JPH10167957A - Intercellular adhesion suppressing agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject suppressing agent useful for treating skin diseases and improving corneum troubles through the action on cells themselves by compounding a specific alcohol as an active component. SOLUTION: This suppressing agent is a composition containing a 15-25C terpene alcohol as an active component preferably in an amount of 0.001-20wt.%. Examples of the above terpene alcohol include a compound of formula I [a dotted line expresses a single bond or a double bond; (n)=2, 3, 4] (e.g. farnesol), a compound of formula II (e.g. geranylgeranylisopropanol), a compound of formula III [(n)=3, 4] (e.g. phytanetriol) or a compound of formula IV (e.g. isophytol). The suppressing agent can be compound with another medicinal component such as a germicidal disinfectant, an astringent agent or a skin softening agent, or an aqueous component, powder, an oil solution, a humectant, etc., which are used as a component of a cosmetic or a percutaneous medicine. The suppressing agent is preferably used as an agent for external use for skin, and ointment, milky lotion, cream, skin lotion, etc., is cited as a dosage form. When used as an agent for external use, the agent is administered 1-3 times a day at a dose of 0.1-2mg/cm<2> on the entire application region.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a cell adhesion inhibitor comprising terpene alcohol as an active ingredient and useful for treating and improving skin diseases and preventing and improving horny layer troubles.

[0002]

2. Description of the Related Art The epidermis is composed of various types of cells, and keratinocytes (keratinocytes) occupy the majority. As the keratinocytes proliferate and move to the upper layer, the outermost layer of the stratum corneum is formed by a differentiation process (keratinization).
Epidermal cells play an important role in the normal keratinization of the epidermis and maintenance of the stratum corneum.

[0003] It is said that these abnormalities of cell adhesion of keratinocytes in the epidermis are responsible for skin diseases such as bullous disease and certain keratosis. Further, it is known that skin troubles such as acne, dandruff, and desquamation due to sunburn are caused by an increase in the stratum corneum due to an increase in cell adhesion.

[0004] Desmosome is a representative device for bonding the epidermis including the stratum corneum. Desmosomes are protein aggregates involved in adhesion between epidermal cells and keratinocytes, and proteins directly involved in adhesion are desmoglein and desmocholine.

[0005] Up to now, an increase in desmosome protein has been observed in horny layer exfoliation caused by rough lips, desquamation of the horny layer caused by sunburn or drying, acne inner horny layer, and dandruff. Therefore, it is considered that these stratum corneum problems are caused by abnormal stratum corneum adhesion function due to an increase in desmosome protein, and it is considered effective to control cell adhesion function by desmosome to prevent and improve these stratum corneum problems. .

As a method for controlling desmosomes, there has been reported a method for improving the acne, dandruff and desquamation by decomposing the desmosome protein accumulated in the stratum corneum with a protease (Japanese Patent Application Laid-Open No. 7-505383;
WO93 / 19732, WO95 / 07687, WO9
5/07688).

[0007]

However, substances which can be used for treating these skin diseases and improving horny layer troubles by acting on cells themselves and effectively inhibiting cell-cell adhesion have been found. Absent. Accordingly, an object of the present invention is to provide an agent that suppresses cell-cell adhesion by desmosomes involved in stratum corneum trouble.

[0008]

The inventors of the present invention have conducted intensive studies to achieve the above object, and as a result, have found that terpene alcohols having a total carbon number of 15 to 25 can effectively inhibit epidermal cell-cell adhesion. And found that the present invention was completed. That is, the present invention has a total carbon number of 15 to 2
It is intended to provide an intercellular adhesion inhibitor containing one or more terpene alcohols as an active ingredient.

[0009]

DETAILED DESCRIPTION OF THE INVENTION The terpene alcohol having a total carbon number of 15 to 25 used as an active ingredient of the cell adhesion inhibitor of the present invention includes, for example, the following general formulas (1) to (1).
The compound shown by (4) is mentioned.

[0010]

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[0011]

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[0012]

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[0013]

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Examples of the compound represented by the above general formula (1) include farnesol, phytol, geranyl cytoronelol, geranylgeraniol, geranyl farnesol and the like. The compound represented by the general formula (2) includes geranylgeranyl isopropanol and the like, the compound represented by the general formula (3) includes phytantriol and the like, and the compound represented by the general formula (4) Examples include isophytol and geranyl linalool. The terpene alcohol used as an active ingredient in the present invention is not limited to these compounds, and any one having a total carbon number of 15 to 25 can be used.

The cell adhesion inhibitor of the present invention is preferably used in the form of an external preparation for skin, and the content of the above-mentioned active ingredient in the external preparation for skin is within a range sufficient to exhibit the effect of suppressing cell adhesion. Although not particularly limited, it is preferably 0.001 to 20% by weight of the whole composition. If the content is less than 0.001% by weight, a sufficient cell-cell-adhesion inhibitory effect cannot be obtained, and 20% by weight.
If the ratio exceeds the above, it is not preferable because stabilization of the composition may be hindered.

The intercellular adhesion inhibitor of the present invention may contain other medicinal components such as a disinfectant, an astringent, an emollient, a hormone, and vitamins. In addition, cosmetics, aqueous ingredients, powders, oils, humectants, alcohols, pH adjusters commonly used as skin medicine ingredients,
Preservatives, ultraviolet absorbers, thickeners, dyes, fragrances, and the like can be appropriately added. Examples of the form of the external preparation include an ointment, a milky lotion, a cream, a lotion, a serum, a cleansing agent, a pack, a cleaning agent, a foundation, a lipstick and the like.

The intercellular adhesion inhibitor of the present invention is used as an external preparation 1 to 3 times daily, over the entire area where the applied amount is 0.1 to ² mg / cm ² .

[0018]

Next, the present invention will be described in more detail with reference to examples, but these examples do not limit the present invention.

(Test Example) The desmosome formation inhibitory effect of the terpene alcohol of the present invention was tested by the following method using desmoglein expression as an index. Human cultured epidermal cells were subcultured on a LoveTech chamber slide, 37 ° C, 5%
The cells were cultured in an incubator under CO ₂ conditions. Immediately before the cells reach confluence, the medium was brought to a calcium concentration of 0.
0.001% by weight of 03 mM terpene alcohol
The medium was exchanged for a% -dissolved medium. The cells were cultured at 37 ° C. and 5% CO ₂ for 12 hours, and the calcium concentration in the medium was increased from 0.03 to 1.5 mM by adding a calcium chloride solution. The cells were fixed by immersing the chamber slide in methanol cooled to −20 ° C. for 10 minutes 24 hours after the calcium switch. Perform immunofluorescence staining using a monoclonal anti-desmoglein antibody as the primary antibody and FITC-labeled anti-mouse IgG as the secondary antibody to observe the intercellular desmosome formation inhibitory effect, observe with a fluorescence microscope, and compare with the group without terpene alcohol. Was determined.

As a result, 24 hours after the calcium concentration switch, in the terpene alcohol-free group, fluorescence showing the presence of desmoglein was remarkably localized between cells, and almost no intercellular space was observed. .
In comparison, in the terpene alcohol-added group of the present invention, the fluorescent staining of desmoglein between cells was very weak, and the cell gap was clearly observed. Table 1 shows the activity intensity of each terpene alcohol compound determined by microscopic observation.
These results indicate that the terpene alcohol of the present invention inhibits desmosome formation of human keratinocytes and inhibits cell-cell adhesion.

[0021]

[Table 1]

Examples of preparing various forms of the intercellular adhesion inhibitor of the present invention containing a terpene alcohol having a total carbon number of 15 to 25 as an active ingredient are described below. The composition in each example is by weight. (Example 1) Cream A cream having the following composition was prepared by an ordinary method. Geranylgeraniol 2 Squalane 5 Stearic acid 2 Glycerin monostearate 10 Ethanol 2 Methyl parahydroxybenzoate 0.2 Cetanol 2 Olive oil 4 Vaseline 5 Ceramide 1 Fragrance, pigment Trace amount Purified water Remaining meter (100.0)

Example 2 Skin Lotion A skin lotion having the following composition was prepared by a conventional method. Geranylgeraniol 2 Glycerin monostearate 1 Ethanol 15 Propylene glycol 4 Isopropyl palmitate 3 Vitamin C 0.5 Lanolin 1 Ceramide 1 Methyl parahydroxybenzoate 0.1 Perfume, pigment Trace amount Purified water Remaining meter (100.0)

(Example 3) Packing agent A packing agent having the following composition was prepared by a conventional method. Geranylgeraniol 3 Polyvinyl alcohol 20 Glycerin 5 Ethanol 16 Fragrance, pigment Trace amount Purified water Remaining meter (100.0)

[0025]

Industrial Applicability The intercellular adhesion inhibitor containing a terpene alcohol having a total carbon number of 15 to 25 as an active ingredient according to the present invention suppresses intercellular adhesion caused by desmosome, and causes blebosis, keratosis, and keratin dysfunction. It has an excellent effect on the treatment and improvement of various skin diseases such as sickness, acne, dandruff, rough skin and rough lips, and the prevention and improvement of horny layer trouble.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code FI C07C 31/125 C07C 31/125 33/02 33/02

Claims (2)

[Claims] A cell adhesion inhibitor comprising at least one terpene alcohol having a total carbon number of 15 to 25 as an active ingredient. 2. A terpene alcohol represented by the following general formula (1):
The intercellular adhesion inhibitor according to claim 1, which is a compound represented by (4). Embedded image Embedded image Embedded image Embedded image