Alkyl polyethylene glycol grafted modified tea saponin-based temperature-sensitive sustained-release skin care hydrogel and preparation method thereof

Abstract

The present application belongs to the technical field of natural daily chemical polymer materials, and aims at the defects of direct compounding of original tea saponin in existing tea saponin washing and protecting products, such as great skin irritation, poor hard water resistance, easy stratification of system, fast active release, short repair time limit and the like, and the present application innovatively adopts amide covalent grafting chemical modification to prepare amphiphilic modified tea saponin, and compounding of N-isopropyl acrylamide temperature-sensitive polymer and camellia oleosa lipid nano microspheres to construct temperature-sensitive slow-release skin care hydrogel. The core innovation points of the present application are as follows: 1. through amide reaction of tea saponin carboxyl and hexadecyl amino PEG500 acyl chloride, C16 hydrophobic alkyl and hydrophilic PEG chain are introduced into the molecule, so that the skin irritation of tea saponin is reduced and the emulsion electrolyte resistance is improved from the molecular structure; 2. a human skin temperature-sensitive three-dimensional cross-linked network of 31~33℃ is constructed, and the slow release of camellia oleosa oil and asiaticoside is triggered by contact body temperature, and the moisturizing and repairing can last for 12 hours; 3. the system is free of sulfate and chemical preservatives, and realizes self-preservation by the natural antibacterial effect of modified tea saponin, and is suitable for high-end daily chemical scenes such as sensitive skin, infants, after-sun repair and the like; 4. low-temperature all-water phase preparation process, without destroying the heat-sensitive plant activity, and strong industrialization adaptability. Through testing, the skin irritation index of the product of the present application is only 0.18, and the product is not stratified after 180 days of normal temperature storage, the antibacterial rate against propionibacterium acnes and malassezia is greater than or equal to 98%, which is better than the existing ordinary tea saponin compounding washing and protecting system.

Description

Technical Field

[0001] This invention relates to natural and green daily chemical polymer materials, which are particularly suitable for low-irritation skin care gels for mothers and infants and for barrier repair. Specifically, it relates to a complete set of preparation processes for covalently modified tea saponins and thermosensitive slow-release hydrogels. Background Technology

[0002] Existing publicly disclosed tea saponin daily chemical patents (CN119656056A, CN120478231A, etc.) all use direct physical compounding formulas of raw crude tea saponin, which have several industry shortcomings: raw tea saponin triterpenoid aglycones are highly irritating, and high additions can easily cause skin redness and stinging, limiting products for infants and those with severely sensitive skin; natural tea saponin has poor resistance to hard water and electrolytes, and is prone to precipitation and stratification when polyols and salt active ingredients are added to the formula, resulting in a short shelf life; there is no sustained-release carrier structure, and the active ingredients are quickly lost after application, with moisturizing and anti-inflammatory effects lasting only 3-4 hours, requiring frequent reapplication; the system requires the addition of chemical preservatives and sulfate surfactants, which does not meet the needs of the natural high-end skincare market; existing technologies only involve simple physical mixing of tea saponin and polyether, without modifying the molecular structure through covalent amide grafting, and cannot fundamentally reduce irritation or improve emulsification performance; there are currently no patents related to temperature-sensitive controlled-release tea saponin skincare gels. Summary of the Invention

[0003] This invention aims to overcome the shortcomings of native tea saponins, such as high irritation, poor system stability, and short duration of efficacy. It provides covalently grafted modified amphiphilic tea saponins, combined with a temperature-sensitive nanolipid sustained-release system, to prepare a low-irritation, long-lasting repairing, and self-preservative skin care hydrogel, suitable for the large-scale production of high-end daily chemical products for mothers and babies and those with damaged skin barriers.

[0004] Core technical innovations of this invention

[0005] (1) Covalent chemical modification of amides (distinguishing it from existing physical compounding)

[0006] The carboxyl group of tea saponin molecule undergoes amide bonding with hexadecylamino polyethylene glycol (PEG) 500 acyl chloride, and the molecule simultaneously introduces a hydrophilic PEG shielding chain and a long C16 hydrophobic alkyl group; the PEG chain encapsulates the irritating triterpenoid skeleton to reduce sensitization, the long alkyl group enhances the oil emulsification and cleaning ability, and the amphiphilic structure significantly improves the stability against hard water and electrolytes.

[0007] Attached image description: Figure 1 This is a diagram of the first step in the activation reaction of the carboxyl group of tea saponin.

[0008] Attached image description: Figure 2 This is a diagram of the second-step amidation reaction.

[0009] (2) Human body temperature-sensitive sustained-release three-dimensional cross-linked network

[0010] NIPAM is polymerized at low temperatures to form a temperature-sensitive framework, which undergoes a phase transition at 30~35℃. Upon contact with the skin, the polymer chains expand, and the internal camellia seed oil nanospheres slowly rupture, continuously releasing moisturizing and anti-inflammatory activities. A single application can provide repair and moisturization for up to 12 hours.

[0011] (3) Natural self-preservation system

[0012] Modified tea saponins have broad-spectrum antibacterial capabilities. The formula does not contain MIT, parabens, or sodium lauryl ether sulfate (SLES) surfactants, meeting the safety standards for maternal and infant skincare.

[0013] (4) Low-temperature green preparation process

[0014] The entire reaction process is carried out at a temperature of ≤45℃, which avoids the high-temperature decomposition of heat-sensitive active ingredients such as camellia seed oil and centella asiatica glycoside. The solvent can be recycled, making the production process environmentally friendly.

[0015] Preferred process parameters of the present invention

[0016] The molar ratio for the synthesis of modified tea saponin was: tea saponin: cetylamino PEG500 acyl chloride = 1:1.1, and the reaction temperature was 42℃.

[0017] Optimal gel formulation: 4% modified tea saponin, 10% N-isopropylacrylamide, 8% camellia seed oil lipid microspheres, 4% glycerin, 4% propylene glycol, and 0.5% asiaticoside;

[0018] Polymerization conditions: polymerization at 25℃ under nitrogen protection for 3 h, critical gel phase transition temperature 32℃.

[0019] Beneficial effects of the present invention

[0020] (1) Significantly reduced irritation: The irritation index after modification is only 0.18, while the irritation index of native tea saponin under the same conditions is 0.72. It can be used safely by sensitive skin and infants.

[0021] (2) Excellent storage stability: No stratification, precipitation, or discoloration after 180 days at room temperature;

[0022] (3) Long-lasting sustained-release efficacy: The active ingredient is continuously released for 12 hours at a body temperature of 32℃, with an antibacterial rate of 98.5% against Malassezia and Propionibacterium acnes;

[0023] (4) The formula is green and non-irritating, requiring no chemical preservatives, mineral oil, or sulfates;

[0024] (5) The raw materials rely on the agricultural and forestry by-products of camellia oil, which are inexpensive and the process is simple and easy to mass-produce. Specific Implementation

[0025] Example 1 (Optimal Process Group)

[0026] Step 1: Preparation of Alkyl PEGamide Grafted Modified Tea Saponin

[0027] 10 g of 97.8% pure tea saponin was dissolved in 100 mL of anhydrous methanol, and 1.8 g of triethylamine acid binder was added. The mixture was stirred in an ice-water bath at 0°C.

[0028] 11.2 g of hexadecylamino PEG500 acyl chloride was dissolved in 30 mL of methanol and added dropwise to the reaction solution at a uniform rate over 1 h. After the addition was complete, the temperature was raised to 42 °C and the reaction was carried out for 5 h.

[0029] Methanol was recovered by vacuum distillation, the product was dissolved in water, dialyzed with a 1000 molecular weight dialysis bag for 48 h, and freeze-dried to obtain a white modified tea saponin powder.

[0030] Step 2: Camellia seed oil nanolipid microspheres

[0031] Oil phase: 8 g camellia seed oil + 2 g lecithin, melt and mix at 50℃;

[0032] Aqueous phase: 4 g of modified tea saponin dissolved in 90 mL of deionized water;

[0033] The oil phase was slowly added dropwise to the aqueous phase, homogenized at 12000 r / min for 10 min, and circulated twice under high pressure microjets at 800 bar to obtain a lipid dispersion with an average particle size of 90 nm.

[0034] Step 3: Preparation of the thermosensitive skin care gel

[0035] To replenish the total volume of the system, add 4 g of glycerol, 4 g of propylene glycol, and 0.5 g of asiaticoside and stir to dissolve.

[0036] Add 10 g N-isopropylacrylamide, 0.2 g N,N'-methylenebisacrylamide, and 0.1 g ammonium persulfate, and dissolve at 25°C in the dark;

[0037] Nitrogen gas was passed through for 30 minutes to remove oxygen, and 8% lipid microsphere dispersion was slowly added dropwise. Polymerization was carried out at a constant temperature for 3 hours, and then cooled to obtain a transparent hydrogel.

[0038] Example 2 (Low-addition modified tea saponin group)

[0039] The modified tea saponin was added at a rate of 2.5%, and the proportions of the remaining raw materials, the synthesis, and the gel preparation process were completely consistent with those in Example 1.

[0040] Example 3 (High Addition of Modified Tea Saponin Group)

[0041] The modified tea saponin was added at 5%, and the proportions of the remaining raw materials, the synthesis, and the gel preparation process were completely consistent with those in Example 1.

[0042] Example 4 (Low content of temperature-sensitive monomer group)

[0043] The N-isopropylacrylamide was adjusted to 8%, and the other parameters were the same as in Example 1.

[0044] Example 5 (Low-addition lipid microsphere group)

[0045] The amount of camellia seed oil lipid microspheres added was 6%, and the other parameters were the same as in Example 1.

[0046] Comparative examples (3 control samples)

[0047] Comparative Example 1: Only the unmodified native high-purity tea saponin was replaced; the rest of the formula and process were exactly the same as in Example 1.

[0048] Comparative Example 2: Without the addition of N-isopropylacrylamide (NIPAM) thermosensitive monomer, a standard gel system was used, with all other raw materials remaining unchanged;

[0049] Comparative Example 3: No camellia seed oil lipid microspheres added, no sustained-release structure, other ingredients unchanged.

[0050] Performance Comparison Data Table

[0051] Table 1. Overall performance test results of each embodiment and comparative example.

[0052] Skin irritation index (48-hour patch) 0.18 0.21 0.17 0.19 0.2 0.72 0.2 0.18 180-day storage condition at room temperature Transparent and uniform, with no layering or precipitation Slight decrease in viscosity, no sedimentation Completely stable Slightly thinner Stablize A white saponin precipitate formed after 30 days. Oil-water separation occurred after 60 days. The system is homogeneous Duration of sustained release of active ingredient at 32℃ (h) 12 9.5 12.5 8 7.2 3.2 3.8 3 Malassezia inhibition rate (%) 98.5 94.2 99.1 95.6 93.8 82.3 97.9 81.6 Inhibition rate of Propionibacterium acnes (%) 98.2 93.7 98.8 94.9 93.1 80.6 97.5 79.4 Hard water stability (300 mg / L calcium and magnesium ions) No turbidity Slight fog Completely Clarified Slightly cloudy Slight fog Large amount of flocculent precipitate Slight turbidity Large amount of sediment Critical phase transition temperature of gel (°C) 32 31.5 32.4 30.8 31.2 No temperature-sensitive response No temperature-sensitive response 32.1

[0053] Data Results Analysis

[0054] (1) Stimulation contrast

[0055] The irritation index of all modified tea saponin samples in the examples was below 0.25, which was much lower than that of the native tea saponin in Comparative Example 1 (0.72), proving that alkyl PEG covalent grafting can effectively shield the irritation of triterpenoid aglycones and is suitable for use by sensitive skin and infants.

[0056] (2) Storage and hard water stability

[0057] Comparative Example 1 showed that native tea saponins rapidly precipitated under hard water and long-term storage conditions; Examples 1 and 3 of the present invention, after molecular modification, remained clear and homogeneous in high-hardness water and within a six-month shelf life, and the amphiphilic block structure significantly improved electrolyte tolerance.

[0058] (3) Temperature-sensitive sustained-release performance

[0059] Comparative Example 2 had no thermosensitive monomers, and Comparative Example 3 had no lipid microspheres, with active release in only 3-4 hours; Implementation 1's optimal formulation had a sustained release time of up to 12 hours, with the thermosensitive network and lipid microspheres working synergistically to achieve long-lasting repair.

[0060] (4) Antibacterial effect

[0061] The higher the amount of modified tea saponin added, the stronger the antibacterial effect; the original tea saponin has a significantly weaker inhibitory effect on skin fungi and brevicor bacteria than the chemically modified products, and grafting modification enhances the antibacterial activity of tea saponin.

[0062] Innovative Distinction Description of This Invention

[0063] (1) The molecular synthesis route is unique: existing daily chemical patents only physically mix tea saponins. This invention uses amide covalent grafting reaction to modify the molecular skeleton of tea saponins and introduces C16-PEG amphiphilic chain. No similar tea saponin daily chemical patents have been disclosed for this chemical modification process.

[0064] (2) Temperature-sensitive sustained-release integrated structure: The existing tea saponin washing and care formula does not have NIPAM temperature-sensitive polymer + camellia seed oil nano lipid controlled release system, which automatically releases activity based on human body temperature, making it a brand new skin care system;

[0065] (3) Formula differentiation: No sulfates, no chemical preservatives, relying on modified tea saponins for self-preservation, precisely covering the high-end niche market of maternal and infant care and barrier repair.

[0066] (4) Performance data to support innovation: The comparison table intuitively proves that the synergistic effect of the modification process, temperature-sensitive skeleton and lipid microspheres brings multiple improvements in irritation, stability and long-lasting efficacy. Existing ordinary tea saponin compound formulas cannot achieve all the advantages at the same time.

Claims

1. An alkyl polyethylene glycol grafted modified tea saponin-based thermosensitive sustained-release skin care hydrogel, characterized in that: The raw materials include chemically grafted modified tea saponin, a thermosensitive polymer matrix, camellia seed oil lipid microspheres, a multi-component moisturizer, and centella asiatica glycoside plant active ingredients; the modified tea saponin is a covalent graft product of high-purity tea saponin and hexadecylamino PEG500 acyl chloride via amidation, and the molecule retains the active skeleton of tea saponin triterpenoid saponins, C16 long hydrophobic alkyl groups, and hydrophilic PEG oligomer chains; the hydrogel has a critical phase transition temperature of 30~35℃ and automatically releases skin care active ingredients upon contact with human skin.

2. The alkyl polyethylene glycol grafted modified tea saponin-based thermosensitive sustained-release skin care hydrogel according to claim 1, characterized in that, The mass percentage of each component is as follows: modified tea saponin 2.5%–5%, N-isopropylacrylamide 8%–12%, crosslinking agent N,N'-methylenebisacrylamide 0.15%–0.3%, initiator ammonium persulfate 0.08%–0.15%, camellia seed oil lipid microspheres 6%–10%, glycerin + propylene glycol complex moisturizer 6%–10%, asiaticoside 0.3%–0.8%, and the balance being deionized water.

3. The method for preparing modified tea saponin according to claim 2, characterized in that... The steps are as follows: Dissolve tea saponin with a purity ≥90% in anhydrous methanol, add triethylamine as an acid-binding agent, and stir at a constant speed in an ice-water bath at 0~5℃; prepare a hexadecylamino PEG500 acyl chloride methanol solution, and slowly add it dropwise to the tea saponin reaction solution for 0.5~1 h; after the addition is complete, raise the temperature to 40~45℃ for amidation reaction for 4~6 h; remove the methanol solvent by vacuum distillation, dissolve the crude product in deionized water, dialyze with a dialysis bag with a molecular weight cutoff of 500~1500 for 24~48 h to remove unreacted small molecule impurities, and freeze-dry to obtain white modified tea saponin powder.

4. The method for preparing thermosensitive sustained-release skin care hydrogel according to any one of claims 1 to 2, characterized in that... It includes three steps: (1) Pre-preparation of nano-lipid microspheres: Camellia seed oil and lecithin are heated and mixed to form the oil phase, and modified tea saponin aqueous solution is used as the aqueous phase. After high-speed homogenization, high-pressure micro-jet circulation is performed to obtain a lipid microsphere dispersion with a particle size of 80~120 nm. (2) Preparation of aqueous substrate: Dissolve glycerol, propylene glycol and asiaticoside in deionized water and stir at room temperature until completely dissolved; (3) Low-temperature light-protected polymerization and crosslinking: N-isopropylacrylamide, crosslinking agent and initiator are added to the aqueous phase, stirred and dissolved at 25-30℃ in the dark, nitrogen gas is introduced to remove oxygen for 30 min, lipid microsphere dispersion is slowly added dropwise, and low-temperature polymerization is carried out at a constant temperature for 2.5-4 h. After cooling, transparent temperature-sensitive skin hydrogel is obtained.

5. The alkyl polyethylene glycol grafted modified tea saponin-based thermosensitive sustained-release skin care hydrogel according to claim 1, characterized in that... It can be used in sensitive skin repair gels, after-sun soothing mask bases, baby moisturizing massage creams, oil-controlling and acne-removing essences, and sulfate-free gentle cleansing gels.

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