deformed, and soft capsules The blocking state was observed and judged according to the following criteria.

(Double-circle): Deformation of a capsule is not seen.
The capsules do not stick together.
○: Deformation of capsule is not observed.
The capsules stick together to form a dumpling, but they can be separated into individual capsules just by lightly unraveling them.
Δ: Capsule deformation is observed.
The capsules stick together to form a dumpling, and when released, they are separated into individual capsules.
X: Capsule deformation is observed.
The capsules stick together to form a dumpling, and cannot be separated into individual capsules even when applied with a relatively strong force.

  Soft capsule No. 1 and no. In No. 2, an inositol layer was formed in the vicinity of the surface of the film, which improved the blocking resistance. In No. 3, the capsules started to melt from the surface of the coating, and adhesion between the capsules was observed.

Experimental Example 5
Soft capsule No. 1 and no. In “Preparation of solution for forming coating G” in No. 2, soft capsule no. 1 and no. In the same manner as in FIG. 4 and no. 5 was produced.

  Soft capsule No. 4 and no. The blocking resistance of No. 5 was evaluated in the same manner as in Example 4. As a result, Soft Capsule No. 4 and no. 5, the soft capsule No. 1 and no. Compared to 2, the inositol layer formation state in the vicinity of the coating surface was poor, and therefore the blocking resistance was poor. The results are shown in Table 4 below.

Experimental Example 6
Soft capsule No. 1, no. 2 and no. 3 and stored at 60 ° C. for 21 days, 2 months later, and 40 ° C. at 75% relative humidity until 3 months later, and evaluated “oxidation resistance of contents” and “delay delay”.
As for the oxidation resistance of the contents, the soft capsules were cut, the contents were quickly taken out, and the change in the peroxide value with time was measured in the same manner as in Experimental Example 2.
The results are shown in Table 5 below.

Soft capsule No. 1 containing components (A), (B) and (C) both in the coating and in the contents. 2 was the most stable with no increase in POV even after 2 months at 60 ° C.
In addition, components (A), (B), and (C) are not contained in the contents, and soft capsule No. contained only in the film. 1 also showed a slight increase in POV after 2 months at 60 ° C., but there was no significant difference. From this, it was found that the increase in the POV of the contents was suppressed even when blended with the film alone. .
On the other hand, soft capsule No. in which components (A), (B) and (C) are not blended in the film or the content liquid. 3 showed a significant increase in POV after 2 months at 60 ° C.
It was found that inclusion of components (A), (B) and (C) in the film is extremely suitable because both the blocking resistance and the oxidation resistance of the contents are improved.

Experimental Example 7
Soft capsule No. 1, no. 2 and no. 3 and set at 40 ° C. and relative humidity 75% RH (Table 6); set at a place irradiated with scattered light near a window at 25 ° C. (Table 7); immersed in DHA and set at 50 ° C. (Table 8); were stored for the period shown in the following Tables 6 to 8 to evaluate “collapse delay”.
The evaluation method of “disintegration delay” was in accordance with the Japanese Pharmacopoeia general test method “disintegration test method”. The “collapse delay” was evaluated by “collapse time” and “opening time”. The results are shown in Tables 6-8.

<Collapse time>
Distilled water was used as a test solution, and the time required for the capsule film to dissolve using an auxiliary plate was defined as the disintegration time.
The criterion for determining the disintegration time was defined as “disintegration time” until the sample residue was not observed in the glass tube of the tester or even when it was recognized, the time was smaller than the mesh. Each was tested with 6 samples.

<Opening time>
Distilled water was used as the test liquid, and the same method as the measurement of the disintegration time, except that the time at which a part of the contents started to be released from the soft capsule was defined as the “opening time”. Each was tested with 6 samples.

In Tables 6 to 8, the upper part of time indicates “opening time”, and the lower part indicates “collapse time”.
In Tables 6-8, “non-disintegration” indicates that it did not open for 30 minutes or more (and therefore did not collapse).

  In the soft capsules of the present invention (soft capsules No. 1 and No. 2), the “collapse time” and the “opening time” were both short under any storage conditions, and there was a tendency for no decay delay to occur. Soft capsule No. which does not contain components (A), (B) and (C) also in the film. In No. 3, the “collapse time” and the “opening time” both became long under any storage condition, and the decay delay occurred.

Soft capsules containing components (A), (B) and (C) only in their contents are also soft capsule Nos. 1 and No. A result almost similar to 2 was obtained.
From this, it was found that the soft capsules containing the components (A), (B), and (C) in either the contents or the film are less likely to be delayed in disintegration.

Experimental Example 8
The soft capsules were produced by removing any one of the components (A), (B), and (C) from the contents F and the coating G, and the decay delay was measured. 1 or No. From “2”, “collapse time” and “opening time” both became longer, resulting in decay delay.
From this, the synergistic effect by including all components (A), (B), and (C) was recognized.

Experimental Example 9
The “solution for forming a coating G” prepared in Experimental Example 4 was molded into a sheet having a thickness of 0.85 mm to obtain a sheet G corresponding to the coating G of the soft capsule.

Instead of the components (A), (B), and (C) of the “solution for G film generation” in Experimental Example 4, the same amount of phytic acid was added, and the same method as the method for preparing the film G generation solution was used. Thus, a “film m-forming solution” was prepared.
The “film m forming solution” was molded into a sheet having a thickness of 0.85 mm to obtain a sheet m corresponding to the film m of the soft capsule.

Instead of the components (A), (B) and (C) of “Film G production solution” in Experimental Example 4, the same amount of citric acid was used except that the same method as the preparation method of the film G production solution was used. “Solution for forming film n” was prepared.
The “solution for forming coating n” was molded into a sheet having a thickness of 0.85 mm to obtain a sheet n corresponding to the coating n of the soft capsule.

Sheets G, m, and n were each cut into an area of 300 mg, immersed in 50 ° C. DHA where oxidation progressed, and “disintegration time” was measured in the same manner as in Experimental Example 7 after 5 days and 7 days.
The results are shown in Table 9.

In the sheet G corresponding to the film G of the soft capsule of the present invention, the disintegration time was short after 5 days and after 7 days.
On the other hand, in the sheet m containing phytic acid and the sheet n containing citric acid instead of the components (A), (B), and (C), the disintegration time becomes longer after 5 days and does not pass through the mesh. Residues of a size remained, and insolubilization was observed after 7 days.

Experimental Example 10
Soft capsule No. 4 of Experimental Example 4 1 and no. 2, soft capsules were produced in the same manner as in Experimental Example 4, except that the same amount of xylitol (melting point: 92 to 96 ° C., solubility in water at 25 ° C .: 10 g / 100 mL) was used instead of component (B) trehalose.
In addition, the soft capsule No. 4 of Experimental Example 4 was used. 1 and no. 2, soft capsules were produced in the same manner as in Experimental Example 4, except that the same amount of xylitol (melting point: 92 to 96 ° C., solubility in water at 25 ° C .: 10 g / 100 mL) was used instead of component (C) inositol.

  Evaluations were made in the same manner as in Experimental Examples 6 and 7. 1 and no. As a result, soft capsule No. 2 was not obtained. The result was about 3.

  The soft capsule containing the specific component of the present invention is very good in terms of storage stability, such as content oxidation inhibition, decay delay inhibition, blocking inhibition, browning inhibition, etc., and is therefore widely used for the preparation of all soft capsules. is there.

Claims (3)

A soft capsule in which a content containing at least an unsaturated fatty acid or an unsaturated fatty acid ester is covered with a film, and the content and / or the film includes the following component (A), component (B) and component (C):
(A) Ginger plant inclusions (B) Sugars or sugar alcohols having a melting point of 150 ° C. or lower and solubility in 100 mL of water at 25 ° C. of 60 g / 100 mL or higher (C) Melting point of 160 ° C. or higher And a saccharide or a sugar alcohol having a solubility in 100 mL of water at 25 ° C. of 30 g / 100 mL or less.   The soft capsule according to claim 1, wherein the component (B) is a disaccharide or higher saccharide having no reducing property.   The soft capsule according to claim 1 or 2, wherein the component (C) is a cyclitol.