阅读说明：本技术 含有源自姜黄的成分、在口腔内咀嚼和/或在口腔内溶解的口服组合物 (Oral composition containing ingredient derived from Curcuma rhizome and capable of being chewed and/or dissolved in oral cavity ) 是由 雨宫优子 田口修也 岸孝礼 平山善丈 于 2019-08-27 设计创作，主要内容包括：在含有源自姜黄的成分、在口腔内咀嚼和/或在口腔内溶解的口服组合物中,抑制摄取时的苦味。在含有源自姜黄的成分、在口腔内咀嚼和/或在口腔内溶解的口服组合物中,通过配合颗粒状的乳酸钙,能够抑制源自姜黄的成分的苦味。另外,在含有源自姜黄的成分的咀嚼片中,通过配合颗粒状的乳酸钙,能够抑制源自姜黄的成分的苦味,并且赋予能够在口腔内容易地咬碎的硬度。(In an oral composition containing a turmeric-derived component and capable of being chewed in the oral cavity and/or dissolved in the oral cavity, bitterness during ingestion is suppressed. In an oral composition containing a turmeric-derived component and capable of being chewed in the oral cavity and/or dissolved in the oral cavity, the bitter taste of the turmeric-derived component can be suppressed by blending a granular calcium lactate. In addition, by blending a granular calcium lactate with a chewable tablet containing a component derived from turmeric, it is possible to impart hardness that can suppress the bitterness of the component derived from turmeric and can be easily bitten into the oral cavity.)

1. An oral composition for chewing in the oral cavity and/or dissolving in the oral cavity comprising:

(A) a component derived from turmeric; and

(B) calcium lactate in particulate form.

2. The composition according to claim 1, wherein the composition,

is an oral tablet which is chewed in the oral cavity.

3. The composition of claim 1 or 2,

the ingredient (A) derived from turmeric comprises:

(A-1) a turmeric extract containing curcumol extracted with water and/or a hydrophilic organic solvent; and

(A-2) curcumin containing curcumin which is processed by coating.

4. The composition of claim 3, wherein,

the calcium lactate is calculated by 1 weight part of calcium lactate, the curcumol is 0.017-1.7 weight parts of myrrh and the curcumin is 1.29-129 weight parts.

5. The composition according to any one of claims 1 to 4,

the content of the granular calcium lactate (B) in terms of calcium lactate pentahydrate is 0.1-10% (w/w).

6. A process for producing an oral tablet to be chewed in the oral cavity,

comprising the step of dry-tabletting a raw material mixture containing:

(A) a component derived from turmeric; and

(B) calcium lactate in particulate form.

7. A method for suppressing bitterness of an oral tablet containing (A) a turmeric-derived component and chewed in the oral cavity,

the method comprises the following steps:

when a raw material mixture containing the turmeric-derived component (a) is dry-compressed to obtain the tablet, the raw material mixture is further added with (B) granular calcium lactate.

Technical Field

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

The present invention also relates to a method for producing an oral tablet containing a turmeric-derived component and chewed in the oral cavity.

The present invention also relates to a method for suppressing the bitterness of an oral tablet containing a turmeric-derived component and chewed in the oral cavity.

Background

Turmeric is a medicinal plant of the genus curcuma of the family zingiberaceae cultivated in tropical and subtropical regions of the world, centered on southeast asia.

The rhizome of Curcuma longa contains various useful components such as oil-soluble curcumin (yellow pigment), water-soluble bisabolol, etc. On the other hand, it is known that useful components derived from turmeric, such as curcumin, exhibit an unpleasant taste such as a bitter taste when orally taken.

In particular, in the case of instant granules which are taken by dissolving in the oral cavity without drinking water, chewable tablets which are taken by chewing, buccal tablets which are taken by dissolving in the oral cavity, and the like, an unpleasant taste which shows an unpleasant taste component such as turmeric can be particularly and remarkably perceived (patent document 1). In order to solve the problem, patent document 1 discloses a coated granulated substance for oral administration, which includes: granules containing ingredients exhibiting an unpleasant taste and a flavoring substance; and a layer which covers the granulated substance and contains a substance that is hardly soluble in water at room temperature.

Patent document 2 describes that a predetermined amount of calcium lactate is added to an orally disintegrating tablet containing a drug having a bitter taste in order to mask the bitter taste. Patent document 2 also describes that an orally disintegrating tablet is produced by adding an aqueous solution of hydroxypropyl cellulose to a raw material such as calcium lactate and granulating the mixture to obtain a tableting powder, and tableting the tableting powder thus obtained.

Patent document 3 describes a granular solid preparation containing a drug, silicic acid compounds, and calcium lactate as a preparation for masking the unpleasant taste of the drug. Patent document 3 describes that a calcium lactate solution is added to a mixture of a drug and calcium silicate, and the mixture is 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 hydroxypropylcellulose as a preparation for masking an unpleasant taste of the drug.

Documents of the prior art

Patent document

Patent document 1: japanese patent laid-open No. 2012 and 87064

Patent document 2: japanese patent laid-open No. 2008-94837

Patent document 3: japanese laid-open patent publication No. 7-126188

Patent document 4: japanese laid-open patent publication No. 2004-189756

Disclosure of Invention

Problems to be solved by the invention

As described in patent document 1, there is a problem that an oral composition containing a turmeric-derived component and being chewed in the oral cavity and/or dissolved in the oral cavity strongly feels a bitter taste of the turmeric-derived component in the oral cavity when ingested.

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

In addition, in the case where the composition is an oral tablet (chewable tablet) to be chewed in the oral cavity, it is required to be easily bitten into the oral cavity at the time of ingestion.

Accordingly, an object of the present invention is to provide an oral tablet containing a turmeric-derived component and chewed in the oral cavity, which tablet has physical properties such that the tablet can be easily bitten into the oral cavity while suppressing bitterness.

Means for solving the problems

The present inventors have found that the bitterness of a turmeric-derived component can be suppressed by blending a granulated calcium lactate in an oral composition containing the turmeric-derived component and being chewed in the oral cavity and/or dissolved in the oral cavity. It has also been found that by incorporating granular calcium lactate into a chewable tablet containing a turmeric-derived component, hardness can be imparted to the tablet so that the tablet can be easily chewed in the oral cavity. Based on these findings, the present invention has been completed as follows. Patent documents 2 and 3 describe preparations containing calcium lactate for masking the bitter taste of the drug, but since the preparations described in these documents are prepared by dissolving calcium lactate in water and then granulating the solution, calcium lactate does not exist in the form of granules in the preparations.

The present invention includes the following inventions.

(1) An oral composition for chewing in the oral cavity and/or dissolving in the oral cavity comprising:

(A) a component derived from turmeric; and

(B) calcium lactate in particulate form.

(2) The composition according to (1), which is an oral tablet chewed in the oral cavity.

(3) The composition according to (1) or (2),

the ingredient (A) derived from turmeric comprises:

(A-1) a turmeric extract containing curcumol extracted with water and/or a hydrophilic organic solvent; and

(A-2) curcumin containing curcumin which is processed by coating.

(4) The composition according to the above (3),

the calcium lactate is calculated by 1 weight part of calcium lactate, the curcumol is 0.017-1.7 weight parts of myrrh and the curcumin is 1.29-129 weight parts.

(5) The composition according to any one of (1) to (4),

the content of the granular calcium lactate (B) in terms of calcium lactate pentahydrate is 0.1-10% (w/w).

(6) A process for producing an oral tablet to be chewed in the oral cavity,

comprising the step of dry-tabletting a raw material mixture containing:

(A) a component derived from turmeric; and

(B) calcium lactate in particulate form.

(7) A method for suppressing bitterness of an oral tablet containing (A) a turmeric-derived component and chewed in the oral cavity,

the method comprises the following steps:

when a raw material mixture containing the turmeric-derived component (a) is dry-compressed to obtain the tablet, the raw material mixture is further added with (B) granular calcium lactate.

The disclosure of japanese patent application No. 2018-162454, which forms the basis of the priority of the present application, is included herein.

Effects of the invention

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

According to the method for producing an oral 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 of the tablet can be suppressed.

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

Drawings

Fig. 1 shows a microscope magnified image of calcium lactate particles used in the examples. The two particles drawn in line in FIG. 1 had lengths of 445 μm (top) and 591 μm (bottom).

Fig. 2 shows a photograph of a cross-section of a calcium lactate-free chewable tablet.

Fig. 3 shows a photograph of a cross-section of a chewable tablet incorporating 2% calcium lactate particles. In fig. 3, the portion enclosed by the dotted line is a particle, and the length along the straight line is 634 μm.

Detailed Description

< ingredient derived from Curcuma rhizome >

The ingredient derived from Curcuma rhizome refers to an ingredient derived from a plant belonging to the genus Curcuma of the family Zingiberaceae. Examples of the plant belonging to the genus Curcuma of the family Zingiberaceae include Curcuma longa, Curcuma aromatica, Curcuma zedoaria, Curcuma phaeocauli, Curcuma kwangsiensis, Curcuma wenyujin, and Curcuma xanthorrhiza, and particularly, Curcuma longa is preferable.

As the ingredient derived from turmeric, particularly preferred is an ingredient derived from the rhizome of a plant belonging to the genus curcuma of the family zingiberaceae. The rhizome-derived component may be a component obtained by cutting the rhizome into an appropriate size or shape, a component obtained in the form of a pulverized product, or a component obtained by appropriately drying these components.

The turmeric-derived component may be a component extracted from a part such as a rhizome of a plant belonging to the genus curcuma with an appropriate solvent.

As particularly preferred ingredients derived from turmeric, there may be used:

(A-1) a turmeric extract containing curcumol extracted with water and/or a 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., and preferably alcohol, water, mixed solvent of alcohol and water. The alcohol is not particularly limited, and ethanol is preferred. The mixing ratio of the mixed solvent of the hydrophilic organic solvent and water is not particularly limited, and is, for example, preferably 10: 90-90: 10, more preferably 20: 80-50: a range of 50. The temperature at the time of extraction is not particularly limited.

As the turmeric extract of (a-1), an extract obtained by extracting from the part, particularly rhizome, of turmeric can be used as it is, and an extract obtained by further subjecting the extract to treatments such as dilution, concentration, and drying can also be used. The method of dilution, concentration, drying and the like can be any conventionally known method. The turmeric extract (A-1) may be solid or liquid, preferably solid, and the turmeric extract (A-1) may be in any form such as particles, granules, powder, etc.

The turmeric extract of (A-1) is characterized by containing curcumol, myrrh. Preferably, the extract contains more than 0.15 wt% of bisabolol. The amount of bisabolol in the turmeric extract can be determined as follows: the turmeric extract was mixed with ethyl acetate, and after ethyl acetate was distilled off under reduced pressure from the supernatant obtained by centrifugation, the liquid dissolved in acetonitrile was used as an analysis sample for High Performance Liquid Chromatography (HPLC). The bisabolol is a compound classified as bisabolane type sesquiterpene, and refers to a compound having the following planar structural formula or a salt thereof. The bisabolol has asymmetric carbons at positions indicated by ×, marks in the plane structural formula, and thus there are various optical isomers, but the bisabolol herein is a concept including any one of the optical isomers.

[ chemical formula 1]

The curcumin of (A-2') is extracted from a part such as a rhizome of a plant belonging to the genus Curcuma containing curcumin. As a method for extracting curcumin-containing curcumin from a plant, a known method can be used, and for example, the following method can be used: extracting rhizome of Curcuma plant with organic solvent (acetone, methyl ethyl ketone, diethyl ketone, methanol, ethanol, etc.), concentrating, and evaporating to remove solvent from the solvent fraction. In addition, a method of extracting by bringing carbon dioxide gas in a supercritical state into contact with the site can also be used. The curcumin of (a-2 ') may be solid or liquid, preferably solid, and the curcumin of (a-2') may be in any form such as particles, granules, powder, etc.

More preferably, the curcumin of (a-2'),

(A-2) curcumin containing curcumin which is processed by coating.

The coating process is generally a process for preventing the tongue from being stained with color when curcumin is orally administered. As the curcumin of (a-2), curcumin-containing curcumin which has been subjected to coating processing with a cellulose derivative useful as a food, such as hydroxypropyl cellulose, is particularly preferably used. The curcumin of (a-2) is obtained by coating the curcumin in any shape such as particles, granules, or powder, and the coated shape may be any shape such as particles, granules, or powder.

< particulate calcium lactate >

Calcium lactate is a commonly used food additive for the purpose of calcium fortification, gel strength improvement, shape retention of fruits and vegetables, discoloration prevention, oxidation resistance, and the like.

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

In the present invention, it is characterized in that calcium lactate in the form of particles is used as calcium lactate.

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

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

< oral composition >

In one embodiment of the present invention, an oral composition that is chewed in the oral cavity and/or dissolved in the oral cavity comprises:

(A) a component derived from turmeric; and

(B) calcium lactate in particulate form.

The composition is ingested by chewing and/or dissolving in the oral cavity.

Examples of oral compositions to be chewed in the oral cavity include chewable tablets which are chewed in the oral cavity and ingested.

Examples of oral compositions that dissolve in the oral cavity include tablets that dissolve in the oral cavity and are taken orally, instant granules, and orally disintegrating agents.

(A) An oral composition containing a turmeric-derived component and being chewed in the oral cavity and/or dissolved in the oral cavity has a problem that the turmeric-derived component is strongly perceived as bitter in the oral cavity when ingested, but when (B) granular calcium lactate is present in the composition, surprisingly, the bitter taste is significantly suppressed.

The above effect due to the presence of (B) calcium lactate in the form of particles is a significant effect that cannot be exerted by non-particulate powdered calcium lactate.

The content of the particulate calcium lactate in the composition of the invention, based on calcium lactate pentahydrate, is preferably 0.1-10% (w/w), more preferably 0.3-7% (w/w), even more preferably 0.5-5.4% (w/w).

The (a) turmeric-derived ingredient is more preferably a mixture comprising:

(A-1) a turmeric extract containing curcumol extracted with water and/or a hydrophilic organic solvent; and

(A-2) curcumin containing curcumin which is processed by coating.

The turmeric extract of (A-1) shows a bitter taste immediately upon oral administration because it has a high hydrophilicity. On the other hand, the curcumin of (a-2) has low hydrophilicity and is coated, and thus shows a bitter taste after a certain period of time from oral administration. Therefore, the mixture of the turmeric extract of (a-1) and the curcumin of (a-2) shows a bitter taste for a long period of time immediately after oral administration, but such a bitter taste over a long period of time can be effectively suppressed by containing the granular calcium lactate. Even when curcumin containing curcumin, which is not subjected to coating processing, is used as a component derived from turmeric in place of the above (a-2), the effects of the present invention, such as suppression of bitterness, can be achieved.

In the case where the (a) component derived from turmeric is the turmeric extract of the (a-1), the turmeric extract of the (a-1) is contained in the following manner: the amount of the curcumol is preferably 0.017 to 1.7 parts by weight, more preferably 0.02 to 0.5 part by weight, and even more preferably 0.03 to 0.35 part by weight, based on 1 part by weight of calcium lactate in terms of calcium.

In the case where the (a) turmeric-derived component is the curcumin of (a-2), the curcumin of (a-2) is contained in the following manner: the curcumin is preferably 1.29 to 129 parts by weight, more preferably 2.0 to 30 parts by weight, and still more preferably 2.3 to 26 parts by weight, based on 1 part by weight of calcium lactate in terms of calcium.

The composition of the present invention may contain other components capable of oral administration in addition to the components (a) and (B). Examples of the other components include excipients, acidulants, sweeteners, lubricants, and flavors.

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

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

The composition of the present invention is more preferably an oral tablet (chewable tablet) chewed in the oral cavity. The chewable tablet is required to be easily chewed in the oral cavity when ingested, but when particulate calcium lactate is present in the chewable tablet, surprisingly, the hardness of the chewable tablet can be reduced to a moderate hardness that is easily chewed. This effect is a significant effect that cannot be exerted by non-particulate powdered calcium lactate. Further, by incorporating calcium lactate in the form of granules, the bitter taste of the turmeric-derived component felt when chewing in the oral cavity can be suppressed.

The method for producing the chewable tablet is not particularly limited, but it is preferably produced by dry-tabletting a raw material mixture containing the (a) turmeric-derived component and the (B) granular calcium lactate so that the calcium lactate is contained in the chewable tablet while maintaining the granular shape. Dry tableting refers to forming chewable tablets by directly tableting a dried raw material mixture substantially free of a binder such as water.

Examples

Chewable tablet

A Curcuma rhizome extract containing curcumol is prepared by extracting rhizome of Curcuma rhizome (Curcuma longa) with water, drying the obtained extractive solution under reduced pressure under heating, and removing water.

Curcumin having curcumin as a main component, which has been subjected to coating processing with hydroxypropyl cellulose, is obtained by coating curcumin with hydroxypropyl cellulose, which is prepared by extracting the rhizome portion of turmeric with acetone, and drying the obtained extract under reduced pressure under heating to remove acetone.

As the calcium lactate particles, products of taiping chemical industry co. The granulate is obtained by granulating and drying calcium lactate by fluidized bed granulation with water as a binder, the calcium lactate being contained as calcium lactate pentahydrate. The calcium lactate particles had a median particle diameter of 336 μm and showed a particle size distribution (measured by laser scattering particle size distribution measuring device LA-950 manufactured by horiba, Ltd.) of up to about 800. mu.m. A microscopic magnified image of calcium lactate particles is shown in fig. 1. The two particles drawn in line in FIG. 1 had lengths of 445 μm (top) and 591 μm (bottom).

As the calcium lactate fine particles, products of taiping chemical industry co. In the fine particles, calcium lactate is contained as calcium lactate pentahydrate. The calcium lactate fine particles have a median particle size of 60.7 μm and show a particle size distribution of up to about 350 μm.

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

[ Table 1]

(unit ═ w/w)

The chewable tablet is prepared by mixing excipient, Curcuma rhizome extract, curcumin, calcium lactate granule or calcium lactate fine granule, sour agent, sweetener, perfume, and other components at a predetermined ratio, and dry-tabletting the mixed powder. The mixed powder may be granulated and then tableted. In the tableting, a single-shot tableting machine, a rotary tableting machine, or the like used for tablet formation 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 incorporating 2% calcium lactate particles. In fig. 3, the portion enclosed by the dotted line is a particle, and the length along the straight line is 634 μm. In the chewable tablet containing 2% calcium lactate particles, it was confirmed that the calcium lactate particles remained as they were.

< test 1 >

The disintegration time and hardness of the chewable tablets were measured.

Determination of disintegration time: the disintegration test method described in the disintegration test of the Japanese pharmacopoeia 15 edition was used.

Measurement of hardness: the hardness was measured by applying a force to the chewable tablet from the diameter direction using a Kiya type durometer.

The disintegration time of each chewable tablet containing no calcium lactate, 2% calcium lactate granules, and 2% calcium lactate fine granules was measured 6 times. The results are shown in the following table. By incorporating calcium lactate in the chewable tablet, the disintegration time is prolonged compared to the case of no incorporation. With respect to the disintegration time, no significant difference was confirmed as to whether calcium lactate was a granule or a fine granule.

[ Table 2]

Disintegration time

Measurement 1

Measurement 2

Measurement 3

Measurement 4

Measurement 5

Measurement 6

Ca lactate free

11:21

11:38

11:40

11:52

11:58

12:10

Ca lactate particles 2%

11:54

12:08

13:00

13:21

13:29

13:30

Ca lactate fine particles 2%

12:22

12:25

13:08

13:14

13:14

13:20

(unit is minutes: seconds)

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

[ Table 3]

Hardness of

	Measurement 1	Measurement 2	Measurement 3	Measurement 4	Measurement 5	Average
							Ca lactate free	9.15	8.90	9.50	9.20	7.50	8.85
Ca lactate particles 2%	7.50	6.55	8.10	6.90	6.50	7.11
							Ca lactate fine particles 2%	10.75	8.95	10.30	10.80	9.75	10.11

(unit ═ kgf)

The hardness of each chewable tablet containing 0.5%, 3% and 5.4% calcium lactate particles was measured 5 times. The results are shown in the following table. It was confirmed that the hardness of the chewable tablet decreased with the increase in the amount of calcium lactate particles incorporated. By appropriately adjusting the amount of calcium lactate particles to be blended, a chewable tablet that is easily disintegrated by chewing in the oral cavity can be produced.

[ Table 4]

Hardness of

	Measurement 1	Measurement 2	Measurement 3	Measurement 4	Measurement 5	Average
							0.5 percent of Ca lactate particles	8.60	8.90	8.85	9.10	8.90	8.87
Ca lactate particles 3%	7.20	7.10	7.60	6.80	6.30	7.00
							Ca lactate particle 5.4%	5.40	4.80	6.10	5.35	5.25	5.38

(unit ═ kgf)

< test 2 >

Regarding each chewable tablet containing no calcium lactate, 2% calcium lactate particles, and 2% calcium lactate fine particles, 6 subjects (subjects 1 to 6) were subjected to sensory evaluation tests, and the bitter taste at the start of chewing (early bitter taste), the bitter taste at the end of chewing (late bitter taste), and the unpleasant taste during chewing were evaluated on 5 ranks of 1 to 5 (the higher the value is, the stronger the unpleasant taste is). The results are shown in the following table. It was confirmed that calcium lactate was a granule, and had minimal bitterness before, after, and unpleasant taste.

[ Table 5]

Anterior bitterness

	Subject 1	Subject 2	Subject 3	Subject to testPerson 4	Subject 5	Subject 6	Average
								Ca lactate free	4	3	4	4	4	5	4.00
Ca lactate fine particles 2%	2	3	3	3	3	4	3.00
								Ca lactate particles 2%	2	2	2	3	2	4	2.50

Aftertaste

	Subject 1	Subject 2	Subject 3	Subject 4	Subject 5	Subject 6	Average
								Ca lactate free	5	4	5	4	4	5	4.50
Ca lactate fine particles 2%	4	4	4	3	4	3	3.67
								Ca lactate particles 2%	2	3	2	3	3	4	2.83

Unpleasant taste

	Subject 1	Subject 2	Subject 3	Subject 4	Subject 5	Subject 6	Average
								Ca lactate free	5	3	4	3	3	3	3.50
Ca lactate fine particles 2%	4	2	2	3	2	3	2.67
								Ca lactate particles 2%	2	2	2	2	2	3	2.17

< test 3 >

In the same manner as in test 2, 6 subjects (subjects 1 to 6) were subjected to sensory evaluation tests on chewable tablets containing 0.5%, 3% and 5.4% calcium lactate particles, and the bitter taste at the start of chewing (pre-bitter taste), the bitter taste at the end of chewing (post-bitter taste) and the unpleasant taste during chewing were evaluated on 5 scales of 1 to 5. The results are shown in the following table. When 3% calcium lactate granules were blended, any of the bitterness before, after, and unpleasant tastes were suppressed as compared with the blend of 0.5% calcium lactate granules. The bitter taste is further suppressed when 5.4% calcium lactate particles are added. The bitterness of the 5.4% calcium lactate-containing granules was increased as compared with the 0.5% calcium lactate-containing granules and the 3% calcium lactate-containing granules, but it was presumed that the bitterness was increased by the bitterness of the calcium lactate-containing granules themselves.

[ Table 6]

Anterior bitterness

	Subject 1	Subject 2	Subject 3	Subject 4	Subject 5	Subject 6	Average
								0.5 percent of Ca lactate particles	2	3	3	3	3	4	3.00
Ca lactate particles 3%	2	1	2	3	2	3	2.17
								Ca lactate particle 5.4%	1	2	1	3	1	4	2.00

Aftertaste

	Subject 1	Subject 2	Subject 3	Subject 4	Subject 5	Subject 6	Average
								0.5 percent of Ca lactate particles	4	3	3	3	3	3	3.17
Ca lactate particles 3%	2	2	2	4	2	2	2.33
								Ca lactate particle 5.4%	2	4	4	4	2	4	3.33

Unpleasant taste

	Subject 1	Subject 2	Subject 3	Subject 4	Subject 5	Subject 6	Average
								0.5 percent of Ca lactate particles	5	3	3	5	3	3	3.67
Ca lactate particles 3%	2	3	2	4	2	3	2.67
								Ca lactate particle 5.4%	2	3	3	3	3	2	2.67

All publications, patents and patent applications cited in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application were specifically and individually indicated to be incorporated herein by reference.