CN113318000A

CN113318000A - Cosmetic preservatives and their use as ingredients in cosmetic formulations

Info

Publication number: CN113318000A
Application number: CN202110590194.5A
Authority: CN
Inventors: 吴峰; 滕景斌; 肖永堂
Original assignee: Fujian Lianke Technology Co Ltd
Current assignee: Fujian Lianke Technology Co Ltd
Priority date: 2021-05-28
Filing date: 2021-05-28
Publication date: 2021-08-31

Abstract

The invention relates to the field of preservatives, in particular to a cosmetic preservative, wherein any compound or more than two compounds in a general formula I of the cosmetic preservative are shown in the specification, wherein R1 represents H, OH, methyl, methoxy, F, Cl or Br; wherein R2 represents any one of H, Na, K, Li, Ca, Zn, Mg, NH4 or a basic amino acid. The invention also relates to the use of the above cosmetic preservatives as ingredients in cosmetic formulations. The cosmetic preservative provided by the invention has the advantages of good stability, good and rapid bacteriostatic effect, low stimulation, no harm to human bodies, no toxic or side effect, stable color, good compatibility with cosmetics and safe application.

Description

Cosmetic preservatives and their use as ingredients in cosmetic formulations

Technical Field

The invention relates to the field of preservatives, and particularly relates to a cosmetic preservative and application thereof as a cosmetic formula component.

Background

At present, with the continuous progress of industrial science and technology, cosmetics become an indispensable part of people's daily life. Wherein some components in the cosmetics, such as organic components of lipids, hydrocarbons, water-soluble polymers and the like, can provide abundant nutrient components such as carbon sources, nitrogen sources and the like for the growth of microorganisms, and the oxidation effect of the components can also provide chemical energy for the growth of the microorganisms. Once in proper environment, microorganisms in the cosmetics grow, multiply and decay. The deterioration of the cosmetics by the microorganisms is mainly shown by decomposing the matrix of the cosmetics, leading the products to appear turbidity, precipitation and color change, changing the pH value of the products by acid products generated by the metabolism, causing foaming and swelling by generated gas, influencing the appearance and the smell of the products, and possibly generating toxin by the microorganisms to cause skin allergy of users and even cause skin infection. In order to prevent secondary pollution of cosmetics, preservatives are mainly added.

The preservative is essentially a protective agent which kills and inhibits microorganisms in the cosmetics and maintains the quality of the cosmetics for a long time. The preservative acts on a plurality of targets of cell membranes, cell walls, enzymes and the like of microorganisms to destroy cell division and inhibit bacterial growth and reproduction, thereby achieving the purpose of preservation.

In recent years, more and more consumers use cosmetics to improve the image and beautify themselves. The cosmetic preservative in the prior art mainly comprises phenoxyethanol, p-hydroxyacetophenone and caprylin, and if necessary, although the existing preservative can have a certain preservative effect, the preservative has a certain stimulation effect on skin under an effective dose, and the preservative effect is not ideal. Therefore, the development of a mild, safe and efficient preservative system has very important practical significance.

Disclosure of Invention

The technical problem to be solved by the invention is as follows: provides the preservative with small dosage, no stimulation and remarkable sterilizing effect.

In order to solve the technical problems, the invention adopts the technical scheme that:

the invention provides a cosmetic preservative which comprises any one compound or more than two compounds in the following general formula I;

wherein R1 represents H, OH, methyl, methoxy, F, Cl or Br;

wherein R2 represents H, Na, K, Li, Ca, Zn, Mg, NH₄Or a basic amino acid.

The invention also relates to the use of the above cosmetic preservatives as ingredients in cosmetic formulations.

The invention has the beneficial effects that: the cosmetic preservative provided by the invention has the advantages of good stability, good and rapid bacteriostatic effect, low stimulation, no harm to human bodies, no toxic or side effect, stable color, good compatibility with cosmetics and safe application.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of Compound 1 in an embodiment of the present invention;

FIG. 2 shows a nuclear magnetic carbon spectrum of Compound 1 in an embodiment of the present invention.

Detailed Description

In order to explain technical contents, achieved objects, and effects of the present invention in detail, the following description is made with reference to the accompanying drawings in combination with the embodiments.

The invention relates to a cosmetic preservative which comprises any one compound or more than two compounds in the following general formula I;

wherein R1 represents H, OH, methyl, methoxy, F, Cl or Br;

wherein R2 represents H, Na, K, Li, Ca, Zn, Mg, NH₄Or a basic amino acid.

Further, in the cosmetic preservative, the compound in the general formula I is selected from:

it is understood that the reference to "two or more compounds" in the present application may be a combination composition of two or more optional components from compounds 1 to 7, for example, a combination composition of compound 1 and compound 2, or a combination composition of compounds 1,2 and 3, or a combination composition of compounds 2, 3, 6 and 7, and so on.

Further, the cosmetic preservative also comprises C3-C8 dihydric alcohol, and the C3-C8 dihydric alcohol is selected from at least one of 1, 2-propylene glycol, 1, 3-butanediol, 1, 2-pentanediol, 1, 2-hexanediol or 1, 2-octanediol.

Further, the cosmetic preservative further comprises at least one selected from phenoxyethanol, p-hydroxyacetophenone, glyceryl caprylate, and ethylhexyl glycerin, which can be understood as antimicrobial ingredients.

Furthermore, in the cosmetic preservative containing C3-C8 dihydric alcohol, the content of the compound of the general formula I is 3-30%.

If the proportion of the compound of the general formula I added in the cosmetic preservative containing the dihydric alcohol C3-C8 is less than 3 percent, in order to achieve the required preservative effect, the using amount of the cosmetic preservative (containing the dihydric alcohol C3-C8) added in a cosmetic system needs to be increased so as to ensure that the content of the compound of the general formula I in the cosmetic system is kept to meet the required standard, but if the content of the cosmetic preservative is increased, the use cost is increased, and meanwhile, the cosmetic formulation formula is not facilitated.

Further, in the cosmetic preservative containing C3-C8 dihydric alcohol and antimicrobial components, the content of the compound is 3-20%.

In the application, the compound of the general formula I accounts for 0.1-1% of the total mass of the cosmetic.

If the proportion is less than 0.1%, the antiseptic challenge test cannot be passed, and if the proportion is more than 1%, slight irritation exists.

Compound 1 (in formula i above, R1 is H and R2 is H) is prepared as follows:

dissolving 34.1g of hydroxylamine hydrochloride in 500ml of methanol, cooling to 0 ℃, adding 52g of potassium hydroxide into the hydroxylamine hydrochloride methanol solution in batches at 0 ℃, continuing stirring for 15min at 0 ℃, adding 50g of methyl cinnamate into the mixed solution, heating to room temperature, reacting for 3h, and completely reacting the raw materials. Spotting plates (developing solvent: petroleum ether: ethyl acetate: 3: 1).

Filtering to remove potassium chloride, concentrating the filtrate to dryness, adding 40ml of water-soluble clear solution, adding 1:1 hydrochloric acid to adjust the pH value to 7, filtering, adding 1:1 hydrochloric acid to the solid, acidifying until the pH value is 1, filtering, and drying at 65 ℃ to obtain 35g of the product.

The process for the preparation of compounds of formula I (above in formula I, R1 is H and R2 is K):

dissolving 100g of the compound 1 in 100ml of absolute ethanol, adding 34g of potassium hydroxide into the ethanol solution of the compound 1 in batches, stirring for 1 hour at room temperature, cooling to 0 ℃, filtering, and drying at 70 ℃.

The nuclear magnetic hydrogen spectrum and nuclear magnetic carbon spectrum data of the compound 1 (in the above formula, R1 is H, R2 is H) are as follows:

referring to FIG. 1, nuclear magnetic hydrogen spectrum (400MHz, DMSO-d6) delta: 7.52(d, J ═ 8.0Hz, 2H), 7.43(d, J ═ 8.0Hz, 1H), 7.31-7.37(m, 3H), 6.44(d, J ═ 8.0Hz, 1H).

Referring to FIG. 2, nuclear magnetic carbon spectrum (100MHz, DMSO-d6) delta: 163.26, 138.87, 135.34, 129.98, 129.46, 127.99, 119.60.

Example 1

The embodiment is a cosmetic preservative which is prepared from the following raw material components in percentage by weight:

15% of compound 1 (in the general formula I, R1 is H, R2 is H) and 85% of 1, 2-propanediol.

It will be appreciated that compound 1 is one of the compounds of formula i mentioned in the present application.

The preparation method of the cosmetic preservative comprises the following steps:

stirring compound 1 and 1, 2-propylene glycol at 55 deg.C until completely dissolved, cooling to room temperature, and making into cosmetic antiseptic.

Example 2

15% of compound 2 (in the general formula I, R1 is methyl, R2 is H), 5% of p-hydroxyacetophenone, 10% of ethylhexyl glycerol, 30% of 1,2 pentanediol and 40% of 1,2 hexanediol.

stirring compound 2, p-hydroxyacetophenone, ethylhexylglycerin, 1, 2-pentanediol and 1, 2-hexanediol at 75 deg.C until completely dissolved, cooling to room temperature, and making into cosmetic antiseptic.

Example 3

10% of compound 4 (in the general formula I, R1 is methoxy, R2 is H), 5% of compound 1 (in the general formula I, R1 is H, R2 is H), 5% of glyceryl caprylate, 10% of ethylhexyl glycerol, and 70% of 1,2 hexanediol.

It is understood that compound 4 (in formula i above, R1 is methoxy and R2 is H) and compound 1 (in formula i above, R1 is H and R2 is H) are the two compounds mentioned in this application.

stirring compound 4, glyceryl caprylate, ethylhexyl glycerol and 1, 2-hexanediol at 80 deg.C until completely dissolved, and cooling to room temperature to obtain cosmetic antiseptic.

Example 4

5% of compound 1 (in the general formula I, R1 is H, R2 is H), 10% of compound 3 (in the general formula I, R1 is OH, R2 is H), 5% phenoxyethanol, 10% ethylhexyl glycerol and 70% of 1,2 hexanediol.

stirring compound 1, compound 3, phenoxyethanol, ethylhexyl glycerol and 1,2 hexanediol at 85 deg.C, dissolving completely, cooling to room temperature, and making into cosmetic antiseptic.

Example 5

5% of compound 5 (in the general formula I, R1 is Cl, R2 is H), 10% of compound 1 (in the general formula I, R1 is H, R2 is H), 15% of ethylhexyl glycerol, and 70% of 1,2 hexanediol.

stirring compound 5, compound 1, ethylhexyl glycerol and 1,2 hexanediol at 85 deg.C, dissolving completely, cooling to room temperature, and making into cosmetic antiseptic.

Example 6

5% of compound 6 (in the general formula I, R1 is F, R2 is H), 10% of compound 1 (in the general formula I, R1 is H, R2 is H), 15% of ethylhexyl glycerol and 70% of 1,2 hexanediol.

stirring 4-fluorine compound 1, compound 6, ethylhexyl glycerol and 1,2 hexanediol at 85 deg.C until completely dissolved, and cooling to room temperature to obtain cosmetic antiseptic.

Example 7

30% of compound 1 (in the general formula I, R1 is H, R2 is H) and 70% of 1, 2-pentanediol.

stirring compound 1 and 1, 2-pentanediol at 85 deg.C until completely dissolved, cooling to room temperature, and making into cosmetic antiseptic.

Example 8

20% of a compound (in the general formula I, R1 is H, R2 is K), 10% of ethylhexyl glycerol and 70% of 1,2 pentanediol.

stirring the above compound, ethyl hexyl glycerol and 1,2 pentanediol at 85 deg.C until completely dissolved, cooling to room temperature, and making into cosmetic antiseptic.

Example 9

3% of a compound (in the general formula I, R1 is H, R2 is K), 10% of ethylhexyl glycerol and 87% of 1,2 pentanediol.

stirring the compound, ethylhexyl glycerol and 1, 2-pentanediol at 75 deg.C until completely dissolved, cooling to room temperature, and making into cosmetic antiseptic.

Example 10

1% of compound 7 (in the general formula I, R1 is Br, R2 is H), 2% of compound 1 (in the general formula I, R1 is H, R2 is H), and 97% of 1,2 pentanediol.

stirring compound 7, compound 1, and 1,2 pentanediol at 75 deg.C until completely dissolved, cooling to room temperature, and making into cosmetic antiseptic.

The Minimum Inhibitory Concentration (MIC) assay was performed with reference to NCCLS us drug susceptibility testing method.

1. Experimental Material

1.1 test materials: the cosmetic preservative obtained by the invention.

1.2 test bacteria: staphylococcus aureus (ATCC6538), Pseudomonas aeruginosa (ATCC9027), Escherichia coli (ATCC8739), Candida albicans (ATCC6538), and Aspergillus niger (ATCC 16404).

2. Experimental methods

2.1 streaking the strain to plate culture medium, culturing at 37 deg.c for 24 hr; selecting a single colony, inoculating the single colony to 100ml of liquid culture medium, and culturing overnight at 37 ℃ to obtain bacterial liquid for later use.

Aspergillus niger was used to elute spores (0.85% NaCl + 0.05% Tween 80 solution) for use.

2.2 dilution of the respective bacteria to 10 with 0.85% sodium chloride solution⁶～10⁷cfu/ml, the MIC value of each test substance was determined by broth dilution. LB culture medium for bacteria, RPMI1640 liquid culture medium for fungi.

Each test article was dissolved in DMSO for use.

2.2.1 bacteria test methods: firstly, respectively adding 2ml of LB culture medium into a 24-pore plate by using a pipette, then adding test substances with different test concentrations into the pores, fully mixing the test substances to ensure that the final concentration of the test substances is 50-1000 ppm, and then sequentially adding bacteria liquid by using the pipette to ensure that the final concentration of the bacteria is 10⁵And (5) about cfu/ml, putting the mixture into an incubator to be cultured for 18-22 h at the temperature of 35 +/-1 ℃, and observing the result.

As a result: the bacteria growing holes are in a dispersed turbid or net-shaped precipitate, and the concentration of the lowest antibacterial test substance contained in the bacteria growing-free holes is the lowest antibacterial concentration.

2.2.2 fungi test methods: firstly, adding 2ml of RPMI1640 culture medium into a 24-pore plate respectively by using a pipette, then adding test substances with different test concentrations into the pores, fully mixing the test substances to ensure that the final concentration of the test substances is 50-1000 ppm, and then sequentially adding bacteria liquid by using the pipette to ensure that the final concentration of candida albicans is 10⁴About cfu/ml, the final concentration of Aspergillus nigerIs 10⁴About cfu/ml, after the culture, the candida albicans is put into an incubator to be cultured for 24 hours at 37 ℃, the aspergillus niger is put into the incubator to be cultured for 48 hours at 35 ℃, and the result is observed.

As a result: the holes with fungus growth are deposited in the shape of round particles and distributed at the bottom of the holes, and the concentration of the lowest antibacterial test object contained in the holes without fungus growth is the lowest antibacterial concentration.

Minimum inhibitory concentration (%)

The results are shown in Table 1;

TABLE 1

Microbial preservation challenge test:

experimental strains: the bacteria used in the experiment are pseudomonas aeruginosa ATCC9027, escherichia coli ATCC8739 and staphylococcus aureus ATCC 6538; the fungi are Candida albicans ATCC10231 and Aspergillus niger ATCC 16404.

Test materials: anti-allergy relieving essence, relieving moisturizing cream and skin moistening shower gel

Comparative example: the cosmetic preservative prepared in example 1 was used as component G of the anti-allergy soothing essence in an amount of 0.6%, and the actual compound 1 contained in the cosmetic in an amount of 0.09%.

Table 2 shows the formula of the anti-allergy soothing essence:

TABLE 2

In table 2, the anti-allergy soothing essence formula table shows that the component G can be selected from the cosmetic preservatives prepared in examples 1 to 8, the cosmetic preservatives prepared in examples 9 to 10, or the cosmetic preservatives in comparative example, wherein the weight percentages of the cosmetic preservatives prepared in examples 1 to 8, the cosmetic preservatives prepared in examples 9 to 10, and the cosmetic preservatives in comparative example as the component G respectively correspond to: 0.8%, 4.0%, 0.6%.

The test method comprises the following steps: the microbial preservative challenge experiment was performed with reference to the requirements of the International Standard ISO11930(Cosmetics microbiological Evaluation of the microbiological technical of the a cosmetic product) experiment followed by an initial inoculum size of 5.0X 10 bacteria⁵～1.0×10⁶cfu/ml, fungal 5.0X 10⁴～1.0×10⁵cfu/ml, the bacterial content was determined on days 7, 14 and 28.

And (3) judging test results: the bacterial count was reduced by more than 3 orders of magnitude at day 7, the fungal count was reduced by more than 1 order of magnitude, the bacterial count was reduced by more than 3 orders of magnitude at day 14, the fungal count was reduced by more than 1 order of magnitude and did not increase further than the last time, and the bacterial count continued to decrease, i.e., passed, within 28 days.

Table 3 is a 7-day antiseptic challenge data table for the anti-allergy soothing essence:

TABLE 3

Table 4 is a table of antiseptic challenge data for anti-allergy soothing essence for 14 days:

TABLE 4

Table 5 is a 28-day preservation challenge data table for anti-allergy soothing essence:

TABLE 5

And (4) judging the result: examples 1-10 both the bacterial count and fungal count decreased by more than 3 orders of magnitude at day 7, continued to decrease at day 14, and continued to decrease at 28 days, so that the preservatives obtained in examples 1-10 for anti-allergy relief serum could pass the preservative challenge.

The comparative example only reduced the E.coli number by 2 orders of magnitude on day 7, so the comparative example failed the preservative challenge.

The compound of the general formula I as the preservative has a certain bacteriostatic effect on microorganisms at a certain concentration, if the compound is lower than a certain value, the bacteriostatic effect of the preservative on the microorganisms is poor, the inhibitory effect of the preservative is lower than the growth trend of the microorganisms, and the compounds grow in an exponential manner because the growth cycle of the microorganisms is short and grow faster.

Table 6 shows the soothing moisturizer formula;

TABLE 6

The test method comprises the following steps: with reference to the requirements of International Standard ISO11930(Cosmetics microbiological Evaluation of the antimicrobial biological protection of a cosmetic product), a microbial preservative challenge experiment was performed, followed by an initial inoculum size of 5.0X 10⁵～1.0×10⁶cfu/ml, fungal 5.0X 10⁴～1.0×10⁵cfu/ml, the bacterial content was determined on days 7, 14 and 28.

And (3) judging test results: the bacterial count was reduced by more than 3 orders of magnitude at day 7, the fungal count was reduced by more than 1 order of magnitude, the bacterial count was reduced by more than 3 orders of magnitude at day 14, the fungal count was reduced by more than 1 order of magnitude and did not increase further than the last time, and the bacterial count continued to decrease, i.e., passed, within 28 days. The results are shown in Table 7;

table 7 is a 7-day preservation challenge data table for soothing moisturizers;

TABLE 7

Table 8 is a 14 day preservative challenge data table for soothing moisturizers;

TABLE 8

Table 9 is a 28-day preservation challenge data table for soothing moisturizers;

TABLE 9

And (4) judging the result: the use of the preservatives of examples 1-8 to soothe the moisturizer can pass the preservative challenge by decreasing by more than 3 orders of magnitude on day 7, continuing to decrease on day 14, and continuing to decrease in 28 days.

Table 10 is the skin lotion shower gel formulation;

watch 10

Table 11 shows the 7-day antiseptic challenge data table for skin moisturizing body wash

TABLE 11

Table 12 is a skin lotion bath 14 day antiseptic challenge data table;

TABLE 12

Table 13 is a skin lotion shower gel 14 day antiseptic challenge data table;

watch 13

And (4) judging the result: both the bacterial and fungal counts decreased by more than 3 orders of magnitude at day 7, continued to decrease at day 14, and continued to decrease within 28 days, so the preservatives from this example 1-8 for skin lotion gels could pass the preservative challenge.

Skin irritation test

Test group samples: an aqueous solution containing 0.8% of the cosmetic preservative of example 1, at which time compound 1 comprises 0.12% of the total aqueous solution.

Comparative group samples: an aqueous solution containing 4% of the cosmetic preservative of example 7, at which time compound 1 accounted for 1.2% of the total aqueous solution.

Multiple skinStimulation test: the method comprises the following steps of taking 8 healthy rabbits with intact skin (4 rabbits in each of a test group and a comparison group), and removing hairs on two sides of the spinal column of the back of the rabbit 24 hours before the test without damaging the skin. The hair removing range is about 3X 3cm on the left and right². The following day 0.5mL of the samples (test and control) were directly smeared onto 2.5X 2.5cm²Removing hair from the skin, covering with a non-irritating plastic film, and fixing with a non-irritating adhesive tape. The other side had hair removed as a blank. The application time was 2h and after the test was completed, the residual sample was removed with warm water. Once daily for 14 days. Shearing before each application, removing residual test substance after applying for 2h, observing the result after one hour, and scoring according to table 14.

TABLE 14 Scoring criteria for skin irritation response

Evaluation of skin irritation test: the animals were scored for erythema and edema formation according to Table 14, the average score per animal per day (irritation index) was calculated according to the following formula, and the level of skin irritation intensity of the test subjects on the animals was rated according to Table 15.

TABLE 15 grading of skin irritation Strength

Index of skin irritation	Stimulation intensity level
		0～0.5	Has no irritation
0.5～2.0	Light irritation
		2.0～6.0	Moderate irritation
6.0～8.0	Strong irritation

And (3) testing results: the integral mean value of skin irritation response of the tested rabbits in the observation period is less than 0.5, and the irritation intensity is as follows: has no irritation.

The integral mean value of skin irritation response of the rabbits of the comparison group in the observation period is 0.5-1.0, and the irritation strength is as follows: is light in irritation.

Acute eye irritation test:

preparation before the test: 0.1mL of the test sample solution was aspirated for use.

Acute eye irritation test: both eyes of 6 healthy rabbits (3 each of the test and control groups) were examined 24h before the start of the experiment. The lower eyelid of the eye at one side of the rabbit is slightly pulled open the next day, 0.1mL of each of the test sample solution and the comparison sample solution is respectively dripped into the conjunctival sac, and the eyelid is closed for 1 s. The other eye was not treated for self-control. The eyes of the animals were examined 1, 24, 48, 72h after instillation of the test substance. Recording the score of ocular irritation response according to the scoring criteria for ocular damage of table 3; the eye stimulus intensities of the test and control samples were judged by eye stimulus response grading according to Table 16.

TABLE 16 Scoring criteria for eye lesions

TABLE 17 grading of the product by eye irritation response

And (3) testing results: the integral of cornea, iris and conjunctiva of the tested rabbits in the observation period is 0, and the rabbits are nonirritating. The rabbit of the control group had a cornea, iris and conjunctiva integral of 1 in the observation period, which was microstimulation.

In conclusion, the cosmetic preservative provided by the invention has the advantages of good stability, good and rapid bacteriostatic effect, low stimulation, no harm to human bodies, no toxic or side effect, stable color, good compatibility with cosmetics and safe application.

The above description is only an embodiment of the present invention, and not intended to limit the scope of the present invention, and all equivalent changes made by using the contents of the present specification and the drawings, or applied directly or indirectly to the related technical fields, are included in the scope of the present invention.

Claims

1. The cosmetic preservative is characterized by comprising any one compound or more than two compounds in the following general formula I;

wherein R1 represents H, OH, methyl, methoxy, F, Cl or Br;

wherein R2 represents H, Na, K, Li, Ca, Zn, Mg, NH₄Or a basic amino acid.

2. The cosmetic preservative according to claim 1, wherein the compound of formula i is selected from:

3. the cosmetic preservative according to any one of claims 1 to 2, further comprising a C3-C8 diol, wherein the C3-C8 diol is at least one selected from the group consisting of 1, 2-propanediol, 1, 3-butanediol, 1, 2-pentanediol, 1, 2-hexanediol, and 1, 2-octanediol.

4. The cosmetic preservative according to any one of claims 1 or 2, further comprising at least one selected from phenoxyethanol, p-hydroxyacetophenone, glyceryl caprylate, and ethylhexylglycerin.

5. The cosmetic preservative according to claim 3, further comprising at least one selected from phenoxyethanol, p-hydroxyacetophenone, glyceryl caprylate, and ethylhexyl glycerin.

6. The cosmetic preservative according to claim 3, wherein the compound of the general formula I is contained in an amount of 3 to 30%.

7. The cosmetic preservative according to claim 5, wherein the compound of the general formula I is contained in an amount of 3 to 20%.

8. Use of the cosmetic preservative of any one of claims 1 to 7 as an ingredient of a cosmetic formulation.

9. Use according to claim 8, characterized in that the compound of formula I represents 0.1 to 1.0% by weight of the total cosmetic mass.