JP2002121133A - Tablet dissolving in oral cavity for prophylaxis of periodontal disease - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a tablet dissolving in the oral cavity capable of raising effectiveness of vitamin C and vitamin E or a calcium ingredient effective in prophylaxis of periodontal diseases and solving the formation of cracking, breakage, etc., and providing an excellent feeling of use. SOLUTION: This tablet dissolving in the oral cavity is obtained by combining the vitamin C and the vitamin E or the calcium ingredient effective in prophylaxis of the periodontal diseases with a sugar alcohol selected from palatinit, maltitol and sorbitol and effective in the prophylaxis of the periodontal diseases.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an orally dissolving tablet for preventing periodontal disease.

[0002]

2. Description of the Related Art Conventionally, for the purpose of preventing periodontal disease, natural products having various cuts such as antibacterial and anti-inflammatory effects have been proposed. For example, JP-A-11-243910 discloses a combination of highly soluble calcium and an antibacterial plant extract comprising oil-soluble licorice extract, soy isoflavone, and tea extract. JP-A-11-302142 discloses vitamin C.
A composition for preventing periodontal disease using a combination of E or E and a natural polyphenol is disclosed. As a food dosage form containing such a composition, a tablet that is dissolved in the oral cavity is useful in expecting local action in the oral cavity.

[0003] Orally dissolving tablets have an adequate hardness for chewing and dissolving in the oral cavity, have no roughness during mouth-opening, and have no abrasion such as chipping or cracking during the production or distribution stages. is necessary. However, when vitamins and calcium components, which are active ingredients for periodontal disease prevention, are blended and the blending amount is increased, the hardness of the tablets does not usually depend on the type of sugar alcohol used in the oral dissolving tablets. In addition, it was found that even if the hardness was high, the abrasion such as cracking and chipping was so large that it could not withstand the impact in the production and distribution stages.

[0004]

DISCLOSURE OF THE INVENTION The present invention provides an orally dissolving tablet for preventing periodontal disease which is moderate in hardness, has low abrasion resistance, has no roughness at the time of mouthing, and has an excellent feeling upon use. .

[0005]

Means for Solving the Problems The present inventors have developed vitamin C
As a result of intensive investigations to improve the feeling of use, such as chipping, cracking, etc., in oral dissolving tablets for preventing periodontal disease containing vitamin E or calcium component as an active ingredient, and surprisingly, certain sugars were found. The above problem can be solved by the combination of alcohols, and the present invention has been completed.

[0006] That is, the present invention relates to: 1) a vitamin C and vitamin E or calcium component as an active ingredient, and palatinit, maltitol,
An orally dissolving tablet for preventing periodontal disease, comprising at least one selected from sugar alcohols composed of sorbitol. Item 2. The oral dissolving tablet for preventing periodontal disease according to Item 1, further comprising one or more selected from polymerization reducing sugars of two or more sugars. Item 3. Any one of Items 1 and 2, wherein the total amount of vitamin C and vitamin E, or the blending amount of the calcium component is 25 to 60% by weight, and the blending amount of the sugar alcohol is 30 to 60% by weight. Item 6. The oral dissolving tablet for periodontal disease prevention according to item 4. Item 4. A tablet obtained by tableting granules prepared by wet granulation, wherein the tablet hardness is 5 kg to 15 kg.
4. The oral dissolving tablet for preventing periodontal disease according to any one of items 2 and 3. Item 5 Further, one or more selected from a plant extract consisting of an oil-soluble liquorice extract, a soy isoflavone extract, a tea extract, and a grape seed extract are mixed. 5. The oral dissolving tablet for preventing periodontal disease according to any one of 4. In the present invention, the term "prevention of periodontal disease" refers to suppressing and preventing the onset of periodontal disease so as not to cause periodontal disease, suppressing and preventing the progress of periodontal disease when it occurs, and living It means reducing the risk of periodontal disease that affects the progression or onset of periodontal disease due to habits, systemic diseases or certain specific systemic conditions.

[0007]

DETAILED DESCRIPTION OF THE INVENTION Vitamin C used in the present invention is:
Salts such as ascorbic acid, sodium ascorbate and calcium ascorbate;
5 to 60% by weight, preferably 25 to 40% by weight can be added. The vitamin E used in the present invention is 0.1 to 10% by weight, preferably 0.1 to 10% by weight of natural or synthetic vitamin E and vitamin E such as esters such as succinic acid, acetic acid and nicotinic acid in the composition. 5% to 5% by weight can be blended.

[0008] Vitamin E is most preferably used in the form of a powdered vitamin E preparation. Powdered vitamin E preparation is, for example, a method in which vitamin E is emulsified with gum arabic or the like, and a powdered base such as dextrin or lactose is added and spray-dried, or a method in which the powder is adsorbed on a porous powder such as silicon dioxide or dextrin. Can be manufactured. Vitamin E is contained in the powdered vitamin E preparation in an amount of 1 to 50% by weight.
-40% by weight. These vitamin C
And the total amount of vitamin E is 25 to 60% by weight, preferably 30 to 50% by weight based on the total amount of the orally-dissolving tablet of the present invention.
Can be blended.

The calcium component used in the present invention may be either natural or synthetic. Natural products are shell calcium, cow bone powder, eggshell calcium, coral calcium,
Dolomite, whey calcium and the like, and as the synthetic calcium, calcium gluconate, calcium lactate, calcium phosphate, calcium glycerophosphate, calcium pantothenate, calcium citrate,
Examples thereof include calcium aspartate. These calcium components are contained in the orally-dissolved tablet of the present invention in an amount of 30%.
６０60% by weight, preferably 30-50% by weight.

[0010] The sugar alcohol used in the present invention is selected from one or more of palatinit, maltitol and sorbitol, and can be blended in an amount of 30 to 60% by weight, preferably 40 to 60% by weight, based on the total amount of the orally dissolving tablet. A product which is free from abrasion such as chipping and the like at the distribution stage, and excellent in use feeling without roughness when chewed and dissolved in the oral cavity is obtained.
Furthermore, two or more polymerized reducing sugars such as polydextrose, reduced dextrin, reduced starch saccharified products containing maltitol, maltotriitol, etc., are added in an amount of 1 to the total amount of the tablet dissolved in the oral cavity.
When it is blended in an amount of from 10 to 10% by weight, abrasion such as chipping can be more improved in the production stage and the distribution stage.

The oil-soluble licorice extract used in the present invention comprises:
Licorice (plant names: Glicyliza glabra, Glicyliza inflata, Glicyliza araleasis) From licorice or its congeners, organic solvents (eg, methanol, ethanol, acetone, ethyl acetate, chloroform, etc.)
It can be produced by extraction using Raw for extraction,
Alternatively, any of dried licorice and its congener plants may be used, and any part may be used, but the root is preferred.

[0012] In addition, the soybean isoflavone extract is a legume family.
(leguminosae) plant, soybean (Glycine max Mer
rill) using the seeds and hypocotyls as raw materials.
It can be obtained as a glycoside by a general method described in 126186. In the present invention, it is preferable that the isoflavone glycoside is hydrolyzed by a known method of hydrolysis using acid heating or β-glucuronidase enzyme in a purification step.

[0013] The tea extract is commonly drunk (Camellia
sinensis), green tea, oolong tea, black tea,
The extract can be selected from Pual tea and the like, and the extract contains epigallocatechins, epicatechins, and gallocatechins. These tea extracts are described, for example, in JP-A-64-90.
No. 124 and Japanese Patent Application Laid-Open No. 1-265023.

The grape seed extract uses European grape (Vitis vinifera) seeds and contains proanthocyanidins and anthocyanidins. For example, Tokuho 0
6-31208, JP-A-63-162885, JP-A-03-200781, JP-A-02-4
No. 8593, JP-A-03-99090 and the like.

These extracts can be used alone or in combination of two or more. The dry weight of the extract is 0.01 to 5% by weight, preferably 0.05%, based on the total amount of the orally-dissolving tablet of the present invention. １1% by weight.

The orally-dissolving tablet of the present invention, in addition to these essential components, can be usually formulated into tablets, for example, acidulants such as citric acid and malic acid, and high-sweetening agents such as sucralose, aspartame, stevia, and acesulfame K. , Sucrose fatty acid esters, lubricants such as magnesium stearate, flavors,
Vitamin C other than vitamin C and vitamin E, minerals such as zinc, and antioxidants, plaque formation inhibitors, bad breath inhibitors and the like can be appropriately added in a range that does not impair the effects of the present invention.

The method for producing the orally-dissolving tablet of the present invention will be described. Although the tableting method is not particularly limited in the present invention, the direct compression method of direct compression is difficult to obtain a tablet having low friability even if sufficient hardness or hardness is obtained. A method of tableting granules produced by a wet granulation method such as granulation, fluidized bed granulation, and mixing and stirring granulation is preferable.

That is, powder mixing of vitamins and plant extracts, sugar alcohols and other excipients (the powder used is 6
0 mesh (the particle size to be passed is 250 μm or less)), alcohol or water, and, if necessary, a powdered mixture of two or more polymerization-reducing sugars such as polydextrose, reduced dextrin, maltitol, and maltotriitol, alone or in combination. The body is moistened and granulated into granules. Finally, the granules are mixed with a fragrance, a lubricant, a useful component which is weak against heat or moisture, and tableted.

The tabletting machine used is a rotary tabletting machine,
Any single-shot tableting machine may be used, but it is preferable to use a rotary tableting machine from the viewpoint of mass productivity. When the punch is circular, the size of the punch used in the tableting machine is preferably 12 to 20 mm or less in diameter. When the punch is triangular or square, the size of one side is preferably about 5 to 15 mm. When obtaining a circular tablet, the thickness of the tablet should be 4 to 7
mm, the weight of one tablet is 500 to 300
0 mg, and the hardness of the tablet is 5 to 15 kg, especially 7 to 13 kg when measured in the diameter direction with a Kiya hardness tester.
Is most preferred. If the weight is less than 5 kg, the tablet itself is brittle and has high abrasion at the production and distribution stages, and in combination with an inorganic powder such as calcium, the powder is particularly powdery and inferior in use feeling. On the other hand, if it exceeds 15 kg, it becomes difficult to chew, and the tongue of the fragments when chewing is not sufficiently obtained, which is not preferable.

[0020]

Next, the present invention will be described in more detail with reference to Examples and Comparative Examples. Needless to say, the present invention is not limited to these Examples, and unless otherwise specified [%]
Indicates [% by weight].

From the formulations shown in the following Tests 1, 2 and 3, powders excluding polydextrose (product name PO-40, manufactured by Towa Kasei Kogyo Co., Ltd.), fragrances and sucrose fatty acid esters were weighed, and the fluidized bed was prepared. In granulation, it was sprayed with water or a 50% solution of polydextrose and granulated. Flavors and sucrose fatty acid esters were added to the obtained granules, and tablets containing ascorbic acid were 20 mm in diameter and weighed 19 per tablet.
It was made to be 100 mg, and it was compressed at a constant compression pressure. In this test, a vitamin E preparation having a vitamin E content of 20% was used.
Tablets containing a calcium component were tableted at a constant tableting pressure so as to have a diameter of 20 mm and a weight per tablet of 2000 mg.

For the obtained tablet, the hardness in the diameter direction of the tablet was measured by a Kiya hardness meter. The hardness is not hard at the time of chewing, even if it is chewed and fragmented, the tongue is good,
Further, a hardness in a range of 5 to 15 kg as a hardness at which abrasion such as chipping does not occur at the time of manufacturing and distribution is accepted. The friability test is based on the friability tester (JP Foru
m Vol.6 No.4 (1997), pp. 14-15). Put 20 tablets in the drum of the friability tester, rotate them at 25 rpm for 1 minute for 10 minutes, and then determine the friability (percentage of the reduced mass with respect to the initial mass), and the friability is 1%.
If it was below, it was judged as pass. The range in which both the hardness and the friability passed were judged to be acceptable. Table 1 shows the results.
3 is shown.

[0023]

[Table 1]

As is apparent from Table 1, when a plant extract, vitamin C, vitamin E or calcium component is used as an active ingredient and sugar alcohol is used as an excipient and formulated by a conventional method, the same sugar alcohol can be used. Only when palatinit, maltitol and sorbitol were used, excellent orally dissolving tablets having moderate hardness, good usability and low friability were obtained.

[0025]

[Table 2]

From Table 2, it can be seen that vitamin C and vitamin E
As the blending amount increases, the hardness becomes less likely to occur and the friability increases. Therefore, the total amount of vitamin C and vitamin E is preferably 60% by weight or less, the amount of sugar alcohol is 30% by weight or more, and polydextrose. It has been clarified that the use of a compound further increases the hardness and reduces the friability.

[0027]

[Table 3]

In Test 3, as the amount of calcium in the shell increased, the hardness did not change, but cracking occurred in the friability test, making it impossible to withstand the impact during production and distribution. Therefore, from Tests 1 and 3, it is preferable to mix the calcium-containing substance at 60% by weight or less and the sugar alcohol at 30% by weight or more.

Next, the following examples were prepared and evaluated in the same manner. As a result, they were excellent oral dissolving tablets having moderate hardness, good usability, and low friability. EXAMPLE 16 INGREDIENTS (%) shell calcium 30.0 oil-soluble licorice extract 0.5 Soybean isoflavone 1.0 vitamin D ₃ formulations (100,000 IU / g) 0.05 Palatinit 21.45 maltitol 30.0 Polydextrose 10.0 Stevia 0.5 Fragrance 2.5 Sucrose fatty acid ester 4.0 Total 100.0 1 tablet 2,000 mg, 20 mm diameter circular tablets were produced. Hardness was 13.5 kg, friability was 0.4%, and feeling of use was good. Met.

Example 17 Ingredients Amount (%) Calcium gluconate 30.0 Calcium lactate 20.0 Tea extract 0.1 Soy isoflavone 2.0 Vitamin D ₃ preparation (100,000 IU / g) 0.1 Vitamin K 0 .01 citric acid 1.0 sorbitol 30.0 palatinit 12.29 sucralose 1.0 perfume 2.5 magnesium stearate 1.0 total 100.0 1 tablet 1800 mg, 18 mm diameter round tablets were produced, hardness 11.5 Also, the sensation of use was good with a friability of 0.4%.

Example 18 Ingredients Amount (%) Ascorbic acid 18.0 Sodium ascorbate 14.0 Vitamin E preparation * 15.0 Grape seed extract 2.0 Palatinit 20.0 Maltitol 21.5 Citric acid 1.0 Apple Acid 0.5 Aspartame 1.5 Fragrance 2.5 Sucrose fatty acid ester 4.0 Total 100.0 * Vitamin E preparation As natural vitamin E, da, ゜,
?, D mixed type, contains 20% as total vitamin E, and contains powdered base such as gum arabic and dextrin as other additives. Spray-dried product. When a tablet with a diameter of 1900 mg and a diameter of 20 mm was produced, the hardness was 11.3, and the friability was 0.7%.

Example 19 Ingredients Amount (%) Ascorbic acid 16.0 Sodium ascorbate 20.0 β-carotene preparation * 0.1 Folic acid 0.01 Vitamin E preparation * 5.0 Grape seed extract 2.0 Palatinit 0 Sorbit 22.49 Aspartame 1.0 Magnesium stearate 1.0 Fragrance 2.5 Total 100.0 * Spray-dried product containing β-carotene ゜ -carotene 1% and other powdered base of gum arabic dextrin. * Vitamin E preparation dl-a-tocopherol impregnated with silicic anhydride. 50% as dl-a tocopherol
Contained. When a tablet having a diameter of 1700 mg and a diameter of 18 mm was produced, the hardness was 14.0 and the friability was 0.7%.

[0033]

According to the present invention, as a preparation for preventing periodontal disease, a combination of vitamin C and vitamin E or a calcium component with a sugar alcohol selected from palatinit, maltitol, and sorbitol provides an effective component for the preparation. Can improve the local efficacy and can solve the problems of physical properties of the orally-dissolving tablet, such as chipping and cracking, and can provide an orally-dissolving tablet with excellent usability. Furthermore, a plant extract comprising one or more of an oil-soluble licorice extract, a soybean isoflavone extract, a tea extract, and a grape seed extract can also be blended.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (Reference) A61K 35/78 A61K 35/78 C 47/10 47/10 47/36 47/36 A61P 1/02 A61P 1 / 02 F-term (reference) 4C076 AA36 BB22 CC31 DD07 DD38A DD41 DD43 DD46 EE30 EE41 EE58 FF04 4C086 AA01 BA09 BA18 HA04 MA03 MA06 MA08 MA35 MA57 NA14 ZA67 ZC75 4C088 AB12 AB45 AB56 AB60 AC04 AC05 AC11 MA10 MA09

Claims (5)

[Claims] 1. A periodontal disease preventive composition comprising vitamin C and vitamin E, or a calcium component as an active ingredient, and one or more sugar alcohols selected from palatinit, maltitol, and sorbitol. Orally dissolving tablets. 2. The orally dissolving tablet for preventing periodontal disease according to claim 1, further comprising one or more selected from polymerization reducing sugars of two or more sugars. 3. The method according to claim 1, wherein the total amount of vitamin C and vitamin E or the amount of calcium component is 25 to 60% by weight, and the amount of sugar alcohol is 30 to 60% by weight. The oral dissolving tablet for preventing periodontal disease according to any one of the above. 4. A tablet obtained by compressing granules prepared by wet granulation and having a tablet hardness of 5 kg to 15 kg for preventing periodontal disease according to claim 1. Orally dissolving tablets. 5. The method according to claim 1, further comprising one or more selected from a plant extract comprising an oil-soluble liquorice extract, a soy isoflavone extract, a tea extract, and a grape seed extract. The oral dissolving tablet for preventing periodontal disease according to any one of 2, 3, and 4.