High-permeability composite flavone composition as well as preparation method and application thereof

Abstract

The invention discloses a high-permeability composite flavone composition as well as a preparation method and application thereof, and relates to the technical field of cosmetics. The invention discloses a composite flavone composition with high permeability. The composite flavone composition is prepared from flavone, lecithin, glycerol, propylene glycol, caprylic / capric triglyceride, tocopheryl acetate and water, the flavonoids are total flavonoids of panax notoginseng and total flavonoids of pericarpium citri reticulatae. In the flavone extraction process, superfine grinding and high-pressure microjet are combined, the superfine grinding is adopted to treat the panax notoginseng and the pericarpium citri reticulatae, the high-pressure microjet is adopted to treat the panax notoginseng solution and the pericarpium citri reticulatae solution, and the flavone content in the extract is increased.

Description

Technical Field

[0001] The invention relates to the technical field of cosmetics, and in particular to a high-permeability composite flavonoid composition and a preparation method and application thereof. Background Art

[0002] Non-enzymatic glycosylation is a series of complex non-enzymatic reactions. Proteins and glucose react in the body to form early glycosylation products such as Schiff bases and Amadori products, which then undergo oxidation, rearrangement, cross-linking and other processes to form irreversible non-enzymatic glycosylation end products (AGEs). AGEs are the products of excess sugar and protein. There are two sources in the body: one is the synthesis of AGEs in the body by excess sugar and protein, and the other is the intake of AGEs in food through eating. AGEs can combine with the body's tissue cells and destroy them. Studies have shown that AGEs accelerate human aging and lead to the occurrence of many chronic degenerative diseases.

[0003] Human skin tissue contains a large amount of collagen and elastin, which mostly exist in a fibrous form and form the skeleton structure of the skin, giving the skin a certain strength and elasticity. AGEs can form cross-links with these two proteins, which not only affects their normal functions, but also affects the adhesion and growth of skin cells. At the same time, the accumulation of cross-links of AGEs and these two proteins in the cell matrix not only reduces the permeability of connective tissue, but also weakens the ability of nutrients and metabolic waste to diffuse in the body, increases the hardness of skin tissue, and thus reduces skin elasticity, ultimately leading to skin aging and wrinkles.

[0004] Flavonoids are widely distributed in the plant kingdom. Most of them exist in the form of glycosides or carbon sugars in plants, and some exist in free form. Flavonoids have attracted much attention due to their significant antioxidant properties. The antioxidant mechanism of flavonoids mainly involves scavenging free radicals, inhibiting oxidase activity, and chelating metal ions. Flavonoids can effectively scavenge reactive oxygen species (ROS), thereby inhibiting oxidative stress reactions, and can also bind to already formed AGEs to inactivate them. However, the application of flavonoids in the cosmetics field has the following three disadvantages:

[0005] (1) The extraction rate is low, which often requires a large amount of raw materials to meet industrial application needs, which can easily cause serious waste and low cost performance;

[0006] (2) Solubility and stability are generally poor, which limits the application of flavonoids in cosmetics;

[0007] (3) During the in vitro application stage, flavonoids are prone to discoloration under conditions such as high temperature, light, and oxidation. During the in vivo application stage, due to the obstruction of the stratum corneum barrier, flavonoids may be degraded or oxidized before reaching the point of action, thereby reducing their activity, which seriously limits their bioavailability and transdermal application.

[0008] There are currently two methods to overcome the above shortcomings. One is to optimize the extraction process of flavonoids; the other is to encapsulate flavonoids into nanocarriers to enhance their solubility and stability while enhancing transdermal permeability. Nanoliposomes stand out among various nanocarriers due to their excellent biocompatibility and low toxicity. Nanoliposomes are composed of phospholipids, and their unique hydrophilic and hydrophobic properties can effectively load hydrophilic active ingredients into the hydrophilic core cavity, and encapsulate hydrophobic active ingredients into the hydrophobic phospholipid bilayer to improve the solubility and bioactivity of the active ingredients. In addition, the lipid bilayer nanostructure of nanoliposomes can also enhance the overall skin stratum corneum penetration effect to promote transdermal penetration.

[0009] In view of this, in order to solve the deficiencies of the prior art, the present invention provides a highly permeable composite flavonoid composition and a preparation method and application thereof. The present invention not only solves the problem of low extraction rate of flavonoid compounds, but also solves the problem of poor permeability of the composite flavonoid composition, and provides a theoretical basis for the application of flavonoid compounds in cosmetics. Summary of the invention

[0010] The purpose of the present invention is to provide a high-permeability composite flavonoid composition and a preparation method and application thereof, which not only improves the extraction rate of flavonoid compounds, but also improves the permeability and stability of the composite flavonoid composition.

[0011] To achieve the above-mentioned purpose of the invention, the technical solution of the present invention is as follows:

[0012] On the one hand, the present invention provides a high-permeability composite flavonoid composition, comprising flavonoids, lecithin, glycerol, propylene glycol, caprylic / capric triglyceride, tocopherol acetate and water; the flavonoids are total flavonoids from Panax notoginseng and total flavonoids from dried orange peel.

[0013] Preferably, the composite flavonoid composition comprises 5 parts of flavonoids, 2-7 parts of lecithin, 10-25 parts of glycerol, 15-35 parts of propylene glycol, 7-13 parts of caprylic / capric triglyceride, 1-3 parts of tocopherol acetate and 12-60 parts of water in parts by weight.

[0014] Further preferably, the composite flavonoid composition comprises 5 parts of flavonoids, 5 parts of lecithin, 20 parts of glycerol, 30 parts of propylene glycol, 10 parts of caprylic / capric triglyceride, 2 parts of tocopherol acetate and 28 parts of water in parts by weight.

[0015] More preferably, the mass ratio of total flavonoids from Panax notoginseng to total flavonoids from dried orange peel in the flavonoids is 4:1-16.

[0016] More preferably, the mass ratio of total flavonoids from Panax notoginseng to total flavonoids from dried orange peel in the flavonoids is 4:1-4.

[0017] Finally, preferably, the mass ratio of total flavonoids from Panax notoginseng to total flavonoids from dried orange peel in the flavonoids is 4:1.

[0018] Preferably, the extraction steps of total flavonoids from Panax notoginseng are as follows: ultrafine grinding is performed on Panax notoginseng, the particle size of the Panax notoginseng powder after ultrafine grinding is <10μm, and then the Panax notoginseng powder is mixed with ethanol at 40-75°C for 15-45min, and then the Panax notoginseng solution is homogenized by microjet, and the homogenized solution is rotary evaporated to obtain total flavonoids from Panax notoginseng; the mass ratio of the Panax notoginseng powder to ethanol is 1:1-10.

[0019] Further preferably, the extraction steps of the total flavonoids from Panax notoginseng are as follows: the Panax notoginseng is ultrafinely ground, the particle size of the Panax notoginseng powder after ultrafine grinding is 2 μm, and then the Panax notoginseng powder is mixed with ethanol at 70°C for 30 minutes, and then the Panax notoginseng solution is homogenized by microjet, and the homogenized solution is rotary evaporated to obtain the total flavonoids from Panax notoginseng; the mass ratio of the Panax notoginseng powder to ethanol is 1:4.

[0020] Preferably, the extraction steps of total flavonoids from tangerine peel are as follows: ultrafine grinding tangerine peel, the particle size of the tangerine peel powder after ultrafine grinding is less than 10 μm, then the tangerine peel powder is mixed with modified ethanol at 30-75° C. for 10-45 min, then the tangerine peel solution is homogenized by micro-jetting, and the homogenized solution is rotary evaporated to obtain total flavonoids from tangerine peel; the mass ratio of tangerine peel powder to ethanol is 1:1-10.

[0021] Further preferably, the extraction steps of the total flavonoids from tangerine peel are as follows: the tangerine peel is subjected to ultrafine grinding, the particle size of the tangerine peel powder after ultrafine grinding is 5 μm, and then the tangerine peel powder is mixed with modified ethanol at 60° C. for 30 minutes, and then the tangerine peel solution is homogenized by microjetting, and the homogenized solution is rotary evaporated to obtain the total flavonoids from tangerine peel; the mass ratio of the tangerine peel powder to ethanol is 3:7.

[0022] On the other hand, the present invention provides a method for preparing the above-mentioned high-permeability composite flavonoid composition, comprising the following steps: uniformly mixing total flavonoids from Panax notoginseng, total flavonoids from dried tangerine peel, lecithin, glycerol, propylene glycol, caprylic / capric triglyceride, tocopherol acetate and water to obtain a mixed phase solution, homogenizing the mixed phase solution by high shear emulsification to obtain a micron-sized crude emulsion, and homogenizing the micron-sized crude emulsion by microfluidization to obtain a high-permeability composite flavonoid composition.

[0023] Preferably, the total flavonoids of Panax notoginseng, total flavonoids of dried tangerine peel, lecithin, glycerol, propylene glycol, caprylic / capric triglyceride, tocopherol acetate and water are mixed uniformly at 60°C.

[0024] Finally, the present invention provides application of the high-permeability composite flavonoid composition in cosmetics or skin care products.

[0025] The beneficial effects of the present invention are:

[0026] (1) In the process of extracting flavonoids, the present invention uses ultrafine grinding and high-pressure microfluidization in combination, ultrafine grinding is used to process Sanqi and dried orange peel, and high-pressure microfluidization is used to process Sanqi solution and dried orange peel solution, thereby increasing the flavonoid content in the extract.

[0027] (2) The present invention performs nano-encapsulation treatment on the total flavonoids of Panax notoginseng and the total flavonoids of dried tangerine peel, thereby improving the permeability of the composite flavonoid composition. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is the surface morphology of the composite flavonoid composition prepared in Example 1 of the present invention.

[0029] Figure 2 This is the result of measuring the composite flavonoid composition prepared in Example 1 of the present invention using a nanoparticle size analyzer. DETAILED DESCRIPTION

[0030] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is only an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the invention of the present invention based on the disclosed content, and they should also fall within the scope of the present invention.

[0031] The present invention is further described below by way of specific examples. The various chemical reagents used in the examples of the present invention are obtained through conventional commercial channels unless otherwise specified. Unless otherwise specified, the contents described below are all weight contents. Unless otherwise specified, it is understood that the process is carried out at room temperature.

[0032] Sanqi is the rhizome of Polygonum amplexicaule var.sinense, a plant of the Polygonaceae family.

[0033] Tangerine peel is the dried mature peel of the Rutaceae plant Citrus reticulata Blanco and its cultivated varieties.

[0034] Modified ethanol: Denatonium benzoate is added to ethanol to improve the flexibility of the system while avoiding oral ingestion.

[0035] Homogenizer: manufacturer IKA, model T25.

[0036] High-pressure microfluidizer: manufacturer: Deheng Nano Technology (Shenzhen) Co., Ltd., model DNH-340.

[0037] Ultrafine grinding instrument: manufacturer: Noze Fluid Technology (Shanghai) Co., Ltd., model: Micron JETMILL 4.

[0038] Example 1

[0039] 1. Extract flavonoids

[0040] 1.1 Extraction of Total Flavonoids from Panax notoginseng

[0041] Weigh 20 parts of Sanqi (Rhizoma Panax notoginseng) and perform ultrafine grinding. The particle size of the Sanqi (Rhizoma Panax notoginseng) powder after ultrafine grinding is 2 μm. Then, the Sanqi (Rhizoma Panax notoginseng) powder and 80 parts of ethanol are stirred and mixed in a constant temperature water bath at 70°C for 30 minutes. Subsequently, a high-pressure microjet homogenizer is used to perform two high-pressure microjet crushing treatments on the Sanqi (Rhizoma Panax notoginseng) solution at a pressure of 25,000 psi. The solution subjected to two high-pressure microjet crushing treatments is subjected to rotary evaporation (temperature of 70°C, time of 50 minutes) to obtain Sanqi (Rhizoma Panax notoginseng) total flavonoids.

[0042] 1.2 Extraction of total flavonoids from dried tangerine peel

[0043] 30 parts of dried tangerine peels were weighed and ultrafinely crushed, the particle size of the dried tangerine peel powder after the ultrafine crushing was 5 μm, and then the dried tangerine peel powder and 70 parts of modified ethanol were stirred and mixed in a constant temperature water bath at 60° C. for 20 minutes, and then the dried tangerine peel solution was subjected to two high-pressure micro-jet crushing treatments at a pressure of 25000 psi using a high-pressure micro-jet homogenizer, and the solution subjected to the two high-pressure micro-jet crushing treatments was subjected to rotary evaporation (temperature was 75° C., time was 50 minutes) to obtain dried tangerine peel total flavonoids.

[0044] 2. Preparation of composite flavonoid composition

[0045] Then take 4 parts of total flavonoids of Panax notoginseng, 1 part of total flavonoids of dried orange peel, 5 parts of lecithin, 20 parts of glycerol and dissolve them in 30 parts of propylene glycol, then add 10 parts of caprylic / capric triglyceride, 2 parts of tocopherol acetate and 28 parts of purified water to stir and dissolve completely, and stir evenly in a 60°C constant temperature water bath (stirring time t≥3min, speed 150r / min). Use a homogenizer to perform high shear homogenization on the mixed phase solution (stirring time t≥10min, speed 6000-8000rpm / min) to obtain micron-sized crude milk. After returning to room temperature, use a microfluidizer to perform microfluidization high pressure homogenization on the micron-sized crude milk, the homogenization pressure is 25000psi, and the composite flavonoid composition is prepared by 2 cycles of homogenization.

[0046] Example 2

[0047] 1. Extract flavonoids

[0048] 1.1 Extraction of Total Flavonoids from Panax notoginseng

[0049] Weigh 20 parts of Sanqi notoginseng and perform ultrafine grinding. The particle size of the Sanqi notoginseng powder after ultrafine grinding is 2 μm. Then, the ultrafine grinding Sanqi notoginseng powder and 20 parts of ethanol are stirred and mixed in a constant temperature water bath at 40°C for 15 minutes. Subsequently, a high-pressure microjet homogenizer is used to perform two high-pressure microjet crushing treatments on the Sanqi notoginseng solution at a pressure of 25000psi. The solution subjected to two high-pressure microjet crushing treatments is subjected to rotary evaporation to obtain Sanqi notoginseng total flavonoids.

[0050] 1.2 Extraction of total flavonoids from dried tangerine peel

[0051] 30 parts of dried tangerine peel were weighed and ultrafinely crushed, the particle size of the dried tangerine peel powder after ultrafine crushing was 5 μm, and then the ultrafinely crushed dried tangerine peel powder and 30 parts of modified ethanol were stirred and mixed in a constant temperature water bath at 30° C. for 10 minutes, and then the dried tangerine peel solution was subjected to two high-pressure micro-jet crushing treatments at a pressure of 25000 psi using a high-pressure micro-jet homogenizer, and the solution subjected to two high-pressure micro-jet crushing treatments was rotary evaporated to obtain total flavonoids from dried tangerine peel.

[0052] 2. Preparation of composite flavonoid composition

[0053] The preparation process is the same as that of Example 1.

[0054] Example 3

[0055] 1. Extract flavonoids

[0056] 1.1 Extraction of Total Flavonoids from Panax notoginseng

[0057] Weigh 20 parts of Sanqi notoginseng and perform ultrafine grinding. The particle size of the Sanqi notoginseng powder after ultrafine grinding is 2 μm. Then, the ultrafine grinding Sanqi notoginseng powder and 200 parts of ethanol are stirred and mixed in a constant temperature water bath at 75°C for 45 minutes. Subsequently, a high-pressure microjet homogenizer is used to perform two high-pressure microjet crushing treatments on the Sanqi notoginseng solution at a pressure of 25000 psi. The solution subjected to two high-pressure microjet crushing treatments is subjected to rotary evaporation to obtain Sanqi notoginseng total flavonoids.

[0058] 1.2 Extraction of total flavonoids from dried tangerine peel

[0059] 30 parts of dried tangerine peel were weighed and ultrafinely crushed, the particle size of the dried tangerine peel powder after ultrafine crushing was 5 μm, then the ultrafinely crushed dried tangerine peel powder and 300 parts of modified ethanol were stirred and mixed in a constant temperature water bath at 90° C. for 30 minutes, and then the dried tangerine peel solution was subjected to high-pressure micro-jet crushing treatment twice at a pressure of 25000 psi using a high-pressure micro-jet homogenizer, and the solution subjected to the two high-pressure micro-jet crushing treatments was rotary evaporated to obtain total flavonoids from dried tangerine peel.

[0060] 2. Preparation of composite flavonoid composition

[0061] The preparation process is the same as that of Example 1.

[0062] Example 4

[0063] 1. Extract flavonoids

[0064] The flavonoid extraction process is the same as in Example 1.

[0065] 2. Preparation of composite flavonoid composition

[0066] Then take 1 part of total flavonoids of Panax notoginseng, 4 parts of total flavonoids of dried orange peel, 5 parts of lecithin, 20 parts of glycerol and dissolve them in 30 parts of propylene glycol, then add 10 parts of caprylic / capric triglyceride, 2 parts of tocopherol acetate and 28 parts of purified water to stir and dissolve completely, and stir evenly in a 60°C constant temperature water bath (stirring time t≥3min, speed 150r / min). Use a homogenizer to perform high shear homogenization on the mixed phase solution (stirring time t≥10min, speed 6000-8000rpm / min) to obtain micron-sized crude milk. After returning to room temperature, use a microfluidizer to perform microfluidization high pressure homogenization on the micron-sized crude milk, the homogenization pressure is 25000psi, and the composite flavonoid composition is prepared by 2 cycles of homogenization.

[0067] Example 5

[0068] 1. Extract flavonoids

[0069] The flavonoid extraction process is the same as in Example 1.

[0070] 2. Preparation of composite flavonoid composition

[0071] Then take 2.5 parts of total flavonoids of Panax notoginseng, 2.5 parts of total flavonoids of dried orange peel, 5 parts of lecithin, and 20 parts of glycerol and dissolve them in 30 parts of propylene glycol, then add 10 parts of caprylic / capric triglyceride, 2 parts of tocopherol acetate and 28 parts of purified water to stir and dissolve completely, and stir evenly in a 60°C constant temperature water bath (stirring time t≥3min, speed 150r / min). Use a homogenizer to perform high shear homogenization on the mixed phase solution (stirring time t≥10min, speed 6000-8000rpm / min) to obtain micron-sized crude milk. After returning to room temperature, use a microfluidizer to perform microfluidization high pressure homogenization on the micron-sized crude milk, the homogenization pressure is 25000psi, and the composite flavonoid composition is prepared by 2 cycles of homogenization.

[0072] Example 6

[0073] 1. Extract flavonoids

[0074] The flavonoid extraction process is the same as in Example 1.

[0075] 2. Preparation of composite flavonoid composition

[0076] Then take 4 parts of total flavonoids of Panax notoginseng, 1 part of total flavonoids of dried orange peel, 2 parts of lecithin, 10 parts of glycerol and dissolve them in 15 parts of propylene glycol, then add 7 parts of caprylic / capric triglyceride, 1 part of tocopherol acetate and 60 parts of purified water to stir and dissolve completely, and stir evenly in a 60°C constant temperature water bath (stirring time t≥3min, speed 150r / min). Use a homogenizer to perform high shear homogenization on the mixed phase solution (stirring time t≥10min, speed 6000-8000rpm / min) to obtain micron-sized crude milk. After returning to room temperature, use a microfluidizer to perform microfluidization high pressure homogenization on the micron-sized crude milk, the homogenization pressure is 25000psi, and the composite flavonoid composition is prepared by 2 cycles of homogenization.

[0077] Example 7

[0078] 1. Extract flavonoids

[0079] The flavonoid extraction process is the same as in Example 1.

[0080] 2. Preparation of composite flavonoid composition

[0081] Then take 4 parts of total flavonoids of Panax notoginseng, 1 part of total flavonoids of dried orange peel, 7 parts of lecithin, 25 parts of glycerol and dissolve them in 35 parts of propylene glycol, then add 13 parts of caprylic / capric triglyceride, 3 parts of tocopherol acetate and 12 parts of purified water to stir and dissolve completely, and stir evenly in a 60°C constant temperature water bath (stirring time t≥3min, speed 150r / min). Use a homogenizer to perform high shear homogenization on the mixed phase solution (stirring time t≥10min, speed 6000-8000rpm / min) to obtain micron-sized crude milk. After returning to room temperature, use a microfluidizer to perform microfluidization high pressure homogenization on the micron-sized crude milk, the homogenization pressure is 25000psi, and the composite flavonoid composition is prepared by 2 cycles of homogenization.

[0082] Comparative Example 1

[0083] 1. Extract flavonoids

[0084] 1.1 Extraction of Total Flavonoids from Panax notoginseng

[0085] Weigh 20 parts of Sanqi notoginseng and perform coarse grinding. The particle size of the Sanqi notoginseng powder after coarse grinding is 100 μm. Then, the Sanqi notoginseng powder and 80 parts of ethanol are stirred and mixed in a constant temperature water bath at 70°C for 30 minutes. Subsequently, a high-pressure microjet homogenizer is used to perform two high-pressure microjet crushing treatments on the Sanqi notoginseng solution at a pressure of 25,000 psi. The solution subjected to two high-pressure microjet crushing treatments is subjected to rotary evaporation to obtain Sanqi notoginseng total flavonoids.

[0086] 1.2 Extraction of total flavonoids from dried tangerine peel

[0087] 30 parts of tangerine peel were weighed and coarsely crushed, and the particle size of the tangerine peel powder after the coarse crushing was 140 μm. The tangerine peel powder and 70 parts of modified ethanol were stirred and mixed in a constant temperature water bath at 60° C. for 20 minutes. Subsequently, a high-pressure microjet homogenizer was used to perform two high-pressure microjet crushing treatments on the tangerine peel solution at a pressure of 25000 psi. The solution subjected to the two high-pressure microjet crushing treatments was subjected to rotary evaporation to obtain tangerine peel total flavonoids.

[0088] Comparative Example 2

[0089] Weigh 20 parts of Sanqi notoginseng and perform ultrafine grinding. The particle size of the Sanqi notoginseng powder after ultrafine grinding is 2 μm. Then, the ultrafine grinding Sanqi notoginseng powder and 80 parts of ethanol are stirred and mixed in a constant temperature water bath at 70°C for 30 minutes. Then, the Sanqi notoginseng solution is rotary evaporated to obtain Sanqi notoginseng total flavonoids.

[0090] 1.2 Extraction of total flavonoids from dried tangerine peel

[0091] 30 parts of dried tangerine peel were weighed and ultrafinely ground, the particle size of the dried tangerine peel powder after ultrafine grinding was 5 μm, and then the ultrafinely ground dried tangerine peel powder and 70 parts of modified ethanol were stirred and mixed in a constant temperature water bath at 60° C. for 20 minutes, and then the dried tangerine peel solution was rotary evaporated to obtain the total flavonoids of dried tangerine peel.

[0092] Detection Methods

[0093] 1. In vitro skin retention performance test

[0094] The skin retention performance test of ex vivo pig skin was conducted with reference to GB / T27818-2011 "In vitro test method for skin absorption of chemicals". The skin of healthy ex vivo Bama pigs (average thickness of about 750μm) stored at -20℃ was taken and thawed naturally at room temperature. After being gently wiped clean with phosphate buffer with a pH of 6.8-7.4, the initial transepidermal water loss value of the skin was measured with a transepidermal water loss meter. The initial transepidermal water loss value was <15g / m 2 h, the stratum corneum of the skin was considered intact. A vertical (Franz) diffusion cell was used as the diffusion device. The prepared ex vivo skin was fixed between the supply cell and the receiving cell, with the stratum corneum facing the supply cell and the dermis facing the receiving cell. 8 mL of phosphate buffer was added to the receiving cell to make the skin in close contact with the receiving solution without bubbles. The transdermal diffusion experiment instrument was turned on, the water level in the water tank was checked, the speed was set to 350 rpm, the temperature to 32 °C, and preheated for 5 min in advance. In each sample test group, 0.2 g / cm 2 Add 100mg FITC to the embodiment / comparative example / control example respectively; remove the diffusion cell at the 48h time point, discard the excess sample in the supply cell and clean the skin surface with ultrapure water, remove the tissue block of the effective penetration part in the middle of the skin, fix it in the tissue fixative and perform frozen sectioning, take the tissue section and observe the distribution of FITC fluorescence signal in the skin tissue under a fluorescence microscope. Then transfer it to a high-throughput tissue grinder to fully grind it into a skin homogenate, add 1mL acetonitrile to extract, stand and filter it, and use a Pursuit XRs C18 (500g / 3L) liquid chromatography column, the mobile phase is a mixed solution of water and acetonitrile (volume ratio is 40:60), the flow rate is 0.3mL / min, the injection volume is 20μL, the column temperature is 30℃, the chromatography time is 15min, and the quantitative detection wavelengths are 271nm and 510nm (corresponding to the absorbance of total flavonoids of dried tangerine peel and total flavonoids of notoginseng, respectively), and the retention amount of compound flavonoids in the skin is calculated cumulatively.

[0095] 2. Transmission electron microscopy morphology observation

[0096] The surface morphology of the composite flavonoid composition prepared in Example 1 was observed using a Hitachi HT7800 high-contrast transmission electron microscope. Before analysis, Example 1 prepared on the first day was diluted to an appropriate concentration with ultrapure water at a pH of 7.0, 10 μL of the diluted Example 1 was dropped on a copper mesh, and after standing for 2 minutes, excess sample around the copper mesh was sucked away, and then the copper mesh was negatively stained with a 2.0wt% uranyl acetate solution for 5 minutes. Excess staining solution was removed with filter paper, and naturally dried at room temperature, and an appropriate amount of sample was dropped on the copper mesh plate, and then photographed and recorded.

[0097] 3. Determination of particle size, PDI and Zeta potential

[0098] The average particle size, PDI and Zeta potential of the composite flavonoid composition prepared in the example were measured using a nanoparticle size analyzer. First, the example prepared on the first day was diluted 100 times with ultrapure water, the test temperature was set to 25°C, the scattering angle was set to 90°, and each sample was scanned 3 times with the average value as the measured value. When measuring the Zeta potential, the sample was not diluted and was directly added to the Zeta potential cell for measurement.

[0099] 4. Determination of flavonoid content

[0100] The total flavonoids content was measured by direct method. First, a standard curve of the standard sample rutin was established, and the absorbance of the total flavonoids of dried tangerine peel and Panax notoginseng was measured at 271nm and 510nm respectively. The content of total flavonoids was calculated based on the obtained standard curve.

[0101] Test results

[0102] 1. In vitro skin retention performance test

[0103] Comparison example Example 1 Example 4 Example 5 Example 6 Example 7 <![CDATA[48h cumulative permeation amount (μg·cm -1 )]]> 23.47 61.31 53.49 55.72 49.61 58.27

[0104] Note: The control example is a free complex flavonol solution, which contains 4 parts of total flavonoids from Panax notoginseng, 1 part of total flavonoids from Citrus aurantium and 95 parts of propylene glycol.

[0105] 2. Determination of particle size, PDI and Zeta potential

[0106] Example 1 Example 4 Example 5 Example 6 Example 7 Particle size (nm) 101.3 103.8 104.9 95.7 105.8 PDI 0.262 0.269 0.273 0.259 0.281 Zeta potential (mV) -5.83 -5.96 -6.01 -5.68 -6.14

[0107] Note: The system's Zeta potential is in the range of -7 to 0 mV, indicating good stability; the system's Zeta potential is in the range of -30 to -8 mV, indicating poor stability.

[0108] 3. Determination of flavonoid content

[0109] Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Flavonoid content (mg / mL) 61.31 55.71 61.73 42.58 45.29

[0110] Compared with Comparative Examples 1 and 2, Example 1 uses ultrafine grinding and high-pressure microfluidization in combination during the flavonoid extraction process, uses ultrafine grinding to process Panax notoginseng and tangerine peel, and uses high-pressure microfluidization to process Panax notoginseng solution and tangerine peel solution, thereby increasing the flavonoid content in the extract.

[0111] Compared with the control example, in Example 1 and Examples 4-7, total flavonoids of Panax notoginseng and total flavonoids of dried orange peel were nano-encapsulated to improve the permeability of the composite flavonoid composition.

[0112] Compared with Example 4 and Example 5, Example 1 improves the permeability and stability of the composite flavonoid composition by limiting the mass ratio of total flavonoids of Panax notoginseng to total flavonoids of dried tangerine peel to 4:1.

[0113] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims

1. A highly permeable composite flavonoid composition, characterized in that: The invention comprises flavonoids, lecithin, glycerol, propylene glycol, caprylic acid / capric acid triglyceride, tocopherol acetate and water; the flavonoids are total flavonoids of Panax notoginseng and total flavonoids of dried orange peel.

2. The composite flavonoid composition according to claim 1, characterized in that: The invention comprises 5 parts of flavonoids, 2-7 parts of lecithin, 10-25 parts of glycerin, 15-35 parts of propylene glycol, 7-13 parts of caprylic / capric triglyceride, 1-3 parts of tocopherol acetate and 12-60 parts of water according to weight parts.

3. The composite flavonoid composition according to claim 2, characterized in that: The mass ratio of the total flavonoids of Panax notoginseng to the total flavonoids of dried orange peel in the flavonoids is 4:1-16.

4. The composite flavonoid composition according to claim 3, characterized in that: The mass ratio of the total flavonoids of Panax notoginseng to the total flavonoids of dried orange peel in the flavonoids is 4:1-4.

5. The composite flavonoid composition according to claim 4, characterized in that: The mass ratio of the total flavonoids of Panax notoginseng to the total flavonoids of dried orange peel is 4:

1.

6. The composite flavonoid composition according to any one of claims 1 to 5, characterized in that: The extraction steps of total flavonoids from Sanqi are as follows: ultrafinely grind Sanqi, wherein the particle size of the Sanqi powder after ultrafine grinding is less than 10 μm, then mix the Sanqi powder with ethanol at 40-75° C. for 15-45 minutes, then homogenize the Sanqi solution by microfluidization, and rotary evaporate the homogenized solution to obtain total flavonoids from Sanqi; the mass ratio of the Sanqi powder to ethanol is 1:1-10.

7. The composite flavonoid composition according to any one of claims 1 to 5, characterized in that: The extraction steps of the total flavonoids from tangerine peel are as follows: superfinely grinding the tangerine peel, wherein the particle size of the tangerine peel powder after the superfine grinding is less than 10 μm, then mixing the tangerine peel powder with modified ethanol at 30-75° C. for 10-45 minutes, then homogenizing the tangerine peel solution in a micro-jet manner, and rotary evaporating the homogenized solution to obtain the total flavonoids from tangerine peel; the mass ratio of the tangerine peel powder to the ethanol is 1:1-10.

8. The method for preparing the composite flavonoid composition according to any one of claims 1 to 7, characterized in that: The following steps are involved: Total flavonoids from Panax notoginseng, total flavonoids from dried orange peel, lecithin, glycerin, propylene glycol, caprylic / capric triglyceride, tocopherol acetate and water are uniformly mixed to obtain a mixed phase solution, the mixed phase solution is homogenized by high shear emulsification to obtain a micron-sized crude emulsion, and the micron-sized crude emulsion is homogenized by microfluidization to obtain a highly permeable composite flavonoid composition.

9. The preparation method according to claim 8, characterized in that: The total flavonoids of Panax notoginseng, total flavonoids of dried orange peel, lecithin, glycerol, propylene glycol, caprylic / capric triglyceride, tocopherol acetate and water are mixed uniformly at 60°C.

10. Use of the complex flavonoid composition according to any one of claims 1 to 7 in cosmetics or skin care products.

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