Lipid microsphere preparation as well as preparation method and application thereof in skin moisturizing

Abstract

The invention belongs to the technical field of cosmetics and health care products, and relates to a lipid microsphere preparation, a preparation method thereof and application of the lipid microsphere preparation in skin moisturizing. The lipid microsphere preparation is prepared by mixing and emulsifying a water phase and an oil phase, the water phase contains water, and the oil phase contains vegetable oil and fat-soluble components. By utilizing the lipid microsphere preparation and the application of the lipid microsphere preparation in skin moisturizing, excellent transdermal performance, moisturizing performance and experience feeling can be achieved when the lipid microsphere preparation is applied and used, and the product stability is good.

Description

Technical Field

[0001] The present invention relates to a cosmetic preparation, in particular to a lipid microsphere preparation and a method for preparing the same. The present invention further relates to the use of the lipid microsphere preparation for skin moisturization, and belongs to the fields of cosmetic and health care preparations. Background Art

[0002] Oral administration, injection and transdermal absorption are three common drug delivery methods. Among them, the transdermal absorption drug delivery system refers to administering drugs on the skin surface, enabling the drugs to penetrate the skin at a constant rate or near-constant rate and producing systemic or local therapeutic effects.

[0003] Compared with oral administration, the advantages of transdermal absorption drug delivery are as follows:

[0004] Avoiding the influence of the unpleasant smell of drugs, being convenient to use, especially suitable for pediatric patients or drugs with strong tastes; the drugs act directly on the skin, and the drug absorption process is not affected by factors such as pH, food, and transit time in the digestive tract; avoiding the first-pass effect of the liver; avoiding the occurrence of gastrointestinal adverse reactions.

[0005] Compared with injection administration, transdermal absorption drug delivery releases drugs continuously and stably, avoiding adverse reactions caused by too high blood concentration due to too fast drug absorption.

[0006] In addition, compared with oral administration and injection administration, the transdermal drug delivery system is convenient to use, can be applied by oneself, and once uncomfortable or adverse reaction events occur, it can be removed immediately. Therefore, it is more convenient and safer for patients to use.

[0007] Transdermal drug delivery has been around since ancient times, such as various plaster-like preparations in classic traditional Chinese medicine prescriptions. However, with the emergence of new transdermal drug delivery technologies, it has become a research hotspot in the current pharmaceutical technology field. Researchers believe that with the emergence of new technologies such as liposomes and lipid microspheres, the transdermal drug delivery system will have a broader prospect. The transdermal drug delivery system will also be widely used not only in the drug field but also in the cosmetic field.

[0008] Cosmetics refer to chemical industrial products or fine chemical products that are spread on any part of the human body surface, such as skin, hair, fingernails, toenails, lips, etc., by smearing, spraying or other similar methods, in order to achieve the purpose of cleaning, maintenance, beautification, modification and change of appearance, or correction of human body odor and maintaining good condition. As one of the transdermal system products, cosmetics have brought many benefits to people's lives since their launch. Facial masks, as one of the essential beauty tools for modern women, are a type of product that uses film-forming materials, plants and organic solvents as a matrix, supplemented with nutrients and drugs, and is applied to the face to form a layer of film or non-film-forming covering on the skin, thereby achieving the purpose of skin care and beauty. As a specific product carrier for the application of transdermal technology in the field of cosmetics, facial masks have significantly expanded the market acceptance of transdermal technology.

[0009] Facial masks can be classified into Chinese herbal masks, mineral masks, plant masks, biological masks, chemical masks, etc. according to their ingredients. The main ingredients of facial masks include water, alcohols, moisturizers, film formers, emollients, colorants, active ingredients, preservatives, surfactants, pH adjusters, flavors, etc. Among them, the more commonly used active ingredients include aloe extract, yeast extract, witch hazel extract, allantoin, collagen, hyaluronic acid and its salts, etc.

[0010] In recent years, new transdermal technologies such as liposomes have also been applied in the field of facial masks. For example, Chinese patent CN106955277B discloses a transdermal drug delivery system and application of alcohol liposomes containing hyaluronic acid, and Chinese patent CN106074220B discloses a nanoliposome facial mask. However, a new technology in the pharmaceutical field - lipid microsphere technology has not been applied in the field of cosmetic transdermal systems.

[0011] Lipid nanospheres (LN) are based on plant oil and have phospholipids on the outside. They are relatively stable oil-in-water (O / W) particle dispersion systems. The average particle size of lipid nanospheres is 200nm, which is much smaller than the diameter of capillaries (7-10μm in diameter) and red blood cells (7-8μm in diameter); its volume ratio to red blood cells is 1 / 28000, and its particle size ratio is 1 / 35-40. As a new type of targeted drug delivery system, lipid nanospheres are also called drug missiles. They can deliver drugs to the diseased area in a targeted manner, making the concentration of therapeutic drugs in the target area several times or even hundreds of times higher than that of traditional preparations; at the same time, the amount of drugs distributed in normal tissues is extremely small, so that adverse reactions can be avoided while exerting their efficacy.

[0012] Due to the superior safety, stability and biocompatibility of lipid microspheres, they have been used in the pharmaceutical field in recent years, especially in the field of injections. Products include alprostadil injection, flurbiprofen axetil injection, etc.

[0013] Lipid microspheres are generally prepared by mixing an oil phase and an aqueous phase, and a small amount of other components such as emulsifiers, stabilizers, and pH regulators are also contained in the oil phase or the aqueous phase. The preparation process of lipid microspheres is to dissolve the drug (including emulsifier) in the aqueous phase or the oil phase, mix the aqueous phase and the oil phase, heat them, and then obtain a coarse emulsion by stirring. Subsequently, the coarse emulsion is cooled and finely emulsified with a homogenization device, the pH is adjusted, and after sterilization, the preparation is completed. For example, Chinese Patent CN101496787B discloses a charged prostaglandin E1 lipid microsphere injection; Chinese Patent CN101627968B discloses a preparation method of alprostadil injection; Chinese Patent CN104922065B discloses a preparation process of flurbiprofen axetil fat emulsion; Chinese Patent Application CN108078928A discloses a preparation process of flurbiprofen axetil fat emulsion injection; Chinese Patent Application CN106714787A discloses a preparation process of propofol lipid microsphere emulsion; Chinese Patent CN109261088B discloses a device and a preparation method for preparing lipid microspheres suitable for industrial production.

[0014] However, as a kind of thermodynamically unstable emulsion dispersion system, the lipid microsphere dispersion system is affected by factors such as its formulation and preparation process, which may lead to flocculation, coalescence, delamination (or sedimentation), demulsification, deformation, and Ostwald ripening, thus making the lipid microsphere products lose their market value. At present, the thermodynamic instability of lipid microsphere products still needs to be further improved.

[0015] In addition, with the increase of age, the content of moisturizing factors in the stratum corneum of human skin decreases, and the skin hydration ability declines. And hydration is one of the three possible ways for lipid microspheres to penetrate the skin. The phospholipid bilayer of lipid microspheres can change the intercellular structure of the stratum corneum, causing the hydrophobic tails of the phospholipid bilayer to be disordered, thereby entering the intercellular space and strengthening the hydration of the stratum corneum. The other two possible ways for lipid microspheres to penetrate the skin are: penetration, lipid microspheres can pass through the stratum corneum cells and their interstices and enter the skin through the skin appendage pathway; fusion, the phospholipids of lipid microspheres fuse with the lipids of the stratum corneum to change the structure of the stratum corneum, making it form a flat granular structure, and through the gaps between lipid particles, lipid microspheres enter the skin to play the lipid fusion role.

[0016] So far, the lipid microsphere technology has not been actually applied in the transdermal field, especially in the cosmetics field. If the lipid microsphere technology can be applied to the cosmetics field, it will surely further enrich the technology and products in this field. Summary of the Invention

[0017] The primary object of the present invention is to provide a lipid microsphere preparation, which can have excellent transdermal performance, moisturizing performance and experience when applied by sticking, and the product has good stability.

[0018] To achieve this purpose, in a basic implementation, the present invention provides a lipid microsphere preparation, which is prepared by emulsifying a mixture of an aqueous phase and an oil phase. The aqueous phase contains water, and the oil phase contains vegetable oil and fat-soluble components.

[0019] In a preferred implementation, the present invention provides a lipid microsphere preparation, wherein the aqueous phase further contains one or more of hyaluronic acid or its hydrolyzate, collagen or its hydrolyzate, witch hazel extract, vitamin C, pH regulator, etc. The pH regulator can also be an additive separate from the aqueous phase and the oil phase.

[0020] Hyaluronic acid or its hydrolyzate is widely present in various parts of the human body, such as bones, joints, skin, vitreous body, etc. Hyaluronic acid or its hydrolyzate can remove wrinkles, increase skin elasticity, lubricate joints, regulate the permeability of blood vessel walls, promote wound repair, improve skin nutritional metabolism, etc. Particularly importantly, hyaluronic acid or its hydrolyzate has a particularly strong water retention ability and can carry more than 1000 times its own weight of water. It is the substance with the best moisturizing property found in nature so far and is called an ideal natural moisturizing factor. Therefore, hyaluronic acid is widely used in products in various fields such as cosmetics. Hydrolyzed hyaluronic acid is easier to penetrate the skin due to its relatively small molecular weight. In the present invention, the dosage of hyaluronic acid or its hydrolyzate in the aqueous phase can reach 20 wt%, preferably 5 - 15 wt%.

[0021] Collagen is the most widely existing animal protein in nature and is the main component in connective tissues, accounting for about 30% of the total connective tissue protein. Due to its good biocompatibility, degradability, compatibility, stability and antibacterial properties, collagen has been applied in many fields, such as food, medical beauty, etc. More importantly, due to its unique structure, collagen has excellent adsorption and compatibility with the skin, can prevent tyrosine in the skin from being converted into melanin, has a good whitening effect, and has an ultraviolet damage repair effect. In addition, since collagen contains a large number of hydrophilic groups with relatively large polarity such as amino groups and hydroxyl groups, it is an excellent moisturizing factor and can still retain 45% of its own weight of water at a relative humidity of 70%. In the present invention, the dosage of collagen or its hydrolyzate in the aqueous phase can be as high as 20 wt%, preferably 3 - 10 wt%.

[0022] Witch hazel extract is a concentrate extracted from the dried bark and branches and leaves of Hamamelis Virginiana. This extract can stop bleeding and has anti-inflammatory effects and is commonly used to treat acne, rashes, etc. In addition, witch hazel extract has been included in the list of used cosmetics and is used in a variety of skin care products, with functions such as antioxidant, whitening, moisturizing, and anti-aging. In the present invention, the dosage of witch hazel extract in the aqueous phase can be as high as 20 wt%, preferably 3 - 16 wt%.

[0023] Vitamin C, also known as ascorbic acid, is a water-soluble vitamin. Vitamin C can scavenge free radicals on the skin surface, playing an antioxidant effect. At the same time, vitamin C can also effectively reduce the activity of tyrosinase and prevent the formation of melanocytes to play a whitening role. In the present invention, the maximum dosage of vitamin C can reach 20 wt%, preferably 0.5 - 10 wt%.

[0024] The pH regulator refers to a substance that can regulate the acidity and alkalinity of the lipid microsphere emulsion. Specifically in terms of types, it can be flexibly selected according to the product situation, such as organic acids like ethylenediaminetetraacetic acid, acetic acid, lactic acid, tartaric acid, oxalic acid, citric acid, and inorganic acids like hydrochloric acid, phosphoric acid, and alkaline substances like sodium hydroxide, potassium hydroxide, sodium bicarbonate, diethanolamine. When preparing the lipid microsphere emulsion, the pH regulator can be added to the aqueous phase or added during the preparation of the primary emulsion. The pH value range regulated by the pH regulator can be 4 - 10, preferably 4.5 - 6.5.

[0025] In a preferred embodiment, the present invention provides a lipid microsphere preparation, wherein the vegetable oil is selected from one or more of soybean oil, cottonseed oil, tea oil, corn oil, sesame oil, peanut oil, etc., preferably soybean oil.

[0026] In a preferred embodiment, the present invention provides a lipid microsphere preparation, wherein the fat-soluble components are selected from one or more of glycerol, niacinamide, lycopene, vitamin E, coenzyme Q10, etc.

[0027] Glycerol, chemically named propanetriol, has good water solubility and hygroscopicity and is widely used as a humectant in cosmetics. Glycerol is an excellent humectant, and its concentration in cosmetics can be as high as 20 wt%. In actual use, the addition amount of glycerol should not be too much, otherwise it will make the skin feel sticky, preferably 1 - 10 wt%.

[0028] Niacinamide, also known as nicotinamide, is an amide compound of nicotinic acid and is a water-soluble vitamin. In the field of topical skin use, niacinamide can block the transmission of melanin and accelerate metabolism, improve the problem of dull skin, reduce fine lines, and maintain elasticity and luster. In actual use, the maximum dosage of niacinamide can reach 10 wt%, preferably 0.1 - 5 wt%.

[0029] Lycopene is mainly derived from the ripe fruits of the solanaceous plant tomato and is the strongest antioxidant found in nature so far. The rate constant of its quenching singlet oxygen is 100 times that of vitamin E. In the present invention, the maximum dosage of lycopene in the oil phase can reach 1 wt%, preferably 0.01 - 0.6 wt%.

[0030] As a fat-soluble vitamin, vitamin E has antioxidant effects and is widely used in the fields of medicine and cosmetics. In the present invention, the maximum dosage of vitamin E in the oil phase can reach 33 wt%, preferably 0.1% - 10 wt%.

[0031] Coenzyme Q10 is a fat-soluble ubiquinone, which has functions such as antioxidant, protecting the heart, and delaying aging, and is widely used in multiple fields such as health products and medical preconception. In the field related to the skin, due to its antioxidant, anti-apoptosis, and anti-skin-aging effects, coenzyme Q10 is also widely used. In the present invention, the maximum dosage of coenzyme Q10 can reach 10 wt%, preferably 0.1 - 5 wt%.

[0032] In a preferred embodiment, the present invention provides a lipid microsphere preparation, wherein the aqueous phase and / or the oil phase further contains an emulsifier, selected from one or more of lecithin, poloxamer, hydrogenated castor oil, polyoxyethylene hydrogenated castor oil, etc., preferably lecithin.

[0033] The emulsifier belongs to a surfactant, and its dosage in the aqueous phase and / or the oil phase can reach 0.1 - 15 wt%.

[0034] Lecithin is a mixture composed of various phospholipids, and can be selected from one or more of egg yolk lecithin, soybean lecithin, hydrogenated egg yolk lecithin, hydrogenated soybean lecithin, distearoyl phosphatidylcholine, palmitoyl phosphatidylcholine, phosphatidylserine, phosphatidic acid, synthetic phospholipids, etc., preferably soybean lecithin. In the present invention, the dosage of lecithin in the oil phase can be as high as 14 wt%, preferably 3 - 10 wt%.

[0035] In a preferred embodiment, the present invention provides a lipid microsphere preparation, wherein the aqueous phase and / or the oil phase further contains a stabilizer, selected from one or more of oleic acid and its salts, cholesterol, cholic acid or deoxycholic acid and its salts, nitrogen, vitamin C, etc.

[0036] The oleate is a sodium salt or a potassium salt, and oleic acid and its salts are preferably oleic acid. In the present invention, the dosage of oleic acid in the oil phase can be as high as 45 wt%, preferably 0.1 - 1 wt%.

[0037] Cholesterol is one of the stabilizers used in the lipid microsphere preparation. In the present invention, the dosage of cholesterol can be selected from 0.001 - 5 wt%, preferably 0.01 - 1 wt%.

[0038] Cholic acid or deoxycholic acid and its salts are one of the stabilizers used in the lipid microsphere preparation, especially the sodium salt. In the present invention, the dosage of cholic acid or sodium deoxycholate can be selected from 0.001 - 5 wt%, preferably 0.01 - 1 wt%.

[0039] In a preferred embodiment, the present invention provides a lipid microsphere preparation, wherein the aqueous phase and / or the oil phase further contains a preservative selected from one or more of benzoic acid and its salts, sorbic acid and its salts, esters of p-hydroxybenzoic acid, etc., preferably an equimolar ratio mixture of methyl p-hydroxybenzoate and propyl p-hydroxybenzoate. In the present invention, the dosage of the preservative is 0.01 - 0.03 wt% of the aqueous phase and / or the oil phase.

[0040] In a preferred embodiment, the present invention provides a lipid microsphere preparation, wherein by weight ratio,

[0041] the aqueous phase contains 5 - 50 parts of purified water, 1 - 15 parts of hydrolyzed hyaluronic acid, 1 - 20 parts of witch hazel extract, and 1 - 30 parts of collagen or its hydrolysate;

[0042] the oil phase contains 1 - 20 parts of soybean oil, 1 - 20 parts of glycerol, 1 - 30 parts of lecithin, 0.2 - 16 parts of oleanolic acid, 0.4 - 15 parts of polyoxyethylene hydrogenated castor oil, 0.2 - 10 parts of vitamin E, 0 - 5 parts of oleic acid, 0 - 12 parts of lycopene, 0 - 12 parts of coenzyme Q10, and 0 - 10 parts of preservative,

[0043] the volume ratio of the aqueous phase to the oil phase is 0.05 - 28:1.

[0044] In a preferred embodiment, the present invention provides a lipid microsphere preparation, wherein by weight ratio,

[0045] the aqueous phase contains 40 parts of purified water, 5 parts of hydrolyzed hyaluronic acid, 6 parts of witch hazel extract, and 4 parts of collagen hydrolysate;

[0046] the oil phase contains 12 parts of soybean oil, 10 parts of glycerol, 7 parts of lecithin, 6 parts of oleanolic acid, 6 parts of polyoxyethylene hydrogenated castor oil, 3 parts of vitamin E, 0.25 parts of oleic acid, 0.44 parts of lycopene, 0.3 parts of coenzyme Q10, and 0.01 part of preservative,

[0047] the volume ratio of the aqueous phase to the oil phase is 1.2:1.

[0048] In a preferred embodiment, the present invention provides a lipid microsphere preparation, wherein by weight ratio,

[0049] the aqueous phase contains 42 parts of purified water, 5 parts of hydrolyzed hyaluronic acid, 8 parts of witch hazel extract, and 4 parts of collagen hydrolysate;

[0050] The oil phase contains 11 parts of soybean oil, 10 parts of glycerol, 8 parts of lecithin, 4 parts of oleanolic acid, 4 parts of polyoxyethylene hydrogenated castor oil, 3 parts of vitamin E, 0.24 parts of oleic acid, 0.45 parts of lycopene, 0.3 parts of coenzyme Q10, and 0.01 parts of preservative.

[0051] The volume ratio of the water phase to the oil phase is 1.4:1.

[0052] In a preferred embodiment, the present invention provides a lipid microsphere preparation, wherein by weight ratio,

[0053] The water phase contains 46 parts of purified water, 6 parts of hydrolyzed hyaluronic acid, 7 parts of witch hazel extract, and 5 parts of collagen hydrolysate.

[0054] The oil phase contains 10 parts of soybean oil, 10 parts of glycerol, 7 parts of lecithin, 2 parts of oleanolic acid, 2 parts of polyoxyethylene hydrogenated castor oil, 4 parts of vitamin E, 0.24 parts of oleic acid, 0.4 parts of lycopene, 0.35 parts of coenzyme Q10, and 0.01 parts of preservative.

[0055] The volume ratio of the water phase to the oil phase is 1.8:1.

[0056] In a preferred embodiment, the present invention provides a lipid microsphere preparation, wherein by weight ratio,

[0057] The water phase contains 49 parts of purified water, 7 parts of hydrolyzed hyaluronic acid, 7 parts of witch hazel extract, and 6 parts of collagen hydrolysate.

[0058] The oil phase contains 10 parts of soybean oil, 8 parts of glycerol, 7 parts of lecithin, 0.5 parts of oleanolic acid, 0.5 parts of polyoxyethylene hydrogenated castor oil, 4 parts of vitamin E, 0.24 parts of oleic acid, 0.6 parts of lycopene, 0.15 parts of coenzyme Q10, and 0.01 parts of preservative.

[0059] The volume ratio of the water phase to the oil phase is 2.2:1.

[0060] In a preferred embodiment, the present invention provides a lipid microsphere preparation, and the preparation method of the lipid microsphere preparation includes the following steps:

[0061] (1) Preparation of water phase: The water phase substances are mixed and dispersed evenly.

[0062] (2) Preparation of oil phase: The oil phase substances are mixed and dispersed evenly.

[0063] (3) Primary emulsification: The oil phase is added to the water phase under stirring, and stirring is continued for a certain time after addition.

[0064] (4) Fine emulsification: The primary emulsification product is subjected to high-pressure homogenization once or multiple times.

[0065] In a preferred embodiment, the present invention provides a lipid microsphere preparation, and the preparation method of the lipid microsphere preparation comprises the following steps:

[0066] (1) Preparation of the aqueous phase: Under nitrogen filling conditions, add aqueous phase substances to the aqueous phase tank, heat to 65 - 75 °C, and perform high-speed shear dispersion at 5000 rpm for 20 minutes, then set aside;

[0067] (2) Preparation of the oil phase: Under nitrogen filling conditions, add oil phase substances to the oil phase tank, heat to 60 - 70 °C, and perform high-speed shear dispersion at 5000 rpm for 15 minutes, then set aside;

[0068] (3) Primary emulsification: Slowly add the oil phase to the aqueous phase, perform high-speed shear emulsification in the aqueous phase tank for 25 - 35 minutes at a rotation speed of 2000 - 3000 rpm, supplement with injection water to the full volume, and adjust the pH value;

[0069] (4) Fine emulsification: Homogenize with a high-pressure homogenizer for more than 4 times, with a homogenization pressure of 1000 - 1500 bar, until the particle size range is 130 - 280 nm, preferably 150 - 220 nm;

[0070] (5) Sterilization: Sterilize the emulsion obtained from fine emulsification with a 0.22 - micron microporous membrane;

[0071] (6) Filling: Fill the sterile emulsion into the prepared packaging bags, and seal them aseptically to obtain the lipid microsphere preparation.

[0072] The second object of the present invention is to provide the use of the above lipid microsphere preparation for preparing health care products, cosmetics or skin care products for skin moisturization, so as to have excellent transdermal performance, moisturizing performance and experience feeling during patch application, and the product has good stability.

[0073] To achieve this object, in a basic embodiment, the present invention provides the use of the above lipid microsphere preparation for preparing health care products, cosmetics or skin care products for skin moisturization.

[0074] The beneficial effect of the present invention is that by using the lipid microsphere preparation of the present invention and its use for skin moisturization, it can have excellent transdermal performance, moisturizing performance and experience feeling during patch application, and the product has good stability. Description of the Drawings

[0075] Figure 1 It is a comparison chart of the moisturizing performance of the example product and the control product of the present invention obtained in Example 2.

[0076] Figure 2 It is a comparison chart of the facial texture of the user before and after using the example product of the present invention obtained in Example 2. Detailed Embodiments

[0077] The following further describes the specific implementation manners of the present invention in conjunction with embodiments.

[0078] Example 1 Preparation of Lipid Microsphere Preparation (I)

[0079] Composition of aqueous phase (parts by weight): 40 parts of purified water, 5 parts of hydrolyzed hyaluronic acid (Jiangsu Hongkang Future Nutrition Technology Co., Ltd., the same below), 6 parts of witch hazel extract (for the preparation method, see: Wei Hong, Yang Chunhua, Xu Qiulin, Wu Yuping. Research on the protection of animal skin by extracts from three Hamamelidaceae plants [J]. China Surfactant Detergent & Cosmetics, 2005(01):27 - 29. the same below), 4 parts of collagen hydrolyzate (Fujian Funing Puming Gelatin Co., Ltd., the same below).

[0080] Composition of oil phase (parts by weight): 12 parts of soybean oil, 10 parts of glycerol, 7 parts of lecithin, 6 parts of oleanolic acid, 6 parts of polyoxyethylene hydrogenated castor oil, 3 parts of vitamin E, 0.25 parts of oleic acid, 0.44 parts of lycopene, 0.3 parts of coenzyme Q10, 0.01 part of preservative (methyl p - hydroxybenzoate: propyl p - hydroxybenzoate = 2:1).

[0081] pH regulator: 10wt% sodium hydroxide solution, adjusting the pH value to 5.0 - 6.0.

[0082] The preparation process is as follows:

[0083] (1) Preparation of aqueous phase: Under nitrogen filling conditions, add the aqueous phase substances to the aqueous phase tank, heat to 70°C, and perform high - speed shear dispersion at 5000 rpm for 20 minutes, and set aside;

[0084] (2) Preparation of oil phase: Under nitrogen filling conditions, add the oil phase substances to the oil phase tank, heat to 65°C, and perform high - speed shear dispersion at 5000 rpm for 15 minutes, and set aside;

[0085] (3) Primary emulsification: Slowly add the oil phase to the aqueous phase, perform high - speed shear emulsification in the aqueous phase tank for 30 minutes at a rotation speed of 2500 rpm, make up the injection water to the full volume, and adjust the pH value;

[0086] (4) Fine emulsification: Homogenize with a high - pressure homogenizer for more than 4 times, with a homogenization pressure of 1200 bar, until the particle size range is 150 nm - 220 nm;

[0087] (5) Sterilization: Sterilize the emulsion obtained by fine emulsification with a 0.22 - micron microporous filter membrane;

[0088] (6) Filling: Immerse the sterile emulsion into the prepared facial non - woven fabric and seal it;

[0089] (7) Finished product: Put the above non - woven fabric into a medicinal packaging bag to obtain the finished product.

[0090] The volume ratio of the above aqueous phase (including the added pH regulator and the additional water for injection) to the oil phase is 1.2:1.

[0091] Preparation of lipid microsphere preparation (II) in Example 2

[0092] Composition of the aqueous phase (parts by weight): 42 parts of purified water, 5 parts of hydrolyzed hyaluronic acid, 8 parts of witch hazel extract, and 4 parts of collagen hydrolyzate.

[0093] Composition of the oil phase (parts by weight): 11 parts of soybean oil, 10 parts of glycerol, 8 parts of lecithin, 4 parts of oleanolic acid, 4 parts of polyoxyethylene hydrogenated castor oil, 3 parts of vitamin E, 0.24 parts of oleic acid, 0.45 parts of lycopene, 0.3 parts of coenzyme Q10, and 0.01 part of preservative (methyl p-hydroxybenzoate: propyl p-hydroxybenzoate = 2:1).

[0094] The specific preparation method is the same as that in Example 1.

[0095] The volume ratio of the above aqueous phase (including the added pH regulator and the additional water for injection) to the oil phase is 1.4:1.

[0096] Preparation of lipid microsphere preparation (III) in Example 3

[0097] Composition of the aqueous phase (parts by weight): 46 parts of purified water, 6 parts of hydrolyzed hyaluronic acid, 7 parts of witch hazel extract, and 5 parts of collagen hydrolyzate.

[0098] Composition of the oil phase (parts by weight): 10 parts of soybean oil, 10 parts of glycerol, 7 parts of lecithin, 2 parts of oleanolic acid, 2 parts of polyoxyethylene hydrogenated castor oil, 4 parts of vitamin E, 0.24 parts of oleic acid, 0.4 parts of lycopene, 0.35 parts of coenzyme Q10, and 0.01 part of preservative (methyl p-hydroxybenzoate: propyl p-hydroxybenzoate = 2:1).

[0099] The specific preparation method is the same as that in Example 1.

[0100] The volume ratio of the above aqueous phase (including the added pH regulator and the additional water for injection) to the oil phase is 1.8:1.

[0101] Preparation of lipid microsphere preparation (IV) in Example 4

[0102] Composition of the aqueous phase (parts by weight): 49 parts of purified water, 7 parts of hydrolyzed hyaluronic acid, 7 parts of witch hazel extract, and 6 parts of collagen hydrolyzate.

[0103] Oil phase composition (parts by weight): 10 parts of soybean oil, 8 parts of glycerol, 7 parts of lecithin, 0.5 part of oleanolic acid, 0.5 part of polyoxyethylene hydrogenated castor oil, 4 parts of vitamin E, 0.24 part of oleic acid, 0.6 part of lycopene, 0.15 part of coenzyme Q10, 0.01 part of preservative (methyl p-hydroxybenzoate: propyl p-hydroxybenzoate = 2:1).

[0104] The specific preparation method is the same as that in Example 1.

[0105] The volume ratio of the above aqueous phase (including the added pH regulator and the added injection water) to the oil phase is 2.2:1.

[0106] Comparative Examples 1-4:

[0107] Remove oleanolic acid and polyoxyethylene hydrogenated castor oil in the oil phase in Examples 1-4 respectively, and the others are exactly the same as those in Examples 1-4.

[0108] Test Example 1 Performance test of lipid microsphere preparation

[0109] Through comparative research (appearance, experience), it is found that there are obvious differences between the products of Comparative Examples 1-4 and those of Examples 1-4:

[0110] The products of Comparative Examples 1-4 have poor formability or poor stability after standing at room temperature for 2 days, and phenomena such as demulsification occur; the products of Examples 1-4 have good stability after standing for several days, and no quality problems such as demulsification occur.

[0111] Test Example 2 Evaluation test on the usability, moisturizing property and fine line change of lipid microsphere preparation

[0112] The following comparative test studies were carried out with the products of the examples of the present invention and the control products (i.e., commercially available products), and the process and results are as follows.

[0113] (1) Usability evaluation test

[0114] In order to evaluate the usability of the products of the present invention, 11 ordinary people (7 males and 4 females) were selected. The products of Examples 1-4 and the commercially available control products (Guangdong Manlun Cosmetics Co., Ltd.) were each cut in half and randomly distributed to 11 subjects, ensuring that each subject applied half of the product of the example and half of the commercially available control product on the left and right sides of the face respectively, and both were applied for 30 minutes. The overall usability was measured according to the evaluation criteria. The evaluation criteria adopted three indicators: usability, irritation, and residue feeling, and the evaluation results were divided into three grades: good, ordinary, and poor. The evaluation results can only support one product and cannot support the products of the examples and the control product at the same time. Those who support are recorded as "+", and those who do not support are recorded as "-". The final results and support rates are shown in Table 1.

[0115] Table 1 Usability evaluation results

[0116] Item Example Reference substance 1 (Example 1 + control) + - 2 (Example 1 + control) + - 3 (Example 1 + control) + - 4 (Example 2 + control) - + 5 (Example 2 + control) + - 6 (Example 2 + control) + - 7 (Example 3 + control) + - 8 (Example 3 + control) + - 9 (Example 3 + control) - + 10 (Example 4 + control) + - 11 (Example 4 + control) + - Total 9(81.8％) 2(18.2％)

[0117] As can be seen from Table 1, the support rate for the products of the examples is significantly higher than that of the commercially available control products, indicating that from the three dimensions of usability, irritation, and residue feeling, the products of the present invention have a better overall usability.

[0118] (2) Moisturizing property evaluation test

[0119] To evaluate the moisturizing performance of the products of the present invention, 4 female and 7 male subjects who participated in the "(1) Usability evaluation test" were selected. The products of Examples 1-4 and the commercially available control product (Guangdong Manlun Cosmetics Co., Ltd.) were each cut in half, and each subject applied half of the product of the example and half of the commercially available control product on the left and right sides of the face respectively. The water content of the left and right sides of each subject's face was measured before the start of the test and 2 hours, 6 hours, and 24 hours after the application was completed using a skin tester (Corneometer CM825, Germany), and the water content increase rate relative to that before the start of the test was calculated. The results are shown in Tables 2-4 and Figure 1 as follows.

[0120] Table 2 Water content increase rate after 2 hours of application

[0121] Item Example Reference substance 1 (Example 1 + control) 27％ 16％ 2 (Example 1 + control) 22％ 3％ 3 (Example 1 + control) 19％ 8％ 4 (Example 2 + control) 20％ 10％ 5 (Example 2 + control) 27％ 11％ 6 (Example 2 + control) 29％ 7％ 7 (Example 3 + control) 25％ 11％ 8 (Example 3 + control) 27％ 10％ 9 (Example 3 + control) 23％ 17％ 10 (Example 4 + control) 26％ 17％ 11 (Example 4 + control) 25％ 9％ Average 24％ 11％

[0122] Table 3 Water content increase rate after 6 hours of application

[0123]

[0124]

[0125] Table 4 Water content increase rate after 24 hours of application

[0126] Item Example Reference substance 1 (Example 1 + control) 10％ 1％ 2 (Example 1 + control) 8％ 1％ 3 (Example 1 + control) 5％ -1％ 4 (Example 2 + control) 6％ -1％ 5 (Example 2 + control) 13％ -6％ 6 (Example 2 + control) 3％ 0％ 7 (Example 3 + control) 2％ -4％ 8 (Example 3 + control) 10％ 4％ 9 (Example 3 + control) 8％ 0％ 10 (Example 4 + control) 9％ 6％ 11 (Example 4 + control) 7％ 0％ Average 10％ 1％

[0127] From Figure 1 the results, it can be seen that as time goes by, although the water content of the face of the products of the examples and the water content of the face of the commercially available control products have a similar development trend, the water content of the face of those who applied the products of the examples is significantly higher. And after 24 hours of application, the water content of the face of some of those who applied the commercially available control product has dropped below the level before the start of the test, while the water content of the face of those who applied the products of the present invention is still higher than the level before the start of the test. Thus, it can be seen that the products of the examples of the present invention significantly have a higher moisturizing performance.

[0128] (3) Fine line change evaluation test

[0129] To evaluate the improvement effect of the product of the present invention on fine lines, 11 subjects who participated in the "(1) Evaluation Test of Usage Experience" were selected. The products of Examples 1-4 and a commercially available control product (Guangdong Manlun Cosmetics Co., Ltd.) were distributed to the 11 subjects and applied to the face. The specific application positions and left-right order were determined by each subject himself / herself. However, no matter where it was applied, the parallel control method was adopted, that is, the products of the examples and the commercially available control product must be symmetrically applied on both sides of the application position. The application period was: apply for 30 minutes before going to bed every day for 2 consecutive weeks. The evaluation index was eye fine lines. The scores of the evaluation indexes of the VISIA skin detector before the start of the test and after application (of the examples and the control product) were recorded and averaged. The specific results are shown in Table 5 below. The lower the score value, the better the improvement degree.

[0130] Table 5 Results of Fine Line Changes

[0131] Item Before the test Example Reference substance 1 (Example 1 + control) 9.3 7.5 8 2 (Example 2 + control) 9.9 6.8 8.1 3 (Example 3 + control) 8.7 6.5 7.7 4 (Example 4 + control) 9.2 7 8.4 5 (Example 1 + control) 8.5 6.1 8 6 (Example 2 + control) 9.6 6.4 8.9 7 (Example 3 + control) 10.7 7.1 9.6 8 (Example 4 + control) 8 6.6 7.8 9 (Example 1 + control) 8.4 6.7 8.1 10 (Example 2 + control) 9 6.2 8.4 11 (Example 3 + control) 9.1 7.9 8.6 Average 9.1 6.8 8.3

[0132] As can be seen from the results in Table 5, the improvement of the eye fine lines of the users after applying the product of the present invention is better than that of the commercially available control product. For example, the comparison of the eye texture of one of the subjects before and after using the product of the present invention (Example 2) is as Figure 2 shown. It can be Figure 2 seen that the product prepared in the example of the present invention has good transdermal performance and can fade fine lines.

[0133] The above results prove that compared with the products in the field of traditional cosmetic transdermal systems, the product of the present invention has the characteristics of good transdermal absorption effect, strong ability to fade fine lines, good moisturizing effect, no discomfort during use, etc., and has good stability and great promotion value.

[0134] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. In this way, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention also intends to include these modifications and variations. The above embodiments or implementation manners are only illustrative examples of the present invention. The present invention can also be implemented in other specific ways or other specific forms without departing from the gist or essential characteristics of the present invention. Therefore, the described implementation manners should be regarded as illustrative rather than restrictive in any aspect. The scope of the present invention should be defined by the appended claims, and any changes equivalent to the intention and scope of the claims should also be included in the scope of the present invention.

Claims

1. A lipid microsphere preparation, characterized in that: The lipid microsphere preparation is prepared by emulsifying a water phase and an oil phase after mixing. The water phase contains water, and the oil phase contains vegetable oil and fat-soluble components.

2. The lipid microsphere preparation according to claim 1, wherein: The water phase further contains one or more of hyaluronic acid or its hydrolyzate, collagen or its hydrolyzate, witch hazel extract, vitamin C, and pH regulator.

3. The lipid microsphere preparation according to claim 1, characterized in that: The vegetable oil is selected from one or more of soybean oil, cottonseed oil, tea oil, corn oil, sesame oil, and peanut oil.

4. The lipid microsphere preparation according to claim 1, characterized in that: The fat-soluble components are selected from one or more of glycerol, niacinamide, lycopene, vitamin E, and coenzyme Q10.

5. The lipid microsphere preparation according to claim 1, characterized in that: The water phase and / or the oil phase further contains an emulsifier selected from one or more of lecithin, poloxamer, hydrogenated castor oil, and polyoxyethylene hydrogenated castor oil.

6. The lipid microsphere preparation according to claim 1, characterized in that: The water phase and / or the oil phase further contains a stabilizer selected from one or more of oleic acid and its salts, cholesterol, cholic acid or deoxycholic acid and its salts, nitrogen, and vitamin C.

7. The lipid microsphere preparation according to claim 1, characterized in that: The water phase and / or the oil phase further contains a preservative selected from one or more of benzoic acid and its salts, sorbic acid and its salts, and esters of p-hydroxybenzoic acid.

8. The lipid microsphere preparation according to claim 1, characterized in that: By weight ratio, the water phase contains 5-50 parts of purified water, 1-15 parts of hydrolyzed hyaluronic acid, 1-20 parts of witch hazel extract, and 1-30 parts of collagen or its hydrolyzate; The oil phase contains 1-20 parts of soybean oil, 1-20 parts of glycerol, 1-30 parts of lecithin, 0.2-16 parts of oleanolic acid, 0.4-15 parts of polyoxyethylene hydrogenated castor oil, 0.2-10 parts of vitamin E, 0-5 parts of oleic acid, 0-12 parts of lycopene, 0-12 parts of coenzyme Q10, and 0-10 parts of preservative; The volume ratio of the water phase to the oil phase is 0.05-28:

1.

9. The lipid microsphere preparation according to any one of claims 1-8, characterized in that, The preparation method of the lipid microsphere preparation comprises the following steps: (1) Preparation of water phase: The water phase substances are mixed and dispersed evenly; (2) Preparation of oil phase: The oil phase substances are mixed and dispersed evenly; (3) Primary emulsification: The oil phase is added to the water phase under stirring, and stirring is continued for a certain time after addition; (4) Fine emulsification: The primary emulsification product is homogenized by high pressure once or multiple times.

10. Use of the lipid microsphere preparation according to any one of claims 1-9 for preparing a health product, cosmetic, or skin care product for skin moisturization.

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