Antibacterial emulsion and its preparation method and application

Abstract

The present invention provides an antibacterial emulsion and a preparation method and application thereof, belonging to the field of biopharmaceutical technology. The antibacterial emulsion of the present invention comprises the following raw materials by weight: 15-50 parts of cinnamaldehyde, 0.5-2 parts of dihydrotanshinone I and 30-50 parts of emulsifier. The present invention uses emulsion as a delivery system to improve the drugability of cinnamaldehyde and dihydrotanshinone I, and studies that the combination of cinnamaldehyde and dihydrotanshinone I has a significant antibacterial effect.

Description

Technical Field

[0001] The invention belongs to the technical field of biopharmaceuticals, and specifically relates to an antibacterial emulsion and a preparation method and application thereof. Background Art

[0002] There are many kinds of bacteria in the living environment, and harmful bacteria such as Staphylococcus aureus, Escherichia coli and Candida albicans can cause diseases to people. As people's awareness of health and hygiene continues to improve, the development and application of antibacterial products are increasing. However, due to the wide variety of antibacterial products sold on the market, their antibacterial effects and related properties are different, leading to improper use. Excessive and abuse of chemical synthetic antibacterial agents may bring some potential problems, such as allergies, irritation reactions and drug resistance; some antibacterial agents may cause potential harm to the environment.

[0003] Cinnamaldehyde is an aldehyde organic compound extracted from cinnamon, a traditional medicinal and edible plant; dihydrotanshinone I is an active substance from the traditional Chinese medicine Salvia miltiorrhiza. The low solubility, poor lipid solubility, and fast metabolism of cinnamaldehyde and dihydrotanshinone I limit their application in aqueous solutions and their efficacy. Therefore, the development of a safe antibacterial emulsion with traditional Chinese medicine ingredients to achieve effective antibacterial effects is a technical problem that needs to be solved at this stage. Summary of the invention

[0004] In view of this, the object of the present invention is to provide an antibacterial emulsion and a preparation method and application thereof, wherein the antibacterial emulsion has a significant inhibitory effect on Escherichia coli, Staphylococcus aureus and Enterococcus faecalis at a minimum drug usage amount.

[0005] In order to solve the above technical problems, the present invention provides the following technical solutions:

[0006] An antibacterial emulsion comprises the following raw materials in parts by weight: 15-50 parts of cinnamaldehyde, 0.5-2 parts of dihydrotanshinone I and 30-50 parts of emulsifier.

[0007] Preferably, the antibacterial emulsion further comprises 22-38 parts of oil phase.

[0008] Preferably, a thickener is added in an amount of 1-3% by volume to the antibacterial emulsion.

[0009] Preferably, the emulsifier includes one or more of castor oil polyoxyethylene ether, polyoxyethylene hydrogenated castor oil, and Tween 80.

[0010] Preferably, the oil phase includes one or both of medium chain triglycerides and caprylic / decanoic acid glyceride.

[0011] Preferably, the thickener includes one of carbomer, sodium hyaluronate and sodium carboxymethyl cellulose.

[0012] The invention provides a method for preparing the antibacterial emulsion, comprising the following steps: uniformly mixing the raw materials in parts by weight to obtain the antibacterial emulsion.

[0013] The present invention also provides a method for preparing the antibacterial emulsion, comprising the following steps: uniformly mixing the raw materials in parts by weight to obtain an oil phase, and dropwise adding the oil phase into an aqueous phase to obtain the antibacterial emulsion.

[0014] Application of the antibacterial emulsion of the present invention or the antibacterial emulsion obtained by the preparation method in antibacterial treatment.

[0015] Preferably, the antibacterial activity includes inhibition of Escherichia coli, Staphylococcus aureus and Enterococcus faecalis.

[0016] Compared with the prior art, the present invention has the following beneficial effects:

[0017] The present invention uses emulsion as a delivery system to improve the drugability of cinnamaldehyde and dihydrotanshinone I, and studies have shown that the combination of cinnamaldehyde and dihydrotanshinone I at low dosage has significant antibacterial effect, and has significant inhibitory effect on Escherichia coli, Staphylococcus aureus and Enterococcus faecalis. The process for preparing the antibacterial emulsion of the present invention is simple and easy, and is suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 The antibacterial circle diagram of each group of drugs. Among them, 1 is DMSO control; 2 is dihydrotanshinone I emulsion; 3 is dihydrotanshinone I raw material drug; 4 is cinnamaldehyde raw material drug; 5 is cinnamaldehyde emulsion; 6 is cinnamaldehyde raw material drug + dihydrotanshinone I raw material drug physical mixture; 7 is the composite self-microemulsion in Example 1; 8 is the antibacterial emulsion of comparative example 12; 9 is the antibacterial emulsion of comparative example 13. DETAILED DESCRIPTION

[0019] The present invention provides an antibacterial emulsion, comprising the following raw materials in parts by weight: 15-50 parts of cinnamaldehyde (CIN), 0.5-2 parts of dihydrotanshinone I (DHI) and 30-50 parts of emulsifier. In one embodiment of the present invention, the antibacterial emulsion comprises the following raw materials in parts by weight: 40-50 parts of cinnamaldehyde, 1-2 parts of dihydrotanshinone I and 40-50 parts of emulsifier. In the antibacterial emulsion formula, the emulsifier of the present invention includes one or more of castor oil polyoxyethylene ether EL, polyoxyethylene hydrogenated castor oil RH, and Tween 80, preferably castor oil polyoxyethylene ether EL or a mixture of castor oil polyoxyethylene ether EL + polyoxyethylene hydrogenated castor oil RH.

[0020] The present invention also provides an antibacterial emulsion, comprising the following raw materials by weight: 15-50 parts of cinnamaldehyde, 0.5-2 parts of dihydrotanshinone I, 30-50 parts of emulsifier and 22-38 parts of oil phase. In one embodiment of the present invention, the antibacterial emulsion comprises the following raw materials by weight: 20-35 parts of cinnamaldehyde, 0.5-1.5 parts of dihydrotanshinone I, 30-50 parts of emulsifier and 24-33 parts of oil phase. In the antibacterial emulsion formula, the emulsifier of the present invention comprises one or more of castor oil polyoxyethylene ether EL and polyoxyethylene hydrogenated castor oil RH, preferably castor oil polyoxyethylene ether EL, polyoxyethylene hydrogenated castor oil RH or castor oil polyoxyethylene ether EL + polyoxyethylene hydrogenated castor oil RH mixture; the oil phase of the present invention comprises one or two of medium carbon chain triglyceride and caprylic acid glyceride, preferably medium carbon chain triglyceride or caprylic acid glyceride.

[0021] The present invention also provides an antibacterial emulsion, comprising the following raw materials by weight: 20-35 parts of cinnamaldehyde, 0.5-1.5 parts of dihydrotanshinone I, 30-50 parts of emulsifier, 24-33 parts of oil phase and 4-6 parts of phospholipids. In the antibacterial emulsion formula, the emulsifier of the present invention is preferably castor oil polyoxyethylene ether EL; the oil phase of the present invention is preferably medium-chain triglyceride.

[0022] The present invention also provides an antibacterial emulsion, and a thickener of 1-3% by mass volume is added to the antibacterial emulsion. In one embodiment of the present invention, the antibacterial emulsion includes the following raw materials in parts by weight: 20-35 parts of cinnamaldehyde, 0.5-1.5 parts of dihydrotanshinone I, 30-50 parts of emulsifier and 24-33 parts of oil phase; a thickener of 1-3% by mass volume is added to the antibacterial emulsion prepared by the formula. The thickener of the present invention includes one of carbomer, sodium hyaluronate and sodium carboxymethyl cellulose. In the above antibacterial emulsion formula, the emulsifier of the present invention includes one or more of castor oil polyoxyethylene ether EL and polyoxyethylene hydrogenated castor oil RH, preferably castor oil polyoxyethylene ether EL. The oil phase of the present invention is preferably a medium carbon chain triglyceride. The purpose of adding the thickener of the present invention is to increase the viscosity of the antibacterial emulsion. The antibacterial emulsion obtained by this embodiment of the present invention can be used for antibacterial smears.

[0023] The present invention also provides a method for preparing the antibacterial emulsion, comprising the following steps: uniformly mixing parts by weight of cinnamaldehyde, emulsifier, dihydrotanshinone I and / or oil phase and / or phospholipid to obtain an antibacterial emulsion. The mixing speed of the present invention is 550-650rpm, preferably 600rpm. The antibacterial emulsion obtained by the preparation method of the present invention can also be called a composite self-microemulsion of co-encapsulated cinnamaldehyde-dihydrotanshinone I.

[0024] The present invention also provides a method for preparing the antibacterial emulsion, comprising the following steps: uniformly mixing parts by weight of cinnamaldehyde, emulsifier, dihydrotanshinone I and / or oil phase to obtain a mixture oil phase, and dropwise adding the mixture oil phase into the water phase to obtain the antibacterial emulsion. In the present invention, the oil phase is added dropwise into the water phase with stirring, and the stirring speed is 550-650rpm, preferably 600rpm. The water phase in the present invention is water.

[0025] The present invention also provides a method for preparing the antibacterial emulsion, comprising the following steps: uniformly mixing parts by weight of cinnamaldehyde, an emulsifier, dihydrotanshinone I and an oil phase to obtain a mixture oil phase, dropping the mixture oil phase into an aqueous phase to obtain an antibacterial emulsion, and adding a thickener having a mass volume percentage (g / mL) of 1-3% to the antibacterial emulsion. The antibacterial emulsion obtained by the preparation method of the present invention can be used for an antibacterial ointment.

[0026] The present invention also provides the use of the antibacterial emulsion or the antibacterial emulsion obtained by the preparation method in antibacterial. The antibacterial of the present invention includes but is not limited to inhibiting Escherichia coli, Staphylococcus aureus and Enterococcus faecalis.

[0027] In the present invention, unless otherwise specified, all raw materials or reagents are commercially available products well known to those skilled in the art.

[0028] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] Example 1

[0030] An antibacterial emulsion is prepared by the following method: 49.14 parts by weight of cinnamaldehyde and 1.72 parts by weight of dihydrotanshinone I are mixed, ultrasonically dispersed evenly, and then 49.14 parts by weight of EL are added, and magnetically stirred evenly at 600 rpm to obtain a composite self-microemulsion containing cinnamaldehyde and dihydrotanshinone I.

[0031] Example 2

[0032] An antibacterial emulsion is prepared by the following method: 32.95 parts by weight of medium-chain triglyceride, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I are weighed, and the mixture is stirred evenly with a magnetic stirrer at 600 rpm to obtain a composite self-microemulsion containing cinnamaldehyde and dihydrotanshinone I.

[0033] Example 3

[0034] An antibacterial emulsion is prepared by the following method: 24.78 parts by weight of medium-chain triglyceride, 49.57 parts by weight of polyoxyethylene castor oil EL, 24.78 parts by weight of cinnamaldehyde, and 0.87 parts by weight of dihydrotanshinone I are weighed, and the mixture is stirred evenly with a magnetic stirrer at 600 rpm to obtain a composite self-microemulsion containing cinnamaldehyde and dihydrotanshinone I.

[0035] Example 4

[0036] An antibacterial emulsion is prepared by the following method: firstly melting phospholipid at 70°C, taking 5.45 parts by weight of phospholipid, sequentially adding 31.15 parts by weight of medium-chain triglyceride, 31.15 parts by weight of polyoxyethylene castor oil EL, 31.15 parts by weight of cinnamaldehyde, and 1.09 parts by weight of dihydrotanshinone I, mixing the above raw materials uniformly and then stirring them uniformly with a magnetic stirrer at 600 rpm to obtain a composite self-microemulsion containing cinnamaldehyde and dihydrotanshinone I.

[0037] Example 5

[0038] On the basis of Example 2, the polyoxyethylene castor oil EL was replaced with polyoxyethylene hydrogenated castor oil RH, and the remaining steps were the same as those in Example 2.

[0039] Example 6

[0040] On the basis of Example 2, the polyoxyethylene castor oil EL was replaced with a mixed emulsifier of polyoxyethylene hydrogenated castor oil RH and polyoxyethylene castor oil EL (weight ratio 1:1), and the remaining steps were the same as those of Example 2.

[0041] Example 7

[0042] Based on Example 1, an antibacterial emulsion preparation method is as follows: 49.14 parts by weight of cinnamaldehyde and 1.72 parts by weight of dihydrotanshinone I are mixed, ultrasonically dispersed evenly, and then 49.14 parts by weight of EL are added, and magnetically stirred at 600 rpm to form a total oil phase, and the total oil phase is dropwise added into pure water (aqueous phase) at a speed of 600 rpm according to an oil-water volume ratio of 1:5 to form an antibacterial emulsion.

[0043] Example 8

[0044] Based on Example 2, an antibacterial emulsion preparation method is as follows: weigh 32.95 parts by weight of medium-chain triglyceride, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I, stir evenly with a magnetic stirrer at 600 rpm to form a total oil phase, and add the total oil phase dropwise into pure water (aqueous phase) at a speed of 600 rpm according to an oil-water volume ratio of 1:5 to form an antibacterial emulsion.

[0045] Example 9

[0046] Based on Example 3, an antibacterial emulsion preparation method is as follows: weigh 24.78 parts by weight of medium-chain triglyceride, 49.57 parts by weight of polyoxyethylene castor oil EL, 24.78 parts by weight of cinnamaldehyde, and 0.87 parts by weight of dihydrotanshinone I, and stir them evenly with a magnetic stirrer at 600 rpm to form a total oil phase. According to the oil-water volume ratio of 1:5, the total oil phase is dropwise added into pure water (aqueous phase) at a rotation speed of 600 rpm to form an antibacterial emulsion.

[0047] Example 10

[0048] On the basis of Example 4, a method for preparing an antibacterial emulsion is as follows: An antibacterial self-microemulsion is prepared as follows: first melt the phospholipid at 70°C, take 5.45 parts by weight of phospholipid, add 31.15 parts by weight of medium-chain triglyceride, 31.15 parts by weight of polyoxyethylene castor oil EL, 31.15 parts by weight of cinnamaldehyde, and 1.09 parts by weight of dihydrotanshinone I in sequence, stir magnetically at 600rpm to form a total oil phase, and according to an oil-water volume ratio of 1:5, add the total oil phase dropwise into pure water (aqueous phase) at 600rpm to form an antibacterial emulsion.

[0049] Embodiment 11

[0050] On the basis of Example 5, a method for preparing an antibacterial emulsion is as follows: an antibacterial self-microemulsion is prepared as follows: 32.95 parts by weight of medium-chain triglyceride, 32.95 parts by weight of polyoxyethylene hydrogenated castor oil RH, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I are weighed, and magnetically stirred at 600 rpm to obtain a composite self-microemulsion containing cinnamaldehyde-dihydrotanshinone I. The total oil phase is uniformly formed by magnetic stirring at 600 rpm, and the total oil phase is added dropwise to pure water (aqueous phase) at an oil-water volume ratio of 1:5 at a speed of 600 rpm to form an antibacterial emulsion.

[0051] Example 12

[0052] Based on Example 6, a method for preparing an antibacterial emulsion is as follows: An antibacterial self-microemulsion is prepared as follows: 32.95 parts by weight of medium-chain triglycerides, 32.95 parts by weight of polyoxyethylene hydrogenated castor oil RH and polyoxyethylene castor oil EL mixed emulsifiers (weight ratio of 1:1), 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I are weighed, and magnetically stirred at 600 rpm to form a total oil phase, and the total oil phase is dropwise added into pure water (aqueous phase) at a speed of 600 rpm according to an oil-water volume ratio of 1:5 to form an antibacterial emulsion.

[0053] Example 13

[0054] On the basis of Example 8, polyoxyethylene castor oil EL was replaced with Tween 80, and the remaining steps were the same as those in Example 8.

[0055] Embodiment 14

[0056] An antibacterial emulsion gel was prepared based on Example 8, the purpose of which was to increase its viscosity for use in antibacterial ointments. The preparation method was as follows: 32.95 parts by weight of medium-chain triglyceride, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I were weighed, and magnetically stirred at 600 rpm to form a total oil phase, and the total oil phase was added dropwise to pure water (aqueous phase) at a rotation speed of 600 rpm according to an oil-water volume ratio of 1:5 to form an antibacterial emulsion.

[0057] 1% (mass / volume, g / mL) of carbomer was added to the above antibacterial emulsion, stirred at room temperature in the dark until the carbomer swelled, and then placed in the dark for stability test.

[0058] Embodiment 15

[0059] An antibacterial emulsion gel was prepared based on Example 8, the purpose of which was to increase its viscosity for use in antibacterial ointments. The preparation method was as follows: 32.95 parts by weight of medium-chain triglyceride, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I were weighed, and magnetically stirred at 600 rpm to form a total oil phase, and the total oil phase was added dropwise to pure water (aqueous phase) at a rotation speed of 600 rpm according to an oil-water volume ratio of 1:5 to form an antibacterial emulsion.

[0060] 1% (mass / volume, g / mL) sodium hyaluronate was added to the antibacterial emulsion formed above, stirred at room temperature in the dark until the sodium hyaluronate swelled, and then placed for stability test.

[0061] Example 16

[0062] An antibacterial emulsion gel was prepared based on Example 8, the purpose of which was to increase its viscosity for use in antibacterial ointments. The preparation method was as follows: 32.95 parts by weight of medium-chain triglyceride, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I were weighed, and magnetically stirred at 600 rpm to form a total oil phase, and the total oil phase was added dropwise to pure water (aqueous phase) at a rotation speed of 600 rpm according to an oil-water volume ratio of 1:5 to form an antibacterial emulsion.

[0063] 2% (mass / volume, g / mL) of sodium carboxymethyl cellulose was added to the antibacterial emulsion formed above, and the mixture was stirred at room temperature in the dark until the sodium carboxymethyl cellulose swelled, and then placed for stability test.

[0064] Comparative Example 1

[0065] An antibacterial self-microemulsion is prepared by the following method: 32.95 parts by weight of olive oil, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I are weighed, and magnetically stirred at 600 rpm to obtain a composite self-microemulsion containing cinnamaldehyde and dihydrotanshinone I.

[0066] Comparative Example 2

[0067] The difference from Comparative Example 1 is that olive oil is replaced by isopropyl myristate, and the remaining steps are the same as those of Comparative Example 1.

[0068] Comparative Example 3

[0069] The difference from Comparative Example 1 is that olive oil is replaced by soybean oil, and the remaining steps are the same as those of Comparative Example 1.

[0070] Comparative Example 4

[0071] The difference from Comparative Example 1 is that olive oil is replaced by isopropyl palmitate, and the remaining steps are the same as those of Comparative Example 1.

[0072] Comparative Example 5

[0073] The difference from Comparative Example 1 is that olive oil is replaced by caprylic decanoic acid glyceride, and the remaining steps are the same as those of Comparative Example 1.

[0074] Comparative Example 6

[0075] An antibacterial emulsion is prepared by the following method: 39.45 parts by weight of medium-chain triglyceride, 19.72 parts by weight of polyoxyethylene castor oil EL, 39.45 parts by weight of cinnamaldehyde, and 1.38 parts by weight of dihydrotanshinone I are weighed, and the mixture is stirred evenly with a magnetic stirrer at 600 rpm to obtain a composite self-microemulsion containing cinnamaldehyde and dihydrotanshinone I.

[0076] Comparative Example 7

[0077] Based on Comparative Example 1, an antibacterial emulsion preparation method is as follows: 32.95 parts by weight of olive oil, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I are weighed, and magnetically stirred at 600 rpm to form a total oil phase, and the total oil phase is dropwise added into pure water (aqueous phase, oil-to-water volume ratio of 1:5) at a rotation speed of 600 rpm to form an antibacterial emulsion.

[0078] Comparative Example 8

[0079] Based on Comparative Example 2, an antibacterial emulsion preparation method is as follows: 32.95 parts by weight of isopropyl myristate, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I are weighed, and magnetically stirred at 600 rpm to form a total oil phase, and the total oil phase is dropwise added into pure water (aqueous phase, oil-to-water volume ratio of 1:5) at a rotation speed of 600 rpm to form an antibacterial emulsion.

[0080] Comparative Example 9

[0081] Based on Comparative Example 3, an antibacterial emulsion preparation method is as follows: 32.95 parts by weight of soybean oil, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I are weighed, and magnetically stirred at 600 rpm to form a total oil phase, and the total oil phase is dropwise added into pure water (aqueous phase, oil-to-water volume ratio of 1:5) at a rotation speed of 600 rpm to form an antibacterial emulsion.

[0082] Comparative Example 10

[0083] Based on Comparative Example 4, an antibacterial emulsion preparation method is as follows: weigh 32.95 parts by weight of isopropyl palmitate, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I, and stir them evenly with a magnetic stirrer at 600 rpm to form a total oil phase, and the total oil phase is dropwise added into pure water (aqueous phase, oil-to-water volume ratio of 1:5) at a rotation speed of 600 rpm to form an antibacterial emulsion.

[0084] Comparative Example 11

[0085] Based on Comparative Example 5, an antibacterial emulsion preparation method is as follows: weigh 32.95 parts by weight of caprylic / capric glyceride, 32.95 parts by weight of polyoxyethylene castor oil EL, 32.95 parts by weight of cinnamaldehyde, and 1.15 parts by weight of dihydrotanshinone I, and stir them evenly with a magnetic stirrer at 600 rpm to form a total oil phase, and the total oil phase is dropwise added into pure water (aqueous phase, oil-to-water volume ratio of 1:5) at a rotation speed of 600 rpm to form an antibacterial emulsion.

[0086] Comparative Example 12

[0087] The difference from Example 1 is that dihydrotanshinone I is replaced by costunolide, and the remaining steps are the same as those in Example 1.

[0088] Comparative Example 13

[0089] The difference from Example 1 is that dihydrotanshinone I is replaced by dehydrocostus lactone, and the remaining steps are the same as those in Example 1.

[0090] Experimental Example 1

[0091] The antibacterial emulsions prepared in Examples 1-6 and Comparative Examples 1-6 were placed at room temperature away from light for 7 days, and their appearance and particle size changes were observed. The results are shown in Table 1, which show that when cinnamaldehyde, medium-chain triglycerides and caprylic decanoic acid glyceride are used as the oil phase, a uniform and stable self-microemulsion can be formed, and a nanoemulsion with uniform particle size can be spontaneously formed after contacting water; while when olive oil, soybean oil, isopropyl palmitate and isopropyl myristate are used as the oil phase, stratification is easy, which is not conducive to the long-term storage of the self-emulsifying system.

[0092] Table 1 Results of self-microemulsification of each prescription

[0093]

[0094] The antibacterial emulsions prepared in Examples 7-13 and Comparative Examples 7-13 were placed at room temperature away from light for 7 days, and their appearance and particle size changes were observed. The results are shown in Table 2, which show that when cinnamaldehyde and medium-chain triglycerides are used as the oil phase, a uniform and stable nanoemulsion can be formed, and the stability after placement is good; while when caprylic acid glyceride, olive oil, soybean oil, isopropyl palmitate and isopropyl myristate are used as the oil phase, dihydrotanshinone I is easy to precipitate, which is not conducive to long-term storage. When the ratio of the oil phase to the emulsifier is less than 2:1, a nanoemulsion with uniform particle size is easily formed, and when the emulsifiers are Tween 80, polyoxyethylene castor oil EL, polyoxyethylene hydrogenated castor oil RH and polyoxyethylene castor oil EL mixed emulsifiers (weight ratio 1:1), nanoemulsions with stable particle size can be formed. When the drug dihydrotanshinone I is replaced with other poorly soluble drugs, such as costusinolide or dehydrocostusinolide, nanoemulsions with stable particle size can also be formed.

[0095] Table 2 Study on the stability of emulsions of Examples 7-13 and Comparative Examples 7-13 at room temperature

[0096]

[0097] Note: - represents not tested.

[0098] In order to further increase the viscosity of the emulsion and expand the scope of application, gel excipients were added to the aqueous emulsion. In Examples 14-16, it was found that the liquid emulsion turned into a milky orange paste after adding different types of gel excipients. After being placed away from light for 2 months, the content was not significantly changed by high performance liquid chromatography. The results are shown in Table 3.

[0099] Table 3 Stability test of Examples 14-16 at 4°C in the dark for 2 months

[0100]

[0101] Experimental Example 2

[0102] 1. Inhibition zone determination

[0103] Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 29213) and Enterococcus faecalis (ATCC 29212) were diluted to 1×10 8 CFU / mL of bacterial liquid, dip the bacterial liquid with a sterile cotton swab, and evenly spread it on an agar plate. Partition the agar plate and place an Oxford cup on the surface, add 100 μL of the drug solution to be tested into the Oxford cup, the drug solution includes cinnamaldehyde raw material, dihydrotanshinone I raw material, cinnamaldehyde raw material and dihydrotanshinone I raw material physical mixture, cinnamaldehyde emulsion, dihydrotanshinone I emulsion, antibacterial self-microemulsion prepared in Example 1, antibacterial emulsion prepared in Comparative Example 12, and antibacterial emulsion prepared in Comparative Example 13; the dosage is about 82 μg / mL of cinnamaldehyde, dihydrotanshinone I or costusinolone or dehydrocostusinolone is about 2.9 μg / mL, and the above-mentioned cinnamaldehyde and dihydrotanshinone I / costusinolone / dehydrocostusinolone are the dosages that have no killing effect on bacteria when each exists alone. Among them, cinnamaldehyde API was added with DMSO to prepare a mother solution with a concentration of 256 mg / ml; dihydrotanshinone I API was added with DMSO to prepare a mother solution with a concentration of 6.4 mg / ml; cinnamaldehyde API and dihydrotanshinone I API physical mixture were added with DMSO to prepare a mother solution with a concentration ratio of 28:1; cinnamaldehyde emulsion and dihydrotanshinone I emulsion were prepared by the method described in Example 1, except that the corresponding non-containing drugs were removed. Cinnamaldehyde emulsion, dihydrotanshinone I emulsion and the above-mentioned API mother solutions were diluted to the target concentration with sterilized water.

[0104] The plate treated with the drug was placed in a 37°C incubator for 24 hours, and the circular area (inhibition zone) without bacterial growth around each Oxford cup was observed. The diameter of the inhibition zone was measured to determine whether the bacteria were sensitive to the drug and the antibacterial ability of the drug. Figure 1 As shown in Table 4, the cinnamaldehyde dihydrotanshinone I composite self-microemulsion in Example 1 has stronger antibacterial ability than a single raw material drug, an emulsion and a physical mixture of the two. And Example 1 has a better effect than the emulsions of Comparative Examples 12 and 13.

[0105] Table 4 Results of inhibition zone determination of drugs against Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis (n=3)

[0106]

[0107] 2. MIC value determination

[0108] Cinnamaldehyde API, dihydrotanshinone I API, physical mixture of cinnamaldehyde API and dihydrotanshinone I API, cinnamaldehyde emulsion, dihydrotanshinone I emulsion, and antibacterial emulsion prepared in Example 1-16 were added to unsolidified culture medium, and diluted to prepare drug-containing agar plates with a final drug concentration of 0.1-1280 μg / mL; Escherichia coli (ATCC25922), Staphylococcus aureus (ATCC 29213), and Enterococcus faecalis (ATCC 29212) were diluted to 5×10 5 CFU / mL of bacterial solution; the sample was scattered on the drug-containing plate ten times, and cultured in a 37°C incubator under aerobic conditions for 24 hours, and the concentration of no bacteria growing on the plate was recorded as the MIC value. The results are shown in Table 5: The antibacterial self-microemulsion prepared in Example 1 has an antibacterial ability that is more than 100 times higher than that of a single raw material drug, a single emulsion, and a physical mixture of the two; and the inactive ingredients in the cinnamaldehyde / dihydrotanshinone I emulsion formula have little effect on its antibacterial effect.

[0109] Table 5 MIC determination of drugs against Escherichia coli, Staphylococcus aureus and Enterococcus faecalis

[0110]

[0111] Note: CIN and DHI in the table are based on the actual measured results after dilution.

[0112] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. An antibacterial emulsion, characterized in that: The method is prepared from the following raw materials in parts by weight: 15-50 parts of cinnamaldehyde, 0.5-2 parts of dihydrotanshinone I, 30-50 parts of emulsifier and 22-38 parts of oil phase; The emulsifier is selected from one or more of castor oil polyoxyethylene ether, polyoxyethylene hydrogenated castor oil, and Tween 80; The oil phase is medium-chain triglyceride.

2. An antibacterial emulsion, characterized in that: The method is prepared from the following raw materials in parts by weight: 15-50 parts of cinnamaldehyde, 0.5-2 parts of dihydrotanshinone I, 30-50 parts of emulsifier, 22-38 parts of oil phase and water; The emulsifier is selected from one or more of castor oil polyoxyethylene ether, polyoxyethylene hydrogenated castor oil, and Tween 80; The oil phase is medium-chain triglyceride.

3. The antibacterial emulsion according to claim 1, characterized in that On the basis of the antibacterial emulsion, a thickener is added in an amount of 1-3% by weight volume.

4. The antibacterial emulsion according to claim 3, characterized in that The thickener is selected from one of carbomer, sodium hyaluronate and sodium carboxymethyl cellulose.

5. The method for preparing the antibacterial emulsion according to claim 1, characterized in that: The method comprises the following steps: uniformly mixing the raw materials in parts by weight to obtain an antibacterial emulsion.

6. The method for preparing the antibacterial emulsion according to claim 2, characterized in that: The method comprises the following steps: uniformly mixing the raw materials in parts by weight to obtain an oil phase, and dropwise adding the oil phase into a water phase to obtain an antibacterial emulsion.

7. Use of the antibacterial emulsion according to any one of claims 1 to 4 or the antibacterial emulsion obtained by the preparation method according to claim 5 or 6 in the preparation of antibacterial products.

8. The use according to claim 7, characterized in that The antibacterial activity includes inhibiting Escherichia coli, Staphylococcus aureus and Enterococcus faecalis.

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