CN116421485A

CN116421485A - Low-irritation cosmetic

Info

Publication number: CN116421485A
Application number: CN202310025885.XA
Authority: CN
Inventors: 伊藤裕子; 西浦英树
Original assignee: Nihon Kolmar Co Ltd
Current assignee: Nihon Kolmar Co Ltd
Priority date: 2022-01-11
Filing date: 2023-01-09
Publication date: 2023-07-14
Also published as: JP2023102152A

Abstract

The present invention provides a preservative accelerator and a low-irritation cosmetic containing the same, wherein the preservative accelerator does not use a preservative which has high preservative property but can induce inflammatory reaction to have high irritation, but has higher preservative property by combining a preservative which has low preservative property but has low irritation. The antiseptic promoter contains at least 3 or more antiseptic agents other than phenoxyethanol, parahydroxybenzoate and 1, 2-hexanediol, and the low-irritation cosmetic contains the antiseptic promoter and is free of phenoxyethanol, parahydroxybenzoate and 1, 2-hexanediol.

Description

Low-irritation cosmetic

Technical Field

The present invention relates to a preservative accelerator, and a method for producing a low-irritation cosmetic or a low-irritation cosmetic containing the preservative accelerator.

Background

Conventionally, various preservatives have been used in compositions such as cosmetics, pharmaceuticals, and medical skin care products (external products for medical use) in order to maintain the preservability of the product. Examples of such preservatives include parahydroxybenzoates (parabens), phenoxyethanol, benzoic acid and salts thereof, salicylic acid and salts thereof, polyols, and the like.

Among these, parahydroxybenzoic acid esters and phenoxyethanol are frequently used as components having excellent effectiveness in cosmetics and the like.

However, formulations which have been made superior in preservative properties by using monomers such as parabens have been accompanied by irritation to consumers of sensitive skin. Therefore, studies have been made on selection of preservatives which are less irritating while retaining the preservative property or on improving the effect of the preservatives while reducing the amount of the preservatives to be used.

Specifically, a method of combining a plurality of preservatives to reduce the amount of the preservatives used has been studied.

Patent document 1 describes a cosmetic excellent in safety and improved in corrosion resistance by using 1, 3-butanediol and 1, 2-pentanediol in combination.

Patent document 2 describes a preservative composition which is excellent in preservative property and can suppress skin irritation by blending 1, 3-propanediol into parahydroxybenzoates or phenoxyethanol.

In recent years, as consumer awareness of safety increases, cosmetics and medical skin care products having low irritation to skin and low allergy are demanded, and thus low irritation cosmetics excellent in corrosion resistance are demanded.

Prior art literature

Patent literature

Patent document 1: japanese patent laid-open No. 11-335258

Patent document 2: japanese patent laid-open publication No. 2005-15401

Disclosure of Invention

However, no cosmetic has been found so far which does not contain phenoxyethanol, parahydroxybenzoate, 1, 2-hexanediol, or the like which are excellent in preservative properties by a monomer, but is excellent in preservative properties and low in irritation.

Accordingly, the present invention provides a preservative which does not use a preservative having high preservative properties but causes an inflammatory reaction to be induced and is accompanied by high irritation, and a low-irritation cosmetic containing the same, and which has high preservative properties by combining a preservative having low preservative properties but also having low irritation.

Namely, the present invention provides a preservative accelerator containing at least 3 or more preservatives other than phenoxyethanol, p-hydroxybenzoate and 1, 2-hexanediol, and a low-irritation cosmetic containing the preservative accelerator, which does not contain phenoxyethanol, p-hydroxybenzoate and 1, 2-hexanediol.

The preservative accelerator of the present invention has excellent preservative properties and is accompanied by low skin irritation by combining 3 or more kinds selected from the group consisting of pentanediol, ethylhexyl glycerol, 1, 3-Butanediol (BG), caprylic acid glyceride, and bisabolol, among preservatives in amounts that do not exhibit sufficient preservative properties when used alone, except phenoxyethanol, p-hydroxybenzoate, and 1, 2-hexanediol. The effect of the present invention is also effective in all cosmetics such as lotions and emulsion compositions containing the preservative.

Detailed Description

The preservative in the present invention is a substance used for the purpose of preventing the proliferation of microorganisms such as bacteria and mold, and generally includes a substance having bactericidal or antibacterial properties in addition to the substance used as a preservative. In the present invention, the term "antiseptic" means an effect of reducing the number of bacteria and all contaminant microorganisms such as bacteria and yeasts.

Examples of the preservative include parahydroxybenzoates (parahydroxybenzoates such as methyl parahydroxybenzoate, ethyl parahydroxybenzoate, propyl parahydroxybenzoate, butyl parahydroxybenzoate, etc.), which are used in cosmetics and medical skin care products; phenoxyethanol; alkane diols such as 1, 2-pentanediol (pentanediol), 1, 2-hexanediol, 1, 2-octanediol, and 1, 3-butanediol; alkyl glycerol ethers such as 2-ethylhexyl glycerol ether (ethylhexyl glycerol); fatty acid glycerides such as caprylic acid glyceride, capric acid glyceride, and (caprylic/capric acid) glyceride; salicylic acid; sodium benzoate; isothiazolinone derivatives such as methyl chloroisothiazolinone and methyl isothiazolinone; imidazolines

Urea; dehydroacetic acid and salts thereof; phenols; halogenated bisphenols such as triclosan, acid amides, and quaternary ammonium salts; triclocarban, zinc pyrithione, benzalkonium chloride, benzethonium chloride, sorbic acid, chlorhexidine gluconate, halocarban, hexachlorophene, hinokitiol; phenol, isopropyl phenol, cresol, thymolOther phenols such as p-chlorophenol, phenylphenol, and sodium phenylphenol; phenethyl alcohol, photoreceptors, antibacterial zeolite, and silver ions are preferable examples.

The present inventors have found that the presence of phenoxyethanol, parahydroxybenzoate and 1, 2-hexanediol among the above preservatives, in particular, makes the expression of inflammatory cytokine genes inducing inflammatory reaction remarkable, and have conducted studies on low-irritation cosmetics not containing these preservatives.

Among the above preservatives, at least 3 or more selected from pentanediol, ethylhexyl glycerol, 1, 3-butanediol, caprylic acid glyceride, and bisabolol are particularly preferably used in combination, from the viewpoint of excellent preservative properties and low skin irritation.

In the present invention, the cosmetic includes, for example, base cosmetics such as lotions, essences, emulsions, creams, facial masks, sun blocks, etc., make-up cosmetics such as foundation, powder, foundation, mascara, eyeliner, eye shadow, lipstick, concealer, blush, nail polish, etc., hair cosmetics such as shampoos, conditioners, hair styling agents, etc., body cleaners such as body washes, make-up remover, facial cleanser, etc., and the topical compositions as medical skin care products may be applied.

The pentanediol, ethylhexyl glycerol, 1, 3-butanediol, caprylic acid glyceride, and bisabolol used in the present invention may be blended with commercially available products.

When the pentanediol is contained in the cosmetic, the pentanediol is preferably 0.1 to 5% by mass, more preferably 0.5 to 4% by mass, and particularly preferably 1 to 3% by mass in the whole cosmetic. The ethylhexyl glycerin is preferably 0.005 to 0.5% by mass, more preferably 0.01 to 0.4% by mass, and particularly preferably 0.05 to 0.3% by mass in the whole cosmetic. The 1, 3-butanediol is preferably 1.0 to 30.0% by mass, more preferably 3.0 to 20.0% by mass, and particularly preferably 5.0 to 15.0% by mass in the whole cosmetic. The content of the caprylic acid glyceride in the whole cosmetic is preferably 0.05 to 1.0% by mass, more preferably 0.1 to 0.5% by mass, and particularly preferably 0.2 to 0.4% by mass. The amount of bisabolol in the whole cosmetic is preferably 0.05 to 1.0% by mass, more preferably 0.1 to 0.8% by mass, and particularly preferably 0.2 to 0.6% by mass.

The low-irritation cosmetic of the present invention may suitably contain components such as moisturizer, oil, surfactant, thickener, pH adjuster, chelating agent, antioxidant, neutralizer, bioactive component, salt, powder (pigment ), ultraviolet absorber, perfume, etc., and may contain all of the components generally commercially available.

The "preservative accelerator" mentioned in the present invention means a substance which gives excellent preservative properties by combining 3 or more of preservatives in amounts that do not exhibit sufficient preservative properties when used alone and is accompanied by low skin irritation, and the "low-irritation cosmetic" means a cosmetic having low skin irritation.

Examples

[ expression of inflammatory cytokine Gene by preservative ]

(1) (study of test concentration) test method

Human epidermal keratinocytes were cultured the day before, and the concentrations of the respective preservatives (methylparaben, pentanediol, 1, 2-hexanediol, ethylhexyl glycerol, phenoxyethanol) were adjusted and added the day after. After 24 hours, cell viability was calculated by MTT assay and is shown in table 1. The concentration at which the cell viability was 70% or more was determined to be the test concentration for gene expression verification (methylparaben: 0.1 mass%, pentanediol: 0.6 mass%, 1, 2-hexanediol: 0.4 mass%, ethylhexyl glycerol: 0.015 mass%, phenoxyethanol: 0.2 mass%).

TABLE 1

(2) (verification of Gene expression) test method

Human epidermal keratinocytes were cultured the previous day, and each preservative (methylparaben, pentanediol, 1, 2-hexanediol, ethylhexyl glycerol, phenoxyethanol) was added to the above test concentration the next day. After 6 hours and 18 hours of culture, the cells were recovered and RNA was extracted. Then, cDNA was prepared, and the expression of inflammatory cytokine genes (IL-6, IL-8, IL-1β, TNF-. Alpha.) was confirmed by real-time PCR, and the gene expression amounts were shown in Table 2.

TABLE 2

6h treatment: n=2, mean±sd

And (3) 18h of treatment: n=3, P < 0.05, vs control group, dunnett, mean±sd

From the results shown in Table 2, it was clearly confirmed that phenoxyethanol, 1, 2-hexanediol significantly increased the expression of IL-6, TNF- α.

This means that in particular phenoxyethanol, 1, 2-hexanediol are factors which lead to inflammation.

[ preservative test ]

Preservative efficacy was determined by the Nihon Kolmar preservation efficacy test method using 7 mixed bacterial inoculations (bacteria/yeast). Table 3 shows the difference between the Nihon Kolmar preservation efficacy test method and the JP method and the ISO method of the general preservative test method. The control formula used in the Nihon Kolmar preservation efficacy test method meets the qualification standard of the JP method and the ISO method.

TABLE 3

< 1. Test bacterium >)

Bacterial 6/Yeast 1 (total 7)

After properly culturing each test bacterium, a bacterium suspension was prepared.

All the bacterial suspensions were mixed in equal amounts to prepare 7 mixed bacterial suspensions.

< 2. Sample preparation and Vaccination >

(1) 20g of the sample is taken and placed in a suitable sterile container.

(2) Samples were inoculated with 0.2mL (1/100 of the sample) of 7 mixed bacterial suspensions.

(3) The samples were stirred to uniformly disperse the 7 mixed bacterial suspensions.

(4) Samples were stored at 32 ℃ until the end of the test.

< 3 test method >)

(1) Starting from the inoculation day of the 7 mixed bacterial suspensions, sampling is carried out in principle after days 1, 4, 7, 11,

microbiological tests were performed by agar plates.

(2) The cells were cultured at 32℃for 3 days (or more) and the number of the cells was measured.

(3) The number of residual bacteria in each 1g of the sample was converted from the number of bacteria measured.

When the number of residual bacteria is less than or equal to the detection limit, the culture medium is transferred from the next test to the liquid culture method.

(4) In the liquid culture method, when the test bacteria are not detected, the test is ended and compared with the preservative judgment standard.

< 4. Antiseptic criterion >

The corrosion resistance was equal to or higher than that of the control formula (meeting the standard of JP and ISO methods of the general test method) described below.

The formula of the control group: toning lotion

(composition)

Methyl parahydroxybenzoate: 0.14 mass%

1, 3-butanediol: 0.01 mass%

Humectant: 12.99% by mass

pH regulator: 0.17 mass%

Purified water: allowance of

(manufacturing method)

A: mixing purified water, humectant, methyl parahydroxybenzoate and 1, 3-butanediol at 80deg.C, and heating to dissolve.

B: the A was cooled to 35℃and the pH was adjusted with a pH adjustor.

The corrosion resistance test results were classified into the following 4 grades.

Antiseptic criterion

And (3) the following materials: has very strong antiseptic effect (bacteria die 3 days earlier than the control group)

And (2) the following steps: has strong antiseptic effect (the bacteria die in the same day as the control group)

Delta: the antiseptic effect is weak (bacteria die 3 days later than the control group)

X: has no antiseptic effect (no difference with TNTC or no death of bacteria)

TNTC (Too Numerous To Count Duoduo cannot be measured)

(examples 1 to 4, comparative examples 1 to 36): preservative accelerator

The above-mentioned preservative test was performed on an aqueous solution containing only a preservative in purified water shown in table 4 below, and the evaluation results are shown in table 4.

TABLE 4

TNTC (Too Numerous To Count. Duoduo)

B, performing BG:1, 3-butanediol

From the evaluation results of examples and comparative examples, it was determined that examples 1 to 4 obtained excellent corrosion resistance by combining 3 or more kinds of corrosion inhibitors in amounts that did not exhibit sufficient corrosion resistance when used alone.

(examples 5 to 8, comparative examples 37 to 46): cosmetic containing antiseptic promoter

The above-mentioned preservative tests were performed on cosmetics containing a preservative promoter shown in table 5 below, and the evaluation results are shown in table 5.

TABLE 5

TNTC (Too Numerous To Count. Duoduo)

B, performing BG:1, 3-butanediol

From the evaluation results of examples and comparative examples, it was confirmed that the cosmetics containing the preservatives of the combinations of examples 1 to 4 (examples 5 to 8) have excellent preservative properties.

The formulation and manufacturing method of each cosmetic are described below.

Formula of cosmetic water raw material (1)

(composition)

Each preservative: table 5 amount of

And (2) a surfactant: 2.0 mass%

pH regulator: 0.07 mass%

Humectant: 3.0 mass%

Purified water: allowance of

(manufacturing method)

A: mixing purified water, humectant, surfactant, and antiseptic at room temperature.

B: the pH of A is adjusted with a pH adjustor.

Formula of raw material (2) of toning lotion

(composition)

Each preservative: table 5 amount of

And (2) a surfactant: 0.20 mass%

pH regulator: 0.14 mass%

Humectant: 6.30 mass%

Purified water: allowance of

(manufacturing method)

A: mixing purified water, humectant, surfactant and antiseptic at room temperature.

B: the pH of A is adjusted with a pH adjustor.

The formula of the raw materials (3) of the toning lotion comprises: example 5

(composition)

BG:3.00 mass%

Ethylhexyl glycerol: 0.05 mass%

Pentanediol: 3.00 mass%

And (2) a surfactant: 1.30% by mass

Humectant: 13.33 mass%

pH regulator: 0.07 mass%

Tackifier: 0.05 mass%

Purified water: allowance of

(manufacturing method)

A: mixing purified water, humectant, ethylhexyl glycerin, pentanediol and tackifier at 80deg.C, and heating to dissolve.

B: cooling the A to 35 ℃, adding the BG and the surfactant, and uniformly mixing.

C: and (3) regulating the pH of the solution B by using a pH regulator.

Emulsion raw material (1) formula

(composition)

And (3) oil agent: 5.50% by mass

Humectant: 11.00 mass%

Each preservative: table 5 amount of

And (2) a surfactant: 1.00 mass%

Emulsion stabilizer: 0.75 mass%

pH regulator: 0.36 mass%

Purified water: allowance of

(manufacturing method)

A: mixing purified water, antiseptic, humectant and emulsion stabilizer at 80deg.C.

B: the oil agent and the surfactant are uniformly mixed at 80 ℃.

C: the A is added into the B and stirred by a homogenizer.

D: c was cooled to 35 ℃ and pH was adjusted with pH adjuster.

(composition)

Formula of raw material (1) of cream

And (3) oil agent: 9.50% by mass

Humectant: 4.00 mass%

Each preservative: table 5 amount of

And (2) a surfactant: 2.70% by mass

Emulsion stabilizer: 3.79 mass%

pH regulator: 0.04 mass%

Purified water: allowance of

(manufacturing method)

A: purified water, preservatives, humectants, emulsion stabilizers (a portion) were mixed homogeneously at 80 ℃.

B: the oil, surfactant, emulsion stabilizer (remaining) were mixed homogeneously at 80 ℃.

C: the A is added into the B and stirred by a homogenizer.

D: c was cooled to 35 ℃ and pH was adjusted with pH adjuster.

The formula of the cream raw material (2) comprises: example 6

(composition)

BG: 5.50% by mass

Ethylhexyl glycerol: 0.10 mass%

Pentanediol: 2.00 mass%

And (3) oil agent: 26.30 mass%

Humectant: 8.00 mass%

And (2) a surfactant: 3.70 mass%

Emulsion stabilizer: 4.20% by mass

pH regulator: 0.11 mass%

Purified water: allowance of

(manufacturing method)

A: purified water, BG, ethylhexyl glycerol, pentanediol, humectants, and emulsion stabilizers (a portion) were mixed uniformly at 80 ℃.

C: the A is added into the B and stirred by a homogenizer.

D: c was cooled to 35 ℃ and pH was adjusted with pH adjuster.

The formula of the cream raw material (3) comprises: example 7

(composition)

BG:6.00 mass%

Glyceryl caprylate: 0.20 mass%

Pentanediol: 2.50% by mass

And (3) oil agent: 27.7% by mass

Humectant: 6.0 mass%

And (2) a surfactant: 5.6% by mass

Emulsion stabilizer: 4.22 mass%

pH regulator: 0.07 mass%

Purified water: allowance of

(manufacturing method)

A: purified water, BG, glyceryl caprylate, pentanediol, humectant, and emulsion stabilizer (a portion) were mixed uniformly at 80 ℃.

C: the A is added into the B and stirred by a homogenizer.

D: c was cooled to 35 ℃ and pH was adjusted with pH adjuster.

The formula of the powder base liquid raw material (1) comprises: example 8

BG:7.00 mass%

Bisabolol: 0.50 mass%

Glyceryl caprylate: 0.05 mass%

And (3) pigment: 16.80 mass%

And (2) a surfactant: 5.00 mass%

Oil-soluble components: 32.90 mass%

Humectant: 3.00 mass%

Emulsion stabilizer: 2.55 mass%

Ultraviolet absorber: 6.95 mass%

Purified water: allowance of

(manufacturing method)

A: uniformly mixing and dissolving the oil agent (part), the ultraviolet absorbent and the caprylic glyceride at 80 ℃.

B: the oil (remainder), the surfactant, the emulsion stabilizer (part), and the pigment were added in this order to the a, and uniformly mixed by dispersion treatment.

C: the humectant, purified water, emulsion stabilizer (remaining) were mixed at room temperature.

D: c and bisabolol were added to B and stirred with a homogenizer.

[ irritation test ]: irritation test

In the verification, the specimens of examples and comparative examples were used on the inner side of the forearm of 5 persons who were considered sensitive skin, and the skin conditions before, immediately after, after 6 hours, and after 24 hours were used as a questionnaire to determine whether or not the skin was stimulated (hot and spicy feeling).

The results of the irritation test were classified into the following 4 grades.

Irritation determination criterion

And (3) the following materials: no skin irritation (no person feeling irritation after coating)

O: skin irritation is weak (1 out of 5 after coating feel irritation)

Delta: the skin irritation is slightly strong (2-3 out of 5 coated feel irritation)

X: the skin irritation is strong (4-5 out of 5 coated feel irritation)

Examples 1 to 4 and comparative examples 1 to 36, the corrosion inhibitors were low in irritation

The above-mentioned irritation test was performed on an aqueous solution containing only a preservative in purified water shown in table 6 below, and the evaluation results are shown in table 6.

TABLE 6

		Before coating	After coating	After 6 hours	After 24 hours	Stimulation determination
							Comparative example 2	0.05 mass% ethylhexyl glycerol	0	0	0	0	◎
Comparative example 3	0.1% by mass of ethylhexyl glycerol	0	3	2	0	△
							Comparative example 8	3.0% by mass of pentanediol	0	0	0	0	◎
Comparative example 10	5.0% by mass of pentanediol	0	2	1	0	△
							Comparative example 33	3.0 mass% BG	0	0	0	0	◎
Comparative example 34	5.0 mass% BG	0	0	0	0	◎
							Comparative example 12	10.0 mass% BG	0	1	1	0	○
Comparative example 13	20.0 mass% BG	0	2	1	0	△
							Comparative example 17	0.25 mass% phenoxyethanol	0	1	0	0	○
Comparative example 20	0.5 mass% phenoxyethanol	0	3	1	0	△
							Comparative example 22	0.1% by mass of methyl parahydroxybenzoate	0	1	0	0	○
Comparative example 24	0.2 mass% of methyl parahydroxybenzoate	0	3	2	0	△
							Comparative example 25	0.1% by mass of glyceryl caprylate	0	0	0	0	◎
Comparative example 26	0.2 mass% of glyceryl caprylate	0	0	0	0	◎
							Comparative example 27	0.1 mass% bisabolol	0	0	0	0	◎
Comparative example 28	0.5 mass% bisabolol	0	1	0	0	○
							Comparative example 29	0.1 mass% bisabolol+5.0 mass% BG	0	0	0	0	◎
Comparative example 30	0.05 mass% ethylhexyl glycerol+5.0 mass% BG	0	0	0	0	◎
							Comparative example 31	0.2 mass% glyceryl caprylate+5.0 mass% BG	0	0	0	0	◎
Comparative example 32	0.3 mass% 1, 2-hexanediol+5.0 mass% BG	0	1	0	0	○
							Comparative example 33	0.25 mass% phenoxyethanol+5.0 mass% BG	0	1	0	0	○
Comparative example 34	2.0 mass% pentanediol+6.0 mass% BG	0	0	0	0	◎
							Comparative example 35	2.5 mass% pentanediol+3.0 mass% BG	0	0	0	0	◎
Comparative example 36	0.12 mass% methyl parahydroxybenzoate+6.0 mass% BG	0	0	0	0	◎
							Example 1	0.05 mass% ethylhexyl glycerol+3.0 mass% pentanediol+3.0 mass% BG	0	0	0	0	◎
Example 2	0.1 mass% ethylhexyl glycerol+2.0 mass% pentanediol+5.5 mass% BG	0	0	0	0	◎
							Example 3	0.2 mass% glyceryl caprylate+2.5 mass% pentanediol+6.0 mass% BG	0	0	0	0	◎
Example 4	0.5 mass% bisabolol+0.05 mass% glyceryl caprylate+7.0 mass% BG	0	0	0	0	◎

B, performing BG:1, 3-butanediol

As is clear from the evaluation results of examples and comparative examples, the number of monitors who felt the stimulus in examples 1 to 4 was 0, and the low-irritation was determined.

Examples 5 and 8 Low irritation cosmetic

The above-described irritation test was performed on examples 5 and 8, which are cosmetics containing the preservative according to the present invention shown in table 7 below, and the evaluation results are shown in table 7.

TABLE 7

BG 1, 3-butanediol

As is clear from the evaluation results of examples, the number of monitors who felt the stimulus in examples 5 and 8 was 0, and the low-irritation was determined.

[ irritation test ]: skin model test

Using skin models

J-TEC LabCyte EPI-MODEL 24 well

By evaluating under a condition more severe than the usual test method prescribed in the OECD guidelines, it is possible to detect a stimulus which cannot be detected by healthy skin, and it is said that the sensitive skin which currently occupies most of japanese is set as a presumed sensitive skin model.

(1) Test method

The skin model was transferred to a 24-well plate and cultured in a medium maintained for 1 hour or more. The sample was exposed by adding 50. Mu.L to the epidermis side. After incubation for 24 hours, washing with PBS (-), transferring to MTT-added medium, culturing for 3 hours, and then extracting with isopropanol to obtain the cell viability by measuring absorbance at OD570 nm.

(2) Determination criterion

The stimulation was determined to be not stimulated when the cell viability was greater than 70%, and to be stimulated when the cell viability was not greater than 70%.

Examples 6 and 7 Low irritation cosmetic

The skin model test was performed on examples 6 and 7, which are cosmetics containing the preservative according to the present invention shown in table 8 below, and the evaluation results are shown in table 8.

TABLE 8

From the evaluation results of examples, it was found that the cell viability of examples 6 and 7 was more than 70%, and the cells were judged to be low in irritation.

[ irritation test ]: patch test

The 24-hour closed patch test was performed according to an ethical committee approved protocol.

(1) Test method

The test samples were sealed and attached to the inner side of the upper arm of 10 subjects who had informed the content of the human body patch test profile and obtained written consent for 24 hours, the tape was peeled off after 24 hours, the first judgment was made after 60 minutes (after 24 hours), and the second judgment was made after 24 hours (after 48 hours).

(2) Determination criterion

The reference photograph (Hehe, visual Dermatology,3 (1), 74-81, 2004) was referred to for determination, the skin irritation index was calculated from the scores of table 9, and the skin irritation index of 5.0 or less was determined as low irritation based on table 10.

TABLE 9

Determination criterion for irritation test (patch test)

Determination of	Scoring of	Reaction
			-	0	No reaction
±	0.5	Slight erythema
			+	1.0	Erythema (red spot)
++	2.0	Erythema and edema
			+++	3.0	Erythema + edema + papule + serous papule, small blister
++++	4.0	Bulla

Japanese reference: chuan village et al, journal of Japanese dermatology 8- (5), 301-314, 1970

(calculation of skin irritation index)

The commercial percentage obtained by dividing the total score of each test sample by the number of subjects was expressed based on the scores after 24 hours and 48 hours of application of the adhesive tape, and the higher value was used as the skin irritation index.

TABLE 10

Calculation of skin irritation index for irritation test (Patch test)

Shellfish, cosmetic chemistry, 19, temporary journal of journal, 49-56, 1995

Example 6 Low irritation cosmetic

The patch test was performed on example 6, which is a cosmetic containing the preservative of the present invention shown in table 11, and the evaluation results are shown in table 11.

TABLE 11

From the evaluation results of examples, the skin irritation index of example 6 was 0, and it was determined that the skin irritation was low.

Industrial applicability

A low-irritation cosmetic excellent in preservative property which can be used by a user of sensitive skin is provided.

Claims

1. A preservative promoter comprises at least 3 or more preservatives other than phenoxyethanol, parahydroxybenzoate and 1, 2-hexanediol.

2. The preservative accelerator according to claim 1, wherein the preservative is at least 3 or more selected from the group consisting of pentanediol, ethylhexyl glycerol, 1, 3-butanediol, caprylic acid glyceride, and bisabolol.

3. A low irritation cosmetic comprising the preservative accelerator according to claim 1 or 2, free of phenoxyethanol, parahydroxybenzoate and 1, 2-hexanediol.

4. A method for producing the low-irritation cosmetic according to claim 3.