JP5328254B2 - Ceramide production promoter - Google Patents
Ceramide production promoter Download PDFInfo
- Publication number
- JP5328254B2 JP5328254B2 JP2008197958A JP2008197958A JP5328254B2 JP 5328254 B2 JP5328254 B2 JP 5328254B2 JP 2008197958 A JP2008197958 A JP 2008197958A JP 2008197958 A JP2008197958 A JP 2008197958A JP 5328254 B2 JP5328254 B2 JP 5328254B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- salt
- ceramide
- formula
- production promoter
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 title claims description 31
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 title claims description 31
- 229940106189 ceramide Drugs 0.000 title claims description 31
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 title claims description 31
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 title claims description 31
- 238000004519 manufacturing process Methods 0.000 title claims description 24
- -1 n-tetradecyl group Chemical group 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 19
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000003906 humectant Substances 0.000 claims description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000002537 cosmetic Substances 0.000 description 11
- 230000003020 moisturizing effect Effects 0.000 description 11
- 210000000434 stratum corneum Anatomy 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000003814 drug Substances 0.000 description 9
- 210000003491 skin Anatomy 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 229910001868 water Inorganic materials 0.000 description 8
- 229940125904 compound 1 Drugs 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000004909 Moisturizer Substances 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 230000004888 barrier function Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 230000001333 moisturizer Effects 0.000 description 6
- 239000010452 phosphate Substances 0.000 description 6
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
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- 239000002904 solvent Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000008591 skin barrier function Effects 0.000 description 3
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- QIAUWGCLDFMEML-UHFFFAOYSA-N 1-butoxy-3-octadecoxypropan-2-ol Chemical compound C(CCCCCCCCCCCCCCCCC)OCC(O)COCCCC QIAUWGCLDFMEML-UHFFFAOYSA-N 0.000 description 2
- KLSNOCPGVDDUFV-UHFFFAOYSA-N 1-ethoxy-3-tetradecoxypropan-2-ol Chemical compound CCCCCCCCCCCCCCOCC(O)COCC KLSNOCPGVDDUFV-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Chemical group CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 125000001204 arachidyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000001483 arginine derivatives Chemical class 0.000 description 2
- 125000002511 behenyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 125000002960 margaryl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 125000001196 nonadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
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- 102000004169 proteins and genes Human genes 0.000 description 2
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- 159000000000 sodium salts Chemical class 0.000 description 2
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000002469 tricosyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- NVKSMKFBUGBIGE-UHFFFAOYSA-N 2-(tetradecoxymethyl)oxirane Chemical compound CCCCCCCCCCCCCCOCC1CO1 NVKSMKFBUGBIGE-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
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- 239000004606 Fillers/Extenders Substances 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
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- 238000000692 Student's t-test Methods 0.000 description 1
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- ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
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- 229920005989 resin Polymers 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 150000003408 sphingolipids Chemical class 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
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- 238000012353 t test Methods 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
本発明は、表皮角層中のセラミドを増加させ、皮膚のバリア機能及び保湿機能を回復させることのできるセラミド産生促進剤及び保湿剤に関する。 The present invention relates to a ceramide production promoter and a humectant capable of increasing ceramide in the stratum corneum and restoring the skin barrier function and moisturizing function.
スフィンゴ脂質の一つであるセラミドは、生体全体の中では微量な脂質であるが、皮膚の最も外側の層である角層中では、脂質の半分以上を占め、皮膚の保湿機構、バリア機構に重要な役割を果たしている。当該セラミドは、表皮細胞中において産生、分泌された後に角層中の細胞間においてラメラ構造を構築することにより機能している。 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. The ceramide functions by building a lamellar structure between cells in the stratum corneum after being produced and secreted in epidermal cells.
しかし、乾燥肌、荒れ肌、アトピー性皮膚炎、老人性乾皮症、乾癬等の皮膚疾患においては、セラミドの健全な代謝が妨げられ、角層中のセラミド量が減少し、皮膚の保湿機能やバリア機能の低下等を引き起こしていることが数多く報告されている。
このような皮膚疾患に対し、減少したセラミドを外部から補給する方法も試みられているが、長期的な効果が認められない、安定性が低い等の問題がある。
However, in skin diseases such as dry skin, rough skin, atopic dermatitis, senile psoriasis and psoriasis, the healthy metabolism of ceramide is impeded, and the amount of ceramide in the stratum corneum is reduced. It has been reported a lot that the barrier function is reduced.
For such skin diseases, attempts have been made to supply reduced ceramide from the outside, but there are problems such as long-term effects not being observed and low stability.
一方、１，３−ジアルキルグリセル２−リン酸又はその塩は、皮膚洗浄効果を有することが知られている（特許文献１）。
しかし、１，３−ジアルキルグリセル２−リン酸又はその塩にセラミド産生促進効果及び保湿効果があることは、これまで知られていない。
However, it has not been known so far that 1,3-dialkylglyceryl 2-phosphate or a salt thereof has a ceramide production promoting effect and a moisturizing effect.
本発明は、皮膚のバリア機能及び保湿機能を回復又は維持し得る化粧品又は医薬品を提供することに関する。 The present invention relates to providing a cosmetic or pharmaceutical product that can restore or maintain the barrier function and moisturizing function of the skin.
本発明者らは、安全性の高い化合物について探索したところ、リン脂質誘導体にセラミド産生促進作用があり、１，３−ジアルキルグリセル２−リン酸又はその塩が角層の高いバリア機能及び保湿機能を回復又は維持し得る医薬品又は化粧品として有用であることを見出した。 When the present inventors searched for a highly safe compound, the phospholipid derivative has a ceramide production promoting action, and 1,3-dialkylglyceryl 2-phosphate or a salt thereof has a high stratum corneum barrier function and moisture retention. It was found useful as a pharmaceutical or cosmetic that can restore or maintain its function.
すなわち、本発明は、下記式（１） That is, the present invention provides the following formula (1):
（式中、Ｒ1は炭素数８〜２４のアルキル基を示し、Ｒ2は炭素数１〜２４のアルキル基を示す。）
で表される化合物又はその塩を有効成分とするセラミド産生促進剤に係るものである。
(In the formula, R 1 represents an alkyl group having 8 to 24 carbon atoms, and R 2 represents an alkyl group having 1 to 24 carbon atoms.)
The ceramide production promoter which uses the compound represented by these, or its salt as an active ingredient.
また、本発明は、下記式（１） Further, the present invention provides the following formula (1):
（式中、Ｒ1は炭素数８〜２４のアルキル基を示し、Ｒ2は炭素数１〜２４のアルキル基を示す。）
で表される化合物又はその塩を有効成分とする保湿剤に係るものである。
(In the formula, R 1 represents an alkyl group having 8 to 24 carbon atoms, and R 2 represents an alkyl group having 1 to 24 carbon atoms.)
The humectant which uses the compound represented by these, or its salt as an active ingredient.
本発明のセラミド産生促進剤は、角層中のセラミドを増加させ、皮膚のバリア機能及び保湿機能を回復又は維持するための化粧品、医薬品等として有用である。 The ceramide production promoter of the present invention is useful as cosmetics, pharmaceuticals, and the like for increasing ceramide in the stratum corneum and restoring or maintaining the skin barrier function and moisturizing function.
式（１）中、Ｒ1で示される、炭素数８〜２４のアルキル基としては、直鎖又は分岐鎖の何れでもよく、好ましくは炭素数１０〜２４、より好ましくは炭素数１２〜２０のアルキル基が挙げられる。
Ｒ1の具体例としては、オクチル基、ノニル基、デシル基、ウンデシル基、ドデシル基、トリデシル基、テトラデシル基、ペンタデシル基、ヘキサデシル基、ヘプタデシル基、オクタデシル基、ノナデシル基、イコシル基、ドコシル基、トリコシル基、テトラコシル基、２−ヘプチルウンデシル基、イソステアリル基、１２−メチルヘプタデシル基、２−オクチルドデシル基、３，７−ジメチルオクチル基、３，７−ジメチルオクタン−３−イル基、２−ヘキシルデシル基、３，７，１１−トリメチルドデシル基、１，１，３，３−テトラメチルブチル基、３，７，１１，１５−テトラメチルヘキサデシル基、３，５，５−トリメチルヘキシル基、１−イソプロピル−１，２−ジメチルプロピル基、１−イソプロピル−１，２，４，４−テトラメチルペンチル等が挙げられ、
このうち、テトラデシル基、ヘキサデシル基、オクタデシル基、イソステアリル基が好ましく、テトラデシル基がより好ましい。
In the formula (1), the alkyl group having 8 to 24 carbon atoms represented by R 1 may be either linear or branched, preferably 10 to 24 carbon atoms, more preferably 12 to 20 carbon atoms. An alkyl group is mentioned.
Specific examples of R 1 include octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, icosyl, docosyl, Tricosyl group, tetracosyl group, 2-heptylundecyl group, isostearyl group, 12-methylheptadecyl group, 2-octyldodecyl group, 3,7-dimethyloctyl group, 3,7-dimethyloctane-3-yl group, 2-hexyldecyl group, 3,7,11-trimethyldodecyl group, 1,1,3,3-tetramethylbutyl group, 3,7,11,15-tetramethylhexadecyl group, 3,5,5-trimethyl Hexyl group, 1-isopropyl-1,2-dimethylpropyl group, 1-isopropyl-1,2,4,4-teto Methylpentyl, and the like,
Among these, a tetradecyl group, a hexadecyl group, an octadecyl group, and an isostearyl group are preferable, and a tetradecyl group is more preferable.
式（１）中、Ｒ2で示される、炭素数１〜２４のアルキル基としては、直鎖又は分岐鎖の何れでもよく、好ましくは炭素数１〜１０、より好ましくは炭素数１〜６のアルキル基が挙げられる。
Ｒ2の具体例としては、例えば、メチル基、エチル基、ｎ−プロピル基、ｉ−プロピル基、ｎ−ブチル基、ｉ−ブチル基、ｔ−ブチル基、ペンチル基、ネオペンチル基、ヘキシル基、ヘプチル基、オクチル基、ノニル基、デシル基、ウンデシル基、ドデシル基、トリデシル基、テトラデシル基、ペンタデシル基、ヘキサデシル基、ヘプタデシル基、オクタデシル基、ノナデシル基、イコシル基、ドコシル基、トリコシル基、テトラコシル基、２−ヘプチルウンデシル基、イソステアリル基、１２−メチルヘプタデシル基、２−オクチルドデシル基、３，７−ジメチルオクチル基、３，７−ジメチルオクタン−３−イル基、２−ヘキシルデシル基、３，７，１１−トリメチルドデシル基、１，１，３，３−テトラメチルブチル基、３，７，１１，１５−テトラメチルヘキサデシル基、３，５，５−トリメチルヘキシル基、１−イソプロピル−１，２−ジメチルプロピル基、１−イソプロピル−１，２，４，４−テトラメチルペンチル基等が挙げられ、メチル基、エチル基、ｎ−プロピル基、ｉ−プロピル基、ｎ−ブチル基、ｉ−ブチル基、ｔ−ブチル基、が好ましく、エチル基がより好ましい。
In formula (1), the alkyl group having 1 to 24 carbon atoms represented by R 2 may be linear or branched, preferably 1 to 10 carbon atoms, more preferably 1 to 6 carbon atoms. An alkyl group is mentioned.
Specific examples of R 2 include, for example, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, t-butyl group, pentyl group, neopentyl group, hexyl group, Heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl, icosyl, docosyl, tricosyl, tetracosyl 2-heptylundecyl group, isostearyl group, 12-methylheptadecyl group, 2-octyldodecyl group, 3,7-dimethyloctyl group, 3,7-dimethyloctane-3-yl group, 2-hexyldecyl group 3,7,11-trimethyldodecyl group, 1,1,3,3-tetramethylbutyl group, 3,7,11 Examples include 15-tetramethylhexadecyl group, 3,5,5-trimethylhexyl group, 1-isopropyl-1,2-dimethylpropyl group, 1-isopropyl-1,2,4,4-tetramethylpentyl group. , Methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group and t-butyl group are preferable, and ethyl group is more preferable.
また、本発明において、式（１）で表される化合物の塩は、薬学上許容しうる塩であればよく、例えば、リチウム塩、ナトリウム塩、カリウム塩等のアルカリ金属塩、カルシウム塩、マグネシウム塩等のアルカリ土類金属塩、トリメチルアミン、トリエチルアミン等のアルキルアミン塩及び4級アンモニウム塩、トリエタノールアミン、ジエタノールアミン、モノエタノールアミン等のアルカノールアミン塩又は、リジン、ヒスチジン、アルギニン等アミノ酸塩が挙げられるが、ナトリウム塩、カリウム塩、アルギニン塩が好ましく、アルギニン塩がより好ましい。 In the present invention, the salt of the compound represented by the formula (1) may be a pharmaceutically acceptable salt, for example, an alkali metal salt such as lithium salt, sodium salt, potassium salt, calcium salt, magnesium, etc. Alkali earth metal salts such as salts, 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 However, sodium salt, potassium salt, and arginine salt are preferable, and arginine salt is more preferable.
本発明における式（１）で表される化合物又はその塩は、公知の方法により製造することができる。
例えば１，３−ジアルキルグリセロールをリン酸エステル化し、必要に応じて適宜上記の塩を形成するようなアルカリで中和することにより得ることができる。リン酸エステル化試薬としては、例えばオキシ塩化リン、三塩化リン、五塩化リン、ポリリン酸、水と無水リン酸、リン酸と無水リン酸等を用いることができる（実験化学講座１，有機化合物の合成I，ｐ２０６−２１０，化学同人社）。得られた化合物は、適宜公知の方法により分離精製を行ってもよい。尚、１，３−ジアルキルグリセロールは、公知化合物であり、その原料であるアルキルグリシジルエーテルは公知の方法により製造することができ（特開昭56-63974号公報）、例えば、アルキルグリシジルエーテルとアルコールとの適当な酸又は塩基の存在下の反応により得ることができる。
The compound represented by the formula (1) or a salt thereof in the present invention can be produced by a known method.
For example, it can be obtained by converting 1,3-dialkylglycerol into a phosphoric ester and neutralizing with an alkali that appropriately forms the above-mentioned salt if necessary. Examples of the phosphoric acid esterifying reagent include phosphorus oxychloride, phosphorus trichloride, phosphorus pentachloride, polyphosphoric acid, water and phosphoric anhydride, phosphoric acid and phosphoric anhydride (Experimental Chemistry Course 1, Organic Compounds) Synthesis I, p206-210, Chemical Dojinsha). The obtained compound may be appropriately separated and purified by a known method. 1,3-dialkylglycerol is a known compound, and alkyl glycidyl ether as a raw material thereof can be produced by a known method (Japanese Patent Laid-Open No. 56-63974). For example, alkyl glycidyl ether and alcohol In the presence of a suitable acid or base.
本発明の式（１）で表される化合物又はその塩は、後記実施例に示すように、正常ヒト角化細胞において、セラミド量を増加させる作用を有する。セラミドは、皮膚の保湿機構、バリア機構に重要な役割を果たしている（芋川玄爾：香粧会誌、１（４）、２５０−２５３、１９９１）。ここで、保湿機能とは、適度な水分を含有することによって皮膚に柔軟性を持たせ、なめらかな美しい肌にする働きを意味し、バリア機能とは、体内の水分が出ていくのを防ぎ、身体が干からびないようにするとともに、外部からの異物が体内に侵入するのを防ぐ働きを意味する。
従って、本発明の式（１）で表される化合物又はその塩は、セラミド産生促進剤或いは保湿剤として使用でき、またセラミド産生促進剤或いは保湿剤を製造するために使用できる。当該セラミド産生促進剤或いは保湿剤は、角層中のセラミドを増加させ、皮膚のバリア機能及び保湿機能を回復又は維持するための医薬品、医薬部外品、化粧品等として使用できる。また、当該セラミド産生促進剤或いは保湿剤は、セラミド産生促進或いは保湿をコンセプトとし、必要に応じてその旨を表示した医薬部外品、化粧品として使用することもできる。
The compound represented by the formula (1) of the present invention or a salt thereof has an action of increasing the amount of ceramide in normal human keratinocytes as shown in Examples below. Ceramide plays an important role in the moisturizing mechanism and barrier mechanism of the skin (Genkawa Ninagawa: Journal of the Cosmetic Society, 1 (4), 250-253, 1991). Here, the moisturizing function means the function of making the skin soft and smooth by containing appropriate moisture, and the barrier function prevents the body's moisture from coming out. It means that it prevents the body from drying out and prevents foreign substances from entering the body.
Therefore, the compound represented by the formula (1) of the present invention or a salt thereof can be used as a ceramide production promoter or moisturizer, and can be used for producing a ceramide production promoter or moisturizer. The ceramide production promoter or moisturizing agent can be used as a pharmaceutical, quasi-drug, cosmetic or the like for increasing ceramide in the stratum corneum and restoring or maintaining the skin barrier function and moisturizing function. Moreover, the said ceramide production promoter or moisturizer can also be used as a quasi-drug or cosmetic that displays ceramide production promotion or moisturization as a concept and displays that effect as necessary.
本発明のセラミド産生促進剤及び保湿剤を医薬品として用いる場合の投与形態としては、例えば錠剤、カプセル剤、顆粒剤、散剤、シロップ剤等による経口投与又は注射剤、軟膏、クリーム等の外用剤、坐剤、経皮吸収剤等による非経口投与のいずれでもよい。当該医薬製剤を調製するには、本発明の式（１）で表される化合物又はその塩を単独で、又は他の薬学的に許容される賦形剤、結合剤、増量剤、崩壊剤、界面活性剤、滑沢剤、分散剤、緩衝剤、保存剤、嬌味剤、香料、被膜剤、担体、希釈剤等を適宜組み合わせて用いることができる。
該製剤中の本発明の式（１）で表される化合物又はその塩の含有量は、０．００１〜２０質量％とするのが好ましく、０．０１〜５質量％とするのがより好ましい。
また、本発明のセラミド産生促進剤及び保湿剤を医薬品として使用する場合、成人１人当たりの１日の投与量は、本発明の式（１）で表される化合物又はその塩として、例えば０．１〜２０００ｍｇとすればよく、１〜５００ｍｇとするのが好ましい。
Examples of dosage forms when the ceramide production promoter and moisturizer of the present invention are used as pharmaceuticals include oral administration such as tablets, capsules, granules, powders, syrups, and external preparations such as injections, ointments and creams, Any of parenteral administration using a suppository or a transdermal absorption agent may be used. In order to prepare the pharmaceutical preparation, the compound represented by the formula (1) of the present invention or a salt thereof alone or other pharmaceutically acceptable excipient, binder, extender, disintegrant, Surfactants, lubricants, dispersants, buffers, preservatives, flavoring agents, fragrances, coating agents, carriers, diluents and the like can be used in appropriate combinations.
The content of the compound represented by the formula (1) of the present invention or a salt thereof in the preparation is preferably 0.001 to 20% by mass, and more preferably 0.01 to 5% by mass. .
Moreover, when using the ceramide production promoter and moisturizer of the present invention as a medicine, the daily dose per adult is, for example, 0. 0 as the compound represented by the formula (1) of the present invention or a salt thereof. It may be 1 to 2000 mg, and is preferably 1 to 500 mg.
また、本発明のセラミド産生促進剤及び保湿剤を医薬部外品や化粧品として用いる場合は、皮膚外用剤、洗浄剤、メイクアップ化粧料とすることができ、使用方法に応じて、美容液、化粧水、マッサージ剤、ローション、乳液、ゲル、クリーム、軟膏剤、粉末、パック、顆粒、ファンデーション、口紅、入浴剤、シャンプー、ヘアコンディショナー、ヘアトニック、錠剤、カプセル、吸収性物品、シート状製品等の種々の剤型で提供することができる。このような種々の剤型の医薬部外品や化粧料は、本発明の式（１）で表される化合物又はその塩を単独で、又は医薬部外品、皮膚化粧料及び洗浄料に配合される、油性成分、保湿剤、粉体、色素、乳化剤、可溶化剤、洗浄剤、紫外線吸収剤、増粘剤、薬効成分、香料、樹脂、防菌防黴剤、植物抽出物、アルコール類等を適宜組み合わせることにより調製することができる。尚、薬効成分としては、ヒアルロン酸ナトリウム等の他の保湿成分が挙げられる。
当該医薬部外品、化粧料中の本発明の式（１）で表される化合物又はその塩の含有量は、０．００１〜２０質量％とするのが好ましく、０．１〜５質量％とするのがより好ましい。
Moreover, when using the ceramide production promoter and moisturizing agent of the present invention as a quasi-drug or cosmetic, it can be used as a skin external preparation, a cleaning agent, or a makeup cosmetic. Lotion, massage agent, lotion, emulsion, gel, cream, ointment, powder, pack, granule, foundation, lipstick, bath preparation, shampoo, hair conditioner, hair tonic, tablet, capsule, absorbent article, sheet-like product, etc. Can be provided in various dosage forms. Such quasi-drugs and cosmetics of various dosage forms include the compound represented by the formula (1) of the present invention or a salt thereof alone or in quasi-drugs, skin cosmetics and cleansing agents. Oily ingredients, moisturizers, powders, pigments, emulsifiers, solubilizers, detergents, UV absorbers, thickeners, medicinal ingredients, fragrances, resins, antibacterial and antifungal agents, plant extracts, alcohols It can prepare by combining etc. suitably. Examples of medicinal components include other moisturizing components such as sodium hyaluronate.
The content of the compound represented by the formula (1) of the present invention or a salt thereof in the quasi drug or cosmetic is preferably 0.001 to 20% by mass, and 0.1 to 5% by mass. Is more preferable.
製造例１：１−ｎ−テトラデシル−３−エチルグリセリル−２−リン酸アルギニン塩（化合物１）の製造
エタノール851.8g(18.5mol)中に、窒素気流下、ナトリウムエトキシド30gを投入し、80℃に昇温した後、テトラデシルグリシジルエーテル500g(1.85mol)を滴下した。同温度にて18時間攪拌した。その後、エタノールを留去し、85％リン酸10.8gを投入し、3回水洗した。水洗後、減圧蒸留して、1-テトラデシル-3-エチルグリセロール446g（収率76.2%）を得た。
トルエン200mlにオキシ塩化リン232g（1.51mol）を溶解し、窒素雰囲気下、10℃以下に冷却したのち、得られた1-テトラデシル-3-エチルグリセロール400.0g（1.26mol）及びトルエン400mlの混合溶液を滴下し、更に、トリエチルアミン140.6g（1.39mol）及びトルエン100mlの混合溶液を30分間かけて滴下した。同温度にて4時間攪拌後、水800gを徐々に投入し、50℃にて1時間攪拌した。トルエン、イソプロピルアルコールを加え、水層を分離後、上層を洗浄し、溶媒留去して、無色透明油状物511gを得た。このうち、200gをエタノール-ヘキサン混合溶媒に溶解し、L-アルギニン86.5g(0.496mol)を加え、60℃にて均一になるまで攪拌後、冷却して、アセトン中に投入し、析出した結晶をろ過後、減圧乾燥して1-n-テトラデシル-3-エチルグリセリル-2-リン酸アルギニン塩266g（収率94%）を得た。
IR（cm-1,ATR法）：3159, 2922, 2853, 1632, 1110, 1053, 919
1H-NMR(D2O,ppm)：0.67-1.73(m,32H),3.03(t,J=6Hz,2H),3.28-3.59(m,11H),4.11(m,1H)
Production Example 1: Production of 1-n-tetradecyl-3-ethylglyceryl-2-phosphate arginine salt (Compound 1) 3085 g of sodium ethoxide was added into 851.8 g (18.5 mol) of ethanol under a nitrogen stream. After raising the temperature to ° C., 500 g (1.85 mol) of tetradecyl glycidyl ether was added dropwise. Stir at the same temperature for 18 hours. Thereafter, ethanol was distilled off, 10.8 g of 85% phosphoric acid was added, and the mixture was washed with water three times. After washing with water and distillation under reduced pressure, 1-tetradecyl-3-ethylglycerol 446 g (yield 76.2%) was obtained.
Dissolve 232 g (1.51 mol) of phosphorus oxychloride in 200 ml of toluene, cool to 10 ° C. or less under a nitrogen atmosphere, and then obtain a mixed solution of 400.0 g (1.26 mol) of 1-tetradecyl-3-ethylglycerol and 400 ml of toluene. Then, a mixed solution of 140.6 g (1.39 mol) of triethylamine and 100 ml of toluene was dropped over 30 minutes. After stirring at the same temperature for 4 hours, 800 g of water was gradually added and stirred at 50 ° C. for 1 hour. Toluene and isopropyl alcohol were added and the aqueous layer was separated. The upper layer was washed and the solvent was distilled off to obtain 511 g of a colorless transparent oil. Of these, 200 g was dissolved in an ethanol-hexane mixed solvent, 86.5 g (0.496 mol) of L-arginine was added, stirred at 60 ° C. until uniform, cooled, poured into acetone, and precipitated crystals After filtration, the residue was dried under reduced pressure to obtain 266 g (yield 94%) of 1-n-tetradecyl-3-ethylglyceryl-2-phosphate arginine salt.
IR (cm −1 , ATR method): 3159, 2922, 2853, 1632, 1110, 1053, 919
1 H-NMR (D 2 O, ppm): 0.67-1.73 (m, 32H), 3.03 (t, J = 6Hz, 2H), 3.28-3.59 (m, 11H), 4.11 (m, 1H)
製造例２：１−ｉ−オクタデシル−３−ブチルグリセリル−２−リン酸ナトリウム塩（化合物２）の製造
テトラヒドロフラン10mlにオキシ塩化リン2.10g（13.7mmol）を溶解し、窒素雰囲気下、10℃以下に冷却したのち、１−ｉ−オクタデシル−３−ブチルグリセロール5.00g（12.5mmol）及びテトラヒドロフラン10mlの混合溶液を滴下し、更に、トリエチルアミン1.26g（12.5mmol）及びテトラヒドロフラン10mlの混合溶液を30分間かけて滴下した。同温度にて2時間攪拌後、水1gを投入し、50℃にて5時間攪拌した。ジエチルエーテルを加え、水層を分離後、上層を洗浄し、溶媒留去して、無色透明油状物6.18gを得た。これに炭酸水素ナトリウム1.05gを水50ｇに溶解したものを加え、50℃にて均一になるまで攪拌後、冷却して、ジエチルエーテルを加え、水層を分離後、減圧乾燥して１−ｉ−オクタデシル−３−ブチルグリセリル−２−リン酸ナトリウム塩3.49g（収率55.5%）を得た。尚、1-i-オクタデシル-3-ブチルグリセロールは、1-i-オクタデシルグリシジルエーテル及びブタノールを用いて製造例１と同様に合成した。
IR（cm-1,ATR法）：2956, 2923, 2854, 1653, 1464, 1377, 1105, 985
1H-NMR(D2O,ppm)：0.65-1.73(m, 42H),3.02(t, J=6Hz,2H),3.28-3.59(m,11H),4.10(m,1H)
Production Example 2: Production of 1-i-octadecyl-3-butylglyceryl-2-phosphate sodium salt (compound 2) 2.10 g (13.7 mmol) of phosphorus oxychloride was dissolved in 10 ml of tetrahydrofuran, and the temperature was 10 ° C. or lower under a nitrogen atmosphere. Then, a mixed solution of 5.00 g (12.5 mmol) of 1-i-octadecyl-3-butylglycerol and 10 ml of tetrahydrofuran was added dropwise, and further a mixed solution of 1.26 g (12.5 mmol) of triethylamine and 10 ml of tetrahydrofuran was added over 30 minutes. And dripped. After stirring at the same temperature for 2 hours, 1 g of water was added and stirred at 50 ° C. for 5 hours. Diethyl ether was added and the aqueous layer was separated. The upper layer was washed and evaporated to give 6.18 g of a colorless transparent oil. A solution obtained by dissolving 1.05 g of sodium hydrogen carbonate in 50 g of water was added thereto, and the mixture was stirred at 50 ° C. until uniform, cooled, diethyl ether was added, the aqueous layer was separated, dried under reduced pressure, and 1-i. -3.49 g (yield 55.5%) of octadecyl-3-butyl glyceryl-2-phosphate sodium salt was obtained. 1-i-octadecyl-3-butylglycerol was synthesized in the same manner as in Production Example 1 using 1-i-octadecylglycidyl ether and butanol.
IR (cm -1 , ATR method): 2956, 2923, 2854, 1653, 1464, 1377, 1105, 985
1 H-NMR (D 2 O, ppm): 0.65-1.73 (m, 42H), 3.02 (t, J = 6Hz, 2H), 3.28-3.59 (m, 11H), 4.10 (m, 1H)
実施例１ セラミド産生促進試験
＜培養条件＞
正常ヒト表皮角化細胞（NHEK(F)）をEpiLife-KG2（KURABO社）６well Plate に播種し、コンフルエントの状態になるまで培養した。その後、EpiLife-KG2（増殖添加因子無し）に換え、製造例において調製した化合物１（5mM）、化合物２（1mM）、control溶液（10%エタノール）を1%量添加した。3日間培養した後、各々の細胞を1wellごとに回収した。
Example 1 Ceramide Production Promotion Test <Culture Conditions>
Normal human epidermal keratinocytes (NHEK (F)) were seeded on EpiLife-KG2 (KURABO) 6-well plate and cultured until confluent. Then, it replaced with EpiLife-KG2 (no growth addition factor), and added 1% amount of compound 1 (5 mM), compound 2 (1 mM), and control solution (10% ethanol) prepared in the production example. After culturing for 3 days, each cell was collected every 1 well.
＜脂質抽出＞
回収した細胞からBligh and Dyer法によって脂質を抽出した。抽出液を窒素乾固した後、クロロホルム、メタノール、に再溶解したものを脂質サンプルとした。なお、タンパク量はBCA法により定量した。
<Lipid extraction>
Lipids were extracted from the collected cells by the Bligh and Dyer method. The extract was dried to nitrogen and then redissolved in chloroform and methanol to obtain a lipid sample. The amount of protein was quantified by the BCA method.
＜セラミド量解析＞
抽出した脂質中を薄膜クロマトグラフィー（TLC）でクロロホルム：メタノール：酢酸＝190:9:1で2回水平展開した。硫酸銅液をスプレーで噴霧した後、ホットプレートで焼き付けセラミドを検出した。その後、各々の蛋白量で割り、セラミド量とした。結果を表１に示す。表の数値はControlのセラミド量を１とした時の相対値を示す。
<Ceramide content analysis>
The extracted lipid was horizontally developed by thin film chromatography (TLC) twice with chloroform: methanol: acetic acid = 190: 9: 1. After spraying the copper sulfate solution with a spray, baking ceramide was detected with a hot plate. Thereafter, the amount was divided by the amount of each protein to obtain the amount of ceramide. The results are shown in Table 1. The numerical values in the table indicate relative values when the amount of ceramide in Control is 1.
実施例２ ヒト角層水分量改善効果試験
１ 試験内容
１．１ 被験者
男性10名（25〜40歳：平均年齢30.5歳）
１．２ サンプル
塗布サンプルは化合物１を１％含む溶液と溶媒のみのプラセボ溶液を用いた。溶媒は95.0％エタノール：1,3-BG：精製水=20:10:70を用いた。
サンプル塗布は1日2回、週5日塗布。1回の塗布量は点眼瓶から2滴分（約100μl）とした。
１．３ 試験方法
試験は片側頬部に１％化合物１配合サンプルを、他方にプラセボ溶液を４週間塗布した後Corneoメーターによって角層水分量の測定を行った。測定は塗布前、４週間塗布後で頬部の同じ領域を測定し、１％化合物１配合サンプル側、プラセボ側で比較した。
Example 2 Human stratum corneum water content improvement effect test 1 Test content 1.1
1.2 Sample Application As a sample, a solution containing 1% of Compound 1 and a placebo solution containing only a solvent were used. As the solvent, 95.0% ethanol: 1,3-BG: purified water = 20: 10: 70 was used.
Samples are applied twice a day, 5 days a week. One application amount was 2 drops (about 100 μl) from the eye drop bottle.
1.3 Test Method In the test, a sample containing 1% compound 1 was applied to one cheek, and a placebo solution was applied to the other for 4 weeks, and then the stratum corneum water content was measured with a Corneo meter. The measurement was carried out by measuring the same area of the cheek before application for 4 weeks and comparing the 1% compound 1 mixed sample side and the placebo side.
２ 結果
結果を図１に示す。
１％ 化合物1配合サンプル塗布群では、４週間の塗布によりプラセボ塗布側と比較し、角層水分量が上昇した。（P<0.1：t-test 両側）
2 Results The results are shown in FIG.
In the 1% compound 1 compound sample application group, the stratum corneum moisture content increased by application for 4 weeks compared to the placebo application side. (P <0.1: t-test both sides)
Claims (5)
で表される化合物又はその塩を有効成分とするセラミド産生促進剤。 Following formula (1)
The ceramide production promoter which uses the compound or its salt represented by these as an active ingredient.
で表される化合物又はその塩を有効成分とする保湿剤。 Following formula (1)
A humectant comprising a compound represented by the formula or a salt thereof as an active ingredient.
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| JP2008197958A JP5328254B2 (en) | 2008-07-31 | 2008-07-31 | Ceramide production promoter |
| CN2009801205557A CN102438629A (en) | 2008-07-31 | 2009-07-30 | Ceramide production promoter |
| PCT/JP2009/003605 WO2010013474A1 (en) | 2008-07-31 | 2009-07-30 | Ceramide production promoter |
| US13/001,701 US8440645B2 (en) | 2008-07-31 | 2009-07-30 | Ceramide production promoter |
| US13/870,315 US20130244984A1 (en) | 2008-07-31 | 2013-04-25 | Ceramide Production Promoter |
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