JPWO2020045440A1 - Orally ingested composition containing turmeric-derived ingredients that is chewed and / or dissolved in the oral cavity - Google Patents

Abstract

In an oral ingestion composition containing a turmeric-derived ingredient, which is chewed in the oral cavity and / or dissolves in the oral cavity, the bitterness at the time of ingestion is suppressed. The bitterness of the turmeric-derived component is suppressed by blending the granular calcium lactate in the composition for oral ingestion, which contains the turmeric-derived component and is chewed and / or dissolved in the oral cavity. Further, in a chewable tablet containing a turmeric-derived component, by blending granular calcium lactate, the bitterness of the turmeric-derived component is suppressed, and hardness that can be easily chewed in the oral cavity is imparted.

Description

The present invention relates to a composition for oral ingestion containing a turmeric-derived component, which is chewed and / or dissolved in the oral cavity.

The present invention also relates to a method for producing an orally ingested tablet that is chewed in the oral cavity and contains a component derived from turmeric.

The present invention also relates to a method for suppressing the bitterness of an orally ingested tablet that is chewed in the oral cavity and contains a component derived from turmeric.

Turmeric is a medicinal plant of the genus Turmeric of the family Zingiberaceae, which is cultivated in tropical and subtropical regions around the world, mainly in Southeast Asia.

Turmeric rhizomes contain various useful ingredients such as oil-soluble curcumin (yellow pigment) and water-soluble bisacurone. On the other hand, useful components such as curcumin derived from turmeric are known to exhibit an unpleasant flavor such as bitterness when taken orally.

In particular, fast-dissolving granules that are dissolved and taken in the oral cavity without drinking water, chewable tablets that are taken by chewing, troches that are dissolved and taken in the oral cavity, etc., contain unpleasant taste components such as turmeric. An unpleasant flavor is particularly noticeable (Patent Document 1). In Patent Document 1, in order to solve this problem, for oral ingestion, a granulated product containing an unpleasant taste component and a flavoring substance, and a layer containing a substance that is poorly soluble in water at room temperature and which covers the granulated product. The coated granules of the above are disclosed.

Patent Document 2 describes that an orally disintegrating tablet containing a drug having a bitter taste contains a predetermined amount of calcium lactate in order to mask the bitter taste. In Patent Document 2, an aqueous solution of hydroxypropyl cellulose is added to a raw material such as calcium lactate to granulate to obtain a tableted powder, and the obtained tableted powder is tableted to produce an orally disintegrating tablet. Has been described.

Patent Document 3 describes a granular solid preparation containing a drug, siliceous acids and calcium lactate as a preparation that masks the unpleasant taste of the drug. Patent Document 3 describes that a calcium lactate solution is added to and mixed with a mixture of a drug and calcium silicate and granulated to obtain a granular solid preparation.

Patent Document 4 describes an oral preparation obtained by wet-granulating a drug and a predetermined amount of low-substituted hydroxypropyl cellulose as a preparation masking the unpleasant taste of the drug.

Japanese Unexamined Patent Publication No. 2012-87064 Japanese Unexamined Patent Publication No. 2008-94837 Japanese Unexamined Patent Publication No. 7-126188 Japanese Unexamined Patent Publication No. 2004-189756

As described in Patent Document 1, a composition for oral ingestion containing a turmeric-derived component that is chewed in the oral cavity and / or dissolves in the oral cavity has a strong bitter taste of the turmeric-derived component in the oral cavity when ingested. There are challenges.

Therefore, an object of the present invention is to suppress bitterness at the time of ingestion in a composition for oral ingestion containing a component derived from turmeric, which is chewed in the oral cavity and / or dissolved in the oral cavity.

Further, when the composition is an oral ingestion tablet (chewable tablet) that is chewed in the oral cavity, it is required that the composition can be easily chewed in the oral cavity at the time of ingestion.

Therefore, an object of the present invention is to provide a tablet for oral ingestion containing a turmeric-derived component that is chewed in the oral cavity while suppressing bitterness and imparting physical properties that can be easily chewed in the oral cavity.

The present inventors have added granular calcium lactate to a composition for oral ingestion, which contains a turmeric-derived component and is chewed and / or dissolved in the oral cavity, so that the bitterness of the turmeric-derived component can be reduced. It was found to be suppressed. It was also found that, in a chewable tablet containing a turmeric-derived component, by blending granular calcium lactate, hardness that can be easily chewed in the oral cavity is imparted. Based on these findings, the following invention has been completed. In Patent Documents 2 and 3, preparations containing calcium lactate for masking the bitterness of a drug are described, but the preparations described in these documents are granulated after dissolving calcium lactate in water. Calcium lactate is not present in the form of granules in the formulation.

The present invention includes the following inventions.
(1) A composition for oral ingestion containing (A) a turmeric-derived component and (B) granular calcium lactate, which is chewed and / or dissolved in the oral cavity.
(2) The composition according to (1), which is a tablet for oral ingestion that is chewed in the oral cavity.
(3) The component derived from (A) turmeric is
(A-1) Containing a turmeric extract containing Bisacurone extracted with water and / or a hydrophilic organic solvent, and (A-2) a coated turmeric pigment containing curcumin, according to (1) or (2). Composition.
(4) The composition according to (3), wherein Bisacurone is 0.017 to 1.7 parts by weight and curcumin is 1.29 to 129 parts by weight with respect to 1 part by weight of calcium lactate in terms of calcium.
(5) Any of (1) to (4), wherein the content of the granular calcium lactate (B) as calcium lactate pentahydrate is 0.1 to 10% (w / w). The composition described.
(6) A method for producing an orally ingested tablet to be chewed in the oral cavity, which comprises dry tableting a raw material mixture containing (A) a turmeric-derived component and (B) granular calcium lactate.
(7) (A) A method for suppressing the bitterness of tablets for oral ingestion, which contains turmeric-derived ingredients and is chewed in the oral cavity.
A method comprising adding (B) granular calcium lactate to the raw material mixture when the raw material mixture containing the turmeric-derived component (A) is dry-tableted to obtain the tablets.

This specification includes the disclosure content of Japanese Patent Application No. 2018-162454, which is the basis of the priority of the present application.

The composition for oral ingestion, which contains a turmeric-derived component of the present invention and is chewed in the oral cavity and / or is dissolved in the oral cavity, suppresses the bitterness of the turmeric-derived component.

According to the method for producing an orally ingested tablet (chewable tablet) chewed in the oral cavity of the present invention, the tablet can be easily disintegrated in the oral cavity at the time of ingestion and the bitterness is suppressed. Can be done.

According to the method of the present invention for suppressing the bitterness of an orally ingested tablet chewed in the oral cavity, the bitterness of a turmeric-derived component in the tablet can be suppressed.

FIG. 1 shows a magnified image of the calcium lactate granules used in the examples under a microscope. The lengths of the two grains drawn in FIG. 1 were 445 μm (top) and 591 μm (bottom). FIG. 2 shows a photograph of a cross section of a chewable tablet without calcium lactate. FIG. 3 shows a photograph of a cross section of a chewable tablet containing 2% calcium lactate granules. In FIG. 3, the portion surrounded by the dotted line was a granule, and the length along the straight line was 634 μm.

<Ingredients derived from turmeric>
Turmeric-derived components refer to components derived from plants of the genus Turmeric in the family Zingiberaceae. Examples of plants belonging to the genus Hidden-lilies of the family Hidden-lilies include Hidden-lilies, Hidden-lilies, Hidden-lilies, Hidden-lilies, Hidden-lilies, Hidden-lilies, Hidden-lilies, Hidden-lilies, Hidden-lilies, Hidden-lilies, Hidden-lilies, Hidden-lilies.

As the turmeric-derived component, a component derived from the rhizome of a plant belonging to the genus Turmeric of the family Zingiberaceae is particularly preferable. The component derived from the rhizome may be a rhizome cut into an appropriate size or shape, a crushed product, or an appropriately dried rhizome.

The turmeric-derived component may be a component extracted with an appropriate solvent at a site such as a rhizome of a plant of the genus Turmeric.

As a particularly preferable turmeric-derived component, (A-1) a turmeric extract containing Bisacurone extracted with water and / or a hydrophilic organic solvent, or (A-2') a turmeric pigment containing curcumin can be used.

In the above (A-1), the "water and / or hydrophilic organic solvent" includes water, hot water, a hydrophilic organic solvent, a mixed solvent of water and a hydrophilic organic solvent, and the like, and includes alcohol, water, and alcohol. A mixed solvent of water is preferable. The alcohol is not particularly limited, but ethanol is preferable. The mixing ratio of the mixed solvent of the hydrophilic organic solvent and water is not particularly limited, but for example, the weight ratio is preferably in the range of 10:90 to 90:10, more preferably in the range of 20:80 to 50:50. The temperature at the time of extraction is not particularly limited.

As the turmeric extract of (A-1), the extract obtained by extraction from the turmeric site, particularly the rhizome, can be used as it is, and the extract is further diluted, concentrated, and dried. It is also possible to use a product that has been subjected to such treatment. Conventionally known methods can be used as methods for dilution, concentration, drying and the like. The turmeric extract of (A-1) may be solid or liquid, but is preferably solid, and the solid turmeric extract of (A-1) may be particles, granules, powder or the like. Can be of any shape.

The turmeric extract of (A-1) is characterized by containing Bisacurone. Bisacurone is preferably contained in an amount of 0.15% by weight or more. The amount of Bisacurone in the turmeric extract is a high-performance liquid using the solution obtained by mixing the turmeric extract with ethyl acetate, centrifuging the supernatant, distilling ethyl acetate under reduced pressure, and then dissolving it in acetonitrile as an analysis sample. It can be determined by subjecting to chromatography (HPLC). Bisacurone is a compound classified into bisabolan-type sesquiterpenes, and means a compound having the following planar structural formula or a salt thereof. Bisacurone has an asymmetric carbon at the position marked with * in the planar structural formula, and therefore there are several types of optical isomers. be.

The turmeric pigment of (A-2') is extracted from a site such as a rhizome of a plant of the genus Turmeric containing curcumin. As a method for extracting the curcumin-containing turmeric pigment from the plant, a known method can be used. For example, an organic solvent (acetone, methyl ethyl ketone, diethyl ketone, methanol, ethanol, etc.) can be used to extract the rhizome of a plant of the genus Hidden. A method of extracting from a site such as the above, concentrating the mixture, and evaporating and removing the solvent from the solvent fraction can be used. Further, a method of extracting by contacting the site with carbon dioxide gas in a supercritical state can also be used. The turmeric pigment of (A-2') may be solid or liquid, but is preferably solid, and the solid turmeric pigment of (A-2') may be particles, granules, powder or the like. Can be any shape of.

The turmeric pigment of (A-2') is more preferably
(A-2) A coated turmeric pigment containing curcumin. The coating process is generally a process performed for the purpose of suppressing the coloring of the tongue and the like when the turmeric pigment is orally ingested. As the turmeric pigment of (A-2), it is particularly preferable to use a turmeric pigment containing curcumin coated with a cellulose derivative that can be used as a food such as hydroxypropyl cellulose. The turmeric pigment of (A-2) is formed by coating the turmeric pigment having an arbitrary shape such as particles, granules, and powder, and the shape after the coating is an arbitrary shape such as particles, granules, and powder. Can be.

<Granular calcium lactate>
Calcium lactate is a food additive generally used for the purposes of fortifying calcium, improving gel strength, maintaining the shape of fruits and vegetables, preventing fading, and preventing oxidation.

Calcium lactate may be in the form of hydrates or salts. For example, it is preferable to use calcium lactate pentahydrate.

The present invention is characterized in that granular calcium lactate is used as the calcium lactate.

The calcium lactate granules are preferably granules obtained by granulating calcium lactate by fluidized bed granulation using water as a binder and drying it.

The size of the calcium lactate granules is not particularly limited, but preferably, the median diameter as measured by a laser scattering type particle size distribution measuring device is 200 μm to 700 μm.

<Composition for oral ingestion>
One aspect of the present invention is
A composition for oral ingestion containing (A) a component derived from turmeric and (B) granular calcium lactate, which is chewed and / or dissolved in the oral cavity. The composition is a composition that is chewed and / or dissolved and ingested in the oral cavity.

Examples of the composition for oral ingestion that is chewed in the oral cavity include tablets that are chewed and ingested in the oral cavity, that is, chewable tablets.

Examples of the composition for oral ingestion that dissolves in the oral cavity include a troche agent that dissolves in the oral cavity and is orally ingested, a fast-dissolving granule, and an orally disintegrating agent.

(A) An oral ingestion composition containing a turmeric-derived component that is chewed in the oral cavity and / or dissolves in the oral cavity has a problem that the bitterness of the turmeric-derived component is strongly felt in the oral cavity at the time of ingestion. (B) When granular calcium lactate is present in the composition, surprisingly, the bitterness is significantly suppressed.

(B) The above-mentioned effect due to the presence of granular calcium lactate is a remarkable effect that is not exhibited by non-granular powdered calcium lactate.

The content of granular calcium lactate in the composition of the present invention as calcium lactate pentahydrate is preferably 0.1 to 10% (w / w), more preferably 0.3 to 10%. It is 7% (w / w), more preferably 0.5 to 5.4% (w / w).

The (A) turmeric-derived component is more preferably
(A-1) A turmeric extract containing Bisacurone extracted with water and / or a hydrophilic organic solvent, and (A-2) a coated mixture containing a curcumin-containing turmeric pigment. Since the turmeric extract of (A-1) is highly hydrophilic, it immediately develops a bitter taste when taken orally. On the other hand, since the turmeric pigment of (A-2) has low hydrophilicity and is coated, it develops a bitter taste after a lapse of a certain period of time from oral ingestion. Therefore, the mixture of the turmeric extract of (A-1) and the turmeric pigment of (A-2) exhibits a bitter taste for a long time immediately after ingestion, but due to the inclusion of granular calcium lactate. , It is possible to effectively suppress such a long-term bitterness. Even when an uncoated turmeric pigment containing curcumin is used as a turmeric-derived component instead of the above (A-2), the effects of the present invention such as suppression of bitterness can be achieved.

When the turmeric-derived component (A) is the turmeric extract of (A-1), Bisacurone is preferably 0.017 to 1.7 parts by weight, based on 1 part by weight of calcium lactate in terms of calcium. The turmeric extract of (A-1) is contained so as to be more preferably 0.02 to 0.5 parts by weight, more preferably 0.03 to 0.35 parts by weight.

When the component derived from (A) turmeric is the turmeric pigment of (A-2), curcumin is preferably 1.29 to 129 parts by weight, more preferably 1 part by weight, based on 1 part by weight of calcium lactate in terms of calcium. The turmeric dye of (A-2) is contained so as to be 2.0 to 30 parts by weight, more preferably 2.3 to 26 parts by weight.

In addition to the above (A) and (B), the composition of the present invention may contain other components that can be orally ingested. Examples of other components include excipients, acidulants, sweeteners, lubricants, and flavors.

As the excipient, sugars such as maltose, polysaccharides such as starch, sugar alcohols, dietary fiber and the like can be used.

As the acidulant, an organic acid such as citric acid or malic acid or a salt thereof can be used.

As the sweetener, licorice extract or the like can be used.

As the lubricant, sucrose ester or the like can be used.

The composition of the present invention is more preferably an orally ingested tablet (chewable tablet) that is chewed in the oral cavity. Chewable tablets are required to be easily chewable in the oral cavity when ingested, but surprisingly, when granular calcium lactate is present in the chewable tablets, the chewable tablets The hardness is reduced to a moderate hardness that is easy to chew. This effect is a remarkable effect that is not achieved by non-granular powdered calcium lactate. In addition, since the chewable tablet contains granular calcium lactate, the bitterness of the turmeric-derived component that is felt when chewed in the oral cavity is suppressed.

The method for producing the chewable tablet is not particularly limited, but the chewable tablet contains the component (A) derived from turmeric and the (B) granular calcium lactate so that the calcium lactate is contained in the chewable tablet while maintaining the shape of the granules. It is preferably produced by dry tableting the raw material mixture. Dry tableting refers to molding a chewable tablet by directly tableting a dry raw material mixture that does not substantially contain a binder such as water.

<Chewable lock>
The turmeric extract containing Bisacurone was prepared by extracting the rhizome portion of turmeric (Curcuma longa) with water and drying the obtained extract under reduced pressure to remove water.

The turmeric pigment coated with hydroxypropyl cellulose and containing curcumin as a main component is a turmeric pigment prepared by extracting the rhizome portion of turmeric with acetone and drying the obtained extract under reduced pressure to remove acetone. Is coated with hydroxypropyl cellulose.

A product of Taihei Kagaku Sangyo Co., Ltd. was used as the calcium lactate granules. These granules are obtained by granulating calcium lactate by fluidized bed granulation using water as a binder and drying it, and calcium lactate is contained as calcium lactate pentahydrate. The median diameter of the calcium lactate granules was 336 μm, and the particle size distribution was shown up to about 800 μm (measured by a laser scattering type particle size distribution measuring device LA-950 manufactured by Horiba Seisakusho Co., Ltd.). A magnified image of calcium lactate granules under a microscope is shown in FIG. The lengths of the two grains drawn in FIG. 1 were 445 μm (top) and 591 μm (bottom).

A product of Taihei Kagaku Sangyo Co., Ltd. was used as the calcium lactate fine granules. In this fine granule, calcium lactate is included as calcium lactate pentahydrate. The median diameter of the calcium lactate fine granules was 60.7 μm, and the particle size distribution was shown up to about 350 μm.

The raw material composition of each chewable tablet is shown in the following table.

In the production of chewable tablets, excipients, turmeric extract, turmeric pigment, calcium lactate granules or calcium lactate granules, acidulants, sweeteners, flavors, etc. are mixed in a predetermined ratio, and the mixed powder thereof is mixed. Was obtained by dry-locking. The mixed powder may be granulated and then tableted. For tableting, a single-shot tableting machine used for molding tablets, a rotary tableting machine, or the like is used.

FIG. 2 shows a photograph of a cross section of a chewable tablet without calcium lactate, and FIG. 3 shows a photograph of a cross section of a chewable tablet containing 2% calcium lactate granules. In FIG. 3, the portion surrounded by the dotted line was a granule, and the length along the straight line was 634 μm. It was confirmed that the calcium lactate granules were retained as they were in the chewable tablets containing 2% of calcium lactate granules.

<Test 1>
The disintegration time and hardness of the chewable tablets were measured.
Measurement of disintegration time: According to the disintegration test method described in the Japanese Pharmacopoeia 15th edition disintegration test.
Measurement of hardness: A force was applied to the chewable lock from the radial direction using a Kiya-type hardness tester to measure the hardness.

The disintegration time of each chewable tablet containing no calcium lactate, 2% calcium lactate granules, and 2% fine calcium lactate granules was measured 6 times. The results are shown in the following table. By adding calcium lactate to the chewable tablets, the disintegration time was extended as compared with the case where it was not added. Regarding the disintegration time, no significant difference was observed depending on whether the calcium lactate was granules or fine granules.

The hardness of each chewable tablet containing no calcium lactate, 2% calcium lactate granules, and 2% fine calcium lactate granules was measured 5 times. The results are shown in the following table. The chewable tablets containing calcium lactate granules had a lower hardness than the chewable tablets containing no calcium lactate, and had the physical characteristics of being easily disintegrated by chewing in the oral cavity. On the other hand, it was confirmed that the chewable tablets containing calcium lactate fine granules have higher hardness than the chewable tablets not containing calcium lactate and are not suitable as chewable tablets.

The hardness of each chewable tablet containing 0.5% and 3% of calcium lactate granules and 5.4% was measured 5 times. The results are shown in the following table. It was confirmed that the hardness of the chewable tablets decreased as the amount of calcium lactate granules increased. By appropriately adjusting the blending amount of calcium lactate granules, it is possible to produce a chewable tablet that easily disintegrates by chewing in the oral cavity.

<Test 2>
A sensory evaluation test was conducted by 6 subjects (subjects 1 to 6) for each chewable tablet containing no calcium lactate, 2% calcium lactate granules, and 2% fine calcium lactate granules, and the bitterness when chewing was started (top). The bitterness), the bitterness at the end of chewing (last bitterness), and the unpleasant aroma felt during chewing were evaluated on a scale of 1 to 5 (the higher the value, the stronger the bitterness and unpleasant aroma). The results are shown in the following table. It was confirmed that calcium lactate was the lowest in the granules for all of the top bitterness, the last bitterness, and the unpleasant aroma.

<Test 3>
Similar to Test 2, a sensory evaluation test was conducted by 6 subjects (subjects 1 to 6) for each chewable tablet containing 0.5% calcium lactate granules, 3%, and 5.4%, and mastication was started. The bitterness at the time of chewing (top bitterness), the bitterness at the end of chewing (last bitterness), and the unpleasant aroma felt during chewing were evaluated on a scale of 1 to 5. The results are shown in the following table. All of the top bitterness, the last bitterness, and the unpleasant scent were suppressed when the calcium lactate granules were mixed with 3% rather than 0.5%. The top bitterness was further suppressed when the calcium lactate granules were blended at 5.4%. Regarding the last bitterness, when the calcium lactate granules were blended at 5.4%, they increased rather than the 0.5% blending and the 3% blending, which is presumed to be due to the bitterness of the calcium lactate granules themselves.

All publications, patents and patent applications cited herein are incorporated herein by reference in their entirety.

Claims (7)

A composition for oral ingestion containing (A) a component derived from turmeric and (B) granular calcium lactate, which is chewed and / or dissolved in the oral cavity. The composition according to claim 1, which is a tablet for oral ingestion that is chewed in the oral cavity. The component derived from (A) turmeric is
The composition according to claim 1 or 2, which comprises (A-1) a turmeric extract containing bisacron extracted with water and / or a hydrophilic organic solvent, and (A-2) a coated turmeric pigment containing curcumin. thing. The composition according to claim 3, wherein Bisacurone is 0.017 to 1.7 parts by weight and curcumin is 1.29 to 129 parts by weight with respect to 1 part by weight of calcium lactate in terms of calcium. The composition according to any one of claims 1 to 4, wherein the content of the granular calcium lactate (B) as calcium lactate pentahydrate is 0.1 to 10% (w / w). thing. A method for producing an orally ingested tablet to be chewed in the oral cavity, which comprises dry tableting a raw material mixture containing (A) a turmeric-derived component and (B) granular calcium lactate. (A) A method for suppressing the bitterness of an orally ingested tablet that contains a turmeric-derived ingredient and is chewed in the oral cavity.
A method comprising adding (B) granular calcium lactate to the raw material mixture when the raw material mixture containing the turmeric-derived component (A) is dry-tableted to obtain the tablets.

Images