Liposome antibacterial and bacteriostatic synergist, and preparation method and application thereof
By utilizing the multi-target blocking mechanism of liposome antibacterial and bacteriostatic synergists, the problems of preservative resistance and safety in daily chemical products have been solved, achieving highly efficient and safe antibacterial and bacteriostatic effects, and making it suitable for a variety of daily chemical products.
Patent Information
- Application Number
- CN202411347432.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-09-26
- Publication Date
- 2025-11-11
- Estimated Expiration
- 2044-09-26
AI Technical Summary
Existing preservatives in daily chemical products have drug resistance issues, leading to increased bacterial resistance. Furthermore, improper use of traditional preservatives may cause skin irritation and excessive microbial levels. The market urgently needs safe and effective antibacterial and bacteriostatic synergists.
The drug employs liposome-based antibacterial and antimicrobial synergists, including metal chelators, efflux pump inhibitors, dispersants, and liposome wall materials. Through the synergistic combination of liposome formulations, it achieves internal bacterial penetration and external blockage, inhibits the efflux pump mechanism and the production of β-lactamase, and blocks biofilm formation, thereby achieving multi-target inhibition of bacterial drug resistance.
It significantly enhances antibacterial and bacteriostatic effects, reduces the amount of preservatives used, improves product safety, has long-lasting stability, and meets the storage and application needs of daily chemical products.
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Figure CN119286598B_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of daily chemical products technology, and in particular to a liposome antibacterial and bacteriostatic synergist, its preparation method and application. Background Technology
[0002] Currently, bacterial resistance to antimicrobial drugs has developed into a global medical crisis, with multidrug-resistant bacteria emerging that cannot be treated with any common antibiotics. Therefore, there is an urgent need for novel antimicrobial and bacteriostatic synergists to restore bacterial sensitivity to these drugs. In the field of daily chemical products, the use of preservatives has always been a subject of considerable concern and controversy.
[0003] On the one hand, preservatives in daily chemical products do pose certain risks, especially when used improperly or exceeding safe concentrations. These can easily trigger allergic reactions, dry skin, skin irritation, and disruption of the skin's microbiome. Common high-risk preservatives in daily chemical products include methylparaben, propylparaben, butylparaben, and methylisothiazolinone. Long-term use of these preservatives may cause serious skin damage and even interfere with female endocrine function. Therefore, topical preservatives like phenoxyethanol, pentylene glycol, and hexanediol are popular in the market. However, because their antibacterial effects are generally weak, these products are prone to exceeding microbial limits.
[0004] On the other hand, due to the emergence of bacterial resistance, some daily chemical companies have had to increase the amount of preservatives used to ensure the normal delivery time of products, thereby increasing the safety issues related to preservative use. Seeking new preservatives with higher safety, or finding ways to reduce the amount of preservatives with potential risks, has become a pressing issue that the industry urgently needs to address.
[0005] Therefore, this study aims to provide a novel antibacterial and antimicrobial synergist that significantly enhances antibacterial and antimicrobial effects, reduces the dosage of risky preservatives, and balances safety and preservative efficacy. This research has significant research and application value in helping daily chemical companies optimize their product preservation systems. Summary of the Invention
[0006] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a liposomal antibacterial and antimicrobial synergist, its preparation method, and its application. The liposomal antibacterial and antimicrobial synergist provided by this invention has a significant synergistic effect against different types of preservatives, can reduce the amount of preservatives used, and has high stability, meeting the storage and application requirements of daily chemical products.
[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows:
[0008] In a first aspect, the present invention provides a liposome antibacterial and bacteriostatic synergist, comprising liposome contents, liposome wall material, dispersant and water, wherein the liposome contents include a metal chelating agent and an efflux pump inhibitor, and the dispersant is a polyol;
[0009] The liposome antibacterial and bacteriostatic synergist comprises, by weight percentage: 0.001-1% metal chelating agent, 2-50% dispersant, 0.01-5% efflux pump inhibitor, 0.1-10% liposome wall material, and the balance being water.
[0010] This invention provides a liposomal formulation of an antibacterial and bacteriostatic synergist with metal chelating agents and efflux pump inhibitors as the main active ingredients. The metal chelating agent chelates, strips, and binds zinc ions to the active site of metallo-β-lactamase (MBL), thereby inhibiting MBL. MBL is a major threat in the field of microbial resistance, as it can induce resistance to almost all β-lactam drugs. By using a metal chelating agent to inhibit the active site of the enzyme, bacterial resistance is reduced, thus enhancing the efficacy of preservatives, bacteriostatic agents, and other drugs from within.
[0011] Efflux pump inhibitors can interfere with the assembly of microbial efflux pumps, thereby blocking the energy source of the efflux pumps and preventing substrates from directly passing through the efflux channels. By interfering with the bacterial efflux function through efflux pump inhibitors, bacterial activity is inhibited, achieving a synergistic antibacterial and bacteriostatic effect from within. Under the specific ratios mentioned above, the metal chelating agent and the efflux pump inhibitor work together to achieve a good synergistic effect, resulting in a significant synergistic antibacterial and bacteriostatic effect; outside the ratio range or when the efflux pump inhibitor acts alone, the effect is poor.
[0012] The key to synergistic antibacterial and bacteriostatic effects lies in using liposomes as wall materials to form liposomes. For Gram-negative bacteria, many drugs struggle to penetrate their outer membranes, which is the main reason why most antibacterial drugs are ineffective against them. Bacterial cell membranes are primarily composed of lipids (mainly phospholipids and cholesterol). Based on the principle of "like dissolves like," using liposome wall materials can achieve membrane permeability, inactivating these permeability barriers and allowing drugs to enter the bacteria.
[0013] Dispersants prevent the formation of biofilms on the extracellular surface of bacteria by biomolecules, thereby reducing bacterial drug resistance. Biofilms are membrane tissues formed by microorganisms, composed of complex extracellular polymers, and are specialized membrane tissues used by microorganisms to resist external stress conditions and maintain survival. Simultaneously, a specific ratio of dispersant can significantly improve the flexibility of the liposome outer layer, resulting in better stability. When the ratio of dispersant to liposome wall material is unsuitable, the stability of the liposomes will decrease significantly, failing to meet the storage and use requirements of daily chemical products.
[0014] The liposomal antibacterial and bacteriostatic synergist provided by this invention addresses the root cause of bacterial resistance by employing a synergistic combination of liposomal formulations. Its small particle size and strong permeability inactivate the extracellular membrane permeability barrier, allowing the drug to penetrate the bacteria and inhibit or block efflux pump mechanisms and β-lactamase production within the microorganism. Externally, it blocks biofilm formation, achieving a comprehensive, multi-target approach to inhibit bacterial resistance and thus enhancing antibacterial and bacteriostatic efficacy. Furthermore, the liposomal antibacterial and bacteriostatic synergist provided by this invention exhibits a sustained-release effect, providing long-lasting antibacterial and bacteriostatic synergistic effects and possessing significant application value in the daily chemical industry.
[0015] Preferably, the liposome antibacterial and bacteriostatic synergist comprises, by weight percentage: 0.03-1% metal chelating agent, 30-40% dispersant, 0.5-2% efflux pump inhibitor, 3-5% liposome wall material, and the balance being water.
[0016] Preferably, the metal chelating agent is at least one selected from soybean oil-based ethylmorpholine nitrogen ethyl sulfate, disodium ethylenediaminetetraacetate, tetrasodium ethylenediaminetetraacetate, disodium ethylenetriacetate, sodium gluconate, and sodium tripolyphosphate.
[0017] Preferably, the efflux pump inhibitor is at least one of glycyrrhizic acid, methylpyrrolidone, artesunate, antisense nucleic acid, oligonucleotide, and amikacin.
[0018] Preferably, the dispersant is at least one selected from ethanol, propylene glycol, butylene glycol, hexanediol, pentanediol, and glycerol.
[0019] Preferably, the liposome wall material is at least one of lecithin, hydrogenated lecithin, hydroxylated lecithin, hydrogenated lysophosphatidylcholine, lysophosphatidylcholine, and soybean lecithin.
[0020] More preferably, the metal chelating agent is disodium ethylenediaminetetraacetate, and the efflux pump inhibitor is glycyrrhizic acid.
[0021] More preferably, the liposome antibacterial and bacteriostatic synergist comprises, by weight percentage: 0.1% metal chelating agent, 40% dispersant, 1% efflux pump inhibitor, 3% liposome wall material, and the balance being water.
[0022] By selecting the specific metal chelating agents and efflux pump inhibitors mentioned above and combining them in the above ratio, the optimal antibacterial and bacteriostatic synergistic effects can be achieved.
[0023] Secondly, the present invention provides a method for preparing the above-mentioned liposome antibacterial and antimicrobial synergist, characterized by comprising the following steps:
[0024] (1) Disperse the metal chelating agent and the external discharge pump inhibitor in water, heat and keep warm, and mix well to obtain phase A;
[0025] (2) Dissolve the liposome wall material in a dispersant, heat and keep warm, and mix well to obtain phase B;
[0026] (3) Under heating and stirring, phase B is added dropwise to phase A to obtain phase C; the heating and stirring temperature is 35-65℃.
[0027] (4) Homogenize the C phase to obtain the liposome antibacterial and bacteriostatic synergist.
[0028] Preferably, in step (1), the dispersion condition is stirring at 500-1200 rpm / min; in step (2), the stirring speed is 500-1200 rpm / min.
[0029] Preferably, in step (4), the homogenization pressure is 500-3000 bar.
[0030] Stable liposome dosage forms can be obtained using the above preparation method.
[0031] Thirdly, the present invention provides the application of the above-mentioned liposome antibacterial and bacteriostatic synergist in daily chemical products.
[0032] The liposome antibacterial and bacteriostatic synergist provided by this invention can be further added and compounded for use in various daily chemical products, such as laundry detergent, pet shampoo, and facial mask liquid. It has a long-lasting and stable liposome formulation, which can reduce the amount of preservatives used. Moreover, it is delivered through the permeation of the outer membrane of the liposome, which is highly safe and meets the application needs of the daily chemical industry.
[0033] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0034] (1) The liposome antibacterial and bacteriostatic synergist provided by the present invention starts from the source of bacterial drug resistance and works synergistically. Inside the bacteria, it inhibits and blocks the efflux pump mechanism and inhibits the production of β-lactamase; outside the bacteria, it blocks the formation of biofilm. It works both inside and outside, blocking the production of bacterial drug resistance at multiple targets, thereby achieving the effect of antibacterial and bacteriostatic synergism.
[0035] (2) The liposome antibacterial and bacteriostatic synergist provided by the present invention is in the form of liposomes with small particle size and strong permeability. The liposome wall material is an outer membrane permeation agent, which can inactivate the permeability barrier of the cell membrane and carry the "drug" into the bacteria to achieve the effect of antibacterial and bacteriostatic synergism. At the same time, it also has a sustained release effect, which can prolong the time of antibacterial and bacteriostatic synergism. Attached Figure Description
[0036] Figure 1 The MIC results are shown for the 1,2-hexanediol compound example, comparative example, and control.
[0037] Figure 2 MIC results for the compounded methylparaben example, comparative example, and control;
[0038] Figure 3 This is a graph showing the particle size distribution of Example 2.
[0039] Figure 4 The result graph shows the Zeta potential as in Example 2;
[0040] Figure 5 The graph shows the release rate of the active ingredient in physiological saline, as in Example 3. Detailed Implementation
[0041] To better illustrate the purpose, technical solution, and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments. Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods; the materials and reagents used, unless otherwise specified, are commercially available reagents and materials.
[0042] Example 1
[0043] An embodiment of the liposome antibacterial and bacteriostatic synergist of the present invention is provided, wherein the liposome antibacterial and bacteriostatic synergist of this embodiment is composed of the following components in weight percentage: 0.2% metal chelating agent, 30% dispersant, 0.35% efflux pump inhibitor, 3% liposome wall material and balance water.
[0044] The preparation method of the liposome antibacterial and antimicrobial synergist described in this embodiment is as follows:
[0045] (1) Weigh 0.2g of disodium ethylenediaminetetraacetate and 0.35g of glycyrrhizic acid and disperse them in 66.45g of deionized water. Heat at 45℃ and maintain a stirring speed of 600rpm / min to obtain phase A1.
[0046] (2) Weigh 3g of soybean lecithin and dissolve it evenly in 30g of 1,3-butanediol. Heat at 45℃ to obtain phase B1.
[0047] (3) Heat at 45℃ and stir at 600 rpm / min, adding phase B1 dropwise into phase A1 to obtain phase C1;
[0048] (4) The C1 phase is homogenized by a high-pressure homogenizer at a pressure of 1000 bar to obtain the liposome antibacterial and bacteriostatic synergist, referred to as "Example 1".
[0049] Example 2
[0050] An embodiment of the liposome antibacterial and bacteriostatic synergist of the present invention is provided, wherein the liposome antibacterial and bacteriostatic synergist of this embodiment is composed of the following components in weight percentage: 1% metal chelating agent, 35% dispersant, 2% efflux pump inhibitor, 5% liposome wall material and balance water.
[0051] The preparation method of the liposome antibacterial and antimicrobial synergist described in this embodiment is as follows:
[0052] (1) Weigh 1g of soybean oil-based ethylmorpholine nitrogen ethyl sulfate and 2g of methylpyrrolidone and disperse them in 57g of deionized water. Heat at 55℃ and maintain a stirring speed of 700rpm / min to obtain phase A2.
[0053] (2) Weigh 5g of hydrogenated lecithin and dissolve it evenly in 35g of 1,2-propanediol. Heat at 55℃ to obtain phase B2.
[0054] (3) Heat at 55℃ and stir at 700 rpm / min, adding phase B2 dropwise into phase A2 to obtain phase C2;
[0055] (4) The C2 phase is homogenized by a high-pressure homogenizer at a pressure of 2000 bar to obtain the liposome antibacterial and bacteriostatic synergist, referred to as "Example 2".
[0056] Example 3
[0057] An embodiment of the liposome antibacterial and bacteriostatic synergist of the present invention is provided, wherein the liposome antibacterial and bacteriostatic synergist of this embodiment is composed of the following components by weight percentage: 0.1% metal chelating agent, 40% dispersant, 1% efflux pump inhibitor, 3% liposome wall material and balance water.
[0058] The preparation method of the liposome antibacterial and antimicrobial synergist described in this embodiment is as follows:
[0059] (1) Weigh 0.1g of tetrasodium ethylenediaminetetraacetate and 1g of glycyrrhizic acid and dissolve or disperse them in 55.9g of deionized water. Heat at 65℃ and maintain a stirring speed of 900rpm / min to obtain phase A3.
[0060] (2) Weigh 3g of lecithin and dissolve it evenly in 40g of glycerol. Heat at 65℃ to obtain phase B3.
[0061] (3) Heat at 65℃ and stir at 900 rpm / min, adding phase B3 dropwise into phase A3 to obtain phase C3;
[0062] (4) The C3 phase is homogenized by a high-pressure homogenizer at a pressure of 2500 bar to obtain the liposome antibacterial and bacteriostatic synergist, referred to as "Example 3".
[0063] Example 4
[0064] This invention provides an embodiment of a liposome antibacterial and bacteriostatic synergist. The only difference between this embodiment and Example 3 is that the dosage remains the same, but the metal chelating agent tetrasodium ethylenediaminetetraacetate is replaced with soybean oil-based ethylmorpholine nitrogen ethyl sulfate.
[0065] Example 5
[0066] This invention provides an embodiment of the liposome antibacterial and bacteriostatic synergist. The only difference between this embodiment and Example 3 is that the dosage remains the same, and the efflux pump inhibitor glycyrrhizic acid is replaced with methylpyrrolidone.
[0067] Comparative Example 1
[0068] The only difference between Comparative Example 1 and Example 1 is that the amount of disodium ethylenediaminetetraacetate was increased, the amount of glycyrrhizic acid was reduced (after dilution before addition), and the amount of deionized water was adjusted accordingly to make the mass percentage of metal chelating agent 2% and efflux pump inhibitor 0.005%. The resulting sample is referred to as "Comparative Example 1".
[0069] Comparative Example 2
[0070] The only difference between Comparative Example 2 and Example 1 is that the metal chelating agent disodium ethylenediaminetetraacetate was removed, the amount of glycyrrhizic acid was increased, and the amount of deionized water was adjusted accordingly to make the mass percentage of the efflux pump inhibitor 10%. The resulting sample is referred to as "Comparative Example 2".
[0071] Comparative Example 3
[0072] The only difference between Comparative Example 3 and Example 3 is that the homogenization operation in step (4) is removed, and no liposome dosage form is formed. The resulting sample is referred to as "Comparative Example 3".
[0073] Comparative Example 4
[0074] The only difference between Comparative Example 4 and Example 1 is that the amount of 1,3-butanediol was reduced to 1g, the amount of soybean lecithin was reduced to 0.05g, and the amount of deionized water was increased accordingly to make the mass percentage of dispersant 1% and liposome wall material 0.05%. The resulting sample is referred to as "Comparative Example 4".
[0075] Comparative Example 5
[0076] The only difference between Comparative Example 5 and Example 1 is that the amount of 1,3-butanediol is increased to 51g, the amount of soybean lecithin is increased to 11g, and the amount of deionized water is correspondingly reduced so that the mass percentages are 51% dispersant and 11% liposome wall material. The resulting sample is referred to as "Comparative Example 5".
[0077] Example of effect 1
[0078] To investigate the antibacterial and antimicrobial synergistic effects of the liposome antibacterial and antimicrobial synergist provided by this invention, the minimum inhibitory concentrations (MICs) of methylparaben (an "intra-table preservative") and 1,2-hexanediol (an "extra-table preservative"), commonly used in daily chemical products, were tested. The MICs of the two preservatives were also tested when 10% (w / w) of the example sample, comparative sample, disodium ethylenediaminetetraacetate, 1,3-butanediol, glycyrrhizic acid, and soybean lecithin were added, respectively. The specific methods are as follows:
[0079] The test was conducted in accordance with the minimum inhibitory concentration test (agar dilution method) of the 2002 edition of the "Disinfection Technical Specifications" issued by the Ministry of Health.
[0080] The tested strains were Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Aspergillus niger.
[0081] (1) The culture medium was prepared using MH agar, according to the product instructions, with a pH of 7.2 to 7.4.
[0082] (2) Preparation of drug-containing agar plates: According to the experimental design, different concentrations of antibacterial drugs, which have been serially diluted, were added to MH agar that had been heated and dissolved and equilibrated in a water bath at 45–50°C. The mixture was thoroughly mixed and poured into sterile Petri dishes, with an agar thickness of 3–4 mm. Drug-containing agar plates were prepared at a ratio of 1:9. The prepared drug-containing agar plates should be placed in sealed plastic bags and stored in a refrigerator at 2–8°C for up to 5 days.
[0083] (3) Preparation of inoculum and inoculation: Prepare a bacterial suspension with a concentration equivalent to 0.5 McFarland standard turbidity tubes, then dilute it 1:10. Use a multi-point inoculator to draw up about 1-2 μl of the prepared bacterial suspension and inoculate it onto the surface of an agar plate. Each spot should contain about 10⁴ CFU of bacteria, forming a bacterial patch with a diameter of 5-8 mm. After inoculation, incubate at 35°C for 16-20 h and observe the results.
[0084] (4) Result Interpretation: Place the plate on a dark, non-reflective surface to determine the endpoint of the experiment. The lowest drug concentration that inhibits bacterial growth is defined as the MIC. Slight bacterial growth is observed on agar plates containing trimethoprim or sulfamethoxazole. The lowest drug concentration that inhibits bacterial growth by more than 80% compared to the growth control is taken as the endpoint concentration.
[0085] If more than two colonies grow on agar plates with drug concentrations higher than the endpoint level, or if no colonies grow on agar plates with low drug concentrations but grow on agar plates with high drug concentrations, the purity of the culture should be checked or the test repeated.
[0086] The test results of MIC are shown in Tables 1-1, 1-2 and 1-3. Figure 1 , 2 As shown, it can be seen that:
[0087] The liposome antibacterial and bacteriostatic synergist provided by this invention does not exhibit synergistic antibacterial effects when used individually. Similarly, in the three comparative examples, the simple combination of components also lacks synergistic antibacterial activity. Only when the components are formulated into a liposome dosage form as in the example samples can a significant synergistic antibacterial and bacteriostatic effect be achieved, resulting in a significant reduction in the MIC value. This may be related to the fact that components such as metal chelators and efflux pump inhibitors can directly contact the cell membrane and interior through the permeation of the outer membrane of the liposomes, assisting the antibacterial and bacteriostatic agents in their function. In summary, the liposome combination and ratio used in Example 3 show the best synergistic antibacterial and bacteriostatic effect. The antibacterial and bacteriostatic synergist provided by this invention has significant synergistic effects against both intracellular and extracellular preservatives, and can achieve good synergistic antibacterial effects against a variety of bacteria, thus possessing high application value.
[0088] Table 1-1 MIC results of the example sample, comparative sample, and control + 1,2-hexanediol
[0089]
[0090] Table 1-2 MIC results of the example sample, comparative sample, and control + methylparaben
[0091]
[0092] Example 2
[0093] To investigate the stability of the liposome antibacterial and antimicrobial synergist provided by this invention, particle size distribution, zeta potential, and temperature stability were tested on samples from Examples 1-3 and Comparative Examples 4 and 5.
[0094] (1) Particle size distribution and zeta potential
[0095] Testing equipment: Malvern Zetasizer Nano;
[0096] Testing basis and methods: The experimental methods refer to the Malvern ZETASIZER NANO series operation manual.
[0097] (2) Temperature stability test
[0098] Samples from Example 1, Example 2, Example 3, Comparative Example 4, and Comparative Example 5 were placed under constant temperature conditions of -17℃, 5℃, 45℃, room temperature under light, and room temperature in a dark room, respectively. The appearance changes and stability were observed after 7 days, 14 days, 28 days, 2 months, and 3 months. Samples were considered stable if no sedimentation or aggregation was observed.
[0099] The particle size distribution and zeta potential test results of Examples 1-3 and Comparative Examples 4 and 5 are shown in Table 2. The particle size distribution and zeta potential results of Example 2 are shown in the figure below. Figure 3 , 4 ;
[0100] The temperature stability test results of Examples 1-3 and Comparative Examples 4 and 5 are shown in Table 3.
[0101] For liposomes, generally, the smaller the particle size, the better the stability; the larger the absolute value of the zeta potential, the better the stability. From Tables 2 and 3, we can conclude that:
[0102] In Examples 1-3, when the amounts of dispersant and liposome wall material are within the limits defined by this invention, liposome formulations with stable average particle size and zeta potential can be prepared as antibacterial and bacteriostatic synergists. These formulations exhibit good long-term stability under different temperature and light conditions, remaining stable even after 3 months of storage, demonstrating high practicality. However, in Comparative Examples 4 and 5, when the amounts of dispersant and liposome wall material are unsuitable, the liposome formulations cannot maintain stability after 7 days of treatment at -17℃ and 45℃, thus affecting the synergistic antibacterial and bacteriostatic effects. Furthermore, they cannot be stored for more than 2 months at 5℃ or room temperature, failing to adequately meet the specific storage and application scenarios of daily chemical products.
[0103] Table 2. Test results of particle size distribution and zeta potential values for samples from Examples 1-3 and Comparative Examples 4 and 5.
[0104]
[0105]
[0106] Table 3. Temperature stability test results of Examples 1-3 and Comparative Examples 4 and 5
[0107]
[0108]
[0109] Example 3
[0110] To investigate the sustained-release effect of the liposome antibacterial and bacteriostatic synergist provided by this invention, 10g of samples from Example 3 and Comparative Example 3 were added to 100g of physiological saline (0.9% NaCl sterile aqueous solution). The content of glycyrrhizic acid, a marker, in the physiological saline solution was measured at 2h, 4h, 8h, 16h, 24h, 32h, 48h, and 96h after addition. The ratio of the measured content to the theoretical maximum content is the release rate of the active ingredient.
[0111] Based on the above results, release rate curves of the active ingredients for Example 3 and Comparative Example 3 were plotted, and the results are shown in Table 4. Figure 5It can be seen that the liposome antibacterial and bacteriostatic synergist provided by the present invention has a good sustained-release effect. In 0.9% NaCl solution, the release rate of the active ingredient is only 74% after 96 hours, while in Comparative Example 3, no liposomes were formed, and the active ingredient was basically released within 8 hours in 0.9% NaCl solution. In comparison, the liposome antibacterial and bacteriostatic synergist provided by the present invention has a sustained-release effect, which can prolong the duration of antibacterial and bacteriostatic synergistic action to a certain extent.
[0112] Table 4. Results of active ingredient release rates for Example 3 and Comparative Example 3.
[0113] Time / Release Rate (%) 2h 4h 8 16h 24h 32h 48h 96h Example 3 5 9 16 28 40 52 66 74 Comparative Example 3 65 94 99 99 99 99 99 99
[0114] Application examples
[0115] The insect-repellent, antibacterial, and mite-removing liposome preparations provided by this invention can be further applied as additives in laundry detergents, facial mask liquids, and pet shampoos to exert antibacterial and bacteriostatic synergistic effects. Taking Examples 1-3 as examples, the specific formulas can be found in Tables 5, 6, and 7.
[0116] Table 5 Application of Example 1 in laundry detergent formulation
[0117]
[0118]
[0119] Table 6. Application of Example 2 in facial mask liquid formulation.
[0120]
[0121] Table 7 Application of Example 3 in Pet Shampoo Formulation
[0122]
[0123]
[0124] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.
Claims
1. A liposome-based antibacterial and antimicrobial synergist, characterized in that, The liposomes include liposome contents, liposome wall material, dispersant and water, wherein the liposome contents include a metal chelating agent and an efflux pump inhibitor, and the dispersant is a polyol. The liposome antibacterial and bacteriostatic synergist comprises, by weight percentage: 0.03-1% metal chelating agent, 30-40% dispersant, 0.5-2% efflux pump inhibitor, 3-5% liposome wall material, and the balance being water; The metal chelating agent is at least one of soybean oil-based ethylmorpholine nitrogen ethyl sulfate, disodium ethylenediaminetetraacetate, and tetrasodium ethylenediaminetetraacetate; the efflux pump inhibitor is at least one of glycyrrhizic acid and methylpyrrolidone. The preparation method of the liposome antibacterial and antimicrobial synergist includes the following steps: (1) Disperse the metal chelating agent and the external discharge pump inhibitor in water, heat and keep warm, and mix well to obtain phase A; (2) Dissolve the liposome wall material in a dispersant, heat and keep warm, and mix well to obtain phase B; (3) Under heating and stirring, phase B is added dropwise to phase A to obtain phase C; the heating and stirring temperature is 35-65℃; (4) Homogenize the C phase to obtain the liposome antibacterial and bacteriostatic synergist.
2. The liposome antibacterial and bacteriostatic synergist as described in claim 1, characterized in that, The dispersant is at least one of propylene glycol, butanediol, hexanediol, pentanediol, and glycerol.
3. The liposome antibacterial and bacteriostatic synergist as described in claim 1, characterized in that, The liposome wall material is lecithin.
4. The liposome antibacterial and bacteriostatic synergist as described in claim 1, characterized in that, The liposome wall material is at least one of hydrogenated lecithin, hydroxylated lecithin, hydrogenated lysophosphatidylcholine, lysophosphatidylcholine, and soybean lecithin.
5. The liposome antibacterial and bacteriostatic synergist as described in claim 1, characterized in that, The metal chelating agent is disodium ethylenediaminetetraacetate, and the efflux pump inhibitor is glycyrrhizic acid.
6. The liposome antibacterial and bacteriostatic synergist as described in claim 5, characterized in that, It comprises, by weight percentage, the following components: 0.1% metal chelating agent, 40% dispersant, 1% efflux pump inhibitor, 3% liposome wall material, and the balance water.
7. The application of the liposome antibacterial and bacteriostatic synergist as described in any one of claims 1-6 in daily chemical products.
Citation Information
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