JP2001122726A - Epidermal cell growth inhibitor and cosmetic, quasi-drug and skin preparation for external use each containing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an epidermal cell growth inhibitor, and to obtain a cosmetic, quasi-drug or skin preparation for external use each containing the above inhibitor, having effect of improving skin disorders due to epidermal cell hyperplasia and also excellent in safety and feeling when applied. SOLUTION: This epidermal cell growth inhibitor contains at least one active ingredient selected from galactomannansaccharide polymers, mucin, trimethylglycine and proteoglycan.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to an epidermal cell proliferation inhibitor and cosmetics, quasi-drugs, and skin preparations containing the epidermal cell proliferation inhibitor.

[0002]

2. Description of the Related Art Conventionally, skin barrier dysfunction caused by parakeratosis, which is the result of abnormal proliferation of epidermal cells forming the epidermal layer in diseases such as atopic dermatitis, psoriasis, and contact dermatitis, and pigmentation External problems such as lichen formation are recognized as skin disorders.

Further, as a result of the research by the present inventors, abnormal stress of epidermal cells is induced by psychological stress as in the above-mentioned diseases, and skin disorders such as abnormal barrier function, dry skin and abnormal skin tone are induced. It became clear that it would be.

[0004] For each of these diseases or skin disorders,
Conventionally, cosmetics, quasi-drugs, and skin external preparations have been developed.

[0005]

However, the effect is not sufficient, the feeling of use is not satisfactory, and cosmetics, quasi-drugs, and skin external preparations corresponding to each disease or skin disorder are required. Since it had to be used, it was inconvenient. Therefore, the development of cosmetics, quasi-drugs, and external preparations for skin that can commonly cope with each disease or skin disorder has been desired.

The present inventors have conducted intensive studies in an attempt to solve such a conventional problem. As a result, in vitro tests showed that galactomannan saccharide polymer, mucin, trimethylglycine and proteoglycan were induced by amphiregulin. In vivo studies have shown that the effect of suppressing hyperproliferation of epidermal cells can be improved by improving skin barrier due to reduced skin function due to thickening of the epidermal layer, skin color change, and decreased moisture retention function. And found that it had excellent usability, and completed the present invention.

The present invention provides a skin cosmetic, a quasi-drug, or an external preparation for skin which has an effect of improving skin disorders caused by hyperproliferation of epidermal cells and is excellent in safety and feeling in use. Is the subject.

[0008]

SUMMARY OF THE INVENTION The present invention has been made to solve such problems, and means for solving the problems includes at least one of a galactomannan saccharide polymer, mucin, trimethylglycine, and proteoglycan. Seeds are included.

A galactomannan saccharide polymer,
The amount of mucin, trimethylglycine, or proteoglycan to be added to skin cosmetics, quasi-drugs, or topical skin preparations is not particularly limited, but may be 0.0005% by weight to 20%.
% By weight.

[0010] When the amount of these components is less than 0.0005% by weight,
The effects aimed at by the present invention are not so satisfactory. On the other hand, even if the amount of these components exceeds 20% by weight, no improvement in the effects commensurate with the increase is observed.

The skin cosmetics, quasi-drugs or external preparations of the present invention can be in the form of lotions, emulsions, creams, packs, ointments and the like.

The skin cosmetics, quasi-drugs, and skin preparations of the present invention can appropriately contain pigments, preservatives, surfactants, fragrances, pigments, and the like.

[0013]

Embodiments of the present invention will be described below.

(Example 1) This example is an example of an epidermal cell proliferation inhibitor, and the effect of a test substance on amphiregulin-induced abnormal epidermal cell proliferation was tested.

Human epidermal cells NHEK (F) (trade name: Epidercell: Kurabo Industries) were seeded at 1000 cells / ml in a 96-well microplate for cell culture, and after 24 hours, a galactomannan saccharide polymer (trade names: phytallonate,
The medium was replaced with a 1 ng / ml amphiregulin-containing medium Hu Media-KG2 (trade name: Kurabo Industries) to which Pentfarm was added.

After culturing for 72 hours, the proliferation of epidermal cells was measured by a neutral red assay.

Hu Media-KG2, which is a culture medium, is composed of Hu Media-KG2 (trade name: Kurabo Industries), which is a basic medium composed of various amino acids, vitamins, inorganic acids, glucose, etc., and insulin, hEGF, hydrocortisone, and antibacterial agent. , BP
It is mixed with Hu Media-KG (trade name: Kurabo Industries) which is a growth additive composed of E.

The results of the measurement of growth inhibition were compared with the growth rate of the control group of 10
It is shown in Table 1 as 0%.

[0019]

[Table 1]

As is clear from Table 1, the content of the galactomannan saccharide polymer was 0.001% by weight and 0.1%, respectively.
In the cultured epidermal cells to which 01% by weight and 0.1% by weight were added, respectively, the proliferation was suppressed as compared with the amphiregulin-induced hyperproliferation of the cultured epidermal cells to which no galactomannan saccharide polymer was added.

(Example 2) This example is another example of an epidermal cell growth inhibitor, and includes
Mucin (trade name: Falconix mucin, Ichimaru Falcos) was used in place of the galactomannan saccharide polymer of Example 1 above.

This mucin was added to the same medium as used in Example 1 to obtain 0.001% by weight, 0.01% by weight and 0.1% by weight.

The epidermal cell proliferation was measured by the neutral red assay in the same manner as in Example 1.

The results of the measurement of growth inhibition were determined by comparing the growth rate of the control group to 10
It is shown in Table 2 as 0%.

[0025]

[Table 2]

As is clear from Table 2, in the cultured epidermal cells containing 0.001% by weight, 0.01% by weight, and 0.1% by weight of mucin, respectively, all of the cultured epidermal cells containing no mucin did not cause the amphiregulin-induced hyperproliferation of the cultured epidermal cells. Proliferation was suppressed in comparison.

(Example 3) This example is another example of an epidermal cell growth inhibitor, and trimethylglycine (trade name: BETAFIN BP, Carter) is used as an epidermal cell growth inhibitor.
Was used.

This trimethylglycine was added to the same medium as used in Example 1, and 0.1 μg / ml, 1 μg / ml, 1 μg / ml
It was 0 μg / ml.

Then, the epidermal cell proliferation was measured by a neutral red assay in the same manner as in Example 1.

The results of the proliferation measurement were determined by comparing the proliferation rate of the control group to 10
It is shown in Table 3 as 0%.

[0031]

[Table 3]

As is apparent from Table 3, in the cultured epidermal cells to which trimethylglycine was added at 0.1 μg / ml, 1 μg / ml, and 10 μg / ml, respectively, the amphiregulin induction of the cultured epidermal cells without any addition of trimethylglycine was observed. Proliferation was suppressed compared to overgrowth.

Example 4 This example is another example of an epidermal cell proliferation inhibitor, in which proteoglycan (trade name: Proteodermin, Kotobuki Chemical Co., Ltd.) was used as an epidermal cell proliferation inhibitor.

This proteoglycan was added to the same medium as used in Example 1, and 0.01% by weight, 0.1% by weight,
1.0% by weight.

Then, the epidermal cell proliferation was measured by the neutral red assay in the same manner as in Example 1.

The results of the proliferation measurement were determined by comparing the proliferation rate of the control group to 10
It is shown in Table 4 as 0%.

[0037]

[Table 4]

As is clear from Table 4, proteoglycan was added in an amount of 0.001% by weight, 0.01% by weight and 0.1% by weight, respectively.
In all of the cultured epidermal cells to which the proteoglycan was added, the proliferation was suppressed as compared to the amphiregulin-induced hyperproliferation of the cultured epidermal cells to which no proteoglycan was added.

(Examples 5 to 8 and Comparative Examples 1 to 3) This example is an example relating to abnormal barrier function and dry skin caused by abnormal cell proliferation. The improvement effect on the model was tested.

The ointment base Plastibase (manufactured by Taisho Pharmaceutical Co., Ltd.) was mixed well so that the concentration with respect to the total amount of the galactomannan saccharide polymer was 0.0005, 0.01% by weight, 1 and 20% by weight. , Example 6, Example 7, and Example 8.

On the other hand, pyrrolidone carboxylic acid was mixed well with plastibase so that the concentration with respect to the total amount was 1% by weight. Further, the case where only the base was applied was designated as Comparative Example 2, and the case where no base was applied was designated as Comparative Example 3.

With respect to the epidermal cell growth inhibitors of Examples 5 to 8 and Comparative Examples 1 to 3, tests for the improvement effect on the atopic dermatitis model as described below were conducted.

That is, the samples of Examples 5 to 8 and Comparative Examples 1 to 3 were continuously used for one week at the inflamed site of NC / Nga mice spontaneously developing dermatitis similar to human atopic dermatitis. The amount of water transpiration and the electrical conductivity of the skin were measured, and the degree of improvement in clinical findings by the naked eye was observed.

[0044]

[Table 5]

[0045]

[Table 6]

[0046]

[Table 7]

As is clear from Table 5, Examples 5 to 8
Then, the transepidermal water loss was smaller than in Comparative Examples 1 to 3.

In particular, since the transepidermal water loss decreases in the order of Example 5, Example 6, Example 7, and Example 8, the higher the concentration of the galactomannan saccharide polymer, the more the transepidermal water loss. It turned out to be less.

As is clear from Table 6, in Examples 5 to 8, the electrical conductivity of the skin was higher than in Comparative Examples 1 to 3.

In particular, since the skin electric conductivity increases in the order of Example 5, Example 6, Example 7, and Example 8, the skin electric conductivity increases as the concentration of the galactomannan saccharide polymer increases. It has been found.

Further, as is clear from the clinical findings in Table 7, in Comparative Examples 1 to 3, the symptoms such as eczema, hyperkeratosis, and scratching were moderate or severe.
At 8, these symptoms were mild or moderate.

From the results shown in Tables 5, 6, and 7, the galactomannan saccharide polymer was found to have an improving effect on the atopic dermatitis model. The higher the concentration of the galactomannan saccharide polymer, the lower the effect. It was observed to increase.

The NC / Nga mouse is one of the inbred strains bred and established by Professor Koji Kondo of the Faculty of Agriculture, Nagoya University, and is derived from a mouse that has been bred as a pet in Japan since ancient times. NC means N of mouse and C of cinnamon of coat color.

It has been known that dermatitis such as erosion is likely to occur in this mouse from the beginning when it was established as a strain, around the face, the head and the auricle.

[Examples 9 to 12 and Comparative Examples 4 to 6] This example is an example relating to a barrier function abnormality and skin dryness caused by abnormal cell proliferation, and to the psychological stress of an epidermal cell proliferation inhibitor. The ameliorating effect on the resulting skin disorders was tested.

The ointment base Plastibase (manufactured by Taisho Pharmaceutical Co., Ltd.) was mixed well so that the concentration based on the total amount of the galactomannan saccharide polymer was 0.0005, 0.01% by weight, 1 and 20% by weight. , Example 10, Example 11, and Example 12.

On the other hand, pyrrolidone carboxylic acid was mixed well with plastibase so that the concentration with respect to the total amount was 1% by weight. Further, the case where only the base was applied was designated as Comparative Example 5, and the case where no base was applied was designated as Comparative Example 6.

The epidermal cell growth inhibitors of Examples 9 to 12 and Comparative Examples 4 to 6 were tested for their effect on improving animal models of psychological stress as follows.

That is, the skin disorders caused by the psychological stress were applied to the above Examples 9 to 12 and Comparative Examples 4 to 6.
Were used continuously for one week, and the transepidermal water loss and the skin electrical conductivity were measured.

[0060]

[Table 8]

[0061]

[Table 9]

As is clear from Table 8, Examples 9 to 12
Then, the transepidermal water loss was smaller than in Comparative Examples 4 to 6.

In particular, since the transepidermal water loss decreases in the order of Example 9, Example 10, Example 11, and Example 12, the higher the concentration of the galactomannan saccharide polymer, the lower the transepidermal water loss. It turned out to be less.

Further, as is clear from Table 9, the skin electrical conductivity of Examples 9 to 12 was higher than that of Comparative Examples 4 to 6.

In particular, since the skin electric conductivity increases in the order of Example 9, Example 10, Example 11, and Example 12, the skin electric conductivity increases as the concentration of the galactomannan saccharide polymer increases. It has been found.

From the results shown in Tables 8 and 9, the galactomannan saccharide polymer was found to have an effect of improving skin disorders caused by psychological stress. The higher the concentration of the galactomannan saccharide polymer, the greater the effect of the improvement. Was allowed to do so.

For the psychological stress, overcrowding that has already been established was used. The present inventors have found that a decrease in skin barrier function and a decrease in skin water retention function accompanied by abnormal growth of epidermal cells by continuing this overcrowding for one week using mice, and the 98th Annual Meeting of the Japanese Dermatological Association ( 1999).

[Examples 13 to 16, Comparative example 7]
This is an example of a cream as an example of a cosmetic, and a practical test for rough skin of the cream was performed.

The preparation of the cream was carried out as follows.

Squalene, cetyl isooctanoate,
After heating and dissolving the microcrystalline wax, the clay mineral and POE glycerol triisostearate were added, the temperature was adjusted to 70 ° C., and the mixture was uniformly dispersed and dissolved to obtain an oily gel.

The galactomannan saccharide polymer was dissolved in purified water of a predetermined concentration, adjusted to 70 ° C., and slowly added to the oily gel with sufficient stirring.

After homogeneously mixing with a homomixer,
After filtration, the mixture was cooled to 30 ° C. to obtain a cream.

The compositions and compounding ratios of the obtained creams of Examples 13 to 16 are as follows.

Example 13 Composition Mixing ratio (% by weight) Squalene 20.0% Cetyl isooctanoate 8.5% Microcrystalline wax 1.0% Clay mineral 1.3% POE glycerol triisostearate 0.2% Galactomannan saccharide polymer 0.0005% Purified water

Example 14 Composition Compounding ratio (% by weight) Squalene 20.0% Cetyl isooctanoate 8.5% Microcrystalline wax 1.0% Clay mineral 1.3% POE glycerol triisostearate 0.2% Galactomannan saccharide polymer 0.01% Purified water

Example 15 Composition Compounding ratio (% by weight) Squalene 20.0% Cetyl isooctanoate 8.5% Microcrystalline wax 1.0% Clay mineral 1.3% POE glycerol triisostearate 0.2% Galactomannan saccharide polymer 1.0% Purified water

Example 16 Composition Mixing ratio (% by weight) Squalene 20.0% Cetyl isooctanoate 8.5% Microcrystalline wax 1.0% Clay mineral 1.3% POE glycerol triisostearate 0.2% Galactomannan saccharide polymer 20.0% Purified water

Using the creams of Examples 13 to 16 thus prepared, a practical test for rough skin was carried out.

The test method is as follows.

For 27 female subjects (23 to 42 years old) who routinely feel stress and complain of rough and dry skin,
The sample and the cream base were applied twice a day twice a day for one month to the affected area.

The evaluation was made by the number of persons who answered that the degree of improvement of rough and dry skin was better in the sample application site compared to the cream base application site.

On the other hand, a cream containing no galactomannan saccharide polymer was subjected to the same test as Comparative Example 7.

Table 10 shows the test results.

[0084]

[Table 10]

As is clear from Table 10, in Examples 12 to 15, the number of persons who answered that the skin roughness was improved was about twice or more as compared with Comparative Example 7.

[Examples 17 to 20, Comparative example 8]
This is an example of a lotion as an example of a cosmetic, and a rough skin practical test was performed on the lotion.

The lotion was prepared as follows.

A lotion base containing the surfactant POE (20) oleyl alcohol ether, the thickener methylcellulose, quince seed and ethanol was prepared, and a predetermined concentration of galactomannan saccharide polymer was added.

The compositions and compounding ratios of the obtained lotions of Examples 17 to 20 are as follows.

Example 17 Composition Mixing ratio (% by weight) POE (20) oleyl alcohol ether squalene 0.5% methyl cellulose 0.2% quince seed 0.1% ethanol 10.0% galactomannan saccharide polymer 0.0005% purified water

Example 18 Composition Mixing ratio (% by weight) POE (20) oleyl alcohol ether squalene 0.5% methyl cellulose 0.2% quince seed 0.1% ethanol 10.0% galactomannan saccharide polymer 0.01% purified water

Example 19 Composition Mixing ratio (% by weight) POE (20) oleyl alcohol ether squalene 0.5% methyl cellulose 0.2% quince seed 0.1% ethanol 10.0% galactomannan saccharide polymer 1.0% purified water

Example 20 Composition Mixing ratio (% by weight) POE (20) oleyl alcohol ether squalene 0.5% methyl cellulose 0.2% quince seed 0.1% ethanol 10.0% galactomannan saccharide polymer 20.0% purified water

Using the lotions of Examples 16 to 19 thus prepared, a practical test for rough skin was carried out.

The test method is as follows.

[0096] Twenty-seven female subjects (23 to 42 years old) who regularly feel stress, complain of rough and dry skin,
The sample and the lotion base were applied twice a day twice a day for one month to the affected area.

The evaluation was made by the number of persons who answered that the degree of improvement of rough skin and dry skin was better in the sample application site than in the lotion base application site.

On the other hand, a lotion containing no galactomannan saccharide polymer was subjected to the same test as Comparative Example 8.

Table 11 shows the test results.

[0100]

[Table 11]

As is clear from Table 11, in Examples 17 to 20, the number of persons who answered that the skin roughness was improved was about 2 to 3 times or more as compared with Comparative Example 8.

[Examples 21 and 22, Comparative Examples 9 and 10] This example is a test on the feeling of use of a cosmetic (cream and lotion) containing a galactomannan saccharide polymer (sensory test).

Example 21 is a sample of Example 15, Comparative Example 9 is a sample of Comparative Example 7, Example 22 is a sample of Example 19, Comparative Example 10
Using the sample of Comparative Example 8, 25 subjects evaluated the characteristics of the sample after using the sample for one week.

The evaluation was made based on the number of respondents who answered that "the skin fits well" in the questionnaire.

Table 12 shows the test results.

[0106]

[Table 12]

As shown in Table 12, in Examples 21 and 22,
Compared with Comparative Examples 9 and 10, about twice as many people answered that "the skin fits well".

[0108]

As described above, the present invention can provide useful skin cosmetics, quasi-drugs and skin external preparations which have a remarkable skin roughness improving effect and are excellent in use feeling. Was.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 17/00 A61K 37/02 (72) Inventor Junko Miyasaka 4-6 Koshien Nibancho, Nishinomiya City, Hyogo Prefecture ( 72) Inventor Akihiro Aioi 2-29-202, Kamigahara-kubancho, Nishinomiya-shi, Hyogo (72) Inventor Kazuhiko Hamada 64-5 Kamigamo-Toyodacho, Kita-ku, Kyoto F-term (reference) 4C083 AB442 AC012 AC022 AC102 AC182 AC352 AC422 AC582 AD211 AD241 AD242 AD262 AD411 CC02 CC04 CC05 DD31 EE13 4C084 AA02 BA03 CA35 MA63 NA14 ZA891 ZB211 ZB212 4C086 AA01 AA02 EA20 MA01 MA04 MA63 NA14 ZA89 ZB21 4C206 AA01 AA02 HA22 MA01 MA04 MA83 NA14 ZA89 ZB21

Claims (4)

[Claims] 1. An epidermal cell growth inhibitor comprising at least one of a galactomannan saccharide polymer, mucin, trimethylglycine, and proteoglycan. 2. A cosmetic comprising at least one galactomannan saccharide polymer, mucin, trimethylglycine or proteoglycan. 3. A quasi-drug containing at least one of a galactomannan saccharide polymer, mucin, trimethylglycine, and proteoglycan. 4. An external preparation for skin comprising at least one of a galactomannan saccharide polymer, mucin, trimethylglycine, and proteoglycan.