Tripterine derivatives as well as preparation method and application thereof

Abstract

The invention discloses a tripterine derivative as well as a preparation method and application thereof. The tripterine derivative provided by the invention is prepared by coupling the tripterine and the sphingosine base compound, retains the anti-inflammatory and antioxidant activity of the tripterine, and has a better effect than the tripterine; meanwhile, the tripterine derivative remarkably reduces the toxicity and irritation of tripterine and improves the skin compatibility and safety, so that the risk in clinical or skin care application is reduced. The preparation method provided by the invention is simple and efficient, adopts a green coupling agent HOPO for reaction, is safe, stable and lower in cost, can prepare a safer and milder tripterine substitute raw material with a better effect, can be used for developing more anti-inflammatory, barrier repair and anti-aging skin care products or cosmetics, and has wide application prospects. And various dosage forms of external washing products such as O / W emulsion, W / O cream and the like containing the tripterine derivative are produced and prepared.

Description

Technical Field

[0001] This invention relates to the fields of pharmaceuticals and cosmetics, and more specifically, to a class of triptolide derivatives, their preparation methods, and applications. Background Technology

[0002] Celastrol (also known as Southern Celastrusin) is derived from the Celastraceae plant Tripterygium wilfordii (Tripterygium wilfordii). Tripterygium wilfordii Pentacyclic triterpenoids extracted from plants of the genus *Celastrus* (Hook. f.) are one of the core active ingredients responsible for the pharmacological effects of *Tripterygium wilfordii*. Its main effects include anti-inflammatory, immunomodulatory, antioxidant, and antitumor activity. It has been shown to inhibit the production of inflammatory factors (such as TNF-α, IL-6, IL-1β, and PGE2), regulate T lymphocyte activity, and possess antioxidant capacity 15 times stronger than tocopherol. Clinically, it is often used to treat autoimmune diseases such as rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, as well as chronic inflammations such as nephritis and inflammatory bowel disease. However, the high toxicity and skin irritation of triptolide limit its application in cosmetic raw materials.

[0003] In the beauty and skincare industry, consumers are increasingly demanding "natural, safe, and effective" active ingredients. While triptolide has demonstrated superior efficacy in anti-inflammatory, whitening, and anti-aging tests, its high toxicity and irritation prevent its direct application in skincare formulations. Current research primarily focuses on exploring triptolide derivatives or low-toxicity, high-efficiency analogs to develop more safe and effective cosmetic ingredients in the future. Current research on triptolide structural modification and derivative development involves modifying the active groups of triptolide (such as carboxyl groups and quinone methylates) to retain its potent pharmacological activity while significantly reducing its toxicity. For example, linking the C-28 carboxyl group to amino acids, glycosides, or other safe molecules creates prodrugs or derivatives to improve safety and water solubility. However, there are currently few triptolide derivatives developed that are highly effective for skincare and cosmetic preparations and possess low toxicity and low irritation. Therefore, developing more derivatives with low toxicity, high safety, and while retaining the core efficacy of natural triptolide is particularly urgent and important. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to overcome the problems of high toxicity and irritation of existing triptolide, which makes it difficult to apply to the skin for external use, skin care or cosmetics. The present invention provides a class of triptolide derivatives, their preparation methods and applications.

[0005] The first objective of this invention is to provide a class of triptolide derivatives.

[0006] A second objective of this invention is to provide a method for preparing triptolide derivatives.

[0007] A third objective of this invention is to provide applications of triptolide derivatives.

[0008] The fourth objective of this invention is to provide a topical product.

[0009] The above-mentioned objective of this invention is achieved through the following technical solution: This invention provides a class of triptolide derivatives, the structural formula of which is shown below: ; In the formula: R1 is selected from One of them.

[0010] This invention utilizes the coupling of triptolide with sphingosine-based base compounds (sphingosine, dihydrosphingosine, or phytosphingosine) to obtain triptolide derivatives that effectively retain the core pharmacological activities of triptolide, including inhibiting PGE2 production, reducing inflammatory factor levels, and enhancing antioxidant enzyme activity to scavenge free radicals. Structural optimization reduces the toxicity of triptolide; compared to triptolide, its derivatives exhibit significantly reduced cytotoxicity and irritation, making them well-suited as anti-inflammatory and antioxidant raw materials for use in anti-inflammatory, soothing, barrier repair, and anti-aging skincare products. Furthermore, this invention provides a method for preparing triptolide derivatives using a green synthetic route. Triptolide is activated with EDCI / HOPO, reacted with a sphingosine base, and then purified to obtain the product. This method is simple to operate and has a high yield (74.5%-80.5%). This invention provides a more effective, safer, and gentler alternative to triptolide, which can be used in the manufacture of chemical pharmaceutical raw materials or preparations and biological drugs. It can also be used to develop more anti-inflammatory, soothing, barrier-repairing, and anti-aging skin care or cosmetic products, and to produce various dosage forms of topical cleansing and care products such as O / W lotions and W / O creams.

[0011] Preferably, the structural formula of the triptolide derivative provided by the present invention is as follows:

[0012] This invention provides a method for preparing triptolide derivatives: under ice bath conditions, triptolide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), and 2-hydroxypyridine-N-oxide (HOPO) are dissolved in an organic solvent and activated; then a catalyst and a sphingosine base compound are added and reacted at room temperature for 12-24 h; after the reaction is complete, the product is washed and purified to obtain triptolide derivatives.

[0013] Preferably, the reaction conditions are: stirring and activation at 5-20℃ under argon protection for 1-3 hours; stirring the reaction system at 20-30℃ for 12-24 hours.

[0014] Preferably, the sphingosine base compound is selected from sphingosine, dihydrosphingosine, or phytosphingosine, and its structural formula is shown below:

[0015] Preferably, the molar ratio of each component in the reaction system is: triptolide: EDCI: HOPO: catalyst: sphingosine base compound = 1: (1-1.5): (1-1.5): (0-0.5): (1-1.2).

[0016] Preferably, the catalyst is selected from 4-dimethylaminopyridine or 4-pyrrolidinylpyridine.

[0017] Preferably, the organic solvent is selected from tetrahydrofuran or 2-methyltetrahydrofuran.

[0018] This invention provides the application of triptolide derivatives in the preparation of anti-inflammatory, antioxidant, and anti-aging products.

[0019] Preferably, the product exerts its anti-aging effect by improving the level of oxidative stress in the skin.

[0020] This invention provides the application of triptolide derivatives in the preparation of skin care or skin barrier repair products.

[0021] Preferably, the product can be used for anti-inflammatory and soothing purposes, acne treatment, and improvement of inflammation-related skin problems.

[0022] More preferably, the product is a skin care product, cosmetic, or topical daily chemical preparation.

[0023] The present invention also provides a topical product containing the above-mentioned triptolide derivative.

[0024] Preferably, the product contains 0.05-1 wt% triptolide derivative.

[0025] Preferably, the product is an O / W emulsion, W / O cream, anhydrous oil gel, transparent oil phase essence, microemulsion, face cream, shampoo / conditioner, or body care product.

[0026] More preferably, the product also contains emulsifiers, soothing agents, preservatives, antioxidants, humectants, auxiliary active ingredients, solvents, etc.

[0027] As a preferred feasible solution, the present invention provides a repairing face cream containing triptolide-phytosphingosine, the main active ingredient being 0.5-1% of a triptolide derivative, and comprising the following components: Emulsifier: Cetearyl alcohol + Cetearyl alcohol polyether-20: 2~5%; Oil phase components: Squalane: 3-8%; Jojoba oil: 1-5%; Octyldodecyl alcohol: 8-15%; Co-active ingredients: Centella asiatica extract: 0.5-2%; Vitamin E acetate: 0.1-1%; Soothing agent: Allantoin: 0.1-1%; Preservative system: Phenoxyethanol: 0.1-1%; Ethylhexylglycerin: 0.1-1%; Solvents: Glycerin: 3-8%; Butylene glycol: 1-5%; Xanthan gum: 0.1-0.8%; Deionized water to bring to 100%.

[0028] The preparation method for this face cream is as follows: (1) Mix the aqueous phase (water, glycerol, butylene glycol, xanthan gum) and heat to 75°C; (2) Mix the oil phase (octyldodecyl alcohol, squalane, jojoba oil, emulsifier) ​​and heat to 85°C. Add tripterygium oleoresin derivative and stir until completely dissolved. (3) After emulsifying the aqueous phase and the oil phase, cool to 40°C, add Centella asiatica extract, vitamin E acetate, allantoin and preservative, and mix well to obtain the final product.

[0029] The present invention has the following beneficial effects: The triptolide derivative provided by this invention is prepared by coupling triptolide with a sphingosine-based base compound. This derivative retains the anti-inflammatory and antioxidant activities of triptolide and has better effects than triptolide. Simultaneously, it significantly reduces the toxicity and irritation of triptolide, improves skin compatibility and safety, and can significantly reduce the risks in clinical or skincare applications. The preparation method of the derivative provided by this invention is simple and efficient, using the green coupling agent HOPO for the reaction. It is safe, stable, and lower in cost, and can produce a more effective, safer, and gentler triptolide alternative raw material. This can be used to develop more anti-inflammatory, barrier repair, and anti-aging skincare or cosmetic products, filling a market gap in the cosmetic field. Furthermore, it can be used to produce more topical care products containing triptolide derivatives in various dosage forms such as O / W emulsions and W / O creams. Attached Figure Description

[0030] Figure 1 The image shows the 1H NMR spectrum of the triptolide-phytosphingosine derivative obtained in Example 1.

[0031] Figure 2 The image shows the 1H NMR spectrum of the triptolide-sphingosine derivative obtained in Example 2.

[0032] Figure 3The image shows the 1H NMR spectrum of the triptolide-dihydrosphingosine derivative obtained in Example 3.

[0033] Figure 4 This is a graph showing the changes in the skin redness a* value of the subjects. Detailed Implementation

[0034] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0035] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0036] The reagents used in the examples were of analytical grade or higher, and the reactions were carried out under an inert atmosphere. The purities of triptolide, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), and 2-hydroxypyridine-N-oxide (HOPO) were all above 98%. The HPLC purities of sphingosine, phytosphingosine, and dihydrosphingosine were above 90%. The catalyst, 4-dimethylaminopyridine (DMAP), was above 98%. Anhydrous tetrahydrofuran (THF) and 2-methyltetrahydrofuran (2-MeTHF) were used as solvents. Monitoring was performed using TLC / HPLC. Purification was performed using silica gel column chromatography or recrystallization.

[0037] NMR spectra were characterized using a Bruker DPX 400 NMR instrument. 1 ¹H NMR was performed at 400 MHz using deuterated chloroform or deuterated methanol as solvent, with tetramethylsilane (TMS) as an internal standard. Chemical shifts are expressed in ppm, and coupling constants are expressed in Hz. 1 In H NMR, δ represents chemical shift, s represents singlet, d represents doublet, t represents triplet, q represents quartet, and m represents multiplet.

[0038] Example 1: Preparation of triptolide-phytosphoside derivatives Tripterygium wilfordii (10 mmol), EDCI (15 mmol), and HOPO (15 mmol) were placed in a 150 mL round-bottom flask, and 50 mL of tetrahydrofuran was added. The mixture was stirred and activated at 5 °C under argon protection for 2 h. Then, 20 mL of a tetrahydrofuran solution containing phytosphingosine (10 mmol) was added. The reaction system was stirred at 25 °C for 18 h until the phytosphingosine feedstock was completely consumed by TLC. The reaction mixture was then quenched with water, washed once with saturated sodium bicarbonate solution, and then washed once with saturated brine. The mixture was dried, filtered, and evaporated to dryness to obtain the crude product. The crude product was purified by column chromatography to obtain 6.01 g of pure product, with a yield of 80.5%. The chemical structure of the obtained compound is shown below: .

[0039] The synthetic route of the compound is as follows: .

[0040] The proton NMR spectrum of the compound is as follows Figure 1 As shown, 1 H NMR and 13 The characterization results of C NMR are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.06 (d, J = 7.0 Hz, 2H), 6.89 (s, 1H), 6.56 (s, 1H), 6.37 (d, J = 7.2 Hz, 1H), 4.02 (s, 1H), 3.84 (s, 1H), 3.63 (s, 1H), 3.47 (s, 2H), 2.36 (d, J = 15.6 Hz, 1H), 2.22 (s, 3H), 2.19 - 1.99 (m, 3H), 1.97 - 1.81 (m, 3H), 1.80 - 1.62 (m, 4H), 1.62 - 1.46 (m, 4H), 1.44 (s, 4H), 1.24 (d, J = 21.8 Hz, 30H), 1.11 (s, 3H), 1.00 (d, J = 13.2 Hz, 1H), 0.89 (t, J = 6.7 Hz, 3H), 0.67 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 179.23, 178.31, 170.99, 165.12, 146.15, 134.91, 127.36, 119.33, 118.21, 117.85, 76.53, 72.50, 61.29, 53.06, 45.14,44.43, 43.12, 40.23, 39.45, 38.18, 36.27, 34.87, 33.87, 33.45, 33.29, 31.95,31.60, 31.43, 30.71, 29.98, 29.77, 29.73, 29.71, 29.45, 29.40, 28.68, 25.79, 22.72, 21.74, 18.53, 14.16, 10.31. Example 2 Preparation of triptolide-sphingosine derivatives Tripterygium wilfordii (10 mmol), EDCI (13 mmol), and HOPO (13 mmol) were placed in a 150 mL round-bottom flask, and 50 mL of tetrahydrofuran was added. The mixture was stirred and activated for 2 h at 10 °C under argon protection. Then, 20 mL of a tetrahydrofuran solution containing DMAP (3 mmol) and sphingosine (11 mmol) was added. The reaction system was stirred at 25 °C for 12 h until TLC monitoring showed complete consumption of the sphingosine starting material. The reaction mixture was quenched with water, washed once with 2N dilute hydrochloric acid aqueous solution, once with saturated sodium bicarbonate aqueous solution, and once with saturated brine. The mixture was dried, filtered, and evaporated to dryness to obtain the crude product. The crude product was purified by column chromatography to obtain 5.75 g of pure product, with a yield of 78.5%. The chemical structure of the obtained compound is shown below: .

[0041] The synthetic route of the compound is as follows: .

[0042] The proton NMR spectrum of the compound is as follows Figure 2 As shown, 1 H NMR and 13 The characterization results of C NMR are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.05 (d, J = 7.0 Hz, 1H), 7.00 (s, 1H), 6.71 (d, J = 6.9 Hz, 1H), 6.54 (s, 1H), 6.36 (d, J = 7.1 Hz, 1H), 5.73 (dt, J = 14.2, 6.7 Hz, 1H), 5.44 (dd, J = 15.4, 5.7 Hz, 1H), 4.17 (d, J = 8.2Hz, 1H), 3.89 - 3.71 (m, 2H), 3.67 - 3.44 (m, 3H), 2.43 (d, J = 15.8 Hz, 1H), 2.22 (s, 3H), 2.19 - 1.81 (m, 10H), 1.81 - 1.64 (m, 3H), 1.64 - 1.47 (m, 5H), 1.44 (s, 4H), 1.38 - 1.17 (m, 26H), 1.13 (s, 4H), 1.07 - 0.96 (m, 1H), 0.89 (t, J = 6.7 Hz, 4H), 0.70 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 178.96, 178.28, 170.77, 165.04, 146.04, 134.65, 133.78, 128.82, 127.34, 119.35, 118.14, 117.49, 74.30, 62.23, 54.85,45.12, 44.44, 43.09, 40.37, 39.46, 38.19, 36.35, 34.90, 34.02, 33.49, 32.33,31.94, 31.63, 31.24, 30.75, 30.11, 29.72, 29.68, 29.65, 29.52, 29.43, 29.38, 29.32, 29.13, 28.66, 22.71, 21.73, 18.45, 14.15, 10.30. Example 3 Preparation of triptolide-dihydrosphingosine derivatives Tripterygium wilfordii (10 mmol), EDCI (11 mmol), and HOPO (11 mmol) were placed in a 150 mL round-bottom flask, and 50 mL of 2-methyltetrahydrofuran was added. The mixture was stirred and activated at 10 °C under argon protection for 2 h. Then, 25 mL of a 2-methyltetrahydrofuran solution containing 4-pyrrolidinylpyridine (5 mmol) and dihydrosphingosine (13 mmol) was added. The reaction system was stirred at 25 °C for 24 h until TLC monitoring showed complete consumption of the dihydrosphingosine starting material. The reaction mixture was quenched with water, washed once with 2N dilute hydrochloric acid aqueous solution, once with saturated sodium bicarbonate aqueous solution, and once with saturated brine. The mixture was dried, filtered, and evaporated to dryness to obtain the crude product. The crude product was purified by column chromatography to obtain 5.48 g of pure product, yield: 74.5%. The chemical structure of the obtained compound is shown below: .

[0043] The synthetic route of the compound is as follows: .

[0044] The proton NMR spectrum of the compound is as follows Figure 3 As shown, 1 H NMR and 13 The characterization results of C NMR are as follows: 1H NMR (400 MHz, Chloroform-d) δ 7.06 (dd, J = 7.1, 1.3 Hz, 1H), 7.00 (s, 1H), 6.80 (d, J = 7.8 Hz, 1H), 6.56 (d, J = 1.4 Hz, 1H), 6.37 (d, J = 7.2Hz, 1H), 3.93 (d, J = 11.0 Hz, 1H), 3.73 (dd, J = 7.3, 3.5 Hz, 1H), 3.70 -3.57 (m, 2H), 2.43 (d, J = 15.8 Hz, 1H), 2.23 (s, 3H), 2.20 - 2.04 (m, 3H), 1.90 (tq, J = 9.6, 5.2, 4.0 Hz, 3H), 1.82 - 1.65 (m, 7H), 1.65 - 1.39 (m, 11H), 1.36 - 1.18 (m, 35H), 1.14 (s, 3H), 1.08 - 0.97 (m, 1H), 0.90 (t, J =6.8 Hz, 3H), 0.70 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 178.45, 178.32, 170.71, 165.03, 146.06, 134.60, 127.35, 119.36, 118.14, 117.47, 74.29, 62.11, 53.83, 45.12, 44.44,43.09, 40.32, 39.45, 38.19, 36.31, 34.94, 34.45, 34.06, 33.47, 31.94, 31.63,31.25, 30.77, 30.08, 29.72, 29.68, 29.64, 29.60, 29.56, 29.41, 29.38, 28.68, 26.01, 22.71, 21.77, 18.41, 14.15, 10.29. Example 4 Cytotoxicity Test Perform HaCaT cell viability testing (MTT): This test is used to evaluate the efficacy of skincare products in protecting the skin's epidermal barrier, repairing the skin, and assessing the gentleness (anti-irritation) of the ingredients. It measures the effects of ingredients on epidermal cells by detecting changes in the viability of immortalized human keratinocytes (HaCaT cells, which mimic skin epidermal cells).

[0045] The experimental samples were grouped as follows: the compound group from Examples 1-3, the triptolide group, and the blank control group (DMEM medium without the drug). DMEM medium was prepared using DMSO-glycerol to dilute the samples, and the concentrations of the compound group and the triptolide group were set at 25 mg / L, 100 mg / L, 200 mg / L, 400 mg / L, and 800 mg / L, respectively. The samples at different concentrations were co-incubated with HaCaT cells for 24 h, and cell viability was then monitored.

[0046] The results are shown in Table 1. The compounds in Examples 1-3 did not exhibit cytotoxicity at concentrations up to 800 mg / L, and showed some effect in enhancing cell viability at low concentrations. At a concentration of 25 mg / L, the compounds in Examples 1-3 enhanced cell viability by 103.8%, 101.2%, and 100.7%, respectively. In contrast, triptolide showed significant cytotoxicity to HaCaT cells at concentrations exceeding 100 mg / L, with cell viability decreasing to 72.45%, 61.23%, and 50.18% at concentrations of 100 mg / L, 200 mg / L, and 400 mg / L, respectively. These results indicate that the triptolide derivatives in Examples 1-3 exhibited significantly lower cytotoxicity and better safety compared to triptolide alone.

[0047] Table 1. Cell viability results under different sample treatments

[0048] Example 5 Stimulation Test Eye irritation safety assessment: The chicken embryo chorioallantoic membrane vascular test (CAMVA) is an important method for assessing eye irritation safety. After the sample has been in contact with the chicken embryo for a period of time, the irritant effect of the test sample is evaluated by comparing the changes in blood vessels before and after sample addition, thus determining whether the test sample is eye irritating.

[0049] Taking advantage of the intact, clear, and transparent chorioallantoic membrane (CAM) vascular system of mid-stage hatched chicken embryos, the test substance was directly exposed to the CAM membrane. After 5 minutes, changes in CAM toxicity indicators (mainly hemorrhage, coagulation, and vascularization) were observed. These indicators reflect changes in the morphology, color, and permeability of blood vessels and vascular networks, as well as phenomena such as chorioallantoic membrane protein denaturation and the degree of damage. These indicators were then combined to obtain a score (referring to the generally accepted scoring standards in this field) to assess the eye irritation of the test substance.

[0050] Test substance grouping: 0.1% of compound samples from Examples 1-3, 0.1% of triptolide sample, negative control 0.9% NaCl solution, positive control 0.1 mol / L NaOH solution.

[0051] The results are shown in Table 2, which shows that the triptolide derivatives of Examples 1-3 are non-irritating / mildly irritating, and are milder and safer than the moderately irritating triptolide.

[0052] Table 2. Conclusions of Eye Irritation Test Assessment

[0053] Example 6 Anti-inflammatory efficacy test The test on the inhibitory effect of prostaglandin E2 (PGE-2) is mainly used to evaluate the anti-inflammatory, soothing, anti-inflammatory and acne-reducing, barrier repair and anti-inflammatory and anti-aging skin efficacy of skin care products. The core is to directly relieve skin inflammation and improve inflammation-related skin problems by reducing the production of the key pro-inflammatory mediator PGE-2.

[0054] The experiment used mouse macrophages RAW cells and constructed an inflammation model group using lipopolysaccharide (LPS). The experimental samples were grouped as follows: 25 mg / L compounds from Examples 1-3, 25 mg / L triptolide, LPS model group, and blank control group (DMEM medium without drugs).

[0055] Cells were incubated in a 5% CO2 environment at 37°C. Two hours after drug administration to each group, 10 μg / mL LPS was added to both the lipopolysaccharide model group and the experimental group, and they were incubated together for 24 hours. The PGE-2 content in each group of cells was then detected by enzyme-linked immunosorbent assay (ELISA).

[0056] The results are shown in Table 3. At a concentration of 25 mg / L, the expression of PGE-2 inflammatory factor in the triptolide derivatives and triptolide samples of Examples 1-3 decreased by 34.7%, 35.1%, 33.2%, and 30.9%, respectively, compared to the LPS model group. This indicates that the triptolide derivatives of Examples 1-3 exhibit better anti-inflammatory efficacy than triptolide, and can be used to develop more safe and gentle anti-inflammatory skincare products, as well as for the preparation of repair products.

[0057] Table 3. Expression of PGE-2 inflammatory factors under different sample treatments

[0058] Example 7 Antioxidant Test The antioxidant effects of different compounds are evaluated by measuring the activity of antioxidant enzymes. Catalase (CAT) can scavenge free radicals and reactive oxygen species produced in the body. With increasing age, the activity of antioxidant enzymes decreases, leading to an excess of free radicals and reactive oxygen species, which causes the body to gradually age.

[0059] HFF-1 cells were used in the experiment. The experimental samples were grouped as follows: 25 mg / L of compounds from Examples 1-3, 25 mg / L triptolide, blank control group (DMEM medium without drugs), model group, and positive control group (25 mg / LVC).

[0060] HFF-1 cells were cultured overnight in a 5% CO2 incubator at 37°C, and the supernatant was discarded after 24 h. Twenty-four h after drug administration, the model group, positive control, and experimental groups were incubated with 8 mM / L H2O2 for 2 h. Total protein was then extracted from each group of cells, and the supernatant was collected after cell lysis. Protein concentration and CAT activity were measured using a BCA protein concentration assay kit.

[0061] The results showed that, with the relative CAT activity of the blank control group set to 1, the CAT activity of the model group was 0.24, and the activity of the positive control group was 0.68. The CAT activities of the compounds in Examples 1-3 at a concentration of 25 mg / L were 0.62, 0.63, and 0.61, respectively. The CAT activity of the triptolide sample at a concentration of 25 mg / L was 0.48. These results indicate that the compounds in Examples 1-3 significantly enhanced CAT expression under H2O2 incubation conditions, thereby inhibiting the overexpression of intracellular free radicals. Compared to triptolide, the triptolide derivatives of Examples 1-3 showed a more significant increase in CAT activity and exhibited better antioxidant effects.

[0062] Example 8: A repairing face cream containing triptolide-phytosphingosine This embodiment provides a product containing the triptolide derivative prepared according to the present invention: a repair cream containing triptolide-phytosphingosine, the formula composition and content (w / w%) of which are as follows: Main component: Tripterygium wilfordii derivative (Example 1): 0.5%; Emulsifier: Cetearyl alcohol + Cetearyl alcohol polyether-20 (mass ratio): 4.0%; Oil phase components: Squalane: 5.0%; Jojoba oil: 3.0%; Octyldodecyl alcohol: 10%; Co-active ingredients: Centella asiatica extract: 0.5%; Vitamin E acetate: 0.5%; Soothing agent: allantoin: 0.5%; Preservative system: Phenoxyethanol: 0.6%; Ethylhexylglycerin: 0.4%; Solvents: Glycerin: 5.0%; Butylene glycol: 3.0%; Xanthan gum: 0.3%; Deionized water: up to 100%.

[0063] The preparation process for this face cream is as follows: (1) Mix the aqueous phase (water, glycerol, butylene glycol, xanthan gum) and heat to 75°C.

[0064] (2) Heat the oil phase (octyldodecyl alcohol, squalane, jojoba oil, emulsifier) ​​to 85°C, add tripterygium oleoresin derivative (Example 1), and stir until completely dissolved.

[0065] (3) After emulsifying the aqueous phase and the oil phase, cool to 40°C, add Centella asiatica extract, vitamin E acetate, allantoin and preservative, and mix well to obtain the final product.

[0066] Meanwhile, skin tests were conducted on 12 volunteers who used the prepared repair cream continuously for 28 days. The results were as follows: Figure 4 As shown, compared with the baseline value, the subjects' skin redness a* value decreased significantly ( p The decrease rate was 15.31% (<0.001), indicating that the product can alleviate and improve skin inflammation and telangiectasia, enhance the skin barrier function, and make the skin more even, fair, and healthy.

[0067] The repair cream containing triptolide-phytosphingosine provided in this embodiment, supplemented with ingredients such as Centella asiatica extract and vitamin E acetate, can effectively achieve anti-inflammatory, antioxidant, repairing, and soothing effects. Compared with triptolide, it reduces the toxicity and irritation of triptolide and has better anti-inflammatory and antioxidant effects. This invention provides a safer, gentler, and more effective alternative to triptolide, which can be used in the manufacture of chemical pharmaceutical raw materials or preparations and biopharmaceuticals, and can also be used to develop more anti-inflammatory, soothing, barrier-repairing, and anti-aging skin care or cosmetic products.

[0068] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A class of celadixine derivatives, characterized in that, The structural formula of the derivative is shown as follows: ； wherein: R1is selected from one of the following:

2. The method for preparing the gossypifolin derivative of claim 1, characterized in that, Triptolide, 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide and 2-hydroxypyridine-N-oxide are dissolved in an organic solvent under ice bath condition for activation; then a catalyst and a sphingosine base compound are added for reaction at room temperature for 12-24 h; after the reaction is completed, the product is washed and purified to obtain the triptolide derivative.

3. The method of claim 2, wherein, The sphingosine base compound is selected from sphingosine, dihydrosphingosine or phytosphingosine.

4. The method of claim 2, wherein, The molar ratio of the components in the reaction system is: triptolide: 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide: 2-hydroxypyridine-N-oxide: catalyst: sphingosine base compound = 1: (1-1.5): (1-1.5): (0-0.5): (1-1.2).

5. The method of claim 4, wherein, The catalyst is selected from 4-dimethylaminopyridine or 4-pyrrolidinopyridine.

6. The method of claim 2, wherein, The organic solvent is selected from tetrahydrofuran or 2-methyltetrahydrofuran.

7. Use of the triptolide derivative of claim 1 in the preparation of anti-inflammatory, antioxidant, anti-aging products.

8. Use of the triptolide derivative of claim 1 in the preparation of skin care or skin barrier repair products.

9. An external use product comprising the triptolide derivative of claim 1.

10. The product of claim 9, wherein The product is an O / W emulsion, a W / O cream, a cream, an anhydrous oil gel, a transparent oil phase essence, a microemulsion, a shampoo / hair care or body care product.

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