Essential oil delivery system based on bionic liposome and preparation method thereof

Abstract

The invention provides an essential oil delivery system based on bionic lipidosome and a preparation method thereof, and belongs to the technical field of cosmetics and pharmaceutical preparations, a membrane material of the bionic lipidosome delivery system contains a component similar to skin cuticle lipid, and an inclusion compound formed by cyclodextrin and volatile active ingredients is encapsulated in the membrane material; the volatile active component is selected from plant essential oil or active components thereof with anti-aging, analgesic, anti-inflammatory or anti-allergy effects; the membrane material is prepared from hydrogenated soybean lecithin, cholesterol, ceramide, phytosphingosine, phytosterol and an antioxidant; according to the bionic liposome delivery system provided by the invention, the volatility of active ingredients can be remarkably reduced, the stability of the active ingredients can be improved, and slow release and synergistic infiltration promotion effects can be realized, so that the effects of the bionic liposome delivery system in anti-aging, pain relieving and other applications can be greatly enhanced.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of cosmetics and pharmaceutical preparations, and specifically provides a liposome-based essential oil delivery system and a preparation method thereof. BACKGROUND

[0002] Liposomes have been widely studied as a common delivery carrier for encapsulating various active ingredients. However, traditional liposomes face problems such as low encapsulation efficiency, easy leakage and volatilization of active ingredients during storage and preparation, and insufficient affinity and permeability to the skin when encapsulating active ingredients with high volatility and high hydrophobicity, such as essential oils.

[0003] In the prior art, there are studies on directly encapsulating cyclodextrin inclusion compounds into liposomes. For example, a study compared conventional liposomes with liposomes containing drug-cyclodextrin complexes and found that the latter had better stability although the encapsulation efficiency was lower. This suggests the potential of combining the two technologies, but the study did not conduct related research on volatile active ingredients, nor did it design the composition of the liposomes to maximize their biomimetic properties and skin delivery efficiency.

[0004] Therefore, there is an urgent need in the art for an innovative liposome technology that can synergistically solve the comprehensive problems of stability, controlled release, and efficient skin delivery of volatile active ingredients, such as essential oils used for anti-aging and pain management. SUMMARY

[0005] In view of the deficiencies of the prior art, the present application provides a liposome-based essential oil delivery system and a preparation method thereof.

[0006] The technical solution of the present application is as follows: A biomimetic liposome delivery system, the membrane material of which comprises components similar to the lipids of the stratum corneum of the skin, and the inside is encapsulated with inclusion compounds formed by cyclodextrin and volatile active ingredients.

[0007] Preferably, in the above biomimetic liposome delivery system, the volatile active ingredient is selected from plant essential oils or active components thereof with anti-aging, analgesic, anti-inflammatory, or soothing efficacy.

[0008] Preferably, in the above biomimetic liposome delivery system, the membrane material comprises hydrogenated soy lecithin, cholesterol, ceramide, phytosphingosine, phytosterol, and an antioxidant.

[0009] Preferably, the composition of the membrane material comprises the following by weight: hydrogenated soy lecithin 110-120 parts, cholesterol 40-50 parts, a mixture of ceramide AP and NP 15-20 parts, phytosphingosine 2-4 parts, beta-sitosterol 10-15 parts, alpha-tocopherol 2-3 parts, and oleic acid 0.4-1 part.

[0010] Preferably, the biomimetic liposomes have a particle size of 150-200 nm and a polydispersity index (PDI) of less than 0.20.

[0011] The preparation method of the above-mentioned biomimetic liposome delivery system includes the following steps: a. Preparation of active ingredient inclusion complexes: Lyophilized powder of cyclodextrin-active ingredient inclusion complexes was prepared by a kinetic temperature-controlled dropwise addition method; b. Preparation of the liposome organic phase: Hydrogenated soybean lecithin, cholesterol, ceramide, phytosphoprotein, β-sitosterol, α-tocopherol and oleic acid are dissolved in an organic solvent to form an organic phase; c. Dispersing the aqueous phase: The lyophilized powder of the inclusion complex obtained in step a is dispersed in a buffer solution and subjected to ultrasonic treatment with a probe to form a nanoscale dispersion; d. Assemble biomimetic liposomes: Inject the organic phase obtained in step b into the aqueous dispersion obtained in step c, mix, and then perform magnetic stirring, conditional probe sonication, and membrane extrusion in sequence to obtain the first generation of liposomes; e. Purification: The primary liposomes obtained in step d are purified to obtain a biomimetic liposome delivery system.

[0012] Preferably, in step c, the ultrasonic power of the probe is 200-300W, a pulse mode is used, and the temperature is controlled below 25°C, so that the particle size of the inclusion complex dispersion reaches 50-80 nm.

[0013] Preferably, in step d, the ultrasonic power of the condition probe is 150-250W, and the pulse is applied; the membrane extrusion uses a polycarbonate membrane with a pore size of 200 nm.

[0014] Beneficial effects of the present invention 1. The essential oil delivery system based on biomimetic liposomes provided by this invention (also known as a biomimetic liposome delivery system) contains key components such as ceramides, phytosphingosine, and phytosterols. This design exhibits extremely high biocompatibility and affinity with the skin, thereby significantly promoting the skin penetration and retention of active ingredients. The biomimetic liposomes encapsulate a complex of cyclodextrin and the active ingredient as a core within the biomimetic liposomes. This is not a simple physical encapsulation, but rather constitutes a dual barrier and controlled release system of "molecular-level inclusion (cyclodextrin) - nano-level encapsulation (liposomes)," working synergistically to fundamentally inhibit volatilization and rapid release.

[0015] 2. The biomimetic liposomes provided by this invention not only provide a physical barrier, but their specific lipid components (such as ceramides) also have the effect of repairing the skin barrier, and can exert a synergistic therapeutic effect with the encapsulated functional active ingredients (such as anti-aging and analgesic essential oils).

[0016] 3. The biomimetic liposome preparation method provided by this invention involves core pre-assembly and nano-sizing, pre-forming cyclodextrin inclusion complexes, which solves the problem of difficulty in direct water dispersion of essential oils. Subsequently, it disperses the liposomes in the aqueous phase to the nanoscale (50-80 nm) using probe ultrasound, laying the foundation for the uniform assembly of subsequent liposomes. Precise assembly and particle size control: Using the ethanol injection method, combined with the combination of "probe ultrasound" and "membrane extrusion" technology, the particle size of the final liposomes is precisely controlled at 170±12 nm, with a PDI<0.20. This particle size range is considered to have the best balance in skin delivery.

[0017] 4. The biomimetic liposomes provided by this invention have the following advantages: Exceptional stability: A dual protection mechanism greatly reduces the volatilization and oxidative degradation of active ingredients; Significant sustained-release effect: The active ingredient must overcome the constraints of the cyclodextrin cavity and the lipid bilayer before it can be released, thus achieving a long-lasting effect; Highly efficient skin delivery: The biomimetic membrane design makes it easy for liposomes to integrate with the stratum corneum of the skin, promoting the transdermal absorption and targeted retention of active ingredients; Synergistic enhancement of efficacy: The biomimetic lipid components and the encapsulated active ingredients work together to achieve a "1+1>2" effect in anti-aging, skin repair, and pain management. Detailed Implementation

[0018] The present invention will be further described in detail below through specific embodiments, but the scope of protection of the present invention is not limited thereto.

[0019] Example 1 A biomimetic liposome for anti-aging compound essential oils (i.e., an essential oil delivery system based on biomimetic liposomes) is prepared as follows: (1) Active ingredients: Formulate an anti-aging compound essential oil mainly composed of frankincense, sandalwood and rose essential oil.

[0020] (2) Preparation of inclusion complex: 3.6000 g of HP-β-CD (hydroxypropyl-β-cyclodextrin) was accurately weighed and the essential oil inclusion complex was prepared by temperature-controlled kinetic addition. After precipitation, centrifugation, washing and drying, the lyophilized powder of the inclusion complex was obtained.

[0021] (3) Preparation of biomimetic liposomes: Accurately weigh each lipid component, as follows: HSPC (hydrogenated soybean lecithin) 117.0mg, plant-derived cholesterol 46.2mg, ceramide AP 8.7mg, ceramide NP 8.9mg, phytosphingosine 2.9mg, β-sitosterol 12.4mg, α-tocopherol 2.2mg, oleic acid 0.5mg.

[0022] The above lipid mixture was dissolved in 10 mL of anhydrous ethanol to obtain the lipid ethanol phase. 250.0 mg of the lyophilized inclusion complex powder prepared in step (2) was weighed, dispersed in 80 mL of PBS, and subjected to probe sonication (power 200-300 W) in pulse mode, with the temperature controlled below 25 °C, until the particle size was 71 nm. The lipid ethanol phase was rapidly injected, and after vortex mixing, magnetic stirring, conditional probe sonication (power 150-250 W), and membrane (polycarbonate membrane, pore size 200 nm) extrusion, the initial liposomes were obtained.

[0023] (4) Purification and quality control: After purification using ultrafiltration tubes, DLS analysis showed that the final liposome particle size was 169 nm and the PDI was 0.17. In vitro release experiments showed that it had obvious sustained-release characteristics.

[0024] Example 2 A biomimetic liposome for pain management compound essential oils (i.e., an essential oil delivery system based on biomimetic liposomes) is prepared as follows: Active ingredient: A compound essential oil formulated with wintergreen, peppermint and lavender essential oils as the main components.

[0025] The other preparation process is the same as in Example 1.

[0026] Quality control and efficacy verification: The final liposome particle size was 172 nm, and the PDI was 0.19.

[0027] Animal model experiments showed that, compared with free essential oils and single inclusion complexes, the pain management compound essential oil biomimetic liposomes prepared in this invention can significantly prolong the analgesic time and reduce local irritation.

[0028] Comparative Example 1 Only HP-β-CD / essential oil inclusion complexes were prepared; liposome encapsulation was not performed.

[0029] Stability test: The biomimetic liposomes prepared in Example 1 and the inclusion complex powder prepared in Comparative Example 1 were stored at 40°C under accelerated conditions for 4 weeks. The results showed that the retention rate of characteristic components in the inclusion complex of Comparative Example 1 was 65%, while the retention rate of characteristic components in the biomimetic liposomes prepared in Example 1 was as high as 92%, demonstrating the additional stabilizing effect provided by the biomimetic liposome shell.

[0030] The biomimetic liposome delivery system provided by this invention can significantly reduce the volatility of active ingredients, improve their stability, and achieve sustained release and synergistic permeation enhancement, thereby greatly enhancing their effects in anti-aging, analgesia and other applications.

Claims

1. A biomimetic liposome delivery system, characterized in that, Its membrane material contains components similar to lipids in the stratum corneum of the skin, and its interior encapsulates inclusion complexes formed by cyclodextrin and volatile active ingredients.

2. The biomimetic liposome delivery system as described in claim 1, characterized in that, The volatile active ingredients are selected from plant essential oils or their active components that have anti-aging, analgesic, anti-inflammatory or soothing effects.

3. The biomimetic liposome delivery system as described in claim 1, characterized in that, The membrane material contains hydrogenated soybean lecithin, cholesterol, ceramide, phytosphoprotein, phytosterol, and antioxidants.

4. The biomimetic liposome delivery system as described in claim 3, characterized in that, The composition of the membrane material, by weight, includes the following: 110-120 parts hydrogenated soybean lecithin, 40-50 parts cholesterol, 15-20 parts a mixture of ceramides AP and NP, 2-4 parts phytosphingosine, 10-15 parts β-sitosterol, 2-3 parts α-tocopherol and 0.4-1 parts oleic acid.

5. The biomimetic liposome delivery system as described in claim 1, characterized in that, The biomimetic liposomes have a particle size of 150-200 nm and a polydispersity index (PDI) of less than 0.

20.

6. A method for preparing the biomimetic liposome delivery system according to any one of claims 1-5, characterized in that, Includes the following steps: a. Preparation of active ingredient inclusion complexes: Lyophilized powder of cyclodextrin-active ingredient inclusion complexes was prepared by a kinetic temperature-controlled dropwise addition method; b. Preparation of the liposome organic phase: Hydrogenated soybean lecithin, cholesterol, ceramide, phytosphoprotein, β-sitosterol, α-tocopherol and oleic acid are dissolved in an organic solvent to form an organic phase; c. Dispersing the aqueous phase: The lyophilized powder of the inclusion complex obtained in step a is dispersed in a buffer solution and subjected to ultrasonic treatment with a probe to form a nanoscale dispersion; d. Assemble biomimetic liposomes: Inject the organic phase obtained in step b into the aqueous dispersion obtained in step c, mix, and then perform magnetic stirring, conditional probe sonication, and membrane extrusion in sequence to obtain the first generation of liposomes; e. Purification: The primary liposomes obtained in step d are purified to obtain a biomimetic liposome delivery system.

7. The preparation method according to claim 6, characterized in that, In step c, the ultrasonic power of the probe is 200-300W, a pulse mode is used, and the temperature is controlled below 25℃ so that the particle size of the inclusion mixture dispersion reaches 50-80 nm.

8. The preparation method according to claim 6, characterized in that, In step d, the ultrasonic power of the condition probe is 150-250W, and the process is pulsed; the membrane extrusion uses a polycarbonate membrane with a pore size of 200 nm.