JP7039967B2 - Acyl amino acid high compound composition - Google Patents

Description

The present invention relates to a composition containing a high concentration of acyl amino acids, an acetophenone derivative and a polyhydric alcohol, which has high antibacterial properties and excellent storage stability, and a cosmetic containing the composition. The present invention also relates to a method for preserving cosmetics, which comprises adding the composition.

Due to the deterioration of the image of preservatives due to the growing safety consciousness in recent years, various preservatives such as parabens that have been conventionally used in the market have become shunned by consumers, and they are not blended. There is a demand for technology for preserving cosmetics. To date, many techniques for preserving cosmetics have been reported by devising combinations of various materials. However, there are many requirements for them, for example, high antiseptic effect at wide pH in cosmetics, wide antibacterial spectrum, cosmetic materials themselves have excellent stability over a wide range of temperatures, and long-term storage. It is required that the performance in the cosmetics does not change even afterwards, that it is hypoallergenic, and that it does not adversely affect the feel of the product, which is important for cosmetics. Not enough have been reported.

As a technique for preserving cosmetics by devising a combination of materials, a method of preserving cosmetics using an acetophenone derivative and polyhydric alcohols (particularly diols) has been proposed (Patent Documents 1 and 2). However, even the combination of the acetophenone derivative and a plurality of types of polyhydric alcohols did not show a good synergistic effect on Pseudomonas aeruginosa and Aspergillus niger. In addition, it has been reported that the acetophenone derivative makes the emulsified droplets in the emulsified composition finer, stabilizes the emulsified system, and improves the functionality of the cosmetic, but it has been tested for storage stability over time. It has not been discussed, and it has not been discussed from the viewpoint of coloring stability (Patent Documents 1 and 2).
Further, small molecule diols have a problem that they have a great influence on usability and formulation, and it is not preferable to increase the blending amount too much, and in some cases, the requirement for hypoallergenicity may not be satisfied.

On the other hand, acyl amino acids are known as mild and highly safe materials. Among them, it has been reported that acylproline or its salt exhibits a moisturizing effect with excellent hygroscopicity and water retention, and that it can provide cosmetics with excellent usability while suppressing the odor of antibacterial agents whose odor is a problem. (Patent Documents 2 and 3). Further, acylglycine or a salt thereof can be used as a cleaning agent composition that is mild and does not have a slimy feeling (Patent Document 4), and in particular, undecilenoylglycine has anti-acne and anti-sweat activities (Patent Document 5). In addition, octanoylglycine is used as an anti-acne, antiperspirant, deodorant, etc., and although it is disclosed that it exhibits an antibacterial effect, it has also been reported that it causes a squeaky feeling in cosmetics (Patent Document). 6). However, the current situation is that acylproline and acylglycine are far from being materials that satisfy all the required conditions in the above-mentioned techniques for preserving cosmetics.

In addition, since the ratio of each material in cosmetics is examined, and the quality control and manufacturing operation of each material are complicated, each material with a high combination effect is contained in high concentration in advance to maintain long-term storage stability even at a wide range of temperatures. There has been a demand for a liquid antiseptic composition that can be easily blended into cosmetics.

Japanese Unexamined Patent Publication No. 2014-172909 WO2014-007290 WO2013-147328 Japanese Unexamined Patent Publication No. 5-156287 EP0983055 Japanese Unexamined Patent Publication No. 2001-31993

The present invention contains a high concentration of acylproline and / or acylglycine and an acetophenone derivative, has a high antiseptic effect without adding a preservative such as paraben, has sufficient storage stability, and has a good usability. It is to provide a feasible composition.

As a result of diligent research, the present inventors have found that a composition containing a high concentration of an acetophenone derivative in advance is not suitable for long-term storage at a wide range of temperatures. The combination of proline and / or acylglycine and polyhydric alcohol has a high antiseptic effect at a wide pH against bacteria and fungi, especially mold, and precipitates, freezes, separates, becomes turbid and colors even after long-term storage at low and high temperatures. The present invention has been completed by finding that it has sufficient storage stability without any problem in performance change, is hypoallergenic, and has a good usability without stickiness or squeak.

That is, the present invention includes the following aspects.
[1] A composition containing the following (A), (B) and (C):
(A) Acylproline represented by the general formula (I) and a salt thereof:

(In the formula, the acyl group represented by R1 ^- CO- represents an acyl group derived from a saturated or unsaturated fatty acid having 4 to 18 carbon atoms), and the acylglycine represented by the general formula (II) and That salt:

(In the formula, the acyl group represented by R ² -CO- represents an acyl group derived from a saturated or unsaturated fatty acid having 6 to 12 carbon atoms).
At least one compound selected from the group consisting of (B) a compound represented by the general formula (III) or a salt thereof:

(In the formula, R ³ and R ⁴ independently represent hydrogen, hydroxy group or -OCH ₃ ),
(C) Multivalent alcohol.
[2] (A) The acyl group represented by R1 ^- CO- in the general formula (I) is an acyl group derived from a saturated or unsaturated fatty acid having 8 to 12 carbon atoms according to [1]. Composition.
[3] The composition according to any one of [1] or [2], wherein (A) is at least one selected from the group consisting of decanoylproline and octanoylglycine.
[3-1] (A) The acylproline represented by the general formula (I) is at least one selected from the group consisting of octanoylproline, decanoylproline, undecilenoylproline and lauroylproline [1]. ] Or [2].
[3-2] (A) The acylglycine represented by the general formula (II) is at least one selected from the group consisting of octanoylglycine, undecilenoylglycine and decanoylglycine [1] or [ 2] The composition according to any one of.
[3-3] The composition according to any one of [1] or [2], wherein (A) is at least one selected from the group consisting of decanoylproline, octanoylglycine and undecilenoylglycine.
[4] The composition according to any one of [1] to [3], wherein (A) is decanoylproline.
[5] (B) The compound represented by the general formula (III) is

The composition according to any one of [1] to [4].
[5-1]
(B) The compound represented by the general formula (III) is

The composition according to any one of [1] to [4], which is at least one selected from the group consisting of.
[6] (B) The composition according to any one of [1] to [5], wherein the compound represented by the general formula (III) is 4-hydroxyacetophenone.
[7] The composition according to any one of [1] to [6], wherein (C) is at least one selected from 1,2-pentanediol and dipropylene glycol.
[8] The composition according to any one of [1] to [7], which further contains (D) a chelating agent.
[9] The composition according to [8], wherein the (D) chelating agent is pentetic acid or a salt thereof.
[10] The composition according to [9], wherein the (D) chelating agent is pentetic acid 5 sodium.
[11] The composition according to any one of [1] to [10], wherein the content of (A) in the composition is 10% by weight or more.
[12] The composition according to any one of [1] to [11], wherein the content of (A) in the composition is 15% by weight or more.
[13] The composition according to any one of [1] to [12], wherein the content of (A) in the composition is 15 to 30% by weight.
[14] The composition according to any one of [1] to [13], wherein the content of (B) in the composition is 5 to 20% by weight.
[15] The composition according to any one of [1] to [14], wherein the content of (C) in the composition is 10 to 60% by weight.
[16] The composition according to any one of [8] to [15], wherein the content of (D) in the composition is 0.01 to 0.5% by weight.
[17] Described in any one of [1] to [16] in which the weight ratio ((A) + (C)) / (B) of the sum of (A) and (C) to (B) exceeds 2.8. Composition.
[18] The composition according to any one of [1] to [17], wherein the pH is 5.5 to 6.5.
[19] The composition according to any one of [1] to [18], which is characterized by being liquid.
[20] The composition according to any one of [1] to [19], which is an antibacterial or antiseptic composition.
[21] A cosmetic comprising the composition according to any one of [1] to [20].
[22] A method for preserving cosmetics, which comprises a step of adding the composition according to any one of [1] to [20] to cosmetics, wherein the composition is 0.1 based on the total weight of the cosmetics. A method characterized by adding ~ 10% by weight to cosmetics.

Since the composition of the present invention contains a high concentration of acetophenone derivative and acyl amino acid, a desired amount can be easily blended into various cosmetics and the like.
According to the present invention, it is possible to provide a cosmetic having excellent storage stability by inhibiting the growth of not only bacteria but also molds at a wide pH.
Further, according to the present invention, it is possible to provide a cosmetic having a desired appearance and an excellent usability.

FIG. 1 shows the effect of the type and amount of the polyhydric alcohol on the coloring stability at 70 ° C. after storage for 3 weeks in terms of transmittance. The vertical axis shows the transmittance (%) at 430 nm. FIG. 2 shows the effect of the type and amount of the polyhydric alcohol on the coloring stability at 70 ° C. after storage for 3 weeks. The vertical axis shows the transmittance (%) at 430 nm. FIG. 3 shows the cytotoxicity expression concentration of the composition of the present application and the wetting agent having an antiseptic function.

[(A-1) Acylproline]
Acylproline in the present invention is represented by the general formula (I).

In general formula (I)

Is also referred to herein as R1 ^- CO-.
The acyl group represented by R1 ^- CO- is an acyl group derived from a saturated or unsaturated fatty acid having 4 to 18 carbon atoms, that is, an acyl residue of the saturated or unsaturated fatty acid, and examples thereof include. Butanoyl group, isobutanoyl group, sec-butanoyl group, tert-butanoyl group, pentanoyl group, sec-pentanoyl group, tert-pentanoyl group, isopentanoyl group, hexanoyl group, heptanoyle group, octanoyl group, 2-ethylhexanoyl group, Examples thereof include a tert-octanoyl group, a nonanoyl group, an isononanoyl group, a decanoyle group, an isodecanoyl group, an undecanoyl group, a lauroyl group, an undecylenoyl group, a myritoyl group, a palmitoyl group and a stearoyl group.

The long-chain acyl group represented by ^R1 -CO-is a naturally-derived mixture of coconut oil fatty acid, castor oil fatty acid, olive oil fatty acid, palm oil fatty acid, etc., in addition to the acyl group derived from a single composition acid. It may be an acyl group derived from a fatty acid or a fatty acid obtained by synthesis (including a branched fatty acid). One of these may be used, or two or more selected from the above group may be mixed and used.

The acyl group represented by R1 ^- CO- is preferably an acyl group derived from a saturated or unsaturated fatty acid having 6 to 14 carbon atoms, and more preferably than a saturated or unsaturated fatty acid having 8 to 12 carbon atoms. It is more preferably an acyl group to be derived, further preferably an acyl group derived from a saturated or unsaturated fatty acid having 8 to 10 carbon atoms, and particularly preferably a decanoyle group.

Among them, as the acylproline represented by the general formula (I), octanoylproline, decanoylproline, undecilenoylproline, and lauroylproline are preferable, and decanoylproline is more preferable.
Therefore, in the formula, R ¹ represents a hydrocarbon group having 3 to 17 carbon atoms. Examples of the "hydrocarbon group" include a chain hydrocarbon group such as an alkyl group and an alkynyl group, but a chain hydrocarbon group is preferable, and a linear or branched chain can be used. .. Of these, the alkyl group is more preferable. The number of carbon atoms of the "hydrocarbon group" is preferably 5 to 13, more preferably 7 to 11, and even more preferably 7 to 9.

Examples of the salt of the compound represented by the general formula (I) include pharmaceutically acceptable salts, and alkali metal salts such as lithium salt, sodium salt and potassium salt; alkalis such as calcium salt and magnesium salt. Examples include earth metal salts; ammonium salts; and basic organic salts. Of these, from the viewpoint of solubility, sodium salt, potassium salt and ammonium salt are preferable, sodium salt and potassium salt are more preferable, and sodium salt is further preferable.

Further, the compound represented by the formula (I) may be a hydrate, a non-hydrate, a non-solvate, or a solvate.

The method for producing acylproline in the present invention is not particularly limited, and can be easily produced by combining known methods. Specifically, acylproline can be prepared by the Schotten-Baumann method by simultaneously dropping a base such as acid chloride and sodium hydroxide to proline. The proline may be L-form, D-form, or a mixture thereof, but is preferably L-form.

[(A-2) Acylglycine]
Acylglycine in the present invention is represented by the general formula (II).

In general formula (II)

Is also referred to herein as R2 ^- CO-.
The acyl group represented by R2 ^- CO- is an acyl group derived from a saturated or unsaturated fatty acid having 6 to 12 carbon atoms, that is, an acyl residue of the saturated or unsaturated fatty acid, and an example thereof includes an acyl group. Examples thereof include a hexanoyl group, a heptanoyle group, an octanoyl group, a 2-ethylhexanoyl group, a tert-octanoyl group, a nonanoyl group, an isononanoyl group, a decanoyl group, an isodecanoyl group, an undecilenoyl group, an undecanoyl group and a lauroyl group.

The long-chain acyl group represented by R2 ^- CO- is obtained by a mixed fatty acid obtained naturally such as coconut oil fatty acid and palm kernel oil fatty acid, or by synthesis, in addition to an acyl group derived from a single composition acid. It may be an acyl group derived from a fatty acid (including a branched fatty acid). One of these may be used, or two or more selected from the above group may be mixed and used.

The acyl group represented by ^R2 -CO-is preferably an acyl group derived from a saturated or unsaturated fatty acid having 8 to 11 carbon atoms, and more preferably an octanoyl group or an undecylenoyl group.

Among them, the acylglycine represented by the general formula (II) is preferably octanoylglycine, undecilenoylglycine, or decanoylglycine, and preferably octanoylglycine and undecilenoylglycine.

Therefore, R ² in the formula represents a hydrocarbon group having 5 to 11 carbon atoms. Examples of the "hydrocarbon group" include chain hydrocarbon groups such as an alkyl group and an alkynyl group. A chain hydrocarbon group is preferable, a linear or branched chain can be used, and an alkyl group is more preferable. Further, the number of carbon atoms is more preferably 7 to 10.

Examples of the salt of the compound represented by the general formula (II) include pharmaceutically acceptable salts, and alkali metal salts such as lithium salt, sodium salt and potassium salt; alkalis such as calcium salt and magnesium salt. Examples include earth metal salts; ammonium salts; and basic organic salts. Of these, from the viewpoint of solubility, sodium salt, potassium salt and ammonium salt are preferable, sodium salt and potassium salt are more preferable, and sodium salt is further preferable.

Further, the compound represented by the formula (II) may be a hydrate, a non-hydrate, a non-solvate, or a solvate.

The method for producing acylglycine in the present invention is not particularly limited, and can be easily produced by combining known methods. Specifically, acylglycine can be prepared by the Schotten-Baumann method by simultaneously dropping a base such as acid chloride and sodium hydroxide to glycine.

In the composition of the present invention, (A) can be used by mixing one or more of acylproline and a salt thereof, and acylglycine and a salt thereof. Of these, acylproline or a salt thereof is preferable.
In the case of mixed use, when acylproline or a salt thereof is used in an amount of 1 part by weight, the amount of acylglycine or a salt thereof is usually 0.01 to 50 parts by weight, preferably 0.1 to 20 parts by weight. 0.1 to 10 parts by weight is more preferable.

The content of (A) in the composition of the present invention is usually 10% by weight or more, preferably 13% by weight or more, more preferably 15% by weight or more, based on the total weight of the composition. On the other hand, from the viewpoint of storage stability and influence on the emulsification system, the content of (A) is usually 40% by weight or less, preferably 35% by weight or less, and more preferably 30% by weight or less.

[(B) Acetophenone derivative]
(B) in the present invention is a compound represented by the following general formula (III) or a salt thereof:

In the general formula (III), R ³ and R ⁴ independently represent hydrogen, a hydroxy group or —OCH ₃ .

The compound represented by the general formula (III) is a compound in which R ³ and R ⁴ are bonded to the acetyl group at the ortho, meta, and / or para positions, and among them,
(III-a) Acetophenone

(III-b) 2-Hydroxyacetophenone

(III-c) 3-Hydroxyacetophenone

(III-d) 4-Hydroxyacetophenone

Alternatively, a mixture of the above compounds is preferable, and one or more selected from the group consisting of (III-b) 2-hydroxyacetophenone, (III-c) 3-hydroxyacetophenone and (III-d) 4-hydroxyacetophenone. The mixture of (III-d) 4-hydroxyacetophenone is more preferable.

Examples of the salt of the compound represented by the general formula (III) include pharmaceutically acceptable salts, and alkali metal salts such as lithium salt, sodium salt and potassium salt; alkalis such as calcium salt and magnesium salt. Examples include earth metal salts; ammonium salts; and basic organic salts. Of these, from the viewpoint of versatility, sodium salts, potassium salts and ammonium salts are preferable, sodium salts and potassium salts are more preferable, and sodium salts are even more preferable.

Further, the compound represented by the formula (III) may be a hydrate, a non-hydrate, a non-solvate, or a solvate.

As the compound represented by the general formula (III) or a salt thereof, any of a chemical synthesis method, a natural one derived from an animal or a plant, a fermentation method or a gene recombination method may be used.

The content of (B) in the composition of the present invention is usually 5% by weight or more, preferably 8% by weight or more, preferably 10% by weight, based on the total weight of the composition, from the viewpoint of antiseptic effect and storage stability. More preferably by weight% or more. The content of (B) is usually 20% by weight or less, preferably 18% by weight or less, and more preferably 15% by weight or less.

In the composition of the present invention, from the viewpoint of antiseptic effect and storage stability, (A) is usually 0.1 to 25 parts by weight and 0.2 to 15 parts by weight with respect to 1 part by weight of (B). Parts are preferable, and 1 to 14 parts by weight are more preferable.

From the viewpoint of the use of the composition in cosmetics, the total weight of (A) and (B) is usually 10% or more, preferably 15% or more, more preferably 20% with respect to the total weight of the composition. As mentioned above, it is more preferably 25% or more, and particularly preferably 28% or more. The upper limit is not particularly limited, but is usually 80% or less, preferably 60% or less.

Further, by using a polyhydric alcohol (C) in combination in addition to the above (A) and (B), the antiseptic effect can be further enhanced and a composition having excellent storage stability can be provided.

(C) Multivalent alcohol In the present invention, the polyhydric alcohol is a compound having two or more hydroxyl groups in one molecule. For example, glycerin, diglycerin, polyglycerin, propylene glycol (1,2-propanediol), butylene glycol (1,3-butanediol), pentylene glycol, methylpropanediol, 1,2-pentanediol, 1,5- Pentandiol, dipropylene glycol, hexylene glycol (2-methyl-2,4-pentanediol)), 1,2-hexanediol, 1,6-hexanediol, neopentyl glycol, isoprene glycol, cyclohexylglycerin, low polymerization Examples thereof include polyethylene glycol, martitol, erythritol, mannitol, xylitol and sorbitol.
Among them, a polyhydric alcohol having 2 to 20 carbon atoms is preferable, and a polyhydric alcohol having 3 to 12 carbon atoms is more preferable, from the viewpoints of long-term storage stability, easy availability, and compatibility with the component (B). Specifically, 1,2-propanediol, 1,3-propanediol, 2-methyl-1,3-propanediol, dipropylene glycol, 1,2-pentanediol, 1,2-hexanediol, 1,6 -Hexanediol is preferable, 1,2-pentanediol, dipropylene glycol, 1,3-propanediol, 1,2-hexanediol, and 1,6-hexanediol are more preferable, and from the viewpoint of long-term storage stability, 1 , 2-Pentanediol and dipropylene glycol are particularly preferred.
These polyhydric alcohols may be used alone or in combination of two or more.
As the polyhydric alcohol, any commercially available product, a chemically synthesized method, a natural one derived from an animal or a plant, or one obtained by a fermentation method or a genetic recombination method may be used.

The content of (C) in the composition of the present invention is usually 10% by weight or more, preferably 20% by weight or more, preferably 25% by weight, based on the total weight of the composition from the viewpoint of antiseptic effect and storage stability. More preferably by weight% or more. The content of (C) is usually 60% by weight or less, preferably 45% by weight or less, and more preferably 35% by weight or less.

From the viewpoint of antiseptic effect and storage stability effect, (A) is usually 10 to 40% by weight, (B) is 5 to 20% by weight, and (C) is 10 to 10 to the total weight of the composition of the present invention. It is preferably 60% by weight, 13 to 35% by weight of (A), 8 to 18% by weight of (B), 20 to 45% by weight of (C), and 15 to 30% by weight of (A). It is more preferable that% by weight, (B) is 10 to 15% by weight, and (C) is 25 to 35% by weight.

In the present invention, the weight ratio ((A) + (C) of the sum of (A) and (C) to (B) is obtained from the viewpoint of long-term storage stability of the composition containing (A) and (B) at high concentrations. )) / (B) usually exceeds 2.8. In particular, the weight ratio is preferably 2.9 or more, more preferably 3.3 or more, and particularly preferably 3.9 or more. Within this numerical range, a composition excellent in long-term storage stability can be provided. The upper limit is 17 or less, preferably 6 or less, for ((A) + (C)) / (B) from the viewpoint of usability. Within this numerical range, a transparent solution can be provided without causing precipitation.

(D) Chelating agent From the viewpoint of long-term storage stability, it is preferable that the composition of the present invention contains a chelating agent as the component (D).
Specific chelating agents include etidronic acid, pentetic acid, EDTA and salts thereof from the viewpoint of long-term storage stability and availability. Among them, etidronic acid, pentetic acid and salts thereof are preferable, pentetic acid or a salt thereof is more preferable from the viewpoint of long-term storage stability, and 5 sodium pentetic acid is particularly preferable from the viewpoint of ease of compounding.

The content of (D) in the composition of the present invention is usually 0.01% by weight or more, and 0.2% by weight or more, based on the total weight of the composition from the viewpoint of antiseptic effect and storage stability. Is preferable. Further, it is usually 0.5% by weight or less, preferably 0.4% by weight or less.

From the viewpoint of antiseptic effect and storage stability, usually (A) 10 to 40% by weight, (B) 5 to 20% by weight, (C) 10 to 60% by weight, based on the total weight of the composition of the present invention. (D) 0.01 to 0.5% by weight is blended, (A) 13 to 35% by weight, (B) 8 to 18% by weight, (C) 20 to 45% by weight, (D) 0.2 to It is preferable that 0.4% by weight is blended, (A) 15 to 30% by weight, (B) 10 to 15% by weight, (C) 25 to 35% by weight, (D) 0.2 to 0%. It is more preferable that 4% by weight is blended.

From the viewpoint of ease of blending into cosmetics, it is preferable to blend water in the composition as the component (E).
The water may be hard water or soft water, and for example, well water, natural water, ground water, tap water, ion-exchanged water, purified water, distilled water, ultrapure water and the like can be used.

The pH of the composition of the present invention is preferably pH 5.5 or more and pH 6.5 or less from the viewpoint of long-term storage stability and ease of production. If the pH is less than 5.5, the acetophenone derivative may be released from the aqueous phase and separated, and if the pH is higher than 6.5, coloring may occur and long-term storage stability may be deteriorated.

Either a diluted acid aqueous solution or a diluted alkaline aqueous solution may be used for adjusting the pH of the composition of the present invention, but due to its operability and ease of blending into cosmetics, dilute hydrochloric acid and citrate aqueous solutions , Dilute sulfuric acid, sodium hydroxide aqueous solution, potassium hydroxide aqueous solution are preferably used.

The composition of the present invention can be used as an antibacterial composition (antibacterial agent), an antiseptic composition (preservative) or an auxiliary agent thereof. The antibacterial agent, the preservative, or an auxiliary agent thereof can be produced by a known method using only the composition of the present invention or by further adding the additives described below.

As used herein, the term "antibacterial" means to prevent the growth of bacteria for a long period of time, and to suppress the growth of bacteria on the surface of a composition such as cosmetics.

As used herein, "preservative" means preventing the invasion, growth and proliferation of microorganisms and preventing spoilage and fermentation. Therefore, the "preservative effect" means the effect of suppressing the growth of fungi such as fungi and bacteria, preventing the deterioration of cosmetics, and enhancing their storage stability.

The form of the composition of the present invention is not particularly limited, and can take any form such as liquid, emulsified, paste, gel, solid, and powder. Of these, liquid, emulsified, paste-like, and gel-like forms are preferable.

A cosmetic containing the composition of the present invention is also included in the present invention, but the cosmetic may contain only the composition of the present invention, or an ingredient which may be added to a normal cosmetic may be added to the effect of the present invention. It may be blended within a range that does not interfere. Specific examples of ingredients that may be added to cosmetics include oils, surfactants, powders, amino acids, polyamino acids and salts thereof, lower alcohols, animal and plant extracts, nucleic acids, vitamins, enzymes, anti-inflammatory agents, etc. Examples thereof include bactericides, preservatives, antioxidants, moisturizers, thickeners, viscosity regulators, ultraviolet absorbers, antiperspirants, pigments, pigments, fragrances, pH regulators, pearlizing agents, wetting agents and the like. These are examples, and of course, other components may be blended.

Fatty acids such as isostearic acid, undecylenic acid, and oleic acid; myristyl myristate, hexyl laurate, decyl oleate, isopropyl myristate, hexyldecyl dimethyloctanate, glycerin monostearate, diethyl phthalate, monostearic acid. Esters such as ethylene glycol, cetyl octanate, octyl oxystearate, alkyl benzoate; hydrocarbons such as liquid paraffin, polyisobutene, vaseline, squalane; waxes such as lanolin, reduced lanolin, carnauba wax; silicone oil, mink oil, Fats and oils such as cacao oil, coconut oil, palm kernel oil, camellia oil, sesame oil, myristic acid, olive oil, and jojoba oil; ethylene, α-olefin, co-oligoene, and the like can be mentioned.

In particular, examples of silicone oil include methylpolysiloxane, highly polymerized methylpolysiloxane, polyoxyethylene / methylpolysiloxane copolymer, polyoxypropylene / methylpolysiloxane copolymer and poly (oxyethylene, oxypropylene) / methyl. Ether-modified silicones such as polysiloxane copolymers; stearoxymethylpolysiloxane; methylhydrogenpolysiloxane, decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, tetrahydrotetramethylcyclotetrasiloxane, methylcyclopolysiloxane and dodecamethylcyclohexane Cyclic silicones such as sasiloxane; amino-modified silicones such as methylphenylpolysiloxane, aminoethylaminopropylsiloxane / dimethylsiloxane copolymer; low molecular weight silicone compounds such as stearoxytrimethylsilane and trimethylsiloxysilicicic acid; silanol-modified polysiloxane, Examples thereof include silicone oils selected from alkoxy-modified polysiloxanes, fatty acid-modified polysiloxanes, fluorine-modified polysiloxanes, epoxy-modified polysiloxanes, alkoxy-modified polysiloxane perfluoropolyethers, polyvinylacetate vinyldimethylpolysiloxanes, and mixtures thereof.

Examples of the surfactant include N-long-chain acyl amino acid salts such as N-long-chain acyl acidic amino acid salt and N-long-chain acyl neutral amino acid salt, N-long-chain fatty acid acyl-N-methyltaurine salt, and alkyl. Sulfate and its alkylene oxide adducts, fatty acid amide ether sulfates, metal and weak base salts of fatty acids, sulfosuccinic acid-based surfactants, alkyl phosphates and their alkylene oxide adducts, anionic surfactants such as alkyl ether carboxylic acids; Ether-type surfactants such as glycerin ether and its alkylene oxide adduct, ether ester-type surfactants such as glycerin ester alkylene oxide adduct, sorbitan ester alkylene oxide adduct, polyoxyalkylene fatty acid ester, glycerin ester, fatty acid. Estel-type surfactants such as polyglycerin ester, sorbitan ester, sucrose fatty acid ester, alkyl glucosides, cured castor oil pyroglutamic acid diester and its ethylene oxide adduct, and nonionic surfactant such as fatty acid alkanolamide; alkylammonium Aliphatic amine salts such as chloride and dialkylammonium chloride, aromatic quaternary ammonium salts such as quaternary ammonium salts and benzalconium salts, cationic surfactants such as fatty acid acylarginine esters; and betaine types such as carboxybetaine. Examples thereof include an amphoteric surfactant such as a surfactant, an aminocarboxylic acid type surfactant, and an imidazoline type surfactant.

Examples of the powder include resin powders such as nylon beads and silicone beads, nylon powder, metal fatty acid soap, yellow iron oxide, red iron oxide, black iron oxide, chromium oxide, cobalt oxide, carbon black, ultramarine blue, and dark blue. Zinc oxide, titanium oxide, zirconium oxide, silicon oxide, aluminum oxide, cerium oxide, mica titanium, boron nitride, barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, magnesium silicate, silicon carbide, dye, rake, sericite, mica , Tark, kaolin, barium plate sulfate, butterfly barium sulfate, fine particle titanium oxide, fine particle zinc oxide, fine iron oxide, acyl lysine, acyl glutamate, acyl arginine, acyl glycine and other acyl amino acids, and further silicone treatment. Surface treatments such as fluorine compound treatment, silane coupling agent treatment, silane treatment, organic titanate treatment, acylated lysine treatment, fatty acid treatment, metal soap treatment, oil preparation treatment, and amino acid treatment may be performed.

Examples of amino acids include glycine, alanine, serine, threonine, arginine, glutamic acid, aspartic acid, isoleucine, leucine, valine and the like.

Examples of polyamino acids and salts thereof include polyglutamic acid and polyaspartic acid.

Examples of the lower alcohol include ethanol, propanol and the like.

As animal and plant extracts, lecithin, gelatin, etc.; as nucleic acids, 5'-disodium inosinate, 5'-disodium uridylate, etc.; as vitamins, vitamins A, C, etc. and derivatives thereof; as enzymes. , Papine, protease, etc .; as an anti-inflammatory agent, potassium glycyrrhizinate, etc .; as a bactericidal agent, triclosan, trichlorocarban, octopirox, zincpyrythion, etc.; as an antiseptic, methylparaben, butylparaben, etc.; as an antioxidant. As a moisturizing agent, urea, pantenol, etc.; as a thickener, hydroxypropyl starch phosphate, etc .; as a viscosity regulator, polyoxyalkylene sorbitan ester, polyoxyethylene glycol distearate, etc. , Ethanol, etc .; As an ultraviolet absorber, octyl methoxycinnamate, etc.; As an antiperspirant, aluminum oxide, etc.; As a pigment, titanium dioxide, etc.; Pigments, etc .; fragrances; citric acid, trisodium citrate, sodium carbonate, phosphoric acid, etc. as pH adjusters; ethylene glycol distearate, etc. as pearlizing agents; betaine, disodium guanylate, etc. as wetting agents Can be mentioned.

Examples of the cosmetics of the present invention include face wash, lotion, milky lotion, cream, gel, beauty liquid, pack, mask, soap, body shampoo, white powder, foundation, lipstick, teak, eyeliner, mascara, eye shadow, etc. Examples include skin cosmetics such as eyebrows, shampoos, conditioners, hair styling agents, and hair cosmetics such as hair treatments. Any cosmetic can be used, but skin cosmetics such as washing pigments, conditioners, milky lotions, creams, gels, beauty essences, packs, masks, and body shampoos, shampoos, conditioners, hair conditioners, hair treatments, etc. It is preferable to use a hair conditioner. Further, it is more preferable to use a skin cosmetic that requires moisturization.

The method for producing the composition and cosmetics of the present invention is not particularly limited, and in addition to the essential ingredients (A), (B) and (C), in addition to (D), a cosmetic composition as needed. Various components (other components mentioned above, water, etc.) necessary for producing the above-mentioned ingredients can be appropriately selected and blended, and the mixture can be produced by a conventional method.

When a cosmetic is prepared by blending the composition of the present invention as a part of a component, usually 0.01 to 15% by weight may be blended with respect to the total weight of the cosmetic. The blending amount can be appropriately determined depending on the type of cosmetics. From the viewpoint that the antiseptic effect and the moisturizing effect can be exerted without significantly changing the hardness and viscosity of the cosmetic or causing the stickiness violently, the blending amount of the composition of the present invention to be blended in the cosmetic is. With respect to the total weight of the cosmetic, 0.1% by weight to 10% by weight is preferable, 0.3% by weight to 6% by weight is more preferable, and 0.5% by weight to 4% by weight is particularly preferable.

A method for preserving cosmetics, which comprises a step of adding the above (A), (B), (C) and (D) to cosmetics, is also a second aspect of the present invention. (A), (B), (C) and (D) may be added first or at the same time. Each definition follows the above.
The addition amount of (A), (B), (C) and (D) is usually the total amount of (A), (B), (C) and (D) 0. It is 1 to 10% by weight, preferably 0.5 to 8% by weight, and more preferably 1 to 5% by weight.

The present invention also includes an antiseptic enhancer for an acetophenone derivative represented by the general formula (III) or a salt thereof, which comprises the above (A).
In the antiseptic enhancer of the present invention, (B) is 1 part by weight, while (A) is usually 0.1 to 25 parts by weight, preferably 0.2 to 15 parts by weight, and more preferably 1 to 14 parts by weight. It is characterized in that it is blended so as to be a part by weight. Other definitions, etc. are based on the above.

Next, the present invention will be described in more detail by way of examples, but the present invention is not limited to the following examples. Hereinafter, unless otherwise specified,% indicates weight%.

<Synthesis Example 1> Synthesis of decanoylproline After dissolving 34.54 g of proline (manufactured by Ajinomoto Co., Inc.) in 100 g of water, 52.01 g of decanoyl chloride (manufactured by Tokyo Kasei Co., Ltd.) and 25% sodium hydroxide aqueous solution are adjusted to pH 12. Added while. After neutralizing by adding 75% sulfuric acid and removing the aqueous layer, water and ethyl acetate were further added to remove the aqueous layer. Ethyl acetate was distilled off under reduced pressure to obtain 68.12 g of decanoylproline.

<Synthesis Example 2> Preparation of decanoylproline sodium salt Decanoyl by suspending the decanoylproline obtained in Synthesis Example 1 with an appropriate amount of water and then neutralizing the pH to 5 with sodium hydroxide. Proline sodium salts were obtained.

<Synthesis Example 3> Synthesis of Octanoyl Glycine Using glycine (manufactured by Ajinomoto Co., Inc.) and octanoyl chloride (manufactured by Tokyo Kasei Co., Ltd.), octanoyl glycine was synthesized by a method similar to that of Synthesis Example 1. That is, glycine (manufactured by Ajinomoto Co., Inc.) was dissolved in water, and octanoyl chloride (manufactured by Tokyo Kasei Co., Ltd.) and a 25% aqueous sodium hydroxide solution were added while adjusting the pH to 12. After neutralizing by adding 75% sulfuric acid and removing the aqueous layer, water and ethyl acetate were further added to remove the aqueous layer. Ethyl acetate was distilled off under reduced pressure to obtain octanoylglycine.

<Synthesis Example 4> Preparation of octanoylglycine sodium salt By suspending the octanoylglycine obtained in Synthesis Example 3 with an appropriate amount of water and then neutralizing the pH to 7.5 with sodium hydroxide. Octanoylglycine sodium salt was obtained.

<Synthesis Example 5> Synthesis of Undecilenoylglycine Using glycine (manufactured by Ajinomoto Co., Inc.) and undecilenoyl chloride (manufactured by Tokyo Kasei Co., Ltd.), undecilenoylglycine was synthesized by a method similar to that of Synthesis Example 1. That is, glycine (manufactured by Ajinomoto Co., Inc.) was dissolved in water, and undecylenoyl chloride (manufactured by Tokyo Kasei Co., Ltd.) and a 25% aqueous sodium hydroxide solution were added while adjusting the pH to 12. After neutralizing by adding 75% sulfuric acid and removing the aqueous layer, water and ethyl acetate were further added to remove the aqueous layer. Ethyl acetate was distilled off under reduced pressure to obtain undecylenoylglycine.

<Test Example 1> Long-term storage stability test at low temperature and high temperature (1) Preparation of composition A composition containing (A), (B), (C) and (D) components and other components shown in Table 1. And water were mixed at the concentrations shown in Table 1, the pH was adjusted to around 5 with NaOH, and the mixture was heated and dissolved at 45 ° C. After allowing to cool to room temperature, the pH was adjusted to 6 with NaOH and each composition was used for the following evaluation (the numbers in the table indicate the blending amount (g), and C10Pro indicates decanoyle proline).

(2) Evaluation of uniformity The uniformity of the obtained sample was visually judged based on the following criteria.
(criterion)
A A transparent and uniform composition can be obtained.
B Although it is a viscous liquid that is opaque as a whole, it is uniformly mixed.
C Insoluble matter, precipitation, etc. are observed, and the dissolved state is non-uniform.

(3) Long-term storage stability test at low and high temperatures A transparent glass bottle with a capacity of 10 mL was filled with the composition, covered, and placed in storage at -5 ° C (low temperature), 50 ° C and 70 ° C, respectively.
For products stored at -5 ° C, the solubility (homogeneity (presence or absence of separation or turbidity), presence or absence of freezing, presence or absence of precipitation) of the composition immediately taken out of the storage is checked every month for 3 months. , The judgment was made visually based on the following judgment criteria.
For products stored at 50 ° C, the products are taken out of the storage and allowed to cool to room temperature every month for 3 months. Judgment was made based on.
For products stored at 70 ° C, it was carried out for 3 weeks, and at the 1st and 3rd weeks, it was taken out from the storage and then allowed to cool to room temperature. Judgment was made based on the judgment criteria. For compositions that reached the following criteria C before storage for 3 months, the subsequent tests were discontinued.

(4) Judgment criteria after storage at -5 ° C (low temperature) A No separation or turbidity, freezing, or precipitation is observed after storage.
B After storage, slight separation or turbidity, freezing, and precipitation are observed.
C After storage, clear separation or turbidity, freezing and precipitation are observed.

(5) Judgment criteria after storage at 50 ° C and 70 ° C: Transparency of appearance, precipitation A No turbidity or precipitation is observed after storage.
B After storage, it becomes slightly turbid and precipitation is observed.
C After storage, clear turbidity and precipitation are observed.

(6) Criteria for determination after storage at 50 ° C.: Coloring After storage at 50 ° C., a 10 mm cell was used for each composition, and the transmittance was measured at a wavelength of 430 nm. Coloring was judged by the following evaluation criteria.
A 65% or more B 40% or more and less than 65% C less than 40%

(7) Criteria for determination after storage at 70 ° C.: Coloring After storage at 70 ° C., a 10 mm cell was used for each composition, and the transmittance was measured at a wavelength of 430 nm. Coloring was judged by the following evaluation criteria.
A 40% or more B 20% or more and less than 40% C less than 20%

Each compounding amount in this preparation example was expressed by weight (g). In addition, the display of weight (g) was omitted in the table, and only the numerical value indicating the blending amount was displayed. In addition, "n.d." in the table indicates that the evaluation has not been carried out.

From Table 1, when a specific polyhydric alcohol is blended and the weight ratio ((A) + (C)) / (B) of the sum of (A) and (C) to (B) is 2.8 or less, It was confirmed that 4-hydroxyacetophenone was deposited at -5 ° C depending on the type of polyhydric alcohol and the slight difference at the time of preparation. When ((A) + (C)) / (B) exceeds 2.8, the composition was found to be superior in long-term storage stability in both low and high temperature environments.

<Test Example 2> Long-term storage stability test at low and high temperatures with polyhydric alcohol (1) Preparation of composition The components (A), (B), (C) and (D) and other components shown in Table 2 After mixing the composition containing the above and water at the concentrations shown in Table 2, the pH was adjusted to around 5 with NaOH and dissolved by heating at 45 ° C. After allowing to cool to room temperature, the pH was adjusted to 6 and each composition was used for the following evaluation (the numbers in the table indicate the blending amount (g)).

(2) Evaluation of uniformity The uniformity of the obtained sample was visually judged based on the same criteria as in Test Example 1.

(3) Long-term storage stability test at low and high temperatures A transparent glass bottle with a capacity of 10 mL was filled with the composition, covered, and allowed to stand in storage at -5 ° C and 70 ° C, respectively.
For products stored at -5 ° C, the solubility (homogeneity (presence / absence of separation or turbidity), presence / absence of freezing, presence / absence of precipitation) of the composition immediately after being taken out from the storage after one month has passed is the same as in Test Example 1. Judgment was made visually based on the judgment criteria.
For products stored at 70 ° C., the product was carried out for 3 weeks, and at the 1st and 3rd weeks, it was taken out of the storage and allowed to cool to room temperature. Judgment was made based on.

From Table 2, when 1,2-pentanediol or dipropylene glycol is blended as the polyhydric alcohol and ((A) + (C)) / (B) is larger than 2.8, the composition is at low temperature and high temperature. It was found to be excellent in long-term storage stability in both environments.

The coloring stability in Table 2 after storage at 70 ° C. for 3 weeks is shown in FIG. 1 (effects of type and addition amount of polyhydric alcohol (14.5% and 29.8%)).

<Test Example 3> Long-term storage stability test at high temperature with polyhydric alcohol (1) Preparation of composition Contains components (A), (B), (C) and (D) and other components shown in Table 3. After mixing the composition and water at the concentrations shown in Table 3, the pH was adjusted to around 5 with NaOH and dissolved by heating at 45 ° C. After allowing to cool to room temperature, the pH was adjusted to 6 and each composition was used for the following evaluation (the numbers in the table indicate the blending amount (g), and C10Pro indicates decanoyle proline).

(2) Long-term storage stability test at high temperature A transparent glass bottle with a capacity of 10 mL was filled with the composition, covered, and allowed to stand in a storage at 70 ° C.
The 70 ° C.-preserved product was carried out for 3 weeks, and at the 1st and 3rd weeks, it was taken out from the storage and allowed to cool to room temperature, and the coloring was judged based on the same criteria as in Test Example 1.

The results are shown in FIG. From this result, it was confirmed that when the polyhydric alcohol was 1,2-pentanediol and dipropylene glycol, the larger the value of ((A) + (C)) / (B), the more the coloration was suppressed. It was also confirmed that the polyhydric alcohol is more preferably 1,2-pentanediol.

When the polyhydric alcohol was dipropylene glycol, it was confirmed that the storage stability at high temperature was improved even with a small amount of the polyhydric alcohol added by using it in combination with 5 sodium pentatetoate as a chelating agent.

<Test Example 4> Antiseptic test 1 of cream to which a high compounding composition is added
(1) Preparation of cream formulation The component of the oil phase component (a) shown in Table 4 is heated and dissolved by stirring in advance, and the aqueous phase is adjusted to pH 6.6 with a 3% sodium hydroxide or citric acid aqueous solution. A mixed component of component (b) + (c) + (d) + (e) was added and emulsified. After allowing to cool with stirring, the pH of the cream was confirmed. The prepared composition was subjected to an antiseptic test and a storage stability test. The composition of the example to which the composition was not added was used as a comparative example.

(2) Antiseptic test 1
The preservation efficacy test was conducted with reference to "17th revised Japanese Pharmacopoeia Reference Information G4. Microorganism-related preservation efficacy test method".

(2-1) Test strain
Ec; Escherichia coli (E. coli) NBRC 3792
Pa; Pseudomonas aeruginosa (Pseudomonas aeruginosa) NBRC 13275
Sa; Staphylococcus aureus (Staphylococcus aureus) NBRC 13276
Ca; Candida albicans NBRC 1594
Ab; Aspergillus brasiliensis NBRC 9455

(2-2) Preparation of test bacterial solution (1) Bacterial culture in SCD agar medium at 32.5 ° C. for 20 hours. The precultured bacteria were scraped off with a platinum loop and suspended in sterile physiological saline to prepare about ¹⁰⁸ cells / mL, which was used as the test bacterial solution.
(2) Incubate in yeast Sabouraud-glucose agar medium at 22.5 ° C. for 48 hours before. The precultured bacteria were scraped off with a platinum loop and suspended in sterile physiological saline to prepare about ¹⁰⁸ cells / mL, which was used as the test bacterial solution.
(3) Pre-culture in mold Saburo / glucose agar medium at 22.5 ° C for 6-10 days. The precultured bacteria were scraped off with a platinum loop and suspended in a sterile physiological saline solution containing 0.05% polysorbate 80, and prepared to about ¹⁰⁸ cells / mL was used as a test bacterial solution.

(2-3) Inoculation and preservation of bacteria For each test bacterium, take 20 g of a sample in a sterile vial and inoculate 0.15 mL of the test bacterium solution. The cells were stored at 22.5 ° C., and the viable cell counts were measured on the 7, 14, 21, and 28 days.

(2-4) Measurement of viable cell count Bacteria are subjected to SCDLP agar medium mixing method, and fungi (yeast, mold) are subjected to Saburo-dextrose LP agar medium mixing method. The evaluation was made according to the following criterion 1.

(Criteria 1)
Regarding bacteria and Candida ⊚: The number of viable bacteria decreased to less than 10 within the test period of 7 days after inoculation, and remained at that level until the end of the test for 28 days thereafter.
×: Does not meet the criteria of ◎.

Regarding Aspergillus niger ◎: Regarding Aspergillus niger, the viable cell count decreased to 0.1% or less compared to the number of bacteria inoculated 7 days after inoculation, and then equal to or equal to that level until the end of the 28-day test. The number of viable bacteria was less than that.
◯: Aspergillus niger, the viable cell count decreased to 1% or less compared to the inoculated bacterial count by 7 days after inoculation, and then viable bacteria equal to or less than the level until the end of the 28-day test. It stayed in the number.
Δ: Aspergillus niger, the viable cell count decreased to 10% or less of the inoculated bacterial count by 7 days after inoculation, and then the viable cell count was equal to or less than that level until the end of the 28-day test. It stayed in the number.
×: Does not meet the criteria of △.

As shown in Table 5, the specimens containing Examples 1 and 2 (compositions containing Preparation Examples 1-1 and 1-2, respectively) were shown to have good antibacterial activity against bacteria and mold.

<Test Example 5> Long-term storage stability test at low and high temperatures (1) Preparation of composition Fill a transparent glass bottle with a capacity of 10 mL with the composition shown in Table 4, cover it, and cover it at -5 ° C, 25 ° C, and 40 ° C. , 50 ° C, cycle (-4 to 40 ° C) storage, respectively. After 3 months from the start of storage, it was taken out from the storage and allowed to cool to room temperature. The viscosity was measured with a B-type viscometer (rotor # 64, 12 rpm, 30 seconds), the viscosity change rate (%) from the initial value was calculated by the following formula, and the determination was made according to the following criteria.

(2) Calculation formula of viscosity change rate Viscosity change rate (%) = {(viscosity after 3 months)-(initial viscosity)} ÷ (initial viscosity) x 100
When the viscosity was reduced, the absolute value was used for the judgment.

(3) Viscosity fluctuation judgment criteria The following judgment was made based on the viscosity change rate:
A: Less than 10% B: 10% or more and less than 30% C: 30% or more.

The results are shown in Table 6.

From the above, it was confirmed that even if the composition of the present invention was added to the cream emulsification system, it did not significantly affect the change in viscosity.

<Test Example 6> Confirmation of synergistic antiseptic effect of acetophenone derivative and acylproline (3-1) Test strain
Ec; Escherichia coli (E. coli) NBRC 3792
Pa; Pseudomonas aeruginosa (Pseudomonas aeruginosa) NBRC 13275
Sa; Staphylococcus aureus (Staphylococcus aureus) NBRC 13276
Ca; Candida albicans NBRC 1594
Ab; Aspergillus brasiliensis NBRC 9455

(3-2) Test method (1) Preparation of test bacterial solution
E.Coli, P. aeruginosa, S. aureus
Each test bacterium is cultured in SCD agar slope medium at 37 ° C. for 20 hours. This 1-platinum loop is transplanted to Mueller-Hinton Bouillon and cultured at 37 ° C for 20 hours. The culture solution was diluted with Mueller-Hinton bouillon and prepared at about ¹⁰⁶ cells / mL, respectively, and used as the test bacterial solution.
C. albicans
The test bacterium was cultured on a potato dextrose agar medium at 25 ° C. for 48 hours, then scraped with a loop loop and suspended in a sterile physiological saline solution to prepare about ¹⁰⁶ cells / mL, which was used as the test bacterium solution.
A. brasiliensis
The test bacteria are cultured in potato dextrose agar slope medium at 25 ° C. for 7 to 14 days. Pour Tween80 0.05% saline on the slope and scrape the spores with a platinum loop. This solution was filtered through sterilized gauze folded in four, diluted with Tween80 0.05% saline, and prepared to about ¹⁰⁶ cells / mL, which was used as the test bacterial solution.

(2) Preparation of antibacterial agent diluted solution Dilute 3 samples of hydroxyacetophenone, decanoylproline, and mixed solution of hydroxyacetophenone and decanoylproline (3: 5 weight ratio) with sterile purified water or dimethylsulfoxide, respectively, from 30%. A serial dilution series of 9% (decanoylproline), 500,000-500 μg / mL (hydroxyacetophenone), 100,000-1000 μg / mL (mixture of hydroxyacetophenone and decanoylproline (3: 5 weight ratio)) was prepared.

(3) Preparation of antibacterial agent-added agar medium 9.0 ml of the agar medium is dispensed into a test tube, sterilized by autoclave, and kept at 50 ° C. in a molten state. To this, 1 ml of the diluted solution of the sample prepared in item (2) is added. After the addition, after mixing well with vortex, pour into a petri dish with a diameter of 60 mm and solidify on a flat plate (the final concentration of the antibacterial agent in the agar medium is 1/10 of each of the adjusted dilution series).

(4) Inoculation and culture The test bacteria prepared in (1) above are collected by a disposable loop (diameter 1 mm), drawn on an antibacterial agent-added agar medium to a length of about 1 cm, and then at the specified temperature and time, respectively. Incubate in.
E.Coli, P. aeruginosa, S. aureus
Mueller-Hinton agar medium: 35 ° C, 48 hours
C. albicans
Potato dextrose agar medium: 25 ° C, 72 hours
A. brasiliensis
Potato dextrose agar medium: 25 ° C, 5 days

(5) Judgment The minimum concentration (MIC) of the antibacterial agent that completely inhibits the growth of the test bacteria is determined.
SI, which is a synergistic effect index of antibacterial effect, was calculated by an industrially accepted method using a ratio determined by the following formula.
When the obtained SI is larger than 1, a synergistic effect is recognized when it is equal to the antagonism 1 and when it is smaller than the additive effect 1. The lower the SI, the greater the synergy exhibited by the mixture.

Coal's equation: SI = Qa / QA + Qb / QB
QA = Concentration (ppm) of hydroxyacetophenone (Compound A) that provides an endpoint when acted alone (MIC of Compound A).
Qa = Concentration (ppm) of compound A that provides the endpoint when acted upon in a mixture.
QB = Concentration (ppm) of decanoylproline (C10Pro; Compound B) that provides an endpoint when acted alone (MIC of Compound B).
Qb = Concentration (ppm) of compound B that provides the endpoint when acted upon in a mixture. ]
Table 7 shows the SI values of hydroxyacetophenone and decanoylproline in each bacterium.

A synergistic effect was confirmed with three strains, Staphylococcus aureus (Staphylococcus aureus), Candida albicans (Candida), and Aspergillus brasiliensis (Aspergillus niger).

<Test Example 7> Long-term storage stability test of a composition containing acylglycine at low and high temperatures (1) Preparation of composition Contains (A), (B), (C) and other components shown in Table 8. After mixing the composition and water at the concentrations shown in Table 8, the pH was adjusted to around 5 with NaOH and dissolved by heating at 45 ° C. After allowing to cool to room temperature, the pH was adjusted to 6 with NaOH and each composition was used for the following evaluation (the numbers in the table indicate the blending amount (g), and C8Gly indicates octanoylglycine).

(2) Evaluation of uniformity The uniformity of the obtained sample was visually judged based on the same criteria as in Test Example 1.

(3) Long-term storage stability test at low and high temperatures A transparent glass bottle with a capacity of 10 mL was filled with the composition, covered, and allowed to stand in storage at -5 ° C (low temperature) and 50 ° C, respectively.
For products stored at -5 ° C, the solubility (homogeneity (presence or absence of separation or turbidity), presence or absence of freezing, presence or absence of precipitation) of the composition immediately taken out of the storage is checked every month for 3 months. , The judgment was made visually based on the same judgment criteria as in Test Example 1.
For the products stored at 50 ° C., every month for 3 months, the products were taken out of the storage and then allowed to cool to room temperature. Judgment was made based on the same criteria.

Each compounding amount in this preparation example was expressed by weight (g). In addition, the display of weight (g) was omitted in the table, and only the numerical value indicating the blending amount was displayed.

From Table 8, in the case of octanoylglycine, it was confirmed that when the polyhydric alcohol was 1,2-pentanediol, both the low temperature stability and the coloring stability under storage at 50 ° C. were the best.

<Test Example 8> Long-term storage stability test of a composition containing acylglycine at low and high temperatures (1) Preparation of composition Contains (A), (B), (C) and other components shown in Table 9. After mixing the composition and water at the concentrations shown in Table 9, the pH was adjusted to around 5 with NaOH and dissolved by heating at 45 ° C. After allowing to cool to room temperature, the pH was adjusted to 6 with NaOH and each composition was used for the following evaluation (the numbers in the table indicate the blending amount (g), and C11Gly indicates undecilenoylglycine). ..

(2) Evaluation of uniformity The uniformity of the obtained sample was visually judged based on the same criteria as in Test Example 1.

(3) Long-term storage stability test at low and high temperatures A transparent glass bottle with a capacity of 10 mL was filled with the composition, covered, and allowed to stand in storage at -5 ° C and 50 ° C, respectively.
For products stored at -5 ° C, the solubility (homogeneity (presence or absence of separation or turbidity), presence or absence of freezing, presence or absence of precipitation) of the composition immediately taken out of the storage is checked every month for 3 months. , The judgment was made visually based on the same judgment criteria as in Test Example 1.
For products stored at 50 ° C, every month for 3 months, the product is taken out of the storage and then allowed to cool to room temperature. Judgment was made based on the criteria.

(4) Criteria for determination after storage at 50 ° C.: Coloring After storage at 50 ° C., a 10 mm cell was used for each composition, and the transmittance was measured at a wavelength of 430 nm. Coloring was judged by the following evaluation criteria.
A 65% or more B 30% or more and less than 65% C Less than 30%

Each compounding amount in this preparation example was expressed by weight (g). In addition, the display of weight (g) was omitted in the table, and only the numerical value indicating the blending amount was displayed. In addition, "n.d." in the table indicates that the evaluation has not been carried out.

From Table 9, it was found that in the case of undecylenoylglycine, the storage stability at 50 ° C. is best when the polyhydric alcohol is dipropylene glycol.

<Test Example 9> Confirmation of irritation of acetophenone derivative and acylproline (1) Test cell line: HaCaT cells were added to and cultured in a 96-well plate and used in the experiment.

(2) Test method (2-1) Preparation of test cell solution HaCaT cells were cultured in DMEM (Dubecco's Modified Eagle Medium) (containing 10% serum) at 37 ° C., 5% CO ₂ , and saturated steam. The confluent cells were seeded in 96-well plates (5 × 10 ⁴ cells / well) and cultured for 1 day.

(2-2) Preparation of evaluation samples DMEM (Dulvecco's Modified Eagle's Medium) is used for the samples shown in Table 10 until the maximum concentration is 0.3% by weight and the minimum concentration is 0.001% by weight. ) (Containing 10% serum) diluted with medium.
Preparation Example 1-1 was prepared by the method described in Test Example 1 (C10Pro: 17.8% + 4 hydroxyacetophenone: 10.7% + 1,2-pentanediol: 29.7%).

(3) Judgment of cytotoxicity
The medium of each well was exchanged with the evaluation sample prepared in (2-2). Twenty-four hours after adding the sample, the cell morphology was observed by microscopic observation, and the cytotoxicity expression concentration was selected. The lowest cytotoxicity expression concentration (%) of each sample is shown in FIG. The higher the concentration, the less irritating.

As shown in FIG. 3, Preparation Example 1-1 was confirmed to be less irritating than other typical wetting agents having an antiseptic function.

INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide a composition containing a high concentration of an acyl amino acid and an acetophenone derivative, which have a high antiseptic effect, excellent storage stability, and can be easily blended into cosmetics and the like.

Claims (22)

Antibacterial or antiseptic composition comprising the following (A), (B) and (C):
(A) Acylproline and salts thereof selected from octanoylproline, decanoylproline, undecilenoylproline and lauroylproline , and salts thereof.
Acylglycine selected from octanoylglycine, undecilenoylglycine and decanoylglycine and salts thereof .
At least one selected from the group consisting of
(B)

At least one compound selected from the group consisting of or a salt thereof,
(C) At least one polyhydric alcohol selected from the group consisting of 1,2-pentanediol, dipropylene glycol, 1,3-propanediol, 1,2-hexanediol and 1,6-hexanediol .
The content in the composition is (A) 10 to 40% by weight, (B) 5 to 20% by weight, and (C) 10 to 60% by weight.
A composition in which the weight ratio ((A) + (C)) / (B) of the sum of (A) and (C) to (B) exceeds 2.8 . The composition according to claim 1, wherein (A) is at least one selected from the group consisting of decanoylproline, octanoylglycine and undecilenoylglycine. The composition according to claim 1 or 2, wherein (A) is at least one selected from the group consisting of decanoylproline and octanoylglycine. The composition according to any one of claims 1 to 3, wherein (A) is decanoylproline. (B ) is

The composition according to any one of claims 1 to 4 , which is a salt thereof. The composition according to any one of claims 1 to 5 , wherein (B ) is 4-hydroxyacetophenone or a salt thereof. The composition according to any one of claims 1 to 6 , wherein (C) is at least one selected from 1,2-pentanediol and dipropylene glycol. The composition according to any one of claims 1 to 7 , further comprising (D) a chelating agent. (D) The composition according to claim 8 , wherein the chelating agent is pentetic acid or a salt thereof. (D) The composition according to claim 9 , wherein the chelating agent is pentetic acid 5 sodium. The composition according to any one of claims 1 to 10 , wherein the content of (A) in the composition is 15 to 40 % by weight. The composition according to any one of claims 1 to 10 , wherein the content of (A) in the composition is 15 to 30% by weight. The composition according to any one of claims 1 to 12 , wherein the content of (B) in the composition is 10 to 15 % by weight. The composition according to any one of claims 1 to 13 , wherein the content of (C) in the composition is 20 to 45 % by weight. The composition according to any one of claims 1 to 13, wherein the content of (C) in the composition is 25 to 35% by weight. The composition according to any one of claims 8 to 15 , wherein the content of (D) in the composition is 0.01 to 0.5% by weight . The composition according to any one of claims 1 to 16 , wherein the weight ratio ((A) + (C)) / (B) of the sum of (A) and (C) to (B) is 3.3 or more. thing. The composition according to any one of claims 1 to 16, wherein the weight ratio ((A) + (C)) / (B) of the sum of (A) and (C) to (B) is 3.9 or more. thing. The composition according to any one of claims 1 to 18 , wherein the pH is 5.5 to 6.5. The composition according to any one of claims 1 to 19 , which is characterized by being liquid. A cosmetic comprising the composition according to any one of claims 1 to 20 . A method for preserving cosmetics, which comprises a step of adding the composition according to any one of claims 1 to 20 to cosmetics, wherein the composition is 0.1 to 10 weights based on the total weight of the cosmetics. A method characterized by adding% to cosmetics.

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