An external composition with perioral or commissure care and a method of making the same

Abstract

The present application relates to the field of cosmetic technology, and discloses an external composition with lip or corner of mouth care and a preparation method thereof, the preparation method comprising the following steps: preparing a ternary emollient and nourishing composition of white pool seed oil-squalane-bee wax, compounding a multilayer antioxidant protection composition of squalene-rosemary extract-propyl gallate-grape seed extract-scullcap extract, adding rosemary extract at 75 DEG C, adding squalene at 60 DEG C, adding water phase polyphenol antioxidant at 40 DEG C, and emulsifying to form a three-dimensional protection emulsion, and finally obtaining a stable product through hydroxypropyl cyclodextrin inclusion and pH adjustment. The present application realizes deep care of rapid penetration-middle layer supplement-surface layer water locking through a three-dimensional nourishing composition, and the multilayer antioxidant composition improves the DPPH free radical clearance rate to more than 80%, significantly improves the problems of dryness, pigmentation and photoaging around the lips, and meets the application requirements of outdoor strong light environment and frequent saliva contact.

Description

Technical Field

[0001] This invention relates to the field of cosmetic technology, and more specifically, to a topical composition for lip or corner mouth care and a method for preparing the same. Background Technology

[0002] The skin around the lips and corners of the mouth has a sparse distribution of sebaceous glands, a thin stratum corneum, and a weak barrier function, making it highly susceptible to dryness, cracking, and peeling. This area is constantly exposed to the external environment, suffering from continuous ultraviolet radiation and oxidative stress damage from environmental pollution, leading to pigmentation, fine lines, and photoaging.

[0003] More importantly, the area around the lips is frequently exposed to saliva. The oxidases and hydrolases in saliva can catalyze the enzymatic oxidation of unsaturated fatty acids in skincare ingredients, generating lipid hydroperoxides and aldehyde and ketone secondary oxidation products, which reduce the nourishing effect and may produce unpleasant odors and irritation.

[0004] Existing products struggle to simultaneously achieve multi-layered deep nourishment through rapid penetration, mid-layer replenishment, and surface hydration, resulting in limited effectiveness in improving dryness and chapping around the lips. Existing antioxidants suffer from poor stability during storage and preparation, leading to significant activity loss and insufficient antioxidant capacity. Many antioxidant components undergo photodegradation or even transform into pro-oxidants under UV irradiation, resulting in a 50-70% loss of antioxidant activity during outdoor use. Traditional chemical antioxidants have limited inhibitory effects on oxidation reactions catalyzed by biological enzymes in saliva, and the product's efficacy significantly decreases after dietary contact. Furthermore, there is a lack of adaptive formulations and process optimizations specifically designed for environments with strong sunlight and frequent saliva contact around the lips. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a topical composition for perilip or corner mouth care and a method for preparing the same.

[0006] A topical composition for perilip or corner-of-mouth care comprises the following components in weight percentage: meadowfoam seed oil 1.8-2.2%, squalane 0.8-1.2%, beeswax 0.15-0.25%, squalene 0.4-0.6%, rosemary extract 0.25-0.35%, propyl gallate 0.15-0.25%, grape seed extract 0.35-0.45%, scutellaria baicalensis extract 0.2-0.3%, tocopherol 0.00003-0.3%, hydroxypropyl cyclodextrin 0.12-0.16%, glycerin 9.5-10.5%, 1,2-hexanediol 0.4-0.6%, and water as the balance;

[0007] The meadowfoam seed oil, squalane, and beeswax form a three-element moisturizing and nourishing system that rapidly penetrates, replenishes the middle layer, and locks in moisture on the surface. The squalene, rosemary extract, propyl gallate, grape seed extract, scutellaria baicalensis extract, and tocopherol form a multi-layered, progressive antioxidant protection system. The propyl gallate inhibits lipoxygenase activity by forming hydrogen bonds with the unsaturated fatty acids in the meadowfoam seed oil through phenolic hydroxyl groups. The hydroxypropyl cyclodextrin forms inclusion complexes with photosensitive phenolic antioxidants to improve photostability.

[0008] Preferably, it further comprises the following components in weight percentage: sorbitan oleate 0.5-0.6%, cetearyl glucoside 0.4-0.5%, polyacrylate crosspolymer-6 0.8-1.2%, carbomer 0.2-0.3%, tromethamine 0.18-0.24%, and disodium EDTA 0.015-0.025%.

[0009] Preferably, the meadowfoam seed oil has an iodine value ≥165 and an acid value ≤3.0 mg KOH / g; the squalane has a purity ≥99%; and the beeswax has an acid value of 5-22 mg KOH / g and a saponification value of 87-104 mg KOH / g.

[0010] Preferably, the squalene has a purity of ≥98%, an unsaturation of ≥99%, and an iodine value of ≥380; the squalene and the squalane are synergistically combined in a weight ratio of 1:2.

[0011] Preferably, the rosemary extract has a caryopsisic acid content of ≥15%, a rosmarinic acid content of ≥5%, and a total phenol content of ≥20%; the purity of the propyl gallate is ≥98%.

[0012] Preferably, the grape seed extract has a proanthocyanidin content of ≥95% and a water solubility of ≥80%; the scutellaria baicalensis extract has a baicalin content of ≥85% and a total flavonoid content of ≥90%.

[0013] Preferably, the degree of substitution of the hydroxypropyl cyclodextrin is 0.6-1.0, and the molecular weight is 1400±200; the tocopherol is α-tocopherol with a purity ≥95%.

[0014] Preferably, it also includes the following skin conditioning ingredients by weight percentage: 0.4-0.5% calendula extract, 0.008-0.012% asiaticoside, 0.025-0.035% asiaticoside, 0.015-0.025% centella asiatica extract, 0.35-0.45% allantoin, and 0.15-0.25% dipotassium glycyrrhizate.

[0015] Preferably, it also includes the following skin feel modifiers by weight percentage: 4.5-5.1% polydimethylsiloxane, 1.0-1.4% polydimethylsiloxane crosspolymer, and 1.8-2.2% phenyl polytrimethylsiloxane.

[0016] A method for preparing a topical composition for perilip or corner mouth care includes the following steps:

[0017] Step 1: Mix propyl gallate with meadowfoam seed oil, squalane, and beeswax at 70-75℃ for 15-20 minutes to form the base oil phase;

[0018] Step 2: Add rosemary extract to the oil phase at 75°C and stir for 10-15 minutes;

[0019] Step 3: After cooling to 60-65℃, add squalene and stir for 5-10 minutes to form an antioxidant oil phase;

[0020] Step 4: Dissolve glycerol, 1,2-hexanediol, grape seed extract, and scutellaria baicalensis extract in purified water at 40-45℃ to form an aqueous phase;

[0021] Step 5: Emulsify the oil phase and the water phase at 50-60℃, and add emulsifier and thickener to form an emulsion;

[0022] Step 6: Add hydroxypropyl cyclodextrin and other active ingredients at a temperature below 40°C;

[0023] Step 7: Add tocopherol at 35-40℃, adjust the pH to 6.0-6.5 with tromethamine, and add disodium EDTA;

[0024] Step 8: Cool to 25-30℃ and package under nitrogen protection.

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

[0026] A ternary composition of meadowfoam seed oil, squalane, and beeswax constructs a three-dimensional nourishing system of "rapid penetration, mid-layer replenishment, and surface moisture locking," achieving a 24-hour moisturizing rate of 82.5%, which is 3.2 times that of conventional lotions (25.7%). After four weeks of continuous use, lip lines showed a 45.7% improvement in depth and a 38.5% reduction in number, with a penetration coefficient of 2.85 × 10⁻⁶. -6 cm / h.

[0027] The multi-layered, progressive antioxidant protective composition achieved a DPPH free radical scavenging rate of 84.2%, which is 3.6 times that of vitamin E alone (23.4%). After 4 weeks of use, malondialdehyde content in the perilipal skin decreased by 52.3%, and superoxide dismutase activity increased by 43.8%.

[0028] After 10 hours of exposure to strong light, the antioxidant activity retention rate reached 91.7%, while the traditional formula only retained 28.4%. The key ingredient, caryopsisic acid, retained 91.6%, and the color stability was excellent (ΔE only 1.68), making it suitable for outdoor use.

[0029] Propyl gallate inhibited lipoxygenase by 68.7% (IC50). 50 (Value 15.2 μM). After 4 hours in a simulated saliva environment, the peroxide value growth rate was only 77.8%, while the traditional formula reached 916.7%, effectively addressing the challenge of frequent contact with saliva around the lips.

[0030] The stepwise temperature-controlled addition process achieves a 95.3% retention rate of active ingredients, significantly superior to the traditional one-time high-temperature addition process (69.7%). The retention rates of oxalic acid, squalene, and proanthocyanidins all exceed 94%.

[0031] After 6 months of accelerated stability testing, the peroxide value was controlled below 5 meq / kg, and the long-term stability was maintained at ≥95% of the active ingredient for 24 months. Clinical trials showed an improvement rate of 92.1% for perilip dryness, an overall satisfaction rate of 96.7%, and a safety evaluation irritation index of 0. Attached Figure Description

[0032] Figure 1 These are the antioxidant activity change curves of different samples under light irradiation conditions according to the present invention;

[0033] Figure 2 This is the curve showing the change of sarcopenic acid content with light exposure time according to the present invention;

[0034] Figure 3 This is a bar chart comparing the retention rate of oxalic acid after 10 hours of light exposure according to the present invention;

[0035] Figure 4 This is a bar graph showing the inhibitory effects of different samples of the present invention on lipoxygenase;

[0036] Figure 5 This is a bar chart showing the half-maximal inhibitory concentration (IC50) of different samples in this invention;

[0037] Figure 6 These are the anti-enzymatic oxidation performance curves of different samples in a simulated saliva environment according to the present invention;

[0038] Figure 7 This is a comparison curve of the 24-hour moisturizing effect of different samples of the present invention;

[0039] Figure 8 This is a bar chart comparing the moisturizing effects of the present invention after 24 hours;

[0040] Figure 9This is a bar graph showing the improvement in lip line depth after 4 weeks of the present invention;

[0041] Figure 10 This is a bar graph showing the improvement in the number of lip lines after 4 weeks of this invention. Detailed Implementation

[0042] The subject matter described herein will now be discussed with reference to exemplary embodiments. It should be understood that these embodiments are discussed only to enable those skilled in the art to better understand and implement the subject matter described herein, and changes may be made to the function and arrangement of the elements discussed without departing from the scope of this specification. Various processes or components may be omitted, substituted, or added as needed in the examples. Furthermore, some features described in the examples may be combined in other examples.

[0043] Example 1

[0044] This embodiment proposes a topical composition for perilip or corner mouth care, comprising the following components by weight percentage: meadowfoam seed oil 2.0%, squalane 1.0%, beeswax 0.20%, squalene 0.5%, rosemary extract 0.30%, propyl gallate 0.20%, grape seed extract 0.40%, scutellaria baicalensis extract 0.25%, tocopherol 0.15%, hydroxypropyl cyclodextrin 0.14%, glycerin 10.0%, 1,2-hexanediol 0.5%, and water as the balance;

[0045] It also includes the following components by weight percentage: sorbitan oleate 0.55%, cetearyl glucoside 0.45%, polyacrylate crosspolymer-6 1.0%, carbomer 0.25%, tromethamine 0.21%, and disodium EDTA 0.020%.

[0046] It also includes the following skin conditioning ingredients by weight percentage: 0.45% Calendula officinalis extract, 0.01% asiaticoside, 0.03% asiaticoside, 0.02% Centella asiatica extract, 0.40% allantoin, and 0.20% dipotassium glycyrrhizate.

[0047] It also includes the following skin feel modifiers by weight percentage: 4.8% polydimethylsiloxane, 1.2% polydimethylsiloxane crosspolymer, and 2.0% phenyl polytrimethylsiloxane.

[0048] Meadowfoam seed oil, squalane, and beeswax form a three-element moisturizing and nourishing system that rapidly penetrates, replenishes the middle layer, and locks in moisture on the surface. Squalene, rosemary extract, propyl gallate, grape seed extract, scutellaria baicalensis extract, and tocopherol form a multi-layered, progressive antioxidant protection system. Propyl gallate inhibits lipoxygenase activity by forming hydrogen bonds with the unsaturated fatty acids in meadowfoam seed oil through phenolic hydroxyl groups. Hydroxypropyl cyclodextrin forms inclusion complexes with photosensitive phenolic antioxidants to improve photostability.

[0049] The iodine value of meadowfoam seed oil is ≥165, and the acid value is ≤3.0mg KOH / g; the purity of the squalane is ≥99%; the acid value of the beeswax is 18mg KOH / g, and the saponification value is 95mg KOH / g.

[0050] The squalene has a purity of ≥98%, an unsaturation of ≥99%, and an iodine value of ≥380; the squalene and the squalane are synergistically combined in a weight ratio of 1:2.

[0051] The rosemary extract has a carrageenan content of ≥15%, a rosmarinic acid content of ≥5%, and a total phenol content of ≥20%; the purity of the propyl gallate is ≥98%.

[0052] The grape seed extract has a proanthocyanidin content of ≥95% and a water solubility of ≥80%; the scutellaria baicalensis extract has a baicalin content of ≥85% and a total flavonoid content of ≥90%.

[0053] The degree of substitution of hydroxypropyl cyclodextrin is 0.8, and the molecular weight is 1400; the tocopherol is α-tocopherol with a purity ≥95%.

[0054] Example 2

[0055] The difference between this embodiment and Embodiment 1 is that:

[0056] The topical composition comprises the following components in weight percentage: meadowfoam seed oil 1.8%, squalane 0.8%, beeswax 0.15%, squalene 0.4%, rosemary extract 0.25%, propyl gallate 0.15%, grape seed extract 0.35%, scutellaria baicalensis extract 0.2%, tocopherol 0.00003%, hydroxypropyl cyclodextrin 0.12%, glycerin 9.5%, 1,2-hexanediol 0.4%, and water as the balance;

[0057] It also includes the following components by weight percentage: sorbitan oleate 0.5%, cetearyl glucoside 0.4%, polyacrylate crosspolymer-6 0.8%, carbomer 0.2%, tromethamine 0.18%, and disodium EDTA 0.015%.

[0058] It also includes the following skin conditioning ingredients by weight percentage: 0.4% Calendula officinalis extract, 0.008% asiaticoside, 0.025% asiaticoside, 0.015% Centella asiatica extract, 0.35% allantoin, and 0.15% dipotassium glycyrrhizate.

[0059] It also includes the following skin feel modifiers by weight percentage: 4.5% polydimethylsiloxane, 1.0% polydimethylsiloxane crosspolymer, and 1.8% phenyl polytrimethylsiloxane.

[0060] The acid value of beeswax is 5 mg KOH / g, and the saponification value is 87 mg KOH / g.

[0061] The degree of substitution of hydroxypropyl cyclodextrin is 0.6, and the molecular weight is 1200.

[0062] Example 3

[0063] The difference between this embodiment and Embodiment 1 is that:

[0064] The topical composition comprises the following components in weight percentage: meadowfoam seed oil 2.2%, squalane 1.2%, beeswax 0.25%, squalene 0.6%, rosemary extract 0.35%, propyl gallate 0.25%, grape seed extract 0.45%, scutellaria baicalensis extract 0.3%, tocopherol 0.3%, hydroxypropyl cyclodextrin 0.16%, glycerin 10.5%, 1,2-hexanediol 0.6%, and water as the balance;

[0065] It also includes the following components by weight percentage: sorbitan oleate 0.6%, cetearyl glucoside 0.5%, polyacrylate crosspolymer-6 1.2%, carbomer 0.3%, tromethamine 0.24%, and disodium EDTA 0.025%.

[0066] It also includes the following skin conditioning ingredients by weight percentage: 0.5% Calendula extract, 0.012% asiaticoside, 0.035% asiaticoside, 0.025% Centella asiatica extract, 0.45% allantoin, and 0.25% dipotassium glycyrrhizate.

[0067] It also includes the following skin feel modifiers by weight percentage: 5.1% polydimethylsiloxane, 1.4% polydimethylsiloxane crosspolymer, and 2.2% phenyl polytrimethylsiloxane.

[0068] The acid value of beeswax is 22 mg KOH / g, and the saponification value is 104 mg KOH / g.

[0069] The degree of substitution of hydroxypropyl cyclodextrin is 1.0, and the molecular weight is 1600.

[0070] Example 4

[0071] This embodiment presents a method for preparing a topical composition for perilip or corner mouth care, comprising the following steps:

[0072] Step 1: At 72°C, propyl gallate is mixed with meadowfoam seed oil, squalane, and beeswax and stirred for 18 minutes to form the base oil phase;

[0073] Step 2: Add rosemary extract to the oil phase at 75°C and stir for 12 minutes;

[0074] Step 3: After cooling to 62℃, add squalene and stir for 8 minutes to form an antioxidant oil phase;

[0075] Step 4: Dissolve glycerol, 1,2-hexanediol, grape seed extract, and scutellaria baicalensis extract in purified water at 43°C to form an aqueous phase;

[0076] Step 5: Emulsify the oil phase and the water phase at 55°C, and add emulsifier and thickener to form an emulsion;

[0077] Step 6: Add hydroxypropyl cyclodextrin and other active ingredients at a temperature below 40°C;

[0078] Step 7: Add tocopherol at 38°C, adjust the pH to 6.3 with tromethamine, and add disodium EDTA;

[0079] Step 8: Cool to 28°C and package under nitrogen protection.

[0080] Example 5

[0081] The difference between this embodiment and embodiment 4 is that:

[0082] Step 1: Mix propyl gallate with meadowfoam seed oil, squalane, and beeswax at 70℃ for 15-20 minutes to form the base oil phase;

[0083] Step 2: Add rosemary extract to the oil phase at 75°C and stir for 10 minutes;

[0084] Step 3: After cooling to 60℃, add squalene and stir for 5 minutes to form an antioxidant oil phase;

[0085] Step 4: Dissolve glycerol, 1,2-hexanediol, grape seed extract, and scutellaria baicalensis extract in purified water at 40°C to form an aqueous phase;

[0086] Step 5: Emulsify the oil phase and the water phase at 50°C, and add emulsifier and thickener to form an emulsion;

[0087] Step 6: Add hydroxypropyl cyclodextrin and other active ingredients at a temperature below 38°C;

[0088] Step 7: Add tocopherol at 40°C, adjust the pH to 6.5 with tromethamine, and add disodium EDTA;

[0089] Step 8: Cool to 30°C and package under nitrogen protection.

[0090] Example 6

[0091] The difference between this embodiment and embodiment 4 is that:

[0092] Step 1: Mix propyl gallate with meadowfoam seed oil, squalane, and beeswax at 75℃ and stir for 20 minutes to form the base oil phase;

[0093] Step 2: Add rosemary extract to the oil phase at 75°C and stir for 15 minutes;

[0094] Step 3: After cooling to 65℃, add squalene and stir for 10 minutes to form an antioxidant oil phase;

[0095] Step 4: Dissolve glycerol, 1,2-hexanediol, grape seed extract, and scutellaria baicalensis extract in purified water at 45°C to form an aqueous phase;

[0096] Step 5: Emulsify the oil phase and the water phase at 60°C, and add emulsifier and thickener to form an emulsion;

[0097] Step 6: Add hydroxypropyl cyclodextrin and other active ingredients at a temperature below 35°C;

[0098] Step 7: Add tocopherol at 40°C, adjust the pH to 6.5 with tromethamine, and add disodium EDTA;

[0099] Step 8: Cool to 30°C and package under nitrogen protection.

[0100] Example 7

[0101] This embodiment presents a method for preparing a topical composition for perilip or corner mouth care, comprising the following steps:

[0102] Step 1: Prepare the enzyme inhibition protective oil phase (preferably at 72±2℃)

[0103] Safety precautions for high-temperature operations: Operating temperatures of 70-75℃ pose a risk of burns. Operators must wear high-temperature resistant gloves (≥100℃), protective goggles, and lab coats. Eyewash stations and burn first-aid kits must be provided in the work area. Reaction vessels must be equipped with temperature alarms and automatic power-off protection against overheating.

[0104] Propyl gallate (0.15-0.25% by weight, preferably 0.2%, purity ≥98%, melting point 147-148℃) is mixed with meadowfoam seed oil (1.8-2.2% by weight, preferably 2%, iodine value ≥165, acid value ≤3.0mg KOH / g), squalane (0.8-1.2% by weight, preferably 1%, purity ≥99%, molecular weight 410.72), and beeswax (0.15-0.25% by weight, preferably 0.2%, acid value 5-22mg KOH / g, saponification value 87-104mg KOH / g, melting point 60-66℃) in a stainless steel reaction vessel (316L material, capacity 1-5L, preferably 3L, to avoid metal ion contamination) equipped with a temperature control system.

[0105] Control the temperature range to 70-75℃ (preferably 72℃, with a temperature control accuracy of ±0.5℃), and the stirring speed to 300-500 rpm (preferably 400 rpm, using a mechanical stirrer with a blade diameter of 1 / 3 of the container diameter). Continue stirring for 15-20 minutes (preferably 18 minutes) until the beeswax is completely melted and forms a uniform, non-layered, and particle-free transparent to semi-transparent oil phase with the other components. At 72℃, the beeswax is completely liquid and forms a uniformly dispersed system with the oil phase components.

[0106] Technical highlights: Propyl gallate contains an ortho-trihydroxybenzene ring structure. Its phenolic hydroxyl group binds to long-chain unsaturated fatty acids (mainly eicosenoic acid, content ≥60%) in meadowfoam seed oil via hydrogen bonds (bond length approximately 2.8 Å), forming a phenolic protective layer with a molecular thickness of approximately 0.5-1.0 nm on the surface of the unsaturated fatty acid molecule. This protective layer prevents lipoxygenase (molecular weight approximately 75 kDa) from recognizing and approaching the substrate double bond through steric hindrance. Simultaneously, the phenolic hydroxyl group competes for coordination with Fe3+ ions at the enzyme's active site, thus inhibiting the enzymatic oxidation reaction through a dual effect.

[0107] Step 2: Add oil-phase antioxidants in stages (preferably at 75±1℃)

[0108] The oil phase obtained in step 1 is heated to 75°C under stirring (heating rate controlled at 3°C / min, using a programmable heater for gradual heating). After the temperature stabilizes, rosemary extract (0.25-0.35% by weight, preferably 0.3%, sarsaparilla acid content ≥15%, rosmarinic acid content ≥5%, total phenol content ≥20%, moisture ≤5%) is added. Stirring is continued at 75°C (temperature fluctuation controlled within ±1°C) for 10-15 minutes (preferably 12 minutes) until the rosemary extract is completely dissolved and uniformly dispersed, maintaining a stirring speed of 300-500 rpm (preferably 400 rpm). After adding the rosemary extract, the oil phase color gradually changes from pale yellow to yellowish-brown, indicating that the phenolic compounds have successfully dissolved.

[0109] Key Technical Points: The phenolic compounds such as rosmarinic acid and sauropic acid in rosemary extract achieve optimal solubility in the oil phase at 75°C (approximately 0.8-1.2 mg / mL), which is 3-5 times higher than at room temperature (25°C). The ortho-hydroxyl structure of the phenolic compounds can undergo hydrogen atom transfer reactions with lipid peroxidation free radicals, with a reaction rate constant k = 10⁸-10⁹ L / (mol·s). This effectively removes primary free radicals generated by the oxidation of easily oxidized components (unsaturated fatty acids) in the oil phase, preventing the initiation and propagation of free radical chain reactions. Unlike existing technologies that involve a single high-temperature addition, this step specifically targets the oil phase for antioxidant protection at the optimal temperature.

[0110] Step 3: Add squalene to form a synergistic antioxidant oil phase (preferably at 62±2℃)

[0111] The oil phase obtained in step 2 is cooled to 60-65℃ while stirring (the cooling rate is controlled at 4℃ / min; water bath cooling or natural cooling can be used to avoid rapid cooling). After the temperature stabilizes, squalene (0.4-0.6% by weight, preferably 0.5%, purity ≥98%, unsaturation ≥99%, molecular weight 410.65, iodine value ≥380, peroxide value ≤5.0 meq / kg) is slowly added using a peristaltic pump (preferably a Longer BT100-1F or equivalent). The dropping rate is controlled at 0.5-1.0 mL / min (preferably 0.8 mL / min). Stirring is continued for 5-10 minutes (preferably 8 minutes) until the squalene is completely mixed and forms a homogeneous golden-yellow solution with the oil phase. The stirring speed is maintained at 300-500 rpm (preferably 400 rpm). Excessive temperature will cause double bond isomerization of squalene, while excessively low temperature will affect the dissolution rate. 62℃ is the optimal operating temperature.

[0112] Key technical points: Squalene contains six unsaturated double bonds, and its conjugated double bond system in its molecular structure endows it with strong antioxidant activity (10-15 times that of vitamin E). However, it is prone to double bond isomerization and polymerization reactions at high temperatures, leading to inactivation. The squalane added in step 1 is a fully saturated hydrocarbon with high stability (peroxide value <1.0 meq / kg, can be stored for 12 months) but weak antioxidant activity.

[0113] Squalene (0.5%) and squalane (1%) form a synergistic combination in a 1:2 weight ratio. At temperatures of 60-65°C (below the thermal decomposition temperature of 80°C), squalene will not be deactivated by excessive oxidation due to high temperatures. Squalane acts as a dilution carrier and protective medium, reducing the molar concentration of squalene in the mixed oil phase to approximately 0.3% (by number of molecules), and decreasing the oxidation rate constant by 60-70%. Both have highly similar molecular structures and similar solubility parameters, forming an ideal mixture with an intermolecular interaction energy of approximately -2.5 kJ / mol, resulting in a homogeneous and stable antioxidant oil phase.

[0114] The unsaturated double bonds of squalene preferentially react with free radicals (reaction activation energy of approximately 25 kJ / mol), acting as a sacrificial antioxidant to protect other components from oxidation.

[0115] Step 4: Prepare an aqueous polyphenol antioxidant buffer composition (preferably at 42±2℃).

[0116] Add purified water (72.0-73.5% by weight, preferably 72.72%, conductivity ≤10 μS / cm, pH 6.5-7.5, microorganisms ≤100 cfu / mL) to a stainless steel stirring container (316L material, capacity 2-8L, preferably 6L) and heat to 40-45℃ (preferably 42℃, temperature control accuracy ±0.5℃). Sequentially dissolve glycerol (9.5-10.5% by weight, preferably 10%, purity ≥99.5%, water ≤0.5%) and 1,2-hexanediol (0.4-0.6% by weight, preferably 0.5%, purity ≥99%, pH 6.0-8.0), stirring at 200-300 rpm (preferably 250 rpm) for 5 minutes until completely dissolved.

[0117] Then, add grape seed extract (0.35-0.45% by weight, preferably 0.4%, proanthocyanidin content ≥95%, water solubility ≥80%, moisture ≤5%, pH 3.5-4.5) and scutellaria baicalensis extract (0.2-0.3% by weight, preferably 0.25%, baicalin content ≥85%, total flavonoid content ≥90%, moisture ≤5%, pH 6.0-7.0) sequentially. After each addition, continue stirring for 3-5 minutes (preferably 4 minutes). Finally, stir for a total of 10-15 minutes (preferably 12 minutes) until the grape seed and scutellaria baicalensis extracts are completely dissolved, forming a clear, homogeneous aqueous phase that is pale yellow to amber in color. If precipitation or turbidity occurs, check if the pH value is within the expected range (pH 4.8-5.2).

[0118] Technical highlights: Grape seed proanthocyanidins are oligomeric or polymeric catechin derivatives with a molecular weight range of 300-3000 Da. They mainly contain epicatechin, catechin and their oligomers, and have excellent photostability. Under ultraviolet irradiation (λ=280-400nm), they do not undergo photodegradation into pro-oxidants, and the photostability half-life is >48 hours (10000 lux continuous irradiation).

[0119] Baicalin is a flavonoid glycoside compound with a molecular weight of 446.36. It has strong ultraviolet absorption in the 280-320 nm wavelength range, which can reduce the initiation of photo-oxidation at the source. Its solubility in water reaches its optimal value at 42℃ (approximately 12-15 mg / mL).

[0120] The two water-soluble polyphenols exhibit suitable solubility at 40-45℃, forming an antioxidant buffer solution with a pH of 4.5-5.5 in the aqueous phase, demonstrating good buffering capacity (buffer capacity β≥0.05). Unlike traditional single antioxidants, this buffer composition, through the synergistic effect between polyphenols (grape seed proanthocyanidins provide sustained free radical scavenging ability, and baicalin provides UV absorption protection), can continuously scavenge free radicals such as DPPH· and ABTS·+ in the aqueous phase and provide photoprotection, reducing the UV transmittance in the 280-320nm wavelength band to ≤15%.

[0121] Step 5: Prepare a three-dimensional antioxidant protective emulsion (preferably at 55±3℃)

[0122] Adjust the temperature of the oil phase obtained in step 3 to 50-60℃ (preferably 55±3℃), and adjust the temperature of the aqueous phase obtained in step 4 to 50-60℃ (preferably 55±3℃), ensuring that the temperature difference between the oil and water phases is ≤2℃. First, add the emulsifier composition to the aqueous phase: sorbitan olive oil ester (0.5-0.6% by weight, preferably 0.55%, HLB value 4.3, saponification value 147-157 mg KOH / g), cetearyl glucoside (0.4-0.5% by weight, preferably 0.45%, HLB value 11-13, moisture ≤3%), and the thickening emulsifier polyacrylate crosspolymer-6 (0.8-1.2% by weight, preferably 1%, pH value 2.5-4.0). Stir at 400-600 rpm for 2-3 minutes to fully disperse the emulsifier.

[0123] Then, use a peristaltic pump to slowly add the oil phase to the aqueous phase at a flow rate of 2-5 mL / min, stirring continuously. Alternative equipment: If a peristaltic pump is unavailable, a graduated dropping funnel or a medical infusion set (adjust the drip rate to approximately 30-60 drops / minute) can be used instead.

[0124] When the oil phase reaches 50% of the total amount, turn on the high-shear emulsification equipment (IKA T25 digital type or equivalent equipment is recommended, power ≥500W, shear head diameter 18mm), speed 6000-8000rpm (preferably 7000rpm), emulsify continuously for 5-8 minutes (preferably 6 minutes) until a milky white homogeneous emulsion is formed.

[0125] After emulsification, add carbomer (0.2-0.3% by weight, preferably 0.25%, particle size ≤200 mesh, pH 2.5-3.5, viscosity ≥30000 mPa·s) in batches while stirring, and continue stirring for 2-3 minutes to form a stable emulsion.

[0126] Technical points: At this point, the oil-phase antioxidants (squalene, rosemary extract, propyl gallate) and the water-phase antioxidants (grape seed extract, scutellaria baicalensis extract) converge at the oil-water interface to form an interfacial antioxidant layer with a thickness of about 5-10 nm, constituting a three-dimensional antioxidant protective emulsion.

[0127] The emulsifier molecules are arranged at an interface density of about 2-5 molecules / nm². Sorbitan olive oil ester, as a water-in-oil emulsifier, stabilizes the internal structure of the oil droplets, while cetearyl glucoside, as an oil-in-water emulsifier, stabilizes the overall emulsion system. The two work synergistically to form a composite interfacial film, reducing the interfacial tension to 2-8 mN / m.

[0128] Unlike existing planar single-layer protection technologies, this emulsion provides antioxidant protection in three regions simultaneously: the oil phase (concentration of lipid-soluble antioxidants), the aqueous phase (concentration of water-soluble antioxidants), and the oil-water interface (enrichment of amphiphilic antioxidant molecules), achieving comprehensive free radical scavenging with an antioxidant synergistic effect coefficient of 2.5-3.2.

[0129] Step 6: Add active ingredients and inclusion stabilizers (preferably at 38±2℃)

[0130] Cool the emulsion obtained in step 5 to below 40°C (preferably 38±2°C) while stirring, controlling the cooling rate at 2-4°C / min. Add the active ingredients in the following order:

[0131] First, add hydroxypropyl cyclodextrin (0.12-0.16% by weight, preferably 0.14%, degree of substitution 0.6-1.0, moisture ≤5%, molecular weight 1400±200), and stir for 3-5 minutes until completely dissolved;

[0132] Then, the following skin conditioning ingredients are added in sequence: Calendula extract (0.4-0.5% by weight, preferably 0.45%, lutein content ≥0.3%, carotenoid content ≥2%, moisture ≤8%), Centella asiatica extracts [asiaticoside (0.008-0.012%, preferably 0.01%, purity ≥98%), hydroxyasiaticoside (0.025-0.035%, preferably 0.03%, purity ≥95%), Centella asiatica extract (0.015-0.025%, preferably 0.02%, total glycoside content ≥80%)], allantoin (0.35-0.45% by weight, preferably 0.4%, purity ≥99%, pH 7.0-9.0), and dipotassium glycyrrhizate (0.15-0.25% by weight, preferably 0.2%, purity ≥98%, pH 10-11);

[0133] Finally, add the skin feel modifiers: polydimethylsiloxane (4.5-5.1% by weight, preferably 4.8%, viscosity 350±50 cSt, cyclosiloxane content ≤10ppm) and polydimethylsiloxane crosspolymer (1.0-1.4% by weight, preferably 1.2%, viscosity ≥10). 6 mPa·s), phenyl polytrimethylsiloxane (1.8-2.2% by weight, preferably 2%, refractive index 1.46-1.47, viscosity 15-25 cSt).

[0134] After each addition, stir at 300-500 rpm for 2-3 minutes until fully dispersed, avoiding the formation of air bubbles.

[0135] Technical highlights: Hydroxypropyl cyclodextrin (HP-β-CD) is a seven-membered cyclic oligosaccharide derivative with the molecular formula C7. 42 H 70 O 35 With an outer diameter of approximately 1.5 nm, an inner cavity diameter of approximately 0.78 nm, and a cavity depth of approximately 0.79 nm, it possesses a hollow structure with a hydrophilic outer layer and a hydrophobic inner layer. It can encapsulate photosensitive phenolic compounds (such as oxalic acid from rosemary extract, with a molecular size of approximately 0.6 × 1.2 nm) within the hydrophobic cavity, forming a 1:1 molar ratio host-guest inclusion complex with an inclusion constant K of approximately 10³–10⁴ M. -1 .

[0136] This inclusion complex is stable through intermolecular hydrogen bonds, van der Waals forces and hydrophobic interactions (binding energy of approximately -25 to -35 kJ / mol). It can block direct light irradiation of the conjugated system of phenolic compounds, preventing photodegradation and photoisomerization reactions. The photostable half-life is extended from 8 hours to more than 72 hours (under continuous irradiation of 10,000 lux).

[0137] The ingredients in the Centella Asiatica series work synergistically through different mechanisms of action to repair the skin: asiaticoside promotes collagen synthesis, hydroxyasiaticoside has anti-inflammatory activity, and Centella Asiatica extract comprehensively regulates cell metabolism. The synergistic coefficient of the three is approximately 1.8-2.3.

[0138] Step 7: pH adjustment and stability optimization (preferably 37±2℃)

[0139] Adjust the temperature of the composition obtained in step 6 to 35-40℃ (preferably 37±2℃), and add tocopherol (α-tocopherol, vitamin E, weight percentage 0.00003-0.3%, preferably 0.15%, purity ≥95%, peroxide value ≤5.0 meq / kg, acid value ≤0.5mg KOH / g).

[0140] First, prepare a 10% diluted solution of tromethamine (0.18-0.24% by weight, preferably 0.21%, purity ≥99%) (pH approximately 9.5-10.0) to reduce the intensity of the reaction. Continuously monitor the pH using a pH meter. Add the diluted tromethamine solution dropwise at a slow rate of 0.1-0.2 mL / min using a burette or peristaltic pump, stirring at 200-300 rpm. Stop adding 0.5 mL at a time and observe the pH change for stabilization (approximately 30 seconds) to prevent sudden pH jumps and localized overheating, until the pH reaches 6.0-6.5 (preferably 6.2±0.1). If the pH overshoots above 6.6, stop adding the solution and allow it to naturally correct itself.

[0141] Then add disodium EDTA (0.015-0.025% by weight, preferably 0.02%, purity ≥99%, pH 4.3-4.7, moisture ≤13%) as a metal ion chelating agent, and stir thoroughly for 5-10 minutes (preferably 8 minutes) until the pH stabilizes. The pH is considered stable if the change is ≤0.05 / 5min.

[0142] Key technical points: Tocopherol is a fat-soluble antioxidant. Its solubility in emulsion systems is approximately 0.8-1.2 mg / mL at 35-40℃, and its antioxidant activity retention rate is ≥95%. Excessively high temperatures (>45℃) can lead to thermal oxidative degradation of tocopherol, generating inactive products such as tocoquinone.

[0143] Tromethamine, a weakly basic amine pH adjuster, has a pKa of 8.1 and exhibits good buffering capacity within a pH range of 6.0-8.0. It undergoes an acid-base neutralization reaction with the carboxyl groups in carbomer, forming an ionicly cross-linked gel network structure. This increases the system viscosity to 15,000-20,000 mPa·s, while simultaneously adjusting the system pH to a suitable weakly acidic range for the skin around the lips (pH 6.0-6.5), matching the pH of healthy skin (5.5-6.5).

[0144] Disodium EDTA reacts with Fe through its four carboxyl groups and two amino groups. 3+ Cu 2+ Once the metal ions form stable chelates (chelation constant lgK is about 18-25), the effective concentration decreases to 10⁻⁶-10⁻⁸ mol / L, preventing the metal ion-catalyzed Fenton reaction and free radical chain reaction, and preventing lipid peroxidation and antioxidant deactivation.

[0145] Step 8: Cooling and stabilizing before packaging (preferably 27±2℃)

[0146] The composition obtained in step 7 is naturally cooled to 25-30℃ (preferably 27±2℃) under stirring, with a cooling rate controlled at 1-3℃ / min. During the cooling process, slow stirring (100-200 rpm) is maintained to prevent layering and precipitation. After cooling is complete, stirring is stopped, and the system stability is observed after standing for 10-15 minutes.

[0147] Stability is assessed according to the following criteria: uniform appearance without layering, no oil-water separation, no precipitation, no bubbles, viscosity change ≤5%, and pH change ≤0.2. After confirming compliance with stability requirements, packaging is carried out.

[0148] Packaging is carried out in a cleanroom environment of Class 10,000 (ISO Class 7) using nitrogen-filled protective sealed packaging: high-purity nitrogen (purity ≥99.9%) is used to replace the packaging container with nitrogen 2-3 times, each replacement time is 3-5 minutes, until the oxygen content in the container is reduced to below 5% (measured by an oxygen detector) and the residual oxygen volume fraction is ≤0.5%.

[0149] The packaging containers use oxygen-barrier materials (oxygen permeability ≤ 0.1 cm³ / (m²·d·0.1MPa)), such as aluminum-plastic composite pipes or oxygen-barrier glass bottles, to ensure that the oxygen content of the product is maintained within a safe range during storage.

[0150] Final product characteristics: A stable final topical composition for perilip care is obtained, which is a milky white, smooth, homogeneous emulsion with a pH of 6.1-6.3 (measured at 25℃ using a glass electrode pH meter), a dynamic viscosity of 18000-22000 mPa·s (25.0±0.1℃, rotor No. 4, 3 rpm), excellent spreadability, DPPH free radical scavenging rate ≥80%, peroxide value ≤3.0 meq / kg, and microbiological indicators: total bacterial count ≤500 cfu / g, total mold and yeast count ≤100 cfu / g, pathogenic bacteria not detectable, and a storage stability period of ≥24 months at 25℃±2℃.

[0151] Experimental verification

[0152] Experiment 1: Experiment on the maintenance of light stability and antioxidant activity

[0153] 1. Experimental Objective

[0154] The study aimed to verify the retention rate of antioxidant activity of the composition under simulated sunlight irradiation conditions, evaluate the advantages of the photostable antioxidant system compared to traditional formulations, and demonstrate the protective effect of the grape seed extract, scutellaria baicalensis extract, and hydroxypropyl cyclodextrin inclusion system on photosensitive phenolic antioxidants.

[0155] 2. Preparation of experimental samples

[0156] Sample 1 (Sample of the present invention): Prepared according to the formulation and process of Embodiment 1, comprising a complete multilayer antioxidant protection system (0.5% squalene, 0.3% rosemary extract, 0.2% propyl gallate, 0.4% grape seed extract, 0.25% scutellaria baicalensis extract, 0.15% tocopherol) and 0.14% hydroxypropyl cyclodextrin.

[0157] Sample 2 (traditional formula control sample): contains only the single antioxidant tocopherol 0.3%, other matrix components are the same as Sample 1, and does not contain grape seed extract, scutellaria baicalensis extract and hydroxypropyl cyclodextrin.

[0158] Sample 3 (acyclodextrin control sample): contains the same combination of antioxidants as Sample 1, but does not contain hydroxypropyl cyclodextrin inclusion stabilizer.

[0159] Each sample was prepared in 100g portions and dispensed into transparent glass petri dishes (90mm in diameter and 15mm in depth), with 20g of sample per dish and a thickness of approximately 3mm to ensure uniform light exposure.

[0160] 3. Experimental conditions

[0161] Illumination equipment: Xenon arc lamp aging test chamber (model: Q-SUN Xe-3, Q-Lab company), equipped with daylight-Q filter.

[0162] Lighting parameters: Illumination intensity: 10000 lux (equivalent to midday sunlight in summer); Irradiance: 0.55 W / m² (at 340nm); Wavelength range: 295-800nm ​​(simulating natural sunlight spectrum); Blackboard temperature: 40±2℃; Relative humidity: 50±5%; Illumination duration: 0h, 2h, 4h, 6h, 8h, 10h.

[0163] Environmental control: A light-protected control group was set up at the same time. The samples were placed in sealed brown bottles and stored in a light-protected environment at 25°C and 60% relative humidity for the same period of time.

[0164] 4. Experimental Procedure

[0165] Step 1: After sample preparation, immediately measure the DPPH radical scavenging rate, ABTS radical scavenging rate, and oxalic acid content at the initial time (0h) as baseline data. Each sample was measured in triplicate.

[0166] Step 2: Place the sample petri dish in a xenon arc lamp aging test chamber and perform light treatment according to the set parameters. Take a sample every 2 hours, with each sample weighing approximately 2g.

[0167] Step 3: DPPH free radical scavenging rate determination: Take 0.1g of sample, dissolve it in anhydrous ethanol and dilute to 10mL. Mix 1mL of sample solution with 3mL of DPPH ethanol solution (0.1mmol / L), react in the dark for 30 minutes, and then measure the absorbance at 517nm. Calculation formula: Scavenging rate (%) = [1 - (Sample A - Sample A blank) / Control A] × 100%.

[0168] Step 4: ABTS free radical scavenging rate determination: The TEAC method was used. The ABTS working solution was prepared by mixing ABTS stock solution (7 mmol / L) and potassium persulfate solution (2.45 mmol / L) at a 1:1 ratio and reacting in the dark for 12-16 hours. Before use, it was diluted with phosphate buffer to an absorbance of 0.70 ± 0.02 (734 nm). 0.2 mL of the sample solution was mixed with 3.8 mL of the ABTS working solution, and the absorbance was measured at 734 nm after reacting for 6 minutes.

[0169] Step 5: Determination of sarsaparilla oxalate content: HPLC was used with a C18 column (4.6 × 250 mm, 5 μm), a mobile phase of acetonitrile-water-glacial acetic acid (30:69.5:0.5, v / v / v), a flow rate of 1.0 mL / min, a column temperature of 30℃, and a detection wavelength of 280 nm. The sample was extracted with methanol before analysis.

[0170] Step 6: Color stability evaluation: The L, a, and b* values ​​of the sample were measured using a colorimeter (model: CR-400, Konica Minolta), and the color difference ΔE was calculated as ΔE = [(ΔL)² + (Δa)² + (Δb*)²]. 0.5 .

[0171] Step 7: Data Recording and Statistical Analysis: All data are expressed as mean ± standard deviation. One-way ANOVA was performed using SPSS 25.0 software. P < 0.05 indicates that the difference is statistically significant.

[0172] 5. Experimental Results

[0173] Table 1: Changes in DPPH radical scavenging rate (%) of different samples under light conditions

[0174]

[0175] Note: Activity retention rate = (scavenging rate at 10h / scavenging rate at 0h) × 100%, and the data is the average of three parallel determinations ± standard deviation.

[0176] Table 2: Changes in oxalic acid content in different samples under light conditions (mg / g)

[0177]

[0178] Table 3: Evaluation of color stability (ΔE value) of different samples

[0179]

[0180] Note: ΔE<2 indicates that the human eye can hardly perceive the color difference, ΔE=2-3.5 indicates a slight difference, and ΔE>3.5 indicates a significant difference.

[0181] Figure 1 Changes in antioxidant activity of different samples under light irradiation conditions;

[0182] Figure 2 The change of sarsaparilla acid content with photoperiod;

[0183] Figure 3 Comparison of oxalic acid retention rates after 10 hours of light exposure.

[0184] 6. Analysis and Summary

[0185] Experimental results show that the composition of the present invention exhibits excellent antioxidant stability under strong light irradiation conditions:

[0186] (1) Significant advantage in maintaining antioxidant activity: After 10 hours of continuous light irradiation, the DPPH free radical scavenging rate of sample 1 remained at 77.2%, and the activity retention rate reached 91.7%, while the scavenging rate of sample 2 with traditional formulation decreased to 23.4%, and the activity retention rate was only 28.4%. The activity retention rate of the present invention is 3.2 times higher than that of the traditional formulation, which verifies the significant advantages of the multilayer antioxidant protection system.

[0187] (2) Key to the inclusion effect of cyclodextrin: Comparison of the data of sample 1 and sample 3 shows that the addition of hydroxypropyl cyclodextrin increased the retention rate of oxalic acid from 40.6% to 91.6%, an increase of 2.3 times. This confirms that cyclodextrin effectively protects photosensitive phenolic compounds from photodegradation through inclusion effect, which is a key technical means to achieve photo-stable antioxidant properties.

[0188] (3) Excellent color stability: The color difference ΔE value of sample 1 was only 1.68 after 10 hours of light exposure, which is far below the threshold that can be detected by the human eye (ΔE=2-3.5), while the ΔE value of the traditional formula reached 11.85, showing obvious browning. This indicates that the composition of the present invention has excellent appearance stability under sunlight exposure and is suitable for daytime outdoor use.

[0189] (4) Synergistic photostability mechanism: Grape seed proanthocyanidins provide continuous free radical scavenging ability, baicalin absorbs ultraviolet light in the 280-320nm wavelength band to reduce photo-oxidation from the source, and hydroxypropyl cyclodextrin blocks light through physical inclusion. The three work together to construct a triple photoprotection mechanism of chemical scavenging, ultraviolet absorption and physical isolation, achieving high stability and antioxidant effect under light environment.

[0190] Experiment 2: Verification Experiment of Enzyme-Inhibited Oxidation Effect

[0191] 1. Experimental Objective

[0192] This study aims to verify the effect of propyl gallate in inhibiting the activity of lipoxygenase (LOX) through hydrogen bonding and steric hindrance mechanisms, evaluate the inhibitory ability of the composition on enzymatic oxidation in a simulated saliva environment, and demonstrate its advantages over traditional chemical antioxidants in a biological enzyme environment.

[0193] 2. Preparation of experimental samples

[0194] Sample A (complete formulation of the present invention): prepared according to Embodiment 1, containing 0.2% propyl gallate, 2% meadowfoam seed oil, 1% squalane, 0.3% rosemary extract and other ingredients.

[0195] Sample B (Propyl Gallate-Free Control): Same composition as Sample A, but without propyl gallate, replaced with an equal amount of squalane to maintain consistent total oil phase content.

[0196] Sample C (conventional antioxidant control): contains only 0.3% tocopherol and 0.1% BHT (di-tert-butyl-p-cresol) as antioxidants, and the other matrix components are the same as those of Sample A.

[0197] Blank control: Matrix composition without any antioxidants.

[0198] Artificial saliva preparation: According to ISO standard (ISO / TR 10271:2011), the formula is KCl 1.2 g / L, NaCl 0.85 g / L, K2HPO4 0.25 g / L, CaCl2·2H2O 0.15 g / L, and mucin 2.5 g / L. The pH is adjusted to 6.8±0.1 with HCl, and sterilized at 121℃ for 15 minutes before use.

[0199] Lipoxygenase solution: Soybean lipoxygenase (Type IB, Sigma, activity ≥50000 units / mg protein) was prepared into an enzyme solution with a final concentration of 5 units / mL using 0.1 M phosphate buffer (pH 9.0) and stored at 4℃.

[0200] 3. Experimental conditions

[0201] In vitro enzyme activity inhibition assay conditions: Reaction system: total volume 3 mL, containing 0.5 mM sodium linoleate solution, 0.5 mL enzyme solution, and 0.2 mL sample extract; reaction temperature: 25±1℃; reaction time: 5 minutes; detection wavelength: 234 nm (monitoring of conjugated diene formation); equipment: UV-2600 UV-Vis spectrophotometer (Shimadzu Corporation).

[0202] Simulated saliva environment oxidation test conditions: Test temperature: 37±0.5℃ (simulated oral temperature); Test medium: artificial saliva, with lipoxygenase added to a final concentration of 2 units / mL; Sample volume: 1.0 g sample dispersed in 10 mL of artificial saliva; Incubation time: 0 h, 0.5 h, 1 h, 2 h, 4 h; Oxidation indicators: peroxide value (POV), thiobarbituric acid value (TBARS).

[0203] 4. Experimental Procedure

[0204] Step 1: In vitro lipoxygenase activity inhibition assay

[0205] 1.1 Sample pretreatment: Take 2g of each sample, extract with 10 mL of ethanol for 30 minutes (ultrasonic aid), centrifuge to obtain the supernatant, and dilute to an appropriate concentration (so that the sample concentration in the final reaction system is 0.1 mg / mL).

[0206] 1.2 Construction of the reaction system: Add the following to a quartz cuvette in sequence: 2.3 mL of 0.1 M phosphate buffer (pH 9.0); 0.2 mL of sample extract; 0.5 mL of sodium linoleate solution (0.5 mM); mix well and preheat at 37°C for 3 minutes.

[0207] 1.3 Enzymatic reaction: Add 0.5 mL (5 units / mL) of lipoxygenase solution, mix immediately, and continuously monitor the absorbance change at 234 nm wavelength for 5 minutes, recording data every 15 seconds.

[0208] 1.4 Enzyme activity calculation: Enzyme activity is calculated based on the slope of absorbance change over time. Enzyme inhibition rate (%) = [1 - (ΔA sample / Δt) / (ΔA control / Δt)] × 100%, where ΔA / Δt is the rate of change of absorbance over time.

[0209] 1.5 IC50 determination: Prepare sample extracts of different concentrations (0.01, 0.05, 0.1, 0.5, 1.0 mg / mL), repeat the above steps, plot the relationship curve between inhibition rate and concentration, and calculate the half-maximal inhibitory concentration (IC50).

[0210] Step 2: Oxidative stability test in simulated saliva environment

[0211] 2.1 Sample dispersion: Accurately weigh 1.0g of each sample, add 10mL of enzyme-containing artificial saliva preheated to 37℃, and place in a constant temperature shaker (37℃, 100 rpm) to simulate the oral environment.

[0212] 2.2 Timed sampling: Take 1 mL of sample at each time point of 0h, 0.5h, 1h, 2h and 4h, immediately add 5 mL of petroleum ether to extract the lipid fraction, and centrifuge to separate the organic phase for peroxide value determination.

[0213] 2.3 Peroxide value (POV) determination: Iodometric method (GB 5009.227) was used. 1 mL of organic phase was taken, 5 mL of chloroform-glacial acetic acid mixture (2:3) was added to dissolve it, 1 mL of saturated KI solution was added, and after standing in the dark for 3 minutes, 30 mL of water was added. The solution was titrated with sodium thiosulfate standard solution (0.01 mol / L) and the POV value (meq / kg) was calculated.

[0214] 2.4 TBARS value determination: Take 0.5 mL of aqueous phase, add 1 mL of 15% trichloroacetic acid and 1 mL of 0.67% thiobarbituric acid solution, incubate in a water bath at 100℃ for 15 minutes, cool, centrifuge, take the supernatant and measure the absorbance at 532 nm, and use malondialdehyde as standard to plot a standard curve to calculate the TBARS value (μmol MDA / g).

[0215] 2.5 Enzyme activity retention test: An equal amount of sample was incubated in enzyme-free artificial saliva as a non-enzymatic oxidation control group to distinguish the contribution of enzymatic oxidation from auto-oxidation.

[0216] 5. Experimental Results

[0217] Table 4: Results of in vitro lipoxygenase activity inhibition assay

[0218]

[0219] Note: NDGA* stands for nordihydroguaiaretic acid, a known potent inhibitor of lipoxygenase, used as a positive control. Data are the mean ± standard deviation of three parallel assays.

[0220] Table 5: Changes in peroxide value (POV) of samples in simulated saliva environment (meq / kg)

[0221]

[0222] Note: Growth rate = [(POV at 4h - POV at 0h) / POV at 0h] × 100%

[0223] Table 6: Changes in TBARS values ​​of samples in simulated saliva environments (μmol MDA / g)

[0224]

[0225] Figure 4 The inhibitory effects of different samples on lipoxygenase;

[0226] Figure 5 : Half-maximal inhibitory concentration (IC50) of different samples;

[0227] Figure 6 : To simulate the anti-enzymatic oxidation properties of different samples in a saliva environment.

[0228] 6. Analysis and Summary

[0229] Experimental results fully demonstrate the significant inhibitory effect of the composition of the present invention on enzymatic oxidation:

[0230] (1) Highly effective enzyme inhibitory activity: Sample A showed an inhibition rate of 68.7% against lipoxygenase with an IC50 value of 15.2 μM, which was significantly better than Sample B (inhibition rate 21.8%, IC50 value 88.5 μM) without propyl gallate and Sample C (inhibition rate 16.3%, IC50 value 105.3 μM), a traditional antioxidant. This indicates that propyl gallate is the key component for achieving highly efficient enzyme inhibition, and its inhibitory effect is close to that of the positive control NDGA (inhibition rate 80.5%), which has practical application value.

[0231] (2) Outstanding stability in the saliva environment: After incubation in enzyme-containing artificial saliva for 4 hours, the peroxide value of sample A only increased to 3.2 meq / kg (growth rate of 77.8%), which was much lower than that of sample B (16.7 meq / kg, growth rate of 778.9%) and sample C (18.3 meq / kg, growth rate of 916.7%). Compared with the enzyme-free control group (POV growth rate of 55.6%), sample A effectively inhibited the enzymatic oxidation reaction, while the POV growth of samples B and C mainly came from the enzymatic oxidation pathway.

[0232] (3) Excellent control of secondary oxidation products: The TBARS value reflects the content of malondialdehyde (MDA), a secondary product of lipid peroxidation. After 4 hours, the TBARS value of sample A was 0.38 μmol MDA / g, which was only 16.7% of that of sample B (2.28 μmol MDA / g) and 14.3% of that of sample C (2.65 μmol MDA / g). This indicates that the present invention not only inhibits the primary oxidation reaction but also effectively controls the generation of secondary oxidation products, fundamentally delaying the oxidation process.

[0233] (4) Validation of the inhibition mechanism: The ortho-trihydroxy structure of propyl gallate forms hydrogen bonds (bond length approximately 2.8 Å) with the unsaturated fatty acids in meadowfoam seed oil, forming a phenolic protective layer on the substrate surface. This molecular-level interaction prevents the recognition and catalysis of the substrate double bond by lipoxygenase (molecular weight approximately 75 kDa) through steric hindrance, achieving competitive inhibition of the substrate. Simultaneously, the phenolic hydroxyl group competes with the Fe3+ ions at the enzyme active site for coordination, further reducing enzyme activity. This dual inhibition mechanism enables the present invention to exhibit superior performance in a biological enzyme environment that is not possessed by traditional chemical antioxidants (such as tocopherol and BHT).

[0234] (5) Practical application significance: The perilip area is frequently exposed to saliva, and the lipoxygenase and peroxidase in saliva catalyze the enzymatic oxidation of skin care ingredients. This invention effectively solves this special environmental challenge through an enzyme inhibition mechanism, keeping the POV consistently below the safe threshold of 5 meq / kg, ensuring that the product maintains its efficacy stability and fresh scent even after eating, thus meeting the practical needs of perilip care products.

[0235] Experiment 3: Verification Experiment on Deep Nourishment and Moisturizing Effects

[0236] 1. Experimental Objective

[0237] This study verifies the "rapid penetration-middle layer replenishment-surface water locking" layered function of the three-element moisturizing and nourishing system (meadowfoam seed oil, squalane, and beeswax) of this invention, evaluates its deep nourishing effect and long-lasting moisturizing performance, and demonstrates its advantages over single moisturizers through multi-dimensional indicators such as skin moisture content, transepidermal water loss rate (TEWL), and stratum corneum thickness.

[0238] 2. Preparation of experimental samples

[0239] Sample I (Complete Formulation of the Invention): Prepared according to Embodiment 1, containing 2% meadowfoam seed oil, 1% squalane, 0.2% beeswax, 10% glycerin and other ingredients.

[0240] Sample II (single moisturizer control): contains only 15% glycerin as a moisturizer, and does not contain meadowfoam seed oil, squalane, or beeswax. Other matrix components are the same as those in Sample I.

[0241] Sample III (Common Emulsion Control): A commercially available conventional moisturizing emulsion, with main ingredients being 8% glycerin, 5% mineral oil, and 2% petrolatum.

[0242] Blank control: No product applied.

[0243] 3. Experimental conditions

[0244] Human efficacy evaluation criteria: Subjects: 30 healthy volunteers (female, aged 25-45 years, mean age 32.5±6.2 years), with no obvious damage or disease to the skin around the lips; Test site: skin around the lips (1cm×1cm area above the upper lip); Test environment: temperature 22±2℃, relative humidity 50±5%; Application amount: 0.05 g / cm²; Test period: single application test (24 hours) and continuous use test (4 weeks).

[0245] Instruments and equipment: Skin moisture meter: Corneometer CM825 (Courage+Khazaka); Transdermal water loss meter: Tewameter TM300 (Courage+Khazaka); Skin image analyzer: VISIA Complexion Analysis (Canfield); Franz diffusion cell: TP-6 ​​(Tianjin Autoshine Instruments); Laser confocal microscope: LSM 880 (Carl Zeiss).

[0246] In vitro permeation test conditions: Permeation membrane: isolated pig ear skin (intact stratum corneum, thickness approximately 0.5 mm); Receiving solution: pH 7.4 phosphate buffer, solubilized with 30% ethanol; Temperature: 32±0.5℃ (simulating skin surface temperature); Effective diffusion area: 3.14 cm²; Sampling time points: 0.5h, 1h, 2h, 4h, 6h, 12h, 24h.

[0247] 4. Experimental Procedure

[0248] Step 1: Short-term moisturizing effect test (24 hours)

[0249] 1.1 Subject preparation: Do not use any skin care products within 24 hours before the test, and equilibrate in the test environment for 30 minutes before the test.

[0250] 1.2 Baseline data acquisition: Initial skin moisture values ​​of each test area were measured using a Corneometer (average of 3 measurements), and initial TEWL values ​​were measured using a Tewameter.

[0251] 1.3 Sample application: Different samples were applied to the designated perilip area of ​​each subject according to random grouping. The amount applied to each area was 0.05 g / cm², and the sample was gently massaged until absorbed.

[0252] 1.4 Timed measurements: Skin moisture and TEWL values ​​were measured at 0.5h, 1h, 2h, 4h, 8h and 24h after application. Three measurements were taken at each time point and the average value was taken.

[0253] 1.5 Moisturizing rate calculation: Moisturizing rate (%) = [(Moisture content at test - Initial moisture content) / (Initial moisture content)] × 100%

[0254] 1.6 TEWL Reduction Rate Calculation: TEWL Reduction Rate (%) = [(Initial TEWL Value - TEWL Value at Test) / (Initial TEWL Value)] × 100%

[0255] Step 2: Long-term nourishing effect test (4 weeks)

[0256] 2.1 Subject grouping: 30 subjects were randomly divided into 3 groups (10 people in each group), and used sample I, sample II and sample III respectively, applying them once in the morning and once in the evening.

[0257] 2.2 Periodic Assessment: The following measurements were performed at week 0 (baseline), week 1, week 2, and week 4: - Skin moisture and TEWL values ​​- VISIA skin imaging analysis: images of the skin texture around the lips were taken, and the depth and number of lip lines were analyzed - Subject self-evaluation: indicators such as improvement in dryness, softness, and improvement in lip lines (out of 5).

[0258] 2.3 Lip line depth measurement: Using VISIA's 3D imaging function, the average depth (μm) and total length (mm) of lip lines were measured, and the improvement rate was calculated.

[0259] Step 3: In vitro osmotic dynamics study

[0260] 3.1 Preparation of excised skin: Fresh pig ear skin (obtained within 2 hours after slaughter) was dehaired using an electric shaver, and the full-thickness skin (approximately 0.5 mm thick) was separated. The skin was then washed with physiological saline and the integrity of the stratum corneum was checked (TEWL < 10 g / m² / h was measured).

[0261] 3.2 Franz diffusion tank installation: Fix the skin between the donor tank and the receiver tank, with the stratum corneum facing the donor tank. The receiver tank has a capacity of 12 mL and is filled with receiver solution (pH 7.4 PBS containing 30% ethanol). Stir magnetically at 600 rpm and control the temperature at 32°C.

[0262] 3.3 Sample application: Add 1.0 g of sample I to the supply cell and coat it evenly to cover the entire effective diffusion area.

[0263] 3.4 Timed sampling: Take 1 mL of sample from the receiving cell at 0.5h, 1h, 2h, 4h, 6h, 12h and 24h, and replenish with an equal amount of fresh receiving solution to maintain a constant volume.

[0264] 3.5 Content determination: The labeled component eicosenoic acid (the main component of meadowfoam seed oil) in the sample was determined by GC method. The injection conditions were HP-5 column (30m×0.32mm×0.25μm), programmed temperature rise, FID detector, and internal standard method for quantification.

[0265] 3.6 Calculation of Permeability Parameters: - Cumulative Permeability Q(t): Total amount of drug in the receiving solution at each time point (μg / cm²) - Steady-state Permeability Rate Js: Slope of the linear portion of the Qt curve (μg / cm² / h) - Permeability Coefficient Kp: Kp = Js / C0, where C0 is the initial drug concentration in the supply tank (μg / cm³) - Lag Time TL: Intersection of the linear portion of the Qt curve extrapolated to the horizontal axis (h)

[0266] Step 4: Visualizing the stratum corneum moisturizing mechanism

[0267] 4.1 Sample preparation: Take isolated pig ear skin, apply sample I and sample II respectively, and take samples 2 hours later.

[0268] 4.2 Cryosectioning: Skin samples were embedded in OCT embedding medium, flash-frozen in liquid nitrogen, and sectioned using a cryostat microtome (10 μm thickness) to prepare serial sections.

[0269] 4.3 Fluorescent staining: Nile Red was used to stain lipids (excitation wavelength 488 nm, emission wavelength 580 nm), and DAPI was used to stain cell nuclei (excitation wavelength 358 nm, emission wavelength 461 nm).

[0270] 4.4 Laser confocal imaging: Z-axis scanning (scanning depth 50 μm, step size 1 μm) was performed using an LSM 880 to acquire fluorescence images of different depths of the stratum corneum.

[0271] 4.5 Image Analysis: ImageJ software was used to analyze the fluorescence intensity distribution, quantify the lipid content at different levels, and plot depth-fluorescence intensity curves.

[0272] 5. Experimental Results

[0273] Table 7: Comparison of short-term moisturizing effects of different samples

[0274]

[0275] Table 8: Improvement effect of transdermal water loss rate (TEWL) on different samples

[0276]

[0277] Note: A higher TEWL reduction rate indicates a better skin barrier function and less moisture loss.

[0278] Table 9: Improvement of lip lines after long-term use (4 weeks)

[0279]

[0280] Note: Ratings* are based on a 5-point scale, with 5 being very satisfied and 1 being unsatisfactory. Data are the mean ± standard deviation of each group (n=10).

[0281] Table 10: In vitro permeation kinetic parameters

[0282]

[0283] Note: Eicosaenoic acid was used as a marker for determination.

[0284] Figure 7 Comparison of 24-hour moisturizing effects of different samples;

[0285] Figure 8 Comparison of moisturizing effects after 24 hours;

[0286] Figure 9 : Improvement in lip line depth after 4 weeks;

[0287] Figure 10 : Improvement in the number of lip lines after 4 weeks.

[0288] 6. Analysis and Summary

[0289] The experimental results fully validated the superior performance of the ternary moisturizing and nourishing system of this invention:

[0290] (1) Significant long-lasting moisturizing advantage: Sample I maintained a high moisturizing rate of 82.5% after 24 hours, which is 4.5 times that of Sample II (18.3%) with a single moisturizer and 3.2 times that of Sample III (25.7%) with a conventional emulsion. This fully demonstrates the significant advantage of the ternary system of meadowfoam seed oil, squalane, and beeswax over traditional single moisturizing strategies. The moisturizing curve shows that the moisturizing rate of Sample II decreased rapidly after 4 hours, while that of Sample I showed a continuous upward trend, reflecting its long-lasting water-locking ability.

[0291] (2) Significantly improved skin barrier function: TEWL test results showed that sample I reduced transdermal water loss by 56.8% after 24 hours, significantly better than sample II (18.5%) and sample III (24.3%). The decrease in TEWL indicates enhanced skin barrier function and reduced water loss. The protective film formed by beeswax on the surface, the replenishment of middle lipids by squalane, and the deep nourishment by meadowfoam seed oil synergistically construct a complete barrier repair system.

[0292] (3) Excellent effect on improving lip lines: After 4 weeks of continuous use, Sample I improved the depth of lip lines by 45.7% and reduced the number of lip lines by 38.5%, which was significantly better than Sample II (depth improvement of 23.1% and number reduction of 18.0%) and Sample III (depth improvement of 29.9% and number reduction of 25.4%). (4) Rapid penetration and long-lasting effect: Franz diffusion cell test showed that eicosenoic acid, the main component of meadowfoam seed oil, has good permeability, with a lag time of only 0.82 hours, a cumulative penetration amount of 24.8 μg / cm² after 12 hours, and 52.3 μg / cm² after 24 hours. The steady-state penetration rate Js was 2.85 μg / cm² / h, and the permeability coefficient Kp was 2.85 × 10⁻⁶. -6 The penetration rate is cm / h, which is considered moderately fast. This confirms that meadowfoam seed oil can quickly penetrate deep into the stratum corneum, providing deep lipid nutrition, rather than just remaining on the surface.

[0293] The embodiments of the present invention have been described above. However, the embodiments are not limited to the specific implementation methods described above. The specific implementation methods described above are merely illustrative and not restrictive. Those skilled in the art can make more equivalent embodiments based on the guidance of the present embodiments, and all of them are within the protection scope of the present embodiments.

Claims

1. A topical composition for perilip or corner mouth care, characterized in that, The product comprises the following components by weight percentage: meadowfoam seed oil 1.8-2.2%, squalane 0.8-1.2%, beeswax 0.15-0.25%, squalene 0.4-0.6%, rosemary extract 0.25-0.35%, propyl gallate 0.15-0.25%, grape seed extract 0.35-0.45%, scutellaria baicalensis extract 0.2-0.3%, tocopherol 0.00003-0.3%, hydroxypropyl cyclodextrin 0.12-0.16%, glycerin 9.5-10.5%, and 1,2-hexanediol 0.4-0.6%. Calendula extract 0.4-0.5%, asiaticoside 0.008-0.012%, asiaticoside 0.025-0.035%, Centella asiatica extract 0.015-0.025%, allantoin 0.35-0.45%, dipotassium glycyrrhizate 0.15-0.25%. Sorbitan oleate 0.5-0.6%, cetearyl glucoside 0.4-0.5%, polyacrylate crosspolymer-6 0.8-1.2%, carbomer 0.2-0.3%, tromethamine 0.18-0.24%, disodium EDTA 0.015-0.025%, water balance; The grape seed extract has a proanthocyanidin content of ≥95% and a water solubility of ≥80%; the scutellaria baicalensis extract has a baicalin content of ≥85% and a total flavonoid content of ≥90%. The hydroxypropyl cyclodextrin has a degree of substitution of 0.6-1.0 and a molecular weight of 1400±200; the tocopherol is α-tocopherol with a purity ≥95%. The meadowfoam seed oil, squalane, and beeswax form a three-element moisturizing and nourishing system that rapidly penetrates, replenishes the middle layer, and locks in moisture on the surface. The squalene, rosemary extract, propyl gallate, grape seed extract, scutellaria baicalensis extract, and tocopherol form a multi-layered, progressive antioxidant protection system. The propyl gallate inhibits lipoxygenase activity by forming hydrogen bonds with the unsaturated fatty acids in the meadowfoam seed oil through phenolic hydroxyl groups. The hydroxypropyl cyclodextrin forms inclusion complexes with photosensitive phenolic antioxidants to improve photostability.

2. The topical composition for perilip or corner mouth care according to claim 1, characterized in that, The meadowfoam seed oil has an iodine value ≥165 and an acid value ≤3.0 mg KOH / g; the squalane has a purity ≥99%; and the beeswax has an acid value of 5-22 mg KOH / g and a saponification value of 87-104 mg KOH / g.

3. The topical composition for perilip or corner mouth care according to claim 1, characterized in that, The squalene has a purity of ≥98%, an unsaturation of ≥99%, and an iodine value of ≥380; the squalene and the squalane are synergistically combined in a weight ratio of 1:

2.

4. The topical composition for perilip or corner mouth care according to claim 1, characterized in that, The rosemary extract has a caryopsisic acid content of ≥15%, a rosmarinic acid content of ≥5%, and a total phenol content of ≥20%; the purity of the propyl gallate is ≥98%.

5. The topical composition for perilip or corner mouth care according to claim 1, characterized in that, It also includes the following skin feel modifiers by weight percentage: 4.5-5.1% polydimethylsiloxane, 1.0-1.4% polydimethylsiloxane crosspolymer, and 1.8-2.2% phenyl polytrimethylsiloxane.

6. A method for preparing a topical composition for perilip or corner-of-mouth care as described in any one of claims 1-5, characterized in that, Includes the following steps: Step 1: Mix propyl gallate with meadowfoam seed oil, squalane, and beeswax at 70-75℃ for 15-20 minutes to form the base oil phase; Step 2: Add rosemary extract to the oil phase at 75°C and stir for 10-15 minutes; Step 3: After cooling to 60-65℃, add squalene and stir for 5-10 minutes to form an antioxidant oil phase; Step 4: Dissolve glycerol, 1,2-hexanediol, grape seed extract, and scutellaria baicalensis extract in purified water at 40-45℃ to form an aqueous phase; Step 5: Emulsify the oil phase and the water phase at 50-60℃, and add emulsifier and thickener to form an emulsion; Step 6: Add hydroxypropyl cyclodextrin and other active ingredients at a temperature below 40°C; Step 7: Add tocopherol at 35-40℃, adjust the pH to 6.0-6.5 with tromethamine, and add disodium EDTA; Step 8: Cool to 25-30℃ and package under nitrogen protection.

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