JP6757130B2 - A composition having an azulene compound, and a discoloration inhibitor and a discoloration prevention method for the azulene compound. - Google Patents

Description

The present invention relates to a compound having an azulene structure, a compound having a hesperidin structure, and a composition containing one or more selected from basic amino acids, and more specifically, a compound having a hesperidin structure or basicity. The present invention relates to a composition and a method for preventing discoloration of a compound having an azulene structure due to an amino acid.

Compounds having an azulene structure are drugs that have anti-inflammatory and anti-allergic effects by suppressing the release of histamine by mast cells, and are widely used for therapeutic and preventive purposes in various medical fields. However, a compound having an azulene structure is gradually decomposed by light to cause discoloration such as fading and hue change, so that there is a problem that the color tone of the product is changed and the medicinal effect is deteriorated.

Generally, chemicals that are unstable to light are shielded from light by the packaging material to be stored, or by using pigment or aluminum as the material of the container, but in the former, the user does not use the packaging material after purchasing the product. There are various problems such as the possibility of being exposed to light and the latter, which makes it impossible to perform a foreign matter contamination test after the filling process. Therefore, it is possible to prepare a compound having a more azulene structure with higher stability. is important.

Therefore, as a method for improving the stability of a compound having an azulene structure that is unstable to light from the aspect of formulation, a composition containing an azulene derivative and xanthins and stabilizing the azulene derivative (see, for example, Patent Document 1). ), Azulene containing velverin, polyvinylpyrrolidone, and chondroitins to improve the long-term stability of azulene (see, for example, Patent Document 2), and azulene derivatives containing organic acids and amino acids as pH buffers. There are aqueous liquids (see, for example, Patent Document 3) which are contained to enhance the stability of the azulene derivative to light.

Japanese Unexamined Patent Publication No. 2003-128537 Japanese Unexamined Patent Publication No. 2005-298364 Japanese Unexamined Patent Publication No. 2005-298452

However, all of these methods have problems such as expensive stabilizers, insufficient stabilizing effect, and restrictions on the dosage form.

Therefore, an object to be solved by the present invention is to provide a composition or method for preventing discoloration of a compound having an azulene structure known to be useful for flame extinguishing or the like and enhancing stability.

In view of such circumstances, the present inventors have diligently studied to solve the above problems, and as a result, by combining a compound having an azulene structure, a compound having a hesperidin structure, or one or more selected from basic amino acids. , It has been found that a compound having an azulene structure exerts a remarkable effect on prevention and stabilization of discoloration due to light, that is, the anti-inflammatory effect of a compound having an azulene structure can be dramatically enhanced, and the present invention is completed. It came to.

That is, the present invention has the following components (A) and (B);
(A) A compound having an azulene structure (B) A composition containing one or more selected from a compound having a hesperidin structure and a basic amino acid.

The present composition provides the above-mentioned composition in which the basic amino acid of the component (B) is one or two selected from arginine and histidine.

The composition provides the above-mentioned composition in which the component (B) is a compound having a hesperidin structure and a basic amino acid.

The present invention provides a discoloration inhibitor of a compound having an azulene structure, which comprises one or more selected from a compound having a hesperidin structure and a basic amino acid as an active ingredient.

The present invention provides a method for preventing discoloration of a compound having an azulene structure by adding one or more selected from a compound having a hesperidin structure and a basic amino acid to a composition containing a compound having an azulene structure.

The composition, discoloration inhibitor, and discoloration prevention method of the present invention can effectively exert the effect of the compound having an azulene structure by improving the stability of the compound having an azulene structure.

It is a figure which shows the absorbance at 568 nm of the product of this invention and the comparative product. It is a figure which shows the absorbance at 568 nm of the product of this invention and the comparative product.

The component (A) compound having an azulene structure in the composition of the present invention (hereinafter, may be referred to as “azulene compound”) is a component having an azulene structure in the molecule. Examples of such compounds include azulene, guaiazulene, kamaazulene, azulene sulfonic acid, guaiazulene sulfonic acid, kamaazulene sulfonic acid, azulenecarboxylic acid, guaiazulenecarboxylic acid, kamaazulenecarboxylic acid and salts and hydrates thereof. Can be mentioned. Examples of the salt include sodium, potassium, monoethanolamine, diethanolamine, triethanolamine and the like. Among these components (A), a compound having a guaiazulene structure is preferable from the viewpoint of medicinal effect, color development and the like, and guaiazulene sulfonate is preferable from the viewpoint of solubility in water. As the component (A), one kind or two or more kinds can be used.

The content of the component (A) in the composition of the present invention is not particularly limited and varies depending on the type of azulene compound used and the like, but is preferably 0.0001 to 5% by mass (hereinafter, simply represented by "%"). , 0.001 to 0.5% is more preferable.

The component (A) azulene compound has a peculiar light absorption near 568 nm, and has a property that the light absorption around a wavelength of 568 nm is reduced when the azulene compound is decomposed or the like. Utilizing this property, the azulene compound is irradiated with light such as sunlight or a fluorescent lamp, and the light absorption near the wavelength of 568 nm is measured to calculate the residual amount and residual rate of the azulene compound and evaluate the stability. be able to.

The component (B) in the composition of the present invention is one or more selected from compounds having a hesperidin structure and basic amino acids. The compound having a hesperidin structure of the component (B) (hereinafter, may be referred to as “hesperidin compound”) is a component having a hesperidin structure in the molecule. Hesperidin, also called vitamin P, is a flavanone glycoside that is abundantly contained in the pericarp and thin skin of Satsuma mandarin, Hassaku, and Daidai, and is the main component of chenpi.

The hesperidin compound of the component (B) in the composition of the present invention is, for example, hesperidin, methyl hesperidin, epid. Hesperidin and the like can be mentioned. Among these hesperidin compounds, glucosyl hesperidin is preferable from the viewpoint of stability of the component (A) and the like.

The basic amino acid of the component (B) in the composition of the present invention is an amino acid having two or more amino groups in the molecule. The component (B) is preferably one or more selected from arginine, histidine, lysine, ornithine and tryptophan, and more preferably two or more. Among the basic amino acids, it is preferable to use arginine and histidine from the viewpoint of the stability of the component (A), and it is more preferable to use these in combination.

Further, it is preferable to use a hesperidin compound and a basic amino acid in combination as the component (B), and even in this case, it is more preferable to use two or more kinds of basic amino acids. For example, a combination of glucosyl hesperidin and arginine, a combination of histidine, and the like can be mentioned.

The content of the component (B) in the composition of the present invention is not particularly limited and varies depending on the dosage form, purpose of use, etc., but from the viewpoint of the stability of the component (A), it is 0.0001 to 5%. It is preferably 0.001 to 0.1%.

The content mass ratio of the component (A) to the component (B) in the composition of the present invention is not particularly limited, but from the viewpoint of the stability of the component (A), 30: 1 to 1:30 is preferable, and 10: 1 to 10: 1 1:10 is more preferable.

The pH of the composition of the present invention is not particularly limited, but from the viewpoint of the stability of the component (A), pH = 6.0 to 8.0 is preferable, and pH = 6.0 to 7.5 is more preferable. , PH = 7.0 is most preferable.

In addition to the above-mentioned ingredients, the composition of the present invention includes cosmetics, external skin preparations, foods, inks, detergents, soft finishes for clothing, air fresheners, as long as the effects of the present invention are not impaired. Ingredients used in preparations such as deodorants and textiles, that is, water (purified water, hot spring water, deep water, etc.), oils, surfactants, metal chelate, gelling agents, powders, alcohols, water-soluble Polymers, film-forming agents, resins, UV protective agents, inclusion compounds, antibacterial agents, fragrances, deodorants, salts, pH adjusters, refreshing agents, animal / microorganism-derived extracts, plant extracts, blood circulation promoters, Astringents, anti-fat leaks, whitening agents, anti-inflammatory agents, active oxygen scavengers, cell activators, moisturizers, chelating agents, keratolytic agents, enzymes, hormones, vitamins and the like can be added.

The method for producing the composition of the present invention is not particularly limited, and is prepared by a conventional method. For example, a method of preparing by adding the above-mentioned components (A) and (B) and, if necessary, the above-mentioned optional component and mixing them can be mentioned.

The composition of the present invention can be carried out in various forms such as liquid, gel, cream, solid, powder, and mousse, and is contained in a nebulosus-sprayable container and atomized. You may use it by spraying on. The dosage form of the product of the present invention is not particularly limited, such as solubilized type, oil-in-water type, water-in-oil type, oil-based type, water-in-oil-in-water type, oil-in-oil-in-oil type, and multi-layer type.

The use of the composition of the present invention is not particularly limited, and is used as a composition for various purposes such as cosmetics, external preparations for skin, foods, inks, detergents, soft finishes for clothing, air fresheners, deodorants, and textiles. be able to. The azulene compound is characterized by having an excellent anti-inflammatory effect and the like, and from that viewpoint, it is preferably used as a cosmetic or an external preparation for skin.

Examples of the cosmetics of the present invention are not particularly limited, and for example, skin care cosmetics such as milky lotion, cream, lotion, beauty liquid, pack, etc., foundation, lipstick, lipstick, eye color, mascara, eyeliner, manicure, etc. It may be in any form such as make-up cosmetics, hair-nourishing agents, hair tonics, shampoos, rinses, hair-wax and other hair cosmetics, facial wash pigments, body soap and other cleaning agents, and the like.

The example of the external preparation for skin of the present invention is not particularly limited, and may be in any form such as an external gel, a cream, an ointment, a liquid, a liniment, and a happ.

Examples of the food (including animal feed) of the present invention include frozen foods, powdered foods, sheet foods, bottled foods, canned foods, retort foods, capsule foods, tablet foods, and the like, as well as proteins, for example. It may be in any form such as a naturally liquid food containing sugars, fats, trace elements, vitamins, emulsifiers, fragrances and the like, a semi-digested nutritional food and a component nutritional food, and a processed form such as a drink.

Further, the discoloration inhibitor of the present invention is an azulene compound discoloration inhibitor containing one or more selected from hesperidin compounds and basic amino acids as active ingredients. Further, the discoloration prevention method of the present invention is a discoloration prevention method for a compound having an azulene structure, in which one or more selected from a hesperidin compound and a basic amino acid is added to a composition containing an azulene compound.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the scope of the present invention is not limited thereto.

<Azulene compound discoloration prevention effect (stabilization effect) test>
Sodium guaizulene sulfonate has light absorption peculiar to a wavelength of 568 nm, and when decomposition of sodium guaiazulene sulfonate occurs, the light absorption at a wavelength of 568 nm is reduced, and the following procedure is followed. The residual amount of sodium guaizulene sulfonate was measured and the stability was evaluated.

Example 1 <pH study>

As a sample, as shown in Table 1, an aqueous solution containing 0.03% of sodium guaiazulene sulfonate and 0.01% of one or more selected from α-monoglucosyl hesperidin and L-arginine. Prepared by a conventional method. Each solution was prepared at each pH using disodium monohydrogen phosphate and monosodium dihydrogen phosphate. Each of these sample solutions was dispensed into a glass No. 5 standard bottle, irradiated with sunlight by the window for 3 days, and then the absorbance at 568 nm was measured, and the results are shown in Table 1.

As is clear from Table 1, the product of the present invention had a higher absorbance at 568 nm at each pH than the comparative product, and was excellent in the discoloration preventing effect of sodium guaiazulene sulfonate. Further, the discoloration preventing effect of sodium guaiazulene sulfonate was excellent at any of pH = 6.0 to 7.5, and among them, pH = 7.0 was the most excellent discoloring preventing effect of sodium guaiazulene sulfonate.

Example 2 <Examination of various drugs>

As a sample, as shown in Table 2, 0.03% of sodium guaizulene sulfonate is contained, D-panthenol, dipotassium glycyrrhizinate, ascorbic acid glucoside, nicotinamide, α-monoglucosyl hesperidin, L as antioxidants. An aqueous solution containing 0.01% of any of -arginine, L-histidine, glycylglycine, and phenylbenzmidazolesulfonic acid (manufactured by Merck, "EUSOLEX232") as an ultraviolet absorber was prepared by a conventional method. Each solution was adjusted to pH 7.0 using disodium monohydrogen phosphate and monosodium dihydrogen phosphate. Each of these sample solutions was dispensed into a glass No. 5 standard bottle, irradiated with sunlight by the window for 3 days, and then the absorbance at 568 nm was measured, and the results are shown in Table 2 and FIG.

As is clear from Table 2 and FIG. 1, the product of the present invention had a higher absorbance at 568 nm than the comparative product, and was excellent in the discoloration preventing effect of sodium guaiazulene sulfonate. On the other hand, the comparative products using antioxidants, ultraviolet absorbers, non-basic amino acids and the like all had low absorbance at 568 nm and were inferior in the discoloration preventing effect of sodium guaiazulene sulfonate.

Example 3 <Examination of effect by combined use of various discoloration inhibitors>

The effects of the hesperidin compound and the basic amino acid, which were found to have the effect of suppressing discoloration of azulene in Example 2, were examined in combination.

As a sample, as shown in Table 3, an aqueous solution containing 0.03% of sodium guaiazulene sulfonate and containing two or more kinds of α-monoglucosyl hesperidin, L-arginine, and L-histidine was prepared by a conventional method. In each case, the amount of the discoloration inhibitor added was adjusted to be 0.01% as the total amount of the discoloration inhibitor. Each solution was adjusted to pH 7.0 using disodium monohydrogen phosphate and monosodium dihydrogen phosphate. Each of these sample solutions was dispensed into a glass No. 5 standard bottle, irradiated with sunlight by the window for 3 days, and then the absorbance at 568 nm was measured, and the results are shown in Table 3 and FIG. Note that FIG. 2 also shows the above-mentioned products 4 to 6 of the present invention, the comparative product 2, and the control product 2.

As is clear from Table 3 and FIG. 2, the products 7 to 10 of the present invention containing two or more kinds of α-monoglucosyl hesperidin and basic amino acids have an absorbance of 568 nm more than that of the products 4 to 6 of the present invention containing one kind. It was high and was excellent in the discoloration prevention effect of sodium guaiazulene sulfonate. From this, it was confirmed that the discoloration prevention effect of sodium guaiazulene sulfonate was further excellent by using two or more kinds of α-monoglucosyl hesperidin and basic amino acids in combination.

Example 4 [Toner]
(Ingredient) (%)
1. 1. Glycerin 5.0
2.1,3-butylene glycol 5.0
3. 3. Glucosyl trehalose 3.0
4. Lactic acid 0.05
5. Sodium lactate 0.1
6. Polyoxyethylene monooleate (20 mol) sorbitan 1.2
7. Ethanol 8.0
8. Trimethylolpropane triisostearate (Note 1) 0.5
9. Methyl paraoxybenzoate 0.1
10. Fragrance 0.05
11. Residual amount of purified water 12. Guaiazulene Sodium Sulfonate 0.04
13. α-monoglucosyl hesperidin 0.02
14. L-histidine 0.02
15. L-Arginine 0.02
(Note 1) Sarakos 6318V (manufactured by Nisshin Oillio)

(Production method)
A: Ingredients 6 to 11 are mixed and dissolved.
B: Components 1 to 5 and 12 are mixed and dissolved.
C: Add A to B and mix.
D: 13 to 15 were added and mixed uniformly to obtain a lotion.

The lotion of Example 4 was a lotion having an excellent effect of preventing discoloration of sodium guaiazulene sulfonate.

Example 5 [milky lotion]
(Ingredient) (%)
1. 1. Polyoxyethylene monostearate (20 mol) sorbitan 1.0
2. 2. Polyoxyethylene trioleate (20 mol) sorbitan 0.5
3. 3. Glyceryl monostearate 1.0
4. Trimethylolpropane tristearate (Note 1) 5.0
5. Stearic acid 0.5
6. Behenyl alcohol 0.5
7. Squalene 4.0
8. Ceramide 2 0.01
9. Carboxyvinyl polymer 0.1
10. Methyl paraoxybenzoate 0.1
11. Sodium hydroxide 0.05
12. Residual amount of purified water 13. Ethanol 5.0
14. Fragrance 0.05
15. Guaiazulene Sulfonate Sodium 0.1
16. α-monoglucosyl hesperidin 0.03
17. L-histidine 0.05

(Production method)
A: Ingredients 1 to 8 are uniformly mixed at 70 ° C.
B: Ingredients 9 to 13 are uniformly mixed at 70 ° C.
C: Add A to B to emulsify and cool to room temperature.
D: 14 to 17 were added and mixed uniformly to obtain a milky lotion.

The emulsion of Example 5 was an emulsion having an excellent effect of preventing discoloration of sodium guaiazulene sulfonate.

Example 6 [Underwater oil type beauty essence]
(Ingredient) (%)
1. 1. Glycerin 10.0
2. 2. Hydrogenated lecithin 0.5
3. 3. Dimethicone 0.1
4. Squalene 1.0
5. Ceramide 2 0.005
6. Cholesterol 0.1
7. β-carotene 0.001
8. Astaxanthin 0.001
9. (Ascorvir / Tocopheryl) Phosphate 0.01
10. Glucosyl trehalose 2.0
11. Disodium monohydrogen phosphate 0.1
12. Monosodium dihydrogen phosphate 0.05
13. (Na acrylate / Na acryloyl dimethyl taurine)
Copolymer 0.5
14. (Vinyl Dimethicone / Meticone Silsesquioxane)
Cross polymer 0.5
15. Ethanol 5.0
16. Carbomer 0.2
17. Hydroxypropyl methylcellulose 0.1
18. Polymethyl methacrylate 1.5
19. L-Arginine 0.1
20. PVP 0.3
21. Sodium hydroxide 0.1
22. Residual amount of purified water 23. Guaiazulene Sodium Sulfonate 0.02
24. α-monoglucosyl hesperidin 0.01
25. Niacinamide 0.01
26. Sodium hyaluronate 0.005
27. EDTA-2 sodium 0.01

(Production method)
A: Ingredients 1 to 8 are uniformly mixed at 70 ° C.
B: Ingredients 9 to 22 are uniformly mixed at 70 ° C. C: Add B to A to emulsify and cool to room temperature.
D: 23 to 27 were added and mixed uniformly to obtain a beauty essence.

The oil-in-water beauty essence of Example 7 was an oil-in-water beauty essence having an excellent effect of preventing discoloration of sodium guaiazulene sulfonate.

Claims (5)

The following components (A) and (B);
(A) Guaiazulene sulfonic acid and one or more of its salts or hydrates 0.001 to 0.5%
(B) A composition containing one or more 0.001 to 0.1% of glucosyl hesperidin and water. Of粧料or skin external agent composition of claim 1. The composition according to claim 1 or 2, further containing a basic amino acid. One or more anti-discoloration agents of guaiazulene sulfonic acid and its salt or hydrate containing one or more of glucosyl hesperidin as an active ingredient. A method for preventing discoloration of a compound having an azulene structure, wherein one or more of glucosyl hesperidin is added to a composition containing one or more of guaizulene sulfonic acid and a salt or hydrate thereof .