JPH04300818A - Composition for oral cavity - Google Patents

Abstract

PURPOSE:To obtain a composition for the oral cavity capable of promoting proliferation of gingival tissues, preventing swelling, edema, hemorrhage, etc., in inflammation and exhibiting excellent effects on prevention and treatment of periodontal diseases such as gingivitis and periodontitis. CONSTITUTION:A composition for the oral cavity is obtained by blending saikogenin A (R is beta-OH) and/or saikogenin D (R is alpha-OH) expressed by the formula as an essential ingredient with other ingredients. The amount of the aforementioned ingredient is preferably 0.0001-1.0wt.%, especially 0.001-0.1wt.% based on the total amount of the composition for the oral cavity. Furthermore, one or more compounds selected from a cell growth factor, tranexamic acid or derivative thereof are preferably used in combination to synergistically enhance effects of the compound expressed by the formula on periodontal diseases. Thereby, the objective composition for the oral cavity having the aforementioned effects is obtained. The amounts of the above-mentioned ingredients based on the total amount of the composition for the oral cavity are preferably 0.00001-0.1wt.% especially 0.0001-0.01wt.% cell growth factor and preferably 0.001-10wt.%, especially 0.01-5wt.% tranexamic acid or derivative thereof.

Description

[Detailed description of the invention]

0001

FIELD OF THE INVENTION This invention relates to oral compositions. More specifically, by incorporating psychogenin A and/or psychogenin D, and by further incorporating cell growth factors, tranexamic acid, or its derivatives, it is possible to prevent and treat periodontal diseases such as gingivitis and periodontitis. The present invention relates to an oral composition having a remarkable effect on the oral cavity.

0002

[Prior Art] It has been reported that sapogenin is the center of expression of the anti-inflammatory and lipid metabolic effects of psychosaponin, a glycoside of psychogenin (Metabolism Vol. 10, pp. 695-701, (1973). In addition, it has been reported that saikosaponin has the effect of promoting skin wound healing when applied transdermally as an external preparation for the skin (Japanese Patent Application Laid-Open No. 61-7216), but the mechanism of action for these effects is unknown. is hardly elucidated. On the other hand, urogastrone (usually called epidermal cell growth factor), which is one of the cell growth factors, has been reported as an external preparation for the skin or a topical preparation for skin diseases. JP-A-61-7216). Furthermore, a skin treatment liniment using a combination of urogastrone and the herbal medicines licorice or saiko has also been reported. (Unexamined Japanese Patent Publication No. 6
0-23325). Furthermore, tranexamic acid is generally used as an anti-plasmin agent, and is known as an ingredient characterized by high safety in cosmetic applications. In addition, it is also included in oral compositions as a component that has a preventive effect on gingivitis and periodontitis due to its anti-plasmin action.

0003

[Problems to be Solved by the Invention] As a result of intensive research into the mechanism of wound healing effect of psychogenin, the present inventors discovered seven types of psychogenin (A to A), each with a different structure.
Of G), when an oral composition containing the following psychogenin A or D is applied, it promotes the growth of gingival tissue, prevents swelling, edema, bleeding, etc. caused by inflammation, and prevents gingivitis and tooth loss. We have discovered that these are extremely effective in the prevention and treatment of periitis, and what is even more surprising is that these and cell growth factors such as epidermal cell factor (EGF) and fibroblast growth factor (FG)
F), Transformisig Growth Factor (TG
The present inventors have discovered that when used in combination with F-β), tranexamic acid, and its derivatives, these effects become synergistic, and the present invention has been completed.

[0004] In addition to psychogenin A and D used in the present invention, B, C, E, F, and G have been isolated and their structures have been fully clarified; however, they are useful for the prevention and treatment of gingivitis and periodontitis. It is psychogenin A or D that has an effect. Incidentally, there are no reports on the effects of psychogenin A or D on periodontal diseases, and no application to oral compositions is known. Furthermore, it is completely unknown that when psychogenin A and D are used in combination with cell growth factors, tranexamic acid, and derivatives thereof, these effects become synergistic.

[0005]

[Means for Solving the Problems] That is, the invention of claim 1 is an oral composition characterized in that it contains psychogenin A (R=β-OH) and/or psychogenin D (R=α-OH). The invention of claim 2 provides psychogenin A (R=β-OH) and/or psychogenin D (
The present invention provides an oral composition characterized in that one or more selected from cell growth factors, tranexamic acid, or derivatives thereof are blended into R=α-OH). Hereinafter, the configuration of the present invention will be explained in detail.

[0006] The blending amount of psychogenin A or D in the present invention is preferably 0.0001 to 1.0% by weight (1 to 10,000 ppm), and 0.001 to 1.0% by weight (1 to 10,000 ppm) based on the total amount of the skin external preparation.
0.1% by weight (10 to 1000 ppm) is more preferred. If it is less than 0.0001% by weight, sufficient effects cannot be obtained, and even if it exceeds 1.0% by weight, no further effects can be expected.

[0007] Cell growth factors used in claim 2 of the present invention include, for example, EGF, FGF, PDGF and TGF-
Examples include β. These drugs inhibit the proliferation of epidermal cells and dermal fibroblasts at extremely low concentrations (0.1 ng/g to 100 n/g).
g/g).

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, and acidic FGF is
A polypeptide consisting of 140 amino acids, basic F
GF 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.

[0012] The tranexamic acid used in the invention according to claim 2 has a melting point of 262 to 267°C, is a white crystal or powder, has no odor, and has a bitter taste. The manufacturing method is patent No. 2406
No. 11, Japanese Patent No. 242,664, Japanese Patent No. 480,411, and Japanese Patent No. 488,168. As derivatives of tranexamic acid, commonly used salts include:
There are metal salts such as Mg, Ca, K, sulfates, etc., vitamin A acid esters, vitamin A esters, vitamin E esters, vitamin C esters, vitamin D esters and other vitamin esters, phenyl esters, N,N- Examples include, but are not limited to, maleoylminotranexamic acid. The amount of the cell growth factor in the invention according to claim 2 is 0.000 in the total amount of the skin external preparation.
01-0.1% by weight (0.1ppm-1000ppm)
is preferable, and 0.0001 to 0.01% by weight (1.0p
pm to 100 ppm) is more preferable. 0.0000
If it is less than 1% by weight, the effect of the present invention will not be sufficiently exhibited, and if it is less than 1% by weight.
Even if the amount exceeds 1% by weight, no further effect can be expected. The amount of tranexamic acid or its derivative in the invention according to claim 2 is 0.001 to 1 in the total amount of the skin external preparation.
0% by weight, preferably 0.01-5% by weight. If it is less than 0.001% by weight, the effect of the present invention will not be fully exhibited, and if it is more than 10% by weight, no further effect can be expected. In the invention according to claim 2, the cell growth factor, tranexamic acid, or a derivative thereof produces a synergistic effect only when used in combination with psychogenin A and D among psychogenins.

In addition to the above-mentioned essential ingredients, the oral composition of the present invention may optionally contain abrasives such as dibasic calcium phosphate and silica, wetting agents such as glycerin, sorbitol, and propylene glycol, depending on the dosage form of the composition. Thickeners such as carboxymethylcellulose, methylcellulose, 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, an emulsion type, or a powder dispersion type.

[0015]

Effects of the Invention Since the oral composition of the present invention contains psychogenin A and/or psychogenin D, it promotes the proliferation of gingival tissue, prevents swelling, edema, bleeding, etc. caused by inflammation, and prevents gingivitis and tooth loss. This is an oral composition that is extremely effective in preventing and treating pericitis. These effects are synergistically enhanced when used in combination with cell growth factors, tranexamic acid, and their derivatives.

[0016]

EXAMPLES The present invention will be explained in detail with reference to Examples below, but the present invention is not limited thereto. Prior to Examples, the test methods and evaluation methods conducted to clarify the periodontal disease preventing effect of the oral composition according to the present invention will be explained.

Gingival cell proliferation promoting effect Fibroblasts obtained from human gingiva were added to Dulbecco's modified Eagle's culture medium (DMEM) with 10% fetal bovine serum (FBS).
Obtain the number of cells required for the experiment by culturing them in a medium containing Next, these cells are made into single cells with trypsin, and 1×10 5 cells are adhered to a cell culture dish. After gluing,
After culturing in a 5% CO2 incubator for 5 hours,
After 24 hours of culturing in a CO2 incubator after changing the medium to DMEM containing 0.2% FBS, psychogenin (final concentration 1 μg/ml) or psychogenin and Epi
Dermal Growth Factor (EG
F, psychogenin and tranexamic acid (final concentration 10 μg/ml), psychogenin and Ep
Internal Growth Factor (E
0.2% FBS-DME containing GF, final concentration 24 ng/ml) and tranexamic acid (final concentration 10 μg/ml)
The medium was exchanged with M and incubated at 37°C. Thereafter, the cells were dispersed with trypsin and the number of cells was counted. In addition, 0.2% FBS-D
A control was prepared using only MEM.

The results are shown in Table 1.

[0019]

[Table 1]

As is clear from Table 1, psychogenin A
and D only markedly promoted the proliferation of gingival fibroblasts, and also markedly promoted the proliferation of gingival fibroblasts in the case of EGF-dependent proliferation and tranexamic acid-dependent proliferation.

[0021] Practical test: Sixty volunteer male office workers who lived in a dormitory and had relatively the same living environment were given the same conditions for using toothbrushes, oral cleaning methods, and sample dentifrice, and brushed their teeth for four weeks. I got it and compared it.

Example 1 Toothpaste

Weight% dicalcium phosphate dihydrate

45.0 Glycerin

15.0 Sorbitol
10
．． 0carboxymethylcellulose sodium
1.5 fragrance

0.8 Psychogenin A

0.01 saccharin sodium
0.2 Sodium lauryl sulfate

1.5 water

remainder

Example 2 Toothpaste

Weight% dicalcium phosphate dihydrate
4
5.0 glycerin

15.0 Sorbitol

10.0 Carboxymethyl cellulose sodium
1.5 fragrance


0.8 Psychogenin A

0.01FGF

0.1 saccharin sodium

0.2 Sodium lauryl sulfate

1.5 water

remainder

0
Example 3 Toothpaste

Weight% dicalcium phosphate dihydrate

45.0 Glycerin

15.0 Sorbitol

10.0
Carboxymethyl cellulose sodium
1.5 fragrance


0.8 Psychogenin A

0.01 tranexamic acid

0.1
saccharin sodium

0.2 Sodium lauryl sulfate

1.5 water

Example 4 Toothpaste

Weight% dicalcium phosphate dihydrate

45.0 Glycerin

15.0 Sorbitol
10
．． 0carboxymethylcellulose sodium
1.5 fragrance

0.8 Psychogenin A

0.01 tranexamic acid
0
．． 1FGF

0.1 saccharin sodium

0.2 Sodium lauryl sulfate
1.5 water

Comparative Example 1 Example 1 except that psychogenin A was removed from Example 1.
Same prescription.

[0027] Objective and subjective symptoms were observed during the examination immediately before the start of the actual use test, and the examination was conducted again 4 weeks later.

The results are shown in Tables 2 and 3.

[0029]

[Table 2]

[0030]

[Table 3] As is clear from Tables 2 and 3, the toothpaste of Example 1 containing psychogenin A exhibited a significantly higher anti-periodontitis effect than the toothpaste of Comparative Example 1. The effect was even more remarkable in Examples 2 to 4 in which FGF and tranexamic acid were blended.

Example 5 Toothpaste

Weight% silicic anhydride

20.0 sorbitol

50.0 carrageenan

0.5 Psychogenin A

1.0 Sodium salt of tranexamic acid
3.0 Carboxymethylcellulose Sodium
1.0 Sodium lauryl sulfate
1.8 Sodium saccharin
0
．． 08 fragrance

0.9 Purified water


remainder

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

Example 6 Pasta for oral cavity

Weight% Psychogenin D

0.0001EGF

0.
2 Vaseline

10.0 Propylene glycol

7.0 stearyl alcohol
10.0 polyethylene glycol 1500
30.0 polyethylene glycol 400
remainder

[Manufacturing method]
according to common law

Example 7 Mouthwash

Weight% psychogenin A

0.001 Psychogenin D

0.001 saccharin sodium
0.05 ethyl alcohol

10.0 polyoxyethylene (10 moles)

1.0 Monooleic acid ester fragrance

0.03 purified water


remainder

[Manufacturing method] According to the conventional method

Example 8 Chewing gum

Weight% Psychogenin D

0.1 gum base

25.0
calcium carbonate

3.0 copper chlorophyll

0.05 fragrance

0.
03 Sorbit powder

remainder

[Manufacturing method] According to the conventional method

Example 9 Toothpaste

Weight% silicic anhydride

20.0 sorbitol

50.0 carrageenan

0.5 Psychogenin A

1.0FGF


0.01 Tranexamic acid vitamin A acid ester
0.01 carboxymethyl cellulose sodium
1.
0 Sodium lauryl sulfate

1.8 Sodium saccharin

0.08 fragrance

0.9 spirit
Made of water

remainder

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

Claims (2)

[Claims] Claim 1: Psychogenin A (R=β-OH) and/or psychogenin D (R
=α-OH). [Chemical I] 2. Psychogenin A (R=β-OH) and/or psychogenin D (R
= α-OH) and one or more selected from cell growth factors, tranexamic acid, or derivatives thereof. [Chemical I]