JP2005082506A - Isopropylmethylphenol glycoside - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an isopropylmethylphenol derivative exhibiting excellent antibacterial actions, antioxidation actions, scalp dandruff and itching-preventing actions, pimple symptom-ameliorating actions and carious tooth and periodontal disease-preventing actions, and a skin care preparation for external uses and a hair cosmetic containing the same. <P>SOLUTION: The isopropylmethylphenol glycoside is represented by formula (1) (wherein R is a residue of a sugar selected from the group consisting of glucose, xylose and maltose). The skin care preparation for external uses and the hair cosmetic contain the isopropylmethylphenol glycoside. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention is excellent in antibacterial action, antioxidant action, anti-dandruff action, and acne symptom improving action, comprising a novel isopropylmethylphenol glycoside, and isopropylmethylphenol glycoside, and its durability, water solubility The present invention relates to a skin external preparation and a hair cosmetic excellent in safety and safety.

About isopropylmethylphenol, antibacterial action (see Patent Document 1), antioxidant action, scalp dandruff, itching prevention action (see Patent Document 2), acne symptom improving action (see Patent Document 3 and Patent Document 4), caries, Periodontal disease preventive action (see Patent Document 5) is already known. However, since isopropylmethylphenol is poorly soluble in water (saturated solubility in water at 25 ° C. is 0.015%), the formulation containing isopropylmethylphenol is limited in its dosage form. As a result, isopropylmethylphenol itself The scope of use was limited.
JP2001-172159 JP 11-269042 JP2001-206820 JP2002-138033 JP-A-11-240816

  The object of the present invention is to solve the above-mentioned problems and to exhibit excellent antibacterial action, antioxidant action, scalp dandruff, itching prevention action, acne symptom improvement action, and caries and periodontal disease prevention action It is an object to provide isopropylmethylphenol derivatives that can be used, and skin external preparations and hair cosmetics containing them.

The present inventor believes that the novel isopropylmethylphenol glycoside represented by the following formula (1) is superior in water solubility compared to isopropylmethylphenol, and is restricted by the dosage form of skin external preparations and hair cosmetics. It can be formulated easily and is gradually decomposed by glycolytic enzymes such as glucosidase present in human skin and skin resident bacteria to produce isopropylmethylphenol as a degradation product continuously. The inventors have found that the function can be exhibited over a long period of time, and as a result, the irritation to the skin and the like is low and can be used safely, thereby completing the present invention.
That is, the present invention provides the following formula (1)

(Wherein, R represents a sugar residue selected from the group consisting of glucose, xylose, and maltose).

  Moreover, this invention provides the skin external preparation containing the isopropylmethylphenol glycoside represented by Formula (1).

  Furthermore, this invention provides the hair cosmetics containing the isopropylmethylphenol glycoside represented by Formula (1).

  The novel isopropylmethylphenol glycoside of the present invention has high water solubility and can be easily blended into external preparations for skin and hair cosmetics. In the preparation, isopropylmethylphenol is stably present as a glycoside, such as glucosidase. Isopropylmethylphenol is gradually released by the action of glycolytic enzymes or by the action of glycolytic enzymes such as normal bacteria on the skin and glucosidase in skin stratum corneum, antibacterial action, antioxidant action, anti-dandruff action , And can continuously exert acne symptom improving action.

The isopropylmethylphenol glycoside represented by the formula (1) according to the present invention is a novel compound.
The isopropylmethylphenol glycoside represented by the formula (1) can be produced according to a known method. For example, isopropylmethylphenol and the desired peracetylated saccharide in an appropriate solvent such as dichloromethane, in the presence of a Lewis acid catalyst such as boron trifluoride, aluminum trichloride, tin tetrachloride and the like, at room temperature for about 30 minutes to 24 hours. By reacting, an acetylated derivative which is a production intermediate of the compound of formula (1) wherein R is an acetylated sugar residue is obtained. The peracetylated sugar used as a starting material is known, but can be produced by acetylating a desired sugar by a known acetylation method. The acetylated derivative thus obtained is deacetylated in the presence of sodium methoxide in an anhydrous methanol, for example, and then treated with an acidic ion exchange resin to obtain a compound of the formula (1). Further, if necessary, it can be purified by a conventional method such as recrystallization.

  Examples of the isopropylmethylphenol glycoside represented by the formula (1) thus obtained include isopropylmethylphenylglucoside, isopropylmethylphenylxyloside, isopropylmethylphenylmaltoside, and the like.

  The isopropylmethylphenol glycoside represented by the formula (1) in the external preparation for skin and hair cosmetics of the present invention is a glycolytic enzyme such as glucosidase (such as glucosidase) present in the skin of human skin such as the scalp, armpit, and limbs. Fragrance Journal, 2002-5, 39, 2002) and isopropylmethylphenol, which is decomposed by skin resident bacteria commonly found on the skin surface, such as Staphylococcus epidermidis, Staphylococcus aureus, Pityrospom, etc. Is estimated to be gradually generated (Japanese Patent Laid-Open No. 10-25244).

  The scope of application of the external preparation for skin and hair cosmetics containing the isopropylmethylphenol glycoside of the present invention includes antibacterial action, antioxidant action, scalp dandruff, itching prevention action, acne symptom improvement action, caries of isopropylmethylphenol There is no particular limitation as long as it is used for the purpose of developing a periodontal disease preventing effect. Examples of external preparations for skin include pharmaceuticals such as ointments for wound treatments, moisturizing preventives, skin care products such as skin creams, hand creams, lip balms, and emulsions, baby powders, and deodorant sprays for bodies. . Examples of hair cosmetics include hair liquids, hair tonics, hair mousses, pomades, and hair nourishing agents.

  The blending concentration of the isopropylmethylphenol glycoside represented by the formula (1) in the skin external preparation and hair cosmetic containing the isopropylmethylphenol glycoside of the present invention is the target skin external preparation and hair cosmetic, Alternatively, it varies depending on various conditions such as the remarkable physiological activity of isopropylmethylphenol, and cannot be generally defined. However, generally, the concentration of isopropylmethylphenol glycoside in an external skin preparation or hair cosmetic is about 0. It is used at a concentration of about 0001 to about 10% by weight, preferably about 0.01 to about 10% by weight. Further, the external preparation for skin and the cosmetic for hair of the present invention comprise a compound of formula (1) that is acceptable on the external preparation for skin or cosmetic for hair, for example, an excipient, a binder, In combination with a solvent, an emulsifier, a suspending agent, and a stabilizer, it can be made into a skin external preparation or a hair cosmetic preparation, for example, an ointment, cream, emulsion, aqueous alcohol solution, and the like.

  Thus, the novel isopropylmethylphenol glycoside of the present invention has a high water solubility and can be easily blended into external preparations for skin and hair cosmetics. In the preparation, isopropylmethylphenol is stably present as a glycoside, such as glucosidase. Isopropyl methylphenol is gradually released by the action of glycolytic enzymes such as glucosidase in skin keratin and skin resident bacteria on the skin, resulting in antibacterial action, antioxidant action, anti-dandruff The effect and the effect of improving acne symptoms can be exerted continuously.

  Hereinafter, the present invention will be described in more detail with reference to examples.

Example 1: Synthesis of isopropylmethylphenyl glucoside To a 100 mL flask was added 3.9 g (10 mmol) of pentaacetylglucose, 3.8 g (25 mmol) of isopropylmethylphenol, and 50 ml of dichloromethane, and boron trifluoride at room temperature in a nitrogen atmosphere. 5.7 g (40 ml) of diethyl ether was added dropwise and stirred at room temperature for 3 hours. The reaction mixture (dichloromethane solution) was washed twice with 200 mL of saturated NaHCO3 aqueous solution, and the dichloromethane layer was dried over anhydrous Na2SO4, and then dichloromethane of the solvent was distilled off under reduced pressure. The obtained crude product (8.0 g) was purified by silica gel chromatography (80 g, n-hexane / ethyl acetate = 9/1 to 1/1) to obtain 2.2 g of a colorless transparent viscous liquid (yield 88 8%). 1.0 g (2.1 mmol) of this material was added to a mixed solvent of 20 mL of dehydrated methanol / 2 mL of anhydrous THF and dissolved by sonication at room temperature, and then 1.6 g (8.3 mmol) of a 28% sodium methylate methanol solution. ) And stirred at room temperature under a nitrogen atmosphere for 3 hours. After completion of the reaction, the reaction mixture was packed in a column packed with a strongly acidic ion exchange resin (Dowex 50WX2-100, 21 mL) and eluted with 200 mL of anhydrous methanol. The collected methanol solution was evaporated under reduced pressure to obtain 0.65 g (yield 100%) of white powder. The product was identified using 1H- and 13C-NMR.

1H-NMR (400MHz, DIMSO-D6) δ: 1.14 (d, J = 7.2Hz, 6H), 2.25 (s, 3H), 3.02 (m, 1H), 3.1-3.3 (overlapped, 4H), 3.43 (dd , J = 6Hz, 12Hz, 1H), 3.67 (dd, J = 2, 12Hz, 1H), 4.77 (d, J = 8Hz, 1H), 6.79 (d, J = 3Hz, 1H), 6.82 (dd, J = 3, 8Hz, 1H), 7.11 ppm (d, J = 8Hz, 1H)
13C-NMR (400MHz, DIMSO-D6) δ: 19.7, 23.96, 28.75, 61.27, 70.30, 73.77, 77.04, 77.52, 101.26, 114.50, 118.67, 126.04, 136.37, 140.53, 155.72ppm

Test example 1
The solubility of isopropylmethylphenylglucoside synthesized in Example 1 in water at 25 ° C. was measured to be 0.1% or more, and from isopropylmethylphenol (saturated solubility in water at 25 ° C. is 0.015%). It was found that water solubility was improved.

Test example 2
1.9 mg (6 μmol) of isopropylmethylphenyl glucoside synthesized in Example 1 is dissolved in 1.0 mL of phosphate buffer solution at pH 6.4, and 1.0 U of almond-derived β-glucosidase is added at 37 ° C. Isopropylmethylphenol was quantified by HPLC. Table 1 shows the production rate of isopropylmethylphenol (molar ratio to the charged isopropylmethylphenylglucoside).

  It was revealed that isopropylmethylphenol was gradually released by β-glucosidase.

Example 2
The isopropylmethylphenyl glucoside obtained in Example 1 was added to obtain an ointment composed of the components shown in Table 2.

Example 3
The isopropyl methyl phenyl glucoside obtained in Example 1 was added to obtain a hand cream in which the isopropyl methyl phenyl glucoside composed of the components shown in Table 3 was dissolved.

Example 4
The isopropyl methyl phenyl glucoside obtained in Example 1 was added to obtain a hair tonic in which isopropyl methyl phenyl glucoside composed of the components shown in Table 4 was dissolved.

Example 5
The isopropyl methyl phenyl glucoside obtained in Example 1 was added to obtain a shampoo in which the isopropyl methyl phenyl glucoside composed of the components shown in Table 5 was dissolved.

Claims (4)

Following formula (1)

(Wherein, R represents a sugar residue selected from the group consisting of glucose, xylose, and maltose). An isopropylmethylphenol glycoside in which R is a glucose residue in the above formula (1). A skin external preparation containing the isopropylmethylphenol glycoside according to claim 1. A hair cosmetic comprising the isopropylmethylphenol glycoside according to claim 1.