JP2017088510A - Composition having azulene compound, and agent and method for preventing discoloration of azulene compound - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a composition that prevents the discoloration of a compound having an azulene structure, and a method therefor.SOLUTION: The present invention provides a composition comprising following components (A) and (B): (A) a compound having an azulene structure and (B) one or more selected from a compound having a hesperidin structure, and a basic amino acid.SELECTED DRAWING: None

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 and a basic composition. The present invention relates to a composition and method for preventing discoloration of a compound having an azulene structure by an amino acid.

  A compound having an azulene structure is a drug having actions such as anti-inflammatory action and anti-allergic action by suppressing histamine release by mast cells, and is widely used for therapeutic and preventive purposes in various medical fields. However, since a compound having an azulene structure is gradually decomposed by light and discoloration such as discoloration or hue change occurs, there is a problem of a change in product color tone or a decrease in medicinal effect.

  In general, light-unstable drugs are shielded by the packaging material they contain, or shaded by using pigments or aluminum as the container material. In the former case, the user does not use packaging after purchasing the product. There are various problems such as the possibility of exposure to light in the latter, and the foreign matter contamination test after the filling process cannot be performed, making it possible to make a compound having a higher azulene structure as a formulation. is important.

  Therefore, as a method for improving the stability of a compound having an azulene structure unstable to light from the viewpoint of preparation, a composition containing an azulene derivative and a xanthine and stabilizing the azulene derivative (see, for example, Patent Document 1) ), An aqueous solution containing berberine, polyvinylpyrrolidone and chondroitin in azulene to improve long-term stability of azulene (see, for example, Patent Document 2), an organic acid and amino acids as pH buffering agents in azulene derivatives Examples thereof include an aqueous liquid agent (for example, see Patent Document 3) in which the azulene derivative is enhanced in light stability.

JP 2003-128537 A JP 2005-298364 A JP-A-2005-298542

  However, all of these methods have problems that the stabilizer is expensive, the stabilizing effect is not sufficient, or the dosage form is limited.

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

  In view of this situation, the present inventors have intensively studied to solve the above problems, and as a result, by combining one or more selected from a compound having an azulene structure, a compound having a hesperidin structure, and a basic amino acid. The present inventors have found that a compound having an azulene structure exhibits a remarkable effect in preventing or stabilizing discoloration due to light, that is, the flame-retarding effect of a compound having an azulene structure can be dramatically improved, thereby completing the present invention. It came to.

That is, the present invention includes 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 is provided.

  The basic amino acid of a component (B) provides the said composition which is 1 type or 2 types chosen from arginine and histidine.

  The component (B) is a compound having a hesperidin structure and a basic amino acid.

  An object of the present invention is to provide a discoloration inhibitor for a compound having an azulene structure, comprising 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, anti-discoloration agent, and anti-discoloration method of the present invention can effectively exhibit the effect of a compound having an azulene structure by improving the stability of the compound having an azulene structure.

It is a figure which shows the light absorbency in 568 nm of this invention product and a comparative product. It is a figure which shows the light absorbency in 568 nm of this invention product and a comparative product.

  The component (A) compound having an azulene structure (hereinafter sometimes referred to as “azulene compound”) in the composition of the present invention 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, azulene carboxylic acid, guaiazulene carboxylic acid, kamaazulene carboxylic 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 and color development, and guaiazulene sulfonate is preferable from the viewpoint of solubility in water. As the component (A), one type or two or more types 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 the azulene compound to be used, but is preferably 0.0001 to 5% by mass (hereinafter simply referred to as “%”). 0.001 to 0.5% is more preferable.

  The component (A) azulene compound has a characteristic light absorption around 568 nm, and has a property that the light absorption around a wavelength of 568 nm decreases when decomposition of the azulene compound occurs. 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, thereby calculating the residual amount and residual rate of the azulene compound and evaluating the stability. be able to.

  Component (B) in the composition of the present invention is one or more selected from a compound having a hesperidin structure and a basic amino acid. The component (B) compound having a hesperidin structure (hereinafter sometimes 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 abundant in pericarp and thin skin such as Satsuma mandarin, Hassaku, Daidai, etc., and is the main component of the skin.

  The hesperidin compound of component (B) in the composition of the present invention includes, for example, hesperidin, methyl hesperidin, epithelial sugar such as glucosyl hesperidin such as α-monoglucosyl hesperidin, α-monoglucosyl hesperidin, α-triglucosyl hesperidin. And hesperidin. Among these hesperidin compounds, glucosyl hesperidin is preferable from the viewpoint of the stability of the component (A).

  The basic amino acid of component (B) in the composition of the present invention is an amino acid having two or more amino groups in the molecule. 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, arginine and histidine are preferably used from the viewpoint of the stability of the component (A), and more preferably used in combination.

  Moreover, it is preferable to use a hesperidin compound and a basic amino acid in combination as the component (B), and in this case, it is more preferable to use two or more basic amino acids. Examples thereof include a combination of glucosyl hesperidin and arginine, and a combination of histidine and the like.

  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 preferable that it is 0.001 to 0.1%.

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

  Moreover, 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. The pH is most preferably around 7.0.

  In the composition of the present invention, in addition to the above components, cosmetics, external preparations for skin, foods, inks, detergents, softeners for clothing, fragrance, Ingredients used in preparations such as deodorants and fabrics, that is, water (purified water, hot spring water, deep water, etc.), oil agents, surfactants, metal soaps, gelling agents, powders, alcohols, water-soluble Polymer, film-forming agent, resin, UV protection agent, inclusion compound, antibacterial agent, fragrance, deodorant, salt, pH adjuster, refresher, animal / microbe-derived extract, plant extract, blood circulation promoter, Astringents, antiseborrheic agents, whitening agents, anti-inflammatory agents, active oxygen scavengers, cell activators, humectants, chelating agents, keratolytic agents, enzymes, hormones, vitamins and the like can be added.

  The manufacturing method of the composition of this invention is not specifically limited, It prepares by a conventional method. For example, the method of preparing by adding the said component (A) and (B) and the said arbitrary component as needed further, and mixing this is mentioned.

  The composition of the present invention can be carried out in various forms such as liquid, gel, cream, solid, powder, mousse, etc., and is contained in a mist sprayable container to form a mist You may spray and use. The dosage form of the product of the present invention is not particularly limited, such as a solubilizing type, an oil-in-water type, a water-in-oil type, an oily type, a water-in-oil-in-water type, an oil-in-water-in-oil type, and a multilayer type.

  There is no restriction | limiting in particular regarding the use of the composition of this invention, It uses as a composition for various uses, such as cosmetics, an external preparation for skin, foodstuffs, ink, detergent, the softening finishing agent for clothes, a fragrance | flavor, a deodorant, and a textile. be able to. An azulene compound is characterized by an excellent anti-inflammatory effect and the like, and from this viewpoint, it is preferably used as a cosmetic or a skin external preparation.

  Examples of the cosmetics of the present invention are not particularly limited. For example, skin care cosmetics such as milky lotion, cream, lotion, cosmetic liquid, pack, foundation, blusher, lipstick, eye color, mascara, eyeliner, nail polish, etc. It may be in any form of makeup cosmetics, hair nourishing agents, hair tonics, shampoos, rinses, hair waxes and other cosmetics, facial cleansers, body soaps and the like.

  Examples of the external preparation for skin of the present invention are not particularly limited, and may be any form such as an external gel, cream, ointment, liquid, liniment, and haptic.

  Examples of the food (including animal feed) of the present invention include frozen food, powdered food, sheet food, bottled food, canned food, retort food, capsule food, tablet food, etc. It may be in any form, such as a natural liquid food, a semi-digested nutritional food, a component nutritional food, a drink, and the like, which are mixed with sugars, fats, trace elements, vitamins, emulsifiers, fragrances, and the like.

  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 an active ingredient. The discoloration prevention method of the present invention is a method for preventing discoloration of a compound having an azulene structure by adding one or more selected from hesperidin compounds and basic amino acids to a composition containing an azulene compound.

  EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated further more concretely, the scope of the present invention is not limited to these.

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

  Example 1 <Investigation of pH>

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

  As is apparent 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 prevention effect of sodium guaiazulene sulfonate. Moreover, in any of pH = 6.0-7.5, it was excellent in the discoloration prevention effect of sodium guaiazulenesulfonate, and pH = 7.0 was the most excellent discoloration prevention effect of sodium guaiazulenesulfonate.

  Example 2 <Examination of various drugs>

  As shown in Table 2, 0.03% of sodium guaiazulene sulfonate was contained as a sample, D-pantenol, dipotassium glycyrrhizinate, ascorbic acid glucoside, nicotinic acid amide, α-monoglucosyl hesperidin, L as an antioxidant, -An aqueous solution containing 0.01% of arginine, L-histidine, glycylglycine, and phenylbenzmidazolesulfonic acid (manufactured by Merck & Co., Ltd., "EUSOLEX 232") 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 glass No. 5 standard bottles, irradiated with sunlight for 3 days at the window, the absorbance at 568 nm was measured, and the results are shown in Table 2 and FIG.

  As is apparent 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 prevention effect of sodium guaiazulene sulfonate. On the other hand, the comparative products using an antioxidant, ultraviolet absorber, non-basic amino acid, etc. all had low absorbance at 568 nm and were inferior in the discoloration preventing effect of sodium guaiazulene sulfonate.

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

  In Example 2, the effect of the combined use of the hesperidin compound and the basic amino acid in which the effect of inhibiting discoloration of azulene was recognized was examined.

  As a sample, as shown in Table 3, an aqueous solution containing 0.03% sodium guaiazulene sulfonate and 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 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 glass No. 5 standard bottles, irradiated with sunlight for 3 days at the window, the absorbance at 568 nm was measured, and the results are shown in Table 3 and FIG. FIG. 2 also shows the above-described inventive products 4 to 6, comparative product 2, and control product 2.

  As is apparent from Table 3 and FIG. 2, the products 7 to 10 of the present invention containing 2 or more kinds of α-monoglucosyl hesperidin and basic amino acids have an absorbance at 568 nm higher than those 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 recognized that the discoloration preventing effect of sodium guaiazulene sulfonate was further improved by using two or more kinds of α-monoglucosyl hesperidin and basic amino acid in combination.

Example 4 [skin lotion]
(Ingredient) (%)
1. Glycerin 5.0
2. 1,3-butylene glycol 5.0
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) Saracos 6318V (Nisshin Oilio Co., Ltd.)

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

  The lotion of Example 4 was a lotion excellent in the discoloration preventing effect of sodium guaiazulene sulfonate.

Example 5 [Emulsion]
(Ingredient) (%)
1. Polyoxyethylene monostearate (20 mol) sorbitan 1.0
2. Polyoxyethylene trioleate (20 mol) sorbitan 0.5
3. Glyceryl monostearate 1.0
4). Trimethylolpropane tristearate (Note 1) 5.0
5. Stearic acid 0.5
6). Behenyl alcohol 0.5
7). Squalane 4.0
8). Ceramide 2 0.01
9. Carboxyvinyl polymer 0.1
10. Methyl paraoxybenzoate 0.1
11. Sodium hydroxide 0.05
12 Purified water remaining amount 13. Ethanol 5.0
14 Fragrance 0.05
15. Sodium guaiazulene sulfonate 0.1
16. α-Monoglucosyl hesperidin 0.03
17. L-histidine 0.05

(Production method)
A: Components 1 to 8 are mixed uniformly at 70 ° C.
B: Components 9 to 13 are mixed uniformly at 70 ° C.
C: A is added to B to emulsify, and cooled to room temperature.
D: 14-17 were added and mixed uniformly to obtain an emulsion.

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

Example 6 [oil-in-water essence]
(Ingredient) (%)
1. Glycerin 10.0
2. Hydrogenated lecithin 0.5
3. Dimethicone 0.1
4). Squalane 1.0
5. Ceramide 2 0.005
6). Cholesterol 0.1
7). β-carotene 0.001
8). Astaxanthin 0.001
9. (Ascorbyl / tocopheryl) phosphate 0.01
10. Glucosyl trehalose 2.0
11. Disodium monohydrogen phosphate 0.1
12 Monosodium dihydrogen phosphate 0.05
13. (Na-acrylate / acryloyldimethyltaurine Na)
Copolymer 0.5
14 (Vinyl dimethicone / methicone 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. Purified water residue 23. Sodium guaiazulene 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: Components 1 to 8 are mixed uniformly at 70 ° C.
B: Components 9 to 22 are uniformly mixed at 70 ° C. C: B is added to A to emulsify, and cooled to room temperature.
D: 23-27 was added and mixed uniformly to obtain a serum.

The oil-in-water essence of Example 7 was an oil-in-water essence excellent in the discoloration prevention effect of sodium guaiazulene sulfonate.

Claims (5)

The following components (A) and (B);
(A) A compound having an azulene structure (B) A composition having one or more selected from a compound having a hesperidin structure and a basic amino acid.   The composition according to claim 1, wherein the basic amino acid of component (B) is one or two selected from arginine and histidine.   The composition according to claim 1 or 2, wherein component (B) is a compound having a hesperidin structure and a basic amino acid.   An agent for preventing discoloration of a compound having an azulene structure, comprising one or more selected from a compound having a hesperidin structure and a basic amino acid as an active ingredient.   A method for preventing discoloration of a compound having an azulene structure, comprising 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.