CN114452227B - Method for preparing alcohol-in-oil-in-water multiple pickering emulsion by anti-solvent recrystallization method - Google Patents
Method for preparing alcohol-in-oil-in-water multiple pickering emulsion by anti-solvent recrystallization method Download PDFInfo
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Abstract
The invention discloses a method for preparing an alcohol-in-oil-in-water multiple pickering emulsion by an anti-solvent recrystallization method, wherein the multiple pickering emulsion comprises oil-water-insoluble active substances, polyalcohol, an oil phase, hydrophilic fumed silica, hydrophobic fumed silica and deionized water; the preparation method adopts the polyalcohol to replace an internal water phase, improves the loading capacity of oil-water two-insoluble active substances, and based on the loading capacity, adopts a two-step method to prepare the alcohol-in-water-in-oil multiple pickering emulsion, and in the second-step emulsification process, the active substances in the internal alcohol phase are subjected to anti-solvent recrystallization precipitation and co-stabilize an oil-water interface with hydrophilic fumed silica, so that the system has super-strong stability. The alcohol-in-oil-in-water multiple pickering emulsion prepared by the invention provides a dissolution environment for the oil-water-insoluble active substances on one hand, and can obviously improve the loading capacity of the oil-water-insoluble active substances in the emulsion; on the other hand, the anti-solvent recrystallization phenomenon in the preparation process can endow the system with super-strong stability.
Description
Technical Field
The invention belongs to the technical field of micro-nano carriers, and particularly relates to a method for preparing an alcohol-in-oil-in-water multiple Pickering emulsion by an anti-solvent recrystallization method.
Background
With the continuous development of synthetic technology and related fields, newly discovered active substances in cosmetics are increasing, wherein a large part of active substances are insoluble active substances, and part of active substances are more difficult to be dissolved in oil and water. However, solubility is an important issue in the development of cosmetic systems that requires attention, directly affecting the percutaneous absorption and bioavailability of the active. The micro-nano carrier technology is an important technology for solving the problems of low solubility and low bioavailability of active ingredients. Compared with the chemical modification technology, the micro-nano carrier technology basically does not influence the functional characteristics of the active ingredients, and the operation method is relatively simple.
At present, common micro-nano carriers comprise liposome, cyclodextrin inclusion compound, microcapsule, emulsion and the like. These carrier technologies increase the solubility and bioavailability of poorly water-soluble ingredients to some extent, but also have some drawbacks such as low loading and poor stability.
For oil-water-insoluble components, it is more difficult to prepare a suitable carrier.
Disclosure of Invention
This section is intended to outline some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section as well as in the description summary and in the title of the application, to avoid obscuring the purpose of this section, the description summary and the title of the invention, which should not be used to limit the scope of the invention.
The present invention has been made in view of the above and/or problems occurring in the prior art.
Therefore, the invention aims to overcome the defects in the prior art and provide the alcohol-in-oil-in-water multiple pickering emulsion prepared by an anti-solvent recrystallization method.
In order to solve the technical problems, the invention provides the following technical scheme: an alcohol-in-oil-in-water multiple pickering emulsion prepared by an anti-solvent recrystallization method comprises,
oil-water-insoluble active, polyol, oil phase, hydrophilic fumed silica, hydrophobic fumed silica and deionized water; wherein, the liquid crystal display device comprises a liquid crystal display device,
according to mass percentage, the polyol is 5-25%, the oil phase is 10-40%, the hydrophilic silicon dioxide is 0.1-10%, the hydrophobic silicon dioxide is 0.1-10%, the deionized water is 40-60%, and the oil-water-insoluble active substance is 1-10% of the polyol.
As a preferable scheme of the alcohol-in-oil-in-water multiple pickering emulsion prepared by the anti-solvent recrystallization method, the invention comprises the following steps: the hydrophilic silicon dioxide is one or more of gas-phase hydrophilic silicon dioxide and hexadecyl silane partially modified hydrophilic silicon dioxide.
As a preferable scheme of the alcohol-in-oil-in-water multiple pickering emulsion prepared by the anti-solvent recrystallization method, the invention comprises the following steps: the hydrophobic silicon dioxide is one or more of hexamethyldisilazane modified hydrophobic silicon dioxide, dimethyl dichlorosilane modified hydrophobic silicon dioxide and dimethyl polysiloxane modified hydrophobic silicon dioxide.
As a preferable scheme of the alcohol-in-oil-in-water multiple pickering emulsion prepared by the anti-solvent recrystallization method, the invention comprises the following steps: the oil-water-insoluble active substance is one or more of quercetin, curcumin, naringenin, rutin, and glycyrrhetinic acid.
As a preferable scheme of the alcohol-in-oil-in-water multiple pickering emulsion prepared by the anti-solvent recrystallization method, the invention comprises the following steps: the polyalcohol is one or more of glycerol, 1, 2-propylene glycol, 1, 3-butanediol and dipropylene glycol.
As a preferable scheme of the alcohol-in-oil-in-water multiple pickering emulsion prepared by the anti-solvent recrystallization method, the invention comprises the following steps: the oil phase is one or more of soybean oil, olive oil, corn oil, coconut oil, sunflower seed oil, macadamia nut oil, evening primrose oil, jojoba oil, grape seed oil, peanut oil, rapeseed oil, castor oil, linseed oil, peppermint oil, rose oil, sweet orange oil, cinnamon oil, camellia oil, shea butter, sesame oil, silicone oil, polysiloxane, liquid paraffin, n-hexane, n-hexadecane, squalane, isopropyl myristate, ethylhexyl palmitate, isopropyl palmitate, caprylic/capric triglyceride, polymethacrylic glyceride, cetyl alcohol, cetostearyl alcohol and stearyl alcohol.
It is still another object of the present invention to overcome the deficiencies of the prior art and to provide a method for preparing an alcohol-in-oil-in-water multiple pickering emulsion.
In order to solve the technical problems, the invention provides the following technical scheme: a preparation method of an alcohol-in-oil-in-water multiple pickering emulsion, which comprises the following steps,
stirring and dissolving the oil-water-insoluble active substance into the polyol to prepare an inner alcohol phase;
uniformly dispersing hydrophobic silicon dioxide into oil to obtain an oil phase;
adding the internal alcohol phase into the oil phase for high-speed dispersion to obtain alcohol-in-oil primary emulsion;
uniformly dispersing hydrophilic silicon dioxide into deionized water to obtain a water phase, adding the alcohol-in-oil primary emulsion into the water phase for high-speed dispersion to obtain the alcohol-in-water-in-oil multiple pickering emulsion.
As a preferable scheme of the preparation method of the alcohol-in-water-in-oil multiple pickering emulsion, the invention comprises the following steps: preparing the alcohol-in-oil colostrum, wherein the dispersing speed is 10000-20000 rpm, and the dispersing time is 1-5 min.
As a preferable scheme of the preparation method of the alcohol-in-water-in-oil multiple pickering emulsion, the invention comprises the following steps: preparing the alcohol-in-oil-in-water multiple Pickering emulsion, wherein the dispersing speed is 3000-10000 rpm, and the dispersing time is 1-5 min.
As a preferable scheme of the preparation method of the alcohol-in-water-in-oil multiple pickering emulsion, the invention comprises the following steps: according to mass percentage, the polyol is 5-25%, the oil phase is 10-40%, the hydrophilic silicon dioxide is 0.1-10%, the hydrophobic silicon dioxide is 0.1-10%, the deionized water is 40-60%, and the oil-water-insoluble active substance is 1-10% of the polyol.
The invention has the beneficial effects that:
(1) The oil-in-water alcohol-in-oil multiple pickering emulsion prepared by the invention loads the oil-water dilemma to the inner alcohol phase, provides a dissolution environment for the oil-water dilemma, improves the solubility of the oil-water dilemma, and promotes the bioavailability of the oil-water dilemma.
(2) In the preparation process of the oil-in-water poorly water-soluble active substance-in-oil-in-alcohol multiple pickering emulsion, a small amount of oil-water poorly water-soluble active substance is recrystallized and separated out in the second-step emulsification process, and the oil-water-insoluble active substance-in-oil-in-water multiple pickering emulsion and hydrophilic silicon dioxide are co-stabilized at a water-oil interface to obtain the high-stability oil-in-water-in-alcohol multiple pickering emulsion.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the description of the embodiments will be briefly described below, it being obvious that the drawings in the following description are only some embodiments of the present invention, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art. Wherein:
FIG. 1 is a schematic illustration of the preparation of an alcohol-in-oil-in-water multiple pickering emulsion prepared by an anti-solvent recrystallization method and a stabilization mechanism;
FIG. 2 is a microscopic image and particle size of the alcohol-in-oil-in-water multiple Pickering emulsions of examples 1-5;
FIG. 3 is an appearance of the alcohol-in-water multiple Pickering emulsions of examples 1-5 and the milk-out index;
FIG. 4 is a fluorescence microscopy image of the alcohol-in-water multiple Pickering emulsions of examples 1-5;
fig. 5 is a microscopic view and an external view of the oil-in-water emulsion described in examples 6 and 7.
Detailed Description
In order that the above-recited objects, features and advantages of the present invention will become more apparent, a more particular description of the invention will be rendered by reference to specific embodiments thereof which are illustrated in the appended drawings.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways other than those described herein, and persons skilled in the art will readily appreciate that the present invention is not limited to the specific embodiments disclosed below.
Further, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic can be included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Example 1
Fumed hydrophilic silica: 0.2g
Dimethylpolysiloxane modified hydrophobic silica: 0.3g
Dipropylene glycol: 0.6g
Glycerol: 0.4g
Evening primrose oil: 3.7g
Deionized water: 4.8g
Uniformly stirring dipropylene glycol and glycerin by magnetic force to prepare an inner alcohol phase;
adding dimethyl polysiloxane modified hydrophobic silica into evening primrose oil, dispersing at 12000rpm for 1min to obtain an oil phase, adding an internal alcohol phase into the oil phase, and dispersing at 12000rpm for 2min to obtain alcohol-in-oil primary emulsion;
adding the gas phase hydrophilic silicon dioxide into deionized water, dispersing at 12000rpm for 1min to obtain a water phase, adding the alcohol-in-oil primary emulsion into the water phase, and dispersing at 9000rpm for 2min to obtain the alcohol-in-oil-in-water multiple emulsion.
The blank alcohol-in-oil-in-water multiple pickering emulsion obtained above was photographed under a super depth of field microscope while its particle size was calculated using Nano Measurer 1.2 software measurement and the emulsion was stored at room temperature for 30 days to further observe its stability.
In fig. 2, a microscopic image and particle size of a blank alcohol-in-oil-in-water multiple pickering emulsion (0%) is shown, from which it can be observed that many small droplets are present in large droplets, with a distinct multiple structure, with a volume average particle size of 97.1 μm.
In fig. 3, the appearance and the emulsion index of a blank alcohol-in-water-in-oil multiple pickering emulsion (0%) are shown, the lower layer of the emulsion has water phase separated out after the emulsion is stored for 30 days at room temperature, the form of multiple emulsion can be still observed through a microscope, and the emulsion has good stability.
Example 2
Quercetin: 15mg of
Fumed hydrophilic silica: 0.2g
Dimethylpolysiloxane modified hydrophobic silica: 0.3g
Dipropylene glycol: 0.6g
Glycerol: 0.4g
Evening primrose oil: 3.7g
Deionized water: 4.8g
Adding the quercetin Pi Sutian into dipropylene glycol and glycerol, magnetically stirring until the mixture is clear and transparent, and preparing an internal alcohol phase;
adding dimethyl polysiloxane modified hydrophobic silica into evening primrose oil, dispersing at 12000rpm for 1min to obtain an oil phase, adding an internal alcohol phase into the oil phase, and dispersing at 12000rpm for 2min to obtain alcohol-in-oil primary emulsion;
adding gas phase hydrophilic silicon dioxide into deionized water, dispersing at 12000rpm for 1min to obtain water phase, adding alcohol-in-oil primary emulsion into water phase, and dispersing at 9000rpm for 2min to obtain multiple emulsion of alcohol-in-oil-in-water.
The resulting oil-in-oil alcohol-in-oil multiple pickering emulsion of the above-described encapsulated quercetin Pi Sushui was photographed by a super depth of field microscope while its particle size was calculated using Nano Measurer 1.2 software measurement, and the emulsion was stored at room temperature for 30 days to further observe its stability.
Microscopic images and particle sizes of the oil-in-oil alcohol-in-oil multiple pickering emulsion (0.15%) of the entrapped quercetin Pi Sushui are shown in fig. 2, and the emulsion still has obvious multiple structures as can be observed from a microscope, which proves that the addition of quercetin has no effect on the multiple structures. The volume average particle size was 92.0 μm, which was reduced compared to the blank alcohol-in-oil-in-water multiple pickering emulsion.
In fig. 3, there is shown the appearance and the emulsion analysis index of the alcohol-in-oil multiple pickering emulsion (0.15%) of the entrapped quercetin Pi Sushui, wherein after 30 days of storage at room temperature, a small amount of water phase is separated out from the lower layer of the emulsion, but the emulsion analysis index is reduced, the emulsion analysis phenomenon is weakened, and the storage stability at room temperature is better than that of the blank alcohol-in-oil multiple pickering emulsion.
Example 3
Quercetin: 30mg
Fumed hydrophilic silica: 0.2g
Dimethylpolysiloxane modified hydrophobic silica: 0.3g
Dipropylene glycol: 0.6g
Glycerol: 0.4g
Evening primrose oil: 3.7g
Deionized water: 4.8g
Adding the quercetin Pi Sutian into dipropylene glycol and glycerol, magnetically stirring until the mixture is clear and transparent, and preparing an internal alcohol phase;
adding dimethyl polysiloxane modified hydrophobic silica into evening primrose oil, dispersing at 12000rpm for 1min to obtain an oil phase, adding an internal alcohol phase into the oil phase, and dispersing at 12000rpm for 2min to obtain alcohol-in-oil primary emulsion;
adding gas phase hydrophilic silicon dioxide into deionized water, dispersing at 12000rpm for 1min to obtain water phase, adding alcohol-in-oil primary emulsion into water phase, and dispersing at 9000rpm for 2min to obtain multiple emulsion of alcohol-in-oil-in-water.
The resulting oil-in-oil alcohol-in-oil multiple pickering emulsion of the above-described encapsulated quercetin Pi Sushui was photographed by a super depth of field microscope while its particle size was calculated using Nano Measurer 1.2 software measurement, and the emulsion was stored at room temperature for 30 days to further observe its stability.
Microscopic images of the oil-in-oil alcohol-in-oil multiple pickering emulsion of entrapped quercetin Pi Sushui (0.30%) and particle size are shown in fig. 2, from which it can be seen that the emulsion still has a distinct multiple structure, further reducing the particle size to 66.4 μm.
In fig. 3, there are shown an appearance diagram and a milk-out index of an alcohol-in-oil multiple pickering emulsion (0.30%) of the entrapped quercetin Pi Sushui, and the emulsion has no milk-out phenomenon after 30 days of storage at room temperature, no obvious change in appearance, and excellent room temperature storage stability.
Example 4
Quercetin: 45mg of
Fumed hydrophilic silica: 0.2g
Dimethylpolysiloxane modified hydrophobic silica: 0.3g
Dipropylene glycol: 0.6g
Glycerol: 0.4g
Evening primrose oil: 3.7g
Deionized water: 4.8g
Adding the quercetin Pi Sutian into dipropylene glycol and glycerol, magnetically stirring until the mixture is clear and transparent, and preparing an internal alcohol phase;
adding dimethyl polysiloxane modified hydrophobic silica into evening primrose oil, dispersing at 12000rpm for 1min to obtain an oil phase, adding an internal alcohol phase into the oil phase, and dispersing at 12000rpm for 2min to obtain alcohol-in-oil primary emulsion;
adding gas phase hydrophilic silicon dioxide into deionized water, dispersing at 12000rpm for 1min to obtain water phase, adding alcohol-in-oil primary emulsion into water phase, and dispersing at 9000rpm for 2min to obtain multiple emulsion of alcohol-in-oil-in-water.
The resulting oil-in-oil alcohol-in-oil multiple pickering emulsion of the above-described encapsulated quercetin Pi Sushui was photographed by a super depth of field microscope while its particle size was calculated using Nano Measurer 1.2 software measurement, and the emulsion was stored at room temperature for 30 days to further observe its stability.
A microscopic image of the oil-in-oil alcohol-in-oil multiple pickering emulsion of entrapped quercetin Pi Sushui (0.45%) and particle size, which is further reduced to 47.5 μm, is shown in fig. 2, where it can be seen from the microscope that the emulsion still has a distinct multiple structure.
In fig. 3, there are shown an appearance diagram and a milk-out index of an alcohol-in-oil multiple pickering emulsion (0.30%) of the entrapped quercetin Pi Sushui, and the emulsion has no milk-out phenomenon after 30 days of storage at room temperature, no obvious change in appearance, and excellent room temperature storage stability.
Example 5
Quercetin: 60mg of
Fumed hydrophilic silica: 0.2g
Dimethylpolysiloxane modified hydrophobic silica: 0.3g
Dipropylene glycol: 0.6g
Glycerol: 0.4g
Evening primrose oil: 3.7g
Deionized water: 4.8g
Adding the quercetin Pi Sutian into dipropylene glycol and glycerol, magnetically stirring until the mixture is clear and transparent, and preparing an internal alcohol phase;
adding dimethyl polysiloxane modified hydrophobic silica into evening primrose oil, dispersing at 12000rpm for 1min to obtain an oil phase, adding an internal alcohol phase into the oil phase, and dispersing at 12000rpm for 2min to obtain alcohol-in-oil primary emulsion;
adding gas phase hydrophilic silicon dioxide into deionized water, dispersing at 12000rpm for 1min to obtain water phase, adding alcohol-in-oil primary emulsion into water phase, and dispersing at 9000rpm for 2min to obtain multiple emulsion of alcohol-in-oil-in-water.
The resulting oil-in-oil alcohol-in-oil multiple pickering emulsion of the above-described encapsulated quercetin Pi Sushui was photographed by a super depth of field microscope while its particle size was calculated using Nano Measurer 1.2 software measurement, and the emulsion was stored at room temperature for 30 days to further observe its stability. Microscopic images of the oil-in-oil alcohol-in-oil multiple pickering emulsion of entrapped quercetin Pi Sushui (0.60%) and particle size are shown in fig. 2, from which it can be seen that the emulsion still has a distinct multiple structure, further reducing the particle size to 40.3 μm. In fig. 3, there are shown an appearance diagram and a milk-out index of an alcohol-in-oil multiple pickering emulsion (0.60%) of the entrapped quercetin Pi Sushui, and the emulsion has no milk-out phenomenon after 30 days of storage at room temperature, no obvious change in appearance, and excellent room temperature storage stability.
FIG. 4 is a fluorescence microscopy image of multiple Pickering emulsions described in examples 1-5. Quercetin is excited to display green fluorescence under 420-485 nm. From a fluorescence microscopic image, the quercetin is mainly distributed on an internal alcohol phase and a water-oil interface, and the quercetin is leaked because the second-step emulsification inevitably causes partial damage to the alcohol-in-oil colostrum, but the dissolved quercetin can be recrystallized to separate out after being leaked to an external water phase to be used as a pickering particle to stabilize the water-oil interface. And with the addition of the quercetin amount, the quercetin at the interface is increased, so that the multiple emulsion has smaller particle size and better stability.
Example 6
Quercetin: 60mg of
Dipropylene glycol: 0.6g
Glycerol: 0.4g
Evening primrose oil: 4g
Deionized water: 5g
Adding quercetin Pi Sutian into dipropylene glycol, glycerol and deionized water, dispersing at 9000rpm for 2min to obtain quercetin aqueous dispersion; adding evening primrose oil into the aqueous dispersion, and dispersing at 12000rpm for 2min to obtain oil-in-water emulsion stabilized with quercetin only.
The obtained quercetin-stabilized oil-in-water emulsion was photographed by a super depth of field microscope while its particle size was calculated using Nano Measurer 1.2 software measurement. Fig. 5A is a microscopic and external view of a quercetin stabilized oil-in-water emulsion. From a microscope, the successful preparation of the oil-in-water emulsion by using only quercetin as an emulsifier can be seen, and further, the fact that the quercetin can be used as pickering particles for stabilizing the water-oil interface is further proved. The volume average particle diameter of the prepared oil-in-water emulsion was 251.1. Mu.m.
Example 7
Quercetin: 60mg of
Dipropylene glycol: 0.6g
Glycerol: 0.4g
Evening primrose oil: 4g
Deionized water: 5g
Adding the quercetin Pi Sutian into dipropylene glycol and glycerol, magnetically stirring until the mixture is clear and transparent, and preparing an alcohol phase; adding deionized water into the alcohol phase, dispersing at 9000rpm for 2min to obtain anti-solvent recrystallized quercetin aqueous dispersion;
adding evening primrose oil into the aqueous dispersion, and dispersing at 12000rpm for 2min to obtain oil-in-water emulsion stabilized with recrystallized quercetin.
The oil-in-water emulsion stabilized by the recrystallized quercetin obtained above was photographed by a super depth of field microscope, and the particle size was calculated by measuring using Nano Measurer 1.2 software.
Fig. 5B is a microscopic and external view of a recrystallized quercetin stabilized oil-in-water emulsion. It can be seen from the microscope that the oil-in-water emulsion stabilized with the anti-solvent recrystallized quercetin had a uniform particle size, which was significantly reduced compared to the untreated oil-in-water emulsion stabilized with quercetin in example 6, and had a volume average particle size of 85.8 μm. And compared with the untreated quercetin-stabilized oil-in-water emulsion, the water phase chromatographed under the anti-solvent recrystallized quercetin-stabilized oil-in-water emulsion is clearer, which proves that the quercetin can be better adsorbed on the water-oil interface through the anti-solvent recrystallization process.
In conclusion, the invention successfully prepares the high-load high-stability alcohol-in-oil-in-water multiple pickering emulsion. FIGS. 2 and 3 are microscopic and external views of multiple emulsions of examples 1-5, showing that the multiple emulsions prepared have a reduced particle size and better room temperature storage stability as the oil-water-insoluble active increases in the system. FIG. 4 is a fluorescence microscopy image of multiple emulsions of examples 1-5, showing that a portion of the oil-water-insoluble active material can adhere to the water-oil interface after recrystallization precipitation, resulting in improved multiple emulsion stability. Fig. 5 is a microscopic view and an external view of examples 6 and 7, further demonstrating that the oil-water-insoluble active can be used as pickering particles to stabilize the water-oil interface, and the oil-water-insoluble active can more effectively stabilize the water-oil interface after the process of anti-solvent recrystallization.
According to the invention, the oil-water-in-oil-alcohol multiple Pickering emulsion is used for coating the oil-water-insoluble active substance for the first time, so that a dissolving environment is provided for the oil-water-insoluble active substance, and the solubility of the oil-water-insoluble active substance in a system is effectively improved. Meanwhile, in the second-step emulsification process, a small amount of active substances are recrystallized and separated out to serve as a water-oil interface of the Pickering particle stability, so that the oil-in-water-in-oil-alcohol multiple Pickering emulsion with excellent stability is obtained. The invention provides reference significance for improving the availability of oil-water-insoluble active substances and preparing high-stability multiple emulsion.
Multiple emulsion is a multi-layer emulsion formed by dispersing one emulsion in another continuous phase, has the advantages of the traditional oil-in-water emulsion and the traditional water-in-oil emulsion, can realize simultaneous entrapment of water-soluble active substances and oil-soluble active substances, has multiple protection and slow release effects on the active substances entrapped in an internal phase, and is widely focused in the field of active substance entrapment. However, multiple emulsions are thermodynamically unstable due to excessive free energy at the surface, limiting their use in practical production and life.
Pickering emulsions are emulsions stabilized by solid particles, which are more stable than traditional surfactant-stabilized emulsions due to the irreversible adsorption of solid particles at the two-phase interface. The multiple emulsion and the pickering emulsion are combined, namely the multiple pickering emulsion can effectively solve the problem of poor stability of the multiple emulsion. Because conventional multiple emulsions are water-in-oil-in-water and oil-in-oil, the actives are supported in either the inner aqueous phase (inner oil phase) or the intermediate oil phase (intermediate water phase), and the oil-water-immiscible actives cannot be supported. Thus, the internal aqueous phase of a conventional water-in-oil-in-water multiple emulsion is replaced with a polyol, and the multiple pickering emulsion is designed as an alcohol-in-water-in-oil multiple pickering emulsion. Wherein, the oil-water-insoluble component is dissolved in the polyol phase, so that the loading problem of the oil-water-insoluble active component is effectively solved, and the solubility and bioavailability of the oil-water-insoluble component are improved.
The invention carries the oil-water-insoluble active matters into the alcohol phase of the alcohol-in-water-in-oil-in-alcohol multiple emulsion so as to improve the solubility and the carrying capacity of the oil-water-insoluble active matters; the stability of the alcohol-in-water-in-oil emulsion can be enhanced by the spontaneous anti-solvent recrystallization process of the active substance in the emulsion preparation process; the surfactant-free and high-stability alcohol-in-water-in-oil multiple pickering emulsion is prepared by using the pure particles.
In conclusion, the alcohol-in-oil-in-water multiple pickering emulsion prepared by the invention provides a dissolution environment for the oil-water-insoluble active substances, and can obviously improve the loading capacity of the oil-water-insoluble active substances in the emulsion; on the other hand, the anti-solvent recrystallization phenomenon in the preparation process can endow the system with super-strong stability.
It should be noted that the above embodiments are only for illustrating the technical solution of the present invention and not for limiting the same, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the present invention may be modified or substituted without departing from the spirit and scope of the technical solution of the present invention, which is intended to be covered in the scope of the claims of the present invention.
Claims (8)
1. A method for preparing an alcohol-in-oil-in-water multiple pickering emulsion based on an anti-solvent recrystallization method is characterized in that: comprising the steps of (a) a step of,
stirring and dissolving the oil-water-insoluble active substance into the polyol to prepare an inner alcohol phase;
uniformly dispersing hydrophobic fumed silica into oil to obtain an oil phase;
adding the internal alcohol phase into the oil phase for high-speed dispersion to obtain alcohol-in-oil primary emulsion;
uniformly dispersing hydrophilic fumed silica into deionized water to obtain a water phase, adding alcohol-in-oil primary emulsion into the water phase for high-speed dispersion to obtain an alcohol-in-oil-in-water multiple pickering emulsion;
wherein, the mass percentage of the raw materials is 5-25%, the oil phase is 10-40%, the hydrophilic fumed silica is 0.1-10%, the hydrophobic fumed silica is 0.1-10%, and the deionized water is 40-60%;
the proportion of the oil-water-soluble active substance is 1-10% of that of the polyalcohol.
2. The method of claim 1, wherein: the hydrophilic silicon dioxide is one or more of gas-phase hydrophilic silicon dioxide and hexadecyl silane modified hydrophilic silicon dioxide.
3. The method of claim 1, wherein: the hydrophobic silicon dioxide is one or more of hexamethyldisilazane modified hydrophobic silicon dioxide, dimethyl dichlorosilane modified hydrophobic silicon dioxide and dimethyl polysiloxane modified hydrophobic silicon dioxide.
4. A method according to claim 1 or 2, characterized in that: the oil-water-insoluble active substance is one or more of quercetin, curcumin, naringenin, rutin, and glycyrrhetinic acid.
5. A method according to claim 1 or 2, characterized in that: the polyalcohol is one or more of glycerol, 1, 2-propylene glycol, 1, 3-butanediol and dipropylene glycol.
6. A method according to claim 1 or 2, characterized in that: the oil phase is one or more of soybean oil, olive oil, corn oil, coconut oil, sunflower seed oil, macadamia nut oil, evening primrose oil, jojoba oil, grape seed oil, peanut oil, rapeseed oil, castor oil, linseed oil, peppermint oil, rose oil, sweet orange oil, cinnamon oil, camellia oil, shea butter, sesame oil, silicone oil, polysiloxane, liquid paraffin, n-hexane, n-hexadecane, squalane, isopropyl myristate, ethylhexyl palmitate, isopropyl palmitate, caprylic/capric triglyceride, polymethacrylic glyceride, cetyl alcohol, cetostearyl alcohol and stearyl alcohol.
7. The method of claim 1, wherein: preparing the alcohol-in-oil colostrum, wherein the dispersing speed is 10000-20000 rpm, and the dispersing time is 1-5 min.
8. The method of claim 1, wherein: preparing the alcohol-in-oil-in-water multiple Pickering emulsion, wherein the dispersing speed is 3000-10000 rpm, and the dispersing time is 1-5 min.
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