A high permeability flavonoid composition and its preparation method and use

Abstract

The application discloses a high-permeability composite flavone composition and a preparation method and application thereof, and relates to the technical field of cosmetics. The application discloses a high-permeability composite flavone composition, wherein the composite flavone composition comprises flavones, lecithin, glycerol, propylene glycol, caprylic acid / capric acid triglyceride, tocopherol acetate and water; the flavones are total flavones of Sanguisorba officinalis and total flavones of Pericarpium Citri Reticulatae. In the process of extracting the flavones, ultrafine grinding and high-pressure microjet are combined, Sanguisorba officinalis and Pericarpium Citri Reticulatae are treated by using the ultrafine grinding, and Sanguisorba officinalis solution and Pericarpium Citri Reticulatae solution are treated by using the high-pressure microjet, so that the content of the flavones in the extract is increased.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and in particular to a highly permeable complex flavonoid composition, its preparation method, and its application. Background Technology

[0002] Non-enzymatic glycosylation is a series of complex non-enzymatic reactions. Proteins and glucose undergo non-enzymatic reactions in the body to form early glycosylation products such as Schiff bases and Amadori products. These products then undergo oxidation, rearrangement, and cross-linking processes to form irreversible advanced glycosylation (AGEs). AGEs are products of excess sugar and protein binding. They have two sources in the body: one is the synthesis of AGEs from excess sugar and protein, and the other is the ingestion of AGEs present in food. AGEs can combine with and damage the body's tissues and cells. Studies have shown that AGEs accelerate aging and lead to many chronic degenerative diseases.

[0003] Human skin tissue contains abundant collagen and elastin, which exist primarily in fibrous form and constitute the skin's skeletal structure, giving it strength and elasticity. AGEs (Advanced Glycation End Products) can cross-link with these two proteins, affecting not only their normal function but also skin cell adhesion and growth. Furthermore, the accumulation of AGEs-related crosslinks in the cell matrix reduces the permeability of connective tissue and weakens the diffusion of nutrients and metabolic waste products within the body, increasing skin tissue stiffness and thus decreasing skin elasticity, ultimately leading to skin aging and wrinkles.

[0004] Flavonoids are widely distributed in the plant kingdom, mostly existing in plants as glycosides or glycosyl groups bound to sugars, though some exist in free form. Flavonoids have attracted much attention due to their significant antioxidant properties, the main mechanisms of which involve scavenging free radicals, inhibiting oxidase activity, and chelating metal ions. Flavonoids can effectively scavenge reactive oxygen species (ROS), thereby inhibiting oxidative stress, and can also bind to already formed advanced aging processes (AGEs), rendering them inactive. However, the application of flavonoids in the cosmetics field has the following three drawbacks:

[0005] (1) The extraction rate is low, which often requires a large amount of raw materials to meet the needs of industrial applications, which easily leads to serious waste and low cost performance.

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

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

[0008] Currently, two methods can overcome the aforementioned shortcomings: one is to optimize the extraction process of flavonoids; the other is to encapsulate flavonoids into nanocarriers, thereby improving their solubility and stability while enhancing transdermal permeability. Nanoliposomes stand out among various nanocarriers due to their excellent biocompatibility and low toxicity. Composed of phospholipids, nanoliposomes possess unique hydrophilic and hydrophobic properties, effectively loading hydrophilic active ingredients into a hydrophilic core cavity and encapsulating hydrophobic active ingredients within a hydrophobic phospholipid bilayer to improve the solubility and bioavailability of the active ingredients. Furthermore, the lipid bilayer nanostructure of nanoliposomes can also enhance the overall skin stratum corneum penetration effect, thus promoting transdermal permeability.

[0009] In view of this, to address the shortcomings of existing technologies, this invention provides a highly permeable composite flavonoid composition, its preparation method, and its application. This invention not only solves the problem of low extraction rates of flavonoid compounds but also addresses the issue of poor permeability of the composite flavonoid composition, providing a theoretical basis for the application of flavonoid compounds in cosmetics. Summary of the Invention

[0010] The purpose of this invention is to provide a highly permeable composite flavonoid composition, its preparation method, and its application, which not only improves the extraction rate of flavonoid compounds but also enhances the permeability and stability of the composite flavonoid composition.

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

[0012] On one hand, the present invention provides a highly permeable composite flavonoid composition comprising flavonoids, lecithin, glycerin, propylene glycol, caprylic / capric triglyceride, tocopheryl acetate, and water; wherein the flavonoids are total flavonoids from Panax notoginseng and total flavonoids from Citrus reticulata peel.

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

[0014] More preferably, the compound flavonoid composition comprises, by weight, 5 parts flavonoids, 5 parts lecithin, 20 parts glycerol, 30 parts propylene glycol, 10 parts caprylic / capric triglyceride, 2 parts tocopheryl acetate, and 28 parts water.

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

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

[0017] Preferably, the mass ratio of total flavonoids from Panax notoginseng to total flavonoids from Citrus reticulata peel is 4:1.

[0018] Preferably, the extraction steps of the total flavonoids from Panax notoginseng are as follows: Panax notoginseng is subjected to ultrafine pulverization, and the particle size of the ultrafine pulverized Panax notoginseng powder is <10μm. Then, the Panax notoginseng powder is mixed with ethanol at 40-75℃ for 15-45min. Subsequently, the Panax notoginseng solution is homogenized by microfluidic jet. The homogenized solution is then subjected to rotary evaporation to obtain the total flavonoids from Panax notoginseng. The mass ratio of Panax notoginseng powder to ethanol is 1:1-10.

[0019] More preferably, the extraction steps for the total flavonoids of Panax notoginseng are as follows: Panax notoginseng is subjected to ultrafine pulverization, and the particle size of the ultrafine pulverized Panax notoginseng powder is 2μm. Then, the Panax notoginseng powder is mixed with ethanol at 70℃ for 30min. Subsequently, the Panax notoginseng solution is homogenized by microfluidic jet. The homogenized solution is then subjected to rotary evaporation to obtain the total flavonoids of Panax notoginseng. The mass ratio of Panax notoginseng powder to ethanol is 1:4.

[0020] Preferably, the extraction steps of total flavonoids from dried tangerine peel are as follows: the dried tangerine peel is subjected to ultra-fine pulverization, and the particle size of the pulverized tangerine peel powder is <10μm. Then, the tangerine peel powder is mixed with modified ethanol at 30-75℃ for 10-45min. Subsequently, the tangerine peel solution is homogenized by microfluidic jet. The homogenized solution is then subjected to rotary evaporation to obtain total flavonoids from dried tangerine peel. The mass ratio of tangerine peel powder to ethanol is 1:1-10.

[0021] More preferably, the extraction steps of the total flavonoids from tangerine peel are as follows: tangerine peel is subjected to ultra-fine pulverization, and the particle size of the tangerine peel powder after ultra-fine pulverization is 5 μm. Then, the tangerine peel powder is mixed with modified ethanol at 60°C for 30 min. Subsequently, the tangerine peel solution is homogenized by microfluidic jet. The homogenized solution is then subjected to rotary evaporation to obtain the total flavonoids from tangerine peel. The mass ratio of tangerine peel powder to ethanol is 3:7.

[0022] In another aspect, the present invention provides a method for preparing the above-mentioned highly permeable composite flavonoid composition, comprising the following steps: mixing total flavonoids of Panax notoginseng, total flavonoids of Citrus reticulata peel, lecithin, glycerol, propylene glycol, caprylic / capric triglyceride, tocopheryl 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 microfluidic jet to obtain a highly permeable composite flavonoid composition.

[0023] Preferably, the total flavonoids of Panax notoginseng, total flavonoids of Citrus reticulata peel, lecithin, glycerin, propylene glycol, caprylic / capric triglyceride, tocopheryl acetate, and water are mixed evenly at 60°C.

[0024] Finally, the present invention provides the application of the above-mentioned highly permeable compound flavonoid composition in cosmetics or skin care products.

[0025] The beneficial effects of this invention are as follows:

[0026] (1) In the process of extracting flavonoids, the present invention uses ultra-fine grinding and high-pressure micro-jet to treat notoginseng and tangerine peel with ultra-fine grinding and high-pressure micro-jet to treat notoginseng solution and tangerine peel solution, thereby increasing the flavonoid content in the extract.

[0027] (2) In this invention, the total flavonoids of Panax notoginseng and the total flavonoids of tangerine peel are nano-encapsulated to improve the permeability of the composite flavonoid composition. Attached Figure Description

[0028] Figure 1 The surface morphology of the composite flavonoid composition prepared in Example 1 of this invention is shown.

[0029] Figure 2 The results of the determination of the composite flavonoid composition prepared in Example 1 of the present invention using a nanoparticle size analyzer are shown. Detailed Implementation

[0030] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following description is merely an exemplary illustration of the scope of protection of the present invention, and those skilled in the art can make various changes and modifications to the invention based on the disclosed content, which should also fall within the scope of protection of the present invention.

[0031] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention were obtained through conventional commercial means. Unless otherwise specified, all contents mentioned below are mass contents. Unless otherwise specified, it is understood that the process was carried out at room temperature.

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

[0033] Dried tangerine peel is the dried, mature peel of Citrus reticulata Blanco and its cultivated varieties, belonging to the Rutaceae family.

[0034] Modified ethanol: Adding benzodiazepine to ethanol improves the system's flexibility while avoiding oral ingestion.

[0035] Homogenizer: Manufacturer: IKA, Model: T25.

[0036] High-pressure micro-jet homogenizer: Manufacturer: Deheng Nanotechnology (Shenzhen) Co., Ltd., Model: DNH-340.

[0037] Instrument for ultrafine grinding: Manufacturer: Nozer Fluid Technology (Shanghai) Co., Ltd., Model: Micron JETMILL 4.

[0038] Example 1

[0039] 1. Extraction of flavonoids

[0040] 1.1 Extraction of total flavonoids from Panax notoginseng

[0041] Twenty parts of Panax notoginseng were weighed and subjected to ultrafine pulverization. The particle size of the ultrafine pulverized Panax notoginseng powder was 2 μm. Then, the Panax notoginseng powder was mixed with 80 parts of ethanol in a constant temperature water bath at 70℃ for 30 min. Subsequently, the Panax notoginseng solution was subjected to two high-pressure micro-jet homogenization treatments at a pressure of 25000 psi. The solution after the two high-pressure micro-jet homogenization treatments was subjected to rotary evaporation (temperature 70℃, time 50 min) to obtain total flavonoids of Panax notoginseng.

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

[0043] Thirty portions of dried tangerine peel were weighed and subjected to ultra-fine pulverization. The particle size of the tangerine peel powder after ultra-fine pulverization was 5 μm. Then, the tangerine peel powder was mixed with 70 portions of modified ethanol in a constant temperature water bath at 60℃ for 20 min. Subsequently, the tangerine peel solution was subjected to two high-pressure micro-jet homogenization treatments at a pressure of 25000 psi. The solution after the two high-pressure micro-jet homogenization treatments was subjected to rotary evaporation (temperature 75℃, time 50 min) to obtain total flavonoids from tangerine peel.

[0044] 2. Preparation of compound flavonoid composition

[0045] Then, 4 parts of total flavonoids from Panax notoginseng, 1 part of total flavonoids from Citrus reticulata peel, 5 parts of lecithin, and 20 parts of glycerol were dissolved in 30 parts of propylene glycol. Then, 10 parts of caprylic / capric triglyceride, 2 parts of tocopheryl acetate, and 28 parts of purified water were added and stirred until completely dissolved. The mixture was stirred evenly in a 60℃ constant temperature water bath (stirring time t ≥ 3 min, rotation speed 150 r / min). The mixed phase solution was homogenized using a homogenizer under high shear (stirring time t ≥ 10 min, rotation speed 6000-8000 rpm / min) to obtain a micron-sized crude emulsion. After returning to room temperature, the micron-sized crude emulsion was subjected to high-pressure microfluidic homogenization using a microfluidic homogenizer at a pressure of 25000 psi for two cycles to obtain the composite flavonoid composition.

[0046] Example 2

[0047] 1. Extraction of flavonoids

[0048] 1.1 Extraction of total flavonoids from Panax notoginseng

[0049] Twenty parts of Panax notoginseng were weighed and subjected to ultrafine grinding. The particle size of the ultrafinely ground Panax notoginseng powder was 2 μm. Then, the ultrafinely ground Panax notoginseng powder was mixed with 20 parts of ethanol in a constant temperature water bath at 40℃ for 15 min. Subsequently, the Panax notoginseng solution was subjected to two high-pressure micro-jet homogenization treatments at a pressure of 25000 psi using a high-pressure micro-jet homogenizer. The solution after the two high-pressure micro-jet homogenization treatments was subjected to rotary evaporation to obtain total flavonoids from Panax notoginseng.

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

[0051] Thirty portions of dried tangerine peel were weighed and subjected to ultra-fine pulverization. The particle size of the tangerine peel powder after ultra-fine pulverization was 5 μm. Then, the ultra-fine pulverized tangerine peel powder was mixed with 30 portions of modified ethanol in a constant temperature water bath at 30°C for 10 min. Subsequently, the tangerine peel solution was subjected to two high-pressure micro-jet homogenization treatments at a pressure of 25000 psi using a high-pressure micro-jet homogenizer. The solution after the two high-pressure micro-jet homogenization treatments was subjected to rotary evaporation to obtain total flavonoids from tangerine peel.

[0052] 2. Preparation of compound flavonoid composition

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

[0054] Example 3

[0055] 1. Extraction of flavonoids

[0056] 1.1 Extraction of total flavonoids from Panax notoginseng

[0057] Twenty parts of Panax notoginseng were weighed and subjected to ultrafine grinding. The particle size of the ultrafinely ground Panax notoginseng powder was 2 μm. Then, the ultrafinely ground Panax notoginseng powder was mixed with 200 parts of ethanol in a constant temperature water bath at 75°C for 45 min. Subsequently, the Panax notoginseng solution was subjected to two high-pressure micro-jet homogenization treatments at a pressure of 25000 psi using a high-pressure micro-jet homogenizer. The solution after the two high-pressure micro-jet homogenization treatments was subjected to rotary evaporation to obtain total flavonoids from Panax notoginseng.

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

[0059] Thirty portions of dried tangerine peel were weighed and subjected to ultra-fine pulverization. The particle size of the tangerine peel powder after ultra-fine pulverization was 5 μm. Then, the ultra-fine pulverized tangerine peel powder was mixed with 300 portions of modified ethanol in a constant temperature water bath at 90℃ for 30 min. Subsequently, the tangerine peel solution was subjected to two high-pressure micro-jet homogenization treatments at a pressure of 25000 psi using a high-pressure micro-jet homogenizer. The solution after the two high-pressure micro-jet homogenization treatments was subjected to rotary evaporation to obtain total flavonoids from tangerine peel.

[0060] 2. Preparation of compound flavonoid composition

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

[0062] Example 4

[0063] 1. Extraction of flavonoids

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

[0065] 2. Preparation of compound flavonoid composition

[0066] Then, 1 part of total flavonoids from Panax notoginseng, 4 parts of total flavonoids from Citrus reticulata peel, 5 parts of lecithin, and 20 parts of glycerol were dissolved in 30 parts of propylene glycol. Then, 10 parts of caprylic / capric triglyceride, 2 parts of tocopheryl acetate, and 28 parts of purified water were added and stirred until completely dissolved. The mixture was then stirred evenly in a 60℃ constant temperature water bath (stirring time t ≥ 3 min, rotation speed 150 r / min). The mixed phase solution was homogenized using a homogenizer under high shear (stirring time t ≥ 10 min, rotation speed 6000-8000 rpm / min) to obtain a micron-sized crude emulsion. After returning to room temperature, the micron-sized crude emulsion was subjected to high-pressure microfluidic homogenization using a microfluidic homogenizer at a pressure of 25000 psi for two cycles to obtain the composite flavonoid composition.

[0067] Example 5

[0068] 1. Extraction of flavonoids

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

[0070] 2. Preparation of compound flavonoid composition

[0071] Then, 2.5 parts of total flavonoids from Panax notoginseng, 2.5 parts of total flavonoids from Citrus reticulata peel, 5 parts of lecithin, and 20 parts of glycerol were dissolved in 30 parts of propylene glycol. Then, 10 parts of caprylic / capric triglyceride, 2 parts of tocopheryl acetate, and 28 parts of purified water were added and stirred until completely dissolved. The mixture was then stirred evenly in a 60℃ constant temperature water bath (stirring time t ≥ 3 min, rotation speed 150 r / min). The mixed phase solution was homogenized using a homogenizer under high shear (stirring time t ≥ 10 min, rotation speed 6000-8000 rpm / min) to obtain a micron-sized crude emulsion. After returning to room temperature, the micron-sized crude emulsion was subjected to high-pressure homogenization using a microfluidic homogenizer at a pressure of 25000 psi for two cycles to obtain the composite flavonoid composition.

[0072] Example 6

[0073] 1. Extraction of flavonoids

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

[0075] 2. Preparation of compound flavonoid composition

[0076] Then, 4 parts of total flavonoids from Panax notoginseng, 1 part of total flavonoids from Citrus reticulata peel, 2 parts of lecithin, and 10 parts of glycerol were dissolved in 15 parts of propylene glycol. Then, 7 parts of caprylic / capric triglyceride, 1 part of tocopheryl acetate, and 60 parts of purified water were added and stirred until completely dissolved. The mixture was then stirred evenly in a 60℃ constant temperature water bath (stirring time t ≥ 3 min, rotation speed 150 r / min). The mixed phase solution was homogenized using a homogenizer under high shear (stirring time t ≥ 10 min, rotation speed 6000-8000 rpm / min) to obtain a micron-sized crude emulsion. After returning to room temperature, the micron-sized crude emulsion was subjected to high-pressure microfluidic homogenization using a microfluidic homogenizer at a pressure of 25000 psi for two cycles to obtain the composite flavonoid composition.

[0077] Example 7

[0078] 1. Extraction of flavonoids

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

[0080] 2. Preparation of compound flavonoid composition

[0081] Then, 4 parts of total flavonoids from Panax notoginseng, 1 part of total flavonoids from Citrus reticulata peel, 7 parts of lecithin, and 25 parts of glycerol were dissolved in 35 parts of propylene glycol. Then, 13 parts of caprylic / capric triglyceride, 3 parts of tocopheryl acetate, and 12 parts of purified water were added and stirred until completely dissolved. The mixture was stirred evenly in a 60℃ constant temperature water bath (stirring time t ≥ 3 min, rotation speed 150 r / min). The mixed phase solution was homogenized using a homogenizer under high shear (stirring time t ≥ 10 min, rotation speed 6000-8000 rpm / min) to obtain a micron-sized crude emulsion. After returning to room temperature, the micron-sized crude emulsion was subjected to high-pressure homogenization using a microfluidic homogenizer at a pressure of 25000 psi for two cycles to obtain the composite flavonoid composition.

[0082] Comparative Example 1

[0083] 1. Extraction of flavonoids

[0084] 1.1 Extraction of total flavonoids from Panax notoginseng

[0085] Twenty parts of Panax notoginseng were weighed and coarsely pulverized. The particle size of the coarsely pulverized Panax notoginseng powder was 100 μm. Then, the Panax notoginseng powder was mixed with 80 parts of ethanol in a constant temperature water bath at 70℃ for 30 min. Subsequently, the Panax notoginseng solution was subjected to two high-pressure micro-jet homogenization treatments at a pressure of 25000 psi using a high-pressure micro-jet homogenizer. The solution after the two high-pressure micro-jet homogenization treatments was subjected to rotary evaporation to obtain total flavonoids from Panax notoginseng.

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

[0087] Thirty parts of dried tangerine peel were weighed and coarsely ground. The particle size of the coarsely ground tangerine peel powder was 140 μm. Then, the tangerine peel powder and 70 parts of modified ethanol were stirred and mixed in a constant temperature water bath at 60℃ for 20 min. Subsequently, the tangerine peel solution was subjected to two high-pressure micro-jet homogenization treatments at a pressure of 25000 psi using a high-pressure micro-jet homogenizer. The solution after the two high-pressure micro-jet homogenization treatments was subjected to rotary evaporation to obtain total flavonoids from tangerine peel.

[0088] Comparative Example 2

[0089] Twenty parts of Panax notoginseng were weighed and subjected to ultra-fine pulverization. The particle size of the ultra-fine pulverized Panax notoginseng powder was 2 μm. Then, the ultra-fine pulverized Panax notoginseng powder was mixed with 80 parts of ethanol in a constant temperature water bath at 70℃ for 30 min. Subsequently, the Panax notoginseng solution was subjected to rotary evaporation to obtain total flavonoids from Panax notoginseng.

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

[0091] Thirty portions of dried tangerine peel were weighed and subjected to ultra-fine pulverization. The particle size of the tangerine peel powder after ultra-fine pulverization was 5 μm. Then, the ultra-fine pulverized tangerine peel powder was mixed with 70 portions of modified ethanol in a constant temperature water bath at 60℃ for 20 min. Subsequently, the tangerine peel solution was subjected to rotary evaporation to obtain total flavonoids from tangerine peel.

[0092] Detection methods

[0093] 1. In vitro skin retention performance test

[0094] The skin absorption performance of isolated pig skin was tested according to GB / T27818—2011 "In vitro test method for skin absorption of chemicals". The vertical Franz diffusion cell method was used. Abdominal and dorsal skin samples (average thickness approximately 750 μm) from healthy 1-month-old Bama pigs stored at -20℃ were thawed naturally at room temperature, gently wiped clean with phosphate buffer solution (pH 6.8-7.4), and the initial transdermal water loss was measured using a transdermal water loss meter. An initial transdermal water loss of <15 g / m² was acceptable. 2 • At h, the stratum corneum of the skin was considered intact. A vertical (Franz) diffusion cell was used as the diffusion device. The prepared excised skin was fixed between the supply and receiving cells, 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 ensure close contact between the skin and the receiving solution, without air bubbles. The transdermal diffusion apparatus was turned on, the water level in the tank was checked, and the rotation speed was set to 350 rpm and the temperature to 32℃, preheating for 5 minutes. In each sample testing group, 0.2 g / cm³ was used. 2 100 mg FITC was added to each of the examples / comparative examples / control examples. At 48 hours, the diffusion cell was removed, excess sample in the supply cell was discarded, and the skin surface was washed with ultrapure water. A tissue block from the effectively permeable portion of the skin was removed, fixed in fixative, and frozen sectioned. The tissue sections were then observed under a fluorescence microscope to observe the distribution of FITC fluorescence signals in the skin tissue. Subsequently, the tissue was thoroughly homogenized in a high-throughput tissue homogenizer, extracted with 1 mL of acetonitrile, allowed to stand, filtered, and then chromatographically analyzed using a Pursuit XRs C18 (500 g / 3 L) column. The mobile phase was a mixture of water and acetonitrile (40:60 v / v), the flow rate was 0.3 mL / min, the injection volume was 20 μL, the column temperature was 30 °C, and the chromatographic time was 15 min. The quantitative detection wavelengths were 271 nm and 510 nm (corresponding to the absorbance of total flavonoids from dried tangerine peel and total flavonoids from Panax notoginseng, respectively). The retention amount of complex flavonoids in the skin was calculated cumulatively.

[0095] 2. Morphological observation by transmission electron microscopy

[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 day 1, was diluted to an appropriate concentration with ultrapure water at pH 7.0. 10 μL of the diluted Example 1 was dropped onto a copper grid, allowed to stand for 2 min, and then excess sample around the grid was aspirated. The grid was then negatively stained with 2.0 wt% uranium acetate solution for 5 min. Excess staining solution was removed with filter paper, and the sample was allowed to air dry at room temperature. A suitable amount of sample was then dropped onto the copper grid and photographed.

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

[0098] The average particle size, PDI, and Zeta potential of the composite flavonoid compositions prepared in the examples were determined using a nanoparticle size analyzer. First, the samples prepared on day 1 were diluted 100-fold with ultrapure water. The test temperature was set to 25°C, the scattering angle to 90°, and each sample was scanned three times, with the average value used as the measured value. For the Zeta potential measurement, the samples were not diluted and were directly added to the Zeta potential cell for measurement.

[0099] 4. Determination of flavonoid content

[0100] The total flavonoid content was determined by the direct method. First, a standard curve for the standard sample rutin was established. The absorbance of total flavonoids from dried tangerine peel and total flavonoids from Panax notoginseng was measured at 271 nm and 510 nm, respectively. The total flavonoid content 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 reticulata peel, 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 has good stability in the range of -7 to 0 mV and poor stability in the range of -30 to -8 mV.

[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 combined ultrafine grinding and high-pressure microjet in the flavonoid extraction process. Ultrafine grinding was used to treat Panax notoginseng and tangerine peel, and high-pressure microjet was used to treat Panax notoginseng solution and tangerine peel solution, which increased the flavonoid content in the extract.

[0111] Compared with the control example, Examples 1 and 4-7 subjected the total flavonoids of Panax notoginseng and total flavonoids of tangerine peel to nano-encapsulation treatment, which improved the permeability of the composite flavonoid composition.

[0112] Compared with Examples 4 and 5, Example 1 improved the permeability and stability of the compound flavonoid composition by limiting the mass ratio of total flavonoids from Panax notoginseng to total flavonoids from Citrus reticulata 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 principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A highly permeable complex flavonoid composition, characterized in that, The product is composed of the following components by weight: 5 parts flavonoids, 5 parts lecithin, 20 parts glycerol, 30 parts propylene glycol, 10 parts caprylic / capric triglyceride, 2 parts tocopheryl acetate, and 28 parts water; the flavonoids are total flavonoids from Panax notoginseng and total flavonoids from Citrus reticulata peel, wherein the mass ratio of total flavonoids from Panax notoginseng to total flavonoids from Citrus reticulata peel is 4:

1. The extraction steps for total flavonoids from Panax notoginseng are as follows: 20 parts of Panax notoginseng were weighed and subjected to ultra-fine pulverization. The particle size of the Panax notoginseng powder after ultra-fine pulverization was 2 μm. Then, the Panax notoginseng powder was mixed with 80 parts of ethanol in a constant temperature water bath at 70°C for 30 min. Subsequently, the Panax notoginseng solution was subjected to two high-pressure micro-jet homogenization treatments at a pressure of 25000 psi. The solution after the two high-pressure micro-jet homogenization treatments was then subjected to rotary evaporation at a temperature of 70°C for 50 min to obtain total flavonoids from Panax notoginseng. The extraction steps for total flavonoids from dried tangerine peel are as follows: 30 parts of dried tangerine peel are weighed and subjected to ultra-fine pulverization. The particle size of the tangerine peel powder after ultra-fine pulverization is 5μm. Then, the tangerine peel powder is mixed with 70 parts of modified ethanol in a constant temperature water bath at 60℃ for 20min. Subsequently, the tangerine peel solution is subjected to two high-pressure micro-jet homogenizer treatments at a pressure of 25000psi. The solution after the two high-pressure micro-jet homogenization treatments is then subjected to rotary evaporation at a temperature of 75℃ for 50min to obtain total flavonoids from dried tangerine peel. The modified ethanol is ethanol with added benzyl dinamate. The preparation method of the compound flavonoid composition includes the following steps: mixing total flavonoids of Panax notoginseng, total flavonoids of Citrus reticulata peel, lecithin, glycerol, propylene glycol, caprylic / capric triglyceride, tocopheryl 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 microfluidic jet to obtain a highly permeable compound flavonoid composition. The total flavonoids of Panax notoginseng, total flavonoids of Citrus reticulata peel, lecithin, glycerin, propylene glycol, caprylic / capric triglyceride, tocopheryl acetate, and water were mixed evenly at 60°C.

2. The compound flavonoid composition according to claim 1, characterized in that, The preparation method of the compound flavonoid composition includes the following steps: total flavonoids from Panax notoginseng, total flavonoids from Citrus reticulata peel, lecithin, glycerol, propylene glycol, caprylic / capric triglyceride, tocopheryl acetate, and water are mixed evenly at 60°C for ≥3 min at a speed of 150 rpm to obtain a mixed phase solution; the mixed phase solution is homogenized by high-shear emulsification for ≥10 min at a speed of 6000-8000 pm to obtain a micron-sized crude emulsion; the micron-sized crude emulsion is homogenized by microfluidic jetting at a pressure of 25000 psi for two cycles to obtain a highly permeable compound flavonoid composition.

3. The use of the compound flavonoid composition according to claim 1 in the preparation of cosmetics.

4. The use of the compound flavonoid composition according to claim 1 in the preparation of skin care products.

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