Oil-in-water-in-oil dual emulsion as well as one-step preparation method and application thereof

Abstract

The invention relates to the technical field of colloid and interface chemistry, in particular to an oil-in-water-in-oil double emulsion, a one-step preparation method of the oil-in-water-in-oil double emulsion and application of the oil-in-water-in-oil double emulsion. A water phase and an oil phase are sheared and stirred at a high speed of 6000-12000 r / min through a one-step process to form an emulsion with a droplet diameter of 1-100 [mu] m. According to the invention, the tedious process of respectively stabilizing the inner and outer oil-water interfaces of the double emulsion through two emulsifiers with different hydrophilic and oleophylic properties in a traditional two-step method is effectively improved, and the O / W / O double emulsion is directly obtained through a one-step process, so that the purpose of simultaneously stabilizing the inner and outer emulsion interfaces of the double emulsion through a single emulsifier is achieved; the method has a huge potential application prospect in the fields of food packaging, drug sustained release and the like.

Description

Technical Field

[0001] The present invention relates to the technical field of colloid and interface chemistry, and in particular to an oil-in-water-in-oil double emulsion and a one-step preparation method and application thereof. Background Art

[0002] Conventional emulsions have limited applications in the field of drug delivery. A water-in-oil (W / O) emulsion system, in which a drug is dissolved in an inner phase consisting of an aqueous phase and surrounded by an outer phase consisting of an oil phase, can only be used as a carrier for hydrophilic drugs; an oil-in-water (O / W) emulsion system, in which a drug is dissolved in an inner phase consisting of an oil phase and surrounded by an outer phase consisting of an aqueous phase, can only be used as a carrier for lipophilic drugs. Both systems cannot meet the requirement of simultaneously encapsulating two drugs with different hydrophilic and lipophilic characteristics in the same emulsification system.

[0003] A double emulsion is an emulsion in which one liquid phase is dispersed in another continuous phase. Microscopically, the emulsion droplets contain smaller droplets. Double emulsions are primarily classified into two types: water-in-oil-in-water (W / O / W) and oil-in-water-in-oil (O / W / O). The multiphase system and two-layer interfacial membrane of double emulsions make them valuable for drug delivery. For example, they can simultaneously transport water-soluble and lipid-soluble drugs, or drugs with a certain solubility in both phases. Drugs easily destroyed by the gastrointestinal environment, such as vitamins, probiotics, and coenzyme Q10, can be encapsulated in one phase to improve their stability and efficacy. Therefore, the development and utilization of double emulsions with simple processes and biocompatible, inexpensive raw materials is extremely urgent.

[0004] Compared to simple water-in-oil (W / O) or oil-in-water (O / W) emulsions, double emulsions possess a unique two-membrane, three-phase structure (two oil-water interfacial layers, two water phases and one oil phase, or two oil phases and one water phase). Therefore, two different emulsifiers are required to jointly stabilize the inner and outer interfacial layers of the double emulsion, resulting in complex production processes. Currently, commonly used lipophilic emulsifiers include lecithin, sucrose esters, Span 80, and PGPR. Hydrophilic emulsifiers are far more diverse than lipophilic emulsifiers, including small-molecule surfactants, polysaccharides, proteins, and protein-polysaccharide complexes. In double emulsions using traditional small-molecule surfactants as emulsifiers, lipophilic surfactants with low HLB values ​​typically stabilize the W / O interface, while hydrophilic surfactants with high HLB values ​​stabilize the O / W interface. Taking O / W / O multiphase emulsion as an example, the first step is to mix the water-soluble emulsifier, the internal oil phase and the water phase, and then use high-intensity emulsification conditions in a high-speed dispersing emulsifier to obtain O / W colostrum. The colostrum is then poured into an oil solution containing an oil-soluble emulsifier, and high-speed emulsification is performed in a high-speed dispersing homogenizer to obtain an O / W / O multiphase emulsion. However, the two-step process of forming a multiphase emulsion is relatively cumbersome. First, two different surfactants must be found, and the ratio of the two surfactants needs to be adjusted to stabilize the internal and external interfaces of the multiphase emulsion. In addition, due to the numerous steps, the droplet size distribution of the obtained emulsion is very wide, which leads to poor emulsion stability and many restrictions on subsequent applications, making it impossible to apply it on a large scale industrially. Summary of the Invention

[0005] In view of this, the purpose of the present invention is to propose an oil-in-water-in-oil double emulsion and its one-step preparation method and application, avoiding the tedious process of using two emulsifiers to emulsify the inner and outer interfaces of the double emulsion respectively in a two-step process. Through a one-step process, an O / W / O emulsion is directly obtained, achieving the purpose of using a single emulsifier to simultaneously stabilize the inner and outer emulsion interfaces of the double emulsion.

[0006] Based on the above objectives, the present invention provides a one-step method for preparing an oil-in-water-in-oil double emulsion, wherein the method uses food-grade polyglycerol ricinoleate as a single emulsion stabilizer, and through a one-step process, the water and oil phases are subjected to high-speed shear stirring at 6000 to 12000 r / min to form an emulsion with a droplet diameter of 1 to 100 μm.

[0007] The one-step method for preparing an oil-in-water-in-oil double emulsion comprises the following steps:

[0008] S1. Add the oil phase and the water phase into the emulsification container in a volume ratio of 31-32:29-28;

[0009] S2, adding polyglycerol ricinoleate to the emulsification container in S1;

[0010] S3. The three substances in the emulsification container of S2 are subjected to a one-step process and stirred at high speed for 1 to 30 minutes to obtain the emulsion containing dispersed droplets.

[0011] Preferably, the mass volume ratio of the polyglycerol ricinoleate to the oil phase is 0.5-0.7 g:31-32 mL.

[0012] Preferably, the organic alkane oil includes hexadecane, tetradecane and dodecane.

[0013] Optionally, the stirring time in S3 is 1 to 30 minutes.

[0014] The present invention also provides an oil-in-water-in-oil double emulsion, which is prepared by adopting the method.

[0015] The present invention also provides application of the oil-in-water-in-oil double emulsion in food packaging or drug sustained release.

[0016] Beneficial effects of the present invention:

[0017] The present invention provides a one-step method for preparing an oil-in-water-in-oil (O / W / O) double emulsion using a single emulsifier. In this one-step process, the emulsifier, aqueous phase, and oil phase are subjected to high-speed shearing to produce an O / W / O double emulsion with dispersed droplets ranging from 1 to 100 μm. This method effectively improves upon the cumbersome two-step process of using two emulsifiers with different hydrophilic and lipophilic properties to stabilize the inner and outer oil-water interfaces of the double emulsion. This one-step process directly produces an O / W / O double emulsion, achieving the goal of simultaneously stabilizing both the inner and outer emulsion interfaces with a single emulsifier. This method has potential applications in areas such as food packaging and sustained drug release.

[0018] The present invention utilizes commercially available PGPR as a single emulsifier to successfully prepare an oil-in-water-in-oil (O / W / O) emulsion through a one-step process. This method develops a new method for simultaneously stabilizing both oil-water interfaces within an O / W / O double emulsion using only a single emulsifier, resulting in a new strategy for a double emulsion stabilization system with a simple process and low raw material costs. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the technical solutions in the present invention or the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only for the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0020] Figure 1 This is a digital photograph of the O / W / O double emulsion obtained in step S3 of Example 1 of the present invention;

[0021] Figure 2 This is a fluorescence microscope image of the O / W / O double emulsion obtained in step S3 of Example 1 of the present invention, wherein the water phase is dyed green by the fluorescent agent, and the undyed black area is the oil phase;

[0022] Figure 3 : This is a particle size distribution diagram of the O / W / O double emulsion obtained in step S3 of Example 1 of the present invention;

[0023] Figure 4 Schematic diagram of the structure of the O / W / O double emulsion obtained in step S3 of Example 1 of the present invention,

[0024] Figure 5 The figures are test images of the emulsions obtained in the comparative example; a is a digital photograph of the emulsions obtained with the volume ratios of dodecane to water of 3.5:2.5, 3.4:2.6, and 3.3:2.7; b is a fluorescence microscopy photograph of the emulsion obtained with the volume ratio of dodecane to water of 3.5:2.5; c is a fluorescence microscopy photograph of the emulsion obtained with the volume ratio of dodecane to water of 3.4:2.6; and d is a fluorescence microscopy photograph of the emulsion obtained with the volume ratio of dodecane to water of 3.3:2.7.

[0025] Figure 6 The present invention is a flow chart of the one-step method for preparing O / W / O double emulsion. DETAILED DESCRIPTION

[0026] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below with reference to specific embodiments.

[0027] It should be noted that, unless otherwise defined, the technical or scientific terms used in the present invention should have the common meanings understood by persons having ordinary skills in the field to which the present invention belongs.

[0028] Example 1

[0029] A method for preparing an oil-in-water-in-oil (O / W / O) double emulsion using a single emulsifier in a one-step process, wherein the specific preparation steps are as follows:

[0030] S1. Add dodecane and water in a volume ratio of 3.2 mL:2.8 mL to the emulsification bottle;

[0031] S2. Add 0.06 g of polyglycerol ricinoleate (PGPR) emulsifier to the emulsification bottle in step S1;

[0032] S3. The three substances in the emulsification bottle of step S2 are emulsified using a one-step process, and are stirred at a high speed of 8000 r / min for 6 minutes to obtain an emulsion containing dispersed droplets; that is, an O / W / O double emulsion is formed.

[0033] like Figure 1 As shown, the emulsion obtained in step S3 is milky white and does not break when stored at room temperature for 3 months, indicating that the prepared emulsion has good stability.

[0034] like Figure 2 As shown in the figure, a microscopic photograph of a double emulsion taken with a fluorescence microscope, in which the water phase is dyed green with a fluorescent dye. The microscopic photograph clearly shows that there are black oil phase regions both inside and outside the droplets composed of the green water phase, which intuitively proves that the obtained emulsion is an oil-in-water-in-oil double emulsion (O / W / O); the droplets are independent of each other in the oil phase and there is no coagulation phenomenon, indicating that the emulsifier plays a good stabilizing role.

[0035] like Figure 3 As shown, it is the particle size distribution diagram of the prepared emulsion droplets. The average particle size of the emulsion droplets is about 11 μm, indicating that the PGPR emulsification and stable dispersion effect is very good, and the prepared emulsion dispersion droplets can reach 10 micron level.

[0036] like Figure 4 The figure shows a schematic diagram of the model of the prepared oil-in-water-in-oil emulsion. The schematic diagram of the simulated fluorescence microscope clearly shows the two-membrane three-cavity structure of the prepared double emulsion, namely the innermost black oil phase, the middle green water phase, and the outer black oil phase.

[0037] Example 2

[0038] A method for preparing an oil-in-water-in-oil (O / W / O) double emulsion using a single emulsifier in a one-step process, wherein the specific preparation steps are as follows:

[0039] S1. Add tetradecane and water in a volume ratio of 3.1 mL:2.9 mL to an emulsifier bottle;

[0040] S2. Add 0.06 g of polyglycerol ricinoleate (PGPR) emulsifier to the emulsification bottle in step S1;

[0041] S3. The three substances in the emulsification bottle of step S2 are emulsified using a one-step process, and are stirred at a high speed of 10,000 r / min for 8 minutes to obtain an emulsion containing dispersed droplets; that is, an O / W / O double emulsion is formed.

[0042] Example 3

[0043] A method for preparing an oil-in-water-in-oil (O / W / O) double emulsion using a single emulsifier in a one-step process, wherein the specific preparation steps are as follows:

[0044] S1. Add hexadecane and water in a volume ratio of 3.1 mL:2.9 mL to an emulsifier bottle;

[0045] S2. Add 0.06 g of polyglycerol ricinoleate (PGPR) emulsifier to the emulsification bottle in step S1;

[0046] S3. The three substances in the emulsification bottle of step S2 are emulsified using a one-step process, and are stirred at a high speed of 12000r / min for 10min to obtain an emulsion containing dispersed droplets; that is, an O / W / O double emulsion is formed.

[0047] Example 4

[0048] A method for preparing an oil-in-water-in-oil (O / W / O) double emulsion using a single emulsifier in a one-step process, wherein the specific preparation steps are as follows:

[0049] S1. Add dodecane and water in a volume ratio of 3.2 mL:2.8 mL to the emulsification bottle;

[0050] S2. Add 0.06 g of polyglycerol ricinoleate (PGPR) emulsifier to the emulsification bottle in step S1;

[0051] S3. The three substances in the emulsification bottle of step S2 are emulsified using a one-step process, and are stirred at a high speed of 11000r / min for 3min to obtain an emulsion containing dispersed droplets; that is, an O / W / O double emulsion is formed.

[0052] Comparative Example

[0053] A method for preparing an oil-in-water-in-oil (O / W / O) double emulsion using a single emulsifier in a one-step process, wherein the specific preparation steps are as follows:

[0054] S1. Add dodecane and water to an emulsifier bottle in a volume ratio of 3.3-3.5 mL:2.7-2.5 mL;

[0055] S2. Add 0.06 g of polyglycerol ricinoleate (PGPR) emulsifier to the emulsification bottle in step S1;

[0056] S3. The three substances in the emulsified bottle in step S2 were emulsified using a one-step process, homogenized at 9000r / min under high-speed shear conditions, stirred by high-speed shear stirring for 5min to obtain an emulsion containing dispersed droplets;

[0057] like Figure 5As shown in (a), the emulsion obtained in step S3 is milky white and does not break when stored at room temperature for 3 months, indicating that the prepared emulsion has good stability.

[0058] like Figure 5 As shown in (b), a fluorescence microscope photograph of an emulsion sample prepared by adding dodecane and water in a volume ratio of 3.5 mL:2.5 mL is shown. The aqueous phase is stained green with a fluorescent dye. The microscopic photograph clearly shows that black oil phase droplets are evenly distributed in the green aqueous phase, which intuitively proves that the obtained emulsion is an oil-in-water (O / W) type, indicating that an O / W / O double emulsion cannot be obtained under this oil-water ratio condition.

[0059] like Figure 5 As shown in (c), a fluorescence microscope photograph of an emulsion sample prepared by adding dodecane and water in a volume ratio of 3.4 mL:2.6 mL is shown. The aqueous phase is stained green with a fluorescent dye. The microscopic photograph clearly shows that black oil phase droplets are evenly distributed in the green aqueous phase, which intuitively proves that the obtained emulsion is an oil-in-water (O / W) type, indicating that an O / W / O double emulsion cannot be obtained under this oil-water ratio condition.

[0060] like Figure 5 As shown in (d), a fluorescence microscope photograph of an emulsion sample prepared by adding dodecane and water in a volume ratio of 3.3 mL:2.7 mL is shown. The aqueous phase is stained green with a fluorescent dye. The microscopic photograph clearly shows that black oil phase droplets are evenly distributed in the green aqueous phase, which intuitively proves that the obtained emulsion is an oil-in-water (O / W) type, indicating that an O / W / O double emulsion cannot be obtained under this oil-water ratio condition.

[0061] Those skilled in the art will understand that the discussion of any of the above embodiments is merely illustrative and is not intended to limit the scope of the present invention to these examples. Within the spirit and principles of the present invention, the technical features of the above embodiments or different embodiments may be combined, the steps may be implemented in any order, and many other variations exist for the various aspects of the present invention described above, which are not provided in detail for the sake of clarity. Any omissions, modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included within the scope of protection of the present invention.

Claims

1. A one-step method for preparing an oil-in-water-in-oil double emulsion, characterized in that: The method adopts food-grade polyglycerol ricinoleate as a single emulsifying stabilizer, and forms an emulsion with a droplet diameter of 1 to 100 μm by subjecting water and oil phases to high-speed shear stirring at 6000 to 12000 r / min through a one-step process.

2. The method for preparing an oil-in-water-in-oil double emulsion by one step according to claim 1, characterized in that: The steps include: S1. Add the oil phase and the water phase into the emulsification container in a volume ratio of 31-32:29-28; S2, adding polyglycerol ricinoleate to the emulsification container in S1; S3. The three substances in the emulsification container of S2 are subjected to a one-step process and stirred at high speed for 1 to 30 minutes to obtain the emulsion containing dispersed droplets.

3. The method for preparing an oil-in-water-in-oil double emulsion by a one-step method according to claim 1 or 2, characterized in that: The mass volume ratio of the polyglycerol ricinoleate to the oil phase is 0.5-0.7 g:31-32 mL.

4. The method for preparing an oil-in-water-in-oil double emulsion by a one-step method according to claim 1 or 2, characterized in that: The oil phase is organic alkane oil.

5. The method for preparing an oil-in-water-in-oil double emulsion in one step according to claim 4, characterized in that: The organic alkane oil includes hexadecane, tetradecane and dodecane.

6. The method for preparing an oil-in-water-in-oil double emulsion by one step according to claim 1 or 2, characterized in that: The stirring time in S3 is 1 to 30 minutes.

7. An oil-in-water-in-oil double emulsion, characterized in that: The product is prepared by the method according to any one of claims 1 to 6.

8. Use of the oil-in-water-in-oil double emulsion according to claim 7 in food packaging or drug sustained release.

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