Liposome antibacterial and bacteriostatic synergist as well as preparation method and application thereof

Abstract

The invention relates to a liposome antibacterial and bacteriostatic synergist as well as a preparation method and application thereof, and belongs to the technical field of daily chemicals. The lipidosome antibacterial and bacteriostatic synergist provided by the invention comprises a lipidosome content, a lipidosome wall material, a dispersing agent and water, the composition comprises the following components in percentage by mass: 0.001-1% of a metal chelating agent, 2-50% of a dispersing agent, 0.01-5% of an efflux pump inhibitor, 0.1-10% of a liposome wall material and the balance of water. According to the liposome antibacterial and bacteriostatic synergist provided by the invention, the antibacterial and bacteriostatic effects are remarkably improved through the synergistic combination of various components from the source of generation of bacterial drug resistance; meanwhile, a slow release effect is achieved, the antibacterial, bacteriostatic and synergistic action time can be prolonged, and high application value is achieved in daily chemicals.

Description

Technical Field

[0001] The invention relates to the technical field of daily chemical products, and in particular to a liposome antibacterial and antimicrobial synergist and a preparation method and application thereof. Background Art

[0002] At present, bacterial resistance to antimicrobial drugs has developed into a global medical crisis, and multidrug-resistant bacteria that cannot be treated with any common antimicrobial drugs have emerged. Therefore, new antimicrobial and antibacterial enhancers are urgently needed to restore the sensitivity of bacteria to antimicrobial and antibacterial drugs. In the field of daily chemicals, the use of preservatives has always attracted much attention and controversy.

[0003] On the one hand, preservatives in daily chemical products do have certain hazards, especially when they are used improperly or exceed the safe concentration, they are prone to cause allergic reactions, dry skin, skin irritation, and disrupt the skin microbial community. Common risk preservatives in daily chemical products include methylparaben, propylparaben, butylparaben, methylisothiazolinone, etc. Long-term use of these preservatives may cause serious damage to the skin and even interfere with female endocrine. Therefore, external preservatives such as phenoxyethanol, pentylene glycol, and hexylene glycol are popular in the market, but because their antibacterial effects are generally weak, the products are prone to quality problems such as excessive microorganisms.

[0004] On the other hand, due to the emergence of bacterial resistance, some daily chemical companies have to increase the amount of preservatives used to ensure the normal delivery time of their products, which increases the safety issues of preservative use. Seeking new preservatives with higher safety or reducing the amount of preservatives with risks has become a pain point that urgently needs to be solved in the industry.

[0005] Therefore, the study provides a new type of antibacterial and antimicrobial enhancer, which can significantly enhance the antibacterial and antimicrobial effects, reduce the dosage of risk preservatives, and take into account both safety and preservative effects. It has great research and application value in helping daily chemical companies optimize their product preservative systems. Summary of the invention

[0006] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a liposome antibacterial and antibacterial synergist and its preparation method and application. The liposome antibacterial and antibacterial synergist provided by the present invention has a significant synergistic effect on different types of preservatives, can reduce the amount of preservatives used, and has high stability, which is suitable for the storage and application requirements of daily chemical products.

[0007] To achieve the above object, the technical solution adopted by the present invention is:

[0008] In a first aspect, the present invention provides a liposome antibacterial and antimicrobial synergist, comprising liposome contents, liposome wall materials, a 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 antimicrobial synergist comprises the following components by mass percentage: 0.001-1% of metal chelating agent, 2-50% of dispersant, 0.01-5% of efflux pump inhibitor, 0.1-10% of liposome wall material and the balance of water.

[0010] The present invention provides a liposome-type antibacterial and antimicrobial synergist with metal chelators and efflux pump inhibitors as main active ingredients. The metal chelator chelates, strips, and binds to zinc ions in the active center of metal β-lactamase (MBL) to inhibit MBL; MBL can develop drug resistance to almost all β-lactam drugs and is a great threat to the field of microbial drug resistance; metal chelators are used to reduce bacterial drug resistance by inhibiting the active center of the enzyme, thereby achieving the effect of enhancing the effects of drugs such as preservatives and antibacterial agents from the inside.

[0011] Efflux pump inhibitors can interfere with the assembly of microbial efflux pumps, thereby blocking the energy source of the efflux pumps and preventing the substrate from passing directly through the efflux channel. Through efflux pump inhibitors, the efflux function of bacteria is interfered with, thereby inhibiting bacterial activity and achieving an antibacterial and antimicrobial synergistic effect from the inside. When metal chelators and efflux pump inhibitors act together under the above-mentioned specific ratios, they can achieve a good synergistic effect and a significant antibacterial and antimicrobial synergistic effect; the effect of efflux pump inhibitors outside the ratio range or acting alone is poor.

[0012] The key to the antibacterial and antimicrobial enhancement effect is to use liposomes as components using liposome wall materials. For Gram-negative bacteria, there are many bacterial outer membranes that are difficult for drugs to penetrate, which is the main reason why most antibacterial drugs are ineffective against Gram-negative bacteria. The bacterial cell membrane is mainly composed of lipids (mainly phospholipids and cholesterol). According to the principle of like dissolves like, the use of liposome wall materials can achieve outer membrane permeabilization, inactivate permeability barriers such as outer membranes, and thus carry drugs into bacteria.

[0013] Dispersants can prevent biomacromolecules from forming biofilms outside bacterial cells, thereby reducing bacterial resistance. Biofilm is a membrane tissue formed by microorganisms, composed of complex extracellular polymers. It is a special membrane tissue that microorganisms use to survive in order to resist external stress conditions. At the same time, dispersants with a specific ratio can also significantly improve the flexibility of the outer layer of liposomes, thereby achieving better stability. When the ratio of dispersants and liposome wall materials is not appropriate, the stability of the liposomes will be greatly reduced, and it will not be able to meet the storage and use requirements of daily chemical products.

[0014] The liposome antibacterial and antibacterial synergist provided by the present invention starts from the source of bacterial drug resistance, adopts a synergistic combination of liposome dosage forms, has a small particle size and a strong permeation effect, inactivates the permeability barrier of the cell outer membrane through outer membrane permeabilization, carries the "drug" into the interior of the bacteria, inhibits and blocks the efflux pump mechanism and inhibits the production of β-lactamase inside the microorganism; outside the bacteria, it blocks the formation of biofilm, repairs both inside and outside, blocks the production of bacterial drug resistance at multiple targets, and achieves the effect of antibacterial and antibacterial synergist; at the same time, the liposome antibacterial and antibacterial synergist provided by the present invention has a sustained release effect, can exert a long-lasting antibacterial and antibacterial synergist, and has a high application value in the field of daily chemicals.

[0015] Preferably, the liposome antibacterial and antimicrobial synergist comprises the following components by mass percentage: 0.03-1% of metal chelating agent, 30-40% of dispersant, 0.5-2% of efflux pump inhibitor, 3-5% of liposome wall material and the remainder of water.

[0016] Preferably, the metal chelating agent is at least one of soybean oil-based ethylmorpholinium ethyl sulfate, disodium ethylenediaminetetraacetate, tetrasodium ethylenediaminetetraacetate, disodium nitrilotriacetate, sodium gluconate, and sodium tripolyphosphate.

[0017] Preferably, the efflux pump inhibitor is at least one of glycyrrhizic acid, methyl pyrrolidone, artesunate, antisense nucleic acid, oligonucleotide, and amikacin.

[0018] Preferably, the dispersant is at least one of ethanol, propylene glycol, butylene glycol, hexylene glycol, pentanediol and glycerol.

[0019] Preferably, the liposome wall material is at least one of lecithin, hydrogenated lecithin, hydroxylated lecithin, hydrogenated lysolecithin, lysolecithin, and soybean lecithin.

[0020] Further preferably, the metal chelator is disodium ethylenediaminetetraacetate, and the efflux pump inhibitor is glycyrrhizic acid.

[0021] Further preferably, the liposome antibacterial and antimicrobial synergist comprises the following components, measured by mass percentage: 0.1% metal chelator, 40% dispersant, 1% efflux pump inhibitor, 3% liposome wall material and the remainder water.

[0022] The optimal antibacterial and antimicrobial synergistic effect can be achieved by selecting the above-mentioned specific metal chelating agents and efflux pump inhibitors and combining them in the above-mentioned ratios.

[0023] In a second aspect, the present invention provides a method for preparing the above-mentioned liposome antibacterial and antimicrobial synergist, characterized in that it comprises the following steps:

[0024] (1) dispersing a metal chelating agent and an efflux pump inhibitor in water, heating and keeping the mixture warm, and mixing the mixture to obtain a phase A;

[0025] (2) dissolving the liposome wall material in the dispersant, heating and keeping warm, and mixing to obtain phase B;

[0026] (3) adding the phase B dropwise into the phase A under heating and heat preservation and stirring to obtain phase C; the heating and heat preservation temperature is 35-65° C.;

[0027] (4) homogenizing the phase C to obtain the liposome antibacterial and antimicrobial enhancer.

[0028] Preferably, in step (1), the dispersion condition is stirring at 500-1200 rpm / min; and in step (2), the stirring speed is 500-1200 rpm / min.

[0029] Preferably, in step (4), the homogenization pressure is 500-3000 bar.

[0030] The above preparation method can be used to prepare a stable liposome dosage form.

[0031] In a third aspect, the present invention provides the use of the above-mentioned liposome antibacterial and antimicrobial enhancer in daily chemicals.

[0032] The liposome antibacterial and antimicrobial enhancer provided by the present invention can be applied to a variety of daily chemical products, such as laundry detergent, pet shampoo, facial mask liquid, etc., by further adding and compounding. It has a long-lasting and stable liposome dosage form, can reduce the amount of preservatives, and is delivered through the outer membrane permeabilization of the liposome, has high safety, and is adapted to the application needs in the field of daily chemicals.

[0033] Compared with the prior art, the present invention has the following beneficial effects:

[0034] (1) The liposome antibacterial and antimicrobial synergist provided by the present invention is a synergistic combination that starts from the source of bacterial resistance. 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, "both inside and outside", and blocks the production of bacterial resistance at multiple targets, thereby achieving the effect of antibacterial and antimicrobial synergist.

[0035] (2) The liposome antibacterial and antibacterial synergist dosage form provided by the present invention is a liposome with a small particle size and strong permeability. The liposome wall material is an outer membrane permeabilizing agent, which has the function of inactivating the permeability barrier of the cell outer membrane and carrying the "drug" into the interior of the bacteria, thereby achieving the effect of antibacterial and antibacterial synergism; at the same time, it also has a sustained release effect, which can prolong the antibacterial and antibacterial synergism effect time. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 The MIC results of the compound example, comparative example and reference substance of 1,2-hexanediol are shown in FIG.

[0037] Figure 2 The MIC results of the compound example, comparative example and reference substance of methylparaben are shown in FIG.

[0038] Figure 3 This is the particle size distribution result diagram of Example 2;

[0039] Figure 4 This is the Zeta potential result diagram of Example 2;

[0040] Figure 5 The release rate curve of the active ingredient in Example 3 in normal saline. DETAILED DESCRIPTION

[0041] In order to better illustrate the purpose, technical scheme and advantages of the present invention, the present invention will be further described below in conjunction with specific examples. The test methods used in the following examples are conventional methods unless otherwise specified; the materials and reagents used are reagents and materials that can be obtained from commercial channels unless otherwise specified.

[0042] Example 1

[0043] An embodiment of the liposome antibacterial and antibacterial synergist of the present invention is composed of the following components in percentage by mass: 0.2% metal chelator, 30% dispersant, 0.35% efflux pump inhibitor, 3% liposome wall material and the remainder water.

[0044] The preparation method of the liposome antibacterial and antimicrobial synergist described in this embodiment is as follows:

[0045] (1) Weigh 0.2 g of disodium ethylenediaminetetraacetate and 0.35 g of glycyrrhizic acid and disperse them in 66.45 g of deionized water, heat at 45° C., and maintain a stirring speed of 600 rpm / min to obtain phase A1;

[0046] (2) Weigh 3 g of soybean lecithin and uniformly dissolve it in 30 g of 1,3-butanediol, and heat at 45°C to obtain phase B1;

[0047] (3) heating at 45°C and stirring at 600 rpm / min, adding phase B1 dropwise into phase A1 to obtain phase C1;

[0048] (4) The C1 phase was homogenized by a high-pressure homogenizer at a homogenization pressure of 1000 bar to obtain a liposome antibacterial and antimicrobial synergist, referred to as "Example 1 sample".

[0049] Example 2

[0050] An embodiment of the liposome antibacterial and antibacterial synergist of the present invention is composed of the following components in percentage by mass: 1% metal chelator, 35% dispersant, 2% efflux pump inhibitor, 5% liposome wall material and the remainder water.

[0051] The preparation method of the liposome antibacterial and antimicrobial synergist described in this embodiment is as follows:

[0052] (1) Weigh 1 g of soybean oil-based ethylmorpholinium ethyl sulfate and 2 g of methylpyrrolidone and disperse them in 57 g of deionized water, heat at 55° C., and maintain a stirring speed of 700 rpm / min to obtain phase A2;

[0053] (2) Weigh 5 g of hydrogenated lecithin and uniformly dissolve it in 35 g of 1,2-propylene glycol, and heat at 55° C. to obtain phase B2;

[0054] (3) heating at 55°C and stirring at 700 rpm / min, adding phase B2 dropwise into phase A2 to obtain phase C2;

[0055] (4) The C2 phase was homogenized by a high-pressure homogenizer at a homogenization pressure of 2000 bar to obtain a liposome antibacterial and antimicrobial synergist, referred to as "Example 2".

[0056] Example 3

[0057] An embodiment of the liposome antibacterial and antibacterial synergist of the present invention is composed of the following components in percentage by mass: 0.1% metal chelator, 40% dispersant, 1% efflux pump inhibitor, 3% liposome wall material and the remainder water.

[0058] The preparation method of the liposome antibacterial and antimicrobial synergist described in this embodiment is as follows:

[0059] (1) Weigh 0.1 g of tetrasodium ethylenediaminetetraacetate and 1 g of glycyrrhizic acid and dissolve or disperse them in 55.9 g of deionized water, heat at 65° C., and maintain a stirring speed of 900 rpm / min to obtain phase A3;

[0060] (2) Weigh 3 g of lecithin and uniformly dissolve it in 40 g of glycerol, and heat it at 65°C to obtain phase B3;

[0061] (3) heating at 65°C and stirring at 900 rpm / min, adding phase B3 dropwise into phase A3 to obtain phase C3;

[0062] (4) The C3 phase was homogenized by a high-pressure homogenizer at a homogenization pressure of 2500 bar, thereby obtaining the liposome antibacterial and antimicrobial synergist, referred to as "Example 3 sample".

[0063] Example 4

[0064] An embodiment of the liposome antibacterial and antimicrobial synergist of the present invention is different from embodiment 3 only in that the metal chelator tetrasodium ethylenediaminetetraacetic acid is replaced by soybean oil-based ethylmorpholinium ethyl sulfate while keeping the dosage unchanged.

[0065] Example 5

[0066] An embodiment of the liposome antibacterial and antimicrobial synergist of the present invention is different from embodiment 3 only in that the dosage is kept unchanged and the efflux pump inhibitor glycyrrhizic acid is replaced by methyl pyrrolidone.

[0067] Comparative Example 1

[0068] The difference between Comparative Example 1 and Example 1 is that the amount of disodium ethylenediaminetetraacetic acid is increased, the amount of glycyrrhizic acid is reduced (added after dilution), and the amount of deionized water is adjusted accordingly so that the mass percentage is 2% of metal chelator and 0.005% of efflux pump inhibitor. The obtained sample is referred to as "Comparative Example 1 sample".

[0069] Comparative Example 2

[0070] The only difference between Comparative Example 2 and Example 1 is that the metal chelator disodium ethylenediaminetetraacetic acid is removed, the dosage of glycyrrhizic acid is increased, and the dosage of deionized water is adjusted accordingly so that the mass percentage of the efflux pump inhibitor is 10%. The obtained sample is referred to as "Comparative Example 2 Sample".

[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 a liposome dosage form is not formed. The obtained sample is referred to as "Comparative Example 3 Sample".

[0073] Comparative Example 4

[0074] The only difference between Comparative Example 4 and Example 1 is that the amount of 1,3-butanediol is reduced to 1 g, the amount of soy lecithin is reduced to 0.05 g, and the amount of deionized water is increased accordingly so that the mass percentage is 1% of dispersant and 0.05% of liposome wall material. The prepared 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 51 g, the amount of soy lecithin is increased to 11 g, and the amount of deionized water is correspondingly reduced so that the mass percentage is 51% of dispersant and 11% of liposome wall material. The prepared sample is referred to as "Comparative Example 5 Sample".

[0077] Effect Example 1

[0078] In order to explore the antibacterial and antibacterial synergistic effect of the liposome antibacterial and antibacterial synergist provided by the present invention, the minimum inhibitory concentration (MIC) of the "internal preservative" - ​​methylparaben and the "external preservative" - ​​1,2-hexanediol commonly used in daily chemical products was tested, and the MIC of the two preservatives when the mass concentration of 10% was added to the embodiment sample, the comparative sample, disodium ethylenediaminetetraacetic acid, 1,3-butylene glycol, glycyrrhizic acid and soybean lecithin was tested, and the specific method was as follows:

[0079] The test was conducted in accordance with the minimum inhibitory concentration test (agar dilution method) in 2.1.8.3 of the Technical Specifications for Disinfection issued by the Ministry of Health in 2002.

[0080] The tested strains were Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans, and Aspergillus niger.

[0081] (1) Culture medium preparation: MH agar was used according to the product instructions, with a pH of 7.2-7.4.

[0082] (2) Preparation of drug-containing agar plates According to the experimental design, add the antimicrobial drugs of different concentrations that have been diluted in multiples to the MH agar that has been heated and dissolved and balanced in a 45-50℃ water bath, mix thoroughly and pour into a sterilized plate. The agar thickness is 3-4mm. Prepare drug-containing agar plates at a ratio of 1:9. The prepared drug-containing agar plates should be placed in a sealed plastic bag and stored in a refrigerator at 2-8℃ for 5 days.

[0083] (3) Preparation of inoculum and inoculation Prepare a bacterial suspension with a concentration equivalent to 0.5 McFarland standard turbidimetric tube, dilute it 1:10, and use a multi-point inoculator to draw the prepared bacterial suspension (about 1-2 μl) and inoculate it on the surface of the agar plate. The number of bacteria per point is about 104 CFU, forming a plaque with a diameter of 5-8 mm. After inoculation, incubate at 35℃ for 16-20 hours and observe the results.

[0084] (4) Result judgment Place the plate on a dark, non-reflective surface to determine the test endpoint, and the lowest drug concentration that inhibits bacterial growth is the MIC. Slight bacterial growth can be seen on the trimethoprim or sulfa agar plate. The lowest drug concentration that inhibits bacterial growth by more than 80% compared with the growth control is the endpoint concentration.

[0085] If more than two colonies grow on agar plates containing drug concentrations higher than the endpoint level, or if colonies do not grow on agar plates with low drug concentrations but grow on agar plates with high drug concentrations, the culture purity should be checked or the test should be repeated.

[0086] The test results of MIC are shown in Tables 1-1, 1-2 and Figure 1 , 2 As shown, we can know:

[0087] The components of the liposome antibacterial and antibacterial synergist provided by the present invention do not have an antibacterial and antibacterial synergist effect when used alone; in the comparative example 3, the simple combination of its components also does not have an antibacterial and antibacterial effect; only after it constitutes a liposome dosage form in the embodiment sample, can it achieve a significant antibacterial and antibacterial synergist effect, and significantly reduce the MIC value, which may be related to the fact that components such as metal chelators and efflux pump inhibitors can directly contact the cell membrane and the interior through the outer membrane permeabilization of the liposome, and assist the antibacterial and antibacterial agent to play a role. On the whole, the antibacterial and antibacterial synergist effect is the best using the liposome combination and ratio of Example 3. The antibacterial and antibacterial synergist provided by the present invention has a significant synergistic effect on both the internal and external preservatives, and can achieve good synergistic antibacterial effects on a variety of bacteria, and has a high application value.

[0088] Table 1-1 MIC results of example samples, comparative example samples, and reference substance + 1,2-hexanediol

[0089]

[0090] Table 1-2 MIC results of example samples, comparative example samples, reference substance + methylparaben

[0091]

[0092] Effect Example 2

[0093] In order to explore the stability of the liposome antibacterial and antimicrobial synergist provided by the present invention, the particle size distribution and Zeta potential value test and temperature stability test were performed on Examples 1-3 and Comparative Examples 4 and 5:

[0094] (1) Particle size distribution and Zeta potential value

[0095] Testing equipment: Malvern ZETASIZER NANO;

[0096] Test basis and method: The experimental method refers to the Malvern ZETASIZER NANO series operation manual.

[0097] (2) Temperature stability test

[0098] The samples of Example 1, Example 2, Example 3, Comparative Example 4 and Comparative Example 5 were placed in constant temperature conditions of -17°C, 5°C, 45°C, room temperature illumination and room temperature dark room, respectively, and the appearance changes of the samples were observed after 7 days, 14 days, 28 days, 2 months and 3 months to evaluate the stability. If no sedimentation or aggregation was observed, it was stable.

[0099] The particle size distribution and Zeta potential value test results of Examples 1-3 and Comparative Examples 4 and 5 are shown in Table 2, wherein the particle size distribution result diagram and Zeta potential result diagram of Example 2 are shown in Table 2. 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 see that:

[0102] In Examples 1-3, when the dosage of the dispersant and the liposome wall material is within the range specified in the present invention, the liposome dosage form antibacterial and antibacterial synergist with stable average particle size and Zeta potential can be obtained, and the stability of long-term storage under different temperature and light conditions is good, and the state is still stable after 3 months of storage, and the practicality is high. However, when the dosage of the dispersant and the liposome wall material in Comparative Examples 4 and 5 is not appropriate, the stable liposome dosage form cannot be maintained after 7 days of treatment at -17°C and 45°C, thereby affecting the antibacterial and antibacterial synergistic effect, and it cannot be stored for more than 2 months at 5°C or room temperature, and cannot be well adapted to the specific storage and application scenarios of daily chemical products.

[0103] Table 2 Particle size distribution and Zeta potential value test results of 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] Effect Example 3

[0110] In order to explore the sustained-release effect of the liposome antibacterial and antibacterial synergist provided by the present invention, 10 g of Example 3 and Comparative Example 3 were added to 100 g of normal saline (0.9% NaCl sterile aqueous solution), and the content of the marker-glycyrrhizic acid in the normal saline solution was detected 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, the release rate curves of the active ingredients of Example 3 and Comparative Example 3 were drawn. The results are shown in Tables 4 and Figure 5. It can be seen that the liposome antibacterial and antibacterial synergist provided by the present invention has a good sustained-release effect. After 96 hours in 0.9% NaCl solution, the active ingredient release rate is only 74%, while in Comparative Example 3, no liposomes are formed, and the release is basically completed within 8 hours in 0.9% NaCl solution. In contrast, the liposome antibacterial and antibacterial synergist provided by the present invention has a sustained-release effect and can prolong the antibacterial and antibacterial synergist effect time to a certain extent.

[0112] Table 4 Active ingredient release rate results of 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 removal liposome preparation provided by the present invention can be further used as an additive in laundry detergent, facial mask liquid and pet shampoo to exert antibacterial and antibacterial synergistic effects. Taking Examples 1-3 as an example, the specific formula can be referred to as shown 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 the facial mask liquid formula

[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 solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. A liposome antibacterial and antimicrobial synergist, characterized in that: It comprises liposome contents, liposome wall materials, dispersants and water, wherein the liposome contents comprise metal chelating agents and efflux pump inhibitors, and the dispersants are polyols; The liposome antibacterial and antimicrobial synergist comprises the following components by mass percentage: 0.001-1% of metal chelating agent, 2-50% of dispersant, 0.01-5% of efflux pump inhibitor, 0.1-10% of liposome wall material and the balance of water.

2. The liposome antibacterial and antimicrobial synergist as claimed in claim 1, characterized in that: The invention comprises the following components by mass percentage: 0.03-1% of metal chelating agent, 30-40% of dispersant, 0.5-2% of efflux pump inhibitor, 3-5% of liposome wall material and the balance of water.

3. The liposome antibacterial and antimicrobial synergist as claimed in claim 1, characterized in that: The metal chelating agent is at least one of soybean oil-based ethylmorpholinium ethyl sulfate, disodium ethylenediaminetetraacetate, tetrasodium ethylenediaminetetraacetate, disodium nitrilotriacetate, sodium gluconate, and sodium tripolyphosphate.

4. The liposome antibacterial and antimicrobial synergist as claimed in claim 1, characterized in that: The efflux pump inhibitor is at least one of glycyrrhizic acid, methyl pyrrolidone, artesunate, antisense nucleic acid, oligonucleotide and amikacin.

5. The liposome antibacterial and antimicrobial synergist as claimed in claim 1, characterized in that: The dispersant is at least one of ethanol, propylene glycol, butylene glycol, hexylene glycol, pentanediol and glycerol.

6. The liposome antibacterial and antimicrobial synergist as claimed in claim 1, characterized in that: The liposome wall material is at least one of lecithin, hydrogenated lecithin, hydroxylated lecithin, hydrogenated lysolecithin, lysolecithin and soybean lecithin.

7. The liposome antibacterial and antimicrobial synergist as claimed in claim 3 or 4, characterized in that: The metal chelator is disodium ethylenediaminetetraacetate, and the efflux pump inhibitor is glycyrrhizic acid.

8. The liposome antibacterial and antimicrobial synergist as claimed in claim 7, characterized in that: The invention comprises the following components by mass percentage: 0.1% of metal chelating agent, 40% of dispersant, 1% of efflux pump inhibitor, 3% of liposome wall material and the balance of water.

9. The method for preparing the liposome antibacterial and antimicrobial synergist according to any one of claims 1 to 8, characterized in that: The following steps are involved: (1) dispersing a metal chelating agent and an efflux pump inhibitor in water, heating and keeping the mixture warm, and mixing the mixture to obtain a phase A; (2) dissolving the liposome wall material in the dispersant, heating and keeping warm, and mixing to obtain phase B; (3) adding the phase B dropwise into the phase A under heating and heat preservation and stirring to obtain phase C; the heating and heat preservation temperature is 35-65° C.; (4) homogenizing the phase C to obtain the liposome antibacterial and antimicrobial enhancer.

10. Use of the liposome antibacterial and antimicrobial synergist as claimed in any one of claims 1 to 8 in daily chemicals.

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