JP2010174049A - Skin whitening agent and vitamin mixed composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a skin whitening agent comprising as an effective ingredient, at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinic-acid amide and calcium pantothenate, and to provide a vitamin blend composition containing three or more selected from the group above and having a skin whitening action. <P>SOLUTION: There is provided a skin whitening agent comprising as an effective ingredient, at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinic-acid amide and calcium pantothenate. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention is characterized by containing a whitening agent containing as an active ingredient at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate, and at least three selected from the group consisting thereof. Relates to a vitamin mixture composition.

  Many people suffer from spots and freckles from a cosmetic point of view. It is said that skin aging such as spots, buckwheat or kusumi or wrinkles is greatly influenced by ultraviolet irradiation, oxidative stimulation, hormonal abnormalities, genetic factors, etc. It is considered. When exposed to ultraviolet rays on the skin surface, free radicals (active oxygen) are generated in the tissue, and when this active oxygen causes cell damage or inflammation, pigmentation occurs via an inflammatory chemical mediator. It is said to provoke.

  It is also known that secretion of a plurality of melanocyte activators such as melanocyte stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH) is promoted by the influence of ultraviolet irradiation and the like, and pigmentation is induced.

  In addition, it is known that stress that continues to increase in modern society also promotes the secretion of multiple melanocyte activators such as melanocyte stimulating hormone (α-MSH) and adrenocorticotropic hormone (ACTH), and induces pigmentation. When exposed to ultraviolet rays in a stress environment, pigmentation becomes remarkably strong, and intractable spots and freckles tend to occur.

  On the other hand, the formation of pigmentation is originally considered as one of the biological defense reactions. That is, melanin pigments are produced in melanin-producing granules called melanosomes in pigment cells (melanocytes) present in epidermal cells in order to protect DNA, which is genetic information, from ultraviolet irradiation and the like on skin surface cells. The melanin pigment produced in this way diffuses to neighboring cells and accumulates in keratinocytes of epidermal cells, and it is thought that keratinocytes usually become the stratum corneum due to metabolism of the skin and eventually fall off the skin, but more than necessary. When excessive melanin pigment is produced, it is considered that it deposits in the epidermis or dermis layer, and as a result, remains as a spot.

  The above melanin pigments can be broadly divided into two types: dark eumelanin and light pheomelanin, both of which contribute to the protection of ultraviolet rays and that melanin synthesis is activated when irradiated with ultraviolet rays. It has been.

  On the other hand, wrinkles are a typical change in skin aging along with stains. The histological changes of the skin with aging are greatly different between the sun-exposed part and the covering part, and are distinguished from photoaging and physiological aging, respectively. In particular, wrinkles on the face are a cosmetic problem, and here, photoaging is significant in addition to physiological aging. This photoaging is considered to be mainly caused by free radicals such as active oxygen generated by ultraviolet rays and the like, and as oxidation disorders by ultraviolet rays, lipid peroxidation, DNA damage, protein denaturation, metabolic abnormalities and the like occur. They are thought to cause acute and chronic inflammation and degeneration of the dermal extracellular matrix, leading to photoaging.

  Degeneration of the dermal extracellular matrix is mainly due to decomposition and fragmentation of the fiber structure of active oxygen and free radicals, and the aging cross-linking of collagen fibers is promoted by active oxygen. It is considered that the elastic fiber is denatured in this way and causes wrinkles.

  Conventionally, various methods have been studied for the purpose of preventing the generation of such spots and wrinkles.

  One of them is a method of suppressing melanin pigment production itself by eliminating free radicals generated by ultraviolet irradiation and inhibiting tyrosinase, an enzyme involved in melanin pigment production.

  Examples of the compound having the above-mentioned action include vitamin C and vitamin E having an antioxidant action, and vitamin C has been used mainly for oral administration as the only pharmaceutical ingredient since ancient times. Moreover, the following contents are known as matters related to vitamins and pigmentation other than the above.

  That is, riboflavin is important as a coenzyme for glutathione reductase, and may suppress the production of lipid peroxide and may act as a free radical scavenger (see, for example, Non-Patent Document 1). It is known that irradiation with ultraviolet rays after local injection of riboflavin is effective in treating blue nevus (see, for example, Non-Patent Document 2).

  Nicotinamide is known to prevent pigmentation by inhibiting melanin transfer from pigment cells to epidermal cells (see, for example, Non-Patent Document 3).

  Calcium pantothenate alone has no effect on pigmentation after ultraviolet irradiation, but is known to have a pigmentation-preventing effect when used in combination with vitamin C (see, for example, Non-Patent Document 4).

  Other than the above, external whitening agents are mainly used. Specifically, hydroquinone derivatives that suppress melanin pigment production itself (for example, see Patent Document 1), ellagic acid (for example, see Non-Patent Document 5) that is expected to have a whitening effect due to tyrosinase inhibition, kojic acid (for example, Patent Documents 2 and 3), arbutin (for example, refer to Patent Document 4) and the like have already been proposed. As described above, melanin pigments are important substances in UV protection, and these components are melanin pigments. Since production itself is suppressed, it is not always preferable.

  However, in both of the above publications and literatures, it is said that at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate efficiently suppresses activation of melanocytes and has a whitening action. There is no disclosure or suggestion. Further, there is no disclosure or suggestion that a vitamin mixture composition containing three or more selected from the group consisting of these has a whitening action more effectively.

Japanese Patent Laid-Open No. 63-246311 Japanese Patent Publication No.32-8100 JP-A-1-275524 JP 63-8314 A Encyclopedia of Food, Asakura Shoten, 2001 Kenji Sato et al. Dermatologic Science, 23, 22 pages, 2000 T.A. Hakozaki et al., British J. et al. Dermatology, 147, 20, p. 2002 Kazuo Aso et al., Nishinichi Skin, 42, 885, 1980 Shinichi Tachibana et al., Fragrance J, Vol. 9, p. 37, 1997

  An object of the present invention is a whitening agent having an excellent whitening action and having one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate as an active ingredient, and a group consisting of these 3 It is in providing the vitamin-mixing composition characterized by containing the seed | species or more.

  According to the study by the present inventors, one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate has surprisingly found an excellent whitening action, and is selected from the group consisting of these 3 The present invention has been completed by finding that a vitamin mixture composition comprising a combination of more than one species has a further excellent whitening effect.

That is, the present invention contains a whitening agent containing one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate as an active ingredient, and three or more selected from the group consisting thereof. It is a vitamin mixture composition characterized.
Preferably, it is a whitening agent containing two or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate, more preferably riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate. A whitening agent containing three or more selected from the group consisting of active ingredients, and most preferably a whitening agent containing riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate as active ingredients.
The present invention also relates to a vitamin mixture composition comprising three or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate.

  The whitening agent comprising one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate of the present invention as an active ingredient exhibits an excellent whitening action, and three or more selected from the group consisting of these The vitamin mixture composition combined with the above showed an excellent whitening effect, and also showed an excellent whitening effect even in a stress environment where pigmentation worsens. Therefore, it is suggested that the whitening agent and vitamin mixture composition of the present invention prevents pigmentation and suppresses deterioration of stains and buckwheat by ultraviolet rays, and is useful as a whitening agent.

  Hereinafter, the present invention will be described in detail.

  Examples of the riboflavin used in the present invention include those described in the 14th revised Japanese Pharmacopoeia (issued by Jiho Co., Ltd., 2001, hereinafter abbreviated as “Pharmacopeia”), pages 749-750.

  Examples of the pyridoxine hydrochloride used in the present invention include those described in Pharmacopeia, page 361.

  Examples of nicotinamide used in the present invention include those described in the Japanese Pharmacopoeia, page 588.

  Examples of the calcium pantothenate used in the present invention include those described in the Japanese Pharmacopoeia, pages 615-616.

  The whitening agent and vitamin mixture composition of the present invention is not particularly limited to solid agents, semi-solid agents, liquid agents, etc., and specifically, tablets, fine granules, granules, powders, capsules, chewable agents , Foods and pharmaceuticals in the form of foaming agents, dry syrups, jelly agents, jelly drop agents, liquid agents and the like.

  The whitening agent and vitamin mixture composition of the present invention can be used as it is by mixing one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate. As the components, those used in ordinary foods and pharmaceuticals can be used. For example, it can be produced by adding an excipient such as crystalline cellulose, sucrose fatty acid ester, sucrose and the like, and granulating it by, for example, dry granulation tableting method or wet granulation tableting method.

  Ordinarily, wetting agents, emulsifiers, dispersion aids, surfactants, sweeteners, acidulants, sugar alcohols, flavors, fragrances, and other excipients used in liquid foods and pharmaceuticals are added to dissolve and liquid It can also be manufactured as a state.

  A whitening agent containing at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinic acid amide and calcium pantothenate according to the present invention, and 3 or more selected from the group consisting of these. The proportion of each active ingredient in the composition varies slightly depending on the type used, but riboflavin is 0.4 to 30 parts by weight, preferably 2 to 30 parts by weight, and pyridoxine hydrochloride is 0 per 1000 parts by weight of the total composition. 0.5-100 parts by weight, preferably 5-100 parts by weight, nicotinamide 2-60 parts by weight, preferably 12-60 parts by weight and calcium pantothenate 5-30 parts by weight, preferably 5-15 parts by weight It is. If it is used within this range, it exhibits an excellent whitening effect and is also effective in terms of cost.

  More specifically, the daily dose is appropriately mixed so as to be 0.4 to 30 mg of riboflavin, 0.5 to 100 mg of pyridoxine hydrochloride, 2 to 60 mg of nicotinamide, and 5 to 30 mg of calcium pantothenate.

The whitening agent and vitamin-mixed composition of the present invention include ascorbic acid, kojic acid, arbutin, placental extract, vitamin E, cysteine, glutathione, etc. used in ordinary pharmaceuticals and foods and drinks in addition to the above-mentioned compounds as essential components Known whitening agents, vitamin B ₁ , vitamin D, amino acids, peptides, proteins and the like can be blended.

  The whitening agent and vitamin mixture composition of the present invention is orally administered as a whitening agent, usually divided into 1 to 3 times per day for an adult.

  Hereinafter, the present invention will be described in detail with reference to test examples. Commercially available riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate were used.

[Test example]
Test Example 1 (Inhibition test of melanocyte proliferation activation after UV irradiation)
(1) Test method Six DBA / 2NCrj mice (male, 6 weeks old) were used as one group. Measure your weight
The test substances shown in Table 1 were dissolved in 1% lecithin and used. Five groups of DBA / 2NCrj mice were administered test samples 1a-1d and control sample 1 respectively directly into the stomach with a sonde. Thereafter, 1 hour after administration, medium wavelength ultraviolet rays were irradiated for 5 minutes at 0.09 J / cm ² using a medical ultraviolet irradiation device Dermaray (manufactured by Clinical Supply). Test sample administration and irradiation were performed once a day for 9 days. Next, on the 10th day, both ears of DBA / 2NCrj mice were collected, placed so that the outer skin was on top, and the skin was collected with a 6 mm trepan from each of the left and right ears. Thereafter, the outer skin was collected, and dopa-positive melanocytes, which are indicators of melanocytes producing melanin pigments, were stained according to a standard method. The number of melanocytes was counted under a microscope, and the number of melanocytes per mm ² was measured. . Note that one group of DBA / 2NCrj mice was not irradiated with medium wavelength ultraviolet light, and was similarly tested (referred to as non-irradiated administration group).

(2) Assay method The results were determined by comparing the number of dopa-positive melanocytes in the control sample administration group 1 and the test sample administration groups 1a to 1d of the present invention. In addition, Dunnett's test was used for the significant difference test.
(3) Test results The results are shown in Table 2. As is apparent from Table 2, riboflavin, pyridoxine hydrochloride, calcium pantothenate and nicotinamide significantly suppress the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation, and the whitening agent of the present invention is effective in preventing pigmentation. It was shown that.

Test Example 2 (Test for inhibiting melanocyte proliferation activation after UV irradiation)
(1) Test method Tests were conducted in the same manner as in Test Example 1 except that the test substances shown in Table 3 were used.

(2) Test method The same method as in Test Example 1 was used.

(3) Test results Table 4 shows the results. As is apparent from Table 4, the vitamin mixture composition of the present invention significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation. Moreover, compared with vitamin C and vitamin E of reference samples 2a to 2c, the vitamin mixed composition of the present invention significantly suppressed an increase in the number of dopa-positive melanocytes due to ultraviolet irradiation.

Test Example 3 (Test for inhibiting melanocyte proliferation activation after UV irradiation)
(1) Test method The test was performed in the same manner as in Test Example 1 except that the test substances shown in Table 5 were used.

(2) Test method The same method as in Test Example 1 was used.
(3) Test results Table 6 shows the results. As is apparent from Table 6, the vitamin mixture composition of the present invention significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation.

In addition, the suppression rate was calculated | required from the following formula.

Inhibition rate (%) = {(control group−stress group) − (each sample group−stress group)} / (control group−stress group) × 100

Test Example 3 (Inhibition test for activation of melanocyte proliferation after irradiation with ultraviolet light in a stress environment)
(1) Test method Six DBA / 2NCrj mice (male, 6 weeks old) were used as a group and reared in a normal environment and in an overstressed stress environment. That is, the non-irradiated administration group (non-ultraviolet irradiation) and the ultraviolet irradiation group (only ultraviolet irradiation) are reared in a normal cage (30 × 20 × 12 cm), and the stress group (overcrowded stress environment only) and ultraviolet irradiation under stress. The group (subject group; ultraviolet irradiation in an overcrowded stress environment rearing) and the test sample administration group were reared in an overstressed stress cage (14 × 7 × 8 cm). In the test, the test substances shown in Table 7 were dissolved in 0.5% carmellose sodium and used. Eight groups of DBA / 2NCrj mice were administered test samples 4a and 4b, reference sample 4 and control sample 4 respectively directly into the stomach with a sonde. Thereafter, 1 hour after administration, medium wavelength ultraviolet rays were irradiated for 5 minutes at 0.045 J / cm ² using a medical ultraviolet irradiation device Dermaray (manufactured by Clinical Supply). DBA / 2NCrj mice reared in an overstressed stress environment were usually caged during UV irradiation. Test sample administration and irradiation were performed once a day for 9 days. DBA / 2NCrj mice were anesthetized with diethyl ether within 5-30 minutes of irradiation on the 9th day, and after collecting blood, both ears were collected and placed so that the outer skin was on top. The skin was collected with a trepan. Thereafter, the outer skin was collected, and dopa-positive melanocytes, which are indicators of melanocytes producing melanin pigments, were stained according to a standard method. The number of melanocytes was counted under a microscope, and the number of melanocytes per mm ² was measured. . In addition, a group of DBA / 2NCrj mice were not irradiated with medium wavelength ultraviolet rays, and the same experiment was conducted. For the collected blood serum, the ACTH concentration in the serum was measured by the ELISA method of MD Bioscience kit.

(2) Assay method The results were determined by comparing the number of dopa-positive melanocytes in the control group, the test sample 4a and 4b administration group of the present invention, and the reference sample 4 administration group. In addition, Dunnett's test was used for the significant difference test.

(3) Test results The results of the number of dopa-positive melanocytes are shown in Table 8, and the ACTH concentration is shown in Table 9. As is apparent from Table 8, the vitamin mixture composition of the present invention significantly suppressed the increase in the number of dopa-positive melanocytes by ultraviolet irradiation under a stress environment. In addition, the composition of the present invention was effective at a low dose as compared with vitamin C as a reference sample, and significantly suppressed the increase in the number of dopa-positive melanocytes due to ultraviolet irradiation. Further, as is apparent from Table 9, it is clear that the composition of the present invention significantly suppresses ACTH that is significantly increased by ultraviolet irradiation under a stress environment, and the composition of the present invention is pigmented. It was suggested that there is a possibility of preventing the deterioration of spots and freckles due to ultraviolet rays.

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

Example 1 (tablets)
(Prescription)
Riboflavin 0.8g
1.0 g of pyridoxine hydrochloride
Nicotinamide 2.0g
Crystalline cellulose 80.0g
6.0g silicon dioxide
Sorbitol 198.2g
Sucrose fatty acid ester 12.0 g
――――――――――――――――――――――――――――――
Total 300.0g

(Production method)
The above ingredients were mixed, and the mixture was tableted into 300 mg tablets with a tableting machine, and each tablet contained 0.8 mg riboflavin, 1.0 mg pyridoxine hydrochloride, and 2.0 mg nicotinamide amide. Get.

Example 2 (tablets)
A tablet of Example 2 is obtained in the same manner as in Example 1 except that 0.8 g of riboflavin and 198.2 g of sorbitol are replaced with 3.2 g of calcium pantothenate and 195.8 g of sorbitol.

Example 3 (tablets)
A tablet of Example 3 is obtained in the same manner as in Example 1 except that 1.0 g of pyridoxine hydrochloride and 198.2 g of sorbitol are replaced with 3.2 g of calcium pantothenate and 196.0 g of sorbitol.

Example 4 (tablets)
The tablets of Example 4 are obtained in the same manner as in Example 1 except that 2.0 g of nicotinamide and 198.2 g of sorbitol are replaced with 3.2 g of calcium pantothenate and 197.0 g of sorbitol.

Example 5 (tablets)
A tablet of Example 5 is obtained in the same manner as in Example 1 except that 198.2 g of sorbitol is replaced with 3.2 g of calcium pantothenate and 195.0 g of sorbitol.

Example 6 (Liquid)
(Prescription)
Riboflavin 1g
5g pyridoxine hydrochloride
Nicotinamide 5g
Citric acid 28g
Malic acid 20g
5g sucralose
Fragrance 10g
Purified water appropriate amount ――――――――――――――――――――――――――――――
Total amount 15kg

(Production method)
Add each of the above components from riboflavin to sucralose and dissolve with heating. After cooling, add fragrance and purified water to a total volume of 15 kg. 100 mL of this solution is dispensed into a container, and the liquid agent of Example 6 is obtained.

Example 7 (Liquid)
A liquid preparation of Example 7 is obtained in the same manner as in Example 6 except that 1 g of riboflavin is replaced with 5 g of calcium pantothenate.

Example 8 (Liquid)
A solution of Example 8 is obtained in the same manner as in Example 6 except that 5 g of pyridoxine hydrochloride is replaced with 5 g of calcium pantothenate.

Example 9 (Liquid)
A liquid preparation of Example 9 is obtained in the same manner as in Example 6 except that 5 g of nicotinic acid amide is replaced with 5 g of calcium pantothenate.

Example 10 (Liquid)
A liquid preparation of Example 10 is obtained in the same manner as in Example 6 except that 5 g of calcium pantothenate is added.

Example 11 (tablets)
A tablet of Example 11 is obtained in the same manner as in Example 1 except that 198.2 g of sorbitol is replaced with 10.0 g of rose petal extract and 188.2 g of sorbitol.

Example 12 (Liquid)
A liquid preparation of Example 12 is obtained in the same manner as in Example 6 except that 5 g of rose petal extract is added.

The whitening agent comprising at least one selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate according to the present invention exhibits an excellent whitening action. A vitamin mixed composition characterized by comprising three or more selected from the group consisting of them exhibits a further excellent whitening effect. Furthermore, the vitamin mixture composition of the present invention clearly has an action of suppressing the secretion of ACTH that increases due to stress, and exhibits an excellent effect on pigmentation that deteriorates due to various stresses received in daily life. It can also be expected to have stubborn stains and freckles.

Claims (1)

A pharmaceutical internal use whitening agent comprising only one or more selected from the group consisting of riboflavin, pyridoxine hydrochloride, nicotinamide and calcium pantothenate as an active ingredient.