Background
There are a wide variety of microorganisms in nature, some of which are friendly to humans or animals and some of which are pathogenic to humans or other animals. For example, Staphylococcus aureus is an important pathogenic bacterium and causes many serious infections, such as suppurative infection of skin and soft tissue, respiratory tract infection, pneumonia, digestive tract infection, etc. Along with the great improvement of living standard of people, people pay more and more attention to the health and safety of self and family pet members, so that washing or no-washing products with the effects of degerming, bacteriostasis and the like are more and more favored by consumers.
Currently, in the commercial products for personal care and pet care, the commonly used bacteriostatic agents are: (1) the bacteriostatic agent with cationic property such as polyaminopropyl biguanide, benzalkonium chloride and sibiramine can be applied to a non-anionic surfactant system; (2) the bacteriostatic agents such as salicylic acid, PCMX (parachlorometaxylenol), triclosan and the like can be applied to a system containing an anionic surfactant, but the bacteriostatic agents have larger irritation; (3) the bacteriostatic agent containing the silver ion source can play a role in bacteriostasis, but has the defects that the bacteriostatic agent can play a comprehensive role only under the condition of higher silver concentration, the problem of certain safety exists when the silver ion concentration is too high, and the cost of the silver ion source is higher; (4) ethanol, hypochlorous acid and the like can be applied to disinfection products to achieve the effect of sterilization and disinfection, have large irritation and can directly contact the skin or cause discomfort.
From the above, the disadvantages of the existing bacteriostatic agents mainly include: firstly, the cationic bacteriostatic agent can only be applied to the product formula of a cationic system or a nonionic system to play a bacteriostatic or degerming effect, and in a system containing an anionic surfactant, the bacteriostatic effect is weakened or the stability is abnormal and the like due to the influence of ionic charges; secondly, the existing bacteriostatic agent commonly used in the anionic surfactant generally has the problems of high addition amount, large irritation and the like. Thirdly, single silver ions are adopted for bacteriostasis, the single silver ion source needs larger concentration to obtain more comprehensive bacteriostasis effect, and the cost is higher. And fourthly, organic solvents such as ethanol and the like are used for bacteriostasis, so that the irritation is large, and certain risks are also generated in the processes of production, storage, transportation and the like.
Chinese patent application No. 202010916247.3 discloses a silver ion antibacterial bath agent and a preparation method thereof, which researches the influence of different addition amounts of silver ions on the antibacterial effect and the safety of the product on the premise of not influencing the moisturizing effect and the cleaning capability of the bath agent;
chinese patent with application number CN201910783679.9 discloses betaine salicylate, and provides a preparation method of the betaine salicylate. The betaine salicylate is a novel mild low-irritation raw material, and mainly solves the problem of large irritation caused by adding the traditional salicylic acid into skin care products and cosmetic formulas; the product becomes mild and low-irritation by grafting the betaine on the group of the salicylic acid, maintains the effects of sterilizing, diminishing inflammation, removing acne and the like of the salicylic acid, and effectively reduces irritation to the skin.
However, the above scheme only reports the performance of a single bacteriostatic agent, such as bacteriostatic effect, or the preparation method of raw materials, and does not relate to how to solve the problems that the existing bacteriostatic agent cannot be simultaneously applied to various different surfactant systems, and the addition amount is large.
Disclosure of Invention
In order to solve the technical problems, the invention provides the efficient mild bacteriostatic agent suitable for various surfactant systems and the application thereof.
The specific technical scheme of the invention is as follows:
in a first aspect, the invention provides a high-efficiency mild bacteriostatic agent suitable for a multi-class surfactant system, which comprises a silver ion source and betaine salicylate; wherein the concentration of the silver ion source in the surfactant system is 2ppm-10ppm, and the mass percent of the betaine salicylate in the surfactant system is 0.4% -1.5%.
The bacteriostatic agent simultaneously contains a silver ion source and betaine salicylate. Wherein, silver ion is a common bacteriostatic agent, Ag+It attracts the mercapto (-SH) groups on the protease in the bacteria, and in combination with this, inactivates the protease, resulting in bacterial death. The betaine salicylate is formed by combining salicylic acid and beet extract trimethyl glycine, in the molecular structure, the anion part of salicylic acid and the anion part of trimethyl glycine share the same charge, so the salicylic acid and the anion part of trimethyl glycine can be combined into a stable compound, and the cation part of trimethyl glycine is separated out, so that the high-efficiency exfoliating composite salicylic acid with strong affinity is finally formed.
In addition, the team of the invention also finds that the silver ion source and the betaine salicylate can generate obvious synergistic effect after being compounded. After the accidental discovery is obtained, the team of the invention finds that the synergistic mechanism which can generate the effect of '1 +1 > 2' after the two are compounded is as follows through further research: when body surface bacteria and fungi are infected, the salicylic acid part of betaine salicylate can soften skin horny layer, when the horny layer falls off, hypha can be removed, the organic acid structure of betaine salicylate can destroy the cell membrane of bacteria, change the ion channel of cell membrane, and promote trace Ag+Faster entry into cell membranes, Ag+Can strongly attract the mercapto (-SH) on the protease in the bacteria body, rapidly combine with the SH to inactivate the protease and cause the bacteria to die, and Ag+Compared with the single action, the bacteriostatic speed and efficiency can be obviously improved. And similar synergistic effect is not found after one of the two is compounded with other common bacteriostatic agents.
In addition, trimethylglycine has strong moisture retention and irritation reduction, can relieve irritation brought by salicylic acid, and silver ions are nontoxic, tasteless, non-irritant and pollution-free green bactericidal substances in a certain concentration range, so that betaine salicylate and silver ion source are a group of mild and efficient antibacterial compositions, do not have charge adsorption and other effects with anionic surfactants, cationic surfactants and the like, influence on product stability and antibacterial effect, and can be suitable for various surfactant systems such as anionic surfactant systems, cationic surfactant systems, nonionic surfactant systems and the like.
Preferably, the concentration of the silver ion source in the surfactant system is 4ppm-10ppm, and the mass percentage of the betaine salicylate in the surfactant system is 0.5% -1.0%.
Preferably, the concentration ratio of the silver ion source to the betaine salicylate in the surfactant system product is 0.1: 200-0.25: 100.
The team of the invention further finds that the optimal synergistic bacteriostatic effect can be realized by controlling the proportion of the silver ion source and the betaine salicylate within the range (the specific data are detailed in the test example part).
Preferably, the source of silver ions is chelated silver.
In a second aspect, the invention provides a surfactant system comprising the high-efficiency mild bacteriostatic agent.
Preferably, the surfactant system is a personal care product or a pet care product.
Preferably, the surfactant system comprises the following components in percentage by mass:
0.1 to 20 percent of surfactant,
the silver ion source (active silver ion antibacterial liquid provided by biological research institute of Guangxi academy of sciences, the silver ion concentration is about 1500ppm),
the betaine salicylate is a salt of a betaine salicylate,
the balance of solvent.
The surfactant system has a pH of 4.0 to 5.5.
Preferably, the surfactant is one or more of an anionic surfactant, a nonionic surfactant and a cationic surfactant.
Further, the anionic surfactant comprises sodium laureth sulfate and/or sodium laureth sulfate; the non-ionic surfactant comprises one or more of lauryl glucoside, octyl/decyl glucoside, and PEG-20 sorbitan cocoate; the cationic surfactant comprises hexadecyl trimethyl ammonium chloride and/or dodecyl trimethyl ammonium chloride.
Compared with the prior art, the invention has the following technical effects:
(1) the bacteriostatic agent simultaneously contains the silver ion source and the betaine salicylate, and compared with a single component, the bacteriostatic agent can generate a remarkable synergistic bacteriostatic effect after being compounded, and can realize quick and efficient bacteriostatic activity under a lower addition amount.
(2) The bacteriostatic composition can be simultaneously suitable for surfactant systems such as anions, cations, non-ions and the like, has mild and low-stimulation components, and can be widely applied to products such as personal care and pet care.
Detailed Description
The present invention will be further described with reference to the following examples.
General examples
A high-efficiency mild bacteriostatic agent suitable for multi-class surfactant system comprises a silver ion source (preferably chelated silver) and betaine salicylate; wherein the concentration of the silver ion source in the surfactant system is 2ppm-10ppm (preferably 4ppm-10ppm), and the mass percentage of the betaine salicylate in the surfactant system is 0.4% -1.5% (preferably 0.5% -1.0%). Meanwhile, the concentration ratio of the silver ion source to the betaine salicylate in the product is 0.1: 200-0.25: 100.
A surfactant system containing the high-efficiency mild bacteriostatic agent comprises the following components in percentage by mass: 0.1-20% of surfactant, a silver ion source (an active silver ion antibacterial liquid provided by biological research institute of Guangxi academy of sciences, the silver ion concentration is about 1500ppm), betaine salicylate (product model YH-10017 of Zhangzhou City exhibition Biotech Co., Ltd.) and the balance of solvent. The surfactant system has a pH of 4.0 to 5.5.
Preferably, the surfactant is one or more of an anionic surfactant, a nonionic surfactant and a cationic surfactant. Further, the anionic surfactant comprises sodium laureth sulfate and/or sodium laureth sulfate; the non-ionic surfactant comprises one or more of lauryl glucoside, octyl/decyl glucoside, and PEG-20 sorbitan cocoate; the cationic surfactant comprises hexadecyl trimethyl ammonium chloride and/or dodecyl trimethyl ammonium chloride.
Test example
The silver ion source, the betaine salicylate and the synergistic antibacterial effect thereof are compared as follows: shampoo formula mainly containing anionic surfactant
TABLE 1 anti-bacteria and antibacterial performances of different silver ion source concentrations
Silver ion source concentration/ppm in the formulation
|
2
|
5.25
|
7.5
|
10
|
12.5
|
Inhibition of Staphylococcus aureus (ATCC 6538)/%
|
39.75
|
62.35
|
64.71
|
67.15
|
79.62
|
Inhibition of E.coli (8099)/%)
|
18.86
|
55.16
|
56.73
|
58.57
|
65.83
|
Candida albicans (ATCC 10231) inhibition ratio%
|
69.23%
|
>99
|
>99
|
>99
|
>99 |
Remarking: the action concentration is 50%, and the action time is 10 min.
TABLE 2 anti-and bacteriostatic properties of different betaine salicylic acid additions
Betaine salicylate addition amount/% in the formulation
|
0.4
|
0.6
|
0.8
|
1.0
|
1.5
|
Inhibition of Staphylococcus aureus (ATCC 6538)/%
|
68.97
|
81.53
|
88.71
|
97.52
|
>99
|
Inhibition of E.coli (8099)/%)
|
60.33
|
69.33
|
78.29
|
92.83
|
>99
|
Candida albicans (ATCC 10231) inhibition ratio%
|
35.73
|
40.12
|
49.37
|
65.47
|
87.96 |
Remarking: the action concentration is 50%, and the action time is 10 min.
TABLE 3 synergistic anti-bacterial and bacteriostatic properties of silver ion source and betaine salicylate in different ratios
Silver ion source concentration/ppm in the formulation
|
5.25
|
5.25
|
7.5
|
5.25
|
2
|
Betaine salicylate addition/% in the formulation
|
0.5
|
0.8
|
0.8
|
1
|
1.5
|
Inhibition of Staphylococcus aureus (ATCC 6538)/%
|
98.96
|
>99
|
>99
|
>99
|
>99
|
Inhibition of E.coli (8099)/%)
|
98.91
|
>99
|
>99
|
>99
|
>99
|
Candida albicans (ATCC 10231) inhibition ratio%
|
98.64
|
>99
|
>99
|
>99
|
74.16 |
Remarking: the action concentration is 50%, and the action time is 10 min.
The safe and effective concentration of silver ion as a bacteriostatic agent needs to be controlled within 10ppm, and Sunjifu et al studies that silver ion shows cytotoxicity at 12.5ppm and the toxicity increases with the increase of concentration. Under the experimental condition, the bacteriostatic effect of singly using silver ions is not ideal. Table 2 shows that the betaine salicylate is used as the bacteriostatic agent alone, and the addition amount is higher, but as the structure of the raw materials is known, the larger the addition amount is, the irritation of the product is relatively increased. Table 3 shows that the silver ions and the betaine salicylate are used synergistically, the antibacterial and bacteriostatic properties can be improved remarkably, and the concentration ratio of the silver ions to the betaine salicylate in the product is controlled to be 0.1: 200-0.25: 100, so that a better synergistic antibacterial and bacteriostatic effect can be achieved.
Case 1:
an anionic surfactant system comprises 7.9% of sodium laureth sulfate, 1.6% of sodium laureth sulfate and 4.0% of cocoyl propyl betaine;
bacteriostatic agent: 5.25ppm of silver ions and 0.8% of betaine salicylate, wherein the concentration ratio of the silver ion source to the betaine salicylate in the product is 0.13125: 200.
Case 2:
an anionic surfactant system comprises 7.9% of sodium laureth sulfate, 1.6% of sodium laureth sulfate and 4.0% of cocoyl propyl betaine;
bacteriostatic agent: silver ion 5.25ppm, hexamidine 1.0%.
Case 3:
an anionic surfactant system comprises 7.9% of sodium laureth sulfate, 1.6% of sodium laureth sulfate and 4.0% of cocoyl propyl betaine;
bacteriostatic agent: 5.25ppm of silver ions and 1.0 percent of PCMX.
Case 4:
an anionic surfactant system comprises 7.9% of sodium laureth sulfate, 1.6% of sodium laureth sulfate and 4.0% of cocoyl propyl betaine;
bacteriostatic agent: betaine salicylate 0.8%, hexamidine 1.0%.
Case 5:
an anionic surfactant system comprises 7.9% of sodium laureth sulfate, 1.6% of sodium laureth sulfate and 4.0% of cocoyl propyl betaine;
bacteriostatic agent: betaine salicylate 0.8%, PCMX 1.0%.
The commercial products (surface living systems mainly including anionic living systems) declared as bacteriostatic in cases 1-5 and 2 were subjected to anti-bacterial and bacteriostatic tests according to the detection and analysis method of QB/T2738-2012 "evaluation method for antibacterial and bacteriostatic effects of daily chemical products" 7.3, and the test results are shown in table 4:
TABLE 4 comparison of the bacteriostatic properties of the bacteriostatic regimens in anionic surfactant systems
And (4) conclusion: according to the test results in table 4, it can be seen that in case 1, in the anionic surfactant formula system, the antibacterial composition of the present invention has an antibacterial rate of 99% or more against staphylococcus aureus, escherichia coli and candida albicans, has strong antibacterial and bacteriostatic effects, and is significantly superior to other antibacterial compositions (cases 4-5) and commercially available samples.
Case 6:
a cationic surfactant system, which contains 0.075 percent of hexadecyl trimethyl ammonium chloride and 0.075 percent of dodecyl trimethyl ammonium chloride;
bacteriostatic agent: 5.25ppm of silver ions and 0.8% of betaine salicylate, wherein the concentration ratio of the silver ion source to the betaine salicylate in the product is 0.13125: 200.
Case 7
A cationic surfactant system, which contains 0.075 percent of hexadecyl trimethyl ammonium chloride and 0.075 percent of dodecyl trimethyl ammonium chloride;
bacteriostatic agent: silver ion 5.25ppm, hexamidine 1.0%.
Case 8
A cationic surfactant system, which contains 0.075 percent of hexadecyl trimethyl ammonium chloride and 0.075 percent of dodecyl trimethyl ammonium chloride;
bacteriostatic agent: 5.25ppm of silver ions and 1.0 percent of PCMX.
Case 9
A cationic surfactant system, which contains 0.075 percent of hexadecyl trimethyl ammonium chloride and 0.075 percent of dodecyl trimethyl ammonium chloride;
bacteriostatic agent: betaine salicylate 0.8%, hexamidine 1.0%.
Case 10
A cationic surfactant system, which contains 0.075 percent of hexadecyl trimethyl ammonium chloride and 0.075 percent of dodecyl trimethyl ammonium chloride;
bacteriostatic agent: betaine salicylate 0.8%, PCMX 1.0%.
The test results of the tests on the cases 6 to 10 are shown in table 5 according to the detection and analysis method of QB/T2738-2012 evaluation method for antibacterial and bacteriostatic effects of daily chemical products 7.3:
TABLE 5 comparison of the bacteriostatic properties of the bacteriostatic regimens in the cationic surfactant system
And (4) conclusion: according to the test results in table 5, it can be seen that in the cationic surfactant system, in case 6, the bacteriostatic rate of the bacteriostatic composition of the present invention on staphylococcus aureus, escherichia coli and candida albicans can reach more than 99%, and the bacteriostatic rate is obviously superior to the anti-bacteriostatic effect produced by the combination of the single bacteriostatic agent and other bacteriostatic agents (cases 7-10) in the composition.
Case 11:
a nonionic surfactant system comprising 1% octyl/decyl glucoside, 1% PEG-20 sorbitan cocoate; bacteriostatic agent: 5.25ppm of silver ions and 0.8% of betaine salicylate, wherein the concentration ratio of the silver ion source to the betaine salicylate in the product is 0.13125: 200.
Case 12:
a nonionic surfactant system comprising 1% octyl/decyl glucoside, 1% PEG-20 sorbitan cocoate;
bacteriostatic agent: silver ion 5.25ppm, hexamidine 1.0%.
Case 13:
a nonionic surfactant system comprising 1% octyl/decyl glucoside, 1% PEG-20 sorbitan cocoate;
bacteriostatic agent: 5.25ppm of silver ions and 1.0 percent of PCMX.
Case 14:
a nonionic surfactant system comprising 1% octyl/decyl glucoside, 1% PEG-20 sorbitan cocoate;
bacteriostatic agent: betaine salicylate 0.8%, hexamidine 1.0%.
Case 15:
a nonionic surfactant system comprising 1% octyl/decyl glucoside, 1% PEG-20 sorbitan cocoate;
bacteriostatic agent: betaine salicylate 0.8%, PCMX 1.0%.
The cases 11 to 15 were subjected to anti-bacterial and bacteriostatic tests, and the test results are shown in table 6 according to the detection and analysis method of QB/T2738-2012 "evaluation method for antibacterial and bacteriostatic effects of daily chemical products" 7.3:
TABLE 6 comparison of the bacteriostatic properties of the bacteriostatic regimens in the nonionic surfactant system
And (4) conclusion: according to the test results in table 6, it can be seen that in case 11 of the nonionic surfactant system, the bacteriostatic composition of the present invention has a bacteriostatic rate of 99% or more against staphylococcus aureus, escherichia coli and candida albicans, and has strong anti-and bacteriostatic effects. Is obviously better than the combination of single bacteriostatic agent and other bacteriostatic agents (cases 12-15) in the using composition to generate the anti-bacteria and bacteriostatic effects.
In conclusion, the betaine salicylate and the silver ion source are a group of mild and efficient antibacterial compositions, do not have charge adsorption and other effects with anionic surfactants, cationic surfactants and the like, influence the stability and antibacterial effect of products, and can be suitable for formula products of various surfactant systems such as anionic, cationic and nonionic surfactant systems.
The basic formula preparation method and the bacteriostasis scheme of the mild bacteriostasis shampoo are the same as those of case 1:
first, anti, bacteriostasis test
The detection basis is as follows: the hygienic standard GB 15979 + 2002 appendix C of the disposable hygienic article.
Detection conditions are as follows: the experimental temperature is 19-21 ℃, and the experiment is repeated for 3 times.
Dilution ratio: diluting at a ratio of 1: 1.
As a result: after repeated experiments for 3 times, the results show that the average value of the bacteriostasis rates of the test sample on escherichia coli for 2min, 5min, 10min and 20min is more than 99.99 percent. See table 7.
After repeated experiments for 3 times, the results show that the average values of the bacteriostasis rates of the test samples on staphylococcus aureus in 2min, 5min, 10min and 20min are all more than 99.99%. See table 8.
After repeated experiments for 3 times, the results show that the average values of the bacteriostatic rates of the test sample on Candida albicans for 2min, 5min, 10min and 20min are all more than 99.99%. See table 9.
And (4) conclusion: the results of 3 times of repeated tests show that the sample has stronger bacteriostatic action on escherichia coli, staphylococcus aureus and candida albicans.
Second, product irritation test
The detection basis is as follows: technical code for disinfection of Ministry of health (2002 edition) 2.3.3.3.1; disinfection product inspection Specification 6.6(3)
And (3) testing a sample: diluting shampoo to 50% water solution
Experimental animals: 3 common-grade New Zealand rabbits with animal quality qualification No. 20210104Cezz0610038740
And (3) test environment: room temperature 20.4-22.1 deg.c and relative humidity 52.6-64.8%
The test steps are as follows: 1. preparation of a test sample: weighing 5.12g of sample stock solution, placing the sample stock solution in a beaker, adding 5.12g of pure water, and fully and uniformly mixing to be detected; 2. shearing off hairs on two sides of the spine of the back of the rabbit 24h before the test, wherein the hair removing ranges are about 3cm multiplied by 3cm respectively at the left side and the right side, and selecting animals with healthy, intact and undamaged skin for testing; 3. 0.5ml of the pre-treated test sample was applied to one side of the skin and the other side served as a control. After 4h of application, the residue was removed by rinsing with warm water. And observing and scoring the results at 1h, 24h and 48h after the test sample is removed, and judging the skin irritation strength. The control zone is treated in the same manner as the test zone.
And (3) test results: the skin reaction of the applied part is observed at 1h, 24h and 48h after the test sample is removed, the highest integral average value of the test sample to the primary intact skin irritation reaction of the rabbit is 0.33, and the detail is shown in a table 10:
and (4) conclusion: the test result of the test object on the rabbit once complete skin irritation test is nonirritant, no other toxicity is seen, and the test result meets the requirement of the disinfection technical specification (2002 edition) of the ministry of health.
Third, product toxicity test
The inspection basis is as follows: acute oral toxicity test: ministry of health Disinfection technical Specification (2002 edition) 2.3.1; disinfection product inspection Specification 6.6 (1).
Evaluation basis: disinfection technical Specification of Ministry of public health (2002 edition)
And (3) test results: LD50 is more than 5062.4mg/kg, and experimental animals do not have any toxic symptoms and toxic death within 14 days after being infected with the toxin; the body weight of the male and female animals is not abnormal. After the experimental observation is finished, the gross anatomy examination of the tested animal has no abnormal change.
And (4) conclusion: the test substance has acute oral median lethal dose LD50 of more than 5000mg/kg for experimental animals (mice), the sample is practically nontoxic according to acute toxicity classification, and the detection result meets the requirement of disinfection technical specification (2002 edition) of Ministry of health. The raw materials and equipment used in the invention are common raw materials and equipment in the field if not specified; the methods used in the present invention are conventional in the art unless otherwise specified.
The above description is only a preferred embodiment of the present invention, and is not intended to limit the present invention, and all simple modifications, alterations and equivalents of the above embodiments according to the technical spirit of the present invention are still within the protection scope of the technical solution of the present invention.