JP2005041861A - Inhibitor for reducing water content in horny layer of skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To improve rough dry skin derived from reduction of the water content in the horny layer of the skin by administering a multivitamin preparation. <P>SOLUTION: The rough dry skin is alleviated by administering the multivitamin preparation comprising a vitamin B<SB>2</SB>, a vitamin B<SB>6</SB>, a vitamin C, and L-cysteine. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a skin stratum corneum water content lowering inhibitor, and more particularly to a general vitamin preparation for internal use which has a suppressive action on the skin stratum corneum water content and is useful for alleviating skin roughness.

Skin roughness is a state accompanied by a decrease in keratin function (moisture retention function, skin barrier function). The skin's moisture retention function involves turnover (skin metabolism), keratinocyte lipids, or natural moisturizing factors, and skin with reduced skin moisture retention has blemishes in the turnover. In other words, it can be said that lipids between keratinocytes and natural moisturizing factors are decreased. In the process of turnover, keratinocyte lipids and natural moisturizing factors are produced (see Non-Patent Document 1).
On the other hand, vitamin B ₂ and vitamin B ₆ act so that turnover is normally performed, and vitamin B ₂ is involved in the synthesis of cholesterol which is a kind of keratinocyte lipid (non-patent document). 2). Vitamin C is present in the basal layer of the skin and is involved in the production of collagen that retains moisture (see Non-Patent Document 3). L-cysteine is only a turnover caused by a decrease in skin moisture retention function. (Non-patent Document 4) is known to have an effect of normalizing the above.
Conventionally, components for improving the moisture retention function as described above and components for improving the skin barrier function have been used to alleviate and improve skin roughness. However, these ingredients are blended in external preparations, and there are no drugs that aim to improve the water retention function with internal vitamins.
Genji Ayukawa, Moisturizing function of skin stratum corneum and role of stratum corneum component, FRAGRANCE JOURNAL special issue No. 17 27-39 (2000) Chihiro Matsui et al., Treatment Experience of Acne Vulgaris, Basic and Clinical 21 (6), 565-567 (1987) The Vitamin Society of Japan, Encyclopedia of Vitamins, 374-375, Asakura Shoten (1996) Hiroshi Abe et al., Development and Application of Amino Acids in the Cosmetics Field, FRAGRANCE JOURNAL Special Issue (15), 2-14 (1996)

  An object of the present invention is to provide a vitamin preparation that exhibits an effect on the skin by internal use.

As a result of various studies to achieve the above-mentioned object, the present inventors have found that vitamin B ₂ and vitamin B ₆ , preferably these, ascorbic acid and L-cysteine, more preferably at a specific ratio. When it was blended in, it was found that it was effective for internal skin with internal use, and the present invention was completed.
That is, the present invention
(1) An internal skin horny layer water content lowering inhibitor characterized by containing vitamin B ₂ and vitamin B ₆ ;
(2) Furthermore, (a) at least one selected from L-cysteine, glycine, glutamic acid and glutathione, and (b) a preparation according to the above (1) containing vitamin C,
(3) The preparation according to the above (1), which is used for the prevention / treatment of rough skin,
(4) in the formulation, vitamin _{B 2} such 3-8 wt%, vitamin _{B 6} such 10 to 28 wt%, the Vitamin C containing 6 to 15 wt% of 18 to 40 wt% and L- cysteine It provides preventive and therapeutic agents for internal skin roughness.

  ADVANTAGE OF THE INVENTION According to this invention, the vitamin preparation which exhibits the effect excellent in the rough skin by internal use can be provided.

The present invention will be specifically described below.
Vitamin B ₂ and B ₆ used in the present invention also include their salts. Examples of the vitamin B ₂ include riboflavin, riboflavin sodium phosphate, and riboflavin butyrate. The vitamin B ₆ such as, for example, pyridoxine hydrochloride, pyridoxal phosphate and the like are used.
In the present invention, 3 to 8% by weight, preferably 3 to 5% by weight of vitamin B ₂ and 10 to 28% by weight, preferably 14 to 16% by weight of vitamin B ₆ based on the total amount of the preparation. To do.

In the preparation of the present invention, preferably, in addition to vitamin B ₂ and vitamin B ₆ , in addition to (a) at least one selected from L-cysteine, glycine, glutamic acid and glutathione, and (b) vitamin C Blend. Component (a) includes those salts, and component (a) is blended in an amount of 6 to 15% by weight, preferably 7 to 10% by weight based on the total amount of the preparation. Cysteine is preferred. In addition, component (b) is blended in an amount of 18 to 40% by weight, preferably 20 to 24% by weight, based on the total amount of the preparation.
Vitamin C includes its salts. As vitamin C, for example, ascorbic acid, sodium ascorbate, calcium ascorbate and the like are used.

In the preparation of the present invention, other vitamins and the like may be appropriately blended as active ingredients in addition to the above components. These components include, for example, nicotinic acid, nicotinamide, biotin, calcium pantothenate, calcium pantothenate type S, vitamin B ₁ derivative (fursultiamine hydrochloride, discetiamine hydrochloride, octothiamine, chicotiamine, bisibutiamine, bis Benamine, benfotiamine, etc.), vitamin B ₁ (thiamine hydrochloride, thiamine nitrate, bisthiamine nitrate, thiamine disulfide, thiamine dicetyl sulfate, etc.), vitamin E (d-α-tocopherol succinate, dl-α succinate) -Tocopherol calcium, d-α-tocopherol acetate, dl-α-tocopherol acetate, etc.), gamma oryzanol, vitamin B ₁₂ (cyanocobalamin, hydroxocobalamin hydrochloride, hydroxocobalamin acetate, mecobalamin, etc.) , Orotic acid, glucuronolactone, glucuronic acid amide, yokuinin, and the like, which can be used alone or in combination of two or more.

The dosage form of the preparation of the present invention is not particularly limited as long as it is a solid dosage form suitable for internal use. For example, fine granules, granules, pills, tablets (film-coated tablets, thin layers) Sugar-coated tablets, sugar-coated tablets and the like), and capsules. The solid preparation of the present invention comprises the above-mentioned vitamin B ₂ class, vitamin B ₆ class, components (a) and (b), active ingredients blended as necessary, and excipients blended as necessary , Binders, disintegrants, lubricants, antioxidants, corrigents, fragrances, colorants and the like can be used in appropriate amounts.
Examples of excipients include lactose, sucrose, D-mannitol, D-sorbitol, starch (corn starch, potato starch, etc.), pregelatinized starch, dextrin, crystalline cellulose, low-substituted hydroxypropylcellulose, sodium carboxymethylcellulose, Examples include gum arabic, dextran, pullulan, light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminate metasilicate, and the like.
Examples of the binder include pregelatinized starch, sucrose, gelatin, gum arabic powder, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, crystalline cellulose, dextrin, pullulan and the like. .
Examples of the lubricant include magnesium stearate, calcium stearate, talc, colloidal silica, and the like.
Examples of the disintegrant include lactose, sucrose, carboxymethylcellulose, low-substituted hydroxypropylcellulose, carmellose calcium, starch (corn starch, potato starch, etc.), light anhydrous silicic acid, croscarmellose sodium, carboxymethyl starch sodium, Examples include carboxymethylcellulose calcium.
These can be produced by a method known per se.
As the preparation of the present invention, a tablet is particularly preferable. For example, in the case of a film-coated tablet, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, aminoalkyl methacrylate copolymer E, aminoalkyl are used as the film coating base. A methacrylate copolymer L, an aminoalkyl methacrylate copolymer RS, an aminoalkyl methacrylate copolymer S, a carboxyvinyl polymer, polyvinyl alcohol, polyvinyl acetal diethylamine acetate, pullulan and the like are used.
In the case of a thin-layer sugar-coated tablet, sucrose, trehalose, lactose, mannitol, sorbitol, xylitol, maltitol, erythritol, powdered reduced maltose starch syrup, pullulan, titanium oxide, polyethylene glycol and the like are used.
In the case of sugar-coated tablets, sucrose, trehalose, lactose, mannitol, sorbitol, xylitol, maltitol, erythritol, powdered reduced maltose starch syrup, pullulan and the like are used.

By taking the preparation of the present invention orally, for example, vitamin B ₂ class 10-30 mg, vitamin B ₆ class 50-100 mg, vitamin C class 100-200 mg, L-cysteine 50-160 mg per day per adult, The desired effect of preventing rough skin can be obtained.

  Next, the present invention will be described in more detail with reference to test examples and examples, but the present invention is not limited thereto.

Test example 1

Using an experimental dry skin model of guinea pigs (Std: Hartley male guinea pigs, Japan SLC Co., Ltd.), the improvement degree and roughness of the preparations of the present invention were examined.
Using a 0.5% aqueous solution of methylcellulose (MC), a mixture of vitamin B ₂ (hereinafter abbreviated as VB ₂ ) and vitamin B ₆ (hereinafter abbreviated as VB ₆ ) and VB ₂ , VB ₆ , vitamin C (hereinafter, An administration solution of a mixture of VC and L-cysteine (hereinafter abbreviated as cys) was prepared.
On the other hand, the abdomen of 5-week-old guinea pigs was depilated, and the skin conductivity was measured after 0, 30, 60, 90 and 120 seconds using a skin keratin water content measuring apparatus (SKICON-200, IBS). From the obtained conductivity:
Area under conductivity curve (μS x sec)
= {(Conductivity of 0 seconds + conductivity of 30 seconds) × 30/2} + {(conductivity of 30 seconds + conductivity of 60 seconds) × 30/2} + {(conductivity of 60 seconds + conductivity of 90 seconds) Degree) × 30/2} + {(conductivity for 90 seconds + conductivity for 120 seconds) × 30/2}
Thus, the area under the conductivity curve (AUC) was calculated and grouped according to the group composition table of Table 1 using AUC as an index.

Table 1 Group composition table

  After grouping, 0.5% MC aqueous solution was administered orally for groups A and B, and the administration solution was administered orally once a day for 24 days (days 0 to 23) for groups C and D. For group E, the 0.5% MC aqueous solution was orally administered continuously until the 16th day from the start of the test, and the administration liquid was continuously administered from the 17th day. Conductivity was measured again before administration on day 13. After measuring the electrical conductivity on the 13th day, a 0.3% sodium dodecyl sulfate (SDS) aqueous solution was applied to a 5 × 5 cm region of the abdomen for 4 days (13th to 16th days) to prepare dry skin. Administration of the test substance was continued during the application of SDS. After the application, the administration solution or 0.5% MC aqueous solution administration was continued until the 23rd day (17th to 23rd days). For Group E, the administration solution was administered. The skin conductivity was measured on days 17, 19, 21 and 23, and the rough skin area was measured on days 17 and 24.

As a result, in the untreated group, almost the same electrical conductivity transition was observed during the test period. In the control group, a significant decrease in electrical conductivity was observed from the day after the end of SDS application, confirming the production of dry skin.
Administration of VB ₂ and VB ₆ mixture and VB ₂ , VB ₆ , VC and cys mixture from 2 weeks before the start of SDS application showed a decrease in conductivity and a reduction in rough skin, and an effect on skin dryness was observed. It was. The transition of AUC is shown in FIG. 1, and the result of measuring the rough skin area on the 17th day is shown in FIG.
When the VB ₂ , VB ₆ , VC and cys mixture was orally administered for only one week after the end of the SDS application, the inhibitory effect on skin dryness was not noticeable. Furthermore, the administration from 2 weeks before the creation of dry skin shows a statistically significant difference between the VB ₂ and VB ₆ mixture and the VB ₂ , VB ₆ , VC and cys mixture. An enhancement was observed. In addition, with the administration of VB ₂ , VB ₆ , VC and cys mixture, there was a statistically significant difference between the administration from 2 weeks before the application of SDS and the administration after completion of the application, and the enhancement of the effect by the previous administration was also observed. It was.

Test example 2

In the same manner as in Test Example 1, a liquid mixture of VB ₂ , VB ₆ , VC and cys was administered once a day for 19 consecutive days at the dose shown in Table 2, and the transition of AUC was examined. The results are shown in FIG. The results are expressed as the average value ± standard error of 10 cases.
Table 2 Group composition table

As a result, in the untreated group, almost the same electrical conductivity transition was observed during the test period. In the control group, a significant decrease in AUC was observed from the day after the application of SDS, confirming the production of dry skin.
In the group administered with the VB ₂ , VB ₆ , VC and cys mixture, the AUC was significantly higher than the control group on the day after the application of SDS, and the decrease in moisturizing ability was suppressed. That is, as compared with the administration group 1 (low dose administration group), the suppression effect was more markedly observed in the administration group 2 (medium dose administration group) and the administration group 3 (high dose administration group). In addition, the degree of suppression in the administration group 2 and the administration group 3 was almost the same, and it was considered that the amount shown in the administration group 2 was optimal for the effect on dry skin exhibited by VB ₂ , VB ₆ , VC and cys.

Riboflavin 300 g, pyridoxine hydrochloride 1000 g, L-cysteine (Ajinomoto, Nippon Protein Co., Ltd.) 600 g, ascorbic acid 1500 g, nicotinic acid amide 600 g, biotin 0.75 g, crystalline cellulose 391.25 g were fluidized bed granulator (FD-5S, The fluid bed granulation was carried out by spraying 2330 g of a 6% hydroxypropyl cellulose (HPC-L) aqueous solution at Paulek). Thereafter, the particles were sized with a sizing machine (Power Mill, Showa Chemical Machinery) to obtain a sized powder.
The obtained sized powder (4078.8 g), low-substituted hydroxypropyl cellulose (216 g) and vegetable magnesium stearate (Taihei Kagaku) (25.2 g) were mixed in a mixer (tumbler mixer, Showa Chemical Machinery). The mixed powder is tableted with a rotary tableting machine using a 8.5 mm diameter mortar and a radius of curvature of 7.0 mm so that the weight per tablet is 240 mg and the thickness is 4.5 mm. Got.
Using a Doria coater (DRC-500, Paulek) to 3240 g of the obtained uncoated tablet, 108 g of hydroxypropylmethylcellulose 2910 (TC-5MW) and 12 g of talc dissolved in purified water, Coating was performed to obtain an undercoated tablet of 245 mg / tablet. Furthermore, the undercoated tablet was coated with a 36% aqueous solution obtained by dissolving and suspending 954 g of erythritol, 504 g of talc, 36 g of titanium oxide, 90 g of crystalline cellulose, and 216 g of gum arabic powder in purified water, and a build-up coating of 335 mg / tablet. I got a tablet. Further, the build-up coated tablet was coated with a 36% aqueous solution in which 270 g of erythritol and 30 g of polyethylene glycol 6000 were dissolved in purified water to obtain 350 mg / tablet syrup-coated tablet. The obtained syrup-coated tablet was polished with a small amount of wax or the like.

  According to the present invention, it is possible to improve skin roughness resulting from a decrease in stratum corneum moisture content by taking a multivitamin preparation.

6 is a graph showing transition of AUC in Test Example 1. It is a graph which shows the measurement result of the rough skin area in Test Example 1. It is a graph which shows AUC transition in Test Example 2.

Explanation of symbols

The symbols in FIG. 2 have the following meanings.
## P <0.01, indicating that Tukey's multiple comparison test is significantly different from the control group.
$ P <0.05, indicating that there is a significant difference in Tukey's multiple comparison test compared to pre-administration group 1.
&& P <0.01, indicating that there is a significant difference in Tukey's multiple comparison test compared to pre-administration group 2.

Claims (4)

For internal use skin stratum corneum water content decreases suppressing agent characterized by compounding vitamin B ₂ acids and vitamin B ₆ compound.   The preparation according to claim 1, further comprising (a) at least one selected from L-cysteine, glycine, glutamic acid and glutathione, and (b) vitamin Cs.   The preparation according to claim 1, which is used for prevention and treatment of skin roughness. In the formulation, vitamin _{B 2} such 3-8 wt%, vitamin _{B 6} such 10 to 28 wt%, there oral skin containing 6 to 15 wt% of 18 to 40 wt% and L- cysteine Vitamin C Prophylactic / therapeutic agent.

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