JPH08245352A - Oral cavity composition - Google Patents

Abstract

PURPOSE: To obtain a composition for oral cavity which contains a coenzyme A derivative as an active ingredient, thus has anti-inflammatory effect and action to promote the collagen production of fibroblast cells and is useful in prophylaxis and remedy for periodontal diseases. CONSTITUTION: This composition contains, as an active ingredient, coenzyme A of the formula (R is H or an organic group) and its derivative or their salts in an amount of 0.001-10wt.% in the whole composition. In addition to the active ingredients, usually used additives, for example, a binder, a thickener, a surfactant and the like are properly used to prepare tooth paste or wetted tooth powder, mouth wash, gingiva massage cream, locally applicable liquid or paste or chewing gum. Coenzyme A is obtained through the fermentation process or by extraction from mammalian organs. This oral cavity composition effectively controls the inflammation of gingivae without disturbance in the oral cavity flora, and markedly promotes the ability of gingiva fibroblast cells to produce collagen. Consequently, the damaged collagen can be satisfactorily regenerated to be efficacious for periodontal diseases such as pyorrhoea alveolaris.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for the oral cavity, which is excellent in suppressing gingival inflammation and promoting collagen production, and which can very effectively prevent and treat periodontal diseases such as alveolar pyorrhea. .

[0002]

BACKGROUND OF THE INVENTION Periodontal diseases such as alveolar pyorrhea affect many people, and the morbidity rate is particularly high in adults. Prevention and treatment of periodontal disease is an important issue. The main cause of this periodontal disease is bacteria in dental plaque that accumulate in periodontal pockets, and among them, anaerobic gram-negative bacteria, particularly Porphyromonas gingivalis, is attracting attention as a periodontal disease-causing bacterium. When these bacteria settle and proliferate in the periodontal pocket, they exert various factors and adversely affect the periodontal tissues.

On the other hand, the living body attempts to eliminate bacteria by mobilizing infection-preventing bacteria such as white blood cells and components to the periodontal pocket in order to prevent bacterial infection, while prostaglandins, active enzymes, etc. It is thought that it produces various inflammatory mediators and tissue-disrupting factors such as collagenase and protease, and exacerbates inflammation of periodontal tissues.

[0004] As a countermeasure, prevention and treatment with bacteria are often carried out, but this method is not very suitable because it disturbs the normal bacterial flora. Further, conventionally, application of various anti-inflammatory agents has been proposed for the purpose of improving gingivitis.
On the other hand, there is also a proposal to prevent the periodontal disease by regenerating the destroyed collagen tissue by blending a fibroblast collagen productivity promoter.

However, it cannot be said that any of the above methods has a sufficient preventive and therapeutic effect on periodontal disease. The reason may be that the effect is not sufficiently exerted only by the action of either anti-inflammation or collagen regeneration. From this, it is considered that a periodontal drug containing a drug capable of exerting both of the above effects simultaneously as an active ingredient. It is desired to develop a more effective oral composition for the prevention and treatment of diseases.

The present invention has been made in view of the above circumstances.
It is an object of the present invention to provide an oral composition which has two effects, an anti-inflammatory effect and a fibroblast collagen production promoting effect, and which is excellent in the preventive and therapeutic effects of periodontal disease.

[0007]

MEANS TO SOLVE THE PROBLEM As a result of intensive studies to achieve the above-mentioned object, the present inventor has found that the coenzyme A represented by the following general formula (I) and its derivatives and salts thereof are unexpectedly In particular, it can effectively suppress the inflammation of the gingiva without disturbing the normal bacterial flora in the oral cavity, and also has the effect of sufficiently regenerating collagen of fibroblasts, therefore,
It was found that an oral composition containing coenzyme A of the general formula (I) or a derivative thereof or a salt thereof as an active ingredient can extremely effectively prevent and prevent periodontal disease such as alveolar pyorrhea, and It was the invention.

[0008]

Embedded image (However, in the formula, R represents a hydrogen atom or an organic group.)

The present invention will be described in more detail below. The oral composition of the present invention comprises toothpaste such as toothpaste and moisturizing toothpaste, mouthwash, gum massage cream, liquid or paste topical application agent, It is prepared and applied as a chewing gum or the like, and contains one or two or more of the coenzyme A represented by the above formula (I) and its derivative and salts thereof as an active ingredient.

Here, the coenzyme A (CoA) is a compound in which R is a hydrogen atom in the above general formula (I), and it can be obtained by fermentation, extraction from animal organs and the like. The derivative of coenzyme A is preferably one in which R in the general formula (I) is a chain organic group, and more preferably one containing an SH group, nitrogen or oxygen. Specific examples include a derivative in which R is an acyl group having 1 to 25 carbon atoms, preferably 1 to 21 carbon atoms, and acetyl CoA (carbon chain 2),
Propionyl CoA (the same 3), butyryl CoA (the same 4), isobutyryl CoA (the same 4), valinyl CoA
(The same 5), isovalinyl CoA (the same 5), hexanoyl CoA (the same 6), heptanoyl CoA (the same 7), octanoyl CoA (the same 8), nonanoyl CoA (the same 9), decanoyl CoA (the same 10), undecanoyl CoA (the same). 11), lauroyl CoA (12), tridecanoyl CoA (13), myristoyl CoA (14), pentadecanoyl CoA (15), palmitoyl CoA
(Id. 16), heptadecanoyl CoA (Id. 17), steroyl CoA (Id. 18), nonadecanoyl CoA (Id. 1)
9), arachidonyl CoA (same 20), heneicosanoyl CoA (same 21), behenoyl CoA (same 22), lignosenoyl CoA (same 24) and the like. In addition, it is also possible to use those which are not mentioned here and whose carbon chain is a straight chain, branched ones, or ones having an unsaturated bond.

In addition to R in the general formula (I) being a carbon chain,
A compound containing an SH group, nitrogen and oxygen is dehydrogenated by oxidizing a compound RH having a coenzyme A and an SH group to dehydrogenate S
It can be obtained by forming an S bond. Further, the group may include a -CONH- bond, a hydroxyl group, an amino group, a carboxylic acid group, a phosphoric acid residue, a ribose residue, and an adenine residue. Specific examples of the SH group-containing compound include coenzyme A, dephosphocoenzyme A, 4′-phosphopantetheine,
4'-phosphopantothenoyl cysteine, pantethein, pantothenoyl cysteine, β-aletein, cysteamine, cysteine, glutathione and the like can be mentioned.
Therefore, R has 1 to 25 carbon atoms, preferably 1 to 2 carbon atoms.
1 organic group may be mentioned.

Further, in the present invention, a metal salt of a phosphoric acid moiety of coenzyme A and its derivative can also be used. Examples of the salt include salts derived from alkali metals such as sodium, potassium and lithium, alkaline earth metals such as calcium and magnesium, and zinc group metals such as zinc. When forming a divalent metal salt, a salt is formed with an adjacent phosphoric acid site.

When the coenzyme A or the derivative of R in the general formula (I) is an acyl group, a monosodium salt, a trisodium salt in which R of the coenzyme A or the general formula (I) is an acyl group, Examples include monopotassium salt, tripotassium salt, monolithium salt, trilithium salt, monocalcium salt, monomagnesium salt, monozinc salt and the like.

In the general formula (I), R is
A compound represented by RH in which R is bonded to a hydrogen atom is a coenzyme, that is, a compound of the following formula (II) (oxidized C
When oA) is used, the disodium salt of the compound of the general formula (II) (oxidized CoA.2Na), hexasodium salt (oxidized CoA.6Na), dipotassium salt (oxidized CoA.2K), Hexapotassium salt (oxidized CoA-6
K), dilithium salt (oxidized CoA.2Li), hexalithium salt (oxidized CoA.6Li), dicalcium salt (oxidized CoA.2Ca), dimagnesium salt (oxidized Co)
A.2Mg), dizinc salt (oxidized CoA.2Zn), and the like.

[0015]

Embedded image

When RH of the general formula (I) is dephosphocoenzyme A, monosodium salt, pentasodium salt, monopotassium salt, pentapotassium salt, monolithium salt, pentalithium salt and the like can be mentioned. , RH is 4′-phosphopantetheine or 4′-phosphopantethenoylcysteine, the disodium salt, tetrasodium salt, dipotassium salt, tetrapotassium salt, dilithium salt, tetralithium salt, etc. of this compound may be Can be mentioned. When RH is pantetheine, panthenoyl cysteine, β-aletein, cysteamine, cysteine and glutathione, the monosodium salt, trisodium salt, monopotassium salt, tripotassium salt, monocalcium salt, monocalcium salt, monocalcium salt, monocalcium salt, monocalcium salt Examples thereof include magnesium salt and monozinc salt.

Of the above, the oxidized CoA of the formula (II) and salts thereof are most effective and preferred.

The amount of the active ingredient selected from the CoAs of the above formula (I) and salts thereof is usually 0.001 to 10% (% by weight, the same applies hereinafter) of the total oral composition, and especially 0.1.
01 to 5% is preferable, and if it is less than 0.001%, a satisfactory effect may not be obtained in some cases.

In addition to the above-mentioned components, the oral composition of the present invention may further contain appropriate components depending on the purpose, type of composition and the like in a usual dose.

For example, in the case of toothpaste, dibasic calcium phosphate dihydrate and anhydrous, monobasic calcium phosphate,
Tertiary calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, anhydrous silicic acid, aluminum silicate, insoluble sodium metaphosphate, third magnesium phosphate, magnesium carbonate, calcium sulfate, polymethyl methacrylate, bentonite,
One or more kinds of zirconium silicate, synthetic resin and the like may be blended.

In the case of a paste-like composition such as toothpaste, a cellulose derivative such as carrageenan, sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, sodium carboxymethylhydroxyethylcellulose as a binder, alginate, propylene glycol alginate. , Xanthan gum, tragacanth gum, karaya gum, gum arabic, etc., polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, synthetic binders such as polyvinylpyrrolidone, silica gel, aluminum silica gel, veegum, inorganic binders such as laponite 1
One kind or two or more kinds may be blended.

Further, for paste or liquid oral compositions such as dentifrice, sorbit, glycerin,
Ethylene glycol, propylene glycol, 1,3-
One or more of butylene glycol, polyethylene glycol, polypropylene glycol, xylitol, maltitol, lactitol and the like may be blended.

As the surfactant, an anionic surfactant, a nonionic surfactant or a zwitterionic surfactant can be used. As an anionic surfactant,
Sodium alkyl sulphate such as sodium lauryl sulphate and sodium myristyl sulphate, sodium N-acyl sarcosinate such as sodium N-lauroyl sarcosinate, sodium N-myristoyl sarcosinate, sodium dodecylbenzene sulfonate, hydrogenated coconut fatty acid monoglyceride sodium monosulfate , N-acylglutamates such as sodium lauryl sulfoacetate and sodium N-palmitoyl glutamate, N-methyl-N-
Acyl taurine sodium, N-methyl-N-acyl alanine sodium, sodium α-olefin sulfonate, sodium dioctyl sulfosuccinate and the like are used.

Examples of the nonionic surfactant include sugar fatty acid esters such as sucrose fatty acid ester, maltose fatty acid ester and lactose fatty acid ester, sugar alcohol fatty acid ester such as maltitol fatty acid ester and lactitol fatty acid ester, and polyoxyethylene sorbitan monolaur. , Polyoxyethylene sorbitan monostearate and other polyoxyethylene sorbitan fatty acid esters, polyoxyethylene hydrogenated castor oil and other polyoxyethylene fatty acid esters, lauric acid mono- or diethanolamide, myristic acid mono- or diethanolamide fatty acid diethanolamide , Sorbitan fatty acid ester, fatty acid monoglyceride, polyoxyethylene higher alcohol ether, polyoxyethylene polyoxypropylene copolymerization , Polyoxyethylene polyoxypropylene fatty acid ester.

As the zwitterionic surfactant, N-alkyldiaminoethylglycine such as N-lauroyldiaminoethylglycine and N-myristyldiaminoethylglycine, N-alkyl-N-carboxymethylammonium betaine, 2-alkyl-1- Hydroxyethyl imidazoline betaine sodium and the like are used.

The composition of the present invention further comprises menthol, anethole, carvone, eugenol, limonene, n-decyl alcohol, citronellol, α-terpineol,
Citronellyl acetate, cineole, linalool, ethyl linalool, wanilin, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, laurel oil, perilla oil, wintergreen oil, Fragrances such as clove oil and eucalyptus oil may be blended alone or in combination of two or more, and sodium saccharin, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartin, thaumatin, asparatyl phenylalanine methyl ester, p.
-A sweetener such as methoxycinnamic aldehyde may be added.

In the present invention, in addition to the above CoAs as an active ingredient, ascorbic acid or a salt thereof, ascorbic acid phosphoric acid ester or a salt thereof, ascorbic acid fatty acid ester, α −
Ascorbic acid derivatives such as glucosyl-L-ascorbic acid or salts thereof, vitamin E or its derivatives such as tocopherol acetate and tocopherol nicotinate, other vitamins, chlorhexidine, benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, decali Cationic fungicides such as aluminum chloride, triclosan, hinokitiol, phenolic compounds such as biosol, dextranase, mutanase,
Enzymes such as lysozyme, amylase, protease, lytic enzyme, superoxide dimstase, alkali metal monofluorophosphates such as sodium monofluorophosphate, potassium nanofluorophosphate, fluorides such as sodium fluoride, stannous fluoride , Tranexamic acid,
Epsilon aminocaproic acid, aluminum chlorohydroxy allantoin, dihydrocholestanol, glycyrrhizinic acid, glycyrrhetinic acid, bisabolol, glycerophosphate, chlorophyll, sodium chloride,
One type or two or more types of active ingredients such as a water-soluble inorganic phosphate compound may be blended.

[0028]

INDUSTRIAL APPLICABILITY The oral composition of the present invention can effectively suppress gingival inflammation without disturbing the bacterial flora in the oral cavity.
It can regenerate damaged collagen sufficiently by dramatically promoting the gingival fibroblast collagen production ability, and can very effectively prevent and prevent periodontal diseases such as alveolar pyorrhea.

[0029]

EXAMPLES The present invention will be specifically described below by showing experimental examples and examples, but the present invention is not limited to the following examples. In addition,% in each example is% by weight. [Experimental Example] Evaluation of gingival fibroblast collagen production promotion rate: 10% FBS (fetal bovine serum, Dulbecco) was applied to a 24-well plate.
Modification Eagle's Med
human normal gingival fibroblasts (Gin-)
1 ATCC CRL 1292) was inoculated and cultured in a CO 2 incubator at 37 ° C. When the cells became confluent, the FBS concentration in the medium was changed to 5%. To this, the test chemicals of the types and concentrations shown in Table 1 were added,
At the same time, [2,3- ³ H] proline was adjusted to 2 μCi / hole, ascorbic acid was adjusted to 25 μg / ml, β-aminopropionitrile was adjusted to 25 μg / ml, and RI was incorporated for 48 hours, and then acidified at 4 ° C. Digested under pepsin. In addition, type I collagen was added, and 25% NaCl (0.5
Collagen-out collagen with (M acetic acid) and centrifuge, then 0.15M
Extraction with NaCl (Trif buffer), 4.5M Na
It was again salted out with Cl (Trif buffer) and centrifuged.
After adding 20% ethanol to this and centrifuging it,
It was dissolved in 5M acetic acid and liquid scintillation was added to measure the radioactivity, and the collagen production promoting rate was determined according to the following formula. The results are shown in Table 1. Collagen production promotion rate (%) = (B−A / A) × 100 A: Radioactivity of sample without addition of drug B: Radioactivity of sample with addition of drug

[0030]

[Table 1]

From the results shown in Table 1, it can be seen that both the compounds of the general formula (I) enhance the collagen-producing ability. Particularly, the oxidized CoA in which the RH of the general formula (I) is the coenzyme A is the coenzyme A. It was also found that R in general formula (I) is more effective than myristoyl CoA, which is an acyl group of carbon chain 14. It was also found that calcium pantothenate, a related compound of coenzyme A, has no effect.

[Experimental Example 2] Evaluation of rat gingivitis ameliorating effect: ODU rats (7 weeks old) were used as animals, and these were bred for 2 months on a powdered diet, and then plaque was accumulated on the lower anterior teeth to carry out an experiment. Caused gingivitis. From this point (0 day), the gels containing the agents shown in Table 3 were applied twice a day from this time (0 day) to the left and right gingiva of the lower jaw for 2 days with a spatula.
The gingival inflammation area on the day was measured under a stereoscopic microscope, and the degree of improvement in inflammation was determined by the following formula. The results are shown in Table 3.

The lower jaw was fixed with formalin, decalcified with formic acid and embedded in paraffin to prepare a tissue section, and then the tissue was observed by hematoxylin staining and azan dye. Gingivitis improvement rate (%) = (A−B) × 100 / A A: Inflamed area on day 0 B: Inflamed area on day 20

[0034]

[Table 2]

The results of Table 2 show that the gel base has the general formula (I)
It can be seen that gingivitis is ameliorated by adding the compound (1), but it is found that the oxidized CoA, in which RH of the general formula (I) is coenzyme A, is particularly effective.

As a result of tissue observation, infiltration of inflammatory cells, especially neutrophils, and disorder and destruction of collagen fibers were observed in the control group and the calcium pantothenate group, but the coenzyme A administration group and the coenzyme A derivative were observed. In the administration group, neutrophil infiltration and collagen fiber destruction were hardly observed.

Example 1 Toothpaste Aluminum hydroxide 45.0% Gelling silica 2.0 Solbit 25.0 Sodium carboxymethyl cellulose 1.0 Sucrose monopalmitate 1.0 Sodium lauryl sulfate 1.5 Sodium saccharin 0 .2 ethanol 0.1 sodium benzoate 0.1 triclosan 0.1 dextranase 0.1 mutanase 0.1 ascorbic acid phosphate magnesium salt 0.1 oxidized CoA 1.0 perfume 1.0 water balance 100 0.0%

Example 2 Toothpaste Precipitable silica 25.0% sorbit 25.0 glycerin 25.0 polyvinylpyrrolidone 1.0 lauroyl polyglycerin ester 1.0 polyoxyethylene (60 mol) sorbitan monolaurate 0. 5 Saccharin sodium 0.2 Ethyl paraoxybenzoate 0.1 Chlorhexidine hydrochloride 0.1 α-Tocopherol nicotinate 0.1 Ascorbic acid phosphoric acid ester magnesium salt 0.1 Carvone 0.05 Menthol 0.1 Mentone 0.05 Oxidized form CoA ・ 2Na 0.1 Fragrance 1.0 Water Residual 100.0%

Example 3 Toothpaste Dicalcium Phosphate Dihydrate 20.0% Dicalcium Phosphate Anhydrate 20.0 Gelling Silica 2.0 Solbit 20.0 Propylene Glycol 2.5 Carboxymethyl Cellulose Sodium 1.0 Lauryl diethanolamide 1.0 Sodium lauryl sulfate 1.5 Lauroyl sarcosine sodium 0.3 Saccharin sodium 0.1 Ethyl paraoxybenzoate 0.1 Cetylpyridinium chloride 0.1 Ascorbic acid phosphate sodium salt 0.2 Mentone 0.05 Oxidized CoA ・ 2Zn 5.0 Perfume 0.8 Water Residual 100.0%

Example 4 Oral Pasta Cetanol 5.0% Squalane 20.0 Precipitable Silica 5.0 Polyoxyethylene (40 mol) Hydrogenated Castor Oil 0.1 Sorbitan Monooleate 1.0 Sodium Lauryl Sulfate 0.2 Glycyrrhetinic acid 0.1 Sodium saccharin 0.6 Menthol 0.2 Carboxyl 0.1 Tranexamic acid 0.05 Oxidized CoA · 2Ca 0.2 Perfume 0.6 Water Residual 100.0%

Example 5 Oral Pasta Liquid Paraffin 15.0% Cetanol 7.0 Glycerin 20.0 Sorbitan Monopalmitate 0.6 Polyoxyethylene (40 mol) Sorbitan Monostearate 5.0 Saccharin Sodium 0.5 Cetylpyridinium chloride 0.05 Menthol 0.2 Menthone 0.05 α-Tocopherol acetate 0.2 Coenzyme A 1.0 Perfume 0.5 Water Residual 100.0%

[Example 6] Mouthwash Sorbit 10.0 Ethanol 5.0 Polyoxyethylene (60 mol) hydrogenated castor oil 0.1 Sucrose monopalmitate 0.2 Saccharin sodium 0.2 Triclosan 0.03 Cetylpyridinium chloride 0.05 Palmitoyl coenzyme A 0.5 Menthol 0.1 Carvone 0.1 Perfume 0.6 Water Residual 100.0%

Example 7 Chewing gum Gum base 20.0% Sugar 15.0 Isomaltose 20.0 Palatinose 20.0 Corn syrup 12.0 Syringe 11.9 Oxidized CoA.6Na 0.02 Menthol 0.1 Menthone 0 0.03 Fragrance 0.6 Total 100.0%

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[Procedure amendment]

[Submission date] August 3, 1995

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be corrected] 0003

[Correction method] Change

[Correction content]

On the other hand, the living body attempts to eliminate bacteria by mobilizing protective cells and components such as white blood cells to the periodontal pocket in order to prevent bacterial infection, while prostaglandins, active enzymes, etc. It is thought that it produces various inflammatory mediators and tissue-disrupting factors such as collagenase and protease, and exacerbates inflammation of periodontal tissues.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0004

[Correction method] Change

[Correction content]

[0004] As a countermeasure against this, prevention / treatment with a bactericide is often carried out, but this method is not suitable because it disturbs the normal bacterial flora. Further, conventionally, application of various anti-inflammatory agents has been proposed for the purpose of improving gingivitis. On the other hand, there is also a proposal of treating a periodontal disease by blending a fibroblast collagen production promoting agent to regenerate the destroyed collagen tissue.

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0007

[Correction method] Change

[Correction content]

[0007]

MEANS TO SOLVE THE PROBLEM As a result of intensive studies to achieve the above-mentioned object, the present inventor has found that the coenzyme A represented by the following general formula (I) and its derivatives and salts thereof are unexpectedly In particular, it can effectively suppress the inflammation of the gingiva without disturbing the normal bacterial flora in the oral cavity, and also has the effect of sufficiently regenerating collagen of fibroblasts, therefore,
It was found that an oral composition containing the coenzyme A of the general formula (I) or a derivative thereof or a salt thereof as an active ingredient can extremely effectively prevent and treat periodontal disease such as alveolar pyorrhea, and It was the invention.

[Procedure amendment 4]

[Document name to be amended] Statement

[Correction target item name] 0013

[Correction method] Change

[Correction content]

When the coenzyme A or the derivative of R in the general formula (I) is an acyl group, a monosodium salt, a trisodium salt in which R of the coenzyme A or the general formula (I) is an acyl group, Examples include monopotassium salt, tripotassium salt, monolithium salt, trilithium salt, monocalcium salt, monomagnesium salt, monozinc salt and the like.

[Procedure Amendment 5]

[Document name to be amended] Statement

[Correction target item name] 0028

[Correction method] Change

[Correction content]

[0028]

INDUSTRIAL APPLICABILITY The oral composition of the present invention can effectively suppress gingival inflammation without disturbing the bacterial flora in the oral cavity.
It can regenerate injured collagen sufficiently by dramatically promoting gingival fibroblast collagen production ability, and extremely effectively prevents and cures periodontal diseases such as alveolar pyorrhea.
Can be treated .

[Procedure correction 6]

[Document name to be amended] Statement

[Name of item to be corrected] 0029

[Correction method] Change

[Correction content]

[0029]

EXAMPLES The present invention will be specifically described below by showing experimental examples and examples, but the present invention is not limited to the following examples. In addition,% in each example is% by weight. [Experimental example] Evaluation of gingival fibroblast collagen production promotion rate: 10% FBS (fetal bovine serum) Dulbecco on a 24-well plate
Modification Eagle's Medi
Human normal gingival fibroblasts (Gin-1) suspended in um
ATCC CRL 1292) and CO at 37 ° C
2 Cultured in an incubator. When the cells became confluent, the FBS concentration in the medium was changed to 5%. To this, the test drug of the type and concentration shown in Table 1 was added,
At the same time, [2,3- ³ H] proline was adjusted to 2 μCi / well, ascorbic acid was adjusted to 25 μg / ml, β-aminopropionitrile was adjusted to 25 μg / ml, and RI was incorporated for 48 hours, and then acidified at 4 ° C. Digested under pepsin. In addition, type I collagen was added, and 25% NaCl (0.5
Collagen-out collagen with (M acetic acid) and centrifuge, then 0.15M
Extraction with NaCl ( Tris buffer ), 4.5M Na
It was again salted out with Cl ( Tris buffer ) and centrifuged.
After adding 20% ethanol to this and centrifuging it,
It was dissolved in 5M acetic acid and liquid scintillation was added to measure the radioactivity, and the collagen production promoting rate was determined according to the following formula. The results are shown in Table 1. Collagen production promotion rate (%) = (B−A / A) × 100 A: Radioactivity of sample without addition of drug B: Radioactivity of sample with addition of drug

[Procedure Amendment 7]

[Document name to be amended] Statement

[Name of item to be corrected] 0032

[Correction method] Change

[Correction content]

[Experimental Example 2] Evaluation of rat gingivitis ameliorating effect: ODU rats (7 weeks old) were used as animals, and these were bred for 2 months on a powdered diet, and then plaque was accumulated on the lower anterior teeth to carry out an experiment. the gingivitis was induced <br/>. From this point (0 day), the gel containing the agents shown in Table 2 was applied twice a day for 20 days to the left and right lower gingiva of the lower jaw with a spatula, and 0 and 20 days each.
The gingival inflammation area on the day was measured under a stereoscopic microscope, and the degree of improvement in inflammation was determined by the following formula. The results are shown in Table 2 .

[Procedure Amendment 8]

[Document name to be amended] Statement

[Correction target item name] 0033

[Correction method] Change

[Correction content]

The lower jaw was fixed with formalin, decalcified with formic acid and embedded in paraffin to prepare a tissue section, and then the tissue was observed by hematoxylin and azan staining . Gingivitis improvement rate (%) = (A−B) × 100 / A A: Inflamed area on day 0 B: Inflamed area on day 20

[Procedure Amendment 9]

[Document name to be amended] Statement

[Correction target item name] 0035

[Correction method] Change

[Correction content]

From the results shown in Table 2, it can be seen that gingivitis is improved by adding the compound of the general formula (I) to the gel base. Particularly, the RH of the general formula (I) is coenzyme A.
It can be seen that the oxidized CoA, which is, has the highest effect.

Claims (2)

[Claims] 1. One or two selected from coenzyme A represented by the following general formula (I) and derivatives thereof and salts thereof.
An oral composition comprising at least one species. Embedded image (However, in the formula, R represents a hydrogen atom or an organic group.) 2. The oral composition according to claim 1, wherein the derivative of coenzyme A is oxidized coenzyme A.