JPH04300817A - Composition for oral cavity - Google Patents

Abstract

PURPOSE:To obtain a composition for the oral cavity, capable of preventing swelling, edema, hemorrhage, etc., in inflammation, excellent in preventive and treating effects on gingivitis and periodontitis, good in safety and usability and useful as dentifrice, pasta for the oral cavity, etc. CONSTITUTION:A composition for the oral cavity is obtained by blending (A) 0.001-10wt.%, especially 0.01-5wt.% tranexamic acid and/or its salt (e.g. metallic salts or sulfates of Mg, Ca or K) or derivative thereof (e.g. vitamin esters such as vitamin A acid esters, phenyl esters or N,N-maleoylminotranexamic acid) with (B) 0.00001-0.1wt.% (0.1-1000ppm), especially 0.0001-0.01wt.% (1.0-100ppm) cell growth factor (e.g. epidermal cell factor, fibroblastic cell growth factor, blood platelet-derived growth factor or transforming growth factor beta) as essential ingredients. The aforementioned composition has the above-mentioned effects.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to oral compositions such as toothpaste and oral pasta. More specifically, the present invention relates to an oral composition that has remarkable effects on the prevention and treatment of periodontal diseases such as gingivitis and periodontitis by incorporating cell growth factors into tranexamic acid and/or its derivatives.

0002

[Prior Art] Generally, periodontal diseases such as gingivitis and periodontitis are said to be chronic inflammation caused by chronic stimulation of periodontal pathogens or metabolites produced by them. Yes, it's not clear yet. For these periodontal diseases, anti-inflammatory agents such as allantoin and glycyrrhizinic acid, anti-plasmin agents such as ε-aminocapropanic acid, hinokitiol, sodium chloride and the like have been used in oral compositions.

[0003] Tranexamic acid is generally used as an anti-plasmin agent, and is known as an ingredient characterized by high safety in cosmetic applications. Also,
It is also included in oral compositions as an ingredient that has the effect of preventing gingivitis and periodontitis due to its anti-plasmin action. Moreover, urogastrone (usually called epidermal cell growth factor), which is one of the cell growth factors, has been reported as an external preparation for skin or a topical preparation for skin diseases. (Japanese Patent Application Laid-open No. 60-23325, Japanese Patent Application Publication No. 61-7216).

0004

Problems to be Solved by the Invention Problems with the Prior Art However, 1. None of these had sufficient effects. 2. It was not effective due to its relationship with other ingredients. 3. There was a problem with its stability. 4. There were problems such as poor usability of the blended system, and it was not always satisfactory.

OBJECTS OF THE INVENTION The present inventors have discovered tranexamic acid and/or its salts,
Its derivatives and epidermal cell factor (E
GF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), or transforming growth factor β (TGF-β) was found to synergistically promote cell proliferation. Focusing on this, we have conducted extensive research into the effects of applying an oral composition containing tranexamic acid and/or its salts, its derivatives, and cell growth factors. The present inventors have discovered that the present invention is extremely effective in preventing and treating gingivitis and periodontitis by preventing swelling, edema, bleeding, etc., and have completed the present invention.

The present invention was made in view of the problems of the prior art, and its purpose is to provide an oral composition that is highly effective in preventing and treating periodontal diseases, and is also safe and easy to use. It is about providing. Incidentally, there have been no reports on the effect of the combined use of tranexamic acid and/or its salts, derivatives thereof, and cell growth factors on periodontal diseases, nor is there any known application to oral compositions.

[0007]

[Means for solving the problems] That is, the present invention has the following features:
The present invention provides an oral composition characterized in that it contains tranexamic acid, a salt thereof, a derivative thereof, and a cell growth factor.

The configuration of the present invention will be explained in detail below. The tranexamic acid used in the present invention is a white crystal or powder with a melting point of 262-267°C, has no odor, and has a bitter taste. In addition, the manufacturing method is patent No. 240611, patent No. 242664,
It is known from Japanese Patent No. 480411 and Japanese Patent No. 488164. Furthermore, it is generally used as an anti-plasmin agent, and is known as a component characterized by high safety in cosmetic applications. (Special application 1972-36
980)

Commonly used salts of tranexamic acid include metal salts such as Mg, Ca, K, and sulfates, and derivatives include vitamin A acid ester, vitamin A ester, vitamin E ester, and vitamin C. Examples include, but are not limited to, esters, vitamin esters such as vitamin D ester, phenyl esters, N,N-maleoylminotranexamic acid, and the like.

[0010] The amount of tranexamic acid and/or its salt, or its derivative in the present invention is preferably 0.001 to 10% by weight, more preferably 0.01 to 5% by weight, based on the total amount of the oral composition. If the amount is less than 0.001% by weight, the effect of the present invention will not be fully exhibited, and if it is added in an amount exceeding 5% by weight, no further effect can be expected.

[0011] Examples of cell growth factors used in the present invention include EGF, FGF, PDGF, and TGF-β, which inhibit the proliferation of epidermal cells and dermal fibroblasts at extremely low concentrations (0.1 ng/g~ 100 ng/g) is known to significantly promote this effect.

Next, the molecular properties and mechanism of action of the above-mentioned cell growth factors are as follows.

1. EGF is a polypeptide consisting of 53 amino acids, has a molecular weight of 6045, is easily dissolved in water, and promotes the proliferation of many types of cells such as epidermal cells and fibroblasts.

2. Two types of FGF have been reported: acidic FGF is a polypeptide consisting of 140 amino acids, and basic FGF is a polypeptide consisting of 146 amino acids. Both are known to promote proliferation of fibroblasts, vascular endothelial cells, etc.

3. PDGF is a complex of an A chain consisting of 125 amino acids and a B chain consisting of 160 amino acids, and is a polypeptide consisting of a combination of AA, AB and BB, respectively. Promotes the proliferation of connective tissue cells such as fibroblasts. It is also known to play an important role in the wound healing process among biological defense mechanisms.

4. TGF-β is a complex consisting of two polypeptide chains each consisting of 112 amino acids, and is known to promote or inhibit the actions of other cell growth factors. It is known to promote the proliferation of fibroblasts and the production of biopolymer components such as collagen and fibronectin.

[0017] The blending amount of cell growth factors in the present invention is as follows:
0.00001 to 0.1% by weight (0.00001 to 0.1% by weight of the total amount of the skin external preparation)
1 ppm to 1000 ppm) is preferable, and 0.0001
-0.01% by weight (1.0ppm - 100ppm) is more preferred. If it is less than 0.00001% by weight, the effect of the present invention will not be fully exhibited, and if it is more than 0.1% by weight, no further effect can be expected.

In addition to the above-mentioned essential ingredients, the oral composition according to the present invention may optionally contain abrasives such as dicalcium phosphate and silica, humectants such as glycerin, sorbitol, and propylene glycol, carboxymethyl cellulose,
Thickeners such as methylcellulose, hydroxyethylcellulose, carrageenan, sodium polyacrylate, surfactants such as sodium lauryl sulfate, sucrose fatty acid ester, lauroyl sarcosinate, higher alcohols, oils such as wax, lower alcohols, fragrances, and pigments. , preservatives, antioxidants, water, and other components commonly used in oral compositions can be blended.

The dosage form of the oral composition of the present invention is arbitrary, and may be any dosage form such as a solid type, a solution type, a solubilized type, or a powder dispersion type.

[0020]

Effects of the Invention The oral composition of the present invention contains tranexamic acid and/or its salts, its derivatives, and cell growth factors, so it prevents swelling, edema, bleeding, etc. during inflammation, and prevents gingivitis. This is an oral composition that is highly effective in preventing and treating periodontitis.

[0021]

[Examples] The present invention will be explained in detail below with reference to Examples, but the present invention is not limited thereto. The blending amount is in weight%. Practical use test (1) Toothpaste formulation to be tested A toothpaste with the formulation shown below was prepared.

Example 1

Weight% tranexamic acid

0.05EGF

0.
005 Dibasic calcium phosphate dihydrate
40.0
glycerin

10.0 sorbitol

10.0 Carboxymethyl cellulose Na
1.5 Sodium lauryl sulfate

1.5 saccharin

0.1 fragrance


1.0 purified water

remainder

Comparative example 1


Weight% tranexamic acid

0.05 dicalcium phosphate dihydrate
40.0 Glycerin

10.0 sorbitol

10.0 Carboxymethyl cellulose Na
1.5 Sodium lauryl sulfate
1.5 saccharin

0.1 fragrance

1.0 purified water

remainder

00
24] Comparative example 2

Weight% EGF

0.005 dicalcium phosphate dihydrate
40.0 Glycerin

10.
0 sorbitol

10.0 Carboxymethyl cellulose Na

1.5 Sodium lauryl sulfate

1.5 saccharin

0.1 fragrance

1
．． 0 purified water

remainder

(2) Experimental method Sixty volunteer male employees who live in a dormitory and have relatively the same living environment were subjected to the same conditions for using toothbrushes, oral cleaning methods, and sample toothpaste.Example 1 and Comparative Example 1-2
The subjects were asked to brush their teeth using this toothpaste for 4 weeks and compared the results. 1st group: Using the toothpaste of Example 1 2nd group: Using the toothpaste of Comparative Example 1 3rd group: Using the toothpaste of Comparative Example 2

(3) Screening Objective and subjective symptoms were observed during the screening immediately before the start of the actual use test, and the same screening was conducted every week for 4 consecutive weeks, a total of 5 times.

(4) Results The results are shown in Table 1.

[0028]

[Table 1]

The first group using the toothpaste of Example 1 was less susceptible to marginal periodontitis, papillary gingivitis, gum bleeding, and the like compared to the second and third groups using the toothpastes of Comparative Examples 1 and 2. It showed excellent synergistic effects on bad breath and discomfort in the mouth upon waking up.

Clinical Experiment The following experiment was conducted at a dental clinic in Tokyo. The target patients were 60 people from an in-house panel who reported having subjective symptoms of periodontal disease (alveolar pyorrhea) but did not have any specific medical disease. The experimental method was the same as the actual use experiment described above. The effectiveness was divided into subjective symptoms and objective findings, and comprehensively evaluated using a 4-point evaluation method. The results are shown in Table 2. The toothpaste used has the following formulation.

Example 2 In place of the tranexamic acid in Example 1, 0.05% sodium salt of tranexamic acid was mixed, and in place of EGF, 0.05% of FGF was added.
005 combination

Comparative Example 3 In place of tranexamic acid in Comparative Example 1, 0.05% of sodium salt of tranexamic acid was blended.

Comparative example 4 Added 0.005 FGF instead of EGF in Comparative Example 2

00
34] 1st group: Using Example 2 2nd group: Using Comparative Example 3 3rd group: Using Comparative Example 4

(2) Results

[Table 2]

As is clear from Table 2, the first group using the toothpaste of Example 2 had a synergistic effect on all symptoms of periodontal disease compared to the second and third groups using the toothpaste of Comparative Examples 3 and 4. It can be seen that it has a positive effect.

Example 3 Toothpaste

Weight% Calcium phosphate dihydrate

42.5 Silicic anhydride

3.0 Glycerin
10.5
Sorbitol

11.0 Carboxymethylcellulose

1.0 Sodium lauryl sulfate

1.8 Flavorings

1.0 Vitamin A acid ester of tranexamic acid
0.1 PDGF

0.01
water

remainder

[Manufacturing method] Follow the conventional method. The toothpaste of the present invention showed excellent effects on marginal periodontitis, gum bleeding, and bad breath.

Example 4 Toothpaste

Weight% Calcium phosphate dihydrate

45.0 Silicic anhydride

2.0 Glycerin

10.0
Sorbitol

10.0 Carboxymethylcellulose

1.0 Sodium lauryl sulfate

1.8 Flavorings

1.0 Potassium salt of tranexamic acid
0.001 TGF-
β
0
．． 01 water

remainder

[Manufacturing method] Follow the conventional method. The toothpaste of the present invention showed excellent effects on marginal periodontitis, gum bleeding, and bad breath.

Example 5 Toothpaste

Weight% Calcium carbonate

39.0 Silicic anhydride

2.0 Glycerin
2
2.0 Sorbitol

10.0 Carboxymethylcellulose

1.1 Sodium lauryl sulfate

1.8 Saccharin

0.1 Fragrance


1.0 Tranexamic acid

0.5 EGF

0.0001
water

remainder

[Manufacturing method] Follow the conventional method. The toothpaste of the present invention showed excellent effects on marginal periodontitis, gum bleeding, and bad breath.

Example 6 Pasta for oral cavity
Weight% Vaseline

10.0 Propylene glycol

7.0 Stearyl alcohol

10.0 Vitamin C ester of tranexamic acid
5.0 FGF

0.005 Polyethylene glycol 1500
30.0 Polyethylene glycol 400
remainder

[Manufacturing method] Follow the conventional method.

Example 7 Mouthwash
Weight% ethanol

40.0 Glycerin

15.0 Polyoxyethylene hydrogenated castor oil
1.0 Saccharin

0. l
fragrance

1.0 Tranexamic acid

0.001 TGF-β

0.0
1 water

remainder

[Manufacturing method] Follow the conventional method.

Example 8 Chewing gum
Weight% Gum base

25.0 Calcium carbonate

2.0 Fragrance


1.0 Copper chlorophyll

0.05 Vitamin A of tranexamic acid
ester
0.05 PDGF

0.0001 water


remainder

[Manufacturing method] According to the conventional method

Claims (1)

[Claims] 1. An oral composition comprising tranexamic acid and/or a salt thereof, a derivative thereof, and a cell growth factor. [Chemical I]