Nano-scale solid lipid carrier, preparation method and cosmetics containing the same

Abstract

The present invention provides a nano-scale solid lipid carrier, a preparation method and cosmetics containing the same, which include 10% to 20% by weight of octanoyl salicylic acid, 10% to 30% of liquid lipids, 15% to 25% of solid lipids and 10% to 15% of surfactants, wherein the liquid lipids are selected from medium-chain fatty acid glycerides. The present invention prepares a nano-scale solid lipid carrier with high concentration of octanoyl salicylic acid, which has high stability, is not easy to delaminate, and has an embedding rate of more than 99.9%. When the carrier is used to prepare cosmetics, the cost can be significantly reduced, and smoother and better-textured cosmetics can be obtained.

Description

Technical Field

[0001] The invention belongs to the field of chemical industry, and particularly relates to a nano-scale solid lipid carrier and a preparation method thereof and cosmetics containing the same, and specifically relates to a nano-scale solid lipid carrier encapsulating high-concentration octanoylsalicylic acid and a preparation method thereof and cosmetics containing the same. Background Art

[0002] With the improvement of living standards, people gradually pay more attention to skin care and beauty, and the function of skin care products is to keep the skin moisturized, restore skin elasticity, and delay aging. Skin care products usually need the assistance of carriers, and embedding is the first choice. The scope of embedding technology is very wide, such as W / O, O / W, W / O / W, liposomes, and lipid carriers. Among them, nano-structured lipid carriers (NLC) are composed of solid lipids as a matrix and a certain amount of liquid lipids. It breaks through the emulsification technology of traditional cosmetics and prepares an oil-in-fat-in-water O / F / W system by mixing solid lipids and liquid lipids in an aqueous solution of surfactants. Because it can improve the chemical stability of active ingredients, increase skin hydration produced by occlusive effects, and enhance the bioavailability of active ingredients on the skin, it has gained attention in the field of cosmetics.

[0003] Salicylic acid (i.e., o-hydroxybenzoic acid) has physiological regulating effects and can be used as a pharmaceutical intermediate and fine chemical raw material and is widely used in agriculture, medicine, chemical industry and other industries. In daily life, salicylic acid can be seen added to many daily skin care products such as facial masks, essences and lotions. Salicylic acid, as an acidic component, can fight against aging keratin on the face, allowing the skin of the face to reach a relatively light and fair state. Salicylic acid can also improve acne and enlarged pores, and has a certain effect on deep cleaning of pores, but salicylic acid also has certain irritation and tissue destructiveness. At present, the concentration of salicylic acid added in general cosmetics is between 0.5-2%. 5-Octanoyl salicylic acid (hereinafter referred to as octanoyl salicylic acid) is a derivative of salicylic acid, which is fat-soluble, milder than salicylic acid, less irritating to the skin, has keratin-promoting, anti-inflammatory, antibacterial and anti-acne activity, can directly penetrate into the pores to dissolve the oil in the pores, and regulate the oil secretion of oily skin and acne-prone skin. At low concentrations, octylosalicylic acid has the effects of moisturizing, softening keratin and exfoliating. At high concentrations, it can be used for "skin resurfacing" in specific hospitals.

[0004] Patent document 1 (CN107595655A) is the research result of the applicant before, and it prepares the nano-scale solid lipid carrier of low-concentration octanoyl salicylic acid with high embedding rate, wherein the concentration of octanoyl salicylic acid is 1-5%. However, when cosmetics are prepared with such concentration, taking the concentration of octanoyl salicylic acid in NLC as 3% as an example, to make octanoyl salicylic acid reach 1% in cosmetics, at least about 33 grams of nano-scale solid lipid carrier is required in 100 grams of cosmetic formula, and the cosmetic formula prepared according to this is likely to face two problems, one is the increase in cost, and the other is that it is not easy to make cosmetics with good texture. Moreover, the nano-scale solid lipid carrier of low-concentration octanoyl salicylic acid is not suitable for use for the purpose of "skin replacement" because the required amount of nano-scale solid lipid carrier is too high. Summary of the invention

[0005] Problem that the invention aims to solve

[0006] In order to solve the above technical problems, the applicant found that if the concentration of octanoylsalicylic acid in NLC is increased, for example, the concentration of octanoylsalicylic acid is increased to 20%, in order to make octanoylsalicylic acid reach 1% in cosmetics, only about 5 grams of nano-scale solid lipid carrier is needed in 100 grams of cosmetic formula, which can reduce costs and easily obtain a smooth cosmetic formula, but at the same time it brings new problems. Due to the increase in the concentration of active ingredients, the amount of surfactant will increase, and the types and amounts of the corresponding components need to be adjusted. When preparing the carrier, the problem of unstable carrier and easy stratification will be faced.

[0007] The inventors have conducted a detailed study on the carrier components and ratios, and provided a nano-scale solid lipid carrier of high-concentration octanoyl salicylic acid, which has high stability, no stratification, and high embedding rate. The cosmetics prepared therefrom have good skin permeability.

[0008] The present invention also provides a method for preparing the aforementioned nano-scale solid lipid carrier.

[0009] The present invention also provides cosmetics comprising the aforementioned nanoscale solid lipid carrier.

[0010] Solutions for solving problems

[0011] The present invention provides the following technical solutions:

[0012] [1] A nanoscale solid lipid carrier, wherein:

[0013] The carrier comprises the following components in weight percentage:

[0014] Capryloyl salicylic acid 10-20%

[0015] Liquid lipids 10-30%

[0016] Solid lipids 15-25%

[0017] Surfactant 10-15%;

[0018] Wherein, the liquid lipid is selected from medium-chain fatty acid glycerides.

[0019] [2] The nanoscale solid lipid carrier according to [1], wherein

[0020] The medium-chain fatty acid glyceride includes one or more of monoglycerides, diesters or triesters of C8-C10 saturated carboxylic acids. Further preferably, the medium-chain fatty acid glyceride is selected from one or more of caprylic acid glyceryl monoester, caprylic acid diglyceride, caprylic acid triglyceride, capric acid glyceryl monoester, capric acid diglyceride, capric acid triglyceride, caprylic acid decanoic acid glyceryl monoester, caprylic acid decanoic acid diglyceride and caprylic acid decanoic acid triglyceride.

[0021] [3] The nanoscale solid lipid carrier according to [1] or [2], wherein

[0022] The solid lipids include one or more of spermaceti, beeswax, palm wax and behenic acid glyceryl ester.

[0023] [4] The nanoscale solid lipid carrier according to any one of the technical solutions [1] to [3], wherein

[0024] The surfactant includes one or more of polysorbate, polyoxyethylene-polyoxypropylene block copolymer and decyl glucoside.

[0025] [5] The nanoscale solid lipid carrier according to any one of the technical solutions [1] to [4], wherein

[0026] The medium-chain fatty acid glyceride is selected from caprylic / decanoic acid triglyceride; further, the solid lipid is selected from beeswax; further, the surfactant is selected from decyl glucoside.

[0027] [6] The nanoscale solid lipid carrier according to any one of the technical solutions [1] to [5], wherein

[0028] The carrier also includes polyols, phospholipids and water.

[0029] [7] The nanoscale solid lipid carrier according to any one of the technical solutions [1] to [6], wherein

[0030] The content ratio of the solid lipid to octanoylsalicylic acid is 1.1-1.6:1.

[0031] [8] The nanoscale solid lipid carrier according to any one of the technical solutions [1] to [7], wherein

[0032] The particle size of the carrier is no more than 1000 nm.

[0033] [9] The nanoscale solid lipid carrier according to any one of the technical solutions [1] to [8], wherein

[0034] The interface potential of the carrier is above |32| mV.

[0035]

[10] The nanoscale solid lipid carrier according to any one of the technical solutions [1] to [9], wherein

[0036] The embedding rate of the carrier is above 99.9%.

[0037]

[11] A method for preparing a nanoscale solid lipid carrier as described in any one of the technical solutions [1] to

[10] , wherein the preparation method comprises the following steps:

[0038] 1) Heat the liquid lipid and solid lipid to 85°C, add capryloyl salicylic acid, and stir until dissolved;

[0039] 2) Mix the surfactant, polyol, phospholipid and water, heat them to 90° C., and stir until they are dissolved to obtain an aqueous phase;

[0040] 3) adding the mixture obtained in step 1) to the aqueous phase obtained in step 2) and maintaining the temperature at 90° C.;

[0041] 4) Pre-emulsification using a pre-homogenizer;

[0042] 5) The mixed phase emulsion after pre-emulsification is fed into a high-pressure homogenizer and subjected to pressure treatment to obtain the carrier.

[0043]

[12] A cosmetic, comprising the nanoscale solid lipid carrier as described in any one of the technical solutions [1] to

[11] .

[0044] Effects of the Invention

[0045] The invention prepares a nano-scale solid lipid carrier with high concentration of octanoyl salicylic acid, which has high stability, is not easy to be delaminated, and has a high embedding rate of more than 99.9%. When the carrier is used to prepare cosmetics, the cost can be significantly reduced, and smoother and better-textured cosmetics can be obtained. The cosmetics prepared by using the carrier of the invention have good skin permeability and can penetrate into the melanin in the skin in a short time to produce an effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 The figure shows the concentration variation trend of the facial cream prepared in the application example of the present invention. DETAILED DESCRIPTION

[0047] The following describes the embodiments of the present invention, but the present invention is not limited thereto. The present invention is not limited to the various structures described below, and various changes can be made within the scope of the invention claim, and the embodiments and embodiments obtained by appropriately combining the technical means disclosed in different embodiments and embodiments are also included in the technical scope of the present invention. In addition, all the documents recorded in this specification are cited in this specification as references.

[0048] Unless defined otherwise, technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0049] In the context of describing the invention (especially in the context of the following claims), the terms "a", "an", and "the" and similar language are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context.

[0050] In this specification, the numerical range expressed using "numerical value A to numerical value B" or "numerical value A-numerical value B" means a range including the endpoints numerical values ​​A and B.

[0051] In this specification, the meaning of "may" includes both the meaning of performing a certain process and the meaning of not performing a certain process. In this specification, "optional" or "optionally" means that the event or situation described below may or may not occur, and the description includes the situation where the event occurs and the situation where the event does not occur.

[0052] In this specification, the references to "some specific / preferred embodiments", "other specific / preferred embodiments", "some specific / preferred technical solutions", "other specific / preferred technical solutions", etc. refer to the specific elements (e.g., features, structures, properties and / or characteristics) related to the embodiments described herein being included in at least one embodiment described herein, and may or may not exist in other embodiments. In addition, it should be understood that the elements may be combined in various embodiments in any suitable manner.

[0053] Unless otherwise specified in the specification and claims of the present invention, "%" refers to mass percentage, that is, wt%.

[0054] The term "comprising" and any variations thereof in the specification and claims of the present invention are intended to cover non-exclusive inclusions. For example, a process, method, system, product or device comprising a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units not listed, or may optionally include other steps or units inherent to these processes, methods, products or devices.

[0055] In the present specification, the use of “substantially” or “essentially” means that the standard deviation from a theoretical model or theoretical data is within a range of 5%, preferably 3%, and more preferably 1%.

[0056] <Nanoscale solid lipid carrier>

[0057] The invention provides a nano-scale solid lipid carrier, wherein the carrier comprises 10% to 20% by weight of active ingredients, liquid lipids, solid lipids and a surfactant.

[0058] Hereinafter, each component will be described in sequence.

[0059] Active ingredients

[0060] Capryloyl Salicylic Acid is the active ingredient or active drug in the carrier of the present invention, also known as 2-hydroxy-5-(1-oxooctyl)benzoic acid, which is salicylic acid with an oxooctyl group attached to the 5th position of the benzene ring. The CAS number of capryloyl salicylic acid is: 78418-01-6, and the chemical formula is C 15 H 20 O4. Capryloyl salicylic acid has an eight-carbon fatty chain attached to the structure of salicylic acid, which makes it more lipophilic and fat-soluble salicylic acid. Its chemical structure is quite stable, which not only maintains the effect of salicylic acid in exfoliating aging keratin, but also enhances its affinity with skin cells. Compared with salicylic acid, it is easier to penetrate into the stratum corneum and can play a more effective micro-exfoliation role. In addition, the pH value of capryloyl salicylic acid is similar to that of human skin, and it will not cause symptoms such as peeling. Its evaluation of skin and human health is much higher than that of salicylic acid. The whitening effect of capryloyl salicylic acid is different from other whitening ingredients that act on the formation of melanin. It acts on the keratin fibers of the skin, peels off necrotic keratin, reorganizes skin cells, makes the skin look white and bright, and has antibacterial and anti-inflammatory effects. It can slowly enter the skin, peel off the dead skin on the surface, unclog the pores, improve the large pores and blackheads of oily skin, and does not cause any discomfort to the human body.

[0061] The present invention encapsulates octanoylsalicylic acid in a carrier by preparing a nano-scale solid lipid carrier, which has high embedding rate, high drug loading, high stability, low irritation and good drug release performance.

[0062] In the present invention, the mass fraction of octanoyl salicylic acid in the carrier is 10% to 20%. If its content is less than 10%, the cost of subsequent cosmetic preparation will increase and the skin feel will be poor. If its content is higher than 20%, the carrier will be unstable.

[0063] The octanoyl salicylic acid of the present invention can be prepared according to a conventional method, for example, including: using n-octanoic acid and SOCl2 as raw materials, dichloromethane as a solvent, preparing octanoyl chloride by a conventional method, then reacting octanoyl chloride and methyl salicylate under the catalysis of aluminum chloride, and then reacting the reaction product with sodium hydroxide to obtain octanoyl salicylic acid. Octanoyl salicylic acid can also be commercially available.

[0064] Liquid lipids

[0065] Liquid lipids are used as solvents for fat-soluble drugs, encapsulating the active ingredients to be encapsulated therein, and can also promote the skin to absorb the active ingredients or drugs, inhibit the evaporation of moisture on the skin surface, and prevent the skin from drying out. The present invention tests the effect of changing the type and amount of oil on the carrier. In the present invention, the inventors found that when medium-chain fatty acid glycerides are used as liquid lipids, it is beneficial to obtain a carrier with high stability and good encapsulation performance in this system.

[0066] Medium-chain glycerides (MCG) are glycerides composed of fatty acids with 6 to 12 (further 8 to 10) carbon atoms, including monoglycerides, diglycerides and triglycerides. Compared with long-chain glycerides (LCT) composed of fatty acids with more than 12 carbon atoms, the inventors found that the system of the present invention using medium-chain glycerides has higher stability and better universality. Furthermore, the medium-chain fatty acid glyceride of the present invention includes one or more of glycerol monoesters, diesters or triesters of C8-C10 saturated carboxylic acids. Compared with unsaturated fatty acid glycerides, glycerol esters of C8-C10 saturated carboxylic acids have better stability in this system. For example, the medium-chain fatty acid glyceride of the present invention is selected from one or more of caprylic acid glycerol monoester, caprylic acid diglyceride, caprylic acid triglyceride, capric acid glycerol monoester, capric acid diglyceride, capric acid triglyceride, caprylic acid decanoic acid glycerol monoester (CAS: 73398-61-5, also known as mixed caprylic acid decanoic acid glycerol monoester), caprylic acid diglyceride and caprylic acid triglyceride. Furthermore, the medium-chain fatty acid glyceride of the present invention is preferably a triglyceride of C8-C10 saturated carboxylic acids. In some preferred embodiments of the present invention, the medium-chain fatty acid glyceride is selected from caprylic acid and capric acid triglyceride (referred to as caprylic acid and capric acid glyceride in the present invention, also known as GTCC), which is a mixed triester of glycerol and medium-chain (6 to 12 carbon atoms) saturated fatty acids, and the mass fraction of caprylic acid and capric acid in the saturated fatty acids is above 90%, and further above 92% or 95%. Caprylic acid and capric acid glyceride is usually a colorless, odorless, transparent liquid with a viscosity half that of ordinary vegetable oils, a low freezing point, good oxidative stability, a high content of saturated fatty acids, good compatibility with the skin, and will not clog pores. It has a non-greasy texture, and can be added to creams or lotions to improve its extensibility, has the effect of lubricating and softening the skin, and has the function of filtering ultraviolet light. The caprylic acid and capric acid glyceride of the present invention can be purchased commercially (such as 812) or self-made. 812 is fractionated coconut oil, containing caprylic and capric triglycerides, with a molecular weight of about 520, a fatty acid composition including no more than 3% C6 (caproic acid), 50-65% C8 (caprylic acid), 30-45% C10 (capric acid), and no more than 5% C12 (lauric acid), an acid value of about 0.1, a saponification value of about 330-345, and an iodine value of 1 at most.

[0067] The present invention also examines other liquid lipids, such as macadamia oil, black currant oil, star fruit oil, sea buckthorn fruit oil and echium oil, etc., but these liquid lipids, when coated with 10% octanoyl salicylic acid, are used in combination with the above liquid lipids and commonly used solid lipids and surfactants, and stratification occurs in many cases. Even if stratification does not occur, the physical properties of the carrier need to be improved, such as a relatively low embedding rate or a relatively large particle size. For liquid lipids that have been stratified when coated with 10% octanoyl salicylic acid, in order to save experimental costs, there is no need to examine the use of them to coat higher concentrations of octanoyl salicylic acid in the present invention. Compared with other liquid lipids, caprylic decanoic acid glyceride unexpectedly can obtain a stable carrier when coated with 10-20% octanoyl salicylic acid by optionally matching solid lipids and surfactants. In fact, in the present invention, the higher the saturated fatty acid content of liquid oils and fats, the more stable it is. The saturated fatty acid content in star fruit oil (6.8%) is significantly lower than that in sea buckthorn fruit oil (32%), but in the system of the present invention, star fruit oil has relatively few stratifications and is relatively more stable.

[0068] The dosage of the medium-chain fatty acid glyceride of the present invention is 10-30%, further 12%-25%, and further 22-25%. Increasing the concentration of capryloyl salicylic acid has no significant effect on the dosage of the medium-chain fatty acid glyceride. In some specific embodiments of the present invention, the weight ratio of the medium-chain fatty acid glyceride to the solid lipid is 0.8-1.8:1, further 1.0-1.7:1. If the liquid lipid content is inappropriate, the carrier is easily unstable.

[0069] Solid lipids

[0070] In the present invention, the solid lipid is used to coat tiny liquid oils and fats to form a nano-lattice, which can increase the loading amount of drugs or active ingredients. The outer periphery of the carrier coated with the solid lipid can also effectively release the active ingredients.

[0071] The solid lipids of the present invention include one or more of spermaceti, palm wax, beeswax and / or behenic acid glyceryl ester. Spermaceti is a solid wax obtained by cooling and squeezing the greasy substance extracted from the head of a sperm whale. It is mainly cetyl hexadecanoate with a freezing point of 41-49°C. It is soluble in ether and carbon disulfide, but insoluble in water. Carnauba wax, also known as Brazilian wax, is a wax extracted from the leaves or petioles of palm trees produced in Brazil, South America. It has a melting point of 82°C to 86°C and a density of 0.996 to 0.998 g / cm 3(25℃), insoluble in water, soluble in hot ethanol, hot ether, carbon tetrachloride, etc., the main components are palmitic acid, beeswax esters and cerotic acid. Palm wax is an amorphous, glossy, hard and tough wax with a pleasant smell and neat cross-section when broken. It can be saponified by strong alkali, with high hardness and melting point. Palm wax is stable in nature and is not prone to auto-oxidation reactions such as discoloration, taste change, and rancidity; it is safe and mild, non-toxic, non-irritating, and non-allergenic; it can significantly improve the hardness, melting point, gloss, and photostability of embedded drugs. Beeswax, also known as beeswax, is wax taken from the hive of bees. The specific quality varies depending on the type of bee and the type of flower from which nectar is collected. It is generally a brown or yellowish brown viscous wax, containing a large amount of myricyl palmitate, solid cerotic acid (cerotinic acid, C 25 H 51 COOH), generally with a melting point of 62℃~67℃. The effect of beeswax can accelerate blood circulation, promote the flow of lymph throughout the body, achieve the effect of detoxification, and reduce edema, wrinkles and dark circles. Beeswax can be used on the face or other parts of the body. When used on the face, vitamin C can thoroughly clean the free radicals on the face and moisturize the skin. Beeswax contains two natural substances, herbs and minerals. Heating can help penetrate the skin, help various skin-beautifying substances to effectively penetrate the skin, and bring various minerals and multiple nutrients to the skin. In addition, the heating effect of beeswax can accelerate the removal of keratin, promote detoxification, and also soothe the orange peel phenomenon of the skin. Glyceryl Behenate (such as Compritol ATO 888) is a white powder with a melting point of 69~74℃. It is insoluble in water and is mainly produced from plant materials. It can be used as a sustained-release material and a masking agent. It is very slightly irritating and corrosive to the skin.

[0072] In the present invention, the above four solid lipids can be used to prepare carriers to embed active ingredients and have substitutability. By fixing the type of liquid oil and changing the type of wax, it can be concluded that in the system of the present invention, behenic acid glyceryl is more stable, followed by palm wax, and spermaceti is relatively less stable. However, considering the requirements of cost, texture, etc., beeswax is preferably used in the present invention.

[0073] In some embodiments of the present invention, the content of the solid lipid is 15-25%. If the content of the solid lipid is too low, the liquid oil may not be well coated. In some embodiments of the present invention, the ratio of the solid lipid to the octanoyl salicylic acid is 1.1-1.6:1, and further 1.2-1.5:1.

[0074] Surfactants

[0075] The main purpose of the surfactant of the present invention includes wetting, cleaning, emulsification, suspension and dispersion. In the system of the present invention, nonionic surfactants are preferably used. In some specific embodiments of the present invention, the surfactant of the present invention includes one or more of polysorbate, polyoxyethylene polyoxypropylene block copolymer and / or decyl glucoside. Polysorbate such as (Tween 80) has excellent emulsification, dispersion, solubilization and lubrication properties, and its stability is relatively high, slows down the aging time of the sample, and is biodegradable. Polyoxyethylene polyoxypropylene block copolymer (such as Poloxamer 188 (Poloxamer 188)) will form a stereo effect, avoid particle agglomeration, have temperature-sensitive properties, and can control the release of active molecules or drugs. Decyl glucoside is a mild nonionic co-surfactant, synthesized from glucose and fatty acid alcohol prepared from corn and coconut, and has the characteristics of both common nonionic and anionic surfactants, foaming stability, good wetting properties, and can improve the conditioning effect of cationic surfactants. The surfactant also has the function of maintaining skin moisture balance and preventing the skin from drying out. Since this surfactant is derived from sugars, it has biologically degradable properties, is extremely mild, non-irritating, and has low toxicity. By fixing the type of liquid oil and changing the type of surfactant, it can be concluded that polysorbate is more stable in the system of the present invention, followed by poloxamer 188, and then decyl glucoside. However, considering the cost, mildness and non-irritation, decyl glucoside is preferably used in the present invention, which can be homemade or commercially available.

[0076] In some specific embodiments of the present invention, the content of the surfactant is 10-15%, and further 12-14%. If the content of the surfactant is too low, the problem of stratification will easily occur. If the content of the surfactant is too high, the texture and safety of the cosmetics will be affected.

[0077] Other components

[0078] The carrier of the present invention also includes polyols, phospholipids and water, which are all part of the composition of the aqueous phase. Polyols mainly have the effects of moisturizing and natural preservation. Polyols include pentylene glycol, which has the effects of moisturizing and inhibiting bacteria. The mass fraction of pentylene glycol is 1-3%, and further 2%. Phospholipids, also known as phospholipids and phospholipids, refer to lipids containing phosphoric acid and belong to complex lipids. Phospholipids are amphiphilic molecules with a hydrophilic nitrogen or phosphorus head at one end and a hydrophobic (lipophilic) long hydrocarbon chain at the other end. Phospholipids can assist emulsification and can also assist whitening active ingredients to penetrate the epidermis and promote skin absorption. Phospholipids include lecithin with a mass fraction of 1%. The balance is water.

[0079] Preparation method

[0080] The present invention also provides a method for preparing a nano-scale solid lipid carrier. The method comprises:

[0081] 1) Heat the liquid lipid and solid lipid to 85°C, add capryloyl salicylic acid, and stir until dissolved;

[0082] 2) Mix the surfactant, polyol, phospholipid and water, heat them to 90° C., and stir until they are dissolved to obtain an aqueous phase;

[0083] 3) adding the mixture obtained in step 1) to the aqueous phase obtained in step 2) and maintaining the temperature at 90° C.;

[0084] 4) Pre-emulsification using a pre-homogenizer;

[0085] 5) The mixed phase emulsion after pre-emulsification is fed into a high-pressure homogenizer and subjected to pressure treatment to obtain the carrier.

[0086] In the present invention, in order to obtain a stable carrier coated with high concentration of octanoyl salicylic acid, the temperature needs to be controlled. If the temperature is lower than 85° C. in steps 1) to 3), it will be difficult to completely emulsify, which may easily lead to clogging of the equipment.

[0087] In some specific embodiments of the present invention, the speed of the pre-emulsification in step 4) is 8000 rpm, and the time is 4.5 to 5.5 minutes. Further, in a specific embodiment of the present invention, the pre-emulsification time is 5 minutes. Due to the increase in the viscosity of the system, it is necessary to control the pre-emulsification time to allow the oil phase and the water phase to be fully mixed, which is conducive to the homogenization process and thus obtain a stable carrier.

[0088] In some specific embodiments of the present invention, in step 6), the feed tank in the high-pressure homogenizer needs to be preheated to 95° C. before starting to feed. By maintaining the temperature at 95° C., the viscosity of the mixed solution decreases and the fluidity is good. The pressure is increased to 600 bar and the carrier preparation is completed after 3 cycles.

[0089] application

[0090] The nano-scale solid lipid carrier obtained by the present invention is a composite nano-lipid carrier of oil-in-fat-in-water (O / F / W), which comprises an innermost layer of oil droplets (liquid lipids) containing active ingredients, wax (solid lipids) embedding the oil droplets, and water embedding the wax. The embedding rate of the carrier of the present invention is very high, which can reach more than 99.9%, and is obtained by analysis using a high-performance liquid chromatograph. Further, the particle size of the carrier of the present invention (i.e., the average particle size detected by a dynamic light scattering particle size analyzer (DLS)) does not exceed 1000nm, further 200-950nm, and more preferably does not exceed 500nm; the measurement of the interface potential of the carrier can evaluate the physical stability of the carrier. In some specific embodiments of the present invention, the interface potential of the carrier of the present invention is above |32|mV (i.e., the absolute value of the interface potential is not less than 32mV), proving that the carrier of the present invention has good stability. In other specific embodiments of the present invention, the crystallinity of the carrier of the present invention is 3% to 30%.

[0091] The carrier of the present invention can be used for the preparation of cosmetics. The carrier of the present invention can significantly reduce the cost of cosmetic preparation due to the high dose of octanoyl salicylic acid, and can also improve the touch to obtain smoother cosmetics. Only a small amount is needed to achieve the effects of brightening the skin tone, removing dark spots, freckles, and acne, and is also convenient for achieving the purpose of "skin resurfacing".

[0092] The technical scheme in the present invention will be further described below in conjunction with specific embodiments. It will be readily understood by those skilled in the art that the specific experimental conditions and results described in the following embodiments are only used to illustrate the present invention, and should not and will not be understood as limiting the present invention. Without departing from the spirit and scope of the present invention, the details and forms of the present invention may be modified and replaced, but these modifications and replacements all fall within the scope of protection of the present invention. In addition, unless otherwise stated, the instruments, materials, reagents, etc. used in the embodiments may be obtained by conventional commercial means.

[0093] Example

[0094] The technical solution of the present invention will be specifically described below through embodiments:

[0095] (raw material)

[0096]

[0097]

[0098] Other raw materials used in the comparative examples were all from Meilian Biotechnology Co., Ltd., Taiwan, China.

[0099] (Test Method)

[0100] The detection methods used in the following embodiments and comparative examples are as follows:

[0101] Particle size analysis: The Zetasizer Nano-ZS (Malven) was used for testing. The sample was diluted 1000 times and then placed in a shaking water tank for 20 minutes. About 3 ml of the diluted sample was injected into the colorimetric tank with a syringe. The colorimetric tank containing the sample was wiped with lens paper and then placed in the instrument for measurement. Each sample was measured 3 times, and the average and standard deviation of the measured particle size and PDI data were calculated and recorded.

[0102] Interface potential measurement: Zetasizer Nano-ZS is used to measure the interface potential of the sample. The sample is diluted 1000 times and then placed in a shaking water tank for 20 minutes. First, the Zeta sample tank is cleaned with ethanol and distilled water several times, and then the residual water in the sample tank is driven out with a high-pressure air gun. Use a clean syringe to draw the sample and inject it into it. After the injection is completed, wipe the copper electrodes at both ends of the sample tank clean to prevent dust from sticking and affecting the experimental results. The sample is placed in the instrument to measure the interface potential. After measuring each sample 3 times, the average value is calculated and recorded, and the interface potential measurement is completed.

[0103] Crystallinity test: The crystallinity of the sample is measured using the SDT-600 synchronous thermal analyzer. The freeze-dried sample is placed in a sample crucible. The sample weight must be between 10 and 15 mg. The crucible containing the sample and the blank crucible are placed in the instrument for analysis. The measurement conditions are set as follows: 1. Heating condition 5°C / min, 2. Heating range 30-110°C. The crystallinity of the sample is calculated based on the melting enthalpy ratio of the NLC dispersed phase to the liposome phase.

[0104] Embedding efficiency test: The embedding efficiency of the vector was analyzed using a high performance liquid chromatography (SUPER CO-150, manufactured by JASCO).

[0105] High performance liquid chromatography: UV detector detection wavelength: 280nm; C18 column; mobile phase: anhydrous ethanol; injection volume: 20μL; flow rate: 0.42mL / min. Preparation method of the sample to be tested: Take 10mg of the sample into a centrifuge tube and add 10mL of anhydrous ethanol. Centrifuge for 20min at a speed of 13500rpm. Take the supernatant, pass it through a 0.22μm filter membrane, and take the filtrate. Use HPLC for detection to obtain the sample concentration (i.e., the concentration of the active ingredient in the extract, which refers to the concentration of the unencapsulated free octanoylsalicylic acid), so as to calculate the embedding rate. The embedding rate calculation formula is as follows (1):

[0106] Embedding rate (%) = (designed embedding concentration of active ingredient - concentration of active ingredient in extract) / designed embedding concentration of active ingredient × 100% Formula (1)

[0107] (Experimental Method)

[0108] 1) The liquid lipid and the solid lipid are heated to 85°C at a constant temperature, and then capryloyl salicylic acid is added and stirred until completely dissolved;

[0109] 2) Heat the distilled water, surfactant, pentanediol and lecithin to 90°C and stir until they are completely dissolved;

[0110] 3) adding the mixture obtained in step 1) to the aqueous phase obtained in step 2) and maintaining the temperature at 90° C.;

[0111] 4) Pre-emulsification was performed using an emulsifier (Kinematica, made in Switzerland) at a speed of 8000 rpm for 5 minutes;

[0112] 5) Feed the pre-emulsified mixed phase emulsion into a high-pressure homogenizer (APV2000, made in Germany), preheat the feed tank to 95°C, start feeding, wait for the residual liquid in the machine to flow out, start pressurizing to 600 bar, cycle 3 times, take a sample of 10 mL, and perform a high-speed centrifugal stratification test (4000 rpm, centrifugal 15 minutes) to confirm whether stratification occurs; if stratification does not occur, perform characteristic analysis such as particle size and interface potential. Take 5 mL of the sample for freeze drying, and after the water is completely dried, perform thermal differential analysis of the sample using an SDT-600TGA / DSC thermal analyzer to confirm the crystallinity.

[0113] Examples 1 to 11 used the aforementioned experimental method to prepare nano-scale solid lipid carriers with the formulation described in Table 1, and the stratification test results were recorded in Table 1. The particle size, interfacial potential, crystallinity, and embedding rate of the carriers prepared in Examples 1 to 9 were analyzed, and the results were recorded in Table 2.

[0114] Table 1: Formulations and layered test results of Examples 1 to 11

[0115]

[0116]

[0117] Table 2 Test results of physical properties of carriers prepared in Examples 1 to 11

[0118]

[0119]

[0120] Comparative Examples 1 to 25 were prepared into nano-scale solid lipid carriers using the aforementioned experimental method with the formulation described in Table 3, and the stratification test results were recorded in Table 3. For those that were not stratified, the particle size, interfacial potential and other characteristics analysis could be performed. 5 mL of the sample was freeze-dried, and after the water was completely dried, the SDT-600 TGA / DSC thermal analyzer was used to perform thermal differential analysis of the sample to confirm the crystallinity. The physical property test results of some comparative examples that were not stratified are shown in Table 4.

[0121] Table 3 Comparative Examples 1 to 25 formulations and layering test results

[0122]

[0123]

[0124]

[0125] Table 4 Test results of carrier properties obtained from some comparative examples without delamination

[0126] serial number Particle size (nm) Interface potential (mV) Crystallinity(%) Embedding rate (%) 3 1580 -55.7 7.03 99.97 5 1038 -50.8 1.704 99.96 8 1544 -43.4 7.121 99.93 10 378.3 -34.9 19.51 99.89 11 254.0 -21.1 18.13 99.93 12 773.1 -35.8 8.803 99.87 13 1193 -51.8 9.785 99.86 14 1322 -56.6 6.865 99.92 15 1046 -38.0 12.69 99.91 17 588.3 -34.0 16.84 99.98 19 566.7 -48.1 6.35 99.93 21 233.7 -31.9 14.86 99.97

[0127] From the results in Tables 1-4, it can be seen that only by selecting liquid lipids that meet the requirements of the present invention and combining them with different solid lipids and different surfactants in a specific ratio, a stable, non-stratified carrier can be obtained when 10-20% of octanoyl salicylic acid is embedded, and the particle size of the obtained carrier is appropriate and the interface potential is above |32|mV, indicating that the obtained system is stable and the particle aggregation is low. In some cases, the interface potential is higher than |50|mV, indicating that the colloid has extremely high stability. Other liquid lipids such as macadamia soybean oil and black currant oil will have stratification problems when mixed with some common solid lipids and surfactants, and star fruit oil will also have stratification problems within a certain concentration range. The universality of the scheme protected by the present invention, the high embedding rate of active ingredients and the high stability of the carrier have exceeded the expectations of those skilled in the art.

[0128] Application Examples

[0129] In a simulation experiment to explore the absorption of octanoyl salicylic acid by the human body, a carrier sample (the carrier obtained in Example 9) encapsulating 20% ​​octanoyl salicylic acid was used to prepare a facial cream with a concentration of 3% and 10%. The formula is shown in Table 5. After the preparation, a percutaneous absorption experiment was carried out. Samples were taken according to time, and HPLC was performed to analyze the change of concentration with time (see the trend diagram of the change of cream concentration for details). Figure 1 ), and then the diffusion flux was calculated using the initial slope method (results are shown in Table 6).

[0130] Table 5 Facial cream ingredients

[0131]

[0132] Table 6 Diffusion coefficients of percutaneous absorption experiments

[0133] Capryloyl salicylic acid concentration in face cream <![CDATA[Diffusion coefficient (m 2 / s)]]> 3％ <![CDATA[4.02×10 -16 ]]> 10％ <![CDATA[4.83×10 -16 ]]>

[0134] According to the literature, the diffusion coefficient of the skin is about 8×10 -12 m 2 / s( et al., 2015), the penetration coefficient is calculated, taking 3% as an example:

[0135]

[0136] The penetration coefficient of 10% is 6×10 -3 .

Claims

1. A nanoscale solid lipid carrier, characterized in that: The carrier comprises the following components in weight percentage: Capryloyl salicylic acid 10-20% Liquid lipids 12-25% Solid lipids 15-25% Surfactant 10-15%; Pentylene glycol 1~3% Lecithin 1% The balance is water; Wherein, the liquid lipid is selected from medium-chain fatty acid glycerides, and the medium-chain fatty acid glycerides are selected from caprylic and capric triglycerides; The solid lipid is selected from beeswax; The surfactant is selected from decyl glucoside; The ratio of the solid lipid to the octanoyl salicylic acid content is (1.2-1.5):1; The embedding rate of the carrier is above 99.9%.

2. The nanoscale solid lipid carrier according to claim 1, characterized in that The carrier comprises the following components in weight percentage: Liquid lipids 22-25%.

3. The nanoscale solid lipid carrier according to claim 1, characterized in that The carrier comprises the following components in weight percentage: Surfactant 12-14%.

4. The nanoscale solid lipid carrier according to claim 1, characterized in that The carrier comprises the following components in weight percentage: Pentylene glycol 2%.

5. The nanoscale solid lipid carrier according to claim 1, characterized in that The particle size of the carrier is no more than 1000 nm.

6. The nanoscale solid lipid carrier according to claim 5, characterized in that: The particle size of the carrier is 200-950 nm.

7. The nanoscale solid lipid carrier according to claim 5 or 6, characterized in that: The particle size of the carrier is no more than 500 nm.

8. The nanoscale solid lipid carrier according to claim 1 or 5, characterized in that: The interface potential of the carrier is above |32| mV.

9. A method for preparing the nanoscale solid lipid carrier according to any one of claims 1 to 8, characterized in that: The preparation method comprises the following steps: 1) Heat the liquid lipid and solid lipid to 85°C, add capryloyl salicylic acid, and stir until dissolved; 2) mixing a surfactant, a polyol, a phospholipid and water, heating them to 90° C. at a constant temperature, and stirring them until they are dissolved to obtain an aqueous phase; the polyol is pentanediol; and the phospholipid is lecithin; 3) adding the mixture obtained in step 1) to the aqueous phase obtained in step 2) and maintaining the temperature at 90° C.; 4) Pre-emulsification using a pre-homogenizer; 5) The mixed phase emulsion after pre-emulsification is fed into a high-pressure homogenizer and subjected to pressure treatment to obtain the carrier.

10. A cosmetic, characterized in that: The cosmetic comprises the nanoscale solid lipid carrier according to any one of claims 1 to 8.

Images