Antimicrobial composition and application thereof

Abstract

The invention discloses an antimicrobial composition and application thereof. The antimicrobial composition comprises: (a) isohexylene glycol; and (b) a second antimicrobial preparation, wherein the second antimicrobial preparation is selected from at least one of capryloyl hydroxamic acid and p-hydroxyacetophenone; the isohexylene glycol disclosed by the invention has good solubility on the capryloyl hydroximic acid or the p-hydroxyacetophenone, so that the capryloyl hydroximic acid and / or the p-hydroxyacetophenone still have good stability under a low-temperature condition; according to the present invention, the synergistic interaction between the isohexylene glycol and the capryloyl hydroximic acid and / or p-hydroxyacetophenone is completely performed, such that the antimicrobial effect is significantly improved, and the antimicrobial composition can be used in daily chemical products, cosmetics, personal care compositions or cleaning compositions, and has advantages of low use amount, safety, effectiveness, nature, low irritation and the like.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of antimicrobial composition, and particularly relates to an antimicrobial composition and application thereof. BACKGROUND

[0002] The antimicrobial composition refers to a substance added in daily-use chemicals, cosmetics, personal care compositions or cleaning compositions for the purpose of inhibiting the growth and reproduction of microorganisms in the daily-use chemicals, cosmetics, personal care compositions or cleaning compositions.

[0003] In the production and use process of daily-use chemicals, cosmetics, personal care compositions or cleaning compositions, some microorganisms are inevitably mixed in, and the mixing of microorganisms will cause the spoilage of daily-use chemicals, cosmetics, personal care compositions or cleaning compositions. The antimicrobial composition can inhibit the growth and reproduction of microorganisms in daily-use chemicals, cosmetics, personal care compositions or cleaning compositions, maintain the stable properties of daily-use chemicals, cosmetics, personal care compositions or cleaning compositions, and make them not easy to deteriorate in the production and use process.

[0004] Traditionally, one or more of the 51 preservatives allowed to be used in cosmetics regulations are compounded to solve the problem of microbial breeding in daily-use chemicals, cosmetics, personal care compositions or cleaning compositions. The 51 preservatives include phenols, esters, halides and quaternary ammonium salts, etc., among which p-hydroxybenzoic acid esters (nipagin esters), isothiazolinones, imidazolidinyl urea and bronopol are the most commonly used preservatives. However, chemical preservatives can easily cause skin problems, for example, isothiazolinones can cause irritant allergy, and bronopol can cause the formation of carcinogens, therefore, many countries have made strict limitations on the types and amounts of them. Traditional chemical preservatives have been unable to meet people's needs, and the research on their substitutes is attracting more and more attention.

[0005] Caprylylhydroxamic acid and p-hydroxyacetophenone have the effect of inhibiting the growth of microorganisms such as bacteria and fungi, are safe and mild, have no irritation to the human body, and can replace traditional preservatives, but when used alone, their antimicrobial growth ability is not strong. In addition, caprylylhydroxamic acid and p-hydroxyacetophenone have low solubility and poor low-temperature stability, for example, in the patent application CN107624758A, one or more of 1,2-propanediol, 1,3-propanediol and polyethylene glycol 400 are used as solvents to dissolve p-hydroxyacetophenone, but the solubility of p-hydroxyacetophenone in these solvents is not high, and it needs to be dissolved by heating. Once the temperature returns to room temperature, p-hydroxyacetophenone will precipitate, and if it is refrigerated or cooled to-18℃, it will precipitate even faster.

[0006] Existing technologies typically address the low solubility and poor low-temperature stability of octanoyl hydroxamic acid and p-hydroxyacetophenone by adding solubilizers, such as alkylphenol polyoxyethylene ethers, fatty alcohol polyoxyethylene ethers, and hydrogenated castor oil polyoxyethylene ethers. However, the addition of solubilizers increases costs, and these solubilizers often contain carcinogenic dioxane components. Summary of the Invention

[0007] To address the shortcomings of the prior art, this invention provides an antimicrobial composition in which isohexyl glycol exhibits good solubility for capryloyl hydroxamic acid or p-hydroxyacetophenone, ensuring that capryloyl hydroxamic acid and / or p-hydroxyacetophenone maintain good stability under low-temperature conditions. By fully leveraging the synergistic effect between isohexyl glycol and capryloyl hydroxamic acid and / or p-hydroxyacetophenone, the antimicrobial effect is significantly improved. This antimicrobial composition can be used in daily chemical products, cosmetics, personal care compositions, or cleaning compositions, and has advantages such as low dosage, safety and effectiveness, and natural low irritation.

[0008] The purpose of this invention is to provide an antimicrobial composition comprising:

[0009] (a) isohexyldiol; and

[0010] (b) A second antimicrobial agent, wherein the second antimicrobial agent is selected from at least one of capryloyl hydroxamic acid and p-hydroxyacetophenone.

[0011] In some embodiments of the present invention, the mass ratio of isohexanediol to the second antimicrobial agent is ≥1.9. This mass ratio includes, but is not limited to, 1.9:1, 2.0:1, 2.1:1, 2.2:1, 2.3:1, 2.5:1, 3.0:1, 3.5:1, 4.0:1, 4.5:1, 5.0:1, 5.5:1, 6.0:1, 6.5:1, 7.0:1, 7.5:1, 8.0:1, 8.5:1, 9.0:1, and 9.5. :1, 10.0:1, 10.5:1, 11.0:1, 12.0:1, 13.0:1, 14.0:1, 15.0:1, 16.0:1, 17.0:1, 18.0:1, 19.0:1, 20.0:1, 21.0:1, 22.0:1, 23.0:1, 24.0:1, 25.0:1, 26.0:1, 27.0:1, 28.0:1, 29.0:1, 30.0:1, 31.0:1, 32.0:1, 33.0:1.

[0012] In some embodiments of the present invention, the mass ratio of isohexyl glycol to the second antimicrobial agent is 2.3-33:1, including but not limited to 2.3:1, 3:1, 5:1, 8:1, 11:1, 14:1, 17:1, 20:1, 23:1, 26:1, 29:1, and 30:1.

[0013] In some embodiments of the present invention, the second antimicrobial agent is selected from capryloyl hydroxamic acid and p-hydroxyacetophenone.

[0014] In some embodiments of the present invention, the mass ratio of capryloyl hydroxamic acid to p-hydroxyacetophenone is 3-10:15-30, including but not limited to 3:15, 4:15, 1:3, 2:5, 7:15, 8:15, 3:5, 2:3, 5:8, 10:17, 5:9, 10:19, 1:2, 10:21, 5:11, 10:23, 5:12, 10:25, 5:13, 10:27, 5:14, and 10:29.

[0015] In some embodiments of the present invention, the antimicrobial composition further includes excipients.

[0016] In some embodiments of the present invention, the mass ratio of isohexyl glycol to excipients is ≥2.

[0017] In some embodiments of the present invention, the mass ratio of isohexyl glycol to excipients is 2-91:1, including but not limited to 2:1, 5:1, 10:1, 15:1, 20:1, 25:1, 30:1, 35:1, 35:1, 40:1, 45:1, 50:1, 55:1, 60:1, 65:1, 70:1, 75:1, 80:1, 85:1, 90:1, and 91:1.

[0018] In some embodiments of the present invention, the excipients include at least one selected from glyceryl caprylate, ethylhexylglycerin, polyglycerol fatty acid ester, 1,2-propanediol, 1,3-propanediol, 1,3-butanediol, methylpropanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, isopentanediol, dipropylene glycol, and glycerol.

[0019] Another object of the present invention is to provide the use of the aforementioned antimicrobial composition as a preservative.

[0020] Another object of the present invention is to provide the application of the aforementioned antimicrobial composition in the preparation of daily chemical products.

[0021] Another object of the present invention is to provide the use of the aforementioned antimicrobial composition in the preparation of cosmetics.

[0022] Another object of the present invention is to provide a personal care composition comprising an effective amount of the aforementioned antimicrobial composition.

[0023] Another object of the present invention is to provide a cleaning composition comprising an effective amount of the aforementioned antimicrobial composition.

[0024] Another object of the present invention is to provide a method for using the aforementioned antimicrobial composition as a preservative.

[0025] Another object of the present invention is to provide a method for preserving daily chemical products, cosmetics, personal care compositions or cleaning compositions by adding the aforementioned antimicrobial composition.

[0026] Another object of the present invention is to provide a method for combating microorganisms by adding the aforementioned antimicrobial composition to daily chemical products, cosmetics, personal care compositions or cleaning compositions.

[0027] In some embodiments of the present invention, the amount of the antimicrobial composition, by weight percentage, is 0.5-3% of the daily chemical or cosmetic product, including but not limited to 0.5%, 0.8%, 1.1%, 1.4%, 1.7%, 2.0%, 2.3%, 2.6%, and 3%.

[0028] In some embodiments of the present invention, the amount of the antimicrobial composition, by weight percentage, is 0.5-3% of the personal care composition, including but not limited to 0.5%, 0.8%, 1.1%, 1.4%, 1.7%, 2.0%, 2.3%, 2.6%, and 3%.

[0029] In some embodiments of the present invention, the amount of the antimicrobial composition is 0.5-3% of the cleaning composition by weight, including but not limited to 0.5%, 0.8%, 1.1%, 1.4%, 1.7%, 2.0%, 2.3%, 2.6%, and 3%.

[0030] Personal care compositions, cleaning compositions, daily chemical products, or cosmetics may contain anti-acne agents, anti-skin aging agents, abrasives, antistatic agents, anti-cellulite agents, anti-dandruff agents, anti-inflammatory agents, antiperspirants, anti-irritants, anti-irritants, antioxidants, astringents, adhesives, bactericides, buffers, carriers, chelating agents, cell stimulants, gelling agents, conditioning agents, depilatory agents, surfactants, deodorants, antiperspirants, emulsifiers, essential oils, color-fixing agents, fibers, emulsifiers, film-forming agents, enzymes, foam forming agents, foam stabilizers, defoamers, stain repellents, foam promoters, gelling agents, hair conditioning agents, hair styling agents, abrasives, silicones, hair straighteners, humectants, moisturizers, humectants, detergents, bleaching agents, strengthening agents, friction reducers, cleansing agents, optical brighteners, and impregnating agents. Additional additives and auxiliaries, including suspending agents, flavoring agents, odorants, skin brightening agents, thickeners, lubricants, polymers, gloss agents, skin healing agents, powders, moisturizing creams, ointments, proteins, fatliquoring agents, skin soothing agents, skin cleansers, skin care agents, skin brighteners, skin protectants, skin softeners, coolants, sunscreens, plasticizers, skin coolants, warming agents, skin warming agents, stabilizers, UV absorbers, covering agents, polishing agents, UV filters, detergents, fabric softeners, vitamins, oils, waxes, fats, phospholipids, saturated fatty acids, dyes, color protectants, monounsaturated or polyunsaturated fatty acids, α-hydroxy acids, polyhydroxy fatty acids, liquefying agents, pigments, polyols, corrosion inhibitors, aromatic substances, surfactants, electrolytes, organic solvents, or silicone derivatives.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] (1) The isohexanediol of the present invention has good solubility for octanoyl hydroxamic acid or p-hydroxyacetophenone, so that octanoyl hydroxamic acid and / or p-hydroxyacetophenone still have good stability under low temperature conditions.

[0033] (2) The present invention significantly improves the antimicrobial effect by giving full play to the synergistic effect between isohexanediol and octanoyl hydroxamic acid and / or p-hydroxyacetophenone.

[0034] (3) The antimicrobial composition of the present invention can be used in daily chemical products, cosmetics, personal care compositions or cleaning compositions, and has the advantages of low dosage, safety and effectiveness, natural and low irritation. Attached Figure Description

[0035] Figure 1 This is a Bliss synergistic score plot of p-hydroxyacetophenone and isohexanediol on Escherichia coli.

[0036] Figure 2 This is a Bliss synergistic score diagram of p-hydroxyacetophenone and isohexyldiol on Burkholderia cepacia.

[0037] Figure 3 This is a synergistic score diagram of octanoyl hydroxamic acid and isohexanediol on Escherichia coli Bliss.

[0038] Figure 4 The graph shows the synergistic score of octanoyl hydroxamic acid and isohexyl glycol against Burkholderia cepacia Bliss. Detailed Implementation

[0039] To enable those skilled in the art to better understand the technical solutions of this invention, the technical solutions of this invention will be clearly and completely described below in conjunction with the embodiments of this invention. Obviously, the described embodiments are only some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of this invention.

[0040] Low temperature stability test:

[0041] The antimicrobial compositions were weighed according to Table 1 and poured into beakers. They were then heated in a water bath at 80±2℃ and stirred until completely dissolved. After cooling to room temperature, the solutions were dispensed and placed in a constant temperature incubator at 0℃±2℃. After one month, the solutions were taken out and their condition was observed.

[0042] Table 1. Results of low-temperature stability tests on the antimicrobial composition.

[0043]

[0044] As shown in Table 1, only isohexyl glycol exhibits excellent low-temperature stability against both capryloyl hydroxamic acid and p-hydroxyacetophenone; dipropylene glycol shows good low-temperature stability against p-hydroxyacetophenone, but poor low-temperature stability against capryloyl hydroxamic acid; 1,3-butanediol and isopentanediol show very poor low-temperature stability against both capryloyl hydroxamic acid and p-hydroxyacetophenone. Furthermore, isohexyl glycol, as a solvent, also demonstrates excellent low-temperature stability against complexes of capryloyl hydroxamic acid and p-hydroxyacetophenone, or those containing other excipients.

[0045] Antimicrobial synergistic effect test:

[0046] The synergistic activity of isohexyl glycol in inhibiting Escherichia coli and Burkholderia cepacia was determined. To calculate the synergistic activity of isohexyl glycol with the secondary antimicrobial active ingredient, the drug combination effect index score was calculated using the Bliss independent model. The procedure and test results are as follows:

[0047] (1) MIC determination of p-hydroxyacetophenone, octanoyl hydroxamic acid, and isohexanediol:

[0048] Indicator bacterial suspension: Escherichia coli and Burkholderia cepacia were selected as indicator bacteria. The indicator bacteria were washed with nutrient broth and resuspended to a concentration of 1×10⁻⁶. 6 CFU / mL bacterial suspension; 8000ppm~125ppm p-hydroxyacetophenone solution, 2400ppm~37.5ppm capryloyl hydroxamic acid solution, and 240000ppm~2500ppm isohexanediol solution were prepared with sterile water. Sterile water was used as the solvent for all bacterial suspensions, p-hydroxyacetophenone solution, capryloyl hydroxamic acid solution, and isohexanediol solution. 100µL of each solution and 100µL of bacterial suspension were added to 96-well plates, respectively, and the plates were incubated at 36℃ for 24h. The absorbance was measured by microplate reader, and the minimum inhibitory concentration (MIC) at which bacteria were inhibited was used as the MIC value.

[0049] Table 2. MICs of p-hydroxyacetophenone, octanoyl hydroxamic acid, and isohexanediol.

[0050]

[0051] The results are shown in Table 2. The MIC of p-hydroxyacetophenone against both Escherichia coli and Burkholderia cepacia was 2000 ppm, the MIC of capryloyl hydroxamic acid against both Escherichia coli and Burkholderia cepacia was 600 ppm, the MIC of isohexyl glycol against Escherichia coli was 60000 ppm, and the MIC of Burkholderia cepacia was 40000 ppm.

[0052] (2) The synergistic effect of isohexylene glycol and the second antimicrobial active ingredient was calculated using the Bliss independent model to calculate the drug combination effect index score:

[0053] The criteria for judgment are as follows: a synergy index greater than 0 indicates a synergistic effect, a synergy index equal to 0 indicates no correlation effect, and a synergy index less than 0 indicates an antagonistic effect.

[0054] Table 3. Synergistic index of p-hydroxyacetophenone, octanoyl hydroxamic acid and isohexanediol, respectively.

[0055]

[0056] The results are shown in Table 3 and Appendix. Figures 1-4As shown, when the Bliss model was used to calculate and analyze the data, the synergistic index of p-hydroxyacetophenone and isohexanediol against Escherichia coli was 18.621, indicating a significant synergistic antibacterial effect; the synergistic index of p-hydroxyacetophenone and isohexanediol against Burkholderia cepacia was 24.22, indicating a strong synergistic effect; the synergistic index of capryloyl hydroxamic acid and isohexanediol against Escherichia coli was 10.44, indicating a significant synergistic antibacterial effect; and the synergistic index of capryloyl hydroxamic acid and isohexanediol against Burkholderia cepacia was 1.02, indicating a synergistic antibacterial effect. Therefore, it is believed that p-hydroxyacetophenone and isohexanediol, and capryloyl hydroxamic acid and isohexanediol, have good synergistic antibacterial and synergistic effects against Escherichia coli and Burkholderia cepacia.

[0057] Preservative efficacy test:

[0058] The preservative efficacy test was conducted according to ISO 11930-2019. The bacteria used in this experiment were *Pseudomonas aeruginosa* ATCC9027, *Escherichia coli* ATCC8739, and *Staphylococcus aureus* ATCC6538; the fungi used were *Candida albicans* ATCC10231 and *Aspergillus niger* ATCC16404, all of which were obtained from the Guangdong Provincial Microbial Culture Collection Center.

[0059] The initial inoculum size of the three bacteria used in the experiment was 10. 5 -10 6 CFU / g, with an initial inoculum of 10 CFU / g of Candida albicans and Aspergillus niger. 4 -10 5 CFU / g was measured on days 7, 14, and 28, and the logarithmic decrease in the number of various microorganisms at the corresponding time points was calculated.

[0060] Antimicrobial compositions were tested for their preservative efficacy in facial mask liquids, body lotions, and shampoos. The tested antimicrobial composition systems and cosmetic formulations are shown in Table 6.

[0061] Table 6. Antiseptic efficacy test of antimicrobial compositions.

[0062]

[0063] Table 7. Ingredients and manufacturing process of facial mask liquid.

[0064]

[0065] Table 8. Body Lotion Ingredients and Manufacturing Process.

[0066]

[0067] Table 9. Shampoo ingredient list and manufacturing process.

[0068]

[0069] The experimental results were determined as follows: the bacterial count decreased by 3 orders of magnitude on day 7, and decreased by 3 orders of magnitude on days 14 and 28 without increasing; the count of Candida albicans decreased by 1 order of magnitude on day 7, and decreased by 1 order of magnitude on days 14 and 28 without increasing; and the count of Aspergillus niger did not increase on day 14 and decreased by 1 order of magnitude on day 28. These results were considered as passing the test. The results are shown in Tables 10-12.

[0070] Table 10. Test data on the preservative efficacy of facial mask liquid.

[0071]

[0072] Table 11. Test data on the preservative efficacy of body lotion.

[0073]

[0074] Table 12. Test data on the preservative efficacy of shampoo.

[0075]

[0076] The results in Tables 10-12 show that the antimicrobial composition of octanoyl hydroxamic acid, p-hydroxyacetophenone alone or in combination with isohexyl glycol and excipients can exert excellent preservative effects in aqueous systems, emulsion systems, and washing and conditioning systems.

[0077] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art should understand that after reading this application specification, they can still modify or make equivalent substitutions to the specific implementation of the present invention, but these modifications or changes do not depart from the protection scope of the pending claims of the present invention.

Claims

1. An antimicrobial composition, characterized in that, include: (a) Isohexanediol; and (b) A second antimicrobial agent, wherein the second antimicrobial agent is selected from at least one of capryloyl hydroxamic acid and p-hydroxyacetophenone.

2. The antimicrobial composition according to claim 1, characterized in that, The mass ratio of isohexyl glycol to the second antimicrobial agent is ≥1.9; Preferably, the mass ratio of isohexyl glycol to the second antimicrobial agent is 2.3-33:

1.

3. The antimicrobial composition according to claim 1, characterized in that, The second antimicrobial agent is selected from capryloyl hydroxamic acid and p-hydroxyacetophenone.

4. The antimicrobial composition according to claim 3, characterized in that, The mass ratio of octanoyl hydroxamic acid to p-hydroxyacetophenone is 3-10:15-30.

5. The antimicrobial composition according to any one of claims 1 to 4, characterized in that, It also includes auxiliary materials.

6. The antimicrobial composition according to claim 5, characterized in that, The mass ratio of isohexyl glycol to excipients is ≥2; Preferably, the mass ratio of isohexyl glycol to excipients is 2-91:

1.

7. The antimicrobial composition according to claim 5, characterized in that, The excipients include at least one of the following: glyceryl caprylate, ethylhexylglycerin, polyglycerol fatty acid ester, 1,2-propanediol, 1,3-propanediol, 1,3-butanediol, methylpropanediol, 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, isopentanediol, dipropylene glycol, and glycerin.

8. The use of the antimicrobial composition according to any one of claims 1 to 7 as a preservative or in the preparation of daily chemical products or cosmetics.

9. A personal care composition, characterized in that, Containing an effective amount of the antimicrobial composition according to any one of claims 1 to 8.

10. A cleaning composition, characterized in that, The antimicrobial composition comprising an effective amount of any one of claims 1 to 7.

11. The application according to claim 8, characterized in that, The amount of the antimicrobial composition used is 0.5-3% of the daily chemical or cosmetic product by weight percentage.

12. The personal care composition according to claim 9, characterized in that, The amount of the antimicrobial composition is 0.5-3% of the personal care composition by weight percentage.

13. The cleaning composition according to claim 10, characterized in that, The amount of the antimicrobial composition is 0.5-3% of the cleaning composition by weight percentage.

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