A eutectic microcapsule encapsulation technology and its application in cosmetics

Abstract

The present invention relates to a eutectic microcapsule encapsulation technology and its application in cosmetics, belonging to the technical field of cosmetics production. The wall materials of the eutectic microcapsule encapsulates of the present invention include at least one of hydrogenated lecithin, caprylic / capric triglyceride, sucrose stearate, PEG-8 caprylic / capric glycerides, PEG-40 hydrogenated castor oil, soy lecithin, cyclodextrin, ethyl palmitate, and troxerutin; the core materials include at least one of salicylic acid, 4-butylresorcinol, glabridin, kava extract, magnolol, ginseng oil, ganoderma spore oil, astaxanthin, coenzyme Q-10, rosemary extract, ceramide, and vitamin E. The present invention can not only form multiple eutectic encapsulations, but also reduce the dosage of the wall materials, saving costs. At the same time, the combination of the wall materials and the core materials can achieve excellent effects of penetration, antioxidant, soothing and anti-allergic, and skin repair, improving the utilization rate of active substances.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics production, and particularly relates to a eutectic microcapsule encapsulation technology and its application in cosmetics. Background Art

[0002] Due to the increasingly diverse and refined demands of modern consumers for cosmetics, in the field of cosmetics, continuously pursuing innovation and excellent technologies to improve the performance and effects of products is an eternal theme of industry development.

[0003] Traditional cosmetic formulations often face problems such as poor stability of active ingredients, easy inactivation, low transdermal absorption efficiency, and strong irritation. These problems greatly limit the efficacy of cosmetics and the user experience of consumers. For example, many active ingredients with antioxidant, soothing, repairing, anti-aging and other effects are easily oxidized and decomposed under the influence of external environmental factors (such as light, temperature, oxygen), thus losing their activity. In addition, the molecular weights of these active ingredients are relatively large, making it difficult to penetrate the skin barrier, resulting in insufficient effective concentration in the skin and affecting the actual effect of the product. To solve these problems, scientific researchers have conducted a large number of studies and explorations, and the microcapsule encapsulation technology has emerged. Early microcapsule encapsulation technologies mainly used liposomes, polymer nanoparticles, etc. as carriers, but these technologies have certain limitations in terms of stability, drug loading capacity, controlled release performance, etc.

[0004] Therefore, a more advanced technology developed on the basis of traditional microcapsule technology, namely the eutectic microcapsule encapsulation technology. Eutectic refers to a crystal formed by two or more substances under specific conditions with specific structures and properties. In the eutectic microcapsule encapsulation technology, the active ingredient and a suitable carrier material form a microcapsule structure through eutectic action. Currently, the existing eutectic microcapsule encapsulation technology still has problems such as incompatibility, uneven effects in terms of stability, absorbability, irritation mitigation, etc. It is necessary to select appropriate carrier materials and preparation processes according to different active ingredients and product requirements to achieve simultaneous encapsulation of multiple active ingredients and good synergistic effects. Summary of the Invention

[0005] Aiming at the problems of incompatibility, uneven effects in terms of stability, absorbability, irritation mitigation, etc. existing in the existing eutectic microcapsule encapsulation technology, it is necessary to continuously develop and improve more suitable eutectic microcapsules for different components. The specific technical solutions are as follows:

[0006] A eutectic microcapsule encapsulation technology, specifically a eutectic microcapsule encapsulant and / or a preparation method. The mass ratio of the core material to the wall material of the eutectic microcapsule encapsulant is core material:wall material = 100:(3 - 6); the wall material includes at least one of hydrogenated lecithin, caprylic / capric triglyceride, sucrose stearate, PEG-8 caprylic / capric glycerides, PEG-40 hydrogenated castor oil, soy lecithin, cyclodextrin, ethyl palmitate, and troxerutin; the core material includes at least one of salicylic acid, 4-butylresorcinol, glabridin, kava extract, magnolol, ginseng oil, ganoderma spore oil, astaxanthin, coenzyme Q-10, rosemary extract, ceramide, and vitamin E.

[0007] In the above technical solution, the wall material includes ethyl palmitate and troxerutin, and the wall material may also include at least one of hydrogenated lecithin, caprylic / capric triglyceride, sucrose stearate, PEG-8 caprylic / capric glycerides, PEG-40 hydrogenated castor oil, soy lecithin, and cyclodextrin. The core material includes rosemary extract, ceramide, and vitamin E, and the core material may also include at least one of salicylic acid, 4-butylresorcinol, glabridin, kava extract, magnolol, ginseng oil, ganoderma spore oil, astaxanthin, and coenzyme Q-10.

[0008] In the above technical solution, the ceramide is at least one of ceramide NP, ceramide NS, ceramide NG, ceramide AS, ceramide EOP, and ceramide AP.

[0009] In the above technical solution, the rosemary extract is an extract with a molecular weight below 3 kDa obtained by co-enzymolysis of rosemary stems and leaves with hemicellulase and pectinase, followed by co-fermentation with Bifidobacterium adolescentis and Clostridium butyricum.

[0010] In the above technical solution, the mass proportion of ethyl palmitate in the wall material is 50% - 60%; the mass proportion of troxerutin in the wall material is 10% - 20%.

[0011] In the above technical solution, the preparation method of the wall material includes the following steps: dissolving the components of the wall material in an ethanol aqueous solution at 50°C - 60°C, stirring evenly to form a wall material system, and removing ethanol and water by negative pressure distillation to obtain the wall material.

[0012] In the above technical solution, the dosage of the ethanol aqueous solution is 15 - 20 times the mass of the wall material; the ethanol volume concentration of the ethanol aqueous solution is 30% - 40%.

[0013] In the above technical solution, the parameters of the negative pressure distillation are: vacuum degree 0.07 MPa - 0.08 MPa, temperature 60°C - 70°C.

[0014] In the above technical solution, the mass ratio of the rosemary extract in the core material is 70% - 80%; the mass ratio of the ceramide in the core material is 0.5% - 3%; the mass ratio of the vitamin E in the core material is 5% - 10%.

[0015] In the above technical solution, the preparation method of the eutectic microcapsule wrapping includes the following steps: dispersing the wall material in an ethanol aqueous solution (ethanol concentration of 30 - 40wt%), forming a dispersion liquid, heating to 45°C - 55°C, adding the core material to the dispersion liquid to form a composite liquid, and repeatedly pressure-filtering the composite liquid through a 0.03μm - 0.05μm filter membrane 3 - 5 times to obtain an eutectic microcapsule wrapping liquid; freeze-drying the eutectic microcapsule wrapping liquid to obtain the eutectic microcapsule wrapping.

[0016] In the above technical solution, the preparation method of the rosemary extract includes the following steps: taking rosemary stems and leaves, crushing them, adding 8 - 10 times the mass of water of the rosemary stems and leaves, adjusting the pH to 5.0 - 5.5 with a hydrochloric acid aqueous solution, adding 0.5% - 1.0% of the mass of the rosemary stems and leaves of hemicellulase and pectinase respectively, enzymolyzing at 45°C - 55°C for 2h - 3h, inactivating the enzyme at high temperature, cooling to room temperature, adjusting the pH to 6.5 - 7.0 with a sodium hydroxide aqueous solution, adding glucose and dipotassium hydrogen phosphate, then adding 0.3% - 0.5% of the mass of the rosemary stems and leaves of Bifidobacterium adolescentis and Clostridium butyricum respectively, anaerobically fermenting at 35°C - 40°C for 15h - 20h, sterilizing at high temperature, cooling to room temperature, adding 3 - 4 times the mass of anhydrous ethanol of the rosemary stems and leaves, extracting for 1h - 2h, then filtering with a 3kDa ultrafiltration membrane to obtain an ultrafiltrate below 3kDa, concentrating and drying to obtain the rosemary extract.

[0017] In the above preparation method of the rosemary extract, the enzyme activity of the hemicellulase is 50,000 U / g - 100,000 U / g; the enzyme activity of the pectinase is 50,000 U / g - 100,000 U / g; the addition amount of glucose is 1.5% - 2.5% of the mass of the rosemary stems and leaves; the addition amount of dipotassium hydrogen phosphate is 0.1% - 0.3% of the mass of the rosemary stems and leaves; the viable count of Bifidobacterium adolescentis is 5 - 10 billion CFU / g; the viable count of Clostridium butyricum is 5 - 10 billion CFU / g; the temperature for inactivating the enzyme at high temperature is 85°C - 95°C, and the time is 15min - 25min; the temperature for sterilizing at high temperature is 121°C - 125°C, and the time is 15min - 20min; the concentration of the hydrochloric acid aqueous solution is 0.5mol / L - 0.8mol / L; the concentration of the sodium hydroxide aqueous solution is 0.5mol / L - 0.8mol / L.

[0018] The eutectic microcapsule wrapping prepared by the above eutectic microcapsule wrapping technology is used for preparing cosmetics.

[0019] A eutectic microcapsule encapsulation technology provided by the present invention and its application in cosmetics have the following beneficial effects compared with the prior art:

[0020] First, the core material of the eutectic microcapsule encapsulation of the present invention includes active ingredients such as rosemary extract, and the wall material contains ingredients such as ethyl palmitate, troxerutin, and hydrogenated lecithin. The present invention selects the wall material and the core material to produce a eutectic effect and achieve eutectic encapsulation; the various components of the wall material and the core material are used in a certain proportion, which can achieve better eutectic microcapsule encapsulation, can well enhance the transdermal absorption ability of the active ingredient, and reduce the irritation of the active ingredient. It enables the rosemary extract to achieve good antioxidant, soothing and anti-allergic, and skin repair effects.

[0021] Second, the rosemary extract is an extract below 3 kDa obtained by co-enzyme hydrolysis of rosemary stems and leaves with hemicellulase and pectinase, and then co-fermentation with Bifidobacterium adolescentis and Clostridium butyricum. Adding hydrochloric acid aqueous solution and using hemicellulase and pectinase for co-enzyme hydrolysis can promote the leaching of proteins and improve the bioavailability. Fermentation with Bifidobacterium adolescentis and Clostridium butyricum can obtain rich functional substances, including active substances such as amino acids and small molecular peptides, which can well improve the antioxidant, soothing and anti-allergic, and skin repair effects.

[0022] Third, wall materials such as hydrogenated lecithin, caprylic / capric triglyceride, sucrose stearate, PEG-8 caprylic / capric glycerides, PEG-40 hydrogenated castor oil, soy lecithin, and cyclodextrin are used as coating materials, which have a moisturizing effect, can form a protective film on the skin surface to prevent water loss and maintain the skin's moisture; moisten the skin, help improve the dry and rough condition of the skin, and make the skin smoother and more delicate; enhance the skin barrier function, can repair the damaged skin barrier, and improve the skin's resistance to external stimuli.

[0023] Fourth, ceramide (core material) can moisturize and lock water, has a strong ability to associate with water molecules, can form a network structure in the skin stratum corneum, firmly lock water; has a good repair effect on the damaged skin barrier, enhances the skin's resistance, and reduces the intrusion of external harmful substances; helps to maintain the normal physiological function of the skin and relieve skin sensitivity, flushing and other problems.

[0024] Fifth, vitamin E (core material) can effectively scavenge free radicals, slow down the process of skin aging, reduce the generation of wrinkles and spots; has a certain moisturizing effect, makes the skin keep soft and elastic; helps to accelerate the healing of wounds and has a repair effect on damaged skin.

[0025] Sixth, ethyl palmitate, as a kind of oil component, can moisten the skin and make the skin smooth and soft; it can adjust the texture and touch of the product in cosmetics, making it easier to apply and absorb.

[0026] VII. Troxerutin can promote blood circulation in the skin, increase the skin's nutrient supply, and make the skin healthier and more radiant; it has a certain soothing and anti-allergic effect on sensitive skin and can relieve skin allergy symptoms.

[0027] The present invention forms a eutectic encapsulation, and the product has excellent effects. It can effectively reduce the dosage of the wall material, save costs, and at the same time, the combination of the wall material and the core material can achieve excellent effects of penetration, protection, antioxidant, soothing and anti-allergic, and skin repair, improve the utilization rate of active substances, and has good practical value. Detailed Embodiments

[0028] The present invention will be further described below in conjunction with specific implementation cases, but the present invention is not limited to these embodiments.

[0029] Example 1

[0030] A eutectic microcapsule encapsulant, in which the mass ratio of the core material to the wall material is core material:wall material = 100:4.5; the wall material includes PEG-40 hydrogenated castor oil, ethyl palmitate, and troxerutin; the core material includes ceramide, vitamin E, glabridin, and rosemary extract; among them, the ceramide is ceramide NP.

[0031] Among them, the mass proportion of ethyl palmitate in the wall material is 60%, the mass proportion of troxerutin in the wall material is 20%, and the balance is PEG-40 hydrogenated castor oil.

[0032] Among them, the mass proportion of ceramide in the core material is 3%, the mass proportion of vitamin E in the core material is 10%, the mass proportion of rosemary extract in the core material is 80%, and the balance is glabridin.

[0033] The preparation method of the wall material includes the following steps: Dissolve the components of the wall material in an ethanol aqueous solution at 55°C. The dosage of the ethanol aqueous solution is 18 times the mass of the wall material, and the ethanol volume concentration of the ethanol aqueous solution is 35%. Stir evenly to form a wall material system. Under the conditions of a vacuum degree of 0.06 MPa and a temperature of 65°C, remove ethanol and water by negative pressure distillation to obtain the wall material.

[0034] Among them, the preparation method of rosemary extract includes the following steps: Take rosemary stems and leaves, crush them, add water with a mass 9 times that of the rosemary stems and leaves, adjust the pH to 5.2 with a hydrochloric acid aqueous solution with a concentration of 0.6 mol / L, add hemicellulase and pectinase respectively accounting for 0.8% of the mass of the rosemary stems and leaves, enzymatically hydrolyze at 50 °C for 2.5 h, inactivate the enzyme at 90 °C for 20 min. After cooling to room temperature, adjust the pH to 6.8 with an aqueous solution of sodium hydroxide with a concentration of 0.6 mol / L, add glucose accounting for 2.0% of the mass of the rosemary stems and leaves and dipotassium hydrogen phosphate accounting for 0.2% of the mass of the rosemary stems and leaves, then add Bifidobacterium adolescentis and Clostridium butyricum respectively accounting for 0.4% of the mass of the rosemary stems and leaves, anaerobically ferment at 37 °C for 18 h, sterilize at 122 °C for 18 min. After cooling to room temperature, add absolute ethanol with a mass 3.5 times that of the rosemary stems and leaves, extract for 1.5 h, then filter with a 3 kDa ultrafiltration membrane to obtain an ultrafiltrate below 3 kDa, concentrate and dry to obtain rosemary extract.

[0035] In this example, the enzyme activity of the hemicellulase used is 100,000 U / g; the enzyme activity of the pectinase is 100,000 U / g; the viable count of Bifidobacterium adolescentis is 10 billion CFU / g; the viable count of Clostridium butyricum is 10 billion CFU / g;

[0036] The preparation method of the above eutectic microcapsule inclusion includes the following steps: Disperse the wall material in an ethanol aqueous solution (ethanol concentration 35 wt%) with a mass 10 times that of the wall material to form a dispersion, heat up to 50 °C, add the core material to the dispersion to form a composite liquid, and repeatedly press-filter the composite liquid through a 0.04 μm filter membrane 4 times to obtain an eutectic microcapsule inclusion liquid; freeze-dry the eutectic microcapsule inclusion liquid to obtain the eutectic microcapsule inclusion.

[0037] Example 2

[0038] A eutectic microcapsule encapsulation technology, the mass ratio of the core material to the wall material of the eutectic microcapsule inclusion is core material:wall material = 100:3; the wall material includes ethyl palmitate, troxerutin, PEG-8 caprylic / capric glycerides, and soy lecithin; the core material includes rosemary extract, ceramide, vitamin E, salicylic acid, and 4-butylresorcinol; among them, the ceramide is ceramide NS and ceramide NG in an equal mass ratio.

[0039] Among them, the mass proportion of ethyl palmitate in the wall material is 58%, the mass proportion of troxerutin in the wall material is 18%, and the balance is PEG-8 caprylic / capric glycerides and soy lecithin in an equal mass ratio.

[0040] Among them, the mass proportion of rosemary extract in the core material is 75%, the mass proportion of ceramide in the core material is 2%, the mass proportion of vitamin E in the core material is 8%, and the balance is salicylic acid and 4-butylresorcinol in an equal mass ratio.

[0041] The preparation method of the wall material comprises the following steps: Dissolve the components of the wall material in an ethanol aqueous solution at 50 °C. The dosage of the ethanol aqueous solution is 15 times the mass of the wall material, and the ethanol volume concentration of the ethanol aqueous solution is 30% - 40%. Stir evenly to form a wall material system. Under the conditions of a vacuum degree of 0.05 MPa and a temperature of 60 °C, remove ethanol and water by negative pressure distillation to obtain the wall material.

[0042] Among them, the preparation method of the rosemary extract comprises the following steps: Take rosemary stems and leaves and crush them. Add water with a mass 8 times that of the rosemary stems and leaves. Adjust the pH to 5.0 with a hydrochloric acid aqueous solution with a concentration of 0.5 mol / L. Respectively add hemicellulase and pectinase with a mass of 0.5% of the rosemary stems and leaves. Enzymatically hydrolyze at 45 °C for 2 h, inactivate the enzyme at 85 °C for 15 min. After cooling to room temperature, adjust the pH to 6.5 with an aqueous solution of potassium hydroxide with a concentration of 0.5 mol / L. Add glucose with a mass of 1.5% of the rosemary stems and leaves and dipotassium hydrogen phosphate with a mass of 0.1% of the rosemary stems and leaves. Then respectively add Bifidobacterium adolescentis and Clostridium butyricum with a mass of 0.3% of the rosemary stems and leaves. Anaerobically ferment at 35 °C for 15 h, sterilize at 121 °C for 15 min. After cooling to room temperature, add absolute ethanol with a mass 3 times that of the rosemary stems and leaves, extract for 1 h, then filter with a 3 kDa ultrafiltration membrane to obtain an ultrafiltrate below 3 kDa, concentrate and dry to obtain the rosemary extract.

[0043] In this example, the enzyme activity of the hemicellulase used is 50,000 U / g; the enzyme activity of the pectinase is 50,000 U / g; the viable count of Bifidobacterium adolescentis is 5 billion CFU / g; the viable count of Clostridium butyricum is 5 billion CFU / g;

[0044] The preparation method of the above eutectic microcapsule inclusion comprises the following steps: Disperse the wall material in an ethanol aqueous solution (ethanol concentration 38 wt%) with a mass 10 times that of the wall material to form a dispersion. Heat up to 45 °C, add the core material to the dispersion to form a composite liquid. Filter the composite liquid through a 0.03 μm filter membrane repeatedly for 3 times to obtain an eutectic microcapsule inclusion liquid; Freeze-dry the eutectic microcapsule inclusion liquid to obtain the eutectic microcapsule inclusion.

[0045] Example 3

[0046] A eutectic microcapsule encapsulation technology, the mass ratio of the core material to the wall material of the eutectic microcapsule inclusion is core material: wall material = 100:3.5; The wall material includes ethyl palmitate, troxerutin, hydrogenated lecithin, caprylic / capric triglyceride and sucrose stearate; The core material includes rosemary extract, ceramide, vitamin E, kava extract, magnolol, ginseng oil and ganoderma spore oil; Among them, the ceramide is a ceramide AS, ceramide EOP and ceramide AP with an equal mass ratio.

[0047] Among them, the mass ratio of ethyl palmitate in the wall material is 55%, the mass ratio of troxerutin in the wall material is 15%, and the balance is hydrogenated lecithin, triglyceride caprylate / caprate, and sucrose stearate with equal mass ratio.

[0048] Among them, the mass ratio of rosemary extract in the core material is 75%, the mass ratio of ceramide in the core material is 1%, the mass ratio of vitamin E in the core material is 6%, and the balance is kava extract, total magnolol, ginseng oil, and ganoderma spore oil with equal mass ratio.

[0049] The preparation method of the wall material includes the following steps: Dissolve the components of the wall material in an ethanol aqueous solution at 60°C. The dosage of the ethanol aqueous solution is 20 times the mass of the wall material, and the ethanol volume concentration of the ethanol aqueous solution is 30% - 40%. Stir evenly to form a wall material system. Under the conditions of a vacuum of 0.06 MPa and a temperature of 70°C, distill off ethanol and water under negative pressure to obtain the wall material.

[0050] Among them, the preparation method of rosemary extract includes the following steps: Crush rosemary stems and leaves, add water with a mass 10 times that of the rosemary stems and leaves, adjust the pH to 5.5 with a hydrochloric acid aqueous solution with a concentration of 0.8 mol / L. Add 1.0% of hemicellulase and pectinase based on the mass of the rosemary stems and leaves respectively, enzymatically hydrolyze at 55°C for 3 h, inactivate the enzyme at 95°C for 25 min. After cooling to room temperature, adjust the pH to 7.0 with a potassium hydroxide aqueous solution with a concentration of 0.8 mol / L. Add 2.5% of glucose and 0.3% of dipotassium hydrogen phosphate based on the mass of the rosemary stems and leaves. Then add 0.5% of Bifidobacterium adolescentis and Clostridium butyricum based on the mass of the rosemary stems and leaves respectively, anaerobically ferment at 40°C for 20 h, sterilize at 125°C for 20 min. After cooling to room temperature, add anhydrous ethanol with a mass 4 times that of the rosemary stems and leaves, extract for 2 h, then filter with a 3 kDa ultrafiltration membrane to obtain an ultrafiltrate below 3 kDa, concentrate and dry to obtain rosemary extract.

[0051] In this example, the enzyme activity of the hemicellulase used is 100,000 U / g; the enzyme activity of the pectinase is 100,000 U / g; the viable count of Bifidobacterium adolescentis is 10 billion CFU / g; the viable count of Clostridium butyricum is 10 billion CFU / g;

[0052] The preparation method of the above eutectic microcapsule inclusion includes the following steps: Disperse the wall material in an ethanol aqueous solution (ethanol concentration 33 wt%) with a mass 10 times that of the wall material to form a dispersion. Heat up to 55°C, add the core material to the dispersion to form a composite liquid. Filter the composite liquid through a 0.05 μm filter membrane repeatedly for 5 times to obtain an eutectic microcapsule inclusion liquid; Freeze-dry the eutectic microcapsule inclusion liquid to obtain the eutectic microcapsule inclusion.

[0053] Example 4

[0054] A eutectic microcapsule encapsulation technology, where the mass ratio of the core material to the wall material of the eutectic microcapsule encapsulant is core material:wall material = 100:5; the wall material includes ethyl palmitate, troxerutin, caprylic / capric triglyceride, sucrose stearate, PEG - 40 hydrogenated castor oil, soy lecithin, and cyclodextrin; the core material includes rosemary extract, ceramide, vitamin E, 4 - butylresorcinol, glabridin, ginseng oil, ganoderma spore oil, astaxanthin, and coenzyme Q - 10; among them, the ceramide is a ceramide NG, ceramide AS, ceramide EOP, and ceramide AP with equal mass ratios.

[0055] Among them, the mass proportion of ethyl palmitate in the wall material is 52%, the mass proportion of troxerutin in the wall material is 12%, and the balance is caprylic / capric triglyceride, sucrose stearate, PEG - 40 hydrogenated castor oil, soy lecithin, and cyclodextrin with equal mass ratios.

[0056] Among them, the mass proportion of rosemary extract in the core material is 73%, the mass proportion of ceramide in the core material is 0.8%, the mass proportion of vitamin E in the core material is 6%, and the balance is 4 - butylresorcinol, glabridin, ginseng oil, ganoderma spore oil, astaxanthin, and coenzyme Q - 10 with equal mass ratios.

[0057] The preparation method of the wall material includes the following steps: Dissolve the components of the wall material in an ethanol - water solution at 50°C, the amount of the ethanol - water solution is 20 times the mass of the wall material, the ethanol volume concentration of the ethanol - water solution is 30% - 40%, stir evenly to form a wall material system, and under the conditions of a vacuum of 0.05 MPa and a temperature of 70°C, remove ethanol and water by negative pressure distillation to obtain the wall material.

[0058] Among them, the preparation method of the rosemary extract includes the following steps: Take rosemary stems and leaves and crush them, add water with a mass 10 times that of the rosemary stems and leaves, adjust the pH to 5.5 with a 0.5 mol / L hydrochloric acid aqueous solution, add 0.5% of hemicellulase and pectinase based on the mass of the rosemary stems and leaves respectively, enzymatically hydrolyze at 55°C for 2 h, inactivate the enzyme at 95°C for 15 min, after cooling to room temperature, adjust the pH to 6.5 with a 0.8 mol / L potassium hydroxide aqueous solution, add 2.5% of glucose and 0.1% of dipotassium hydrogen phosphate based on the mass of the rosemary stems and leaves respectively, then add 0.5% of Bifidobacterium adolescentis and Clostridium butyricum based on the mass of the rosemary stems and leaves respectively, anaerobically ferment at 35°C for 20 h, sterilize at 121°C for 20 min, after cooling to room temperature, add anhydrous ethanol with a mass 3 times that of the rosemary stems and leaves, extract for 2 h, then filter with a 3 kDa ultrafiltration membrane to obtain an ultrafiltrate below 3 kDa, concentrate, and dry to obtain the rosemary extract.

[0059] In this example, the enzyme activity of the hemicellulase used is 50,000 U / g; the enzyme activity of the pectinase is 100,000 U / g; the viable count of Bifidobacterium adolescentis is 5 billion CFU / g; the viable count of Clostridium butyricum is 10 billion CFU / g;

[0060] The preparation method of the above eutectic microcapsule inclusion complex includes the following steps: Dispersing the wall material in an ethanol aqueous solution (ethanol concentration 30 wt%) with a mass 10 times that of the wall material to form a dispersion liquid, heating it to 45 °C, adding the core material to the dispersion liquid to form a composite liquid, and repeatedly pressure-filtering the composite liquid through a 0.05 μm filter membrane 3 times to obtain a eutectic microcapsule inclusion liquid; Freeze-drying the eutectic microcapsule inclusion liquid to obtain the eutectic microcapsule inclusion complex.

[0061] Example 5

[0062] A eutectic microcapsule encapsulation technology, the mass ratio of the core material to the wall material of the eutectic microcapsule inclusion complex is core material:wall material = 100:6; The wall material includes ethyl palmitate, troxerutin, hydrogenated lecithin, caprylic / capric triglyceride, sucrose stearate, PEG-8 caprylic / capric glycerides, PEG-40 hydrogenated castor oil, soy lecithin and cyclodextrin; The core material includes rosemary extract, ceramide, vitamin E, salicylic acid, 4-butylresorcinol, glabridin, kava extract, total magnolol, ginseng oil, ganoderma spore oil, astaxanthin and coenzyme Q-10; Among them, the ceramide is a ceramide NP, ceramide NS, ceramide NG, ceramide AS, ceramide EOP and ceramide AP with an equal mass ratio.

[0063] Among them, the mass proportion of ethyl palmitate in the wall material is 50%, the mass proportion of troxerutin in the wall material is 10%, and the balance is hydrogenated lecithin, caprylic / capric triglyceride, sucrose stearate, PEG-8 caprylic / capric glycerides, PEG-40 hydrogenated castor oil, soy lecithin and cyclodextrin with an equal mass ratio.

[0064] Among them, the mass proportion of rosemary extract in the core material is 70%, the mass proportion of ceramide in the core material is 0.5%, the mass proportion of vitamin E in the core material is 5%, and the balance is salicylic acid, 4-butylresorcinol, glabridin, kava extract, total magnolol, ginseng oil, ganoderma spore oil, astaxanthin and coenzyme Q-10 with an equal mass ratio.

[0065] The preparation method of the wall material includes the following steps: Dissolving the components of the wall material in an ethanol aqueous solution at 60 °C, the amount of the ethanol aqueous solution is 15 times the mass of the wall material, the ethanol volume concentration of the ethanol aqueous solution is 30% - 40%, stirring evenly to form a wall material system, and under the conditions of a vacuum degree of 0.06 MPa and a temperature of 60 °C, removing ethanol and water by negative pressure distillation to obtain the wall material.

[0066] Among them, the preparation method of rosemary extract includes the following steps: Take rosemary stems and leaves, crush them, add water with a mass 8 times that of the rosemary stems and leaves, adjust the pH to 5.0 with a hydrochloric acid aqueous solution with a concentration of 0.8 mol / L, add 1.0% of hemicellulase and pectinase based on the mass of the rosemary stems and leaves respectively, enzymatically hydrolyze at 45°C for 3 h, inactivate the enzyme at 85°C for 25 min, after cooling to room temperature, adjust the pH to 7.0 with a potassium hydroxide aqueous solution with a concentration of 0.5 mol / L, add 1.5% of glucose and 0.3% of dipotassium hydrogen phosphate based on the mass of the rosemary stems and leaves, then add 0.3% of Bifidobacterium adolescentis and Clostridium butyricum based on the mass of the rosemary stems and leaves respectively, anaerobically ferment at 40°C for 15 h, sterilize at 125°C for 15 min, after cooling to room temperature, add anhydrous ethanol with a mass 4 times that of the rosemary stems and leaves, extract for 1 h, then filter with a 3 kDa ultrafiltration membrane to obtain an ultrafiltrate below 3 kDa, concentrate and dry to obtain rosemary extract.

[0067] In this example, the enzyme activity of the hemicellulase used is 100,000 U / g; the enzyme activity of the pectinase is 50,000 U / g; the viable count of Bifidobacterium adolescentis is 10 billion CFU / g; the viable count of Clostridium butyricum is 5 billion CFU / g;

[0068] The preparation method of the above eutectic microcapsule inclusion complex includes the following steps: Disperse the wall material in an ethanol aqueous solution (ethanol concentration 40 wt%) with a mass 10 times that of the wall material to form a dispersion, heat up to 55°C, add the core material to the dispersion to form a composite liquid, repeatedly press-filter the composite liquid through a 0.03 μm filter membrane 5 times to obtain an eutectic microcapsule inclusion complex liquid; freeze-dry the eutectic microcapsule inclusion complex liquid to obtain the eutectic microcapsule inclusion complex.

[0069] Comparative Example 1

[0070] The rosemary extract is not encapsulated with the eutectic microcapsule; other parameters and methods are the same as those in Example 1.

[0071] Comparative Example 2

[0072] Ethyl palmitate is not added to the components of the wall material, and the component of ethyl palmitate is replaced with PEG-40 hydrogenated castor oil; other parameters and methods are the same as those in Example 1.

[0073] Comparative Example 3

[0074] Troxerutin is not added to the components of the wall material, and the component of troxerutin is replaced with PEG-40 hydrogenated castor oil; other parameters and methods are the same as those in Example 1.

[0075] Comparative Example 4

[0076] In the preparation method of rosemary extract, rosemary stems and leaves are taken and crushed, water 9 times the mass of the rosemary stems and leaves is added, anhydrous ethanol 3.5 times the mass of the rosemary stems and leaves is added, and extraction is carried out for 1.5 h. Then, filtration is carried out using a 3 kDa ultrafiltration membrane to obtain an ultrafiltrate below 3 kDa, which is concentrated and dried to obtain rosemary extract. Other parameters and methods are the same as those in Example 1.

[0077] Comparative Example 5

[0078] In the preparation method of rosemary extract, Bifidobacterium adolescentis is not added during fermentation; other parameters and methods are the same as those in Example 1.

[0079] Comparative Example 6

[0080] In the preparation method of rosemary extract, Clostridium butyricum is not added during fermentation; other parameters and methods are the same as those in Example 1.

[0081] The product samples of the above examples and comparative examples are detected for their antioxidant, soothing and anti-allergic, and skin repair effects.

[0082] I. Antioxidation

[0083] Mouse adherent macrophages are used as test cells. The product sample: purified water is prepared at a ratio of 1:100 to obtain a product sample reagent.

[0084] The fluorescence probe DCFH-DA is used for reactive oxygen species detection. DCFH-DA itself has no fluorescence and can freely penetrate the cell membrane. After entering the cell, it is hydrolyzed by intracellular esterase to generate DCFH. DCFH cannot penetrate the cell membrane, so the probe can be easily loaded into the cell. Intracellular reactive oxygen species can oxidize non-fluorescent DCFH to generate fluorescent DCF. Detecting the fluorescence of DCF can know the level of intracellular reactive oxygen species.

[0085] Blank control sample: DCFH-DA is diluted with serum-free culture medium at a ratio of 1:1000 to make the final concentration 10 μmol / L to obtain a DCFH-DA dilution. After the cells are collected, they are suspended in the DCFH-DA dilution with a cell concentration of 5 million / mL, and then purified water equal to the volume of the DCFH-DA dilution is added. Incubate in a 37 °C cell culture incubator for 30 min. Invert and mix evenly every 5 min to make the probe and cells fully contact. Wash the cells three times with serum-free cell culture medium to fully remove the DCF-DA that has not entered the cells. Detect the fluorescence intensity at an excitation wavelength of 488 nm and an emission wavelength of 525 nm using a fluorescence microplate reader, and the reactive oxygen species ROS value is recorded as R0.

[0086] Examples and comparative examples: Dilute DCFH-DA with serum-free culture medium at a ratio of 1:1000 to make the final concentration 10 μmol / L, obtaining a DCFH-DA dilution. After collecting the cells, suspend them in the DCFH-DA dilution with a cell concentration of 5 million / mL, and then add the product sample reagent with the same volume as the DCFH-DA dilution (corresponding to the product samples of each example and comparative example). Incubate in a cell culture incubator at 37 °C for 30 min. Invert and mix well every 5 min to ensure full contact between the probe and the cells. Wash the cells three times with serum-free cell culture medium to fully remove the DCFH-DA and product samples that have not entered the cells. Detect the fluorescence intensity with a fluorescence microplate reader at an excitation wavelength of 488 nm and an emission wavelength of 525 nm, and record the reactive oxygen species (ROS) value as R1.

[0087] Calculation formula for relative improvement rate of ROS: R% = (R0 - R1) / R0 * 100%; The test results are shown in Table 1 below.

[0088] Table 1 Antioxidant test results

[0089]

[0090]

[0091] From the above results, it can be seen that the eutectic microcapsule encapsulates have good antioxidant effects in Examples 1 to 5. From the result of Comparative Example 1, it can be seen that when rosemary extract is not encapsulated by eutectic microcapsules, the penetration effect is poor, the utilization rate of rosemary extract is low, which affects the absorption of cells and reduces the antioxidant effect of cells. From the result of Comparative Example 2, it can be seen that when ethyl palmitate is not added to the composition of the wall material, the coating effect of the wall material will be reduced, the penetration effect will be reduced, which affects the absorption of cells and reduces the antioxidant effect of cells. From the result of Comparative Example 3, it can be seen that without adding troxerutin, the encapsulation effect is poor, the penetration effect is poor, the utilization rate of rosemary extract is low, which affects the absorption of cells and reduces the antioxidant effect of cells. From the result of Comparative Example 4, it can be seen that when rosemary extract is obtained by the conventional ethanol aqueous solution extraction method, the antioxidant effect is significantly reduced. From the results of Comparative Example 5 and Comparative Example 6, it can be seen that without adding Bifidobacterium adolescentis or Clostridium butyricum during fermentation, the product components are affected differently, which will reduce the antioxidant effect.

[0092] II. Soothing and anti-allergic

[0093] Hyaluronidase is a participant in type I allergic reactions. Most allergic reactions are type I allergic reactions related to the activity of hyaluronidase in the body. The inhibitory ability of the product sample reagent on hyaluronidase reflects its ability to inhibit type I allergic reactions. The greater the inhibition rate of hyaluronidase, the stronger the anti-allergic activity.

[0094] Take 11.55 mL of glacial acetic acid and dissolve it in 1 L of distilled water to prepare a 0.2 mol / L acetic acid solution; take 16.4 g of anhydrous sodium acetate and dissolve it in 1 L of distilled water to prepare a 0.2 mol / L sodium acetate solution; take 4.8 mL of the acetic acid solution and 45.2 mL of the sodium acetate solution, mix them, and make up to 100 mL with distilled water to prepare an acetic acid buffer solution with a pH of 5.6.

[0095] Using the acetic acid buffer solution as the solvent, prepare a hyaluronidase solution with a concentration of 500 U / mL.

[0096] Using the acetic acid buffer solution as the solvent, prepare a sodium hyaluronate solution with a concentration of 0.5 mg / mL.

[0097] Using the acetic acid buffer solution as the solvent, prepare a product sample solution with a concentration of 0.5 mg / mL.

[0098] Prepare an acetylacetone solution by using 50 mL of 1.0 mol / L sodium carbonate solution and 3.5 mL of acetylacetone.

[0099] P-DAB color reagent: Take 0.8 g of p-dimethylaminobenzaldehyde and dissolve it in a mixture of 15 mL of concentrated hydrochloric acid and 15 mL of absolute ethanol to prepare the P-DAB color reagent.

[0100] Test tube A: 0.5 mL of the product sample solution + 0.5 mL of the hyaluronidase solution, incubate at 37 °C for 20 min; add 0.1 mL (2.5 mmol / L) of CaCl2, incubate at 37 °C for 20 min; add 0.5 mL of the sodium hyaluronate solution; keep warm at 37 °C for 40 min, let stand at room temperature for 10 min, add 0.5 mL of the acetylacetone solution, 0.1 mL of NaOH solution (5 mol / L), and 0.5 mL of distilled water, heat in a boiling water bath for 15 min, immediately cool in ice water for 5 min, add 1 mL of the P-DAB color reagent, shake well, add 3.5 mL of absolute ethanol, let stand for 30 min for color development, measure the OD value at 530 nm, and record it as A.

[0101] Test tube B: 0.5 mL of the product sample solution + 0.5 mL of the hyaluronidase solution, incubate at 37 °C for 20 min; add 0.1 mL (2.5 mmol / L) of CaCl2, incubate at 37 °C for 20 min; add 0.5 mL of the acetic acid buffer solution; keep warm at 37 °C for 40 min, let stand at room temperature for 10 min, add 0.5 mL of the acetylacetone solution, 0.1 mL of NaOH solution (5 mol / L), and 0.5 mL of distilled water, heat in a boiling water bath for 15 min, immediately cool in ice water for 5 min, add 1 mL of the P-DAB color reagent, shake well, add 3.5 mL of absolute ethanol, let stand for 30 min for color development, measure the OD value at 530 nm, and record it as B.

[0102] Tube C: 0.5 mL of distilled water + 0.5 mL of acetate buffer solution, incubated at 37 °C for 20 min; add 0.1 mL (2.5 mmol / L) of CaCl₂, incubated at 37 °C for 20 min; add 0.5 mL of sodium hyaluronate solution; incubated at 37 °C for 40 min, left at room temperature for 10 min, add 0.5 mL of acetylacetone solution, 0.1 mL of NaOH solution (5 mol / L) and 0.5 mL of distilled water, boiled in a water bath for 15 min, immediately cooled in ice water for 5 min, add 1 mL of P-DAB chromogenic reagent, shake well, add 3.5 mL of absolute ethanol, left for 30 min for color development, and measure the OD value at 530 nm, denoted as C.

[0103] Tube D: 0.5 mL of distilled water + 0.5 mL of acetate buffer solution, incubated at 37 °C for 20 min; add 0.1 mL (2.5 mmol / L) of CaCl₂, incubated at 37 °C for 20 min; add 0.5 mL of acetate buffer solution; incubated at 37 °C for 40 min, left at room temperature for 10 min, add 0.5 mL of acetylacetone solution, 0.1 mL of NaOH solution (5 mol / L) and 0.5 mL of distilled water, boiled in a water bath for 15 min, immediately cooled in ice water for 5 min, add 1 mL of P-DAB chromogenic reagent, shake well, add 3.5 mL of absolute ethanol, left for 30 min for color development, and measure the OD value at 530 nm, denoted as D.

[0104] Hyaluronidase inhibition rate (%) = [(C - D) - (A - B)] / (C - D) × 100%; the test results are shown in Table 2 below.

[0105] Table 2 Results of soothing and anti-allergic tests

[0106]

[0107] From the above results, it can be seen that the eutectic microcapsule encapsulates of Examples 1 to 5 have good hyaluronidase inhibition effects and can play a good role in soothing and anti-allergic. From the results of Comparative Example 1, it can be seen that in in vitro tests, when rosemary extract is not encapsulated in eutectic microcapsules, ethyl palmitate is not added to the composition of the wall material, and troxerutin is not added to the composition of the wall material, it has little effect on the in vitro hyaluronidase inhibition effect. From the results of Comparative Example 4, it can be seen that when rosemary extract is obtained by the conventional ethanol-water solution extraction method, its effect of inhibiting hyaluronidase and soothing and anti-allergic decreases significantly. From the results of Comparative Example 5 and Comparative Example 6, it can be seen that when fermentation does not add Bifidobacterium adolescentis or Clostridium butyricum, its effect of inhibiting hyaluronidase and soothing and anti-allergic decreases significantly.

[0108] III. Skin repair

[0109] Product sample: Prepared by mixing the product sample and purified water at a ratio of 1:100 to obtain the product sample reagent. Soak the facial mask paper in the product sample reagent to prepare the facial mask. Select 66 female subjects with healthy and intact skin, and randomly divide them into 10 groups, with 6 subjects in each group. Each group uses the facial masks of each example and each comparative example respectively. Apply the facial mask on the inner side of the forearm for 10 minutes every night for 28 days. After cleansing the face every night, apply the facial mask on the face for 10 minutes for 28 days.

[0110] (1) Use the TM300 tester to detect respectively: the transepidermal water loss (TEWL) on the inner side of the forearm before the test, on the 14th day, and on the 28th day; TEWL value decline rate = (A0 - An) / A0 × 100%; where A0 is the TEWL value before the test, and An is the TEWL value on the nth day. A positive TEWL value decline rate indicates that the skin barrier is repaired, and the greater the TEWL value decline rate, the better the skin barrier repair effect. The test results are shown in Table 3 below.

[0111] Table 3 TEWL value decline rate results (average value)

[0112]

[0113] (2) Use the UC22 skin ultrasound tester to detect respectively: the thickness D of the skin epidermal layer before the test, on the 14th day, and on the 28th day; D value increase rate = (D0 - Dn) / D0 × 100%; where D0 is the epidermal layer thickness before the test, and Dn is the epidermal layer thickness on the nth day. A positive D value increase rate indicates that the skin barrier is repaired, and the greater the D value increase rate, the better the skin barrier repair effect. The test results are shown in Table 4 below.

[0114] Table 4 D value increase rate results (average value)

[0115]

[0116] From the above results, it can be seen that the eutectic microcapsule encapsulates have a good effect on repairing the skin, thickening the skin and improving water retention. From the results of Comparative Example 1, it can be seen that when rosemary extract is not encapsulated by eutectic microcapsules, the penetration effect is poor, the utilization rate of rosemary extract is low, which affects the absorption of cells and reduces the effect of repairing the skin. From the results of Comparative Example 2, it can be seen that without adding ethyl palmitate to the composition of the wall material, the coating effect of the wall material will be reduced, the penetration effect will be reduced, which affects the absorption of cells and reduces the effect of repairing the skin. From the results of Comparative Example 3, it can be seen that without adding troxerutin, the coating effect is poor, the penetration effect of the microcapsules is poor, the utilization rate of rosemary extract is low, which affects the absorption of cells and reduces the effect of repairing the skin. From the results of Comparative Example 4, it can be seen that when rosemary is extracted by the conventional method of ethanol aqueous solution, the effect of repairing the skin is greatly reduced. From the results of Comparative Example 5 and Comparative Example 6, it can be seen that without adding Bifidobacterium adolescentis or Clostridium butyricum during fermentation, the different product components will be affected, which will reduce the effect of repairing the skin.

Claims

1. A method for preparing a eutectic microcapsule inclusion, characterized in that: The mass ratio of the core material to the wall material of the eutectic microcapsule is core material: wall material = 100: (3-6); The wall material comprises at least one of hydrogenated lecithin, caprylic / capric triglyceride, sucrose stearate, PEG-8 caprylic / capric glycerides, PEG-40 hydrogenated castor oil, soybean lecithin, cyclodextrin, ethyl palmitate and troxerutin; The core material comprises at least one of salicylic acid, 4-butylresorcinol, glabridin, kava extract, magnolol, ginseng oil, ganoderma lucidum spore oil, astaxanthin, coenzyme Q-10, rosemary extract, ceramide and vitamin E; The rosemary extract is an extract with a molecular weight of less than 3 kDa obtained by hydrolyzing rosemary stems and leaves with hemicellulase and pectinase and then fermenting with Bifidobacterium adolescentis and Clostridium butyricum; The mass proportion of the palmitic acid ethyl ester in the wall material is 50% to 60%; the mass proportion of the troxerutin in the wall material is 10% to 20%; The mass proportion of the rosemary extract in the core material is 70% to 80%; the mass proportion of the ceramide in the core material is 0.5% to 3%; the mass proportion of the vitamin E in the core material is 5% to 10%; The preparation method of the eutectic microcapsule inclusions comprises the following steps: dispersing the wall material in an ethanol aqueous solution to form a dispersion liquid, heating the dispersion liquid to 45°C to 55°C, adding the core material to the dispersion liquid to form a composite liquid, repeatedly filtering the composite liquid through a 0.03μm to 0.05μm filter membrane for 3 to 5 times to obtain a eutectic microcapsule inclusion liquid; and freeze-drying the eutectic microcapsule inclusion liquid to obtain the eutectic microcapsule inclusions.

2. The method for preparing a eutectic microcapsule inclusion according to claim 1, characterized in that: The ceramide is at least one of ceramide NP, ceramide NS, ceramide NG, ceramide AS, ceramide EOP and ceramide AP.

3. The method for preparing a eutectic microcapsule inclusion according to claim 1 or 2, characterized in that: The preparation method of the wall material comprises the following steps: dissolving the components of the wall material in an ethanol aqueous solution at 50° C. to 60° C., stirring evenly to form a wall material system, and removing ethanol and water by negative pressure distillation to obtain the wall material.

4. The method for preparing a eutectic microcapsule inclusion according to claim 3, characterized in that: The amount of the ethanol aqueous solution is 15 to 20 times the weight of the wall material; the ethanol volume concentration of the ethanol aqueous solution is 30% to 40%; The parameters of the negative pressure distillation are: vacuum degree 0.07MPa-0.08MPa, temperature 60°C-70°C.

5. The method for preparing a eutectic microcapsule inclusion according to claim 1, characterized in that: The preparation method of the rosemary extract comprises the following steps: taking rosemary stems and leaves and crushing them, adding water 8 to 10 times the mass of the rosemary stems and leaves, adjusting the pH value to 5.0 to 5.5 by using a hydrochloric acid aqueous solution, respectively adding hemicellulase and pectinase in an amount of 0.5 to 1.0% by mass of the rosemary stems and leaves, performing enzymolysis at 45 to 55° C. for 2 to 3 hours, inactivating the enzymes at high temperature, and adjusting the pH value to 6.5 to 7.0 by using a sodium hydroxide aqueous solution after the temperature drops to room temperature, adding glucose and dipotassium hydrogen phosphate, and then respectively adding bifidobacterium adolescentis and clostridium butyricum in an amount of 0.3 to 0.5% by mass of the rosemary stems and leaves, performing anaerobic fermentation at 35 to 40° C. for 15 to 20 hours, performing high temperature sterilization, and after the temperature drops to room temperature, adding anhydrous ethanol in an amount of 3 to 4 times the mass of the rosemary stems and leaves, extracting for 1 to 2 hours, filtering by using a 3 kDa ultrafiltration membrane to obtain an ultrafiltrate below 3 kDa, concentrating, and drying to obtain the rosemary extract.

6. The method for preparing a eutectic microcapsule inclusion according to claim 5, characterized in that: The enzymatic activity of the hemicellulase is 50,000 U / g to 100,000 U / g; the enzymatic activity of the pectinase is 50,000 U / g to 100,000 U / g; the added amount of the glucose is 1.5% to 2.5% of the mass of the rosemary stems and leaves; the added amount of the dipotassium hydrogen phosphate is 0.1% to 0.3% of the mass of the rosemary stems and leaves; the bacterial activity of the Bifidobacterium adolescentis is 5 billion CFU / g to 10 billion CFU / g; the bacterial activity of the Clostridium butyricum is 5 billion CFU / g to 10 billion CFU / g; the temperature of the high-temperature enzyme inactivation is 85°C to 95°C, and the time is 15min to 25min; the temperature of the high-temperature sterilization is 121°C to 125°C, and the time is 15min to 20min; the concentration of the hydrochloric acid aqueous solution is 0.5mol / L to 0.8mol / L; the concentration of the sodium hydroxide aqueous solution is 0.5mol / L to 0.8mol / L.

7. A eutectic microcapsule inclusion, prepared by the method for preparing a eutectic microcapsule inclusion according to claim 1, characterized in that: The eutectic microcapsule is used for preparing cosmetics.

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