A composition having anti-glycation inhibiting RAGE and lightening effects, its preparation method, formulation product and application

Abstract

The present application relates to a kind of composition with anti-glycation inhibiting RAGE and lightening effect, its preparation method, preparation product and application, belong to medical instrument field, medical or dressing preparation field, biological medicine manufacturing technology field and preparation manufacturing technology field.The composition includes sapota bark extract, tetrahydrocurcumin, mirabilis jalapa extract, surfactant, polyol, phospholipid and solvent.The preparation method provided in the present application includes using 1,3-butanediol with 25%~35% 1,3-butanediol formula amount of 1,3-butanediol and surfactant, sapota bark extract, tetrahydrocurcumin are mixed and dissolved;And the remaining polyol and phospholipid are mixed and the like steps, improve the light stability and high temperature stability of the obtained composition, have unexpected technical effects, and simple operation, without high pressure mean equipment, equipment cost is low.In addition, the composition provided in the present application has high bioavailability, has good antioxidant lightening effect and inhibiting lipofuscin and RAGE level effect.

Description

Technical Field

[0001] This invention relates to the fields of medical devices, medical or cosmetic formulations, biopharmaceutical manufacturing, and pharmaceutical preparation manufacturing, specifically to a composition with anti-glycation, RAGE inhibition, and brightening effects, its preparation method, formulation products, and applications. Background Technology

[0002] AGEs refer to a series of highly reactive end products formed when sugar molecules covalently bind to macromolecules such as DNA, proteins, and lipids in a non-enzymatic reaction. AGEs can develop even under normal blood sugar conditions, but their formation is greatly accelerated under hyperglycemic conditions, oxidative stress, or prolonged ultraviolet radiation.

[0003] In the Maillard reaction, the electrophilic carbonyl group of a sugar molecule reacts with the free amino group of a protein, lipid, or nucleic acid to form a Schiff base. This unstable Schiff base contains a carbon-nitrogen double bond, with the nitrogen atom attached to an aryl or alkyl group. The Schiff base rapidly rearranges to form a more stable ketamine, known as the Amadori product. At this point, the Amadori product can: ① undergo the reverse reaction; ② undergo an irreversible reaction with lysine or arginine to produce stable AGEs in the form of protein cross-linking; ③ undergo further decomposition reactions, such as oxidation, dehydration, and polymerization, thereby producing many other types of AGEs. RAGE (Receptor for Advanced Glycation End Products) is a multi-ligand member of the cell surface receptor immunoglobulin superfamily and one of the AGEs-binding proteins. Once involved, it can generate a strong pro-inflammatory response in many cell types. RAGE linkage not only induces the expression of inflammatory genes but also triggers a positive feedback loop: inflammatory stimulation activates NF-κB, inducing RAGE expression, which in turn continuously activates NF-κB, causing an inflammatory response and accelerating skin pigmentation. Lipofuscin, as a combination of intracellular denatured proteins and lipid peroxides, is deposited in cells due to skin glycation and aging, thus exacerbating pigmentation and leading to dull skin. To address this issue, we focus on four aspects: inhibiting the generation of AGEs at its source, blocking the AGEs-RAGE pathway, clearing AGEs accumulation, and reducing lipofuscin accumulation. These measures aim to reduce and delay skin glycation, thereby achieving antioxidant and brightening effects.

[0004] Tetrahydrocurcumin (THC) is a hydrogenated derivative of curcumin. By reducing the unsaturated double bonds in the curcumin molecule, it exhibits higher stability and bioactivity. It reduces the accumulation of AGEs (advanced aging processes); decreases collagen cross-linking; and prevents AGEs from binding to RAGE and inducing the NF-κB and VEGF pathways, thus achieving an anti-glycation effect. Simultaneously, it synergistically enhances the antioxidant capacity of Dalbergia odorifera bark extract, reducing lipofuscin through antioxidant action and resulting in a brightening effect.

[0005] Currently, the preparation and application of products containing tetrahydrocurcumin on the market face the following challenges:

[0006] 1) It has low water and fat solubility, making it difficult to disperse evenly in cosmetic or pharmaceutical bases.

[0007] 2) It is easily oxidized and discolored. When exposed to light or air, it is easily oxidized and precipitated, causing the formula to change color (such as yellowing) and lose its activity.

[0008] 3) It has poor stability under high temperature and light, and is prone to degradation under high temperature or light, especially under light conditions, which leads to a decrease in the content of tetrahydrocurcumin in the product and affects the efficacy of the product.

[0009] Therefore, there is still an urgent need for a tetrahydrocurcumin-containing composition and / or its preparation method for cosmetics that has good stability, antioxidant and brightening effects, and the ability to inhibit lipofuscin levels. Summary of the Invention

[0010] To address the aforementioned technical problems, the present invention provides the following technical solutions.

[0011] In a first aspect, the present invention provides a method for preparing a composition.

[0012] A method for preparing a composition, said composition comprising the following components in parts by weight:

[0013] Dalbergia odorifera bark extract: 0.4 to 2 parts by weight (e.g., 0.4, 0.5, 0.9, 1, 1.5 or 2 parts by weight).

[0014] Tetrahydrocurcumin: 0.3~1.0 parts by weight (e.g., 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0 parts by weight);

[0015] Four o'clock extract: 0.1~0.5 parts by weight (e.g., 0.1, 0.2, 0.3, 0.4 or 0.5 parts by weight);

[0016] Surfactant: 3~30 parts by weight (e.g., 3, 5, 8, 8.5, 9, 10, 15, 18, 19, 20, 25 or 30 parts by weight);

[0017] Polyols: 50-80 parts by weight (e.g., 50, 55, 60, 65, 70, 75 or 80 parts by weight);

[0018] Stabilizer: 0.01~0.5 parts by weight (e.g., 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, 0.3, 0.4 or 0.5 parts by weight);

[0019] Phospholipids: 0.5 to 1 part by weight (e.g., 0.5, 0.6, 0.7, 0.8, 0.9 or 1 part by weight);

[0020] Solvent: 5 to 45.6 parts by weight (e.g., 5, 5.5, 5.9, 6, 6.5, 7, 8, 9, 9.5, 9.57, 10, 15, 17, 17.5, 17.9, 18, 18.1, 20, 25, 30, 35, 40, 45, 45.29, 45.6 parts by weight, or any value within the range of any two of these values);

[0021] in,

[0022] The polyols include 1,3-butanediol and 1,3-propanediol;

[0023] The stabilizer includes disodium ethylenediaminetetraacetate (EDTA-2Na);

[0024] The solvent includes water;

[0025] The content ratio of 1,3-butanediol to 1,3-propanediol is 1:1 to 5:1.

[0026] The preparation method includes the following steps:

[0027] (1) Take 25%~35% of the 1,3-butanediol formulation amount of 1,3-butanediol and mix it with surfactant, Dalbergia odorifera bark extract and tetrahydrocurcumin to obtain solution 1;

[0028] (2) Mix the remaining polyol with phospholipids and heat until completely dissolved to obtain solution 2;

[0029] (3) Mix solution 1 and solution 2 thoroughly to obtain solution 3;

[0030] (4) Mix the stabilizer and solvent evenly to obtain solution 4;

[0031] (5) Mix solution 4 with solution 3, stir, and then mix with the four o'clock extract to obtain the composition.

[0032] In some embodiments, the amount of 1,3-butanediol added in step (1) is 25%, 26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, or 35% of the 1,3-butanediol formulation. In some embodiments, the amount of 1,3-butanediol added in step (1) is 28% to 32% of the 1,3-butanediol formulation.

[0033] Pterocarpus marsupium bark extract is a natural active ingredient extracted from the bark of the Pterocarpus marsupium tree. Its core active ingredient is pterostilbene, which belongs to the polyhydroxystilbene class of compounds. Pterostilbene is a methylated derivative of resveratrol and is known as "second-generation resveratrol" due to its higher bioavailability and stability. This component is widely found in plants such as sandalwood and blueberries, but is particularly abundant in Pterocarpus marsupium. This active ingredient can effectively protect the integrity of protein structure and inhibit non-enzymatic glycation by occupying the glycosylation sites of proteins and competitively binding to proteins through hydrogen bonds and van der Waals forces. Furthermore, it reduces glycosylation reactions by inhibiting the activity of AR and RAGE, and its antioxidant activity can neutralize free radicals, thereby reducing oxidative stress caused by AGEs. In some embodiments, the mixing and dissolving temperature in step (1) is 45°C to 65°C. In some embodiments, the mixing and dissolving temperature in step (1) is 45°C, 50°C, 55°C, 60°C, 65°C, or any value within the range of any two of these values.

[0034] In some embodiments, the composition comprises or consists of the following components in parts by weight:

[0035] Dalbergia odorifera bark extract: 0.4 to 2 parts by weight (e.g., 0.4, 0.5, 0.9, 1, 1.5 or 2 parts by weight, or any value within the range of any two of these values).

[0036] Tetrahydrocurcumin: 0.3~1.0 parts by weight (e.g., 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0 parts by weight, or any value within any two of these ranges).

[0037] Four o'clock extract: 0.1~0.5 parts by weight (e.g., 0.1, 0.2, 0.3, 0.4 or 0.5 parts by weight, or any value within the range of any two of these values);

[0038] Surfactant: 3 to 30 parts by weight (e.g., 3, 5, 8, 8.5, 9, 10, 15, 18, 19, 20, 25 or 30 parts by weight, or any value within the range of any two of these values);

[0039] Polyols: 50 to 80 parts by weight (e.g., 50, 55, 60, 65, 70, 75 or 80 parts by weight, or any value within the range of any two of these values);

[0040] Stabilizer: 0.01~0.5 parts by weight (e.g., 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, 0.3, 0.4 or 0.5 parts by weight, or any value within the range of any two of these values);

[0041] Phospholipids: 0.5 to 1 part by weight (e.g., 0.5, 0.6, 0.7, 0.8, 0.9 or 1 part by weight, or any value within the range of any two of these values).

[0042] Solvent: 5.9 to 45.29 parts by weight (e.g., 5.9, 6, 6.5, 7, 8, 9, 9.5, 9.57, 10, 15, 17, 17.5, 17.9, 18, 18.1, 20, 25, 30, 35, 40, 45 or 45.29 parts by weight, or any value within the range of any two of these values).

[0043] In some embodiments, the composition comprises or consists of the following components in parts by weight:

[0044] Dalbergia odorifera bark extract: 0.4 to 2 parts by weight (e.g., 0.4, 0.5, 0.9, 1, 1.5 or 2 parts by weight, or any value within the range of any two of these values).

[0045] Tetrahydrocurcumin: 0.3~1.0 parts by weight (e.g., 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0 parts by weight, or any value within any two of these ranges).

[0046] Four o'clock extract: 0.1~0.5 parts by weight (e.g., 0.1, 0.2, 0.3, 0.4 or 0.5 parts by weight, or any value within the range of any two of these values);

[0047] Surfactant: 3 to 30 parts by weight (e.g., 3, 5, 8, 8.5, 9, 10, 15, 18, 19, 20, 25 or 30 parts by weight, or any value within the range of any two of these values);

[0048] Polyols: 50 to 80 parts by weight (e.g., 50, 55, 60, 65, 70, 75 or 80 parts by weight, or any value within the range of any two of these values);

[0049] Stabilizer: 0.01~0.5 parts by weight (e.g., 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, 0.3, 0.4 or 0.5 parts by weight, or any value within the range of any two of these values);

[0050] Phospholipids: 0.5 to 1 part by weight (e.g., 0.5, 0.6, 0.7, 0.8, 0.9 or 1 part by weight, or any value within the range of any two of these values).

[0051] Solvent: 5.9 to 45.29 parts by weight (e.g., 5.9, 6, 6.5, 7, 8, 9, 9.5, 9.57, 10, 15, 17, 17.5, 17.9, 18, 18.1, 20, 25, 30, 35, 40, 45 or 45.29 parts by weight, or any value within the range of any two of these values);

[0052] The total weight of the extracts of Dalbergia odorifera bark, tetrahydrocurcumin, Mirabilis jalapa extract, surfactants, polyols, stabilizers, phospholipids and solvents is 100%.

[0053] In some embodiments, the composition comprises or is composed of the following components in parts by weight:

[0054] Dalbergia odorifera bark extract: 0.4 parts by weight;

[0055] Tetrahydrocurcumin: 0.5 parts by weight;

[0056] Mirabilis jalapa extract: 0.3 parts by weight;

[0057] Surfactant: 3 parts by weight;

[0058] Polyols: 50 parts by weight;

[0059] Stabilizer: 0.01 parts by weight;

[0060] Phospholipids: 0.5 parts by weight;

[0061] Solvent: 45.29 parts by weight.

[0062] In some embodiments, the composition comprises or is composed of the following components in parts by weight:

[0063] Dalbergia odorifera bark extract: 0.9 parts by weight;

[0064] Tetrahydrocurcumin: 0.3 parts by weight;

[0065] Mirabilis jalapa extract: 0.2 parts by weight;

[0066] Surfactant: 8.5 parts by weight;

[0067] Polyols: 80 parts by weight;

[0068] Stabilizer: 0.03 parts by weight;

[0069] Phospholipids: 0.5 parts by weight;

[0070] Solvent: 9.57 parts by weight.

[0071] In some embodiments, the composition comprises or is composed of the following components in parts by weight:

[0072] Dalbergia odorifera bark extract: 1.5 parts by weight;

[0073] Tetrahydrocurcumin: 1.0 part by weight;

[0074] Mirabilis jalapa extract: 0.5 parts by weight;

[0075] Surfactant: 18 parts by weight;

[0076] Polyols: 60 parts by weight;

[0077] Stabilizer: 0.1 parts by weight;

[0078] Phospholipids: 1 part by weight;

[0079] Solvent: 17.9 parts by weight.

[0080] In some embodiments, the composition comprises or is composed of the following components in parts by weight:

[0081] Dalbergia odorifera bark extract: 2 parts by weight;

[0082] Tetrahydrocurcumin: 0.5 parts by weight;

[0083] Mirabilis jalapa extract: 0.1 parts by weight;

[0084] Surfactant: 30 parts by weight;

[0085] Polyols: 60 parts by weight;

[0086] Stabilizer: 0.5 parts by weight;

[0087] Phospholipids: 1 part by weight;

[0088] Solvent: 5.9 parts by weight.

[0089] In some embodiments, the composition comprises or consists of the following components in parts by weight:

[0090] Dalbergia odorifera bark extract: 0.4 to 2 parts by weight (e.g., 0.4, 0.5, 0.9, 1, 1.5 or 2 parts by weight, or any value within the range of any two of these values).

[0091] Tetrahydrocurcumin: 0.3~1.0 parts by weight (e.g., 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0 parts by weight, or any value within any two of these ranges).

[0092] Four o'clock extract: 0.1~0.5 parts by weight (e.g., 0.1, 0.2, 0.3, 0.4 or 0.5 parts by weight, or any value within the range of any two of these values);

[0093] Oleyl alcohol polyether-20: 1.5 to 8 parts by weight (e.g., 1.5, 2, 2.5, 3, 4, 5, 6, 7 or 8 parts by weight, or any value within the range of any two of these values);

[0094] Polyglycerol-10 stearate: 0.5 to 9 parts by weight (e.g., 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5 or 9 parts by weight, or any value within the range of any two of these values);

[0095] Polyglycerol-10 oleate: 1 to 13 parts by weight (e.g., 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5 or 13 parts by weight, or any value within the range of any two of these values);

[0096] 1,3-Butanediol: 40 to 50 parts by weight (e.g., 40, 45 or 50 parts by weight, or any value within any two of these ranges).

[0097] 1,3-Propanediol: 10 to 35 parts by weight (e.g., 10, 15, 20, 25, 30 or 35 parts by weight, or any value within the range of any two of these values);

[0098] Stabilizer: 0.01~0.5 parts by weight (e.g., 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, 0.3, 0.4 or 0.5 parts by weight, or any value within the range of any two of these values);

[0099] Phospholipids: 0.5 to 1 part by weight (e.g., 0.5, 0.6, 0.7, 0.8, 0.9 or 1 part by weight, or any value within the range of any two of these values).

[0100] Solvent: 5.9 to 45.29 parts by weight (e.g., 5.9, 6, 6.5, 7, 8, 9, 9.5, 9.57, 10, 15, 17, 17.5, 17.9, 18, 18.1, 20, 25, 30, 35, 40, 45 or 45.29 parts by weight, or any value within the range of any two of these values).

[0101] In some embodiments, the composition comprises or is composed of the following components in parts by weight:

[0102] Dalbergia odorifera bark extract: 0.4 to 2 parts by weight (e.g., 0.4, 0.5, 0.9, 1, 1.5 or 2 parts by weight, or any value within the range of any two of these values).

[0103] Tetrahydrocurcumin: 0.3~1.0 parts by weight (e.g., 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0 parts by weight, or any value within any two of these ranges).

[0104] Four o'clock extract: 0.1~0.5 parts by weight (e.g., 0.1, 0.2, 0.3, 0.4 or 0.5 parts by weight, or any value within the range of any two of these values);

[0105] Oleyl alcohol polyether-20: 1.5 to 8 parts by weight (e.g., 1.5, 2, 2.5, 3, 4, 5, 6, 7 or 8 parts by weight, or any value within the range of any two of these values);

[0106] Polyglycerol-10 stearate: 0.5 to 9 parts by weight (e.g., 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5 or 9 parts by weight, or any value within the range of any two of these values);

[0107] Polyglycerol-10 oleate: 1 to 13 parts by weight (e.g., 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5 or 13 parts by weight, or any value within the range of any two of these values);

[0108] 1,3-Butanediol: 40 to 50 parts by weight (e.g., 40, 42, 45, 47 or 50 parts by weight, or any value within the range of any two of these values);

[0109] 1,3-Propanediol: 10 to 35 parts by weight (e.g., 10, 15, 20, 25, 30 or 35 parts by weight, or any value within the range of any two of these values);

[0110] Stabilizer: 0.01~0.5 parts by weight (e.g., 0.01, 0.02, 0.03, 0.04, 0.05, 0.1, 0.2, 0.3, 0.4 or 0.5 parts by weight, or any value within the range of any two of these values);

[0111] Phospholipids: 0.5 to 1 part by weight (e.g., 0.5, 0.6, 0.7, 0.8, 0.9 or 1 part by weight, or any value within the range of any two of these values).

[0112] Solvent: 5.9 to 45.29 parts by weight (e.g., 5.9, 6, 6.5, 7, 8, 9, 9.5, 9.57, 10, 15, 17, 17.5, 17.9, 18, 18.1, 20, 25, 30, 35, 40, 45 or 45.29 parts by weight, or any value within the range of any two of these values);

[0113] The total weight of the extracts of Dalbergia odorifera bark, tetrahydrocurcumin, Mirabilis jalapa extract, surfactants, polyols, stabilizers, phospholipids and solvents is 100%.

[0114] In some embodiments, the composition comprises or is composed of the following components in parts by weight:

[0115] Dalbergia odorifera bark extract: 0.4 parts by weight;

[0116] Tetrahydrocurcumin: 0.5 parts by weight;

[0117] Mirabilis jalapa extract: 0.3 parts by weight;

[0118] Oleyl alcohol polyether-20: 1.5 parts by weight;

[0119] Polyglycerol-10 stearate: 0.5 parts by weight;

[0120] Polyglycerol-10 oleate: 1 part by weight;

[0121] 1,3-Butanediol: 40 parts by weight;

[0122] 1,3-Propanediol: 10 parts by weight;

[0123] Stabilizer: 0.01 parts by weight;

[0124] Phospholipids: 0.5 parts by weight;

[0125] Solvent: 45.29 parts by weight.

[0126] In some embodiments, the composition comprises or is composed of the following components in parts by weight:

[0127] Dalbergia odorifera bark extract: 0.9 parts by weight;

[0128] Tetrahydrocurcumin: 0.3 parts by weight;

[0129] Mirabilis jalapa extract: 0.2 parts by weight;

[0130] Oleyl alcohol polyether-20: 2.5 parts by weight;

[0131] Polyglycerol-10 stearate: 2.5 parts by weight;

[0132] Polyglycerol-10 oleate: 3.5 parts by weight;

[0133] 1,3-Butanediol: 45 parts by weight;

[0134] 1,3-Propanediol: 35 parts by weight;

[0135] Stabilizer: 0.03 parts by weight;

[0136] Phospholipids: 0.5 parts by weight;

[0137] Solvent: 9.57 parts by weight.

[0138] In some embodiments, the composition comprises or is composed of the following components in parts by weight:

[0139] Dalbergia odorifera bark extract: 1.5 parts by weight;

[0140] Tetrahydrocurcumin: 1.0 part by weight;

[0141] Mirabilis jalapa extract: 0.5 parts by weight;

[0142] Oleol polyether-20: 6 parts by weight;

[0143] Polyglycerol-10 stearate: 4 parts by weight;

[0144] Polyglycerol-10 oleate: 8 parts by weight;

[0145] 1,3-Butanediol: 50 parts by weight;

[0146] 1,3-Propanediol: 10 parts by weight;

[0147] Stabilizer: 0.1 parts by weight;

[0148] Phospholipids: 1 part by weight;

[0149] Solvent: 17.9 parts by weight.

[0150] In some embodiments, the composition comprises or is composed of the following components in parts by weight:

[0151] Dalbergia odorifera bark extract: 2 parts by weight;

[0152] Tetrahydrocurcumin: 0.5 parts by weight;

[0153] Mirabilis jalapa extract: 0.1 parts by weight;

[0154] Oleol polyether-20: 8 parts by weight;

[0155] Polyglycerol-10 stearate: 9 parts by weight;

[0156] Polyglycerol-10 oleate: 13 parts by weight;

[0157] 1,3-Butanediol: 50 parts by weight;

[0158] 1,3-Propanediol: 10 parts by weight;

[0159] Stabilizer: 0.5 parts by weight;

[0160] Phospholipids: 1 part by weight;

[0161] Solvent: 5.9 parts by weight.

[0162] In some embodiments, the heating temperature in step (2) is 55°C to 65°C. In some embodiments, the heating temperature in step (2) is 55°C, 60°C, 65°C, or any value within a range of any two of these values.

[0163] In some embodiments, the temperatures of solution 1 and solution 2 before mixing in step (3) are independently selected from 50°C to 70°C. In some embodiments, the temperatures of solution 1 and solution 2 before mixing in step (3) are independently selected from 50°C, 55°C, 60°C, 65°C, 70°C, or any value within the range of any two of these values.

[0164] In some embodiments, in step (5), before mixing solution 4 and solution 3, the temperatures of solution 3 and solution 4 are independently selected from 38℃-45℃. In some embodiments, in step (5), before mixing solution 4 and solution 3, the temperatures of solution 3 and solution 4 are independently selected from 38℃, 39℃, 40℃, 41℃, 42℃, 43℃, 44℃, 45℃, or any value within the range of any two of these values.

[0165] In some embodiments, the stirring temperature in step (5) is 38°C to 45°C. In some embodiments, the stirring temperature in step (5) is 38°C, 39°C, 40°C, 41°C, 42°C, 43°C, 44°C, 45°C, or any value within a range of any two of these values.

[0166] In some embodiments, the surfactant includes at least one of oleyl alcohol polyether-20, polyglycerol-10 stearate, and polyglycerol-10 oleate.

[0167] In some embodiments, the phospholipids include soybean lecithin.

[0168] In some embodiments, the four o'clock extract comprises four o'clock (Mirabilis jalapa) extract and glycerin.

[0169] In some embodiments, the four o'clock extract is composed of four o'clock flower (Mirabilis jalapa) extract and glycerin, wherein the content of the four o'clock flower (Mirabilis jalapa) extract in the four o'clock extract is 10 wt% to 30 wt%. In some embodiments, the four o'clock extract is composed of four o'clock flower (Mirabilis jalapa) extract and glycerin, wherein the content of the four o'clock flower (Mirabilis jalapa) extract in the four o'clock extract is 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, or any value within the range of any two of these values.

[0170] In some embodiments, the four o'clock flower (Mirabilis jalapa) extract is at least one selected from four o'clock flower (Mirabilis jalapa) extract, four o'clock leaf (Mirabilis jalapa) extract, or four o'clock stem (Mirabilis jalapa) extract. In some embodiments, the four o'clock flower (Mirabilis jalapa) extract is a four o'clock flower extract.

[0171] In some embodiments, the four o'clock extract is OvernightEnhance [MJ+C] Repairing and Enhancing Four O'clock Extract.

[0172] In some embodiments, the surfactant, polyol, and phospholipid form a flexible liposome membrane structure, and the palm bark extract and tetrahydrocurcumin are encapsulated within the flexible liposomes.

[0173] In some embodiments, the composition comprises the following components: Dalbergia odorifera bark extract, tetrahydrocurcumin, Mirabilis jalapa extract, surfactant, polyol, stabilizer, phospholipid and solvent.

[0174] In some embodiments, the content of the *Dalbergia odorifera* bark extract, calculated based on the total weight of the composition, is 0.4 wt% to 2 wt%. In some embodiments, the content of the *Dalbergia odorifera* bark extract, calculated based on the total weight of the composition, is 0.4 wt%, 0.5 wt%, 0.6 wt%, 0.7 wt%, 0.8 wt%, 0.9 wt%, 1 wt%, 1.5 wt%, or 2 wt%, or any value within the range of any two of these values.

[0175] In some embodiments, the content of tetrahydrocurcumin, calculated based on the total weight of the composition, is 0.1 wt% to 1.0 wt%. In some embodiments, the content of tetrahydrocurcumin, calculated based on the total weight of the composition, is 0.3 wt% to 1.0 wt%. In some embodiments, the content of tetrahydrocurcumin, calculated based on the total weight of the composition, is 0.3 wt%, 0.4 wt%, 0.5 wt%, 0.6 wt%, 0.7 wt%, 0.8 wt%, 0.9 wt%, 1.0 wt%, or any value within the range of any two of these values.

[0176] In some embodiments, the content of the four o'clock flower extract is 0.1 wt% to 0.5 wt% based on the total weight of the composition. In some embodiments, the content of the four o'clock flower extract is 0.1 wt%, 0.2 wt%, 0.3 wt%, 0.4 wt%, or 0.5 wt% based on the total weight of the composition, or any value within a range of any two of these values.

[0177] In some embodiments, the total content of the surfactant, calculated by the total weight of the composition, is 3 wt% to 30 wt%. In some embodiments, the total content of the surfactant, calculated by the total weight of the composition, is 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, 15 wt%, 16 wt%, 17 wt%, 18 wt%, 19 wt%, 20 wt%, 21 wt%, 22 wt%, 23 wt%, 24 wt%, 25 wt%, 26 wt%, 27 wt%, 28 wt%, 29 wt%, or 30 wt%, or any value within a range of any two of these values.

[0178] In some embodiments, the total content of the polyol, calculated by the total weight of the composition, is 50 wt% to 80 wt%. In some embodiments, the total content of the polyol, calculated by the total weight of the composition, is 50 wt%, 55 wt%, 60 wt%, 65 wt%, 70 wt%, 75 wt%, 80 wt%, or any value within a range of any two of these values.

[0179] In some embodiments, the stabilizer content is 0.01 wt% to 0.5 wt% based on the total weight of the composition. In some embodiments, the stabilizer content is 0.01 wt%, 0.02, 0.03, 0.04 wt%, 0.05 wt%, 0.1 wt%, 0.15 wt%, 0.2 wt%, 0.25 wt%, 0.3 wt%, 0.35 wt%, 0.4 wt%, 0.45 wt%, 0.5 wt%, or any value within the range of any two of these values, based on the total weight of the composition.

[0180] In some embodiments, the phospholipid content is 0.5 wt% to 3.0 wt% based on the total weight of the composition. In some embodiments, the phospholipid content is 0.5 wt% to 1.0 wt% based on the total weight of the composition. In some embodiments, the phospholipid content is 0.5 wt%, 1.0 wt%, 1.5 wt%, 2.0 wt%, 2.5 wt%, 3.0 wt%, or any value within the range of any two of these values, based on the total weight of the composition.

[0181] In some embodiments, the solvent content, calculated based on the total weight of the composition, is 5 wt% to 45.6 wt%. In some embodiments, the solvent content, calculated based on the total weight of the composition, is 5 wt%, 5.7 wt%, 5.9 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%, 9.57 wt%, 9.6 wt%, 10 wt%, 11 wt%, 12 wt%, 12.4 wt%, 13 wt%, 14 wt%, 15 wt%, 15.5 wt%, 16 wt%, 17 wt%, 17.9 wt%, 18 wt%, 18.1 wt%, 19 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 45.29 wt%, 45.6 wt%, or any value within a range of any two of these values.

[0182] In some embodiments, the content of any one of the surfactants, calculated by the total weight of the composition, is independently selected from 0.5 wt% to 13.0 wt%. In some embodiments, the content of any one of the surfactants, calculated by the total weight of the composition, is independently selected from 0.5 wt%, 1.0 wt%, 1.5 wt%, 2.0 wt%, 2.5 wt%, 3.0 wt%, 3.5 wt%, 4.0 wt%, 4.5 wt%, 5.0 wt%, 5.5 wt%, 6.0 wt%, 6.5 wt%, 7.0 wt%, 7.5 wt%, 8.0 wt%, 8.5 wt%, 9.0 wt%, 9.5 wt%, 10.0 wt%, 10.5 wt%, 11.0 wt%, 11.5 wt%, 12.0 wt%, 12.5 wt%, 13.0 wt%, or any value within the range of any two of these values.

[0183] In some embodiments, the content of oleyl alcohol polyether-20 is 1.5 wt% to 8 wt% (e.g., 1.5 wt%, 2 wt%, 2.5 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, or 8 wt%, or any value within the range of any two of these values) based on the total weight of the composition.

[0184] In some embodiments, the content of polyglycerol-10 stearate is 0.5wt% to 9wt% (e.g., 0.5wt%, 1wt%, 1.5wt%, 2wt%, 2.5wt%, 3wt%, 3.5wt%, 4wt%, 4.5wt%, 5wt%, 5.5wt%, 6wt%, 6.5wt%, 7wt%, 7.5wt%, 8wt%, 8.5wt%, or 9wt%, or any value within the range of any two of these values) based on the total weight of the composition.

[0185] In some embodiments, the content of polyglycerol-10 oleate, calculated based on the total weight of the composition, is 1 wt% to 13 wt% (e.g., 1 wt%, 1.5 wt%, 2 wt%, 2.5 wt%, 3 wt%, 3.5 wt%, 4 wt%, 4.5 wt%, 5 wt%, 5.5 wt%, 6 wt%, 6.5 wt%, 7 wt%, 7.5 wt%, 8 wt%, 8.5 wt%, 9 wt%, 9.5 wt%, 10 wt%, 10.5 wt%, 11 wt%, 11.5 wt%, 12 wt%, 12.5 wt%, or 13 wt%, or any value within the range of any two of these values).

[0186] In some embodiments, the content of 1,3-butanediol is 40 wt% to 50 wt% (e.g., 40 wt%, 42 wt%, 45 wt%, 47 wt%, or 50 wt%, or any value within the range of any two of these values) based on the total weight of the composition.

[0187] In some embodiments, the content of 1,3-propanediol is 10 wt% to 35 wt% (e.g., 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, or 35 wt%, or any value within the range of any two of these values) based on the total weight of the composition.

[0188] In some embodiments, the content of each of the polyols, calculated by the total weight of the composition, is independently selected from 10 wt% to 50 wt%. In some embodiments, the content of each of the polyols, calculated by the total weight of the composition, is independently selected from 10 wt%, 15 wt%, 20 wt%, 25 wt%, 30 wt%, 35 wt%, 40 wt%, 45 wt%, 50 wt%, or any value within the range of any two of these values.

[0189] In some embodiments, the composition comprises any one of the following groups:

[0190] (1) Based on the total weight of the composition, the content of the Dalbergia odorifera bark extract is 0.4 wt%~2 wt%, the content of the tetrahydrocurcumin is 0.3 wt%~1.0 wt%, the content of the Mirabilis jalapa extract is 0.1 wt%~0.5 wt%, the total content of the surfactant is 3 wt%~30 wt%, the total content of the polyol is 50 wt%~80 wt%, the content of the stabilizer is 0.01 wt%~0.5 wt%, the content of the phospholipid is 0.5 wt%~1.0 wt%, and the content of the solvent is 5 wt%~45.6 wt%;

[0191] (2) Based on the total weight of the composition, the content of the Dalbergia odorifera bark extract is 0.4 wt%~2 wt%, the content of the tetrahydrocurcumin is 0.3 wt%~1.0 wt%, the content of the Mirabilis jalapa extract is 0.1 wt%~0.5 wt%, the total content of the surfactant is 3 wt%~30 wt%, the total content of the polyol is 50 wt%~80 wt%, the content of the stabilizer is 0.01 wt%~0.5 wt%, the content of the phospholipid is 0.5 wt%~1.0 wt%, and the content of the solvent is 5.9 wt%~45.29 wt%;

[0192] (3) The surfactants include oleyl alcohol polyether-20, polyglycerol-10 stearate and polyglycerol-10 oleate; based on the total weight of the composition, the content of the Dalbergia odorifera bark extract is 0.4 wt% to 2 wt%, the content of the tetrahydrocurcumin is 0.3 wt% to 1.0 wt%, the content of the Mirabilis jalapa extract is 0.1 wt% to 0.5 wt%, the total content of the surfactants is 3 wt% to 30 wt%, wherein the content of any one of the surfactants is independently selected from 0.5 wt% to 13.0 wt%; the total content of the polyols is 50 wt% to 80 wt%, the content of the stabilizer is 0.01 wt% to 0.5 wt%, the content of the phospholipids is 0.5 wt% to 1.0 wt%, and the content of the solvent is 5 wt% to 45.6 wt%.

[0193] (4) The surfactants include oleyl alcohol polyether-20, polyglycerol-10 stearate and polyglycerol-10 oleate; the polyols include 1,3-butanediol and 1,3-propanediol; based on the total weight of the composition, the content of the *Palmaria lobata* bark extract is 0.4wt%~2wt%, the content of the tetrahydrocurcumin is 0.3wt%~1.0wt%, the content of the *Mirabilis jalapa* extract is 0.1wt%~0.5wt%, the total content of the surfactants is 3wt%~30wt%; the total content of the polyols is 50wt%~80wt%, wherein the content of any one of the polyols is independently selected from 10wt%~50wt%; the content of the stabilizer is 0.01wt%~0.5wt%, the content of the phospholipid is 0.5wt%~1.0wt%, and the content of the solvent is 5.9wt%~45.29wt%;

[0194] (5) The surfactants include oleyl alcohol polyether-20, polyglycerol-10 stearate and polyglycerol-10 oleate; the polyols include 1,3-butanediol and 1,3-propanediol; based on the total weight of the composition, the content of the *Palmaria lobata* bark extract is 0.4 wt% to 2 wt%, the content of the tetrahydrocurcumin is 0.3 wt% to 1.0 wt%, the content of the *Mirabilis jalapa* extract is 0.1 wt% to 0.5 wt%, the total content of the surfactants is 3 wt% to 30 wt%, wherein the content of any one of the surfactants is 0.5 wt% to 13.0 wt%; the total content of the polyols is 50 wt% to 80 wt%, wherein the content of any one of the polyols is independently selected from 10 wt% to 50 wt%; the content of the stabilizer is 0.01 wt% to 0.5 wt%, the content of the phospholipid is 0.5 wt% to 1.0 wt%, and the content of the solvent is 5 wt% to 45.6 wt%;

[0195] (6) The surfactants include oleyl alcohol polyether-20, polyglycerol-10 stearate and polyglycerol-10 oleate; the polyols include 1,3-butanediol and 1,3-propanediol; based on the total weight of the composition, the content of the *Palmaria lobata* bark extract is 0.4 wt% to 2 wt%, the content of the tetrahydrocurcumin is 0.3 wt% to 1.0 wt%, the content of the *Mirabilis jalapa* extract is 0.1 wt% to 0.5 wt%, the total content of the surfactants is 3 wt% to 30 wt%, wherein the content of any one of the surfactants is independently selected from 0.5 wt% to 13.0 wt%; the total content of the polyols is 50 wt% to 80 wt%, wherein the content of any one of the polyols is independently selected from 10 wt% to 50 wt%; the content of the stabilizer is 0.01 wt% to 0.5 wt%, the content of the phospholipid is 0.5 wt% to 1.0 wt%, and the remainder is the solvent;

[0196] (7) The surfactant comprises oleyl alcohol polyether-20, polyglycerol-10 stearate, and polyglycerol-10 oleate; the polyol comprises 1,3-butanediol and 1,3-propanediol; and, based on the total weight of the composition, the content of the *Dalbergia odorifera* bark extract is 0.4 wt% to 2 wt%, the content of the tetrahydrocurcumin is 0.3 wt% to 1.0 wt%, the content of the *Mirabilis jalapa* extract is 0.1 wt% to 0.5 wt%, and the content of the oleyl alcohol polyether-20 is 1.5 wt% to 8 wt%. The content of the polyglycerol-10 stearate is 0.5wt%~9wt%, the content of the polyglycerol-10 oleate is 1wt%~13wt%, the content of the 1,3-butanediol is 40wt%~50wt%, the content of the 1,3-propanediol is 10wt%~35wt%, the content of the stabilizer is 0.01wt%~0.5wt%, the content of the phospholipid is 0.5wt%~1.0wt%, and the content of the solvent is 5wt%~45.6wt%.

[0197] (8) The surfactant comprises oleyl alcohol polyether-20, polyglycerol-10 stearate, and polyglycerol-10 oleate; the polyol comprises 1,3-butanediol and 1,3-propanediol; and, based on the total weight of the composition, the content of the *Palmaria lobata* bark extract is 0.4 wt% to 2 wt%, the content of the tetrahydrocurcumin is 0.3 wt% to 1.0 wt%, the content of the *Mirabilis jalapa* extract is 0.1 wt% to 0.5 wt%, and the content of the oleyl alcohol polyether-20 is 1.5 wt% to 8 wt%. The content of the polyglycerol-10 stearate is 0.5wt%~9wt%, the content of the polyglycerol-10 oleate is 1wt%~13wt%, the content of the 1,3-butanediol is 40wt%~50wt%, the content of the 1,3-propanediol is 10wt%~35wt%, the content of the stabilizer is 0.01wt%~0.5wt%, the content of the phospholipid is 0.5wt%~1.0wt%, and the balance is the solvent.

[0198] In a second aspect, the present invention provides a composition.

[0199] A composition prepared according to the preparation method described in the first aspect.

[0200] Thirdly, the present invention provides a formulation product.

[0201] A pharmaceutical product comprising a composition prepared by the preparation method described in the first aspect.

[0202] In some embodiments, the formulation product includes a medical device or a cosmetic.

[0203] In some embodiments, the medical device includes medical dressings.

[0204] In some embodiments, the cosmetic is a functional cosmetic.

[0205] Fourthly, the present invention provides an application of the composition prepared by the preparation method described in the first aspect.

[0206] The use of a composition prepared by the method described in the first aspect in the preparation of an anti-aging pharmaceutical product.

[0207] In some embodiments, the anti-aging effect includes at least one of anti-oxidation, anti-glycation, and skin brightening.

[0208] In some embodiments, the anti-glycation includes inhibiting AGEs.

[0209] In some embodiments, the inhibition of AGEs includes inhibiting advanced glycation end product receptors.

[0210] In some embodiments, the antioxidant includes at least one of inhibiting lipofuscin and lightening pigmentation.

[0211] In some embodiments, brightening skin tone includes at least one of inhibiting lipofuscin and lightening pigmentation.

[0212] In some embodiments, the formulation product includes a medical device or a cosmetic.

[0213] In some embodiments, the medical device includes medical dressings.

[0214] In some embodiments, the cosmetic is a functional cosmetic.

[0215] Beneficial effects

[0216] Compared with the prior art, at least one of the following beneficial effects is present in a certain embodiment of the present invention:

[0217] (1) Compared with step (1) which uses other polyols or other polyol combinations, step (1) of the present invention preferably uses 1,3-butanediol to dissolve surfactant, palm bark extract and tetrahydrocurcumin, which is more conducive to improving the stability of the obtained composition under high temperature, light and high and low temperature cycling, and has unexpected technical effects.

[0218] (2) Compared with step (2) which uses other polyols or combinations of other polyols, step (2) of the present invention preferably uses 1,3-butanediol and 1,3-propanediol to dissolve phospholipids, which is more conducive to improving the stability of the obtained composition under high temperature, light and high and low temperature cycling, and has unexpected technical effects.

[0219] (3) Compared with the method of dissolving polyols with surfactants, rosewood bark extract, tetrahydrocurcumin and phospholipids without separate feeding, the present invention uses a portion of the formulation amount of 1,3-butanediol to mix and dissolve surfactants, rosewood bark extract and tetrahydrocurcumin; and the remaining polyols (1,3-butanediol and 1,3-propanediol) to mix with phospholipids. This method is more conducive to improving the stability of the obtained composition under high temperature, light and high and low temperature cycling, and has unexpected technical effects.

[0220] (4) Compared with conventional preparation methods, the present invention includes steps such as mixing and dissolving a portion of the formulation amount of 1,3-butanediol with surfactant, Dalbergia odorifera bark extract and tetrahydrocurcumin; and mixing the remaining polyols (1,3-butanediol and 1,3-propanediol) with phospholipids, which are more conducive to improving the stability of the obtained composition under high temperature, light and high and low temperature cycling, and have unexpected technical effects.

[0221] (5) Compared with other stabilizers, the stabilizer (EDTA-2Na) provided by the present invention is more conducive to improving the stability of the obtained composition under high temperature, light and high and low temperature cycling, and has unexpected technical effects.

[0222] (6) In this invention, 1,3-butanediol is preferably used to dissolve the surfactant, the extract of Dalbergia odorifera bark, and tetrahydrocurcumin. 1,3-Butanediol and 1,3-propanediol are preferably used to dissolve the phospholipids. A portion of the formulation of 1,3-butanediol is mixed with the surfactant, the extract of Dalbergia odorifera bark, and tetrahydrocurcumin for dissolution. The remaining polyols (1,3-butanediol and 1,3-propanediol) are mixed with the phospholipids for treatment. The stabilizer (EDTA-2Na) provided by this invention is preferably used. These techniques are synergistic and indispensable to each other. They synergistically promote the stability of the obtained composition under high temperature, light, and high and low temperature cycling, resulting in unexpected technical effects.

[0223] (7) The preparation method provided by the present invention is simple to operate, does not require high pressure averaging equipment, and has low equipment cost.

[0224] (8) The composition provided by the present invention has high bioavailability and good antioxidant brightening effect, as well as the effect of inhibiting lipofuscin and RAGE levels.

[0225] Terminology Explanation

[0226] In the description of this invention, "a plurality of" means two or more, unless otherwise explicitly specified.

[0227] The term “room temperature” refers to ambient temperature, which is between approximately 10°C and approximately 30°C, or approximately 20°C and approximately 30°C, or approximately 25°C.

[0228] The term "wt%" indicates a weight percentage.

[0229] The term "%vol" represents a volume percentage.

[0230] "Parts by weight" is a term without a fixed unit that expresses the relative weight ratio of each component in a composition. For example, 50 parts by weight of component A and 10 parts by weight of component B means that the weight ratio of component A to component B is 50:10.

[0231] "Balance" refers to the total weight of the system after adding all the clearly labeled components to reach 100 wt%.

[0232] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0233] In the following content, all figures disclosed herein, whether or not they use the words "approximately" or "about," are approximate values. The value of each figure may vary by 1%, 2%, 5%, 7%, 8%, 10%, 15%, or 20%. Whenever a figure with a value of N is disclosed, any figure with a value of N+ / -1%, N+ / -2%, N+ / -3%, N+ / -5%, N+ / -7%, N+ / -8%, N+ / -10%, N+ / -15%, or N+ / -20% will be explicitly disclosed, where "+ / -" indicates addition or subtraction. Detailed Implementation

[0234] To enable those skilled in the art to better understand the technical solutions of the present invention, some non-limiting embodiments are further disclosed below to provide a more detailed description of the present invention.

[0235] All reagents used in this invention can be purchased commercially or prepared by the methods described in this invention.

[0236] I. The sources or preparation methods of some of the reagents used in the various embodiments or comparative examples of this invention are as follows:

[0237] Dalbergia odorifera bark extract: purchased from Guangzhou Qingnang Biotechnology Co., Ltd., product number 23121401, product name Dalbergia odorifera bark extract.

[0238] Mirabilis jalapa extract: purchased from Naolys; contains 20 wt% Mirabilis jalapa (MIRABILIS JALAPA) extract and 80 wt% glycerin; product name: OvernightEnhance [MJ+C] Repairing and Enhancing Mirabilis jalapa.

[0239] II. Test method for tetrahydrocurcumin content

[0240] The content of tetrahydrocurcumin in the sample was determined by high performance liquid chromatography (HPLC). The chromatographic conditions for the HPLC method were as follows:

[0241] Column: Agilent Zorbax Extend C18 (4.6×150mm, 5μm);

[0242] Mobile phases: Mobile phase A: 0.1% vol phosphoric acid aqueous solution; Mobile phase B: acetonitrile;

[0243] Detection wavelength: 280nm;

[0244] Elution procedure: gradient elution, the specific elution procedure is shown in Table 1.

[0245] Table 1:

[0246]

[0247] Flow rate: 1.0 mL / min;

[0248] Column temperature: room temperature (25°C).

[0249] Examples 1-4: Preparation of the Composition

[0250] Formula: See Table 2.

[0251] Table 2: Formulation of the Composition

[0252]

[0253] Preparation methods of Examples 1 and 4:

[0254] (1) Take 30% (25%~35%) of the formulation amount of 1,3-butanediol, and mix and dissolve it with surfactant, palm bark extract and tetrahydrocurcumin at 50℃ (45℃~65℃) to obtain solution 1;

[0255] (2) Mix the remaining polyol (the remaining amount of 1,3-butanediol in the formulation + 100% of the amount of 1,3-propanediol in the formulation) with phospholipids and heat to 60°C (or 55°C~65°C) to dissolve completely to obtain solution 2;

[0256] (3) Adjust the temperature of both solution 1 obtained in step (1) and solution 2 obtained in step (2) to 50℃ (50℃~70℃), then mix and stir evenly to obtain solution 3;

[0257] (4) Mix the stabilizer and solvent evenly to obtain solution 4;

[0258] (5) Adjust the temperature of both solution 4 obtained in step (4) and solution 3 obtained in step (3) to 40°C (the temperature can be selected independently from 38°C to 45°C), then mix solution 4 and solution 3, stir, and then mix with the four o'clock extract to obtain the composition.

[0259] Preparation method of Example 2: The difference from the preparation method of Example 1 is that the amount of 1,3-butanediol added in step (1) is 25% of the 1,3-butanediol formulation amount.

[0260] Preparation method of Example 3: The difference from the preparation method of Example 1 is that the amount of 1,3-butanediol added in step (1) is 35% of the 1,3-butanediol formulation amount.

[0261] Comparative Example 1: Investigation of the types of polyols added in step (1)

[0262] Comparative Example 1: The only difference from Example 1 is that:

[0263] (1) Take 30% of the 1,3-propanediol formulation amount of 1,3-propanediol and the surfactant, the extract of the bark of the rosewood tree and the tetrahydrocurcumin and mix and dissolve them at 50°C to obtain solution 1;

[0264] (2) Mix the remaining polyol (1,3-butanediol in 100% of the formulation amount + 1,3-propanediol in ...

[0265] Steps (3) to (5) are the same as steps (3) to (5) in Example 1.

[0266] Comparative Example 2: Investigation of the types of polyols added in step (1)

[0267] Comparative Example 2: The only difference from Example 1 is that:

[0268] (1) Take 15% 1,3-butanediol formulation amount of 1,3-butanediol, 15% 1,3-propanediol formulation amount of 1,3-propanediol, surfactant, Dalbergia odorifera bark extract, and tetrahydrocurcumin and mix and dissolve them at 50℃ to obtain solution 1;

[0269] (2) Mix the remaining polyol (the amount of 1,3-butanediol in the formula and the amount of 1,3-propanediol in the formula) with phospholipids and heat to 60°C until completely dissolved to obtain solution 2;

[0270] Steps (3) to (5) are the same as steps (3) to (5) in Example 1.

[0271] Comparative Examples 3-4: Investigation of the types of polyols added in step (1)

[0272] Comparative Example 3: The only difference from Example 1 is that 1,3-butanediol in the formulation and preparation method is replaced with glycerol, and the other conditions are the same as in Example 1.

[0273] Comparative Example 4: The only difference from Example 1 is that 1,3-butanediol in the formulation and preparation method is replaced with isohexanediol, and the other conditions are the same as in Example 1.

[0274] Comparative Example 5: Investigation of the types of polyols added in step (2)

[0275] Comparative Example 5: The only difference from Example 1 is that:

[0276] (1) Take 100% of the 1,3-butanediol formulation amount of 1,3-butanediol and the surfactant, the extract of the bark of the rosewood tree and the tetrahydrocurcumin and mix and dissolve them at 50°C to obtain solution 1;

[0277] (2) Mix the remaining polyol (1,3-propanediol in 100% of the formulation amount) with phospholipids and heat to 60°C (or 55°C-65°C) to dissolve completely to obtain solution 2;

[0278] Steps (3) to (5) are the same as steps (3) to (5) in Example 1.

[0279] Comparative Examples 6-7: Investigation of the types of polyols added in step (2)

[0280] Comparative Example 6: The only difference from Example 1 is that 1,3-propanediol in the formulation and preparation method is replaced with dipropaneglycol, and the other conditions are the same as in Example 1.

[0281] Comparative Example 7: The only difference from Example 1 is that 1,3-propanediol in the formulation and preparation method is replaced with 1,2-pentanediol, and the other conditions are the same as in Example 1.

[0282] Comparative Example 8: Polyols are not fed separately

[0283] Comparative Example 8: The formulation of Comparative Example 8 is the same as that of Example 1, and its preparation method includes:

[0284] (1) 1,3-Butanediol, 1,3-propanediol, surfactant, Dalbergia odorifera bark extract, tetrahydrocurcumin and phospholipids were mixed and dissolved at 50°C to obtain solution A;

[0285] (2) Mix the stabilizer with water until homogeneous to obtain solution B;

[0286] (3) Adjust the temperature of both solution B obtained in step (2) and solution A obtained in step (1) to 40°C, then pour solution B into solution A, stir until completely homogeneous, and finally add the four o'clock extract to obtain the composition.

[0287] Comparative Example 9: Conventional Preparation Method

[0288] Comparative Example 9: The only difference from Example 1 is the preparation method. The preparation method of Comparative Example 9 includes:

[0289] (1) Mix surfactant, polyol and phospholipid, heat to 65℃~70℃ to dissolve, then add rosewood bark extract and tetrahydrocurcumin and mix and dissolve at 65℃~70℃ to obtain solution 1;

[0290] (2) Cool solution 1 to 45℃~48℃ and mix it with water at 45℃-48℃ to obtain solution 2. Cool it to 30℃-35℃ and then mix and dissolve solution 2 with the extract of Mirabilis jalapa and the stabilizer to obtain solution 3.

[0291] (3) The composition was obtained by homogenizing solution 3 under high pressure (600 bar, 4 times, 3 min each time).

[0292] Comparative Examples 10-11: Investigation of Stabilizers

[0293] Comparative Example 10: The only difference from Example 1 is that the stabilizer is replaced with citric acid, and the other conditions are the same as in Example 1.

[0294] Comparative Example 11: The only difference from Example 1 is that the stabilizer is replaced with arginine, and the other conditions are the same as in Example 1.

[0295] Comparative Example 12: Conventional preparation method without adding stabilizers

[0296] Formula: See Table 3.

[0297] Table 3:

[0298]

[0299] Preparation method: The only difference between this preparation method and that of Comparative Example 9 is that no stabilizer is added; the rest of the operation is the same as that of Comparative Example 9.

[0300] Experimental Example 1: Stability Study

[0301] High-temperature stability test: The products obtained in the above examples and test examples were placed at 50°C to test product stability (appearance and tetrahydrocurcumin content) for 3 months. The results are shown in Tables 4 and 5.

[0302] Strong light irradiation test: The products obtained in each of the above embodiments or comparative examples were placed in transparent containers and placed in a light box with an illuminance of 4500 lx ± 500 lx for 10 days. Samples were taken on the 5th and 10th days for testing. The results are shown in Tables 4 and 5.

[0303] High and low temperature cycling: The sample to be tested was placed in a high and low temperature cycling chamber. The conditions were set as follows: placed at 45℃ for 24 hours, then restored to room temperature for 12 hours, then placed at -15℃ for 24 hours, and then restored to room temperature for 12 hours. This constitutes one high and low temperature cycle. Each sample to be tested needs to be tested for six cycles, and its stability is observed. The results are shown in Tables 4 and 5.

[0304] Table 4: Results of appearance characteristics during stability study

[0305]

[0306] Table 5: Results of the stability study on tetrahydrocurcumin content

[0307]

[0308] The tetrahydrocurcumin mentioned in Experimental Example 1 represents the percentage of the measured amount of tetrahydrocurcumin to the theoretical amount.

[0309] Results analysis:

[0310] (1) Compared with step (1) which uses other polyols or other polyol combinations (see Comparative Examples 1 to 4), step (1) of the present invention preferably uses 1,3-butanediol to dissolve surfactants, Dalbergia odorifera bark extract and tetrahydrocurcumin, which is more conducive to improving the stability of the obtained composition under high temperature, light and high and low temperature cycling, and has unexpected technical effects.

[0311] (2) Compared with step (2) which uses other polyols or other polyol combinations (see Comparative Examples 5 to 7), step (2) of the present invention preferably uses 1,3-butanediol and 1,3-propanediol to dissolve phospholipids, which is more conducive to improving the stability of the obtained composition under high temperature, light and high and low temperature cycling, and has unexpected technical effects.

[0312] (3) Compared with the method of dissolving polyols with surfactants, rosewood bark extract, tetrahydrocurcumin and phospholipids without separate feeding, the present invention uses a portion of the formulation amount of 1,3-butanediol to mix and dissolve surfactants, rosewood bark extract and tetrahydrocurcumin; and the remaining polyol (1,3-butanediol + 1,3-propanediol) is mixed with phospholipids for treatment, which is more conducive to improving the stability of the obtained composition under high temperature, light and high and low temperature cycling, and has unexpected technical effects.

[0313] (4) Compared with conventional preparation methods (see Comparative Examples 9 and 12), the present invention includes steps such as mixing and dissolving a portion of the formulation amount of 1,3-butanediol with surfactant, Dalbergia odorifera bark extract and tetrahydrocurcumin; and mixing the remaining polyol (1,3-butanediol + 1,3-propanediol) with phospholipids, which is more conducive to improving the stability of the obtained composition under high temperature, light and high and low temperature cycling, and has unexpected technical effects.

[0314] (5) Compared with other stabilizers (see Comparative Examples 10 and 11), the stabilizer (EDTA-2Na) provided by the present invention is more conducive to improving the stability of the obtained composition under high temperature, light and high and low temperature cycling, and has unexpected technical effects.

[0315] (6) In this invention, 1,3-butanediol is preferably used to dissolve the surfactant, the extract of Dalbergia odorifera bark, and tetrahydrocurcumin. 1,3-Butanediol and 1,3-propanediol are preferably used to dissolve the phospholipids. A portion of the formulation of 1,3-butanediol is mixed with the surfactant, the extract of Dalbergia odorifera bark, and tetrahydrocurcumin for dissolution. The remaining polyol (1,3-butanediol + 1,3-propanediol) is mixed with the phospholipids for treatment. The stabilizer (EDTA-2Na) provided by this invention is preferably used. These techniques are synergistic and indispensable to each other. They synergistically promote the stability of the obtained composition under high temperature, light, and high and low temperature cycling, resulting in unexpected technical effects.

[0316] Experiment Example 2: Human Efficacy Evaluation Experiment

[0317] (1) Human skin color L test

[0318] Thirty-two eligible volunteers, half male and half female, aged 23–47 years, were selected. Test areas were marked on the left and right sides of each volunteer's face (the left cheek was the test sample (containing the composition of Example 1), and the right cheek was a blank sample without any treatment). The lotion was applied twice daily, once at 9:00 AM and once at 8:00 PM. During the experiment, volunteers were not allowed to apply any other cosmetics to the test areas. After one month of continuous use of the test lotion, on days 7, 14, 21, and 28, volunteers washed the applied areas with water, and the testers measured the skin color L-value of the applied areas using a spectrophotometer. The skin color L-value characterizes the brightness of the skin; the higher the L-value, the more lustrous the skin. The test results are shown in Table 6.

[0319] Table 6: Results of Human Skin Color L-Value Test

[0320]

[0321] Results analysis: As shown in Table 5 of the human efficacy test results, after 14 and 28 days of continuous use of the product containing the composition test sample, the subjects' skin L value was significantly improved compared with the baseline value, indicating that the test sample has the effect of improving skin brightness.

[0322] (2) RAGE inhibition

[0323] Human skin fibroblasts (HSF) in the logarithmic growth phase were digested with 0.25% trypsin, centrifuged, and then prepared into a cell suspension of appropriate density (1.0*10⁻⁶) using complete culture medium. 5 Cells were seeded into 12-well plates at a concentration of 1 mL per well and incubated at 37°C with 5% CO2 for 24 ± 2 h. The culture medium in the cell culture plates was discarded, and drug administration was performed. Serum-free culture medium was added to the blank wells, serum-free culture medium containing 0.5 mM MGO (methylglyoxal) and 0.1 wt% (based on the total weight of the test composition) of the test composition was added to the test sample wells, serum-free culture medium containing 0.5 mM MGO was added to the model group wells, and serum-free culture medium containing 0.5 mM MGO and 0.5 mM aminoguanidine hydrochloride was added to the positive control wells. 1 mL of the solution was added to each well of the 12-well plate (aminoguanidine hydrochloride was used as a positive control). The plates were then incubated in a CO2 incubator for 4 h ± 15 min. After incubation, discard the culture medium in the cell culture plate, add 1 mL of DPBS to each well for washing, and collect RNA and determine the concentration according to the kit (Human Advanced Glycosylation Advanced Product Receptor (RAGE;AGER) ELISA Kit, Nanjing Boyan Biotechnology, Catalog No.: BY-EH111412). The test results are shown in Table 7.

[0324] Table 7: RAGE inhibition rate results

[0325]

[0326] Results analysis: The composition provided by the present invention has excellent RAGE inhibition effect, indicating that the composition provided by the present invention has excellent anti-glycation and anti-skin aging effects.

[0327] (3) Inhibition of lipofuscin

[0328] Human skin fibroblasts (HSF) in the logarithmic growth phase were digested with 0.25% trypsin, centrifuged, and then prepared into a cell suspension of appropriate density (1.0*10⁻⁶) using complete culture medium. 5Cells were seeded into 24-well plates at a concentration of 0.5 mL per well and incubated at 37°C with 5% CO2 for 24 ± 2 h. The culture medium in the cell culture plates was discarded, and drug administration was performed. Serum-free culture medium was added to the blank wells, serum-free culture medium containing 0.5 mM MGO (methylglyoxal) and 0.1 wt% (based on the total weight of the test composition) of the test composition was added to the test sample wells, serum-free culture medium containing 0.5 mM MGO was added to the model group wells, and serum-free culture medium containing 0.5 mM MGO and 0.5 mM aminoguanidine hydrochloride (aminoguanidine hydrochloride was the positive control drug) was added to the positive control wells. 0.5 mL of the solution was added to each well of the 24-well plate. The plates were then incubated in a CO2 incubator for 4 h ± 15 min. After incubation, discard the culture medium in the culture plate, wash once with DPBS (Dupuy's phosphate-buffered saline), add 0.5 ml of 4% paraformaldehyde to each well for cell fixation, and fix at room temperature for 30 min. After fixation, wash three times with DPBS, add 0.2 ml of Oil Red O staining solution to each well, and incubate at room temperature for 60 min. After incubation, discard the staining solution, gently rinse the cells 2-3 times with PBS (phosphate-buffered saline), observe and photograph under a microscope, and measure the absorbance using a microplate reader (detection wavelength: 450 nm). The test results are shown in Table 8.

[0329] Table 8: Results of Lipofuscin Inhibition Rate

[0330]

[0331] Results analysis: The composition provided by the present invention has excellent inhibitory effects on lipofuscin, indicating that the composition provided by the present invention has excellent antioxidant, age spot lightening, pigmentation lightening, and skin aging delaying effects.

[0332] The method of this invention has been described through preferred embodiments. Those skilled in the art will readily be able to modify or appropriately alter and combine the methods and applications described herein within the scope, spirit, and context of this invention to implement and apply the technology of this invention. Those skilled in the art can refer to the content herein to appropriately improve process parameters. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included within the scope of this invention.

Claims

1. A method for preparing a composition having anti-glycation, inhibitory effect on advanced glycation end product receptors, and brightening effect, characterized in that, The composition comprises the following components in parts by weight: Dalbergia odorifera bark extract: 0.4~2 parts by weight; Tetrahydrocurcumin: 0.3~1.0 parts by weight; Mirabilis jalapa extract: 0.1~0.5 parts by weight; Surfactant: 3-30 parts by weight; Polyols: 50-80 parts by weight; Stabilizer: 0.01~0.5 parts by weight; Phospholipids: 0.5~1 part by weight; Solvent: 5~45.6 parts by weight; in, The polyols are 1,3-butanediol and 1,3-propanediol; The stabilizer is disodium ethylenediaminetetraacetate; The solvent includes water; The weight ratio of 1,3-butanediol to 1,3-propanediol is 1:1 to 5:

1. The surfactant is selected from at least one of oleyl alcohol polyether-20, polyglycerol-10 stearate, and polyglycerol-10 oleate; The preparation method includes the following steps: (1) Take 25%~35% of the 1,3-butanediol formulation amount of 1,3-butanediol and mix it with surfactant, Dalbergia odorifera bark extract and tetrahydrocurcumin to obtain solution 1; (2) Mix the remaining polyol with phospholipids and heat until completely dissolved to obtain solution 2; (3) Mix solution 1 and solution 2 thoroughly to obtain solution 3; (4) Mix the stabilizer and solvent evenly to obtain solution 4; (5) Mix solution 4 with solution 3, stir, and then mix with the four o'clock extract to obtain the composition.

2. The preparation method according to claim 1, characterized in that, The mixing and dissolution temperature in step (1) is 45℃~65℃; and / or The heating temperature in step (2) is 55℃~65℃; and / or In step (3), the temperature of solution 1 and solution 2 before mixing is 50℃~70℃; and / or In step (5), before solution 4 is mixed with solution 3, the temperatures of solution 3 and solution 4 are independently selected from 38℃ to 45℃; and / or The stirring temperature in step (5) is 38℃~45℃.

3. The preparation method according to claim 1, characterized in that, The phospholipids include soybean lecithin; and / or The four o'clock extract includes four o'clock extract and glycerin.

4. The preparation method according to any one of claims 1 to 3, characterized in that, The four o'clock extract is composed of four o'clock extract and glycerin, wherein the content of four o'clock extract in the four o'clock extract is 10 wt% to 30 wt%.

5. The preparation method according to any one of claims 1 to 3, wherein the composition comprises the following components: Extracts from the bark of the rosewood tree, tetrahydrocurcumin, extract from the four o'clock flower, surfactants, polyols, stabilizers, phospholipids, and solvents.

6. The preparation method according to any one of claims 1 to 3, wherein, based on the total weight of the composition, the content of the *Palmaria lobata* bark extract is 0.4 wt% to 2 wt%, the content of the tetrahydrocurcumin is 0.3 wt% to 0.8 wt%, the content of the *Mirabilis jalapa* extract is 0.1 wt% to 0.5 wt%, the total content of the surfactant is 3 wt% to 30 wt%, the total content of the polyol is 50 wt% to 80 wt%, the content of the stabilizer is 0.01 wt% to 0.5 wt%, the content of the phospholipid is 0.5 wt% to 1.0 wt%, and the content of the solvent is 5 wt% to 45.6 wt%.

7. A composition having anti-glycation, inhibitory effects on advanced glycation end product receptors, and brightening effects, characterized in that, It is prepared according to any one of claims 1 to 6.

8. A pharmaceutical preparation, characterized in that, The composition includes the preparation method according to any one of claims 1 to 6; the formulation product is a medical dressing or a cosmetic.

9. The formulation product according to claim 8, wherein the cosmetic is a functional cosmetic.

10. The use of the composition prepared by the method according to any one of claims 1 to 6 in the preparation of an anti-aging pharmaceutical product; wherein the pharmaceutical product is a medical dressing or a cosmetic.

11. The application according to claim 10, wherein the cosmetic is a functional cosmetic.

12. The application according to claim 10, wherein the composition has a skin-brightening effect.

13. The application according to claim 10, wherein the composition has the effect of inhibiting lipofuscin.

14. The application according to claim 10, wherein the composition has the effect of inhibiting advanced glycation end product receptors.

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