Nanoliposome particles for encapsulating active ingredients and preparation method and application thereof

Abstract

The present invention relates to a nanoliposome particle for encapsulating active ingredients and a preparation method and application thereof, and belongs to the technical field of cosmetics. The nanoliposome particle for encapsulating active ingredients of the present invention comprises the following components in parts by weight: 0.1 to 5 parts of active substance, 0.2 to 16 parts of emulsifier, 0.1 to 8 parts of oil, and 31 to 99.5 parts of solvent. The preparation process of the nanoliposome particle of the present invention does not use high-pressure homogenization, thus avoiding the destruction of the active substance, improving the solubility and stability of the active substance in water, and being able to improve its compatibility in the formula, being able to stably and efficiently encapsulate the active ingredient, being able to completely enclose the active ingredient in the lipid cavity, having better stability, being able to keep the active ingredient more stable at high temperature, and having better skin permeability, and adding a solvent (aqueous phase) in the process of preparing the nanoparticle, which improves the convenience of the nanoparticle when in use, and being easy to be added into various dosage forms.

Description

Technical Field

[0001] The invention belongs to the technical field of cosmetics, and particularly relates to nanoliposome particles for encapsulating active ingredients, a preparation method and an application thereof. Background Art

[0002] Nanoliposome technology is one of the most widely used delivery systems for encapsulating, preserving and controlling the release of bioactive compounds in the cosmetics industry. Liposomes are spherical vesicles composed of a phospholipid bilayer and a water core, and can range in size from nanometers to micrometers. Liposomes with a size less than 1000nm are called nanoliposomes. Compared with liposomes, nanoliposomes have a larger surface area, which increases solubility and bioavailability, and improves controlled release. In transdermal administration, liposome technology can increase the permeability of low-permeability and low-water-soluble drugs through the skin. On the one hand, this is because the phospholipid bilayer membrane of the liposome has a composition and structure similar to that of the cell membrane, which makes it easy to reach the deep skin through the intercellular lipids. On the other hand, the surface charge of the liposome can interact with the skin to help the drug improve its permeability.

[0003] Traditional lipid nanocapsules are generally composed of an oil phase, an aqueous phase, and a nonionic surfactant, and usually a co-surfactant, generally lecithin, is added. The disadvantages of this technology include poor batch repeatability of phospholipids, high phospholipid costs, and high energy consumption and technical requirements for high-pressure homogenization methods. Based on this, the present invention provides a new lipid nanoparticle, which is composed of a lipid with good biocompatibility and a surfactant, and can be used to encapsulate various small molecules and macromolecular active substances with different functions, and has a wide range of uses. Summary of the invention

[0004] The purpose of the present invention is to provide a nanoliposome particle for encapsulating active ingredients, a preparation method and an application thereof, a preparation method and an application thereof of the nanoliposome particle with high loading capacity, maintaining the stability of the active substance at high temperature, good skin permeability, good water solubility and excellent compatibility, and the method does not require high-pressure homogenization of the raw materials, thereby avoiding damage to the active substance.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] A nano liposome particle for encapsulating an active substance comprises the following components in parts by weight: 0.1 to 5 parts of an active substance, 0.2 to 16 parts of an emulsifier, 0.1 to 8 parts of oil, and 31 to 99.5 parts of a solvent.

[0007] As a preferred embodiment of the present invention, the nanoliposome particles for encapsulating active substances include the following components in parts by weight: 0.1 to 5 parts of active substances, 0.2 to 12 parts of emulsifiers, 0.1 to 6 parts of oils and fats, and 31 to 99.5 parts of solvents.

[0008] As a preferred embodiment of the present invention, the active ingredient is an active ingredient acceptable in cosmetics, such as at least one of acne-removing and anti-inflammatory active ingredients, skin whitening and brightening active ingredients, anti-aging / antioxidant active ingredients, and moisturizing and repairing active ingredients. The active ingredient can be a water-soluble active ingredient or an oil-soluble active ingredient.

[0009] Exemplarily, the anti-acne and anti-inflammatory active ingredients include at least one of thyme extract, aescin, magnolia bark extract, myrtle fruit extract, totarol, meadowsweet extract, white willow bark extract, picolinin, niacinamide, andrographis paniculata extract, salicylic acid, o-cymene-5-ol, kava extract, rhodiola rosea root extract, azelaic acid and its derivatives, olive leaf extract, camellia seed extract, purslane extract, houttuynia cordata extract, honeysuckle flower extract, oldenlandia diffusa extract, dandelion extract, rehmannia root extract, momordica charantia fruit extract, bisabolol, lotus seed extract, mangosteen peel extract, magnolia bark extract, and pomegranate peel extract, but are not limited thereto.

[0010] Exemplarily, the whitening and skin-lightening active ingredients include at least one of glutathione, tranexamic acid, sialic acid, vitamin C and its derivatives, resveratrol, arbutin, ellagic acid, phenylethylresorcinol, 4-butylresorcinol, hexylresorcinol, clary lactone, daisy flower extract, glycyrrhiza glabra root extract, osmanthus fragrans rhizome extract, wolfberry fruit extract, sophora flavescens root extract, pyracantha fruit extract, grape seed extract, rice germ extract, kudzu root extract, alpine edelweiss extract, snow lotus extract, licorice root extract, and sea buckthorn extract, but are not limited to these.

[0011] Exemplarily, the moisturizing and repairing active ingredients include at least one of ceramide, resurrection grass extract, Centella asiatica extract, Centella asiatica glycoside, aloe vera extract, ginger root extract, Scutellaria baicalensis root extract, Sophora flavescens root extract, ectoine, hyaluronic acid and its derivatives, oat beta-glucan, sodium polyglutamate, caper fruit extract, Fucus vesiculosus extract, Dendrobium officinale stem extract, cactus extract, carbohydrate isomers, and glycerol glucoside, but are not limited to these.

[0012] Exemplarily, the anti-aging / antioxidant active ingredients include at least one of astaxanthin, ergothioneine, coenzyme Q10, idebenone, fullerene, ferulic acid, sea fennel callus culture filtrate, caffeine, carnosine, retinol and its derivatives, peach resin extract, biosaccharide gum, polypeptides, black truffle extract, raspberry fruit extract, kangaroo paw extract, sausage tree fruit extract, Cordyceps sinensis mycelium powder, Matsumura extract, peony root extract, Rosa damascena flower extract, rose flower extract, ginseng root extract, Ganoderma lucidum extract, cherry flower extract, black tea extract, tea extract, camellia extract, pomegranate fruit extract, and fish egg extract, but are not limited thereto.

[0013] Preferably, the emulsifier is at least one of lecithin and its derivatives, hydrogenated phosphatidylcholine, cholesterol polyether-10, polyglyceryl-10 stearate, PEG-20 glyceryl triisostearate, sorbitan stearate, PEG-8 glyceryl isostearate, and glyceryl stearate.

[0014] Preferably, the emulsifiers of the present invention are hydrogenated phosphatidylcholine and glyceryl stearate.

[0015] Preferably, the phosphatidylcholine (PC) described in the present invention is a major component of living cell membranes, which contains unsaturated fatty acids and saturated (hydrogenated) fatty acids, and its lipophilic part is formed by two fatty acids bound to a glycerol backbone, and the polar end group is composed of phosphorylcholine bound to the glycerol backbone.

[0016] Preferably, the content of the emulsifier is 0.2-16%; for example, it can be 0.3%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%;

[0017] Preferably, the oil can be at least one of isopropyl palmitate, cholesterol, cholesterol, phytosterol, caprylic / capric triglyceride, isopropyl isostearate, and oleth-3 phosphate;

[0018] Caprylic / capric triglyceride and phytosterol combinations are preferred in the present invention.

[0019] Preferably, the oil content is 0.1% to 8%; for example, it can be 0.1%, 0.3%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 5%, 6%, 7%, 8%;

[0020] Preferably, the solvent is at least one of water and a polyol, and the polyol is at least one of glycerol, 1,3-propylene glycol, 1,2-hexanediol, 4-tert-butyl cyclohexanol, sorbitol, 1,2-pentanediol, inositol, dipropylene glycol, caprylyl glycol, erythritol, and ethylhexylglycerol;

[0021] The more preferred polyol of the present invention is a combination of glycerol, inositol, erythritol, caprylyl glycol, and 1,3-propylene glycol; this can reduce the use of glycerol, effectively improve the skin feel of the nanoparticle product, and better promote skin absorption; it can also reduce the use of preservatives and reduce skin irritation.

[0022] The method for preparing the nanoliposome particles encapsulating active substances described in the present invention is as follows:

[0023] (1) After the oil and emulsifier are mixed at 70-80°C and uniformly blended, the temperature is lowered to 40-50°C and then the water-insoluble active ingredient is added and slowly stirred to dissolve it quickly to obtain an oil phase;

[0024] (2) heating the solvent and water to 70-85° C. at the same time, keeping the temperature for 20-30 min, then cooling to 40-50° C., adding the water-soluble active ingredient, and mixing evenly to obtain an aqueous phase;

[0025] (3) The aqueous phase is added to the oil phase and stirred evenly to obtain nanoliposome particles for encapsulating the active substance.

[0026] Preferably, the heating temperature of the oil and emulsifier is 80°C.

[0027] Preferably, the solvent heating temperature is 80°C.

[0028] Preferably, the stirring speed is 400-500 r / min.

[0029] In addition to the substances mentioned above, the nanoliposome particles of the present invention can selectively add other substances, such as penetration enhancers, etc. according to actual product needs.

[0030] The present invention also provides the use of the nanoliposome particles described above in skin care products. Preferably, the dosage form of the cosmetics is lotion, essence, emulsion, cream or mask.

[0031] Preferably, the mass proportion of the nanoparticles in the cosmetic is 0.1 to 15%, more preferably 0.5 to 8%.

[0032] The present invention provides a skin care product comprising the nano liposome particles described above.

[0033] Preferably, the skin care product further comprises auxiliary materials, and the auxiliary materials are conventional auxiliary materials in the art, for example, at least one of an emollient, an antioxidant, a skin conditioner, a solubilizer, a thickener, etc.

[0034] The nanoparticles encapsulating active substances of the present invention adopt a combination of emulsifiers, oils and solvents of specific types and proportions. The combination of the three components in the proportions can significantly improve the stability and water solubility of the obtained liposomes. DETAILED DESCRIPTION

[0035] In order to better illustrate the purpose, technical solutions and advantages of the present invention, the present invention will be further described below in conjunction with specific embodiments.

[0036] The raw materials used in the following examples are all commercially available.

[0037] Examples 1 to 11 and Comparative Examples 1 to 5

[0038] The formulas of Examples 1 to 11 of the present invention are shown in Table 1-1, and the formulas of Comparative Examples 1 to 5 are shown in Table 1-2. The preparation method is as follows: (1) After the oil and emulsifier are mixed at 70 to 80° C. and uniformly blended, the temperature is lowered to 40 to 50° C., and then retinol is added and slowly stirred to dissolve it quickly to obtain an oil phase;

[0039] (2) heating the solvent and water to 70-85° C. at the same time, keeping the temperature for 20-30 min, then cooling to 40-50° C., adding ferulic acid, and mixing well to obtain an aqueous phase;

[0040] (3) The aqueous phase is added to the oil phase and stirred evenly to obtain nanoliposome particles for encapsulating the active substance.

[0041] Table 1-1 Formula

[0042]

[0043] Table 1-2 Formula

[0044]

[0045]

[0046] Test Example 1: Security Test

[0047] The performance tests were performed on the compositions prepared in the above examples and comparative examples. The specific test methods are as follows:

[0048] Specific experimental methods:

[0049] 48 social volunteers who met the requirements, aged 20 to 45 years old, were selected and randomly divided into 16 groups, 3 in each group, and the nano solutions prepared by Examples 1 to 11 and Comparative Examples 1 to 5 were tried respectively by group, and 0.020-0.025 mL of the tested samples were taken respectively and placed in the small chamber of the spot tester, and no treatment was done on the control well. The spot tester with the tested substance was applied to the side of the forearm of the subject with a low-allergenic tape, and the palm of the hand was gently pressed to make it evenly applied to the skin for 24 hours. The skin reaction was observed according to the standards in Table 1 at 30 minutes (after the indentation disappears), 24 hours and 48 hours after the tested substance spot device was removed.

[0050] Table 2 Skin grading reaction

[0051]

[0052]

[0053] The compositions of Examples 1 to 11 and Comparative Examples 1 to 5 were compared according to the above method. The experimental results are shown in Table 3.

[0054] Table 3 Skin reactions of various embodiments and comparative examples

[0055] Skin reactions Skin reactions Example 1 Negative reaction Example 9 Negative reaction Example 2 Negative reaction Example 10 Negative reaction Example 3 Negative reaction Embodiment 11 Negative reaction Example 4 Negative reaction Comparative Example 1 Negative reaction Example 5 Negative reaction Comparative Example 2 Negative reaction Example 6 Negative reaction Comparative Example 3 Negative reaction Example 7 Negative reaction Comparative Example 4 Negative reaction Example 8 Negative reaction Comparative Example 5 Negative reaction

[0056] The results show that Examples 1 to 11 of the present invention and Comparative Examples 1 to 5 all have negative reactions, indicating that the nanoliposome particles involved in the present invention are safe and will not cause adverse reactions such as skin irritation and sensitization (except for people who are prone to allergies or are allergic to this product).

[0057] Test Example 2 Particle Size Test

[0058] The nanoliposome particles prepared in Examples 1 to 11 and Comparative Examples 1 to 5 were tested for particle size, PDI (polydispersity index), and transmittance using Anton Paar Litesizer 500. The results are shown in Table 4.

[0059] Table 4 Determination results of different nanoliposome particles

[0060]

[0061]

[0062] As can be seen from Table 4, when the same amount of glycerol stearate is used in Examples 1 to 4, within a certain range, as more hydrogenated phosphatidylcholine is added, the particle size of the liposome becomes smaller, and the decrease in PDI indicates that the stability of the liposome is improved; the smaller the particle size, the more transparent the liposome, and the better the transmittance of the diluent of the liposome; by comparing Example 3 and Examples 8, 9, 10, and 11, it can be seen that when the amount of caprylic / capric triglyceride is constant, within a certain range, as the phytosterol increases, the particle size of the liposome gradually increases, and the PDI also gradually increases, indicating that too high a lipid content is unfavorable to the system; wherein the results of Examples 3, 8, and 9 are similar. Since Comparative Examples 1 to 5 lack water or a certain compounding component in an emulsifier and oil, the particle size of the result of compounding each substance in the Example is smaller than that of a single substance compared with the Comparative Example, indicating that compounding each substance can improve the stability of the liposome, with a small and more uniform particle size and good stability.

[0063] Test Example 3 Determination of dissolution rate

[0064] The same mass of the nanoliposome particles obtained in Examples 1 to 11 and the nanoliposome particles prepared in Comparative Examples 1 to 5 were dissolved in deionized water respectively, and the speed at which the nanoliposome particles were completely dissolved in water was measured. The results are shown in Table 5.

[0065] Table 5 Dissolution rate table

[0066]

[0067]

[0068] It can be seen from the data in Table 5 above that the liposomes prepared in Examples 1 to 11 all dissolve quickly in water, which improves the convenience of the liposomes in use and makes them easy to add to various dosage forms. However, since Comparative Examples 1 to 5 lack water or a certain compound component of the emulsifier and the oil, the dissolution time of Comparative Examples 1 to 5 increases significantly relative to the Examples.

[0069] Experimental Example 4: Stability Test

[0070] 1. Centrifugal stability test

[0071] The nanoliposome particles prepared in Example 3 and Comparative Examples 1 to 5 were subjected to a centrifugation test at 25° C. and 3000 rpm for 20 min to observe whether the samples were stratified and whether the particle size and PDI changed.

[0072] 2. Storage stability test

[0073] The nanoliposome particles prepared in Example 3 and Comparative Examples 1 to 5 were stored at 4° C., 25° C. and 40° C., respectively, and the particle sizes were tested at 7, 14, 21 and 28 days to observe whether the nanoparticles in the system aggregated.

[0074] 3. Dilution stability test

[0075] The nanoliposome particles prepared in Example 3 and Comparative Examples 1 to 5 were diluted to 10, 20, 50, 100, and 200 times, respectively, and left to stand overnight to detect the change in particle size. The effect of different dilution multiples on the particle size of the system was observed. The specific test results are shown in Table 6.

[0076] Table 6 Stability test

[0077]

[0078]

[0079] From the perspective of stability, since comparative examples 1 to 5 lack water or a certain compound component of emulsifier and oil, compared with comparative examples 1 to 5, in various stability tests, the particle size and PDI of Example 3 of the present invention did not change significantly, and no particle aggregation occurred. At the same time, from the dilution stability experiment, it can be seen that the system of the present invention can still maintain the original structure and state at different dilution multiples, and no aggregation or demulsification occurs, and it can be directly diluted and used. Compared with the comparative example, the substances used in the present invention can interact better with each other, increasing the stability of the nanoparticles.

[0080] Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solution of the present invention can be modified or replaced by equivalents without departing from the essence and scope of the technical solution of the present invention.

Claims

1. A nanoliposome particle for encapsulating an active substance, characterized in that: The composition comprises the following components in parts by weight: 0.1 to 5 parts of active ingredients, 0.2 to 16 parts of emulsifiers, 0.1 to 8 parts of oils and fats, and 31 to 99.5 parts of solvents; The emulsifier includes glyceryl stearate and hydrogenated phosphatidylcholine, and the mass ratio of glyceryl stearate to hydrogenated phosphatidylcholine is 2:0.5-2.4; The oil comprises caprylic acid / capric acid triglyceride and phytosterol, and the mass ratio of the caprylic acid / capric acid triglyceride to the phytosterol is 1.5:0.5-2; The solvent is water and polyol; the polyol includes glycerol, inositol, caprylyl glycol and 1,3-propylene glycol, and the mass ratio of glycerol, inositol, caprylyl glycol and 1,3-propylene glycol is 37-60:6:5:

7.

2. The nanoliposome particles for encapsulating active substances according to claim 1, characterized in that: The active substance is an active ingredient acceptable in cosmetics.

3. The method for preparing nanoliposome particles for encapsulating active substances according to claim 1 or 2, characterized in that: The steps include: (1) After the oil and emulsifier are mixed evenly at 70-80°C, the temperature is lowered to 40-50°C and then the water-insoluble active ingredient is added. The mixture is stirred slowly to dissolve quickly to obtain the oil phase. (2) Heat the solvent and water to 70-85°C at the same time, keep warm for 20-30 minutes, then cool to 40-50°C, add the water-soluble active ingredient, mix well, and obtain an aqueous phase; (3) The aqueous phase is added to the oil phase and stirred evenly to obtain nanoliposome particles for encapsulating the active ingredient.

4. Use of the nanoliposome particles for encapsulating active substances according to claim 1 or 2 in the preparation of cosmetics.

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