JP4576171B2 - Difractose anhydride-containing topical skin preparation - Google Patents

Description

  The present invention relates to an external preparation for skin such as pharmaceuticals and cosmetics.

It is effective to give a skin moisturizing effect to various types of external preparations for skin to improve rough skin, such as sugars such as glucose, sorbitol, maltitol, sugar alcohols, glycerin, 1,3-butylene glycol. Moisturizers such as polyhydric alcohols such as sodium pyrrolidone carboxylate, organic acid salts such as sodium lactate, and amino acids have been used. However, when the blending amount is increased in order to fully exhibit the moisturizing effect, the feeling of use deteriorates, for example, “stickiness” occurs. Therefore, a moisturizing agent having a high moisturizing effect and a good feeling of use has been proposed. Raffinose with high moisturizing ability at the time of drying (Patent Document 1: Japanese Patent Laid-Open No. 11-322574), sulfated trehalose with good feel and high skin effect (Patent Document 2: Japanese Patent No. 2711597), moisturizing with little stickiness Trehalose, oil, natural skin extract containing natural extract (Patent Document 3: Japanese Patent Laid-Open No. 2001-39848), trehalose, monosaccharides, disaccharides that have good moisturizing properties without spreading when applied. Has been proposed (Patent Document 4: Japanese Patent Laid-Open No. 9-77650). However, saccharides are excellent in moisture retention and have little stickiness, but there is a problem that squeaking occurs after familiarization.
In recent years, with changes in the environment, there are an increasing number of people with allergic diseases such as atopic dermatitis and so-called sensitive skin, and these people are sensitive to skin. There are many cases where irritation such as itching is felt, and a lower skin irritation preparation is required.

The skin external preparation contains many irritating components such as alcohols, thickeners, pigments, fragrances, fats and oils, plant extracts and the like. For this purpose, trehalose monofatty acid ester (Patent Document 5: Japanese Patent Application Laid-Open No. 10-45560), etc. as a skin mucosa irritation relieving agent, and phenyl alcohol-α-glucoside, phenylethyl-β-glucoside, etc. A glucose derivative (Patent Document 6: JP-A-8-283121) and the like have been proposed. However, a component having a higher function and an excellent effect of alleviating irritation is demanded.
JP-A-11-322574 Japanese Patent No. 2711597 JP 2001-39848 A JP-A-9-77650 Japanese Patent Laid-Open No. 10-45560 JP-A-8-283121

  An object of the present invention is to improve the feeling of “squeaking” after familiarization when a skin external preparation containing difructose anhydride having a high moisturizing function, non-stickiness, and irritation relaxation is used. .

The main configuration of the present invention is as follows.
1. A skin external preparation containing difructose anhydride and a polyhydric alcohol.
2. An external preparation for skin containing difructose anhydride and silicone oil.

  According to the present invention, it is possible to provide an external preparation for skin having high moisture retention, stickiness is suppressed, does not become squeezed after being used, and is excellent in an alleviating stimulus.

Details of the present invention will be described below.
The difructose anhydride (DFA) as used in the present invention is a cyclic disaccharide in which the reducing ends of two fructose are bonded to a hydroxyl group other than one reducing end. Conventionally, it has been known to exist in caramel and the like, but industrially, inulin is produced by an inulin-degrading enzyme such as Artrinbacter sp. H65-7 strain (EC 2.4.1.93). Or levan can be fermented with levanfructotransferase (EC 2.4.1.10) produced by Arthrobacter nicotinovorans GS-9. There are five types of derivatives due to the difference in the binding mode of bimolecular fructose, which are referred to as DFAI, DFAII, DFAIII, DFAIV, and DFAV, respectively. The DFA as used in the present invention refers to all of them. In the present invention, DFAIII (di-D-fructofuranose-1,2 ′) which is excellent in industrial production efficiency, stability after purification, etc. : 2,3'dianhydride) and DFAIV (di-D-fructofuranose-2,6 ': 6,2'dianhydride) are preferably used.

0.001-30 mass% is preferable with respect to the skin external preparation whole quantity.
Examples of the polyhydric alcohol of the present invention include glycerin, 1,3-butylene glycol, 1,2-pentanediol, 1,2-hexylene glycol, dipropylene glycol, isoprene glycol, polyethylene glycol, diglycerin, polyglycerin and the like. be able to. 1-50 mass% is preferable with respect to the skin external preparation whole quantity, and, as for the compounding quantity of a polyhydric alcohol, 3-30 mass% is more preferable.

  Examples of the silicone oil of the present invention include dimethylpolysiloxane, methylphenylpolysiloxane, dimethylcyclopolysiloxane and the like. 0.1-80 mass% is preferable with respect to the skin external preparation whole quantity, and, as for the compounding quantity of silicone oil, 0.5-50 mass% is more preferable.

  The skin external preparation of the present invention includes skin external pharmaceuticals, skin external quasi-drugs, and cosmetics. Examples of the external preparation for skin include anti-inflammatory external preparations, anti-acne external preparations, and bactericidal external preparations. Examples of quasi-drugs for external skin use include quasi-drugs for whitening, quasi-drugs for improving rough skin, and quasi-drugs for acne. The cosmetics of the present invention include lotions, emulsions, skin creams, hand creams, body milks, sunscreen agents, liquid foundations, hair conditioners and the like.

  The skin external preparation of the present invention includes fats and oils such as vegetable oils, higher fatty acids, higher alcohols, anionic surfactants, cationic surfactants, amphoteric surfactants, depending on the use, purpose of use, dosage form, etc. Nonionic surfactants, preservatives, saccharides, sequestering agents, powder components, UV absorbers, UV blockers, moisturizers such as hyaluronic acid, fragrances, pH adjusters, and the like can be included. Vitamins, skin activators, blood circulation promoters, resident bacteria control agents, active oxygen scavengers, anti-inflammatory agents, whitening agents, bactericides, and other medicinal and physiologically active components can also be included.

  Examples of the fats and oils include camellia oil, evening primrose oil, macadamia nut oil, olive oil, rapeseed oil, corn oil, sesame oil, jojoba oil, germ oil, wheat germ oil, glycerin trioctanoate, cocoa butter, coconut oil, Solid oils such as hydrogenated coconut oil, palm oil, palm kernel oil, brown owl kernel oil, hydrogenated oil, hydrogenated castor oil, wax such as beeswax, candelilla wax, cotton wax, nutca wax, lanolin, lanolin acetate, liquid lanolin, sugarcane wax And liquid paraffin, squalene, squalane, microcrystalline wax and the like.

  Examples of higher fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and the like.

  Examples of the higher alcohol include linear alcohols such as lauryl alcohol, stearyl alcohol, cetyl alcohol, and cetostearyl alcohol, and branched chain alcohols such as monostearyl glycerin ether, lanolin alcohol, cholesterol, phytosterol, and octyldodecanol.

  Examples of the anionic surfactant include fatty acid salts such as sodium laurate, higher alkyl sulfates such as sodium lauryl sulfate, alkyl ether sulfates such as POE lauryl sulfate triethanolamine, N-acyl sarcosine acid, sulfosuccinate N-acylamino acid salts and the like.

  Examples of the cationic surfactant include alkyltrimethylammonium salts such as stearyltrimethylammonium chloride, benzalkonium chloride, and benzethonium chloride.

  Examples of amphoteric surfactants include betaine surfactants such as alkyl betaines and amide betaines.

  Examples of nonionic surfactants include sorbitan fatty acid esters such as sorbitan monooleate and hardened castor oil derivatives.

  Examples of preservatives include methyl paraben and ethyl paraben.

  Examples of the sequestering agent include edetates such as disodium ethylenediaminetetraacetate, edetic acid, and sodium edetate.

  In order to suppress stickiness and color, powder components include, for example, talc, kaolin, mica, silica, zeolite, polyethylene powder, polystyrene powder, cellulose powder, inorganic white pigment, inorganic red pigment, titanium oxide coated Mention may be made of pearl pigments such as mica, titanium oxide coated talc and colored titanium oxide coated mica, and tar dyes such as red 201 and red 202.

  Examples of the ultraviolet absorber include paraaminobenzoic acid, phenyl salicylate, isopropyl paramethoxycinnamate, octyl paramethoxycinnamate, 2,4-dihydroxybenzophenone, and the like.

  Examples of the ultraviolet blocking agent include titanium oxide, talc, carmine, bentonite, kaolin, and zinc oxide.

  Examples of the humectant include xylitol, maltitol, maltose, sorbitol, glucose, fructose, sucrose, lactose, sodium chondroitin sulfate, sodium hyaluronate, sodium lactate, pyrrolidone carboxylic acid, cyclodextrin and the like.

  Medicinal components include, for example, vitamin A oils such as vitamin A oil and retinol, vitamin B2 such as riboflavin, B6 such as pyridoxine hydrochloride, L-ascorbic acid, L-ascorbic acid phosphate, L-ascorbic acid- Water-soluble ascorbic acids such as 2-glucoside, pantothenic acids such as calcium pantothenate, vitamin Ds such as vitamin D 2 and cholecalciferol, vitamin E such as α-tocopherol, tocopherol acetate, DL-α-tocopherol nicotinate, etc. Can give vitamins.

  In addition, whitening agents such as placenta extract, glutathione, and yukinoshita extract, skin activators such as royal jelly, beech tree extract, blood circulation such as capsaicin, gingeron, cantalis tincture, ictamol, caffeine, tannic acid, γ-oryzanol, etc. Accelerators, glycyrrhizic acid derivatives, glycyrrhetinic acid derivatives, anti-inflammatory agents such as azulene, amino acids such as arginine, serine, leucine and tryptophan, maltose sucrose condensates of resident bacteria control agents, lysozyme chloride and the like.

  Furthermore, in order to obtain a synergistic effect, chamomile extract, parsley extract, wine yeast extract, grapefruit extract, honeysuckle extract, rice extract, grape extract, hop extract, rice bran extract, loquat extract, buckwheat extract, yakuinin extract, assembly extract, merirot extract, birch Extract, licorice extract, peony extract, bonito extract, loofah extract, red pepper extract, lemon extract, gentian extract, perilla extract, aloe extract, rosemary extract, sage extract, thyme extract, tea extract, seaweed extract, cucumber extract, clove extract , Various extracts such as Maronnier extract, Hamamelis extract, Mulberry extract and the like.

[Sensory evaluation test example 1]
The effect of improving the squeak after blending when glycerin and 1,3-butylene glycol were blended with DFA III was evaluated by sensory evaluation. Moreover, the moisturizing effect of DFAIII was evaluated.
Note that “squeak” means that the finger feels when the finger is moved in contact with the skin in the horizontal direction on the skin.
A lotion having the composition shown in Table 1 was prepared, and 7 women in their thirties were evaluated for creaking after familiarization. The numerical values in the table indicate mass%. The moisturizing feeling was evaluated by 6 women in their 20s to 30s. The results are shown in Tables 2-4.
Table 2 shows the squeaks after Example 1 was compared with Comparative Example 1. Table 3 shows the squeak after Example 2 is compared with Comparative Example 1. Table 4 shows which has a strong moisturizing feeling compared to Example 1 and Comparative Example 2.

It was found that the squeakiness after familiarization derived from DFA III can be improved by blending polyhydric alcohols such as glycerin and 1,3-butylene glycol.

It was found that the moisturizing feeling was remarkably improved by adding DFAIII to the lotion.

[Sensory evaluation test example 2]
The effect of improving the creaking after blending when dimethylpolysiloxane was blended with DFA III was evaluated by sensory evaluation. Moreover, the moisturizing effect of DFAIII was evaluated.
Creams having the composition shown in Table 5 were prepared, and 7 women in their 30s were evaluated for creaking after familiarization. The moisturizing feeling was evaluated by 6 women in their 20s to 30s. The results are shown in Tables 6 and 7.
Table 6 shows the squeak after Example 3 is compared with Comparative Example 3. Table 7 shows which has a strong moisturizing feeling when comparing Example 3 and Comparative Example 4.

It has been found that the blending of dimethylpolysiloxane can improve the squeak after blending derived from DFAIII.

  It was found that the moisturizing feeling was remarkably improved by adding DFAIII to the cream.

[Reference Experimental Example 1]
(In vitro moisture retention test)
Sample preparation 10% by mass of DFA III, xylitol, D-mannitol, and an aqueous trehalose solution were prepared .

Measuring method
A 5 g sample was placed in a polyethylene container and allowed to stand for 3 days under conditions of a temperature of 23 ° C. and a humidity of 30%, and the sample weight was measured. Ten samples were measured for each sample and averaged.

The percentage of the amount of water remaining on the third day (the sample weight on the third day minus the amount of moisturizer (0.5 g)) relative to the amount of moisturizer (0.5 g) in the sample for evaluating moisturizing properties Obtained by the formula.
(Sample weight on the third day-0.5 g) /0.5 g x 100 (%)
The results are shown in Table 8.

  In this test, the moisture retention (water retention) of DFAIII is clearly superior to xylitol, trehalose, and D-mannitol.

[Reference Experiment 2]
(In vivo moisturizing test)
Sample preparation 10% by mass of DFA III, xylitol, D-mannitol, and an aqueous trehalose solution were prepared .

Measuring device skin stratum corneum moisture measuring device SKICON-200EX

Measurement method The inner part of the forearm was washed with tap water, wiped with a towel, and allowed to stand for 15 minutes. The stratum corneum water content of the test site (2 cm × 2 cm) is measured before sample application. Next, 40 μl of each sample is dropped onto each test site, spread and blended. Thereafter, the stratum corneum moisture content was measured after 1 hour and 2 hours later. The measurement was performed five times for each test site, and the three measured values excluding the maximum value and the minimum value were averaged.

Measurement environment temperature 24-25 ° C, humidity 42-52%

Calculation of rate of change of stratum corneum water content The rate of change of stratum corneum water content was determined by the following equation.
Rate of change in stratum corneum moisture = stratum corneum moisture after sample application / stratum corneum moisture before sample application x 100 (%)
Table 9 shows the measurement results.

Even when the sample was not applied, the stratum corneum moisture content tended to decrease to 90% after 1 hour and 82% after 2 hours, but 109% after 2 hours and 2 hours by applying the DFA III aqueous solution. After that, a high water content of 92% could be maintained. On the other hand, when trehalose, xylitol, and a D-mannitol aqueous solution were applied, it was dried more than when it was not applied.
The moisturizing property of DFAIII is clearly superior to trehalose, xylitol and D-mannitol.

[Reference Experiment 3]
(Evaluation of irritation mitigation action) In the test of irritation mitigation action, a surfactant was used as an irritation index.
For glycerin, fructose, and DFAIII, the stimulating and mitigating action by the surfactant was evaluated by the following method. The reference stimulus was a cultured human epidermal keratinocyte treated with 0.005% sodium lauryl sulfate aqueous solution alone. A 0.005% aqueous sodium lauryl sulfate solution to which sugars of various concentrations were added was allowed to act, and the stimulation mitigating action of each agent was measured by the MTT reduction method, and the cell viability was determined by comparison. MTT reduction method means that MTT [3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide] is reduced to a blue product by succinate dehydrogenase in the mitochondria. In this method, after the product is dissolved and colored, the absorbance is measured and used as an indicator of the amount of living cells. The stimulation relaxation rate was determined and evaluated from the following equation.
Stimulation relaxation rate (%) = (A−A0) / (A1−A0) × 100
However, A1 is the cell viability before treatment, A0 is the cell viability when the sodium lauryl sulfate aqueous solution acts, and A is the cell viability one hour after the action of the sodium lauryl sulfate aqueous solution added with the plant extract. Table 10 shows the relationship between the concentration of plant extract added (%) and the relaxation rate (%).
As shown in Table 10, glycerin hardly shows a stimulus mitigating action. Fructose, which is a kind of saccharide, shows a slight irritation mitigating action at addition amounts of 1.25% and 2.5%, but no irritation mitigating action at 5% addition amount. On the other hand, DFAIII showed a significant stimulus relaxation effect in a concentration-dependent manner.

  As described above, it is clear that difructose anhydride has an action of greatly relieving irritation to skin, hair, mucous membranes, etc., and as an irritation reducing agent and a hypoallergenic composition containing the same. Useful.

[Prescription Example 1]
A lotion was produced according to the following formulation.
Ingredient name Compounding amount (% by mass)
(1) Glycerin 9.5
(2) 1,3-butylene glycol 4.5
(3) DFAIII 1.5
(4) Ethanol 5.0
(5) Carboxyvinyl polymer 0.02
(6) Dipotassium glycyrrhizinate 0.1
(7) Sodium hyaluronate 0.1
(8) Citric acid 0.05
(9) Sodium citrate 0.1
(10) Potassium hydroxide 0.01
(11) Residual ion exchange water

[Production Method] At room temperature, the components (1) to (10) were added to the above component (11), dissolved by stirring, and uniformly dissolved to obtain a lotion.
[Usage feeling] Highly moist, non-sticky, uncomfortable after familiarization, and no irritation to skin.

[Prescription Example 2]
An emulsion was produced according to the following formulation.
Ingredient name Compounding amount (% by mass)
(1) Squalane 6.0
(2) Jojoba oil 3.0
(3) POE (20) cetyl ether 0.5
(4) POE (50) hydrogenated castor oil 1.0
(5) Stearic acid 2.0
(6) Behenyl alcohol 3.0
(7) Ethyl paraoxybenzoate 0.15
(8) Propyl paraoxybenzoate 0.1
(9) 1,3-butylene glycol 7.0
(10) Concentrated glycerin 2.5
(11) DFA III 3.0
(12) Carboxymethyldextran sodium 1.0
(13) Carboxyvinyl polymer 0.07
(14) L-aspartic acid 0.1
(15) Potassium hydroxide 0.04
(16) Purified water residue

[Production Method] Oil phase components (1) to (8) and aqueous phase components (9) to (16) are heated to 78 to 85 ° C. and completely dissolved. The oil phase component is added to the water phase component and emulsified with an emulsifier. The obtained emulsion was cooled to obtain an emulsion.
[Usage feeling] Highly moist, non-sticky, uncomfortable after familiarization, and no irritation to skin.

Formulation Example 3
A cream was produced according to the following formulation.
Ingredient name Compounding amount (% by mass)
(1) Purified water residue (2) Dipropylene glycol 10.0
(3) Carboxyvinyl polymer 0.12
(4) Glycerin 3.0
(5) Betaine 3.0
(6) DFAIII 3.0
(7) Jojoba oil 8.5
(8) Squalane 10.0
(9) Dimethylpolysiloxane (50cs) 2.0
(10) New oil type glyceryl monostearate 3.0
(11) Sorbitan monostearate 1.5
(12) Polyoxyethylene monostearate 1.0
Sorbitan (20E.O.)
(13) Parsley extract 0.1
(14) Potassium hydroxide 0.05
[Manufacturing method] The water phase components (1) to (6) and the oil phase components (7) to (12) are respectively heated and dissolved, and the oil phase component is mixed with the water phase component and emulsified with an emulsifier. After cooling, ingredients (13) and (14) were mixed to obtain a cream.
[Usage feeling] Highly moist, non-sticky, uncomfortable after familiarization, and no irritation to skin.

[Prescription Example 4]
A sunscreen was produced according to the following formulation.
Ingredient name Compounding amount (% by mass)
(1) Fine particle titanium oxide 5.0
(2) Silica / cerium oxide composite particles 5.0
(3) Fine zinc oxide 3.0
(4) Octenyl succinate corn starch 5.0
Ester aluminum (5) Silicic anhydride 3.0
(6) Polyglycerol fatty acid ester 3.0
(7) Dimethylpolysiloxane (50 cs) 10.0
(8) Sodium chloride 1.0
(9) 1,3-butylene glycol 5.0
(10) DFA III 2.0
(11) Remaining amount of purified water

[Production Method] Components (6) and (7) are mixed uniformly, and components (1) to (5) are further added and mixed uniformly. To this was added a uniform mixture of components (8) to (11) and emulsified to obtain a sunscreen.
[Usage feeling] Highly moist, non-sticky, uncomfortable after familiarization, and no irritation to skin.

Claims (2)

  A skin external preparation containing difructose anhydride and a polyhydric alcohol.   An external preparation for skin containing difructose anhydride and silicone oil.