CN111135142A - Isoliquiritigenin nanoemulsion and preparation method thereof - Google Patents
Isoliquiritigenin nanoemulsion and preparation method thereof Download PDFInfo
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Abstract
The invention provides an isoliquiritigenin nanoemulsion, which consists of isoliquiritigenin and auxiliary materials; the auxiliary material comprises the following components in percentage by volume: 20-40% of oil phase, 35-48% of mixed emulsifier and 18-40% of distilled water; the ratio of the isoliquiritigenin to the auxiliary materials is 0.2-1.0 g: 100 ml; the mixed emulsifier consists of an emulsifier and a co-emulsifier; the mass ratio of the emulsifier to the co-emulsifier is as follows: 0.8-1.8:1. The invention also provides a preparation method of the composition. The isoliquiritigenin nanoemulsion can improve the solubility of isoliquiritigenin and improve the bioavailability and pharmacological activity of the medicament.
Description
Technical Field
The invention belongs to the technical field of medicinal preparations, and particularly relates to isoliquiritigenin nanoemulsion and a preparation method thereof.
Background
Isoliquiritigenin (Isooliquiticigenin) is a flavonoid candidate with a variety of pharmacological activities and medicinal potential. It is originally named as the dried root and rhizome of Glycyrrhiza uralensis Fisch (Glycyrrhiza uralensis Fisch) belonging to Leguminosae, and is one of the main effective components of Glycyrrhiza uralensis. A large body of literature research shows: the isoliquiritigenin has obvious effects of resisting cancer, oxidation and aging, resisting ulcer, relieving spasm and improving immunity; is also effective component for resisting AIDS (HIV); it can inhibit furfural reductase and reduce sorbitol accumulation in erythrocytes, and can be used for adjuvant treatment of diabetes. Therefore, the isoliquiritigenin has a wide development prospect, but the water solubility of the isoliquiritigenin is poor, the bioavailability after oral administration is low, the applicant researches and discovers that the oral bioavailability of rats is 22.70-33.62%, and the isoliquiritigenin has various pharmacological activities but needs to be further improved.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides isoliquiritigenin nanoemulsion and a preparation method thereof. Can obviously improve the solubility of the medicine, and can obviously improve the bioavailability and the pharmacological activity after oral administration or injection administration.
The invention provides an isoliquiritigenin nanoemulsion, which consists of isoliquiritigenin and auxiliary materials; the auxiliary material comprises the following components in percentage by volume: 20-40% of oil phase, 35-48% of mixed emulsifier and 18-40% of distilled water;
the ratio of the isoliquiritigenin to the auxiliary materials is 0.2-1.0 g: 100 ml;
the mixed emulsifier consists of an emulsifier and a co-emulsifier; the mass ratio of the emulsifier to the co-emulsifier is as follows: 0.8-1.8:1.
Preferably, the oil phase is diisopropyl peroxydicarbonate, isopropyl myristate or caprylic/capric triglyceride; diisopropyl peroxydicarbonate is preferred.
Preferably, the emulsifier is Tween-20, Tween-80 or poloxamer 188; tween-20 is preferred.
Preferably, the coemulsifier is n-butanol, polyethylene glycol 400 or polyethylene glycol 600; n-butanol is preferred.
Preferably, the mass ratio of the emulsifier to the co-emulsifier is 1: 1.
Preferably, the mass ratio of the mixed emulsifier to the oil phase is 9:1-1: 9; preferably in a mass ratio of 6: 4.
The invention provides a preparation method of the isoliquiritigenin nanoemulsion, which is prepared by adopting a water titration method.
Preferably, isoliquiritigenin is dissolved in the oil phase, completely dissolved by ultrasonic, then the emulsifier and the co-emulsifier are added, and distilled water is added dropwise under stirring.
Preferably, the stirring speed during stirring is 200r/min-800 r/min; preferably, the stirring speed is 500 r/min.
Preferably, when the distilled water is added, the dropping speed is 1min/1100 mu l-7min/1100 mu l; preferably, the dropping speed is 5min/1100 μ l or 1min/1100 μ l; most preferably, the dropping rate is 5 min/1100. mu.l.
The isoliquiritigenin nanoemulsion can improve the solubility of isoliquiritigenin and improve the bioavailability and pharmacological activity of the medicament.
Drawings
The accompanying drawings, which are included to provide a further understanding of the invention and are incorporated in and constitute a part of this specification, illustrate embodiments of the invention and together with the description serve to explain the principles of the invention and not to limit the invention. In the drawings:
FIG. 1 is a diagram of a pseudo-ternary phase for determining the ratio of mixed emulsifier to oil phase.
Figure 2 is a graph of the effect of water droplet acceleration on nanoemulsion stability.
Figure 3 is a graph of the effect of agitation speed on nanoemulsion stability.
FIG. 4 shows the prepared isoliquiritigenin nanoemulsion.
FIG. 5 is a transmission electron micrograph (40X 1000 times) of the isoliquiritigenin nanoemulsion.
Fig. 6 is a particle size distribution of isoliquiritigenin nanoemulsion.
FIG. 7 is ZetaPotentifinal of isoliquiritigenin nanoemulsion.
FIG. 8 is a graph showing the drug effect of rats (SD, male, 200. + -.20 g) orally administered isoliquiritigenin nanoemulsion and isoliquiritigenin solution (both administered in an amount of 100mg/kg isoliquiritigenin).
FIG. 9 shows the experimental results of mouse tumor-suppressing animals with isoliquiritigenin nanoemulsion, wherein 1 is negative control, 2 is positive control, 3 is 10mg/kg isoliquiritigenin suspension, 4 is 20mg/kg isoliquiritigenin suspension, 5 is 40mg/kg isoliquiritigenin suspension, 6 is 10mg/kg isoliquiritigenin nanoemulsion, 7 is 20mg/kg isoliquiritigenin nanoemulsion, and 8 is 40mg/kg isoliquiritigenin nanoemulsion.
Detailed Description
The following examples are given to facilitate a better understanding of the invention, but do not limit the invention. The experimental procedures in the following examples are conventional unless otherwise specified. The test materials used in the following examples are commercially available unless otherwise specified.
The isoliquiritigenin nanoemulsion consists of isoliquiritigenin and auxiliary materials; the auxiliary material comprises the following components in percentage by volume: 20-40% of oil phase, 35-48% of mixed emulsifier and 18-40% of distilled water;
the ratio of the isoliquiritigenin to the auxiliary materials is 0.2-1.0 g: 100 ml;
the mixed emulsifier consists of an emulsifier and a co-emulsifier; the mass ratio of the emulsifier to the co-emulsifier is as follows: 0.8-1.8:1.
The oil phase is diisopropyl peroxydicarbonate, isopropyl myristate or caprylic/capric triglyceride.
The emulsifier is Tween-20, Tween-80 or poloxamer 188.
The coemulsifier is n-butyl alcohol, polyethylene glycol 400 or polyethylene glycol 600.
The mass ratio of the emulsifier to the co-emulsifier is preferably 1: 1.
The mass ratio of the mixed emulsifier to the oil phase is 9:1-1: 9.
The preparation method of the isoliquiritigenin nanoemulsion adopts a water titration method to prepare; specifically, isoliquiritigenin is dissolved in oil phase, ultrasonic wave is carried out to completely dissolve the isoliquiritigenin, then emulsifier and co-emulsifier are added into the oil phase, and distilled water is added dropwise under the stirring condition.
The stirring speed during stirring is 200r/min-800 r/min.
When distilled water is added, the dropping speed is 1min/1100 mu l-7min/1100 mu l.
Example 1
The formula of the isoliquiritigenin nanoemulsion comprises the following components:
0.4g of isoliquiritigenin, 30.0ml of IPP, 2020.6 ml of Tween-n-butanol, 25.9ml of n-butanol and 26.5ml of distilled water.
The preparation method adopts a water titration method and comprises the following steps: dissolving isoliquiritigenin with formula amount in IPP, and completely dissolving by ultrasonic oscillation. Adding Tween-20 and n-butanol into oil phase (IPP) containing dissolved medicine, and dropwise adding distilled water at a dropping speed of 1100 μ l/5min under stirring speed of 500r/min to obtain yellowish clear transparent isoliquiritigenin nanoemulsion.
Example 2
The formula of the isoliquiritigenin nanoemulsion comprises the following components:
0.32g of isoliquiritigenin, 22.1ml of IPP, 2016.8ml of Tween-n-butanol, 22.8ml of n-butanol and 38.3ml of distilled water.
The preparation method of this example is the same as example 1.
Example 3
The formula of the isoliquiritigenin nanoemulsion comprises the following components:
0.24g of isoliquiritigenin, 20.8ml of IPP, 2020.8 ml of Tween-n-butanol, 26.6ml of n-butanol and 31.8ml of distilled water.
The preparation method of this example is the same as example 1.
Example 4
The formula of the isoliquiritigenin nanoemulsion comprises the following components:
0.63g of isoliquiritigenin, 36.1ml of IPP, 2020.3 ml of Tween-n-butanol, 25.4ml of n-butanol and 18.2ml of distilled water.
The preparation method of this example is the same as example 1.
Example 5
The formula of the isoliquiritigenin nanoemulsion comprises the following components:
0.37g of isoliquiritigenin, 23.2ml of IPP, 2023.9 ml of Tween-n-butanol, 22.1ml of n-butanol and 30.8ml of distilled water.
The preparation method of this example is the same as example 1.
Example 6
The formula of the isoliquiritigenin nanoemulsion comprises the following components:
isoliquiritigenin 0.81g, IPP 40.0ml, Tween-2017.5 ml, n-butanol 17.5ml, and distilled water 25.0 ml.
The preparation method of this example is the same as example 1.
Example 7
The formula of the isoliquiritigenin nanoemulsion comprises the following components:
isoliquiritigenin 0.20g, IPP 21.4ml, Tween-2018.5 ml, n-butanol 20.1ml, and distilled water 39.0 ml.
The preparation method of this example is the same as example 1.
Example 8
The formula of the isoliquiritigenin nanoemulsion comprises the following components:
isoliquiritigenin 0.53g, IPP 28.4ml, Tween-2023 ml, n-butanol 28.5ml, and distilled water 20.1 ml.
The preparation method of this example is the same as example 1.
The experiment of the optimization process of the isoliquiritigenin nanoemulsion of the invention is as follows:
1 Instrument and reagent
Constant temperature heating magnetic stirrer (model CL-2, Prov. Waals, Inc., China), Sartorius1-14 high speed centrifuge, Zetasizer nano ZS (British) nanosize and zeta potential and molecular weight analyzer. Agilent 1200 high performance liquid chromatograph (G1311A quaternary pump, G1329A autosampler, G1315B DAD detector, G1316A column oven.
Isoliquiritigenin (Shanghai Bang chemical industry Co., Ltd., purity 99.0%), Tween20 (Shanghai chemical reagent procurement supply station, voyage), Tween80 (Tween80, Tianjin Xin Shunfu Fine chemical research institute), Poloxamer188 (Poloxamer, Beijing Phoenix Jing Cheng Jing Cheng Shu Du Cai Ju, original production area: German BASF), n-butanol (Zhenzhou chemical reagent factory), polyethylene glycol 400(PEG400, Tianjin Kaixin chemical industry Co., Ltd., original Tianjin Tianhe chemical reagent factory), polyethylene glycol 600(PEG600, Shanghai reagent factory, Shanghai), IPP (diisopropyl peroxydicarbonate, Zhejiang substance Mei Biotechnology Co., Ltd.), IPM (isopropyl myristate, Zhejiang substance Mei Biotechnology Co., Ltd.), GTCC (caprylic acid tricaprylin, Zhejiang substance Mei caprate substance Mei Biotechnology Co., Ltd.).
Preparation of 2-isoliquiritigenin nano-emulsion
Accurately weighing isoliquiritigenin, dissolving in oil phase, and dissolving completely by ultrasonic oscillation. Precisely weighing emulsifier and co-emulsifier, adding into oil phase dissolved with isoliquiritigenin, stirring at 500r/min, and adding distilled water at 1100 μ l/5min to obtain isoliquiritigenin nanoemulsion.
The amount of isoliquiritigenin added is based on the solubility of isoliquiritigenin in IPP (about 25 deg.C), and it is required that no excessive drug is separated out.
3 optimization method and optimization results
According to preliminary experiments, with emulsifiers: the nanoemulsion was prepared with the co-emulsifier mass ratio of 3:2 or 1:1, and was found to be present as an emulsifier: co-emulsifier 3:2 the prepared nanoemulsion is very unstable and can be settled after being placed for a long time. And (2) adding an emulsifier: the nanoemulsion obtained by using the coemulsifier as 1:1 is relatively stable. I.e. the previous experiment with emulsifiers: and preparing the mixed emulsifier with the mass ratio of the auxiliary emulsifier being 1: 1.
Mixing an emulsifier: and respectively mixing the oil phase with 9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8 and 1:9 in mass ratio, placing the mixture in a test tube, stirring, dropwise adding the water phase to obtain a clear and transparent nanoemulsion, and observing the stability of the nanoemulsion by naked eyes to determine that the oil phase is most stable when the mass ratio is 9: 1. I.e. the previous experiment to mix emulsifiers: the mass ratio of the oil phase was 9: 1.
3.1 selection of the oil phase
Selecting IPP (diisopropyl peroxydicarbonate), IPM (isopropyl myristate) and GTCC (caprylic/capric triglyceride) as oil phases, tween20 as an emulsifier, and n-butanol as a co-emulsifier, and mixing the emulsifiers: the mass ratio of the oil phase is 9:1, and the weight ratio of the emulsifier: mixing the auxiliary emulsifier with the mass ratio Km to l to 1, and preparing the nano-emulsion by a water phase titration method. And (3) measuring the light transmittance of the prepared nano emulsion under an ultraviolet-visible spectrophotometer (396nm), centrifuging for 8min at 14000r/min, measuring the light transmittance by the ultraviolet-visible spectrophotometer after centrifuging, and screening the oil phase according to the difference of the light transmittance. The results are shown in Table 1.
Table 1 selection results of oil phase
As can be seen from the data in table 1, the oil phase IPP was finally selected as the prescribed oil phase because the difference in light transmittance of the oil phase IPP was minimal from the viewpoint of stability.
3.2 selection of emulsifiers
Selecting Tween-20 (Tween 20), Tween-80 (Tween 80) and Poloxamer188 (Poloxamer 188) as emulsifiers, IPP as an oil phase, n-butanol as a co-emulsifier, and mixing the emulsifiers: the mass ratio of the oil phase is 9:1, and the weight ratio of the emulsifier: mixing the auxiliary emulsifier with the mass ratio Km to l to 1, and preparing the nano-emulsion by a water phase titration method. And (3) measuring the light transmittance of the prepared nano-emulsion in an ultraviolet-visible spectrophotometer (396nm), centrifuging for 8min at 14000r/min, measuring the light transmittance by the ultraviolet-visible spectrophotometer after centrifuging, and screening the emulsifier according to the difference of the light transmittance. The results are shown in Table 2.
TABLE 2 selection of emulsifiers
As can be seen from the data in Table 2, Tween20 was finally selected as the emulsifier for the formulation due to the minimal difference in light transmittance of Tween20 from stability point of view.
3.3 screening of optimal Co-emulsifier
Selecting n-butyl alcohol, polyethylene glycol 400 and polyethylene glycol 600 as co-emulsifiers, IPP as an oil phase, Tween-20 as an emulsifier, and mixing the emulsifiers: the mass ratio of the oil phase is 9:1, and the weight ratio of the emulsifier: the mass ratio Km ═ l of the co-emulsifier: 1, and preparing the nano emulsion by a water phase titration method. And (3) measuring the light transmittance of the prepared nano emulsion in an ultraviolet-visible spectrophotometer (396nm), centrifuging at 14000r/min, measuring the light transmittance by the ultraviolet-visible spectrophotometer after centrifuging, and screening the co-emulsifier according to the difference of the light transmittance. The results are shown in Table 3.
TABLE 3 screening results of coemulsifiers
From the data, it can be seen that n-butanol was finally selected as the co-emulsifier for the prescription because the light transmittance difference of n-butanol was the smallest for stability.
3.4 ratio of Mixed emulsifier to oil phase
Taking Tween20 as an emulsifier, n-butanol as an auxiliary emulsifier, IPP as an oil phase, and the emulsifier: the mass ratio km of the co-emulsifier is 1:1, the mixed emulsifier and the oil phase are placed in a test tube according to the mass ratio of 9:1, 8:2, 7:3, 6:4, 5:5, 4:6, 3:7, 2:8 and 1:9, and the critical point of the emulsion is observed when the emulsion turns from clear to turbid and turns from turbid to clear, so that a pseudo-ternary phase diagram is obtained, as shown in figure 1.
FIG. 1 is a diagram of a pseudo-ternary phase for determining the ratio of mixed emulsifier to oil phase.
The results show that when the mass ratio of the mixed emulsifier to the oil phase is 6:4, the emulsion area is larger, i.e., the emulsion is more easily formed. The mass ratio of the mixed emulsifier to the oil phase was chosen to be 6:4 in order to obtain a larger milk area and better stability.
3.5 Effect of Water droplet acceleration on nanoemulsion stability
Screening Tween20 as an emulsifier, n-butanol as an auxiliary emulsifier, IPP as an oil phase, and mixing the emulsifiers, wherein the mass ratio of the oil phase is 6:4, and the emulsifiers are: the mass ratio km of the co-emulsifier is 1:1, the distilled water is dropwise added according to the acceleration of water drops of 1min/1100 mul, 2min/1100 mul, 3min/1100 mul, 4min/1100 mul, 5min/1100 mul, 6min/1100 mul and 7min/1100 mul, and the experiment is repeated three times, and the results are shown in Table 4 and figure 2.
TABLE 4 Effect of Water droplet acceleration on nanoemulsion stability
Figure 2 is a graph of the effect of water droplet acceleration on nanoemulsion stability.
The result shows that the difference value of the acceleration of the water drop is maximum at 4min/1100 mu l, namely, the difference value is unstable, and the integral light transmittance difference value is reduced to minimum at 5min/1100 mu l, namely, the formed nano-emulsion is stable; although the stability of formation was high at 1 min/1100. mu.l, 5 min/1100. mu.l was selected because the time was too short to facilitate handling at the time of dropping.
3.6 Effect of agitation speed on nanoemulsion stability
Taking tween20 as an emulsifier, n-butanol as an auxiliary emulsifier, IPP as an oil phase, and mixing the emulsifier with the oil phase in a mass ratio of 6:4, wherein the emulsifier: the mass ratio km of the co-emulsifier is 1:1, the stirring speed is respectively adjusted to the scales of 200r/min, 300r/min, 400r/min, 500r/min, 600r/min, 700r/min and 800r/min by the rotating speed of a CL-2 type constant temperature heating magnetic stirrer, the water drop acceleration is 5min/1100 mu l, and the steps are repeated three times, and the results are shown in Table 5 and figure 3.
TABLE 5 influence of stirring speed on nanoemulsion stability
Figure 3 is a graph of the effect of agitation speed on nanoemulsion stability.
The results show that when the stirring speed is 500r/min, the prepared nano-emulsion is most stable.
Optimal preparation method of 4-isoliquiritigenin nanoemulsion
Accurately weighing 0.4g isoliquiritigenin, dissolving in 30ml IPP, and ultrasonic vibrating to dissolve completely (or ultrasonic and heating to 25 deg.C to dissolve if necessary). Precisely weighing 20.6ml of Tween-20 and 25.9ml of n-butanol, adding into the oil phase dissolved with the medicine, stirring at 500r/min, and adding 26.5ml of distilled water at the dropping speed of 1100 μ l/5min to obtain the yellowish clear and transparent isoliquiritigenin nanoemulsion.
5 quality and performance evaluation of isoliquiritigenin nanoemulsion prepared in step 4
The isoliquiritigenin has poor water solubility, the solubility of the isoliquiritigenin in water is only 17.07 +/-1.02 mug/ml measured by a high performance liquid chromatography, the drug content of the isoliquiritigenin nanoemulsion prepared by the invention can reach 10 +/-0.24 mg/ml, the drug solubility is greatly improved, the prepared isoliquiritigenin nanoemulsion is shown in figure 4, and as can be seen from figure 4, the isoliquiritigenin nanoemulsion is a faint yellow clear and transparent emulsion.
FIG. 5 is a transmission electron micrograph (40X 1000 times) of the isoliquiritigenin nanoemulsion. As can be seen from fig. 5, the isoliquiritigenin nanoemulsion is a spherical particle with uniform size and good roundness.
Fig. 6 is a particle size distribution of isoliquiritigenin nanoemulsion. As can be seen from fig. 6, the isoliquiritigenin nanoemulsion has a monomodal particle size distribution and a narrow distribution range. The average particle size was 317.9 nm. The particle size of the prepared isoliquiritigenin nanoemulsion meets the following standard: the total number of milk particles with an average particle size of less than 1 μm should not be less than 95%, the milk particles with an average particle size of more than 1 μm should not exceed 3%, and milk particles with an average particle size of more than 5 μm should not be detected.
FIG. 7 shows Zeta Potential of isoliquiritigenin nanoemulsion. As can be seen from FIG. 7, the average ZetaPotential of the isoliquiritigenin nanoemulsion was-19.0 mv.
The pharmacokinetic study carried out on the isoliquiritigenin nanoemulsion prepared in the step 4 shows that: the isoliquiritigenin nanoemulsion can obviously promote the absorption of isoliquiritigenin after being orally taken, improve the blood concentration of isoliquiritigenin and improve the bioavailability of the medicament. After the isoliquiritigenin nanoemulsion and the isoliquiritigenin solution (the administration dose is 100mg/kg of isoliquiritigenin) are respectively orally administered to rats (male, 200 +/-20 g), 0.08,0.25,0.5,1,1.5,2,3,4,6,9,12 and 24h of the rats are anesthetized by ether after administration, 0.3mL of blood is taken from the fundus venous plexus to a centrifugal tube soaked by 1% heparin sodium solution, the blood is centrifuged at 4500rpm for 10min, and then upper plasma is taken and stored at-20 ℃. Taking a plasma sample frozen at minus 20 ℃, naturally thawing at room temperature, precisely measuring 100 mu L, adding 40 mu L of internal standard working solution of 2.5 mu g.mL < -1 >, adding 60 mu L of methanol, performing vortex for 1min, centrifuging at 12000rpm for 10min, taking 20 mu L of supernate, injecting sample, detecting a drug peak and an internal standard peak, substituting the result into a regression equation, and calculating the blood concentration to obtain a drug time curve shown in figure 5.
The preparation method of the isoliquiritigenin solution comprises the following steps: isoliquiritigenin is dissolved in medical ethanol-Tween 80-0.9% sodium chloride solution (v/v/v) with the ratio of 10:15: 75.
FIG. 8 is a graph showing the drug effect of isoliquiritigenin nanoemulsion and isoliquiritigenin solution (both the dose of isoliquiritigenin is 100mg/kg) administered orally to rats (SD, male, 200 + -20 g).
An anti-tumor animal experiment carried out by using the isoliquiritigenin nanoemulsion prepared in the step 4 shows that the isoliquiritigenin nanoemulsion mouse has an obvious anti-tumor effect after intraperitoneal injection, and the result is shown in figure 9.
FIG. 9 shows the experimental results of mouse tumor-suppressing animals with isoliquiritigenin nanoemulsion, wherein 1 is negative control, 2 is positive control, 3 is 10mg/kg isoliquiritigenin suspension, 4 is 20mg/kg isoliquiritigenin suspension, 5 is 40mg/kg isoliquiritigenin suspension, 6 is 10mg/kg isoliquiritigenin nanoemulsion, 7 is 20mg/kg isoliquiritigenin nanoemulsion, and 8 is 40mg/kg isoliquiritigenin nanoemulsion.
The preparation method of the isoliquiritigenin suspension comprises the following steps: dispersing 1ml isoliquiritigenin ethanol solution (5mg/ml) in double distilled water.
Finally, it should be noted that: although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that changes may be made in the embodiments and/or equivalents thereof without departing from the spirit and scope of the invention. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. An isoliquiritigenin nanoemulsion is characterized in that: the isoliquiritigenin nanoemulsion consists of isoliquiritigenin and auxiliary materials; the auxiliary material comprises the following components in percentage by volume: 20-40% of oil phase, 35-48% of mixed emulsifier and 18-40% of distilled water;
the ratio of the isoliquiritigenin to the auxiliary materials is 0.2-1.0 g: 100 ml;
the mixed emulsifier consists of an emulsifier and a co-emulsifier; the mass ratio of the emulsifier to the co-emulsifier is as follows: 0.8-1.8:1.
2. The isoliquiritigenin nanoemulsion of claim 1, wherein: the oil phase is diisopropyl peroxydicarbonate, isopropyl myristate or caprylic/capric triglyceride; diisopropyl peroxydicarbonate is preferred.
3. The isoliquiritigenin nanoemulsion of claim 1, wherein: the emulsifier is Tween-20, Tween-80 or poloxamer 188; tween-20 is preferred.
4. The isoliquiritigenin nanoemulsion of claim 1, wherein: the coemulsifier is n-butyl alcohol, polyethylene glycol 400 or polyethylene glycol 600; n-butanol is preferred.
5. The isoliquiritigenin nanoemulsion of claim 1, wherein: the mass ratio of the emulsifier to the co-emulsifier is 1: 1.
6. The isoliquiritigenin nanoemulsion of claim 1, wherein: the mass ratio of the mixed emulsifier to the oil phase is 9:1-1: 9; preferably in a mass ratio of 6: 4.
7. The method for preparing an isoliquiritigenin nanoemulsion of any one of claims 1-6, wherein: prepared by a water titration method.
8. The method of claim 7, wherein: dissolving isoliquiritigenin in oil phase, ultrasonic dissolving completely, adding emulsifier and co-emulsifier, and adding distilled water dropwise under stirring.
9. The method of claim 8, wherein: the stirring speed during stirring is 200r/min-800 r/min; preferably, the stirring speed is 500 r/min.
10. The method of claim 8, wherein: when distilled water is added, the dropping speed is 1min/1100 mu l-7min/1100 mu l; preferably, the dropping speed is 5min/1100 μ l or 1min/1100 μ l; most preferably, the dropping rate is 5 min/1100. mu.l.
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| CN113813229A (en) * | 2021-10-11 | 2021-12-21 | 河南中医药大学 | Isoliquiritigenin self-microemulsion, preparation method and application thereof in EOE model mice |
| CN116211829A (en) * | 2021-12-03 | 2023-06-06 | 香港大学 | An oral nanometer preparation and its preparation method |
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