A kind of oil-in-oil microcapsule loaded with guaiacylamine and its preparation method and application

Abstract

The invention discloses an oil-in-oil microcapsule loaded with guaiazulene and a preparation method and application thereof, and belongs to the technical field of cosmetics. The composition of the oil-in-oil microcapsule of the invention includes guaiazulene, liquid lipids, ceramides, phytosterol esters, waxes, surfactants and solid lipids. The oil-in-oil microcapsule of the invention utilizes the synergistic antioxidant effect of liquid lipids and guaiazulene and the physical barrier effect of the dense lipid capsule shell formed by waxes and solid lipids, and the dual effects synergize to improve the stability of guaiazulene; and the lipid capsule shell of the microcapsule has strong skin affinity with the skin, and can promote the penetration of the microcapsule and the guaiazulene therein in the skin through the fusion effect with the lipids of the skin stratum corneum, and further exert the efficacy of guaiazulene in the skin.

Description

Technical Field

[0001] The present invention relates to the technical field of cosmetics, and in particular to an oil-in-oil microcapsule loaded with guaiacylglycerol and a preparation method and application thereof. Background Art

[0002] Guaiazulene, also known as guaiazulene (chemical name 1,4-dimethyl-7-isopropylazulene), is a blue-black crystalline hydrocarbon from natural plants. Guaiazulene can be used as an adjuvant in cosmetics to relieve skin irritation and allergic reactions caused by other substances. It is a common topical antiallergic agent. It also has obvious anti-inflammatory function and is used in sunscreen products to prevent or treat sunburn. It is also antibacterial. Adding 0.1% to oral hygiene products can inhibit microorganisms. It can also be used as a cosmetic pigment and has good application prospects. However, guaiazulene has defects such as poor water solubility and light sensitivity, which limits its application in cosmetics.

[0003] At present, the above problems of other similar fat-soluble active ingredients in cosmetics are mainly solved by constructing encapsulation and transportation carriers. Commonly used encapsulation systems include: oil-in-water emulsions, liposomes, microcapsule powders, etc. However, looking at the above carriers, their common point is that they all use water-soluble interface shells to encapsulate fat-soluble active ingredients. Most of these carriers have the problem that the interface shell is not dense and the active ingredients are prone to leakage. Summary of the invention

[0004] In view of the shortcomings of the prior art, the present invention provides an oil-in-oil microcapsule loaded with guaiaczulene and a preparation method and application thereof. The present invention improves the stability of guaiaczulene through the preparation of the oil-in-oil microcapsule, and promotes the penetration of the system in the skin, so that guaiaczulene can better exert its efficacy.

[0005] The technical solution of the present invention is as follows:

[0006] The first aspect of the present invention provides an oil-in-oil microcapsule loaded with guaiazulene, wherein the oil-in-oil microcapsule comprises, by mass percentage, 1-20% guaiazulene, 1-50% liquid lipid, 0-10% ceramide, 0-10% phytosterol ester, 1-35% wax, 0.1-15% surfactant, and 1-35% solid lipid.

[0007] Furthermore, the mass ratio of the wax to the solid lipid is 3:10 to 1.2:1.

[0008] Furthermore, the liquid lipids include one or more of egg yolk oil, camellia seed oil, echium seed oil, avocado oil, calendula oil, comfrey oil, sea buckthorn fruit oil, milk thistle seed oil, elderberry oil, moringa seed oil, evening primrose oil, perilla seed oil, and bridgeberry oil; the ceramides include one or more of ceramide I, ceramide II, ceramide III, ceramide IV, and ceramide VI.

[0009] Furthermore, the phytosterol esters include one or more of phytosterol oleate, phytosterol isostearate, phytosterol rice bran oleate, phytosterol sunflower seed oleate, phytosterol caprylate / caprate, phytosterol macadamia oleate, phytosterol rapeseed oleate, and phytosterol stearate.

[0010] Furthermore, the wax includes one or more of channa dahlia wax, carnauba wax, candelilla wax, beeswax, lanolin wax, rice bran wax, raspberry leaf wax, narcissus wax, jojoba seed wax, and sunflower seed wax.

[0011] Further, the surfactant includes one or more of polyglyceryl-3 beeswax, sorbitol polyether-20 beeswax, N-palmitoyl hydroxyproline cetyl ester, dioctyldodecyl lauroyl glutamate, polyglyceryl-6-dioleate, polyglyceryl-6-distearate, polyglyceryl-10-dioleate, polyglyceryl-10-dilaurate, dioctyldodecyl lauroyl glutamate, distearyl alcohol polyether-5 lauroyl glutamate, di(octyldodecyl polyether-2) lauroyl glutamate, and di(octyldodecyl polyether-5) lauroyl glutamate.

[0012] Furthermore, the solid lipids include one or more of palmitic acid triglyceride, cetyl palmitate, glyceryl monostearate, glyceryl monolaurate, and glyceryl distearate.

[0013] The second aspect of the present invention provides a method for preparing the oil-in-oil microcapsule described in the first aspect, the preparation method comprising the following steps:

[0014] S1: According to the mass percentage, 1-20% guaiazulene and 1-50% liquid lipid are mixed and heated to dissolve to obtain oil phase A;

[0015] S2: 0.01-10% ceramide, 0-10% phytosterol ester, 1-35% wax, 0-15% surfactant, and 1-35% solid lipid are mixed, heated and dissolved to obtain oil phase B, and the heating is continued;

[0016] S3: Pumping the oil phase A and the oil phase B into the channels of the coaxial microfluidic chip respectively, so that the oil phase B covers the oil phase A to form microbeads, and cooling the microbeads in an ice bath to obtain oil-in-oil microcapsules in which the oil phase B covers the oil phase A.

[0017] Furthermore, in step S1, the heating temperature is 45-60°C; in step S2, the heating temperature is 75-90°C; in step S3, the pumping flow rate of the oil phase A is 3-7 µL / min and the pumping flow rate of the phase B is 12-18 µL / min.

[0018] The third aspect of the present invention provides an application of the oil-in-oil microcapsule described in the first aspect, or an application of the oil-in-oil microcapsule prepared by the preparation method described in the second aspect, wherein the oil-in-oil microcapsule is used in cosmetics.

[0019] The beneficial technical effects of the present invention are:

[0020] (1) In order to solve the problem that the interface of most water-soluble oil-in-shell carriers is not dense and the active ingredients are prone to leakage, the present invention adopts solid lipid shells to encapsulate oil-soluble active ingredients. However, the traditional process cannot achieve the preparation of the carrier. The present invention uses microfluidic technology and a reasonable combination of internal and external oil phases and external surfactants to obtain guaiacyl oil-in-oil microcapsules that can be dispersed in water phase and have a particle size distribution of 1-50 μm.

[0021] (2) The oil-in-oil microcapsules prepared by the present invention can help inhibit the oxidative degradation of guaiazulene in the carrier during storage through the dense capsule shell formed by wax and solid lipids in the outer oil phase and the inherent antioxidant effect of liquid oil in the inner oil phase, thereby improving its storage stability. In addition, the ceramide and phytosterol esters in the outer oil shell have good compatibility with the lipids in the stratum corneum of the skin, and can further promote the penetration of the system in the skin through the lipid fusion effect, thereby enabling guaiazulene to better exert its efficacy. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is an appearance diagram of guaiazulene microcapsules obtained in Examples 1, 2, and 3 of the present invention dispersed in water;

[0023] Among them, a, Example 1; b, Example 2; c, Example 3.

[0024] Figure 2 The figure shows the change in the average particle size of the guaiazulene microcapsules obtained in Examples 1, 2 and 3 of the present invention during storage at 45°C for one month.

[0025] Figure 3 The graph is a result of applying the microcapsules of Example 3 of the present invention and the solution of Comparative Example 8 to the release experiment.

[0026] Figure 4 The microcapsules of Example 3 and Example 12 of the present invention and the solution of Comparative Example 8 are applied to transdermal absorption.

[0027] Figure 5 A graph showing the change in the average moisture content of the stratum corneum of the skin of the test subject when the skin care cream prepared with the microcapsules prepared in Example 3 of the present invention was subjected to a stratum corneum moisture test.

[0028] Figure 6 A graph showing the change in the average value of the transepidermal water loss rate of the test subjects' skin when the skin care cream prepared with the microcapsules prepared in Example 3 of the present invention was tested for transepidermal water loss rate.

[0029] Figure 7 A graph showing the change in the average value of the skin erythema index (EI) of the subjects when the skin care cream prepared with the microcapsules prepared in Example 3 of the present invention was subjected to a skin erythema test.

[0030] Figure 8 A graph showing the change in the average percentage of facial red area of ​​the test subjects when the facial red area test was performed on the skin care cream prepared by the microcapsules prepared in Example 3 of the present invention.

[0031] Fig. 9 A graph showing the change in the total average lactic acid stinging score of the subjects when the skin care cream prepared by the microcapsules prepared in Example 3 of the present invention was subjected to a lactic acid stinging test.

[0032] Fig.10 Schematic diagram of the microfluidic chip of the present invention. DETAILED DESCRIPTION

[0033] The present invention is described in detail below in conjunction with the accompanying drawings and embodiments.

[0034] In view of the problem of the density of the existing coating structure, the present invention proposes to use a more dense solid lipid capsule shell to encapsulate the active substance. Furthermore, based on the traditional carrier preparation equipment, such as high-pressure homogenization, microfluidization, etc., due to its one-pot preparation method, all oil phases are mixed together, and the directional distribution of different oil phase substances at the interface and the inner oil phase cannot be achieved, so the preparation of oil-in-oil microcapsules cannot be achieved. Therefore, the present invention proposes to combine the microfluidic preparation technology, and through the control of the internal and external phase oils and surfactants, the oil-in-oil microcapsules of guaiacylglycerol are constructed, and the components contained in the outer oil phase are compatible with the lipids in the stratum corneum of the skin, which can further promote the penetration of the system in the skin, so that guaiacylglycerol can better exert its efficacy.

[0035] It is understandable that, in theory, the oil phase and the oil phase will be mixed together. In the present invention, wax is used as the external phase oil, and the wax is rapidly cooled in an ice bath to form a capsule shell. At the same time, good encapsulation is achieved by the selection of surfactants. The present invention has found that different surfactants in the wax determine whether the wax layer can well encapsulate the inner oil phase.

[0036] The first aspect of the present invention provides an oil-in-oil microcapsule loaded with guaiazulene. The oil-in-oil microcapsule comprises the following raw materials by mass percentage: 1-20% guaiazulene, 1-50% liquid lipid, 0-10% ceramide, 0-10% phytosterol ester, 1-35% wax, 0.1-15% surfactant, and 1-35% solid lipid.

[0037] The mass ratio of the wax to the solid lipid is 3:10 to 1.2:1, including but not limited to 3:10, 4:10, 6:10, 8:10, 1:1, 1.1:1, and 1.2:1.

[0038] The first aspect of the present invention provides an oil-in-oil microcapsule loaded with guaiazulene. The oil-in-oil microcapsule comprises the following raw materials by mass percentage: 1-20% guaiazulene, 1-50% liquid lipid, 0.01-10% ceramide, 0.01-10% phytosterol ester, 1-35% wax, 0.1-15% surfactant, and 1-35% solid lipid.

[0039] In some embodiments, the oil-in-oil microcapsules loaded with guaiazulene comprise the following raw materials, by mass percentage: 5-20% guaiazulene, 5-50% liquid lipids, 0.01-10% ceramides, 0.01-10% phytosterol esters, 1-35% waxes, 0.1-15% surfactants, and 1-35% solid lipids.

[0040] Preferably, the oil-in-oil microcapsules loaded with guaiazulene comprise the following raw materials, by mass percentage: 15% guaiazulene, 40% liquid lipids, 5% ceramides, 5% phytosterol esters, 10% waxes, 10% surfactants, and 15% solid lipids.

[0041] In some embodiments, the liquid lipid includes one or more of egg yolk oil, camellia seed oil, Echium plantain seed oil, avocado oil, calendula oil, comfrey oil, sea buckthorn fruit oil, milk thistle seed oil, elderberry oil, moringa seed oil, evening primrose oil, perilla seed oil, and bridge fruit oil. The liquid lipid used in the present invention can synergistically inhibit the oxidation of guaiazulene and improve its stability. Preferably, the liquid lipid used in the present invention is egg yolk oil, purchased from Zhuoke Biological (Hainan) Co., Ltd.

[0042] In some embodiments, the ceramide includes one or more of ceramide I, ceramide II, ceramide III, ceramide IV and ceramide VI. Preferably, the ceramide is ceramide III, which has a moderate molecular weight compared to other ceramides and can cooperate with other components to promote the penetration of microcapsules on the skin surface. It also has good stability and is not easily degraded during storage.

[0043] In some embodiments, the phytosterol ester includes one or more of phytosterol oleate, phytosterol isostearate, phytosterol rice bran oleate, phytosterol sunflower oleate, phytosterol caprylate / caprate, phytosterol macadamia oleate, phytosterol rapeseed oleate, and phytosterol stearate. Preferably, the phytosterol ester is phytosterol oleate, which has the characteristics of low melting point and easy addition compared to other phytosterol esters. It can be well soluble in ceramide in the preparation of microcapsules and co-oriented in the lipid capsule shell. Preferably, in the present invention, phytosterol oleate is purchased from Shanghai Meiyan Biotechnology Co., Ltd.

[0044] In some embodiments, the wax includes one or more of channa wax, carnauba wax, candelilla wax, beeswax, lanolin wax, rice bran wax, raspberry leaf wax, narcissus wax, jojoba seed wax, and sunflower seed wax. Preferably, the wax is carnauba wax, which has the characteristics of being able to quickly form a lipid capsule shell compared to other waxes, and can better protect guaiazulene in microcapsule preparation. Preferably, in the present invention, carnauba wax is purchased from FONCEPI, a Brazilian tree.

[0045] In some embodiments, the surfactant includes one or more of polyglyceryl-3 beeswax, sorbitol polyether-20 beeswax, N-palmitoyl hydroxyproline cetyl ester, dioctyldodecyl lauroyl glutamate, polyglyceryl-6-dioleate, polyglyceryl-6-distearate, polyglyceryl-10-dioleate, polyglyceryl-10-dilaurate, dioctyldodecyl lauroyl glutamate, distearyl alcohol polyether-5 lauroyl glutamate, di(octyldodecyl polyether-2) lauroyl glutamate, and di(octyldodecyl polyether-5) lauroyl glutamate. Preferably, the surfactant is polyglyceryl-3 beeswax and / or polyglyceryl-10-dioleate, and more preferably, the surfactant is preferably polyglyceryl-3 beeswax and / or polyglyceryl-10-dioleate, with a mass ratio of 1:1. Compared with other surfactants, it has the characteristics of being easy to quickly form an oil-in-oil microcapsule interface, which can be beneficial to the formation of a capsule shell of wax and solid lipids in microcapsule preparation, thereby effectively encapsulating liquid lipids. Preferably, in the present invention, polyglycerol-3 beeswax ester is purchased from Hubei Langbowan Biopharmaceutical Co., Ltd.

[0046] In some embodiments, the solid lipid includes one or more of palmitic acid triglyceride, cetyl palmitate, monostearic acid glyceryl, monolauric acid glyceryl, and distearic acid glyceryl. Preferably, the solid lipid is cetyl palmitate, which has the characteristics of moderate melting point compared with other solid lipids, and can cooperate with wax in microcapsule preparation to form a dense lipid network space to encapsulate guaiazulene. Preferably, in the present invention, cetyl palmitate is purchased from Shanghai Maitian Chemical Co., Ltd.

[0047] It is understandable that the dense capsule shell formed by the wax and solid lipids in the outer oil phase and the inherent antioxidant effect of the liquid oil in the inner oil phase of the oil-in-oil microcapsule jointly help inhibit the oxidative degradation of guaiazulene in the carrier during storage, thereby improving its storage stability. In addition, the ceramide and phytosterol esters in the outer oil shell have good compatibility with the lipids in the stratum corneum of the skin, and through the lipid fusion effect, the penetration of the system in the skin is further promoted, thereby enabling guaiazulene to better exert its efficacy.

[0048] The second aspect of the present invention provides a method for preparing the oil-in-oil microcapsule of the first aspect, comprising the following steps:

[0049] S1: According to the mass percentage, 1-20% guaiazulene and 1-50% liquid lipid are mixed and heated to dissolve to obtain oil phase A.

[0050] S2: 0-10% ceramide, 0-10% phytosterol ester, 1-35% wax, 0.1-15% surfactant, and 1-35% solid lipid are mixed, heated and dissolved to obtain oil phase B, and the heating is continued.

[0051] S3: Pumping the oil phase A and the oil phase B into the channels of the coaxial microfluidic chip respectively, so that the oil phase B covers the oil phase A to form microbeads, and cooling the microbeads in an ice bath to obtain oil-in-oil microcapsules in which the oil phase B covers the oil phase A.

[0052] In some embodiments, in step S1, the heating temperature is 45-60°C, including but not limited to 45°C, 50°C, 55°C, and 60°C.

[0053] In some embodiments, in step S2, the heating temperature is 75-90°C, including but not limited to 75°C, 80°C, 85°C, and 90°C.

[0054] In some embodiments, step S2 can also be to mix 0.01-10% ceramide, 0.01-10% phytosterol ester, 1-35% wax, 0.1-15% surfactant, and 1-35% solid lipid, heat and dissolve to obtain oil phase B, and continue heating.

[0055] In some embodiments, in step S3, the pumping flow rate of the oil phase A is 3-7 µL / min and the pumping flow rate of the phase B is 12-18 µL / min, including but not limited to 12 µL / min, 14 µL / min, 16 µL / min, 18 µL / min. In some embodiments, in step S3 of the present invention, cooling the microbeads in an ice bath means that the prepared microbeads are directly cooled in an ice bath after being formed in the microfluidic chip.

[0056] In some embodiments, the structure of the microfluidic chip is as follows: Fig.10 shown.

[0057] In some embodiments, the oil-in-oil microcapsule is an opaque uniform liquid with a particle size of 1 to 50 μm.

[0058] The third aspect of the present invention provides an application of the oil-in-oil microcapsule prepared by the oil-in-oil microcapsule of the first method or the oil-in-oil microcapsule prepared by the preparation method of the second aspect, that is, the oil-in-oil microcapsule is used in cosmetics.

[0059] The present invention will be further described below by way of examples and the like.

[0060] Example 1

[0061] An oil-in-oil microcapsule is composed of the following components: guaiazulene: 5g, egg yolk oil: 50g, ceramide III: 5g, phytosteryl oleate: 5g, carnauba wax: 10g, cetyl palmitate: 15g, polyglyceryl-3 beeswax acid ester: 5g, and polyglyceryl-10-dioleate: 5g.

[0062] The preparation method of oil-in-oil microcapsules is as follows:

[0063] S1: Mix guaiacyl ether and egg yolk oil, heat to 50°C to dissolve, and obtain oil phase A.

[0064] S2: Mix ceramide III, phytosteryl oleate, carnauba wax, polyglyceryl-3 beeswax ester, polyglyceryl-10-dioleate and cetyl palmitate, heat to 85°C to dissolve, obtain oil phase B, and continue heating.

[0065] S3: Adjust the flow rate of phase A to 5 μL / min and the flow rate of phase B to 15 μL / min, use a coaxial microfluidic chip to prepare microcapsules in which oil phase B encapsulates oil phase A, and quickly cool the microcapsules in an ice bath to obtain oil-in-oil microcapsules in which oil phase B encapsulates oil phase A.

[0066] Example 2

[0067] An oil-in-oil microcapsule is composed of the following components: 10g of guaiazulene, 45g of egg yolk oil, 5g of ceramide III, 5g of phytosteryl oleate, 10g of carnauba wax, 15g of cetyl palmitate, 5g of polyglyceryl-3 beeswax acid ester and 5g of polyglyceryl-10-dioleate.

[0068] The preparation method of oil-in-oil microcapsules is as follows:

[0069] S1: Mix guaiacyl ether and egg yolk oil, heat to 50°C to dissolve, and obtain oil phase A;

[0070] S2: Ceramide III, phytosteryl oleate, carnauba wax, polyglyceryl-3 beeswax ester, polyglyceryl-10-dioleate and cetyl palmitate are mixed, heated to 85°C to dissolve, and an oil phase B is obtained, and the heating is continued;

[0071] S3: Adjust the flow rate of phase A to 5 μL / min and the flow rate of phase B to 15 μL / min, use a coaxial microfluidic chip to prepare microcapsules of oil phase B encapsulating oil phase A, and quickly cool the microcapsules in an ice bath.

[0072] Example 3

[0073] An oil-in-oil microcapsule is composed of the following components: 15g of guaiazulene, 40g of egg yolk oil, 5g of ceramide III, 5g of phytosteryl oleate, 10g of carnauba wax, 15g of cetyl palmitate, 5g of polyglyceryl-3 beeswax acid ester and 5g of polyglyceryl-10-dioleate.

[0074] The preparation method of oil-in-oil microcapsules is as follows:

[0075] S1: Mix guaiacyl ether and egg yolk oil, heat to 50°C to dissolve, and obtain oil phase A;

[0076] S2: Ceramide III, phytosteryl oleate, carnauba wax, polyglyceryl-3 beeswax ester and polyglyceryl-10-dioleate are mixed, heated to 85°C to dissolve, and an oil phase B is obtained, and the heating is continued;

[0077] S3: Adjust the flow rate of phase A to 5 μL / min and the flow rate of phase B to 15 μL / min, use a coaxial microfluidic chip to prepare microcapsules of oil phase B encapsulating oil phase A, and quickly cool the microcapsules in an ice bath.

[0078] Figure 1 1 is an appearance diagram of the guaiazulene microcapsules obtained in Examples 1, 2, and 3 of the present invention dispersed in water. As can be seen from the appearance diagram, the change in the concentration of guaiazulene has no effect on the water phase dispersibility and appearance of the microcapsules. The particle size of the guaiazulene microcapsules obtained in Examples 1, 2, and 3 above was further measured using a particle size distribution instrument. The results are as follows: Figure 2 As shown in the figure, there is no significant difference in the particle size values, all of which are distributed around 25 μm. Moreover, the particle size of these three microcapsules did not change significantly when stored at 45°C for one month.

[0079] Example 4

[0080] It is basically the same as Example 3, except that the type of liquid lipid is changed. In Example 4, the liquid lipid is perilla seed oil, and the added amount is 40g.

[0081] Example 5

[0082] It is basically the same as Example 3, except that the type of liquid lipid is changed. In Example 4, the liquid lipid is Briech fruit oil, and the added amount is 40g.

[0083] Embodiment 6-9

[0084] It is basically the same as Example 3, except that the type of surfactant is changed. Among them, the surfactant in Example 6 is 5g of polyglyceryl-3 beeswax acid ester and 5g of di(octyl dodecanol polyether-2) lauroyl glutamate. The surfactant in Example 7 is 5g of polyglyceryl-3 beeswax acid ester and 5g of di(octyl dodecanol polyether-5) lauroyl glutamate. The surfactant in Example 8 is 5g of sorbitol polyether-20 beeswax and 5g of polyglyceryl-10-dioleate. The surfactant in Example 93 is 5g of polyglyceryl-6-dioleate and 5g of polyglyceryl-10-dioleate.

[0085] Embodiment 10-11

[0086] It is basically the same as Example 3, except that the amount of surfactant used is changed. In Example 10, the surfactant is 2.5g polyglycerol-3 beeswax acid ester and 2.5g polyglycerol-10-dioleate. In Example 11, the surfactant is 7g polyglycerol-3 beeswax acid ester and 7g polyglycerol-10-dioleate.

[0087] Example 12

[0088] The method is basically the same as Example 3, except that ceramide and phytosterol ester are not added, but the mass ratio of carnauba wax to cetyl palmitate is ensured to be 2:3.

[0089] Comparative Example 1-2

[0090] It is basically the same as Example 3, except that the type of liquid lipid is changed. The types of liquid lipids in Comparative Examples 1-2 are caprylic capric triglyceride and squalane, respectively, and the added amount is 40g.

[0091] Comparative Examples 3-7

[0092] It is basically the same as Example 3, except that the mass ratio of wax and solid lipid is changed. The ratios of carnauba wax and cetyl palmitate in Comparative Examples 3-7 are 0:5, 1:4, 3:2, 4:1 and 5:0, respectively.

[0093] Comparative Example 8

[0094] The unencapsulated guaiazulene / egg yolk oil solution is prepared by directly dissolving guaiazulene with a mass fraction of 15% in egg yolk oil, and heating and stirring at 50° C. to dissolve.

[0095] Test Case

[0096] Test Example 1

[0097] The guaiazulene microcapsules prepared in Example 3 were applied to the determination of the in vitro release curve and compared with the unencapsulated guaiazulene / egg yolk oil solution in Comparative Example 8, as follows:

[0098] The dialysis method was used: the samples of the embodiments and comparative examples to be tested were accurately weighed and placed in a pre-treated dialysis bag, and a phosphate buffer solution (pH 7.4) with 1% Tween 80 added was used as the release medium. The samples were shaken in a constant temperature shaker at 37°C, and 1 mL of the dialysate was taken out from the dialysis bag at the end of 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 hours, respectively, and an equal amount of fresh dialysis medium was added at the same temperature. The samples were filtered through a microporous membrane and then the concentration of guaiazulene was determined by HPLC. The results are shown in FIG. Figure 3 As shown in the figure, the guaiazulene microcapsules have a good controlled release effect compared with the unencapsulated guaiazulene / egg yolk oil solution.

[0099] Test Example 2

[0100] The encapsulation efficiency was used to evaluate the encapsulation performance of the microcapsules of the embodiments and comparative examples on guaiazulene, and the specific method was as follows: a certain amount of samples of the embodiments and comparative examples were taken, centrifuged at 11000 rpm for 40 min, the supernatant was taken, demulsified with ethanol, fixed to volume, and then filtered through an organic membrane (pore size 220 nm), and the guaiazulene content W1 was determined by high performance liquid chromatography; a certain amount of samples were taken, demulsified with ethanol, fixed to volume, and then filtered through an organic membrane (pore size 220 nm), and the guaiazulene content W2 was determined by high performance liquid chromatography, therefore, encapsulation efficiency (%) = W1×100% / W2; the results are shown in Table 1.

[0101] The storage stability of the microcapsules of the examples and comparative examples was evaluated by the retention rate. The specific method was as follows: the microcapsules prepared in the examples and comparative examples were stored at 45°C for 1 month, and then a certain amount of samples were taken to break the emulsions with ethanol, and the volume was fixed. Then, the samples were filtered with an organic membrane (pore size 220 nm), and the content of guaiazulene W3 was determined by high performance liquid chromatography. Therefore, the retention rate (%) = W3×100% / W2. The results are shown in Table 1.

[0102] Table 1 Encapsulation efficiency and retention rate of microcapsules prepared in Examples and Comparative Examples

[0103]

[0104] Test Example 3

[0105] The guaiazulene microcapsules prepared in Example 3 were applied to transdermal absorption and compared with the guaiazulene oil solution without entrapment in Comparative Example 8 and the carrier without ceramide and phytosterol ester added in Example 12, the method is as follows:

[0106] The Bama miniature pig skin was placed between the supply pool and the receiving pool of the Franzs diffusion cell, 1 g of unencapsulated guaiazulene / egg yolk oil solution containing the same guaiazulene concentration and the guaiazulene microcapsules in Example 1 were added to the supply pool, and the cells were placed in a transdermal diffusion tester, the temperature was controlled at 32°C, and the transdermal penetration was 12 h. After the transdermal penetration, the content of guaiazulene in the stratum corneum was determined by the tape stripping method: the stratum corneum of the Bama miniature pig skin was pasted with 3M tape, the first layer was discarded, and 20 layers were continued to be pasted; the guaiazulene was collected in a centrifuge tube, an extractant was added for extraction, and the content of guaiazulene was determined by HPLC, which was the content of guaiazulene in the stratum corneum.

[0107] The skin remaining after removing the stratum corneum by 21 layers of 3M tape was cut into pieces and collected in a centrifuge tube. The extractant was added for extraction, and the content of guaiacylceramide was determined by HPLC, which is the content of guaiacylceramide in the vital epidermis and dermis.

[0108] The results are as follows Figure 4 As shown, the results of applying the guaiazulene microcapsules and guaiazulene oil solutions obtained in Example 3, Example 12 and Comparative Example 8 of the present invention to transdermal absorption show that the guaiazulene microcapsules and guaiazulene oil solutions can effectively promote the transdermal delivery of guaiazulene after being encapsulated in the microcapsules.

[0109] Test Example 4

[0110] The guaiazulene microcapsules in Example 3 were further added to the skin care cream to prepare an emulsion cream containing 2% guaiazulene microcapsules, and 33 subjects were selected, including 16 females and 17 males, with an age range of 22-40 years old. The subjects took an appropriate amount of cream and applied it evenly on the face in the morning and evening according to the instructions, massaged slightly until absorbed, and used the test sample for 28 consecutive days. The sensory score of lactic acid stinging before using the sample (D0), 14 days after using the sample (D14), and 28 days after using the sample (D28) was evaluated, and the changes in the moisture content of the stratum corneum (using a skin moisture loss meter Corneometer® CM825), the transepidermal moisture loss rate of the skin (using a skin moisture loss meter Tewameter® TM Hex), the erythema index (using a skin melanin and hemoglobin tester Mexameter MX 18) and the facial red area (using a facial image analyzer Visia-CR) were evaluated to evaluate whether the test sample had a repairing and soothing effect. The results are presented as the average value of 33 subjects, and the data between different days are tested at a significance level of ɑ=0.05. If there is a significant difference in the test results before and after the sample is used (P<0.05), it is considered that the sample has a corresponding efficacy in the test area.

[0111] The results of the moisture content of the skin stratum corneum are as follows Figure 5As shown, after 14 days of use, the moisture content of the skin in the test area was significantly improved, and the measured value reached 46.08CU, which was 11.2% higher than D0; after 28 days of use, the moisture content of the skin in the test area was significantly improved compared with 0D, and the measured average value reached 48.45CU, which was 16.91% higher than D0.

[0112] The results of transepidermal water loss rate are as follows Figure 6 As shown in Figure 2, after 14 days of use, the transepidermal water loss of the test area was significantly improved, with the average value dropping to 17.85 g / h / m 2 , which was 16.93% lower than that on day 0; after 28 days of use, the transepidermal water loss of the skin in the test area was significantly improved, with the average value dropped to 15.945 g / h / m 2 , down 25.82% from day 0.

[0113] The results of the skin erythema index are as follows Figure 7 As shown, after 14 days of use, the erythema index of the test area was significantly reduced, and the measured average value dropped to 446.37, which was 3.7% lower than that of day 0; after 28 days of use, the erythema index of the test area was improved very significantly, and the measured average value dropped to 440.55, which was 5% lower than that of day 0.

[0114] The results of facial red area ratio are as follows Figure 8 The results show that the red zone area ratio in the test area did not decrease significantly after 14 days of use, but decreased significantly after 28 days of continuous use, down 9.22% from day 0.

[0115] The results of the sum of lactic acid sting scores are as follows Fig. 9 As shown, the lactic acid stinging score was significantly reduced after 28 days of use, down 36.38%.

[0116] The present invention uses microfluidic technology to innovatively encapsulate guaiac in a lipid capsule shell, and the oil in the lipid capsule shell has a good affinity with the oil in the stratum corneum of human skin, which can promote the transdermal penetration of the lipid carrier in the skin, further bring guaiac into the skin, and play a corresponding soothing and repairing effect.

[0117] The above is only a preferred embodiment of the present invention, and the present invention is not limited to the above embodiments. It is understood that other improvements and changes directly derived or associated by those skilled in the art without departing from the spirit and concept of the present invention should be considered to be included in the protection scope of the present invention.

Claims

1. An oil-in-oil microcapsule loaded with guaiazulene, characterized in that: The oil-in-oil microcapsule comprises, by mass percentage, 1-20% guaiazulene, 1-50% liquid lipid, 0.01-10% ceramide, 0.01-10% phytosterol ester, 1-35% wax, 0.1-15% surfactant, and 1-35% solid lipid; The mass ratio of the wax to the solid lipid is 3:10 to 1.2:1; The liquid lipids include one or more of egg yolk oil, perilla seed oil, and bridge fruit oil; The ceramide includes one or more of ceramide I, ceramide II, ceramide III, ceramide IV and ceramide VI; The phytosterol esters include one or more of phytosterol oleate, phytosterol isostearate, phytosterol rice bran oleate, phytosterol sunflower oleate, phytosterol caprylate / caprate, phytosterol macadamia oleate, phytosterol rapeseed oleate, and phytosterol stearate; The wax includes one or more of channa dahlia wax, carnauba wax, candelilla wax, beeswax, lanolin wax, rice bran wax, raspberry leaf wax, narcissus wax, jojoba seed wax, and sunflower seed wax; The surfactant includes one or more of polyglyceryl-3 beeswax, sorbitol polyether-20 beeswax, N-palmitoyl hydroxyproline cetyl ester, polyglyceryl-6-dioleate, polyglyceryl-6-distearate, polyglyceryl-10-dioleate, polyglyceryl-10-dilaurate, dioctyldodecyl lauroyl glutamate, distearyl alcohol polyether-5 lauroyl glutamate, di(octyldodecyl polyether-2) lauroyl glutamate, and di(octyldodecyl polyether-5) lauroyl glutamate; The solid lipids include one or more of palmitic acid triglyceride, cetyl palmitate, monostearic acid glyceryl, monolauric acid glyceryl, and distearic acid glyceryl; The method for preparing the oil-in-oil microcapsule comprises the following steps: S1: According to the mass percentage, 1-20% guaiazulene and 1-50% liquid lipid are mixed and heated to dissolve to obtain oil phase A; S2: 0.01-10% ceramide, 0.01-10% phytosterol ester, 1-35% wax, 0.1-15% surfactant, and 1-35% solid lipid are mixed, heated and dissolved to obtain oil phase B, and the heating is continued; S3: Pumping the oil phase A and the oil phase B into the channels of the coaxial microfluidic chip respectively, so that the oil phase B covers the oil phase A to form microbeads, and cooling the microbeads in an ice bath to obtain oil-in-oil microcapsules in which the oil phase B covers the oil phase A; In step S3, the pumping flow rate of the oil phase A is 3-7 µL / min and the pumping flow rate of the phase B is 12-18 µL / min.

2. The preparation method according to claim 1, characterized in that: The mass ratio of the wax to the solid lipid is 2:

3.

3. The guaiazulene-loaded oil-in-oil microcapsules according to claim 1, characterized in that: In step S1, the heating temperature is 45-60°C; in step S2, the heating temperature is 75-90°C.

4. An application of the oil-in-oil microcapsule according to any one of claims 1 to 3, characterized in that: The oil-in-oil microcapsule is used in cosmetics.

Images