TWI825159B - Composition for oral ingestion that contains ingredients derived from turmeric and is chewed and/or dissolved in the oral cavity - Google Patents

Abstract

The composition for oral ingestion of the present invention, which contains an ingredient derived from turmeric and is chewed and/or dissolved in the oral cavity, can suppress the bitter taste when ingested. The composition for oral ingestion of the present invention, which contains an ingredient derived from turmeric and is chewed and/or dissolved in the oral cavity, suppresses the bitter taste of the ingredient derived from turmeric by blending granular calcium lactate. In addition, chewable tablets containing ingredients derived from turmeric suppress the bitter taste of the ingredients derived from turmeric and provide hardness that can be easily chewed in the mouth by blending granular calcium lactate.

Description

Composition for oral ingestion that contains ingredients derived from turmeric and is chewed and/or dissolved in the oral cavity

The present invention relates to a composition for oral ingestion that contains an ingredient derived from turmeric and is chewed and/or dissolved in the oral cavity.

The present invention also relates to a method for manufacturing a tablet for oral ingestion that contains an ingredient derived from turmeric and is chewed in the mouth.

The present invention also relates to a method for suppressing the bitter taste of tablets for oral ingestion that contain ingredients derived from turmeric and are chewed in the mouth.

Turmeric is a medicinal plant of the genus Curcuma of the Zingiberaceae family that is cultivated in tropical and subtropical areas around the world, centered in Southeast Asia.

The rhizome of turmeric contains various useful ingredients such as oil-soluble curcumin (yellow pigment) or water-soluble myrrh curcumol (Bisacurone). On the other hand, it is known that useful ingredients such as curcumin derived from turmeric have unpleasant flavors such as bitterness when ingested orally.

Especially in fast-dissolving granules that are taken by dissolving in the mouth without drinking water, chewable tablets that are taken by chewing, and buccal tablets that are taken by dissolving in the mouth, the effects of unpleasant-tasting ingredients such as turmeric are particularly noticeable. Unpleasant flavor (Patent Document 1). In order to solve this problem, Patent Document 1 discloses a coated granulated substance for oral ingestion, which includes granulated substances containing unpleasant taste components and flavoring substances, and a granulated substance that coats the granulated substance and exhibits water retardancy at normal temperature. layer of soluble substances.

Patent Document 2 describes that an orally disintegrating tablet containing a bitter-tasting drug contains a specific amount of calcium lactate to mask the bitter taste. Patent Document 2 describes adding a hydroxypropylcellulose aqueous solution to a raw material such as calcium lactate and granulating it to obtain a tablet powder. The obtained tablet powder is tableted to produce an orally disintegrating tablet.

Patent Document 3 describes a granular solid preparation containing a drug, silicates, and calcium lactate as a preparation for masking the unpleasant taste of the drug. Patent Document 3 describes adding and mixing a calcium lactate solution to a mixture of a drug and calcium silicate, followed by granulation to obtain a granular solid preparation.

Patent Document 4 describes an oral preparation obtained by wet-granulating a drug and a specific amount of low-substituted hydroxypropylcellulose as a preparation for masking the unpleasant taste of the drug. [Prior technical literature] [Patent Document]

[Patent Document 1] Japanese Patent Application Laid-Open No. 2012-87064 [Patent Document 2] Japanese Patent Application Publication No. 2008-94837 [Patent Document 3] Japanese Patent Application Laid-Open No. 7-126188 [Patent Document 4] Japanese Patent Application Laid-Open No. 2004-189756

[Problem to be solved by the invention]

As described in Patent Document 1, compositions for oral ingestion containing ingredients derived from turmeric that are chewed and/or dissolved in the oral cavity have a problem that the bitter taste of the ingredients derived from turmeric is strongly felt in the oral cavity during ingestion.

Therefore, an object of the present invention is to suppress the bitter taste of an oral ingestion composition containing an ingredient derived from turmeric when it is chewed and/or dissolved in the oral cavity.

Moreover, when the said composition is a tablet for oral ingestion (chewable tablet) which is chewed in the oral cavity, it is required that it can be easily chewed in the oral cavity at the time of ingestion.

Therefore, an object of the present invention is to suppress the bitter taste and provide physical properties that can be easily chewed in the oral cavity to tablets for oral ingestion that contain ingredients derived from turmeric and are chewed in the oral cavity. [Technical means to solve problems]

The present inventors found that by blending granular calcium lactate into a composition for oral ingestion that contains an ingredient derived from turmeric and is chewed and/or dissolved in the oral cavity, the bitter taste of the ingredient derived from turmeric is suppressed. Furthermore, it was discovered that chewable tablets containing ingredients derived from turmeric are given hardness that can be easily chewed in the mouth by blending granular calcium lactate. Based on these findings, the following invention was completed. Furthermore, Patent Documents 2 and 3 describe preparations containing calcium lactate in order to mask the bitter taste of medicines. However, the preparations described in these documents are obtained by dissolving calcium lactate in water and then granulating it. Therefore, Calcium lactate does not exist in the form of particles in the preparation.

The present invention includes the following inventions. (1) A composition for oral ingestion that is chewed and/or dissolved in the oral cavity, containing (A) Ingredients derived from turmeric, and (B) Granular calcium lactate. (2) The composition according to (1), which is a tablet for oral ingestion that is chewed in the oral cavity. (3) The composition as described in (1) or (2), wherein The above (A) ingredients derived from turmeric contain (A-1) Turmeric extract containing myrrh curcumol extracted by water and/or hydrophilic organic solvent, and (A-2) Coated curcumin containing curcumin. (4) The composition according to (3), wherein the myrrh curcumol is 0.017 to 1.7 parts by weight and the curcumin is 1.29 to 129 parts by weight based on 1 part by weight of calcium lactate in terms of calcium. (5) The composition as described in any one of (1) to (4), wherein the content of the above-mentioned (B) granular calcium lactate as calcium lactate pentahydrate is 0.1 to 10% (w/w) . (6) A method of manufacturing a tablet for oral ingestion that is chewed in the mouth, which includes preparing a tablet containing (A) Ingredients derived from turmeric, and (B) The raw material mixture of granular calcium lactate is dry-pelletized. (7) A method for suppressing the bitter taste of tablets for oral ingestion that are chewed in the mouth and contain (A) a component derived from turmeric, including When the above-mentioned raw material mixture containing (A) the component derived from turmeric is dry-tableted to obtain the above-mentioned tablet, (B) granular calcium lactate is further added to the above-mentioned raw material mixture.

This specification contains the disclosure content of Japanese Patent Application No. 2018-162454, which is the basis for the priority of this case. [Effects of the invention]

In the composition for oral ingestion of the present invention that contains the turmeric-derived component and is chewed and/or dissolved in the oral cavity, the bitter taste of the turmeric-derived component is suppressed.

According to the method of manufacturing a tablet for oral ingestion (chewable tablet) that is chewed in the oral cavity of the present invention, the tablet can be easily disintegrated in the oral cavity upon ingestion and has a suppressed bitter taste.

According to the method for suppressing the bitter taste of tablets for oral ingestion that are chewed in the mouth of the present invention, the bitter taste of ingredients derived from turmeric in the above-mentioned tablets can be suppressed.

＜Ingredients derived from turmeric＞ Ingredients derived from turmeric refer to ingredients derived from plants of the genus Curcuma of the Zingiberaceae family. Examples of plants of the genus Curcuma of the Zingiberaceae family include: Curcuma longa (curcuma longa), Curcuma aromatic (curcuma longa), Curcuma zedoaria (Eshu), Curcuma phaeocaulis (Eshu), Curcuma kwangsiensis (Guangxi Eshu), Curcuma wenyujin (Zingiberaceae plant warm (Eshu), Curcuma xanthorrhiza (Indonesia), especially Curcuma longa (turmeric).

As the component derived from turmeric, a component derived from the rhizome of a plant of the genus Curcuma of the Zingiberaceae family is particularly preferred. The component derived from the rhizome may be obtained by cutting the rhizome into an appropriate size or shape, or may be in the form of a crushed product, or may be obtained by suitably drying the rhizome.

The components derived from turmeric can also be components extracted from the rhizome and other parts of the Curcuma longa plant by using an appropriate solvent.

As a particularly good ingredient from turmeric, be usable (A-1) Turmeric extract containing myrrh curcumol extracted by water and/or hydrophilic organic solvent, or (A-2') Curcumin containing curcumin.

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

As the turmeric extract of the above (A-1), an extract obtained by extracting parts of turmeric, especially the rhizome, may be used directly, or an extract obtained by subjecting the extract to dilution, concentration, drying, etc. may be used. For methods such as dilution, concentration, and drying, conventionally known methods can be used. The above-mentioned turmeric extract (A-1) may be solid or liquid, but is preferably solid. The solid above-mentioned turmeric extract (A-1) may be in any shape such as particles, granules, powder, etc.

The above-mentioned turmeric extract (A-1) is characterized by containing myrrhol curcumol. Myrrh curcumol preferably contains 0.15% by weight or more. The amount of myrrh-curcumol in the turmeric extract can be determined by mixing the turmeric extract and ethyl acetate, centrifuging to obtain a supernatant, and distilling the ethyl acetate from the supernatant under reduced pressure. Then, the liquid obtained by dissolving in acetonitrile was used as an analysis sample, and high performance liquid chromatography (HPLC) was performed. Myrrhocurcumol is a compound classified as bisabolane-type sesquiterpene, and means a compound having the following planar structural formula or a salt thereof. Myrrho-curcumol has an asymmetric carbon at the position represented by the * mark in the planar structural formula, so there are several optical isomers. However, the term "myrrho-curcumol" in this specification also includes any of its optical isomers. The concept of things.

[Chemical 1]

The curcumin of the above-mentioned (A-2') is extracted from the rhizome and other parts of Curcuma longa plants containing curcumin. As a method for extracting curcumin containing curcumin from plants, a known method can be used. For example, the following method can be used: using an organic solvent (acetone, methyl ethyl ketone, diethyl ketone, methanol, ethanol, etc.), from turmeric It is obtained by extracting the rhizome and other parts of the plant, concentrating it, and evaporating the solvent part to remove the solvent. Furthermore, a method of extracting the above-mentioned parts by contacting them with carbon dioxide in a supercritical state may also be used. The above-mentioned curcumin (A-2') may be solid or liquid, but is preferably solid. The solid above-mentioned curcumin (A-2') may be in any shape such as particles, granules, or powder.

The curcumin of the above (A-2') is more preferably (A-2) Coated curcumin containing curcumin. Coating processing refers to processing generally performed for the purpose of suppressing coloration of tongue, etc. when curcumin is orally ingested. As the curcumin of the above-mentioned (A-2), it is particularly preferable to use a curcumin-containing curcumin coated with a cellulose derivative that can be used as a food such as hydroxypropylcellulose. The curcumin of the above-mentioned (A-2) is formed by coating the curcumin in any shape such as particles, granules, and powders. The shape after the coating process can be any shape such as particles, granules, and powders.

＜Granular calcium lactate＞ Calcium lactate is a commonly used food additive for the purpose of fortifying calcium, improving gel strength, maintaining the shape of fruits and vegetables, resisting fading, and antioxidant.

Calcium lactate can be in the form of hydrate or salt. For example, calcium lactate pentahydrate is preferably used.

The present invention is characterized by using granular calcium lactate as calcium lactate.

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

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

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

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

Examples of compositions for oral ingestion that dissolve in the oral cavity include oral tablets that dissolve in the oral cavity and are orally ingested, rapidly dissolving granules, orally disintegrating agents, and the like.

Compositions for oral ingestion containing (A) turmeric-derived ingredients that are chewed and/or dissolved in the oral cavity have a problem that the bitter taste of the turmeric-derived ingredients is strongly felt in the oral cavity during ingestion, but ( B) When granular calcium lactate is present in the composition, surprisingly, the bitterness is significantly suppressed.

The above-mentioned effects obtained by the presence of (B) granular calcium lactate are not significant effects that cannot be exerted by granular powdered calcium lactate.

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

The above-mentioned (A) turmeric-derived component more preferably contains (A-1) Turmeric extract containing myrrh curcumol extracted by water and/or hydrophilic organic solvent, and (A-2) Coated curcumin containing curcumin mixture. Since the turmeric extract of (A-1) above has high hydrophilicity, it immediately exhibits a bitter taste when ingested orally. On the other hand, the curcumin (A-2) mentioned above has low hydrophilicity and is coated, so it develops a bitter taste after a certain period of time after oral ingestion. Therefore, the mixture of the above-mentioned turmeric extract (A-1) and the above-mentioned curcumin (A-2) continues to have a bitter taste for a long time immediately after oral ingestion, but it can be effectively suppressed by containing granular calcium lactate. This bitter taste lasts for a long time. Furthermore, even when uncoated curcumin-containing curcumin is used as a component derived from turmeric instead of the above (A-2), the effects of the present invention, such as suppressing bitterness, are also exerted.

When the component derived from turmeric (A) is the turmeric extract of (A-1), the sweet myrrh curcumol is preferably 0.017 to 1.7 per part by weight in terms of calcium relative to calcium lactate. The turmeric extract of the above (A-1) is contained in parts by weight, 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 turmeric (A) is the curcumin of (A-2), the curcumin is preferably 1.29 to 129 parts by weight based on 1 part by weight of calcium lactate, more preferably It is preferably 2.0 to 30 parts by weight, more preferably 2.3 to 26 parts by weight, and contains the curcumin (A-2) mentioned above.

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

As excipients, sugars such as maltose, polysaccharides such as starch, sugar alcohols, dietary fibers, etc. can be used.

As the sour agent, organic acids such as citric acid and malic acid or salts thereof can be used.

As a sweetener, licorice extract and the like can be used.

As a lubricant, sucrose ester and the like can be used.

The composition of the present invention is more preferably a tablet for oral ingestion (chewable tablet) that is chewed in the oral cavity. Chewable tablets are required to be easily chewable in the mouth when ingested. However, when granular calcium lactate is present in the chewable tablets, surprisingly, the hardness of the chewable tablets is reduced to a moderate level that is easy to chew. hardness. This effect is a significant effect that non-granular powdered calcium lactate cannot exert. In addition, by containing granular calcium lactate, the chewable tablet suppresses the bitter taste derived from the turmeric component that is felt when chewing in the mouth.

The manufacturing method of the chewable tablet is not particularly limited, but it is preferable to include the calcium lactate in the chewable tablet while maintaining the shape of the granules. The raw material mixture of calcium lactate is produced by dry tableting. Dry tableting refers to directly tableting a dried raw material mixture that does not contain substantially any binder such as water to form chewable tablets. [Example]

＜Chewable Tablets＞ A turmeric extract containing myrrh curcumol can be prepared by extracting the rhizome of turmeric (Curcuma longa) with water, and heating and drying the obtained extract under reduced pressure to remove water.

Curcumin containing curcumin as the main component is obtained by coating curcumin with hydroxypropyl cellulose. The curcumin is obtained by extracting the rhizome of turmeric with acetone. The extract is heated and dried under reduced pressure to remove acetone and is prepared.

As calcium lactate granules, products from Taiping Chemical Industry Co., Ltd. were used. The granules are obtained by granulating and drying calcium lactate through fluidized bed granulation using water as a binder, and the calcium lactate is contained in the form of calcium lactate pentahydrate. The median particle size of calcium lactate particles is 336 μm, showing a particle size distribution up to approximately 800 μm (measured by a laser scattering particle size distribution measuring device LA-950, manufactured by Horiba Manufacturing Co., Ltd.). The magnified image of calcium lactate particles using a microscope is shown in Figure 1. The lengths of the two grains underlined in Figure 1 are 445 μm (top) and 591 μm (bottom).

As calcium lactate fine particles, products manufactured by Taiping Chemical Industry Co., Ltd. were used. In the fine particles, calcium lactate is contained in the form of calcium lactate pentahydrate. The median particle size of calcium lactate fine particles is 60.7 μm, showing a maximum particle size distribution of approximately 350 μm.

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

[Table 1]

Chewable tablets are produced by mixing excipients, turmeric extract, curcumin, calcium lactate granules or calcium lactate fine granules, sourness, sweeteners, spices, and others in a specific ratio, and the mixed powder is Produced by dry beating. The mixed powder may also be granulated and then tableted. Tablet making uses a single-blade tableting machine, a rotary tableting machine, etc. used for tablet molding.

Figure 2 shows a cross-sectional photograph of a chewable tablet without calcium lactate, and Figure 3 shows a cross-sectional photograph of a chewable tablet containing 2% calcium lactate granules. In Figure 3, the part enclosed by the dotted line is the particle, and the length along the straight line is 634 μm. It was confirmed that in the chewable tablets formulated with 2% calcium lactate granules, the calcium lactate granules remained unchanged.

＜Test 1＞ The disintegration time and hardness of the chewable tablets were measured. Determination of disintegration time: based on the disintegration test method recorded in the 15th edition of the Japanese Pharmacopoeia. Determination of hardness: Use a log cabin hardness tester to apply force on the chewing tablet from the diameter direction to measure the hardness.

The disintegration time of each chewable tablet without calcium lactate, formulated with 2% calcium lactate granules, and formulated with 2% calcium lactate fine granules was measured 6 times. The results are shown in the table below. By blending calcium lactate into chewable tablets, the disintegration time is prolonged compared to the case where no chewable tablets are blended. Regarding the disintegration time, no significant difference was recognized depending on whether the calcium lactate was granular or fine.

[Table 2]

The hardness of each chewable tablet without calcium lactate, formulated with 2% calcium lactate granules, and formulated with 2% calcium lactate fine granules was measured five times. The results are shown in the table below. It was confirmed that chewable tablets formulated with calcium lactate granules have a lower hardness than chewable tablets not formulated with calcium lactate and have physical properties that allow them to be easily disintegrated by chewing in the oral cavity. On the other hand, chewable tablets formulated with calcium lactate fine particles have a higher hardness than chewing tablets not formulated with calcium lactate and are not suitable as chewable tablets.

[table 3]

The hardness of each chewable tablet prepared with 0.5%, 3% and 5.4% calcium lactate granules was measured five times. The results are shown in the table below. It was confirmed that as the amount of calcium lactate particles prepared increased, the hardness of the chewable tablets decreased. By appropriately adjusting the amount of calcium lactate granules to be prepared, a chewable tablet that is easily disintegrated by chewing in the oral cavity can be produced.

[Table 4]

＜Test 2＞ Regarding each chewable tablet without calcium lactate, formulated with 2% calcium lactate granules, and formulated with 2% calcium lactate fine granules, a sensory evaluation test was conducted on 6 subjects (subjects 1 to 6). Bitterness (top bitterness), bitterness at the end of chewing (last bitterness), and disgusting odor felt during chewing are evaluated in five stages from 1 to 5 (the higher the value, the bitterer, disgusting the stronger the smell). The results are shown in the table below. It was confirmed that any of the first (top) bitter taste, the last (last) bitter taste, and the offensive odor was the least when calcium lactate was in the form of granules.

[table 5]

＜Test 3＞ For each chewable tablet containing 0.5%, 3%, and 5.4% calcium lactate granules, a sensory evaluation test was conducted on six subjects (subjects 1 to 6) in the same manner as in Test 2, and the bitterness at the beginning of chewing was determined. The five stages are evaluated from 1 to 5 (the initial (top) bitter taste), the bitter taste at the end of chewing (last (last) bitter taste), and the offensive odor felt during chewing. The results are shown in the table below. The initial (top) bitter taste, the final (last) bitter taste, and the offensive odor are all suppressed when the calcium lactate granules are formulated at 3% compared to 0.5%. Regarding the initial (top) bitter taste, it was further suppressed when 5.4% of calcium lactate granules were formulated. Regarding the final (last) bitterness, when the calcium lactate granules were blended with 5.4%, it increased compared with the blends with 0.5% and 3%. It is speculated that the reason is due to the bitter taste of the calcium lactate granules themselves.

[Table 6]

All publications, patents, and patent applications cited in this specification are incorporated by direct reference into this specification.

Figure 1 shows an enlarged image of the calcium lactate particles used in the examples using a microscope. The lengths of the two grains underlined in Figure 1 are 445 μm (top) and 591 μm (bottom). Figure 2 is a photograph showing a cross-section of a calcium lactate-free chewable tablet. Figure 3 is a photograph showing the cross-section of a chewable tablet containing 2% calcium lactate granules. In Figure 3, the part surrounded by the dotted line is the particle, and the length along the straight line is 634 μm.

Claims (9)

A composition for oral ingestion that is chewed and/or dissolved in the oral cavity, containing (A) an ingredient derived from turmeric, and (B) granular calcium lactate. The composition of claim 1 is a tablet for oral ingestion that is chewed in the oral cavity. The composition of claim 1 or 2, wherein the above-mentioned (A) ingredient derived from turmeric contains (A-1) a turmeric extract containing myrrh curcumol extracted by water and/or a hydrophilic organic solvent, and ( A-2) Coated curcumin containing curcumin. For example, the composition of claim 3, wherein, relative to 1 part by weight of calcium lactate in terms of calcium, the amount of myrrh curcumol is 0.017~1.7 parts by weight, and the amount of curcumin is 1.29~129 parts by weight. The composition of claim 1 or 2, wherein the content of the above-mentioned (B) granular calcium lactate as calcium lactate pentahydrate is 0.1~10% (w/w). The composition of claim 3, wherein the content of the above-mentioned (B) granular calcium lactate as calcium lactate pentahydrate is 0.1~10% (w/w). The composition of claim 4, wherein the content of the above-mentioned (B) granular calcium lactate as calcium lactate pentahydrate is 0.1 to 10% (w/w). A method of manufacturing a tablet for oral ingestion that is chewed in the mouth, which includes dry tabletting a raw material mixture containing (A) a component derived from turmeric and (B) granular calcium lactate. A method for suppressing the bitter taste of tablets for oral ingestion that are chewed in the mouth and containing (A) an ingredient derived from turmeric, and the method includes dry-processing the raw material mixture containing (A) an ingredient derived from turmeric. When the above-mentioned tablet is obtained by tableting, (B) granular calcium lactate is further added to the above-mentioned raw material mixture.