JP2012167023A - Ceramide production promoter, humectant, and skin care preparation for external use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a ceramide production promoter, a humectant and a skin care preparation for external use.SOLUTION: The ceramide production promoter, the humectant and the skin care preparation for external use contain as an effective ingredient a compound represented by general formula (1). In the formula, R-Rare each independently hydrogen, a hydroxy group or an acyloxy group; Ris a hydroxy group or an acyloxy group; when Ris a hydroxy group, Ris hydrogen and X is C=O; and when Ris an acyloxy group, Ris hydrogen, a hydroxy group or an alkoxy group and X is C=O or CRR.

Description

  The present invention relates to a ceramide production promoter, a humectant, and a skin external preparation.

  Ceramide, one of the sphingolipids, is a very small amount of lipid in the whole body, but in the stratum corneum, which is the outermost layer of the skin, it occupies more than half of the lipid, and is a moisturizing and barrier mechanism for the skin. Plays an important role. This ceramide functions by constructing a lamellar structure between cells in the stratum corneum after being produced and secreted in epidermal cells. However, in skin diseases such as dry skin, rough skin, atopic dermatitis, senile psoriasis and psoriasis, the healthy metabolism of ceramide is hindered, and the amount of ceramide in the stratum corneum is reduced, resulting in skin moisturizing ability and It has been reported a lot that the barrier ability is lowered.

Ceramide also has bone resorption inhibitory action, bone strengthening action, and alveolar bone loss inhibitory action, and is useful for prevention and improvement of osteoarthritis such as osteoporosis, fractures, low back pain, rheumatism, and prevention of periodontal disease. Has been reported to be effective (see Patent Document 1). Furthermore, it has been reported that ceramide has an effect of imparting firmness and stiffness to hair and improving touch (see Patent Document 2). Therefore, a ceramide production promoting substance can also be expected to have a therapeutic effect on such diseases.
Regarding such skin diseases, promotion of bone formation, and improvement of hair firmness and stiffness, methods for supplying reduced ceramide from the outside have been tried, but the effect is not necessarily sufficient at present.

JP 2001-158735 A Japanese Patent Laid-Open No. 10-152421

  An object of the present invention is to provide a ceramide production promoter having a high ceramide production promotion effect. Another object of the present invention is to provide a moisturizing agent and a skin external preparation excellent in the action of promoting ceramide production.

  In view of the above-mentioned problems, the present inventors have intensively studied to search for a new material having a ceramide production promoting action. As a result, it was found that the compound represented by the following general formula (1) has a high ceramide production promoting action, and the knowledge that the compound is useful as a novel moisturizing component was obtained. The present invention has been made based on this finding.

  That is, this invention relates to the ceramide production promoter which contains the compound represented by following General formula (1) as an active ingredient.

（式中、Ｒ^１〜Ｒ^３は、それぞれ独立に水素原子、ヒドロキシル基又は炭素数１〜１２のアシルオキシ基を表す。Ｒ^４はヒドロキシル基又は炭素数１〜１２のアシルオキシ基を表す。
Ｒ^４がヒドロキシル基の場合、Ｒ^５は水素原子を表し、ＸはＣ＝Ｏを表す。
Ｒ^４が炭素数１〜１２のアシルオキシ基の場合、Ｒ^５は水素原子、ヒドロキシル基又は炭素数１〜５のアルコキシ基を表し、ＸはＣ＝Ｏ、又はＣＲ^６Ｒ^７を表す。Ｒ^６及びＲ^７は、それぞれ独立に水素原子、ヒドロキシル基、又は炭素数１〜５のアルコキシ基を表す。Ｒ^５及びＲ^６は互いに結合して、Ｒ^５及びＲ^６が結合している炭素原子とともに−Ｏ−を含有する環状エーテル構造を形成してもよい。）

^(Wherein, R 1 to R ³ each independently represent a hydrogen atom, is .R ⁴ representing a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms represents a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms.
When R ⁴ is a hydroxyl group, R ⁵ represents a hydrogen atom and X represents C═O.
When R ⁴ is an acyloxy group having 1 to 12 carbon atoms, R ⁵ represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 5 carbon atoms, and X represents C═O or CR ⁶ R ⁷ . R ⁶ and R ⁷ each independently represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 5 carbon atoms. R ⁵ and R ⁶ may be bonded to each other to form a cyclic ether structure containing —O— together with the carbon atom to which R ⁵ and R ⁶ are bonded. )

The present invention also relates to a humectant containing the compound represented by the general formula (1) as an active ingredient.
Furthermore, this invention relates to the skin external preparation which contains the compound represented by the said General formula (1) as an active ingredient.

  According to the present invention, a ceramide production promoter can be provided. Moreover, according to this invention, the moisturizer and skin external preparation excellent in the ceramide production promotion effect can be provided.

Hereinafter, the present invention will be described in detail.
The ceramide production promoter, moisturizer and skin external preparation of the present invention contain a compound represented by the following general formula (1) as an active ingredient. As demonstrated in Examples described later, this compound has a high ceramide production promoting action.

In general formula (1), R < ¹ > -R < ³ > represents a hydrogen atom, a hydroxyl group, or a C1-C12 acyloxy group each independently. R ⁴ represents a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms.
When R ⁴ is a hydroxyl group, R ⁵ represents a hydrogen atom and X represents C═O.
When R ⁴ is an acyloxy group having 1 to 12 carbon atoms, R ⁵ represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 5 carbon atoms, and X represents C═O or CR ⁶ R ⁷ . R ⁶ and R ⁷ each independently represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 5 carbon atoms. R ⁵ and R ⁶ may be bonded to each other to form a cyclic ether structure containing —O— together with the carbon atom to which R ⁵ and R ⁶ are bonded.

In R ^{1 to} R ⁴ , the acyloxy group having 1 to 12 carbon atoms includes a formyloxy group, a substituted or unsubstituted aliphatic acyloxy group having 2 to 12 carbon atoms, and a substituted or unsubstituted aromatic group having 6 to 12 carbon atoms. Group acyloxy group. Examples of the aliphatic acyloxy group include a linear, branched or cyclic alkylcarbonyloxy group, a linear, branched or cyclic alkenylcarbonyloxy group, and a linear, branched or cyclic alkynylcarbonyloxy group. Examples of alkylcarbonyloxy groups include methylcarbonyloxy group (acetoxy group), ethylcarbonyloxy group, n-propylcarbonyloxy group, isopropylcarbonyloxy group, n-butylcarbonyloxy group, isobutylcarbonyloxy group, sec-butylcarbonyl Examples thereof include an oxy group, a tert-butylcarbonyloxy group, an n-pentylcarbonyloxy group, and an isopentylcarbonyloxy group. Examples of the aromatic acyloxy group include a benzoyloxy group and a naphthoyloxy group.

In R ^{5 to} R ⁷ , examples of the alkoxy group having 1 to 5 carbon atoms include linear, branched or cyclic alkoxy groups, such as a methoxy group, an ethoxy group, a propoxy group, an isopropoxy group, a cyclopropoxy group, Examples thereof include an n-butoxy group and a tert-butoxy group.

R ¹ is preferably a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms, more preferably a hydroxyl group or an acyloxy group having 2 to 5 carbon atoms, and particularly preferably a hydroxyl group or an acetoxy group.
R ² is preferably a hydrogen atom or an acyloxy group having 1 to 12 carbon atoms, more preferably a hydrogen atom or an acyloxy group having 2 to 5 carbon atoms, and particularly preferably a hydrogen atom or an acetoxy group.
R ³ is preferably an acyloxy group having 1 to 12 carbon atoms, more preferably an acyloxy group having 2 to 5 carbon atoms, and particularly preferably an acetoxy group.
R ⁴ is preferably a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms, more preferably a hydroxyl group or an alkylcarbonyloxy group having 1 to 12 carbon atoms, still more preferably a hydroxyl group or 2 to 5 carbon atoms. And particularly preferably a hydroxyl group, an acetoxy group, an isopropylcarbonyloxy group, or a sec-butylcarbonyloxy group.
When R ⁴ is an acyloxy group having 1 to 12 carbon atoms, R ⁵ and R ⁶ are bonded to each other to form a cyclic ether structure containing —O— with the carbon atom to which R ⁵ and R ⁶ are bonded. It is preferable.
As a preferable combination of R ^{1 to} R ⁷ , R ¹ and R ³ are acetoxy groups, R ² is a hydrogen atom or an acetoxy group, R ⁴ is an alkylcarbonyloxy group having 2 to 5 carbon atoms, and R ⁵ and R ⁶ are To form a cyclic ether structure containing —O— with the carbon atom to which R ⁵ and R ⁶ are bonded, a combination in which R ⁷ is a hydrogen atom, R ¹ and R ⁴ are hydroxyl groups, Examples include a combination in which R ² and R ³ are a hydrogen atom or an acetoxy group.

  In the present invention, the compound represented by the general formula (1) includes a salt thereof. Examples of the salt include, but are not limited to, alkali metal salts such as lithium salt, sodium salt and potassium salt, alkaline earth metal salts such as calcium salt and magnesium salt, alkylamine salts such as trimethylamine and triethylamine, and quaternary ammonium salts. , Alkanolamine salts such as triethanolamine, diethanolamine and monoethanolamine, or amino acid salts such as lysine, histidine and arginine. Moreover, in this invention, when the compound represented by General formula (1) can take tautomerism, the tautomer is also included.

  Although the specific example of a compound represented by General formula (1) below is given, this invention is not limited by these. In the following exemplary compounds (a) to (e), Ac represents an acetyl group.

The method for producing the compound represented by the general formula (1) used in the present invention is not particularly limited, and a chemically synthesized product may be used, which may be extracted or purified from a natural product-derived material. May be. Moreover, what is marketed as a reagent can also be used.
As a production method by chemical synthesis, for example, the compound towsendanine can be used as a starting material, and the hydroxyl group of the towsendanine can be acylated by a general acylation method (Reference: Experimental Chemistry Course 5th Edition 16). p42). The compound towsendanine can be obtained as a reagent from AvaChem.

Examples of a method for obtaining the compound represented by the general formula (1) from a material derived from a natural product include simple methods from plants such as towsendan (scientific name: Melia toosendan Sieb. Et Zucc.) And sendan (scientific name: Melia azedarach ). Can be separated.
These plants can be used in any arbitrary part (whole tree, whole grass, root, rhizome, stem, branch, stem, leaf, bark, sap, resin, flower, fruit, seed, etc.). is there. In particular, when isolated from towsendan, it is preferable to use fruits and bark. In addition, herbal medicines obtained by using tousendan fruit as the base plant, river lion (senrenshi), herbal medicines obtained using bark as the base plant, and bitter skin (clenpi) can also be used. When isolated from Sendang, it is preferable to use the bark. It is also possible to use herbal medicine, krempi, obtained by using the bark of Sendang as a base plant.
Moreover, the compound represented by the said General formula (1) can also be isolated using combining each plant or each site | part suitably.

A method for isolating the compound represented by the general formula (1) from these plants is not particularly limited. For example, the plant extract obtained by extracting the above-described plant using an appropriate solvent is obtained. And a method of isolating the compound represented by the general formula (1) by a technique such as chromatography.
For the preparation of the plant extract, the above plant may be used as it is, or dried and ground. Solvents used for extraction are those usually used for extraction of plant components, such as water, petroleum ether, n-hexane, toluene, chloroform, ether, ethyl acetate, acetone, methanol, ethanol, propanol, butanol, ethylene glycol, propylene. Glycol, butylene glycol, and a mixed solution thereof can be used. Moreover, normal conditions can be applied as extraction conditions. For example, the above-described plant may be immersed or heated to reflux at 5 to 80 ° C. for 2 hours to 60 days.
As specific extraction and isolation methods, the methods shown in the Examples described later can be used, but the present invention is not limited thereto.

The compound represented by the general formula (1) has an excellent ceramide production promoting action. Ceramide is an important substance for maintaining and adjusting the skin moisturizing mechanism and barrier mechanism, and the promotion of ceramide production normalizes the ceramide production mechanism of the living body, increases the ceramide in the reduced stratum corneum, and has a high barrier function And it leads to regaining skin having a moisturizing function. In addition, it is useful for improving the elasticity and stiffness of hair and promoting bone formation.
Therefore, a ceramide production promoter and a humectant can be obtained by containing the compound represented by the general formula (1) as an active ingredient. It has never been known that the compound represented by the general formula (1) has a ceramide production promoting action, which is a new finding obtained by the present inventors.

  As the ceramide production promoter and humectant of the present invention, the compound represented by the general formula (1) may be used as it is. Moreover, the compound represented by the general formula (1) may be contained as an active ingredient, and additives, other medicinal ingredients, and the like may be added within a range that does not affect the effect. For example, an appropriate liquid or solid excipient or extender such as titanium oxide, calcium carbonate, distilled water, lactose, starch or the like can be added to form a ceramide production promoter. Moreover, a known ceramide production promoter, pseudo ceramide, natural ceramide, sugar ceramide, and the like can be added to the compound represented by the general formula (1) to make a humectant. As a medicinal component other than the moisturizer, a skin aging inhibitor, a whitening agent, and the like may be added together.

The ceramide production promoter that can be used in combination with the compound represented by the general formula (1) is not particularly limited. For example, acetylhydroxyproline, potassium glycyrrhizinate, L-carnitine, ascorbic acid, ascorbyl glucoside, Magnesium ascorbyl phosphate, dl-α-tocopheryl-dl-ascorbyl phosphate, dl-α-tocopheryl phosphate, nicotinamide, tocopherol nicotinate, L-lactic acid, vitamin C, asparagus extract, butcher bloom, genquanine , Rosemary, lavender, sage, jujube, black (red) ganoderma, touki, kujin, yokuinin, beniceanne extract, rice power extract and the like.
The pseudo ceramide is not particularly limited. For example, commercially available ceramide R (manufactured by Unilever), ceramide PC-104 (manufactured by Taiheiyo Chemical), ceramide HO3 (manufactured by sederma), Erduo PS-203 (Ajinomoto) Manufactured).
The sugar ceramide is not particularly limited, and examples thereof include glucosyl ceramide, galactosyl ceramide, etc., and commercially available nip ceramide (manufactured by Nippon Flour), oryzah ceramide (manufactured by Oriza Yoka), Nissan Examples include ceramide, neo-liquid ceramide N (manufactured by NOF Corporation), ceramide (manufactured by Unitika) and the like.

  The compound represented by the general formula (1) can express a ceramide production promoting effect at a low concentration. The amount of the compound represented by the general formula (1) contained in the ceramide production promoter or moisturizer of the present invention is not particularly limited, but the compound represented by the general formula (1) is 0.00000001 to 10. It is preferably contained in an amount of about mass%, particularly preferably about 0.0000001 to 0.1 mass%.

  The agent of the present invention can take various dosage forms such as liquid, solid, emulsion, paste, gel, powder (powder), granule, pellet, stick, etc. Includes all forms that can be applied to the skin, nails, mucous membranes, hair and the like.

The ceramide production promoter and humectant of the present invention can be applied to uses such as cosmetics, pharmaceuticals, quasi drugs and foods.
When used in cosmetics, pharmaceuticals, quasi drugs, etc., the agent of the present invention can be used, for example, in the form of a skin external preparation. In addition to the compound represented by the general formula (1), the above-mentioned various additives and other medicinal ingredients can be added as appropriate to the external preparation for skin, and further, the external preparation for skin according to the dosage form that can be taken Various components that are usually used can be blended. Specific dosage forms for external preparations for skin include creams, serums, lotions, emulsions, lotions, massage agents, foundations, lipsticks, bath preparations, shampoos, hair conditioners, hair tonics, tablets, capsules, gels, ointments. , Pastes, packs, massage agents, foundations, lipsticks, bathing agents, shampoos, hair conditioners, sheet-like products, and the like, and various dosage forms that can be applied for external use. Examples of these dosage forms include various oils, Surfactants, gelling agents, preservatives, antioxidants, solvents, alcohol, water, chelating agents, thickeners, UV absorbers, emulsion stabilizers, pH adjusters, dyes, fragrances, and the like can be blended. .
The amount of the compound represented by the general formula (1) contained in the external preparation for skin is the same as the amount of the compound represented by the general formula (1) in the ceramide production promoter and moisturizer described above. .

When used in food applications, in addition to general food and drink, the concept is the effect of improving and maintaining the skin's moisturizing ability or barrier function. It can be added to and blended with food and drink for the sick.
There is no particular limitation on the form of the food, for example, beverages such as fruit juice beverages, milk beverages, tea beverages, confectionery such as candy, drop, jelly, cookies, chocolate, cakes, yogurt, gum, seasonings, cooking Examples include oil, dairy products, breads, noodles, and processed rice. Moreover, it is good also as beauty foods, health foods, etc., such as a tablet (tablet), a capsule, a granule, and a syrup.
For these beverages or foods, for example, additives such as sweeteners, colorants, antioxidants, vitamins, fragrances, minerals, etc., and food ingredients such as proteins, lipids, carbohydrates, carbohydrates, dietary fibers, etc. are used in appropriate combinations. It can be prepared by incorporating the compound represented by the general formula (1) into various food forms according to a conventional method.

  When the ceramide production promoter or moisturizing agent of the present invention is used as cosmetics, pharmaceuticals, quasi-drugs, foods, etc., the use or intake is appropriately selected depending on the conditions such as the form, the age, sex, etc. Can be done. In general, it is preferable to use or ingest 0.1 ng to 1 g of the compound represented by the general formula (1) per day per adult, and particularly preferable to ingest or use 1 ng to 1 mg.

  EXAMPLES Hereinafter, although this invention is demonstrated further in detail based on an Example, this invention is not limited to this.

Production Example 1: Exemplary compound (a)
10 mg of Toosendanin (Toosendanin, manufactured by AvaChem) was dissolved in 200 mL of a mixed solvent of acetic anhydride / pyridine (1/3) and stirred for 19 hours. After concentration, the mixture was partitioned with ethyl acetate-0.1N HCl aqueous solution, and the ethyl acetate layer was further washed with water and concentrated. The resulting concentrated residue was purified using HPLC to obtain 3.9 mg (yield 36%) of exemplary compound (a) (sendanin).
The resulting compound was identified by NMR. The results of structural analysis by NMR are shown in Table 1. In Table 1, Ac represents an acetyl group.

Production Examples 2 to 4: Exemplified compounds (b) to (d)
When 80 g of Clenpi (purchased from Shinwa Bussan Co., Ltd.) was extracted with 800 mL of methanol and the solvent was concentrated, 3.2 g of extracted solid content was obtained. The obtained extracted solid was subjected to liquid-liquid partition with ethyl acetate-water to obtain 1 g of ethyl acetate layer (yield 31%). The ethyl acetate layer was fractionated by a silica gel column to obtain 41 mg (yield 1.28%) of fraction (1) and 45 mg (yield 1.4%) of fraction (2). Further, these fractions were fractionated by HPLC. From fraction (1), fraction (3) 0.3 mg (yield 0.01%) and fraction (4) 0.31 mg (yield 0. 01%) was obtained, and 0.17 mg (yield 0.005%) of fraction (5) was obtained from fraction (2).
These fractions (3), (4) and (5) were subjected to NMR structural analysis. Fraction (3) was exemplified compound (b) (12-O-acetyl azedarachin B), and fraction (4) was The exemplified compound (c) (12-O-acetyl trichilin B) and the fraction (5) were identified as the exemplified compound (d) (Trichilin H). The results of structural analysis by NMR are shown in Tables 2-4. In Tables 2 to 4, Ac represents an acetyl group, and Me represents a methyl group.

Production Example 5: Exemplary compound (e)
870 g of Tousendan fruit (Senrenshi, purchased from Shinwa Bussan Co., Ltd.) was extracted with 8.7 L of 50% ethanol at 20 to 35 ° C. for 7 days, and the solvent was concentrated to obtain 129 g of an extracted solid content. The obtained extracted solid content was fractionated using as an index ceramide production promoting activity by the method of the test example described later. When liquid-liquid partition was performed using water and ethyl acetate, the activity was concentrated in 15.1 g (yield 11.7%) of the ethyl acetate layer. The ethyl acetate layer was further fractionated with a silica gel column to obtain 7.30 g (yield 5.65%) of fraction (1). Further, this fraction was fractionated using a silica gel column to obtain 838 mg (yield: 0.64%) of fraction (2). Of this, 500 mg was fractionated by HPLC to obtain 55 mg (yield 0.072%) of fraction (3). Of this, 50 mg was further fractionated by HPLC to obtain 10.2 mg (yield 0.014%) of fraction (4). Of this, 7 mg was further purified by HPLC to obtain 2.1 mg (yield 0.004%) of fraction (5). This fraction (5) was subjected to structural analysis using NMR.
As a result, the active ingredient isolated from towsendan was a compound having the structure shown in Table 5 below, and this compound was identified as the exemplary compound (e) (12-hydroxyamoorastatone). . In addition, Phytochemstry (1994), 36 (6), 1493-1496. Was used as a comparative literature value. The results of structural analysis by NMR are shown in Table 5. In Table 5, Ac represents an acetyl group.

Production of Comparative Compound 1 10 mg of Tousendanin (Toosendanin, manufactured by AvaChem) was dissolved in 200 mL of a mixed solvent of acetic anhydride / pyridine (1/3) and stirred for 19 hours. After concentration, the mixture was partitioned with ethyl acetate-0.1N HCl aqueous solution, and the ethyl acetate layer was further washed with water and concentrated. The resulting concentrated residue was purified using HPLC to obtain 1 mg (yield 9%) of Comparative Compound 1 (7-acetyl sendanin).
The resulting compound was identified by NMR. The results of structural analysis by NMR are shown in Table 6. In Table 6, Ac represents an acetyl group.

Production of Comparative Compound 2 20 mg of Toosendanin (manufactured by AvaChem) was dissolved in 400 mL of methanol, and 40 mL of 10% aqueous potassium hydroxide solution was added and stirred for 2 hours. Thereafter, a small amount of acetic acid was added, and after quenching, methanol was removed by evaporation and liquid separation was performed with ethyl acetate. The obtained ethyl acetate layer was concentrated to obtain 15.5 mg of a concentrated residue. The residue was purified using an UltraPack column (manufactured by Yamazen) to obtain 9.9 mg (yield: 58%) of Comparative Compound 2 (deacylated toosendanin).
The resulting compound was identified by NMR. The results of structural analysis by NMR are shown in Table 7.

(Test example) Verification of ceramide production promoting effect Normal human epidermal keratinocytes (trade name: NHEK (F), KURABO) in culture solution (trade name: EpiLife-KG2, manufactured by KURABO) using a culture plate Manufactured at 37 ° C. and 5% CO ₂ .
After that, the culture solution is changed to EpiLife-KG2 excluding growth factors such as epidermal growth factor, and as an evaluation sample,
Exemplified compounds (a) to (e) produced in Production Examples 1 to 5
Comparative compounds 1, 2
50% ethanol (control solution)
One of the above was added in an amount of 0.01% so that the concentrations shown in Table 8 were obtained.
After culturing for 3 days, each cell was collected together with 1 well.

The organic phase from which the lipid was extracted from the collected cells by the Bligh and Dyer method was transferred to a glass tube, solidified with nitrogen, and then redissolved with chloroform and methanol to obtain a lipid sample.
In addition, 0.1N NaOH, 1% SDS aqueous solution is added to the cells after lipid extraction, and the protein is solubilized by heating at 60 ° C. for 2 hours, cooled to room temperature, and then neutralized by adding 2N HCl. The amount of protein was quantified by the BCA method.

The prepared lipid sample was horizontally developed by thin film chromatography (TLC) twice with chloroform: methanol: acetic acid = 190: 9: 1. The copper sulfate solution was sprayed and sprayed with a hot plate to detect ceramide, and the amount was determined.
The results are shown in Table 8. In addition, the amount of ceramide shown in Table 8 shows a relative value when the control solution addition group is 1.

(Reference example)
1. Preparation of Eucalyptus Extract 40 g of Eucalyptus globulus Labillardiere (purchased from Shinwa Bussan Co., Ltd.) was cut into small pieces, added with 400 mL of 50% ethanol, and extracted for 7 days at room temperature and standing conditions. Then, it filtered and 291 mL of eucalyptus extracts were obtained. About the obtained extract, when the evaporation residue was computed by the following method, the evaporation residue was 3.16% (w / v).

2. Verification of ceramide production promoting effect Using the obtained eucalyptus extract, the ceramide production promoting effect was verified by the same method as in the above test example. In addition, 0.001% of the extract adjusted so that a density | concentration might be 1% (w / v) in conversion of solid content added to the cell.
The results are shown in Table 8. Eucalyptus extract is known as a moisturizing ingredient having a ceramide production promoting action.

  As is apparent from Table 8, in the system to which the exemplary compounds (a) to (e) were added, an increase in ceramide yield was observed compared to the control system. On the other hand, in Comparative Compounds 1 and 2 not included in the compound represented by the general formula (1), no increase in ceramide yield was observed. From these results, it was found that the compound represented by the general formula (1) of the present invention has an excellent ceramide production promoting action and is useful as a ceramide production promoting agent. Furthermore, the compound represented by the general formula (1) has a ceramide production promoting effect equivalent to or higher than that of a known eucalyptus extract (reference example), which is a known moisturizing component, and therefore is useful as a moisturizing agent. I understood.

(Prescription example)
A skin lotion, 0 / W (oil-in-water) type emulsion, W / O (water-in-oil) type cream, sunscreen agent having the composition shown below, with the compound represented by the general formula (1) as an active ingredient, Gel-like cosmetics, liquid baths, foods in tablet form, hair lotions, and hair treatments were each prepared by conventional methods.

1. Preparation of lotion (composition) (formulation: mass%)
Exemplary Compound (a) 0.000005
Polyethylene glycol (trade name: PEG-1540, manufactured by Sanyo Chemical Co., Ltd.) 1.00
Polyoxyethylene (20) sorbitan monolaurate 1.50
Glycerin 2.00
Paraben 0.10
Purified water residue

2. Preparation of 0 / W emulsion (composition) (formulation: mass%)
Exemplary compound (b) 0.001
Polyethylene glycol (trade name: PEG-2000, manufactured by Sanyo Chemical Co., Ltd.) 1.00
Pullulan (trade name: Pullulan PT-20, manufactured by Hayashibara) 0.40
Cetyl alcohol 1.00
Vaseline 2.00
Squalane 6.00
Dimethylpolysiloxane 2.00
Glycerin 2.00
Pseudoceramide (N- (3-hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethylhexadecaminad) 1.00
Polyoxyethylene (10) monooleate 1.00
Glycerol monostearate 1.00
Acid heteropolysaccharide derived from plant callus (1% by weight aqueous solution of tuberose polysaccharide) 2.00
Paraben 0.20
Purified water residue

3. Preparation (composition) of W / O type cream (Formulation: mass%)
Exemplary Compound (c) 1.00
Alkyl acrylate copolymer (trade name: Yodosol GH810, manufactured by Kanebo NSC)
1.30
Polyvinylpyrrolidone (Brand name: Rubiscol K-90, manufactured by BASE Japan)
0.70
Dimethylpolysiloxane 10.00
Methylphenylpolysiloxane 3.00
Octamethylcyclotetrasiloxane 12.00
Polyoxyalkylene modified silicone 5.00
1,3-butylene glycol 6.00
Pseudoceramide (N- (3-hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethylhexadecaminad) 1.20
Paraben 0.20
Perfume Trace amount Purified water Residual

4). Preparation (composition) of sunscreen agent (formulation: mass%)
Exemplary compound (d) 0.002
Alkyl acrylate copolymer (trade name: Yodosol GH810, manufactured by Kanebo NSC)
1.00
Polyethylene glycol (trade name: PEG-4000S, manufactured by Sanyo Chemical Co., Ltd.) 1.00
Octyl paramethoxycinnamate 5.00
Silicon coated zinc oxide 6.00
Silicon coated titanium oxide 0.50
Dimethylpolysiloxane 5.00
Octamethylcyclotetrasiloxane 20.00
Polyoxyalkylene-modified silicone 3.00
Ethanol 3.00
Glycerin 3.00
Magnesium sulfate 1.00
Paraben 0.20
Perfume Trace amount Purified water Residual

5. Preparation (composition) of gel cosmetic (formulation: mass%)
Exemplary compound (e) 0.50
Polyethylene glycol (trade name: PEG-2000, manufactured by Sanyo Chemical Co., Ltd.) 0.50
Xanthan gum (trade name: Neosoft XKK, manufactured by Kojinsha) 0.20
Glycerin 3.00
Ethanol 3.00
Carboxyvinyl polymer 0.50
Potassium hydroxide 0.15
Polyoxyethylene hydrogenated castor oil 1.00
Citric acid 0.80
Trisodium citrate 0.80
Nylon powder 1.00
Paraben 0.10
Perfume Trace amount Purified water Residual

6). Preparation of liquid bathing agent (composition) (formulation: mass%)
Exemplary compound (a) 0.000001
Pseudoceramide (N- (3-hexadecyloxy-2-hydroxypropyl) -N-2-hydroxyethylhexadecaminad) 0.10
Isopropyl myristate 15.00
Polyoxyethylene (12) oleyl ether 10.00
Polyoxyethylene (6) oleyl ether 6.00
Acid heteropolysaccharide derived from plant callus (1% by weight aqueous solution of tuberose polysaccharide) 2.00
Paraben 0.30
Perfume Trace amount Liquid paraffin Residue

7). Preparation of food Each material was mixed according to the following composition and formed into a tablet.
(Composition) (Composition: Mass%)
Exemplary Compound (b) 0.5
Crystalline cellulose 89.0
Whey calcium residue

8). Preparation of hair lotion Each material was mixed according to the following composition and manufactured by a conventional method.
(Composition) (Composition: Mass%)
Exemplary Compound (c) 0.00001
Ethanol 60.0
Propylene glycol 2.0
Methylparaben 0.1
Fragrance 2.0
Purified water residue

9. Preparation of hair treatment Each material was mixed according to the following composition and manufactured by a conventional method.
(Composition) (Composition: Mass%)
Exemplary Compound (d) 0.01
Cetylstearyl alcohol 5.0
Glycine 1.0
Methylparaben 0.1
Fragrance 0.5
Purified water residue

Claims (3)

The ceramide production promoter which contains the compound represented by following General formula (1) as an active ingredient.

^(Wherein, R 1 to R ³ each independently represent a hydrogen atom, is .R ⁴ representing a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms represents a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms.
When R ⁴ is a hydroxyl group, R ⁵ represents a hydrogen atom and X represents C═O.
When R ⁴ is an acyloxy group having 1 to 12 carbon atoms, R ⁵ represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 5 carbon atoms, and X represents C═O or CR ⁶ R ⁷ . R ⁶ and R ⁷ each independently represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 5 carbon atoms. R ⁵ and R ⁶ may be bonded to each other to form a cyclic ether structure containing —O— together with the carbon atom to which R ⁵ and R ⁶ are bonded. ) A humectant containing a compound represented by the following general formula (1) as an active ingredient.

^(Wherein, R 1 to R ³ each independently represent a hydrogen atom, is .R ⁴ representing a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms represents a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms.
When R ⁴ is a hydroxyl group, R ⁵ represents a hydrogen atom and X represents C═O.
When R ⁴ is an acyloxy group having 1 to 12 carbon atoms, R ⁵ represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 5 carbon atoms, and X represents C═O or CR ⁶ R ⁷ . R ⁶ and R ⁷ each independently represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 5 carbon atoms. R ⁵ and R ⁶ may be bonded to each other to form a cyclic ether structure containing —O— together with the carbon atom to which R ⁵ and R ⁶ are bonded. ) A skin external preparation containing a compound represented by the following general formula (1) as an active ingredient.

^(Wherein, R 1 to R ³ each independently represent a hydrogen atom, is .R ⁴ representing a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms represents a hydroxyl group or an acyloxy group having 1 to 12 carbon atoms.
When R ⁴ is a hydroxyl group, R ⁵ represents a hydrogen atom and X represents C═O.
When R ⁴ is an acyloxy group having 1 to 12 carbon atoms, R ⁵ represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 5 carbon atoms, and X represents C═O or CR ⁶ R ⁷ . R ⁶ and R ⁷ each independently represents a hydrogen atom, a hydroxyl group, or an alkoxy group having 1 to 5 carbon atoms. R ⁵ and R ⁶ may be bonded to each other to form a cyclic ether structure containing —O— together with the carbon atom to which R ⁵ and R ⁶ are bonded. )