A stable emulsion of a triterpenoid compound in a water-in-oil self-emulsifying type and a preparation method thereof

Abstract

The present invention provides a stable emulsion of a triterpenoid compound in a water-in-oil self-emulsifying type and a preparation method thereof. The emulsion uses the triterpenoid compound as an emulsifier. The preparation method includes the following steps: dispersing triterpenoid compound particles in a liquid edible vegetable oil under continuous stirring at a specific temperature to obtain a triterpenoid compound dispersion system; mixing the triterpenoid compound dispersion system obtained in step 1 with an aqueous phase in a certain proportion, and obtaining a stable W / O emulsion after treatment under specific homogenization conditions, and immediately storing it in a sealed manner. The present invention uses the triterpenoid compound as an emulsifier or a gelling agent to stabilize the emulsion or the high internal phase emulsion gel, and the obtained stable emulsion improves the bioavailability of the triterpenoid compound.

Description

Technical Field

[0001] The present invention belongs to the technical field of oil processing, and particularly relates to a stable emulsion of triterpenoid compound self-emulsifying water-in-oil type and a preparation method thereof. Background Art

[0002] Triterpenoid compounds are a series of structurally diverse natural compounds formed by the condensation of triterpenoid sapogenins and one or more sugar groups and / or other chemical groups. They are plant-derived secondary metabolites, which are most widely distributed in the plant kingdom and are mainly distributed in the roots, stems, barks, leaves, seeds and fruits of plants in the Araliaceae, Leguminosae, Hippocastanaceae, Papilionaceae, Campanulaceae, Polygalaceae, Hippocastanaceae, Primulaceae, Sapindaceae, Theaceae, etc. There are also a small amount derived from marine organisms and some animals. Tetracyclic triterpenoids and pentacyclic triterpenoids are the two most common types of triterpenoid compounds. Pentacyclic triterpenoid compounds are a class of triterpenoid compounds composed of 6 isoprene structural units linked together. According to the different structural types, pentacyclic triterpenoid compounds are mainly divided into four major types, namely oleanane type, ursane type, lupane type and friedelane type. The typical representative of the oleanane type is oleanolic acid; the most common representative of the ursane type is ursolic acid; the representative of the lupane type is betulin. At present, it has been found that pentacyclic triterpenoid compounds, as secondary metabolites of plants, have a wide range of biological activities and pharmacological activities, and have important effects such as anti-cancer, anti-inflammatory, anti-allergic, antibacterial, treatment of leukemia, anti-viral, hypoglycemic, prevention and treatment of cardiovascular and cerebrovascular diseases. Recent studies have also shown that triterpenoid compounds also have significant effects in inhibiting digestive enzyme activity, regulating appetite, regulating lipid metabolism, increasing energy consumption, regulating intestinal microflora, etc.

[0003] Triterpenoid compounds can be applied to industries such as cosmetics and medicine. However, the vast majority of triterpenoid compounds have extremely low solubility in water, and the bioavailability of oral preparations is poor. Currently, invention patents such as ursolic acid freeze-dried powder preparations, ursolic acid sustained-release tablets, ursolic acid solid dispersible tablets, ursolic acid lipid microspheres, oleanolic acid solid dispersible tablets, and hair conditioners containing betulin have been reported. However, these dosage forms are difficult to process, have high costs, are not suitable for large-scale production and application, and there is no report on stable water-in-oil emulsions or high internal phase emulsion gels of triterpenoid compounds including ursolic acid.

[0004] Traditional plastic fats endow plastic fat products with good appearance and functional properties during the hydrogenation process by using a saturated fat crystal network. Although some functional improvements can be made to this traditional liquid oil structuring process, systems based on the three-dimensional network structure formed by saturated fat or trans-fat crystallization are not beneficial to health because consuming a large amount of trans fatty acids and saturated fatty acid groups is highly likely to induce nutritional safety problems such as hyperlipidemia and heart disease.

[0005] Therefore, how to improve the bioavailability of triterpenoids including ursolic acid, and at the same time obtain a new type of oil that can replace traditional plastic fats, is a problem that needs to be solved. Summary of the Invention

[0006] Aiming at the problems existing in the prior art, the purpose of the present invention is to provide a stable water-in-oil self-emulsifying emulsion of triterpenoids and its preparation method. Firstly, triterpenoids are used as emulsifiers or gelling agents to stabilize emulsions or high internal phase emulsion gels, and the obtained stable emulsion improves the bioavailability of triterpenoids themselves, thereby effectively enhancing the pharmacological functions of such compounds.

[0007] The purpose of the present invention is achieved through the following technical solutions:

[0008] A preparation method of a stable water-in-oil self-emulsifying emulsion of triterpenoids, wherein the emulsion uses triterpenoids as emulsifiers, and the preparation method includes the following steps:

[0009] Step 1, dispersing triterpenoid particles in oil and continuously stirring to obtain a triterpenoid dispersion system;

[0010] Step 2, adding the triterpenoid dispersion system obtained in Step 1 to the water phase after stirring evenly, and obtaining a W / O emulsion after homogenization treatment;

[0011] Step 3, immediately sealing and storing the W / O emulsion prepared in Step 2, which is the stable water-in-oil self-emulsifying emulsion of triterpenoids.

[0012] Further, the triterpenoids include pentacyclic triterpenoids such as ursolic acid, betulinol, and oleanolic acid.

[0013] Further, the oil includes rapeseed oil, tea oil, soybean oil, olive oil, corn oil, sunflower oil, and perilla oil.

[0014] Further, the mass concentration of the triterpenoid particles in Step 1 is 1% - 20%.

[0015] Further, the stirring in Step 1 is carried out under constant temperature heating conditions, and the temperature is 60°C - 120°C.

[0016] Furthermore, the mass concentration of the triterpenoid compound dispersion system in the aqueous phase in step 2 is 10% - 90%.

[0017] Furthermore, the homogenization treatment in step 2 includes high-speed homogenization, high-pressure homogenization, ultrasonic homogenization, and microfluidic homogenization.

[0018] Furthermore, the W / O emulsion in step 3 is sealed and stored at room temperature.

[0019] On the other hand, the present invention:

[0020] A stable self-emulsifying water-in-oil emulsion of triterpenoid compounds, which is prepared by the above preparation method.

[0021] The beneficial effects of the present invention compared with the prior art are as follows:

[0022] 1. Natural triterpenoid compounds are substances formed by connecting several isoprenes end to end after removing hydroxyl groups. Triterpenoid compounds are relatively common in nature and can be isolated from animals and plants. Some are in the free state, called triterpenoid sapogenins, and the other part is combined with sugar to form glycosides, called triterpenoid saponins. Common sapogenins are mostly tetracyclic triterpenes and pentacyclic triterpenes, composed of 6 isoprene units and containing 30 carbon atoms. Triterpenoid components are widely distributed in nature. At present, triterpenoid saponins have become one of the most active and fastest-developing fields in natural product research, with a variety of important biological activities and extensive pharmacological effects, such as anti-cancer, anti-inflammatory, anti-allergic, treating leukemia, anti-viral, hypoglycemic, preventing and treating cardiovascular and cerebrovascular diseases, etc.; in the present invention, natural triterpenoid compounds are used as emulsifiers in the preparation of water-in-oil stable emulsions, which improves the bioavailability of triterpenoid compounds themselves;

[0023] 2. Ursolic acid, a representative of three types of pentacyclic triterpenoid compounds, not only has a wide range of pharmacological effects such as anti-hepatitis, anti-tumor, anti-inflammatory, anti-viral, lipid-lowering, anti-atherosclerotic and immune-enhancing effects, but also has low toxicity and few adverse reactions. In the stable self-emulsifying water-in-oil emulsion of ursolic acid described in the present invention, ursolic acid (UA, Uosolic Acid) is used as an emulsifier or gelling agent. Using the hydrophobicity of UA particles, various oils can be wetted, and after adding UA, the interfacial tension between oil and water only decreases slightly. There is a Pickering stabilization mechanism in the system, and the obtained emulsion has good storage stability and rheological properties, is easy to store, and there are no phenomena such as aggregation and precipitation during storage at room temperature;

[0024] 3. Compared with O / W emulsions, W / O emulsions are more difficult to form. This is mainly because the high fluidity of water droplets leads to poor emulsion stability, and the low conductivity of the oil phase results in the absence of an electrostatic repulsion mechanism in the emulsion. Therefore, there are few emulsifiers currently used to stabilize W / O emulsions, especially stabilizers of natural origin;

[0025] 4. The triterpenoid compound self-emulsifying water-in-oil stable emulsion described in the present invention has higher nutritional value than traditional plastic fat products and can replace the water-in-oil emulsions prepared by traditional hydrogenation methods; meanwhile, the emulsion also serves as a carrier for triterpenoid compounds, significantly improving the solubility of triterpenoid compounds, which can enhance the bioavailability of triterpenoid compounds, facilitate delaying oxidation and increasing stability;

[0026] 5. The preparation method of the triterpenoid compound self-emulsifying water-in-oil stable emulsion described in the present invention is simple, efficient, green and environmentally friendly, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The present invention will be further described below with reference to the drawings and embodiments:

[0028] Figure 1 It is a graph of the particle size results of the emulsion prepared under the conditions of different mass concentrations of UA particles in Example 1;

[0029] Figure 2 It is a graph of the particle size results of the emulsion prepared under the conditions of different oil-water ratios in Example 1;

[0030] Figure 3 It is a photograph of the state of the emulsion prepared under the conditions of different mass concentrations of UA particles in Example 1;

[0031] Figure 4 It is a photograph of the state of the emulsion prepared under the conditions of different oil-water ratios in Example 1;

[0032] Figure 5 It is a rheological result graph of the emulsion prepared under the conditions of different mass concentrations of UA particles and different oil-water ratios in Example 1;

[0033] Figure 6 It is a photograph of the appearance state of the emulsion gel prepared under the conditions of different mass concentrations of oleanolic acid particles in Example 4;

[0034] Figure 7 It is an optical microscope image of the emulsion gel prepared under the conditions of different mass concentrations of oleanolic acid particles in Example 4;

[0035] Figure 8 It is a rheological result graph of the emulsion gel prepared under the conditions of different mass concentrations of oleanolic acid particles in Example 4. Detailed implementation mode

[0036] The following is a further description of the present invention in combination with embodiments. However, these embodiments are only used to explain the present invention and do not constitute any limitation to the protection scope of the present invention.

[0037] Embodiment 1

[0038] This embodiment provides a preparation method of a self-emulsifying water-in-oil stable emulsion of ursolic acid. The emulsion uses ursolic acid as an emulsifier, and the preparation method includes the following steps:

[0039] Step 1: Disperse ursolic acid particles in rapeseed oil, and continuously stir for 20 min under the condition of a constant temperature water bath at 80 °C to obtain an ursolic acid dispersion system;

[0040] To explore the effects of UA concentration on the particle size, storage stability, rheological properties, etc. of the formed emulsion, the mass concentrations of UA particles are respectively 1%, 3%, and 5%;

[0041] Step 2: After stirring evenly the ursolic acid dispersion system obtained in Step 1, add it to the water phase, and after homogenization treatment in a digital display high-speed disperser, obtain a W / O emulsion;

[0042] The homogenization treatment conditions are 13600 rpm for 2 min;

[0043] To explore the effects of the oil-water ratio on the particle size, storage stability, rheological properties, etc. of the formed emulsion, the mass concentrations of the ursolic acid dispersion system in water are respectively 60%, 70%, 80%, and 90%;

[0044] Step 3: After the W / O emulsion described in Step 2 is prepared, immediately seal it and store it in a 20 ml serum bottle at room temperature, which is the self-emulsifying water-in-oil stable emulsion of ursolic acid.

[0045] As Figure 1 、 Figure 2 shown, the particle sizes of the emulsions prepared under different mass concentrations of UA particles and different oil-water ratios are respectively shown. The results show that the UA concentration and different oil-water ratios have little effect on the emulsion particle size, but by increasing the UA concentration or increasing the proportion of the water phase, the uniformity of the emulsion droplets is improved. And the particle size of the freshly prepared emulsion is maintained at 6-7 μm. After one week of storage, the droplets may coalesce to form larger droplets, and the interfacial area also increases.

[0046] As Figure 3 、 Figure 4As shown, the state photos of the emulsions prepared under different mass concentrations of UA particles and different oil-water ratios are shown respectively, reflecting the storage stability of the solutions under different conditions. The appearance diagram shows that except for the emulsions formed under extreme oil-water ratios (9:1) and extreme UA concentration values (1%), the stabilities of the other emulsions are good, and there is no obvious oil-water stratification phenomenon.

[0047] As Figure 5 shown, the rheological properties of the emulsions prepared under different mass concentrations of UA particles and different oil-water ratios are shown respectively. The emulsion as a whole presents a fluid form (G”>G’), has a large dependence on frequency, and belongs to a shear-thinning pseudoplastic fluid. Increasing the UA concentration or increasing the proportion of the aqueous phase can improve the elastic properties (G’) and shear viscosity of the emulsion.

[0048] Example 2

[0049] This example provides a preparation method of a self-emulsifying water-in-oil stable emulsion gel of ursolic acid. The emulsion gel uses ursolic acid as an emulsifier, and the preparation method includes the following steps:

[0050] Step 1: Disperse ursolic acid particles in soybean oil, and continuously stir for 5 min under the condition of a constant temperature oil bath at 120 °C to obtain an ursolic acid dispersion system;

[0051] To explore the effects of UA concentration on the particle size, storage stability, rheological properties, etc. of the formed emulsion gel, the mass concentrations of UA particles are 4%, 7%, and 10% respectively;

[0052] Step 2: After stirring evenly the ursolic acid dispersion system obtained in Step 1, add it to the aqueous phase, and after ultrasonic homogenization treatment, obtain a W / O emulsion gel;

[0053] The conditions for ultrasonic homogenization treatment are a power of 300 W, ultrasonic on for 3 s, off for 5 s, and a total time of 5 min;

[0054] To explore the effects of the oil-water ratio on the particle size, storage stability, rheological properties, etc. of the formed emulsion gel, the mass concentrations of the ursolic acid dispersion system in water are 10%, 20%, 30%, and 40% respectively;

[0055] Step 3: After the W / O emulsion gel described in Step 2 is prepared, immediately seal and store it in a 20 ml centrifuge tube and store it at room temperature to obtain the self-emulsifying water-in-oil stable emulsion gel of ursolic acid.

[0056] Example 3

[0057] This example provides a preparation method of a self-emulsifying water-in-oil stable emulsion of betulinol. The emulsion uses betulinol as an emulsifier, and the preparation method includes the following steps:

[0058] Step 1: Disperse betulinol particles in olive oil and continuously stir for 20 min under the condition of a constant temperature water bath at 80 °C to obtain a betulinol dispersion system;

[0059] Among them, the mass concentration of betulinol particles in olive oil is 3%;

[0060] Step 2: After stirring the betulinol dispersion system obtained in Step 1 evenly, add it to the water phase and homogenize it in a digital display high-speed disperser to obtain a W / O emulsion;

[0061] The homogenization conditions are 13,600 rpm and 2 min;

[0062] Among them, the mass concentration of the betulinol dispersion system in water is 70%;

[0063] Step 3: After the W / O emulsion described in Step 2 is prepared, immediately seal and store it in a 20 ml serum bottle and store it at room temperature to obtain the betulinol self-emulsifying water-in-oil stable emulsion.

[0064] Example 4

[0065] This example provides a preparation method of an oleanolic acid self-emulsifying water-in-oil high internal phase emulsion gel. The emulsion gel uses oleanolic acid as an emulsifier, and the preparation method includes the following steps:

[0066] Step 1: Disperse oleanolic acid particles in rapeseed oil and continuously stir for 20 min under the condition of a constant temperature water bath at 80 °C to obtain an ursolic acid dispersion system;

[0067] To explore the effects of oleanolic acid concentration on the particle size, storage stability, rheological properties, etc. of the formed emulsion gel, the mass concentrations of oleanolic acid particles are prepared to be 1%, 3%, and 5% respectively;

[0068] Step 2: After stirring the oleanolic acid dispersion system obtained in Step 1 evenly, add it to the water phase and homogenize it in a digital display high-speed disperser to obtain a W / O emulsion;

[0069] The homogenization conditions are 13,600 rpm and 15 min;

[0070] Step 3: After the W / O emulsion described in Step 2 is prepared, immediately seal and store it in a 20 ml serum bottle and store it at room temperature to obtain the oleanolic acid self-emulsifying water-in-oil high internal phase emulsion gel.

[0071] As Figure 6, showing the state photos of the emulsion gels prepared under the conditions of different mass concentrations of oleanolic acid particles. From the appearance and texture of the emulsion gels, after increasing the oleanolic acid concentration, the texture of the samples becomes more viscous and more similar to the form of solid cream. It shows that to obtain a better emulsion gel product, it is necessary to increase the amount of emulsifier to achieve it.

[0072] Such as Figure 7 , showing the electron microscopy result diagrams of the emulsion gels prepared under the conditions of different mass concentrations of oleanolic acid particles, reflecting the particle size and storage stability of the emulsion gels.

[0073] Such as Figure 8 , showing the rheological properties of the emulsion gels prepared under the conditions of different mass concentrations of oleanolic acid particles.

[0074] Finally, it should be noted that the above is only used to illustrate the technical solution of the present invention and not to limit it. Although the present invention has been described in detail with reference to the preferred arrangement, those of ordinary skill in the art should understand that the technical solution of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solution of the present invention.

Claims

1. A method for preparing a self-emulsifying water-in-oil stable emulsion of triterpenoid compounds, characterized in that, The emulsion uses triterpenoids as emulsifiers, and the preparation method includes the following steps: Step 1: Disperse triterpenoid particles in oil and continuously stir to obtain a triterpenoid dispersion system; Step 2: After stirring the triterpenoid dispersion system obtained in Step 1 evenly, add it to the aqueous phase, and obtain a W / O emulsion after homogenization treatment; Step 3: After the W / O emulsion described in Step 2 is prepared, store it, which is the self-emulsifying water-in-oil stable emulsion of triterpenoids; The triterpenoids are ursolic acid or oleanolic acid.

2. The preparation method according to claim 1, characterized in that, The oil is a liquid vegetable oil including rapeseed oil, tea oil, soybean oil, olive oil, corn oil, sunflower seed oil, and perilla oil.

3. The preparation method according to claim 1, wherein The mass concentration of the triterpenoid particles in Step 1 is 1% - 20%.

4. The preparation method according to claim 1 or 2, characterized in that, The stirring in Step 1 is carried out under constant temperature heating conditions, and the temperature is 60°C - 120°C.

5. The preparation method according to claim 1, wherein The mass concentration of the triterpenoid dispersion system in the aqueous phase in Step 2 is 10% - 90%.

6. The preparation method according to claim 1 or 3, characterized in that, The homogenization treatment in Step 2 includes high-speed homogenization, high-pressure homogenization, ultrasonic homogenization, and microfluidic homogenization.

7. A stable water-in-oil self-emulsifying emulsion of a triterpenoid compound, characterized in that, The stable emulsion is prepared by the preparation method according to any one of claims 1 - 6.

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