A compound essential oil nanoemulsion, its preparation method and application

Abstract

The present invention relates to an o / w type high-content composite essential oil nanoemulsion, its preparation method and application. The median particle size of the composite essential oil nanoemulsion is not greater than 45 nm. It comprises plant essential oil, polyethylene glycol glycerol ricinoleate with an HLB value of 10-14, a co-solvent, water, vitamin E acetate and disodium ethylenediaminetetraacetate. The plant essential oil is selected from two or more of carvacrol, cinnamaldehyde, oleoresin capsici and thymol. This composite essential oil nanoemulsion solves the key technical problems of high-content loading and compounding of multiple plant essential oil nanoemulsions, is conducive to exerting the synergistic effect of different essential oils, and reduces the addition amount of essential oils while achieving the same physiological function. In addition, the particle size of this composite essential oil nanoemulsion reaches the nanoscale, can form a homogeneous clear liquid, rapidly diffuses in the water line or water environment, is more conducive to absorption, and at the same time it also has the advantages of good stability and long shelf life, and is more competitive in practical applications.

Description

Technical Field

[0001] The present invention relates to the technical field of nanoemulsion, and particularly relates to an o / w type composite essential oil nanoemulsion, a preparation method thereof and an application thereof. Background Art

[0002] Plant essential oils such as carvacrol, cinnamaldehyde, thymol, etc. have various physiological activities such as antibacterial, antioxidant, immune regulation, etc., and can be used as feed additives in livestock production. However, most of these plant essential oils are in single or composite formulations, and there are the following problems when used: First, most plant essential oils have strong volatility, and during the processes of feed processing, storage and transportation, the essential oil components are easily volatilized and lost, resulting in a decrease in the content of their active ingredients, thereby affecting their expected physiological activities. Second, the active ingredients in plant essential oils are prone to chemical changes under conditions such as light, high temperature, oxidation, etc., resulting in changes in their structures and functions. For example, cinnamaldehyde is easily oxidized under light to generate other inactive or less active substances. Third, most plant essential oils are lipophilic substances and are difficult to be uniformly dispersed in the animal digestive tract, resulting in a limited contact area with the digestive tract mucosa, and further reducing their absorption efficiency. For example, the solubility of carvacrol and thymol in water is low, and they cannot be directly added to the water line, with limited application scenarios, which is not conducive to on-site use or rapid supplementation, and it is difficult for animals to effectively absorb them. Fourth, due to the large differences in density and polarity between plant essential oils and feed matrices, it is difficult to be uniformly distributed in the feed after direct addition. This will result in unstable dosages of essential oils ingested by animals, affecting the exertion of their physiological effects. For example, during the feed processing process, essential oils may aggregate in certain parts of the feed, while there are almost no essential oil components in other parts. Fifth, in order to achieve antibiotic substitution or certain special effects, the addition amount of plant essential oils is often very high, which is not only uneconomical but also has poor palatability.

[0003] Although some researchers have prepared plant essential oils into emulsion preparations, in the existing emulsion preparations, the particle size of plant essential oils is relatively large, usually in the micron level, which results in poor absorption effects in animals. The relatively large particle size will limit the contact area between essential oil molecules and the digestive tract mucosa, thereby reducing their bioavailability. In addition, the emulsion with a large particle size has poor stability and is prone to stratification and precipitation, further affecting its uniform distribution in the feed and long-term storage.

[0004] Therefore, it is of great practical significance to develop a new type of feed additive that can effectively solve problems such as large particle size of plant essential oils, poor absorption, single or high-content loading in compound formulations, etc. Summary of the Invention

[0005] An object of the present invention is to provide a clear composite essential oil nanoemulsion with a small particle size, good stability and a long shelf life.

[0006] The second object of the present invention is to provide a preparation method of the composite essential oil nanoemulsion as described above.

[0007] The third object of the present invention is to provide an application of the composite essential oil nanoemulsion as described above.

[0008] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0009] On the one hand, the present invention provides a composite essential oil nanoemulsion. Based on the total mass of the composite essential oil nanoemulsion being 100%, the composite essential oil nanoemulsion includes:

[0010] Plant essential oil 15% - 30%, and the plant essential oil is selected from two or more of carvacrol, cinnamaldehyde, oleoresin capsici, and thymol;

[0011] Polyethylene glycol glycerol ricinoleate 40% - 60%, and the HLB value of the polyethylene glycol glycerol ricinoleate is 10 - 14;

[0012] Cosolvent 10% - 30%;

[0013] Water 5% - 30%;

[0014] Vitamin E acetate 0.01% - 0.5%;

[0015] Ethylenediaminetetraacetate 0 - 0.1%,

[0016] The median particle size of the composite essential oil nanoemulsion is not greater than 45 nm.

[0017] During the extraction process, plant essential oils are usually dispersed in the extraction solvent in the form of droplets, and the particle size of the essential oil droplets is usually between microns and several hundred microns, with a relatively large particle size. It is difficult to prepare plant essential oil nanoemulsions (usually between 10 nm and 100 nm), especially nanoemulsions with a high content of plant essential oils. The applicant uses polyethylene glycol glycerol ricinoleate with an HLB value of 10 - 14 as an emulsifier, which effectively reduces the oil-water interfacial tension, making it easier for the oil phase and the water phase to form a stable emulsion system. Moreover, it can form an interfacial film with a certain strength and elasticity at the oil-water interface, preventing the aggregation and coalescence of emulsion droplets, and further optimizing the stability and particle size of the nanoemulsion. The applicant also adds cosolvents, vitamin E acetate, etc. Through their synergistic effect with the emulsifier, the dispersity of the emulsifier can be increased, assisting the emulsifier to better play the role of liquid coating at the oil-water interface, reducing the interfacial tension, reducing oxidative decay, promoting the formation of nanoemulsion droplets, and optimizing the physicochemical properties of the nanoemulsion, such as particle size distribution, stability, etc.; at the same time, it can also increase the solubility of the oil phase in the water phase, enabling more plant essential oils to be evenly dispersed in the nanoemulsion and increasing the essential oil content in the nanoemulsion. In addition, it can effectively prevent the negative effects or freezing caused by low temperature in cold regions.

[0018] Preferably, the median particle size of the composite essential oil nanoemulsion is 5 nm to 45 nm, such as 5 nm, 15 nm, 30 nm, 35 nm, 40 nm, 45 nm, etc.

[0019] Preferably, the plant essential oil is carvacrol, cinnamaldehyde, oleoresin capsici, and thymol.

[0020] More preferably, the mass content of carvacrol in the composite essential oil nanoemulsion > the mass content of cinnamaldehyde in the composite essential oil nanoemulsion > the mass content of oleoresin capsici in the composite essential oil nanoemulsion > the mass content of thymol in the composite essential oil nanoemulsion.

[0021] In some embodiments, the mass content of carvacrol in the composite essential oil nanoemulsion is 7% to 12%, more preferably 7% to 9%, such as 7%, 7.5%, 8%, 8.5%, 9%.

[0022] In some embodiments, the mass content of cinnamaldehyde in the composite essential oil nanoemulsion is 5% to 10%, more preferably 5% to 7%, such as 5%, 5.5%, 6%, 6.5%, 7%.

[0023] In some embodiments, the mass content of oleoresin capsici in the composite essential oil nanoemulsion is 2% to 5%, more preferably 3% to 5%, such as 3%, 3.5%, 4%, 4.5%, 5%.

[0024] In some embodiments, the mass content of thymol in the composite essential oil nanoemulsion is 1% to 4%, more preferably 1% to 3%, such as 1%, 1.5%, 2%, 2.5%, 3%.

[0025] In some specific and preferred embodiments, based on the total mass of the composite essential oil nanoemulsion being 100%, the composite essential oil nanoemulsion includes:

[0026] Carvacrol 7% - 10%,

[0027] Cinnamaldehyde 5% - 10%,

[0028] Oleoresin capsici 2% - 5%,

[0029] Thymol 1% - 4%,

[0030] Polyethylene glycol glycerol ricinoleate 40% - 60%,

[0031] Co - solvent 15% - 30%,

[0032] Water 5% - 30%,

[0033] Tocopheryl acetate 0.01% - 0.2%,

[0034] Ethylenediaminetetraacetate 0.01 - 0.05%.

[0035] Further, based on the total mass of the composite essential oil nanoemulsion being 100%, the composite essential oil nanoemulsion comprises:

[0036] Carvacrol 7% - 9%,

[0037] Cinnamaldehyde 5% - 7%,

[0038] Paprika oleoresin 3% - 5%,

[0039] Thymol 1% - 3%,

[0040] Polyethylene glycol glycerol ricinoleate 45% - 55%,

[0041] Cosolvent 15% - 25%,

[0042] Water 5% - 15%,

[0043] Tocopheryl acetate 0.01% - 0.2%,

[0044] Ethylenediaminetetraacetate 0.01 - 0.05%.

[0045] Preferably, the cosolvent is selected from one or more of polyethylene glycol and propylene glycol.

[0046] Preferably, the ethylenediaminetetraacetate is disodium ethylenediaminetetraacetate.

[0047] Preferably, the water is selected from one or more of purified water, deionized water, and distilled water.

[0048] The second aspect of the present invention provides a preparation method of the composite essential oil nanoemulsion as described above, comprising the following steps:

[0049] (1) Mix the plant essential oil and tocopheryl acetate, and stir evenly to form an oil phase;

[0050] (2) Mix the oil phase of step (1) with polyethylene glycol glycerol ricinoleate, and stir evenly to form a mixture;

[0051] (3) Mix the cosolvent and water, and optionally add disodium ethylenediaminetetraacetate, and stir evenly to form an aqueous phase;

[0052] (4) Mix the mixture of step (2) with the aqueous phase of step (3), and stir evenly to prepare the composite essential oil nanoemulsion.

[0053] The preparation method of the present invention is simple. It only needs simple mechanical stirring to prepare the nanoemulsion, which is easy for large-scale industrial production, has low production cost, and has remarkable practicability and economy.

[0054] Preferably, the mixing temperatures of steps (1) to (4) are independently selected from 30°C to 60°C, and further preferably 40°C to 50°C.

[0055] Preferably, the stirring speeds of steps (1) to (4) are independently selected from 1000 r / min to 3000 r / min, and further preferably 1500 r / min to 2500 r / min.

[0056] The third aspect of the present invention also provides an application of the composite essential oil nanoemulsion as described above, and the application includes adding the composite essential oil nanoemulsion as a feed additive to feed or drinking water.

[0057] Preferably, the addition amount of the composite essential oil nanoemulsion is 50 - 500 g / ton of feed.

[0058] Further preferably, the addition amount of the composite essential oil nanoemulsion is 50 - 150 g / ton of feed.

[0059] Preferably, the composite essential oil nanoemulsion is diluted and then sprayed onto the feed.

[0060] Due to the application of the above technical solutions, the present invention has the following advantages compared with the prior art:

[0061] The composite essential oil nanoemulsion of the present invention not only has a high essential oil content, but also its particle size can reach the nano level, which is more conducive to absorption. At the same time, it also has the advantages of good stability and long shelf life, and can maintain excellent physical and chemical properties during long-term storage and transportation, and is more competitive in practical applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0062] Figure 1 It is a physical picture of the composite essential oil nanoemulsion of Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0063] The present invention will be further described below in conjunction with examples. However, the present invention is not limited to the following examples. The implementation conditions adopted in the examples can be further adjusted according to different requirements of specific use, and the implementation conditions not specified are conventional conditions in the industry. The technical features involved in each implementation manner of the present invention can be combined with each other as long as they do not conflict with each other.

[0064] Unless otherwise specified, the raw materials involved in the following examples and comparative examples are all commercially available products. Among them, oleoresin capsicum, oil-soluble, from Guangdong Tiansheng Food Technology Co., Ltd.; polyethylene glycol, from Liaoning Aoke Chemical Co., Ltd., PEG400.

[0065] Example 1: A method for preparing a composite essential oil nanoemulsion, comprising the following steps:

[0066] (1) Mix 80 parts by mass of carvacrol, 60 parts by mass of cinnamaldehyde, 40 parts by mass of oleoresin capsicum, 20 parts by mass of thymol and 1 part by mass of vitamin E acetate, and stir evenly at 45 °C with a stirring speed of 2000 r / min to prepare an oil phase.

[0067] (2) Add 500 parts by mass of polyethylene glycol glycerol ricinoleate (HLB = 10 - 14, from Nouryon Surface Chemistry AB, Sweden, Blidox 694 and Blidox 688 compounded according to a mass ratio of 9:1) to the oil phase in step (1), and stir evenly at 45 °C with a stirring speed of 2000 r / min to prepare a mixture.

[0068] (3) Mix 200 parts by mass of polyethylene glycol, 100 parts by mass of purified water and 0.2 part by mass of disodium ethylenediaminetetraacetate, and stir evenly to prepare an aqueous phase.

[0069] (4) Mix the mixture in step (2) and the aqueous phase in step (3), and stir evenly at 45 °C with a stirring speed of 2000 r / min to prepare a nanoemulsion, as Figure 1 shown.

[0070] Example 2: This example is substantially the same as Example 1, except that: disodium ethylenediaminetetraacetate is not added in step (3).

[0071] Comparative Example 1: This comparative example is substantially the same as Example 1, except that:

[0072] ① Polyethylene glycol glycerol ricinoleate is not added, that is, the operation in step (2) is not carried out, and the oil phase in step (1) and the aqueous phase in step (3) are directly mixed and stirred evenly.

[0073] ② The amount of purified water used in step (3) is 600 parts by mass.

[0074] Comparative Example 2: This comparative example is substantially the same as Example 1, except that: an equal mass of sodium cholate is used to replace polyethylene glycol glycerol ricinoleate.

[0075] Comparative Example 3: This comparative example is substantially the same as Example 1, except that: an equal mass of lysophosphatidylcholine is used to replace polyethylene glycol glycerol ricinoleate.

[0076] Comparative Example 4: This comparative example is substantially the same as Example 1, except that: polyethylene glycol glycerol ricinoleate with HLB = 8.9 (Brij 683, supplied by Nouryon Surface Chemistry AB, Sweden) is used to replace the polyethylene glycol glycerol ricinoleate in step (2).

[0077] Comparative Example 5: This comparative example is substantially the same as Example 1, except that: polyethylene glycol glycerol ricinoleate with HLB = 18 (Brij 688, supplied by Nouryon Surface Chemistry AB, Sweden) is used to replace the polyethylene glycol glycerol ricinoleate in step (2).

[0078] Comparative Example 6: This comparative example is substantially the same as Example 1, except that: the amounts of polyethylene glycol glycerol ricinoleate and purified water used are different.

[0079] In this comparative example, the amount of polyethylene glycol glycerol ricinoleate used is 400 parts by mass, and the amount of purified water used is 400 parts by mass.

[0080] Comparative Example 7: This comparative example is substantially the same as Example 1, except that: the amounts of polyethylene glycol glycerol ricinoleate and purified water used are different.

[0081] In this comparative example, the amount of polyethylene glycol glycerol ricinoleate used is 300 parts by mass, and the amount of purified water used is 500 parts by mass.

[0082] Comparative Example 8: This comparative example is substantially the same as Example 1, except that: the amounts of polyethylene glycol glycerol ricinoleate and purified water used are different.

[0083] In this comparative example, the amount of polyethylene glycol glycerol ricinoleate used is 200 parts by mass, and the amount of purified water used is 300 parts by mass.

[0084] Comparative Example 9: This comparative example is substantially the same as Example 1, except that: the amounts of polyethylene glycol glycerol ricinoleate and purified water used are different.

[0085] In this comparative example, the amount of polyethylene glycol glycerol ricinoleate used is 100 parts by mass, and the amount of purified water used is 300 parts by mass.

[0086] Comparative Example 10: This comparative example is substantially the same as Example 1, except that: polyethylene glycol is not added in step (3).

[0087] Performance Test:

[0088] 1. Appearance: Observe the appearance and transparency of the sample at rest.

[0089] 2. Median Particle Size Test: Using a laser particle size distribution analyzer, dilute the nanoemulsion to the concentration required for testing by the laser particle size distribution analyzer, calculate the particle size distribution by measuring light scattering, and obtain the median particle size therefrom.

[0090] 3. Centrifugal stability: Dilute the nanoemulsion 5 - fold or 10 - fold with deionized water, then place it in a centrifuge and centrifuge for 15 min at a rotational speed of (3000 - 10000) / min. After centrifugation, observe whether the sample shows any layering.

[0091] 4. Storage stability: Seal and store the nanoemulsion in the dark at room temperature (25 °C) for 90 days. Take it out every 15 days to measure its particle size and compare it with the particle size before storage. If the ratio of the absolute value of the difference in particle size before and after storage to the particle size before storage is less than 10%, it is considered storage - stable; otherwise, it is considered unstable.

[0092] 5. Heat - treatment stability: Place the nanoemulsion under the conditions of 40 °C and 90 ± 5% RH and observe for 3 weeks. Measure its particle size and compare it with the particle size before heat - treatment. If the ratio of the absolute value of the difference in particle size before and after heat - treatment to the particle size before heat - treatment is less than 10%, it is considered heat - treatment - stable; otherwise, it is considered unstable.

[0093] 6. Shelf - life: Seal and store the nanoemulsion in the dark at room temperature (25 °C), and regularly detect indicators such as appearance, particle size, and Zeta potential of the nanoemulsion. At the same time, observe whether there are phenomena such as layering, precipitation, and deterioration until the emulsion no longer meets the quality requirements, so as to determine its shelf - life.

[0094] For the performance test data of the above - mentioned examples and comparative examples, see Table 1.

[0095]

[0096] The nanoemulsion with a small particle size can be absorbed by animals more quickly, reducing the degradation and loss of active ingredients in the gastrointestinal tract, thereby improving the bioavailability of the nanoemulsion. As can be seen from the above table, the nanoemulsion prepared in the examples of the present invention has a smaller particle size, with a median particle size of only about 45 nm, and the proportion of active ingredients (carvacrol, cinnamaldehyde, oleoresin capsici, and thymol) in the nanoemulsion is high, close to 20%. At the same time, this nanoemulsion has a long shelf - life and better stability, which is convenient for storage and transportation under different environmental conditions, and can ensure that the nanoemulsion does not degrade, deteriorate, or become ineffective during storage and transportation, ensuring that the active ingredients still maintain a high level of activity when reaching the action site, thereby improving the efficacy of the nanoemulsion.

[0097] By comparing Example 1 with Comparative Examples 1 to 9, it can be seen that the emulsifier components and dosage have a significant impact on the performance of the nanoemulsion. Selecting polyethylene glycol glycerol ricinoleate with an HLB value of 10 - 14 as the emulsifier can significantly reduce the particle size of the emulsion to the nanoscale. However, once the dosage of polyethylene glycol glycerol ricinoleate is too small (less than 35% of the total mass of the nanoemulsion) or too large (more than 60% of the total mass of the nanoemulsion), it will cause the particle size of the emulsion to be too large, with poor stability and a short shelf - life.

[0098] By comparing Example 1 and Comparative Example 10, it can be seen that by adding a cosolvent (such as polyethylene glycol), it can act synergistically with other components to improve the stability and shelf life of the nanoemulsion.

[0099] By comparing Example 1 and Example 2, it can be seen that by adding disodium ethylenediaminetetraacetate, it can chelate metal ions in the nanoemulsion, thereby further improving the stability of the nanoemulsion and extending the shelf life.

[0100] Application test: 2000 7-day-old broiler chickens were randomly divided into 5 representative groups, with 400 chickens in each group. They were allowed to eat and drink freely. The preliminary test period was 7 days, and the test period was 21 days. The control group was fed a basal diet. In addition to the basal diet, the nanoemulsions of Example 1, Comparative Examples 1 to 3 were added to Test Groups 1 to 4 respectively, and the addition amount was 100 g / t diet (sprayed after dilution with water). The results are shown in Table 2.

[0101]

[0102] Among them, feed conversion rate = daily feed intake / daily weight gain. The lower the feed conversion rate value, the less feed is required per unit of weight gain, and the higher the breeding efficiency.

[0103] It can be seen that the nanoemulsion of the embodiment of the present invention has the best growth rate and feed conversion rate of broiler chickens. It shows that the nanoemulsified essential oil has a better dispersion effect and better bioavailability when added to the diet by spraying after dilution with water. In addition, the applicant's further research also found that when the proportion of oleoresin capsici in the nanoemulsion is too low (less than 3% of the total mass of the nanoemulsion) or too high (more than 5% of the total mass of the nanoemulsion), it will lead to a decrease in feed intake and affect the weight gain of broiler chickens.

[0104] The above has described the present invention in detail. The purpose is to enable those skilled in this field to understand the content of the present invention and implement it. It should not be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit and essence of the present invention should be covered within the protection scope of the present invention.

Claims

1. A composite essential oil nanoemulsion, characterized in that, Based on the total mass of the composite essential oil nanoemulsion being 100%, the composite essential oil nanoemulsion comprises: Plant essential oil 15% - 30%, and the plant essential oil is selected from two or more of carvacrol, cinnamaldehyde, oleoresin capsici, and thymol; Polyethylene glycol glycerol ricinoleate 40% - 60%, and the HLB value of the polyethylene glycol glycerol ricinoleate is 10 - 14; Cosolvent 10% - 30%; Water 5% - 30%; Vitamin E acetate 0.01% - 0.5%; Ethylenediaminetetraacetate 0 - 0.1%, The median particle size of the composite essential oil nanoemulsion is not more than 45 nm.

2. The nanoemulsion of compound essential oil according to claim 1, wherein The median particle size of the composite essential oil nanoemulsion is 5 nm - 45 nm.

3. The composite essential oil nanoemulsion according to claim 2, wherein The composite essential oil nanoemulsion is a homogeneous liquid and is transparent.

4. The nanoemulsion of compound essential oil according to claim 1, characterized in that The plant essential oil is carvacrol, cinnamaldehyde, oleoresin capsici, and thymol, and the mass content of carvacrol in the composite essential oil nanoemulsion > the mass content of cinnamaldehyde in the composite essential oil nanoemulsion > the mass content of oleoresin capsici in the composite essential oil nanoemulsion > the mass content of thymol in the composite essential oil nanoemulsion.

5. The compound essential oil nanoemulsion according to claim 4, wherein The mass content of carvacrol in the composite essential oil nanoemulsion is 7% - 12%; and / or, The mass content of cinnamaldehyde in the composite essential oil nanoemulsion is 5% - 10%; and / or, The mass content of oleoresin capsici in the composite essential oil nanoemulsion is 2% - 5%; and / or, The mass content of thymol in the composite essential oil nanoemulsion is 1% - 4%.

6. The composite essential oil nanoemulsion according to claim 1, wherein Based on the total mass of the composite essential oil nanoemulsion being 100%, the composite essential oil nanoemulsion comprises: Carvacrol 7% - 10%, Cinnamaldehyde 5% - 10%, Oleoresin capsici 2% - 5%, Thymol 1% - 4%, Polyethylene glycol glycerol ricinoleate 40% - 60%, Cosolvent 15% - 30%, Purified water 5% - 30%, Vitamin E acetate 0.01% - 0.2%, Ethylenediaminetetraacetate 0.01 - 0.05%.

7. The nanoemulsion of compound essential oil according to claim 1, wherein The cosolvent is selected from one or more of polyethylene glycol and propylene glycol; and / or, The ethylenediaminetetraacetate is disodium ethylenediaminetetraacetate.

8. The preparation method of the composite essential oil nanoemulsion according to any one of claims 1 to 7, characterized in that, Comprises the following steps: (1) Mix the plant essential oil and vitamin E acetate, and stir evenly to form an oil phase; (2) Mix the oil phase of step (1) with polyethylene glycol glycerol ricinoleate, and stir evenly to form a mixture; (3) Mix the cosolvent and water, add ethylenediaminetetraacetate, and stir evenly to form an aqueous phase; (4) Mix the mixture of step (2) with the aqueous phase of step (3), and stir evenly to prepare the composite essential oil nanoemulsion.

9. The preparation method of the composite essential oil nanoemulsion according to claim 8, characterized in that, The mixing temperature of steps (1) to (4) is independently selected from 30°C - 60°C; and / or, The stirring speed of steps (1) to (4) is independently selected from 1000 r / min - 3000 r / min.

10. Use of the composite essential oil nanoemulsion according to any one of claims 1 to 7, wherein the use comprises adding the composite essential oil nanoemulsion as a feed additive to feed or drinking water.

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