JP2005298493A - Medicinal composition for preventing and/or treating chapped skin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new medicinal composition for preventing and/or treating the chapped skin in which lowering of water content contained in the skin is suppressed by internal use thereof. <P>SOLUTION: The medicinal composition for preventing and/or treating the chapped skin by the internal use comprises glucosamine hydrochloride and glucuronic acids and as necessary, at least one kind of vitamin selected from vitamin B<SB>2</SB>s and vitamin B<SB>6</SB>s, and vitamin C. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a pharmaceutical composition for the prevention and / or treatment of skin irritation, and more specifically, the prevention of skin irritation by internal use which has an inhibitory effect on the decrease in the amount of water in the horny layer in the skin and is useful for improving skin irritation. The present invention relates to a therapeutic pharmaceutical composition.

Skin roughness is a state accompanied by a decrease in keratin function (horny layer moisture retention function, skin barrier function). Skin moisture function involves turnover (skin metabolism), keratin intercellular lipids, or natural moisturizing factors, and skin with poor skin moisture retention may have blemishes in turnover. It can be said that keratinocyte lipids and natural moisturizing factors are reduced. In the process of turnover, keratinocyte lipids and natural moisturizing factors are produced (see Non-Patent Document 1).
Conventionally, it is known that glucosamine hydrochloride promotes the synthesis of chondroitin sulfate and hyaluronic acid and exerts an effect on dry skin (see Non-Patent Document 2).
On the other hand, glucuronic acid is blended mainly in beverage components of pharmaceuticals for the purpose of improving liver function. Glucuronic acid and glucosamine are known to be involved in the synthesis of hyaluronic acid, a kind of glycosaminoglycan, in vivo (see Non-Patent Document 3). However, the effect on the skin is not known.
Genji Ayukawa, Moisturizing function of skin stratum corneum and role of stratum corneum component, FRAGRANCE JOURNAL special issue No. 17 27-39 (2000) Enomoto Osamu, clinical effect of glucosamine hydrochloride on dry skin DONALD VOET ・ JUDITH G. VOTE Vault Biochemistry Second Edition

  An object of the present invention is to provide a novel pharmaceutical composition for preventing and / or treating skin roughness that is useful for improving skin roughness by internal use.

The inventors of the present invention have made various studies to achieve the above object, and as a result, glucosamine hydrochloride and glucuronic acid are combined with each other particularly at a specific ratio, and preferably, these are combined with vitamin B ₂ and vitamin B _6. More preferably, by combining these with ascorbic acid, it has been found that a preparation that exhibits an effect on the skin can be obtained by internal use, and the present invention has been completed.
That is, the present invention
(1) A pharmaceutical composition for preventing and / or treating skin irritation by internal use, characterized by containing glucosamine hydrochloride and glucuronic acid,
(2) The pharmaceutical composition according to the above (1), wherein the weight ratio of glucosamine hydrochloride: glucuronic acid is a ratio of 1: 0.5-2;
(3) The pharmaceutical composition according to (1), further comprising at least one selected from vitamin B ₂ and vitamin B ₆ ; and (4) further (a) vitamin B ₂ and vitamin B ₆ The pharmaceutical composition according to the above (1), comprising at least one selected from the group and (b) vitamin C is provided.

  The pharmaceutical composition of the present invention suppresses a decrease in the amount of water contained in the skin by internal use, and exhibits an excellent effect in prevention and treatment of skin roughness.

The glucosamine hydrochloride (glucosamine hydrochloride) used in the pharmaceutical composition of the present invention is not particularly limited, and may normally be used as a pharmaceutical ingredient. Usually, glucosamine hydrochloride is blended in the pharmaceutical composition of the present invention in an amount of 10 to 85% by weight, preferably 15 to 50% by weight.
The glucuronic acids used in the present invention include their salts, and for example, glucuronic acid amides and glucuronolactones are used.
In this invention, it mix | blends so that the weight ratio of glucosamine hydrochloride: glucuronic acid in a pharmaceutical composition may be set to the ratio of 1: 0.5-2, Preferably, 1: 0.75-1.5.

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. These can be used alone or in combination of two or more.
Usually, based on the total amount of the composition, vitamin _{B 2} such 3-8 wt%, preferably 3-5 wt%, vitamin _{B 6} such 10 to 28 weight percent, preferably formulated 14-16 wt%.

  Vitamin C includes its salts. As vitamin C, for example, ascorbic acid, sodium ascorbate, calcium ascorbate and the like are used. Usually, vitamin C is blended in an amount of 1 to 30% by weight, preferably 4 to 20% by weight, based on the total amount of the composition.

In addition to the above-mentioned components, other vitamins and the like as active ingredients may be appropriately blended in the pharmaceutical composition of the present invention. 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, and yokuinin. These may be used alone or in combination of two or more.

The pharmaceutical composition of the present invention is not particularly limited as long as it is a dosage form suitable for internal use. For example, fine granules, granules, pills, tablets (film-coated tablets, thin-layer sugar-coated tablets) And oral preparations such as solid preparations such as capsules, drinks, dipping agents / decoction, syrups, spirits, suspensions, and emulsions. The pharmaceutical composition of the present invention comprises an excipient, a binder, a disintegrant, a lubricant and, if necessary, a solubilizing agent, a buffering agent, a preservative, a solubilizer, an antioxidant, together with the above-described components. An appropriate amount of conventional formulation additives such as additives, flavoring agents, fragrances, and coloring agents can be contained.
Examples of excipients include lactose, sucrose, purified sucrose, D-mannitol, D-sorbitol, erythritol, starch (such as corn starch and potato starch), pregelatinized starch, dextrin, crystalline cellulose, and low-substituted hydroxypropylcellulose. , Sodium carboxymethylcellulose, 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, carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, carmellose calcium, starch (corn starch, potato starch, etc.), light anhydrous silicic acid, croscarmellose sodium, carboxymethyl starch sodium, Examples include carboxymethylcellulose calcium.
These preparations can be produced by a method known per se.
The pharmaceutical composition of the present invention is preferably a solid preparation, particularly a tablet. For example, in the case of a film-coated tablet, methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, aminoalkyl methacrylate are used as the film coating base. Copolymer E, aminoalkyl methacrylate copolymer L, aminoalkyl methacrylate copolymer RS, aminoalkyl methacrylate copolymer S, 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.

  The pharmaceutical composition of the present invention can provide desired prevention and treatment effects of skin roughness by adjusting the daily dose of adults to, for example, 200 to 1000 mg of glucosamine hydrochloride and glucuronic acid, respectively.

  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, Nippon SLC Co., Ltd.), the degree of difficulty in improving the skin roughness of a mixture of glucosamine hydrochloride and glucuronic acid amide was examined.
An injection solution of a mixture of glucosamine hydrochloride and glucuronic acid amide was prepared using water for injection.
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.

After grouping, water for injection was administered orally for groups A and B, and test substance was orally administered once a day for 19 consecutive days for group C. Before the administration on the 15th day, the electric conductivity was measured again. After the measurement was completed, a 0.3% sodium dodecyl sulfate (SDS) aqueous solution was applied to the 5 × 5 cm region of the abdomen for 4 days (15 to 18 days) and dried. Skin was prepared. The day after application was completed, the skin conductivity was measured.
As a result, in the untreated group, almost the same change in conductivity was observed during the test period. In the control group, the transition was similar to that at the time of grouping on the 15th day from the start of the test. However, after the SDS application (on the 19th day from the start of the test), a significant decrease in conductivity was observed compared to the untreated group, and the dryness The production of the skin was confirmed.
In the group to which the glucosamine hydrochloride and glucuronic acid amide mixture was administered, a decrease in electrical conductivity was suppressed as compared with the control group, and an inhibitory effect on dry skin was observed.
The transition of AUC is shown in FIG.

Test example 2

A test similar to Test Example 1 was conducted except that glucosamine hydrochloride alone and a mixture of glucosamine hydrochloride and glucuronolactone were used as test substances, and then the amount of hyaluronic acid in the stratum corneum of the skin was measured. The test guinea pigs were grouped as shown in the group composition table of Table 2.

After completion of the test, the abdominal skin of the guinea pig was peeled off, and the peeled skin was heated to separate only into the stratum corneum. Protease etc. was added to this stratum corneum to decompose protein and extract hyaluronic acid (Shingo Sakai, Rie Yasuda, Tetsuya Sayo, Osamu Ishikawa and Shintaro Inoue. Hyaluronan Exists in the Normal Stratum Corneum, J. Invest Dermatol. 2000 114 (6): 1184-7). The extracted hyaluronic acid was measured with a hyaluronic acid measurement kit (Seikagaku Corporation).
The results are shown in Table 3 and FIG. In the group to which a mixture of glucosamine hydrochloride and glucuronolactone was administered, the amount of hyaluronic acid in the stratum corneum increased compared with the control group and the group to which glucosamine hydrochloride was administered alone, and an inhibitory effect on skin dryness was observed.

Riboflavin 300 g, pyridoxine hydrochloride 1000 g, L-cysteine 600 g, ascorbic acid 1500 g, glucosamine hydrochloride 4000 g, glucuronic acid amide 4000 g, and crystalline cellulose 1000 g in a fluidized bed granulator (FD-5S, Paulek) with 6% hydroxypropyl methylcellulose (FD HPC-L) Fluidized bed granulation is performed by spraying 8330 g of aqueous solution. Thereafter, the particles are sized by a sizing machine (Power Mill, Showa Chemical Machinery) to obtain a sized powder.
The resulting granulated powder, 700 g of low-substituted hydroxypropyl cellulose, and 1000 g of vegetable magnesium stearate (Taihei Chemical) are mixed in a mixer (tumbler mixer, Showa Chemical), and the resulting mixed powder is a rotary tablet press. And tablets with a mortar with a diameter of 9.0 mm and an R facet with a curvature medium diameter of 7.0 mm so that the weight per tablet is 300 mg and the thickness is 6.1 mm to obtain an uncoated tablet.
Using a Doria coater (DRC-500, Paulek) on the resulting uncoated tablet 3000 g, a 10% aqueous solution in which 120 g of hydroxypropylmethylcellulose 2910 (TC-5TW) and 20 g of talc are dissolved in purified water is coated on the uncoated tablet. 614 mg / tablet undercoated tablets are obtained. Furthermore, the undercoated tablet was coated with 36% aqueous solution in which 1210 g of erythritol, 600 g of talc, 45 g of titanium oxide, 115 g of crystalline cellulose, and 276 g of gum arabic powder were dissolved and suspended in purified water. obtain. Further, the build-up coated tablet is coated with a 36% aqueous solution in which 270 g of erythritol and 30 g of polyethylene glycol 6000 are dissolved in purified water to obtain a 435 mg / tablet syrup-coated tablet. The resulting syrup-coated tablet is polished with a small amount of wax or the like.

  As described above, according to the present invention, it is possible to provide a pharmaceutical composition for preventing and / or treating skin irritation that suppresses a decrease in the amount of water contained in the skin and exhibits an excellent skin irritation improving effect by internal use. .

6 is a graph showing transition of AUC in Test Example 1. 6 is a graph showing the amount of hyaluronic acid in the stratum corneum of skin in Test Example 2.

Claims (4)

  A pharmaceutical composition for preventing and / or treating skin irritation by internal use, comprising glucosamine hydrochloride and glucuronic acid.   The pharmaceutical composition according to claim 1, wherein the weight ratio of glucosamine hydrochloride: glucuronic acid is in a ratio of 1: 0.5-2. Furthermore, the pharmaceutical composition according to claim 1, further comprising at least one selected from vitamin B ₂ acids and vitamin B ₆ compound. The pharmaceutical composition according to claim 1, further comprising (a) at least one selected from vitamin B ₂ and vitamin B ₆ and (b) vitamin C.

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