Compound essential oil self-microemulsion for clearing and activating channels and collaterals and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicine compound essential oil for external use, and provides a compound essential oil self-microemulsion capable of clearing and activating the channels and collaterals and a preparation method thereof.The compound essential oil self-microemulsion capable of clearing and activating the channels and collaterals comprises compound essential oil, a mixed surfactant and deionized water, it can be understood that the compound essential oil self-microemulsion capable of clearing and activating the channels and collaterals is prepared by adopting a water drop method, high pressure, high temperature or high shear force is not needed, and the microemulsion can be formed only through slow titration of a water phase and mild stirring; the polarity gradient and the particle size distribution of the microemulsion can be accurately controlled by gradually adjusting the proportion of the water phase; slowly titrating to enable the surfactant to be fully adsorbed to an oil-water interface to form a compact interface film; and a complex essential oil formula can be flexibly adapted.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine compound external essential oils, and more specifically, to a self - microemulsion of a meridians - dredging and collaterals - activating compound essential oil and a preparation method thereof. Background Art

[0002] Traditional Chinese medicine compound essential oil is a compound essential oil product extracted by compatibility under the guidance of traditional Chinese medicine theory. It can be used with base oils (such as sweet almond oil, jojoba oil, coconut oil, etc.) in massage and beauty processes to promote the transdermal absorption of active ingredients, reduce friction, and at the same time achieve the effects of soothing the body and mind, relieving muscle fatigue or improving skin condition through the active ingredients of the essential oil; traditional Chinese medicine formula essential oil needs to follow the theories of the nature, flavor, meridian tropism, efficacy and indications of traditional Chinese medicine, and extract compound essential oil through multi - formula compatibility to achieve the synergistic effect of volatile components in traditional Chinese medicine; the microemulsion of traditional Chinese medicine compound essential oil can be used as a penetration - promoting component in patches, films in drugs and cosmetics, and also as a penetration - promoting agent component in medical gels and electrode patches of medical devices.

[0003] The existing preparation methods of compound essential oil self - microemulsion include phase - inversion method, high - pressure homogenization method, spontaneous emulsification method, etc.; the rapid phase transition of the phase - inversion method will cause local supersaturation when the aqueous phase is added, leading to droplet coalescence, resulting in turbidity, and it is difficult to accurately control the critical water content for the formation of microemulsion, and it is easy to delaminate; the high - pressure homogenization method will cause the rupture of the interfacial film, resulting in the oxidation of essential oil components, the broadening of the particle size distribution, and the decline of the system stability; the spontaneous emulsification method depends on the instantaneous compatibility of surfactants and essential oils. Direct mixing causes the imbalance of component ratios when the aqueous phase is added, resulting in HLB deviation, and it is also easy to form a lamellar phase rather than a microemulsion, showing gelation or turbidity.

[0004] To solve the above problems, a self - microemulsion of a meridians - dredging and collaterals - activating compound essential oil and a preparation method thereof are proposed in this application. Summary of the Invention

[0005] The purpose of the present invention is to provide a self - microemulsion of a meridians - dredging and collaterals - activating compound essential oil and a preparation method thereof. By using the water - drop method to prepare the compound essential oil microemulsion, it has the effects of clear liquid, no delamination, uniform dispersion and stable system.

[0006] The purpose of the present invention can be achieved by the following technical solutions:

[0007] A self - microemulsion of a meridians - dredging and collaterals - activating compound essential oil, calculated by mass ratio, the self - microemulsion of the compound essential oil comprises the following components: 0.5 g - 4.5 g of compound essential oil, 4.5 g - 0.5 g of mixed surfactant, and 30 - 45 g of deionized water.

[0008] Further, the self - microemulsion of the compound essential oil comprises the following components: 3.5 g - 1.5 g of compound essential oil, 1.5 g - 3.5 g of mixed surfactant.

[0009] Furthermore, the self - microemulsion of the compound essential oil comprises the following components: 3.0 g - 2.0 g of compound essential oil and 2.0 g - 3.0 g of mixed surfactant.

[0010] Furthermore, the self - microemulsion of the compound essential oil comprises the following components: 2.5 g of compound essential oil and 2.5 g of mixed surfactant.

[0011] Furthermore, for the self - microemulsion of the compound essential oil: the corresponding mass of the mixed surfactant and the compound essential oil, with a total mass of 5 g;

[0012] Furthermore, the compound essential oil comprises the following components: white mustard seed, Corydalis yanhusuo, speranskia tuberculata, ginger, safflower, and actinidia arguta leaves, which are prepared by supercritical CO2 extraction according to the mass ratio of 1:1:1:1:1:1.

[0013] Furthermore, the mixed surfactant comprises the following components: the surfactant and the co - surfactant are placed on a magnetic stirrer and stirred for one hour according to a certain mass ratio (the ratio Km = 2, 3, 4) to form the mixed surfactant.

[0014] Furthermore, the surfactant is one of Tween 80, Tween 85, Tween 60, Tween 20, and polyoxyethylene castor oil.

[0015] Furthermore, the co - surfactant is one of absolute ethanol, glycerol, and 1,2 - propanediol.

[0016] Furthermore, when the total mass of the self - microemulsion of the compound essential oil is 10 g, the mass ratio of deionized water: compound essential oil: mixed surfactant is 6 g - 9 g: 3.667 g - 0.917 g: 0.333 g - 0.083 g, forming a clear and transparent microemulsion.

[0017] On the other hand, the present invention also provides a preparation method of a self - microemulsion of a compound essential oil for dredging channels and activating collaterals, and the preparation method comprises the following steps:

[0018] S1. Prepare the compound essential oil: Grind white mustard seed, Corydalis yanhusuo, speranskia tuberculata, ginger, safflower, and actinidia arguta leaves to 40 mesh according to the mass ratio of 1:1:1:1:1:1, and use supercritical CO2 extraction. Add an ethanol solution as an entrainer, and adjust the pressure and temperature to the predetermined values for extraction;

[0019] S2. Prepare the mixed surfactant: Mix Tween 80 or Tween 85 with absolute ethanol or glycerol according to the mass ratio of 3 - 4:1, and mix well by magnetic stirring;

[0020] S3. Mix the mixed surfactant and the compound essential oil evenly according to the mass ratio of 4:1 or 11:1;

[0021] S4. While magnetically stirring, dropwise add deionized water to the mixture.

[0022] The pharmacology and functions of each component used in the present invention are as follows:

[0023] White mustard seed: contains sulfur glycosides (such as sinigrin), which generate isothiocyanates after hydrolysis, having a local stimulating effect, promoting skin microcirculation, and relieving pain; having the functions of warming the meridians and dispelling cold, reducing swelling and alleviating pain, and is commonly used for external treatment of cold pain in joints and muscle stiffness.

[0024] Corydalis yanhusuo: contains tetrahydropalmatine (corydalis yanhusuo alkaloid), which is a central and peripheral analgesic component, can inhibit prostaglandin synthesis, and regulate calcium ion channels; having the functions of promoting blood circulation and qi movement, relieving pain, and having a synergistic analgesic effect on traumatic injuries and rheumatic arthralgia.

[0025] Speranskia tuberculata: contains flavonoids (such as quercetin) and alkaloids, can inhibit inflammatory factors (such as TNF-α, IL-6), and enhance local blood circulation; having the functions of dispelling wind and dampness, relaxing tendons and activating collaterals, and is commonly used for rheumatic arthritis and soft tissue injury.

[0026] Ginger: contains gingerol (such as 6-gingerol), promotes capillary dilation by activating TRPV1 receptors, and accelerates the transdermal absorption of drugs; having the functions of warming the meridians and dispelling cold, anti-inflammatory, enhancing the permeability of other components and having a synergistic cold-dispelling effect.

[0027] Safflower: contains safflower yellow pigment and safflor yellow A, has the effect of inhibiting platelet aggregation, reducing blood viscosity, and improving microcirculation; having the functions of warming the meridians and dispelling cold, anti-inflammatory, enhancing the permeability of other components and having a synergistic cold-dispelling effect.

[0028] Actinidia arguta leaf: contains polyphenols and triterpenoids, has antioxidant and anti-inflammatory effects, and can reduce oxidative stress damage to local tissues; having the functions of clearing heat and detoxifying, assisting in anti-inflammatory, balancing the warm property of the formula, and reducing the risk of skin irritation.

[0029] Tween 80: reduces the interfacial tension between oil and water, forms a microemulsion system, improves the solubility and stability of essential oils in the aqueous phase; enhances the transdermal absorption efficiency of lipophilic components (such as gingerol and safflower yellow pigment).

[0030] Absolute ethanol: synergistically reduces the viscosity of the system with Tween 80; as a penetration enhancer, temporarily destroys the lipid structure of the stratum corneum to promote drug penetration; has a mild bactericidal effect and prolongs the shelf life of the preparation.

[0031] Deionized water: as a solvent dispersion system, regulates the viscosity of the preparation, reduces the irritation of essential oils directly contacting the skin, and ensures the safety of use.

[0032] The beneficial effects of the present invention:

[0033] The present invention uses the water-drop method to prepare with low energy consumption. The formation of microemulsion can be completed only by slowly titrating water and combining with gentle stirring, without relying on high-pressure, high-temperature or high-shear equipment. This not only reduces the energy consumption cost but also effectively protects heat-sensitive essential oil components (such as terpenes and esters) from degradation. In addition, this method has precise controllability. By gradually adjusting the proportion of the aqueous phase, the polarity gradient and particle size distribution of the microemulsion can be precisely optimized;

[0034] Slow titration enables the surfactant to be fully adsorbed onto the oil-water interface, forming a dense and stable interfacial film, thereby obtaining uniform nano-droplets and a relatively high Zeta potential, significantly improving the storage stability;

[0035] In summary, compared with the traditional high-pressure homogenization or phase inversion method, the water-drop method performs better in terms of retaining the activity of essential oils, reducing energy consumption, and adapting to complex systems. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0037] Figure 1 Pseudo-ternary phase diagrams of microemulsions of composite essential oils with different surfactants: The shaded part represents the area of the microemulsion;

[0038] Figure 2 Pseudo-ternary phase diagrams of microemulsions of composite essential oils with different co-surfactants involved;

[0039] Figure 3 Pseudo-ternary phase diagrams of microemulsions of composite essential oils with different Km values;

[0040] Figure 4 Particle sizes and PDIs of microemulsions at different S / O values;

[0041] Figure 5 Microemulsions with S / O = 4:1 and 11:1;

[0042] Figure 6 Conductivity diagrams of microemulsions (11:1) with different water contents;

[0043] Figure 7 Particle sizes and PDIs of microemulsions with different water contents;

[0044] Figure 8 Electron micrographs of microemulsions (S / O = 11:1). DETAILED DESCRIPTION OF THE INVENTION

[0045] In order to make the objectives, technical solutions and advantages of the present invention more clear and understandable, the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without making creative efforts fall within the protection scope of the present invention.

[0046] Example 1

[0047] This example provides a self-microemulsion of a compound essential oil for dredging channels and activating collaterals, comprising the following components:

[0048] Compound essential oil, prepared by supercritical CO2 extraction from white mustard seed, Corydalis yanhusuo, Speranskia tuberculata, ginger, safflower, and Actinidia arguta leaves in a mass ratio of 1:1:1:1:1:1;

[0049] Mixed surfactant, composed of a surfactant and a co-surfactant, wherein the surfactant is Tween 80, the co-surfactant is absolute ethanol, and the mass ratio of the surfactant to the co-surfactant is 1:4; wherein, the mass ratio of the mixed surfactant to the compound essential oil is 11:1, and they are mixed evenly by magnetic stirring;

[0050] The content of deionized water is 80%.

[0051] This example also provides a preparation method of the self-microemulsion of the compound essential oil for dredging channels and activating collaterals. Referring to Cui Yuhan of Tianjin University of Commerce. Research on the preparation of clove essential oil microemulsion and its compound chitosan on the preservation effect of mangoes, the water-drop method is used for preparation, including the following steps:

[0052] S1. Weigh white mustard seed, Corydalis yanhusuo, Speranskia tuberculata, ginger, safflower, and Actinidia arguta leaves (1:1:1:1:1:1) in the formula, grind them into granular form (40 mesh), put them into supercritical CO2 extraction, and check the tightness of the extraction system. Add the entrainer ethanol solution, adjust the pressure and temperature to the predetermined values, and then carry out extraction. After the specified extraction time, calculate the extraction rate according to the total volatile oil content.

[0053] Through the variance analysis of the response surface experiment results, the optimal extraction conditions are obtained: extraction time 88 min, extraction temperature 56 °C, extraction pressure 27 MPa, and CO2 flow rate 25 L / h. The results of three verification experiments show that the extraction rate results of the volatile oil of the formula actually detected are slightly different from the response surface prediction results. The experimental data are shown in Table 1.

[0054]

[0055] Table 1 shows the extraction rate of the compound volatile oil under the optimal conditions of the supercritical CO2 extraction response surface model

[0056] S2. Prepare the mixed surfactant: Mix Tween 80 and absolute ethanol in a mass ratio of 4:1, and mix evenly by magnetic stirring for 1 h;

[0057] S3. Mix the mixed surfactant and the compound essential oil evenly in a mass ratio of 11:1;

[0058] S4. While magnetically stirring, add deionized water dropwise to the mixture, and the content of deionized water is 80%.

[0059] Example 2

[0060] The difference from Example 1 is that the surfactant is one of Tween 20, Tween 60, Tween 85, and polyoxyethylene castor oil, as shown in Table 2 and Figure 1 The following shows the comparison data between Example 2 and Example 1.

[0061]

[0062]

[0063] Table 2 shows the HLB values of different surfactants and the areas of the microemulsions formed

[0064] Example 3

[0065] The difference from Example 1 is that the co-surfactant is one of glycerol and 1,2-propanediol, as shown in Table 3 and Figure 2 The following shows the comparison data between Example 3 and Example 1.

[0066] Cosurfactant HLB value State Proportion of microemulsion area Absolute ethanol 8 Clear and transparent 16.33％ Glycerol 6.7 Clear and transparent 12.92％ 1,2 - Propylene glycol 6.5 Clear and transparent 9.38％

[0067] Table 3 shows the HLB values of the co-surfactants and the areas of the microemulsions formed

[0068] Example 4

[0069] The difference from Example 1 is the other mass ratios of the mixed surfactant and the co-surfactant, such as

[0070] Table 4 and Figure 3 The following shows the comparison data between Example 4 and Example 1.

[0071] Km value State Proportion of microemulsion area 2 Clear and transparent 11.11％ 3 Clear and transparent 12.58％ 4 Clear and transparent 16.33％

[0072] Table 4 shows the areas of the microemulsions at different Km values

[0073] Example 5

[0074] The difference from Example 1 is that the mixed surfactant and the compound essential oil are in other mass ratios, as shown in Table 5 and Figure 4 The following shows the comparison between Example 5 and Example 1.

[0075]

[0076]

[0077] Table 5 shows the mass of the mixed surfactant and the composite essential oil

[0078] Example 6

[0079] Different from Example 1, the content of deionized water is in other ratios. It can be seen from Figure 6 that when the water content ranges from 0 to 50%, the conductivity increases rapidly with the increase of the water content, and the system is of the W / O type at this time. This is because in the W / O system, when the water content increases, the microemulsion particles in the system also increase, and the particles attract and collide with each other, forming small water channels in the continuous oil phase. The water channels allow counterions to pass through, resulting in a sharp increase in the conductivity of the microemulsion system. When the water content is about 60% to 70%, the conductivity increases slowly with the increase of the water content, and the system is of the B / C type at this time. This is because large-scale collisions occur among the particles in the W / O microemulsion in the early stage of the system, and there will be oil channels in the water phase and small water channels in the oil phase in the system at the same time. When the water content is 80% to 90%, the conductivity decreases with the increase of the water content, and the system is of the O / W type at this time. When the water content is above 70%, the dilution factor of the microemulsion becomes larger, and the concentration of microemulsion particles in the system decreases, resulting in a decrease in conductivity.

[0080] During the experiment, when the water content is 10% to 20%, the system has a high viscosity and low fluidity, and the system does not form a standard W / O microemulsion. When the water content is 30% to 50%, the system viscosity is relatively large, exceeding the detection range of the instrument. Therefore, only the microemulsions with a water content of 60% to 90% are used for particle size and PDI measurement. As Figure 7 shown, when the water content of the system is 60%, the particle size is greater than 1000 nm, and the system is a typical B / C type at this time. When the water content of the system increases to 80%, the particle size is less than 100 nm, and 0.2 < PDI < 0.3. The system at this time is of the O / W type, and the microemulsion particles are small and evenly dispersed.

[0081] Microscopic morphology observation:

[0082] Use a FEL Tecnai Spirit electron microscope to observe the particle morphology of the O / W microemulsion; drop 1 μL of the composite essential oil microemulsion onto a clean oily membrane paper, cover the copper mesh on the microemulsion drop, air dry for 1 minute naturally, then perform negative staining with 3% phosphotungstic acid for 30 seconds, blot the excess water on the copper mesh with filter paper, and observe under the microscope.

[0083] Identification of microemulsion morphology:

[0084] The S / O is 11:1, the water content of the microemulsion is 80%, and the sample is observed under an electron microscope after treatment. The results are as Figure 8 shown. The microemulsion particles are spherical in distribution and are relatively evenly dispersed in the system without aggregation.

[0085] It can be understood that the present invention uses the water-drop method to prepare the microemulsion of the Tongjing Huoluo compound essential oil. Without high pressure, high temperature or high shear force, the microemulsion can be formed only by slowly titrating the aqueous phase and gently stirring; by gradually adjusting the proportion of the aqueous phase, the polarity gradient and particle size distribution of the microemulsion can be precisely controlled; the slow titration enables the surfactant to be fully adsorbed to the oil-water interface to form a dense interfacial film; and it can be flexibly adapted to complex essential oil formulations.

[0086] In the description of the present invention, unless otherwise specified, "a plurality of" means two or more; it should be understood that the terms "open hole", "upper", "lower", "thickness", "top", "middle", "length", "inner", "periphery", etc. indicating the orientation or position relationship are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the components or elements referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus cannot be understood as a limitation to the present invention.

[0087] Finally, it should be noted that the above are only the preferred embodiments of the present invention and are not used to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions recorded in the foregoing embodiments, or perform equivalent replacements for some of the technical features. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A self - microemulsifying compound essential oil for dredging channels and activating collaterals, characterized in that, It includes the following components: Compound essential oil, which is prepared by supercritical CO2 extraction from white mustard seed, Corydalis yanhusuo, Speranskia tuberculata, ginger, safflower, and Actinidia arguta leaves in a mass ratio of 1:1:1:1:1:

1. Mixed surfactant, which is composed of a surfactant and a co-surfactant. The surfactant is Tween 80 or Tween 85, and the co-surfactant is absolute ethanol or glycerol. The mass ratio of the surfactant to the co-surfactant is 3 - 4:

1. Among them, the mass ratio of the mixed surfactant to the compound essential oil is 4:1 or 11:1, and they are mixed evenly by magnetic stirring. Deionized water, and the water content in the compound essential oil microemulsion system is 60% to 90%.

2. The self - microemulsifying compound essential oil for dredging channels and activating collaterals according to claim 1, wherein: The surfactant is Tween 80, and the co-surfactant is absolute ethanol.

3. The self - microemulsion of a compound essential oil for dredging channels and activating collaterals according to claim 2, characterized in that: The mass ratio of Tween 80 to absolute ethanol is 1:

4.

4. The self - microemulsifying compound essential oil for dredging channels and activating collaterals according to claim 3, wherein: The mass ratio of the mixed surfactant to the compound essential oil is 11:

1.

5. The self - microemulsion of a compound essential oil for dredging channels and activating collaterals according to claim 1, characterized in that: The content of deionized water is 80%.

6. The preparation method of a dredging meridian and activating collaterals compound essential oil self-microemulsion according to claim 1, characterized in that: It includes the following steps: S1. Prepare the compound essential oil: Grind white mustard seed, Corydalis yanhusuo, Speranskia tuberculata, ginger, safflower, and Actinidia arguta leaves to 40 mesh in a mass ratio of 1:1:1:1:1:1, and use supercritical CO2 extraction. Add an ethanol solution as an entrainer, and adjust the pressure and temperature to the predetermined values for extraction. S2. Prepare the mixed surfactant: Mix Tween 80 or Tween 85 with absolute ethanol or glycerol in a mass ratio of 3 - 4:1, and mix evenly by magnetic stirring. S3. Mix the mixed surfactant and the compound essential oil evenly in a mass ratio of 4:1 or 11:

1. S4. While magnetically stirring, slowly add deionized water to the mixture.

7. A self - microemulsifying compound essential oil for dredging channels and activating collaterals and its preparation method according to claim 6, characterized in that: In step S2, the surfactant is Tween 80, and the co-surfactant is absolute ethanol.

8. A self - microemulsifying compound essential oil for dredging channels and activating collaterals and its preparation method according to claim 6, characterized in that: In step S2, the mass ratio of Tween 80 to absolute ethanol is 4:

1.

9. A self - microemulsifying compound essential oil for dredging channels and activating collaterals and its preparation method according to claim 6, characterized in that: In step S3, the mass ratio of the mixed surfactant to the compound essential oil is 11:

1.

10. A self - microemulsifying compound essential oil for dredging channels and activating collaterals and its preparation method according to claim 6, characterized in that: In step S4, the content of deionized water is 80%.

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