WO2018097274A1 - シワ改善剤 - Google Patents
シワ改善剤 Download PDFInfo
- Publication number
- WO2018097274A1 WO2018097274A1 PCT/JP2017/042338 JP2017042338W WO2018097274A1 WO 2018097274 A1 WO2018097274 A1 WO 2018097274A1 JP 2017042338 W JP2017042338 W JP 2017042338W WO 2018097274 A1 WO2018097274 A1 WO 2018097274A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- acid
- group
- phenyl
- aminomethylcyclohexylcarbonyl
- wrinkle
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/44—Aminocarboxylic acids or derivatives thereof, e.g. aminocarboxylic acids containing sulfur; Salts; Esters or N-acylated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
- A61K8/41—Amines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/08—Anti-ageing preparations
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/02—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton
- C07C225/14—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated
- C07C225/16—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings
- C07C225/18—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones having amino groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being unsaturated and containing six-membered aromatic rings the carbon skeleton containing also rings other than six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Definitions
- the present invention relates to a wrinkle improving agent having an excellent wrinkle improving action.
- Wrinkles are one of the skin aging symptoms caused by factors such as aging, stress, and exposure to ultraviolet rays. Therefore, interest in wrinkles and how to improve them is very high.
- the above-mentioned factors cause cell damage and cell apoptosis that is enhanced by the damage, and the proliferation activity of fibroblasts, which are the main cells in the dermis, and collagen due to a decrease in the synthesis function of collagen, etc.
- fibroblasts which are the main cells in the dermis
- collagen due to a decrease in the synthesis function of collagen, etc.
- wrinkle improving agents since various factors influence each other and are involved in a complicated manner in the mechanism of wrinkle formation, various components have been proposed as wrinkle improving agents.
- retinol and its metabolite retinoic acid, amino acids such as alanine and glycine, polymers such as collagen and hyaluronic acid, ascorbic acid, tocopherol and the like are known to have a wrinkle improving action.
- tranexamic acid amide derivatives also promote the production of vascular endothelial growth factor C and can be active ingredients in wrinkle improving agents (Patent Document 1).
- the conventional wrinkle improving agent may not sufficiently satisfy the wrinkle improving effect, or may cause other undesirable effects (side reactions) at a concentration that exhibits the wrinkle improving action. Therefore, there is a demand for a new component that exhibits a wrinkle improving effect.
- the aminocarboxylic acid derivative described in Patent Document 2 has been confirmed to have an anti-ulcer action and has been proposed for use as a pharmaceutical product.
- the structure of the compound partially matches with tranexamic acid.
- An object of the present invention is to provide a wrinkle improving agent having an excellent wrinkle improving action.
- one aspect of the present invention is a wrinkle improving agent containing a compound represented by the following general formula (1) or an acid addition salt thereof.
- X represents a C 1-2 alkylene group in which a hydrogen atom may be substituted with a methyl group
- Y represents COOR 1 or CH 2 OR 2
- R 1 has a hydrogen atom or a branched group.
- R 2 represents a hydrogen atom or an optionally substituted acyl group having 1 to 6 carbon atoms.
- Another aspect of the present invention is a composition for external use for improving wrinkles, which contains the wrinkle improving agent.
- the skin external composition is preferably a cosmetic.
- a wrinkle improving agent having an excellent wrinkle improving action is provided.
- the skin external composition for wrinkle improvement containing this wrinkle improving agent is also provided, and this is suitable as cosmetics.
- Such an external composition for skin is in line with the trend of expecting anti-aging effects in cosmetics and meets the needs of consumers.
- the wrinkle improving agent of the present invention contains a compound represented by the following general formula (1) or an acid addition salt thereof.
- X represents an alkylene group having 1 to 2 carbon atoms in which a hydrogen atom may be substituted with a methyl group.
- the alkylene group having 1 or 2 carbon atoms is a methylene group or an ethylene group.
- X is preferably —CH (CH 3 ) — or —CH 2 —CH 2 —.
- Y represents COOR 1 or CH 2 OR 2
- R 1 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms which may have a branch
- R 2 represents a hydrogen atom or An acyl group having 1 to 6 carbon atoms which may have a branch is represented.
- R 1 when Y is COOR 1, when R 1 is a hydrogen atom Y is a carboxyl group, Y when the alkyl group R 1 is 1 carbon atoms which may have a branch 1-6 is an ester group.
- the alkyl group having 1 to 6 carbon atoms which may have a branch include a methyl group, an ethyl group, an n-propyl group, an iso-propyl group, an n-butyl group, an iso-butyl group, and a tert-butyl group. , N-pentyl group, n-hexyl group and the like.
- R 1 is particularly preferably a hydrogen atom, and when R 1 is an alkyl group, the carbon number is more preferably smaller.
- Y when Y is CH 2 OR 2, Y when R 2 is a hydrogen atom is a hydroxy methyl group, Y when the acyl group R 2 is ⁇ carbon atoms 1 may have a branch 6 is an ester group It is.
- the acyl group having 1 to 6 carbon atoms which may have a branch include a formyl group, an acetyl group, an acryloyl group, a propionyl group, a propioyl group, a butyryl group, an isobutyryl group, a methacryloyl group, a valeryl group and a caproyl group. Is mentioned. From the viewpoint of wrinkle improving action, R 2 is particularly preferably a hydrogen atom, and when R 2 is an acyl group, a smaller carbon number is more preferred.
- the 1,4-cyclohexylene group may be either a chair type or a boat type. Further, the two bonds may be in a cis or trans relationship. Preferably, it is in the form of a chair and is in a trans relationship.
- Examples of the acid addition salt of the compound represented by the following general formula (1) include salts with inorganic acids, organic carboxylates, or organic sulfonic acids.
- inorganic acids include hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, and phosphoric acid.
- organic carboxylates include acetic acid, propionic acid, maleic acid, fumaric acid, oxalic acid, citric acid, butyric acid, and lactic acid.
- And tartaric acid, and examples of the organic sulfonic acid include methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and paratoluenesulfonic acid.
- inorganic acid salts are preferred, and hydrochlorides are more preferred.
- the active ingredient of the wrinkle improving agent of the present invention may be either the compound represented by the general formula (1) or an acid addition salt thereof, but an acid addition salt is more preferable.
- the compound represented by the general formula (1) can be obtained by synthesis and purification by a conventional method.
- it can be synthesized by an acylation reaction in the presence of Lewis acid of an acid addition salt of an aminocarboxylic acid halide described in Patent Document 2, and can be produced through an appropriate isolation / purification method.
- wrinkle improvement means that the skin crevice becomes shallower or narrower and wrinkles become inconspicuous.
- the present invention can also be referred to as a wrinkle improvement method including applying the compound represented by the general formula (1) or an acid addition salt thereof.
- the present invention can be said to be a use of the compound represented by the general formula (1) or an acid addition salt thereof for wrinkle improvement.
- the present invention can be said to be the use of the compound represented by the general formula (1) or an acid addition salt thereof in the production of a wrinkle improving agent.
- the present invention can also be referred to as a compound represented by the general formula (1) used for wrinkle improvement or an acid addition salt thereof.
- the structure of the compound represented by the general formula (1) partially matches with tranexamic acid and the tranexamic acid amide derivative described in Patent Document 1, but it is known that it is not metabolized to tranexamic acid in vivo. That is, the wrinkle improving action of the compound represented by the general formula (1) is considered to be due to a mechanism different from that of the tranexamic acid amide derivative, and at least the structure of (4-aminomethylcyclohexylcarbonyl) phenyl group exhibits the action. It is presumed to be involved in
- the wrinkle improving agent of the present invention can be contained in a composition for improving wrinkles, and is preferably a composition for external use that can be expected to have an effect of transdermal absorption.
- the form of the external composition for skin is not particularly limited as long as it is applied externally to the skin, and preferred examples include cosmetics (including quasi-drugs) and pharmaceuticals.
- the compound represented by the general formula (1) has been confirmed to have high safety, and can be continuously applied in the form of a daily-use cosmetic.
- the dosage form of the external composition for skin is not particularly limited. For example, a lotion dosage form, an emulsifier type such as an emulsion or cream (O / W type, W / O type, etc.), an oil type, a gel type, a pack And cleaning fee.
- the amount of the wrinkle-improving agent of the present invention is preferably 0.01% to 20% by mass, more preferably 0.1%, based on the total amount of the composition.
- the content is ⁇ 10% by mass, a desired effect can be easily obtained, and the degree of freedom in formulation design can be secured.
- composition for external use for improving wrinkles according to the present invention can optionally contain, in addition to the agent for improving wrinkles according to the present invention, components that are blended in an ordinary composition for external use as long as the effects of the present invention are not impaired.
- components include macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil, and hardened oil.
- Anionic surfactants such as fatty acid soap (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, alkylsulfuric acid triethanolamine ether; cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide Class: Imidazoline amphoteric surfactant (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy disodium salt, etc.), betaine surfactant (alkyl betaine, amide betaine, sulfobetaine, etc.), acyl Amphoteric surfactants such as methyl taurine; sorbitan fatty acid esters (such as sorbitan monostearate and sorbitan sesquioleate), glycerin fatty acids (such as glyceryl monostearate), propylene glycol Fatty acid esters (such as propylene glycol monostearate), hydrogenated cast
- Moisturizing components such as sodium pyrrolidone carboxylate, lactic acid, sodium lactate; mica, talc, kaolin, synthetic mica, calcium carbonate, magnesium carbonate, anhydrous silicic acid (silica), aluminum oxide, sulfuric acid, which may be treated on the surface Powders such as barium; inorganic pigments such as bengara, yellow iron oxide, black iron oxide, cobalt oxide, ultramarine, bitumen, titanium oxide, and zinc oxide that may be treated on the surface; even if the surface is treated Pale agents such as good mica titanium, fish phosphorus foil, bismuth oxychloride; red 202, red 228, red 226, yellow 4 and blue 404, which may be laked, yellow No. 5, Red No. 505, Red No.
- Organic dyes such as Red No. 204; Organic powders such as polyethylene powder, polymethyl methacrylate, nylon powder, organopolysiloxane elastomer; Paraaminobenzoic acid UV absorbers; Anthranilic acid UV absorbers; Salicylic acid UV absorbers Agents: Cinnamic acid UV absorbers; Benzophenone UV absorbers; Sugar UV absorbers; 2- (2'-hydroxy-5'-t-octylphenyl) benzotriazole, 4-methoxy-4'-t-butyl UV absorbers such as dibenzoylmethane;
- Vitamin B such as ⁇ -tocopherol, ⁇ -tocopherol, ⁇ -tocopherol, vitamin E such as vitamin E acetate, vitamin D, vitamin H, vitamins such as pantothenic acid, panthetin, pyrroloquinoline quinone, etc .
- methylparaben Antibacterial agents (preservatives) such as ethylparaben, butylparaben, phenoxyethanol; anti-inflammatory agents such as glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, salicylic acid derivatives, hinokitiol, zinc oxide, allantoin; alkylresorcinol, Whitening agents such as place
- the produced replica is fixed to the sample stage of the stereomicroscope, irradiated with light at an angle of 45 degrees, and the replica is rotated to obtain a shadow image (1 ⁇ 1 cm 2 ) in a direction in which the shadow of the skin groove is strongly observed. Imported into the analyzer.
- the image has low brightness at deep wrinkles and high brightness at no wrinkles, forming a shadow.
- the luminance distribution in the shadow image is obtained, and with the median value of the luminance as a boundary, the bright spot with the luminance higher than the median value is converted to the maximum luminance, and the bright spot with the luminance less than the median value is converted to the luminance 0, and binarization is performed.
- the wrinkle improvement rate was calculated based on the following equation. The average value of each group is shown in Table 2.
- Wrinkle improvement rate (%) (area ratio of shadow part before test ⁇ area ratio of shadow part after test) / (area ratio of shadow part before test) ⁇ 100
- the skin lotion which is an external preparation for skin of this invention was prepared with the formulation shown in Table 3. That is, the component A was heated at room temperature and the component B was heated and mixed at 60 ° C., and B was gradually added to A with stirring, followed by cooling with stirring to obtain a lotion. It was confirmed that when this lotion was applied to the skin, a wrinkle improving effect was obtained.
- a skin lotion that is an external preparation for skin of the present invention was prepared. That is, the component A was heated at room temperature and the component B was heated and mixed at 60 ° C., and B was gradually added to A with stirring, followed by cooling with stirring to obtain a lotion. It was confirmed that when this lotion was applied to the skin, a wrinkle improving effect was obtained.
- emulsion which is the skin external preparation of this invention was prepared by the prescription shown in Table 6. That is, the components A and B were heated and mixed at 80 ° C., and B was gradually added to A under stirring, followed by stirring and cooling to obtain an emulsion. It was confirmed that when this emulsion was applied to the skin, a wrinkle improving effect was obtained.
- W / O cream which is an external preparation for skin of the present invention was prepared. That is, the components A and B were heated and mixed at 80 ° C., and A was gradually added to B under stirring, followed by stirring and cooling to obtain a W / O cream. It was confirmed that when this W / O cream was applied to the skin, a wrinkle improving effect was obtained.
- a W / O foundation that is an external preparation for skin of the present invention was prepared. That is, the components A and B were heated and mixed at 80 ° C., and A was gradually added to B under stirring, followed by stirring and cooling to obtain a W / O foundation. It was confirmed that when this W / O foundation was applied to the skin, a wrinkle improving effect was obtained.
- W / O sunscreen which is a skin external preparation of the present invention
- the components A and B were heated and mixed at 80 ° C., respectively, and A was gradually added to B under stirring, followed by stirring and cooling to obtain a W / O sunscreen.
- This W / O sunscreen was confirmed to provide a wrinkle improving effect when applied to the skin.
- the wrinkle improving agent of the present invention has an excellent wrinkle improving effect, it can be suitably contained in an external skin composition for wrinkle improvement and is very useful industrially.
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Abstract
Description
しかしながら、シワが形成されるメカニズムは複雑で、実験的に再現することも困難であるため、現在においてもそのメカニズムは完全に解明されるには至っていない。それでも、近年の研究では、皮膚の老化症状は、加齢が重要な因子であることに加えて、乾燥、酸化、糖化、紫外線なども大きく関与する因子であることが分かってきた。具体的には、前記因子、とりわけ紫外線曝露が、細胞の損傷とそれにより亢進する細胞のアポトーシス、真皮における主要な細胞である線維芽細胞の増殖活性やコラーゲン等の合成機能の低下によるコラーゲン等の線維成分のターンオーバー速度の低下、炎症性サイトカインの亢進による線維束の崩壊、血管系の減少による老廃物の蓄積、栄養供給の低下などを引き起こし、その結果として皮膚の弾力がなくなり、シワが発生すると考えられる。
しかしながら、従来のシワ改善剤ではシワ改善効果が十分に満足いくものではなかったり、シワ改善作用を発揮する濃度では望まない他の作用(副反応)が生じたりする場合がある。そのため、シワ改善作用を発揮する新たな成分の需要がある。
本発明のシワ改善剤の有効成分としては、一般式(1)で表される化合物又はその酸付加塩のいずれでもよいが、酸付加塩のほうがより好ましい。
2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]酢酸、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]酢酸メチル、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]酢酸エチル、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]酢プロピル、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]酢酸ブチル、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]酢酸ペンチル、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]酢酸ヘキシル;
2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]エタノール、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]エチルホルメート、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]エチルアセテート、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]エチルプロピオネート、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]エチルブチレート、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]エチルペンタノエート、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]エチルヒエキサノエート;
2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸メチル、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸エチル、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸プロピル、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸ブチル、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸ペンチル、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸ヘキシル;
2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロパノール、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルホルメート、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルアセテート、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルプロピオネート、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルブチレート、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルペンタノエート、2-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルヒエキサノエート;
3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸(化合物1)、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸メチル、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸エチル、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸プロピル、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸ブチル、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸ペンチル、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピオン酸ヘキシル(化合物2);
3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロパノール(化合物3)、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルホルメート、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルアセテート、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルプロピオネート、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルブチレート、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルペンタノエート、3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルヘキサノエート(化合物4);
2-メチル-3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロパノール、2-メチル-3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルホルメート、2-メチル-3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルアセテート、2-メチル-3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルプロピオネート、2-メチル-3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルブチレート、2-メチル-3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルペンタノエート、2-メチル-3-[p-(4-アミノメチルシクロヘキシルカルボニル)フェニル]プロピルヘキサノエート(化合物5)。
なお、本明細書においてシワ改善とは、肌の皮溝が浅くなったり細くなったりして、シワが目立たなくなることをいう。
本発明は、別の側面から、一般式(1)で表される化合物又はその酸付加塩の、シワ改善のための使用ということもできる。
本発明は、別の側面から、一般式(1)で表される化合物又はその酸付加塩の、シワ改善剤の製造における使用ということもできる。
本発明は、別の側面から、シワ改善のために使用される一般式(1)で表される化合物又はその酸付加塩ということもできる。
皮膚外用組成物の剤型としては、特に限定されず、例えば、ローション剤型、乳液やクリーム等の乳化剤型(O/W型、W/O型等)、オイル剤型、ジェル剤型、パック、洗浄料等が挙げられる。
かかる成分としては、例えば、マカデミアナッツ油、アボガド油、トウモロコシ油、オリーブ油、ナタネ油、ゴマ油、ヒマシ油、サフラワー油、綿実油、ホホバ油、ヤシ油、パーム油、液状ラノリン、硬化ヤシ油、硬化油、モクロウ、硬化ヒマシ油、ミツロウ、キャンデリラロウ、カルナウバロウ、イボタロウ、ラノリン、還元ラノリン、硬質ラノリン、ホホバロウ等のオイル、ワックス類;流動パラフィン、スクワラン、プリスタン、オゾケライト、パラフィン、セレシン、ワセリン、マイクロクリスタリンワックス等の炭化水素類;オレイン酸、イソステアリン酸、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、ベヘン酸、ウンデシレン酸等の高級脂肪酸類;セチルアルコール、ステアリルアルコール、イソステアリルアルコール、ベヘニルアルコール、オクチルドデカノール、ミリスチルアルコール、セトステアリルアルコール等の高級アルコール等;イソオクタン酸セチル、ミリスチン酸イソプロピル、イソステアリン酸ヘキシルデシル、アジピン酸ジイソプロピル、セバチン酸ジ-2-エチルヘキシル、乳酸セチル、リンゴ酸ジイソステアリル、ジ-2-エチルヘキサン酸エチレングリコール、ジカプリン酸ネオペンチルグリコール、ジ-2-ヘプチルウンデカン酸グリセリン、トリ-2-エチルヘキサン酸グリセリン、トリ-2-エチルヘキサン酸トリメチロールプロパン、トリイソステアリン酸トリメチロールプロパン、テトラ-2-エチルヘキサン酸ペンタンエリトリット等の合成エステル油類;ジメチルポリシロキサン、メチルフェニルポリシロキサン、ジフェニルポリシロキサン等の鎖状ポリシロキサン;オクタメチルシクロテトラシロキサン、デカメチルシクロペンタシロキサン、ドデカメチルシクロヘキサンシロキサン等の環状ポリシロキサン;アミノ変性ポリシロキサン、ポリエーテル変性ポリシロキサン、アルキル変性ポリシロキサン、フッ素変性ポリシロキサン等の変性ポリシロキサン等のシリコーン油等の油剤類;
表1に記載の化粧料(実施例1~7、比較例、及び参考例)を、それぞれ定法で調製した。
調製した各化粧料について、以下の方法でシワ改善効果を評価した。すなわち、目尻のシワが気になる女性45名(40~60歳)を5名ずつ9群に分け、各群に対しそれぞれ実施例1~7、比較例、及び参考例のいずれかの化粧料を渡し、毎日朝晩2回、連続して8週間目尻に塗布してもらった。試験の前後に、定法により目尻の皮膚表面形態を写し取り、レプリカを作製した。なお、レプリカ基剤には光を透過させない白色のレプリカのものを用いた。作製したレプリカを実体顕微鏡の標本台に固定し、45度の角度で光を照射し、レプリカを回転させて、皮溝の陰影が強く観察される方向の陰影画像(1×1cm2)を画像解析装置に取り込んだ。この画像はシワの凹凸に従って、シワの深いところは輝度が低く、シワのないところは輝度が高く、陰影を形成する。陰影画像における輝度の分布を求め、輝度のメジアン値を境に、メジアン値以上の輝度の輝点は最大輝度に、メジアン値未満の輝度の輝点は輝度0に変換して、二値化を行い、陰影部分(輝度0の部分)の面積率を求め、次式に基づきシワ改善率を算出した。各群の平均値を表2に示す。
シワ改善率(%)=(試験前の陰影部分の面積率-試験後の陰影部分の面積率)/(試験前の陰影部分の面積率)×100
表3に示す処方で、本発明の皮膚外用剤である化粧水を調製した。すなわち、Aの成分を常温で、Bの成分を60℃でそれぞれ加温して混合し、攪拌下でAにBを徐々に加え、攪拌冷却して化粧水を得た。
この化粧水は皮膚に適用したときにシワ改善効果が得られることが確認された。
表4に示す処方で、本発明の皮膚外用剤である化粧水を調製した。すなわち、Aの成分を常温で、Bの成分を60℃でそれぞれ加温して混合し、攪拌下でAにBを徐々に加え、攪拌冷却して化粧水を得た。
この化粧水は皮膚に適用したときにシワ改善効果が得られることが確認された。
表5に示す処方で、本発明の皮膚外用剤であるエッセンスを調製した。すなわち、A及びBの成分を80℃でそれぞれ加温して混合し、攪拌下でAにBを徐々に加え、攪拌冷却してエッセンスを得た。
このエッセンスは皮膚に適用したときにシワ改善効果が得られることが確認された。
表6に示す処方で、本発明の皮膚外用剤である乳液を調製した。すなわち、A及びBの成分を80℃でそれぞれ加温して混合し、攪拌下でAにBを徐々に加え、攪拌冷却して乳液を得た。
この乳液は皮膚に適用したときにシワ改善効果が得られることが確認された。
表7に示す処方で、本発明の皮膚外用剤であるO/Wクリームを調製した。すなわち、A及びBの成分を80℃でそれぞれ加温して混合し、攪拌下でAにBを徐々に加え、攪拌冷却してO/Wクリームを得た。
このO/Wクリームは皮膚に適用したときにシワ改善効果が得られることが確認された。
表8に示す処方で、本発明の皮膚外用剤であるW/Oクリームを調製した。すなわち、A及びBの成分を80℃でそれぞれ加温して混合し、攪拌下でBにAを徐々に加え、攪拌冷却してW/Oクリームを得た。
このW/Oクリームは皮膚に適用したときにシワ改善効果が得られることが確認された。
表9に示す処方で、本発明の皮膚外用剤であるO/Wファンデーションを調製した。すなわち、A及びBの成分を80℃でそれぞれ加温して混合し、攪拌下でAにBを徐々に加え、攪拌冷却してO/Wファンデーションを得た。
このO/Wファンデーションは皮膚に適用したときにシワ改善効果が得られることが確認された。
表10に示す処方で、本発明の皮膚外用剤であるW/Oファンデーションを調製した。すなわち、A及びBの成分を80℃でそれぞれ加温して混合し、攪拌下でBにAを徐々に加え、攪拌冷却してW/Oファンデーションを得た。
このW/Oファンデーションは皮膚に適用したときにシワ改善効果が得られることが確認された。
表11に示す処方で、本発明の皮膚外用剤であるO/W日焼け止めを調製した。すなわち、A及びBの成分を80℃でそれぞれ加温して混合し、攪拌下でAにBを徐々に加え、攪拌冷却してO/W日焼け止めを得た。
このO/W日焼け止めは皮膚に適用したときにシワ改善効果が得られることが確認された。
表12に示す処方で、本発明の皮膚外用剤であるW/O日焼け止めを調製した。すなわち、A及びBの成分を80℃でそれぞれ加温して混合し、攪拌下でBにAを徐々に加え、攪拌冷却してW/O日焼け止めを得た。
このW/O日焼け止めは皮膚に適用したときにシワ改善効果が得られることが確認された。
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