Fatty acylation split-ring iridoid glycoside as well as preparation method and application thereof

Abstract

The invention provides fatty acylation split-ring iridoid glycoside as well as a preparation method and application thereof, the fatty acylation split-ring iridoid glycoside comprises at least one of fatty acyl gentiopicroside, fatty acyl sweroside and fatty acyl swertiamarin, and the fatty acyl gentiopicroside is at least one of fatty acyl gentiopicroside, fatty acyl sweroside and fatty acyl swertiamarin. Wherein the fatty acyl gentiopicroside, the fatty acyl swertiamarin and the fatty acyl swertiamarin are respectively represented by a structural formula (I), a structural formula (II) and a structural formula (III), and a group R1, a group R2 and a group R3 are respectively and independently selected from alkyl or alkenyl with the carbon atom number of 5-21. The preparation method of the fatty acylation split-ring iridoid glycoside is also applied to preparation of a fatty acylation gentian plant extract. The fatty acylation split-ring iridoid glycoside and the fatty acylation gentian plant extract are used as raw materials to be applied to the field of medicine to play the roles of relieving, removing red, resisting inflammation, relieving itching, cleaning, emulsifying and resisting bacteria, and are also used as functional raw materials to be applied to the field of daily chemicals to play the roles of relieving, removing red, resisting inflammation, relieving itching, cleaning, emulsifying and resisting bacteria.

Description

A class of fatty acylated cleaved iridoid ether glycosides, their preparation methods and applications Technical Field

[0001] This invention belongs to the field of chemical pharmaceutical raw materials, specifically, it relates to a class of fatty acylated cleaved iridoid glycosides, their preparation methods, and applications. Background Technology

[0002] Gentian and its processed products are included in the Pharmacopoeia of the People's Republic of China (Part I, 2020), which has strict requirements on the content of gentiopicrin. Gentianopicrin, swertiamarin, and swertiamarin are three of the most representative secoiridoid glycosides, generally extracted from plants of the Gentian genus. Gentianopicrin has pharmacological effects such as protecting the liver, analgesia and anti-inflammation, anti-oxidation, anti-pruritus, and promoting wound healing (Feng Miaomiao, Li Menghan, Dang Linjie, et al. Research progress on extraction process and pharmacological activity of gentiopicrin in gentian [J]. Shandong Chemical Industry, 2023, 52(08):104-107.). Gentian has a lactone ring, intracyclic double bonds, exocyclic double bonds, and glycosidic bonds in its structure, which makes it prone to chemical bond breakage under alkaline, acidic, and oxidative conditions, generating uncertain products (Liu Bin, Guo Dadong. Research progress of gentiopicrin in the treatment of immune-related diseases [J]. Chinese Journal of Traditional Chinese Medicine, 2024, 39(11):5999-6002.). Gentianiopicrin is highly polar and has good water solubility, making it difficult to be effectively transported in biological membranes and resulting in poor bioavailability (Chen Yinfang, Wang Yan, Song Xiaoling, et al. Optimization of gentiopicrin structure modification process and analysis of physicochemical properties of the product [J]. Chinese Journal of Experimental Traditional Medical Formulae, 2016, 22(18):13-16.).

[0003]

[0004] Numerous papers and patent applications report the preparation of new gentiopicroside derivatives through acetylation, glycosyl modification, olefin metathesis, and complexation, aiming to effectively improve the stability and bioavailability of gentiopicroside.

[0005] Gentianoside acetal derivatives, gentianoside ketal derivatives, gentianoside benzoyl chloride-substituted derivatives, and gentianoside derivatives obtained by olefin metathesis reactions of hydroxylated gentianoside with terminal alkenes have been reported in papers (Yang Feixia. Design, Synthesis and Anti-inflammatory Activity Study of Novel Gentianoside Amide Derivatives [D]. Gansu University of Traditional Chinese Medicine, 2022.). Acetylation of the hydroxyl groups on the sugar molecules of gentianoside yields tetraacetylated gentianoside, increasing its lipophilicity to improve oral absorption and bioavailability (Zeng Wenxue. Preparation and Characterization of Tetraacetylated Gentianoside [D]. Guangzhou University of Traditional Chinese Medicine, 2013.). Twenty-three diindolemethane pseudomonoterpenoid indole alkaloid analogs were synthesized by condensation reaction (modified vinyl) of gentianoside and tryptophan derivatives (active unit fragments of indole structures). Some compounds can effectively reduce the resistance of paclitaxel-resistant strains of human lung cancer cells, showing good potential for reversing resistance. (Chen Yuewei, Li Jiang, Deng Lulu, et al. Synthesis of diindolemethane pseudomonoterpenoid indole alkaloid analogs based on gentiopicroside and their antitumor and paclitaxel resistance reversal activities [J]. Chemistry Bulletin, 2022, 85(12):1488-1498+1487.)

[0006] Patent application CN 120154557 A discloses an acne-removing composition containing ceramides, including a gentiopicrin-vitamin C cocrystal. Patent application CN 119638763 A discloses a gentiopicrin amide derivative, wherein the 6' hydroxyl group of gentiopicrin is modified to an amino group, and then reacted with benzoyl chloride containing one substituent to generate a gentiopicrin amide derivative, used in the preparation of anti-inflammatory drugs. Patent application CN118831094 A discloses a gentiopicrin strontium complex, used in bone repair. Patent application CN 116239639 A discloses iridoid compounds, including 2'-O-caffeoyl gentiopicrin or 2',6'-bis-O-(4-O-glucosylcaffeoyl)gentiopicrin, etc. Patent application CN 113817007 B authorizes gentiopicroside derivatives and their preparation and application. In gentiopicroside, the vinyl group is modified to an ethyl group, the hydroxyl hydrogen of the hydroxymethyl group is modified to -COOCH2CH3 or -COCH3, and the remaining hydroxyl groups are modified to acetate. The modified gentiopicroside derivatives are used in the preparation of drugs that promote the elongation of cellular neurites and prevent and treat neurodegenerative diseases, including Alzheimer's disease. Patent applications CN 115607555 A and US 2023172945 A1 disclose the application of a series of compounds in inhibiting or killing mites, including gentiopicroside and its derivatives. The hydroxymethyl group of gentiopicroside can be modified to a carboxyl group (or the hydrogen of the hydroxymethyl group can be modified to 2-methyltetrahydropyran-3,4,5-triol), and the vinyl group can be modified to several groups containing 0-11 carbon atoms. Patent application CN109422807 A discloses a conjugate of gentiopicroside, wherein the hydroxyl group of gentiopicroside is coupled to an immunogenic carrier protein via an amide bond. Patent CN107253989 B authorizes a method for preparing an artificial antigen of gentiopicroside and establishing an indirect competitive ELISA detection method, wherein the hapten molecule is an ester formed by gentiopicroside and 1,4-succinic acid (hydroxymethyl esterification). Patent application CN106770525 A discloses a method for preparing a highly sensitive benzothiazide molecularly imprinted electrochemical sensor, wherein gentiopicroside is used as the functional monomer and evodiolactone is used as the cross-linking agent. Patent application CN106525937 A discloses a method for preparing a highly sensitive amoxapine molecularly imprinted electrochemical sensor, wherein gentiopicroside is used as the functional monomer and isothomyl lactone is used as the cross-linking agent. The invention patent with publication number CN 106674310 B authorizes a method for synthesizing gentiopicroside derivatives, which involves grafting benzyl, phenethyl, p-methoxyphenethyl, 4-ethyl-1,2-dimethoxybenzene or 5-ethyl-2-methoxyphenol onto the vinyl group of gentiopicroside.

[0007] The aforementioned papers and patent applications all modified and altered gentiopicroside, but none of them found a scheme to modify the hydroxymethyl group of gentiopicroside with a medium- or long-chain linear fatty acyl group to transform gentiopicroside into fatty acyl gentiopicroside. Moreover, the aforementioned patent applications focused on modifying multiple hydroxyl groups or positions of gentiopicroside, or using multifunctional groups to modify gentiopicroside, without preserving the original structure of gentiopicroside to the greatest extent possible, thereby enabling it to exert its original efficacy. In addition, they did not modify gentiopicroside to impart surface activity and improve stability, making it both hydrophilic and lipophilic, making it easier to apply in products and exert its efficacy.

[0008] Swertiatoside, swertiamarin, and gentiopicrin all belong to the secoiridoid family of terpenoids, and their molecular structures are highly similar (Luo Shiyu, Mi Yahui, Cui Jiamin, et al. Chemical constituents of Gentiana scabra 'Blue' LC-MS). n Qualitative analysis and determination of multiple components by HPLC-UV method [J]. Journal of China Pharmaceutical University, 2025, 56(06):710-718.), the problems and research status of swertiamarin and swertiamarin are similar to those of gentiopicrin. Summary of the Invention

[0009] To address the issues of poor stability, high polarity, and poor bioavailability (poor skin absorption, etc.) of the aforementioned schizocyclic ether glycosides (gentiopicrin, swertiamarin, swertiamarin), this application provides a novel class of schizocyclic ether glycoside derivatives, namely fatty acyl schizocyclic ether glycosides (fatty acyl gentiopicrin, fatty acyl swertiamarin, fatty acyl swertiamarin). These derivatives exhibit improved stability, possess both hydrophilic and lipophilic properties, good skin affinity, and soothing, redness-reducing, anti-inflammatory, antipruritic, cleansing, and emulsifying effects. They show promising potential for use as raw materials in pharmaceutical and daily chemical products.

[0010] Therefore, the purpose of this invention is to provide a class of fatty acylated cleaved cyclohexene glycosides, their preparation methods, and applications.

[0011] To achieve the above objectives, the present invention provides the following technical solution:

[0012] A class of fatty acylated cleaved iridoid glycosides, selected from at least one of fatty acyl gentiopicroside, fatty acyl swertiamarin, and fatty acyl swertiamarin, wherein fatty acyl gentiopicroside, fatty acyl swertiamarin, and fatty acyl swertiamarin are represented by structural formulas (I), (II), or (III), respectively:

[0013]

[0014] Among them, group R1, group R2, and group R3 are each independently selected from alkyl or alkenyl groups having 5 to 21 carbon atoms.

[0015] According to a preferred embodiment of the present invention, the groups R1, R2, and R3 in the structural formulas (I), (II), and (III) are each independently selected from straight-chain alkyl or straight-chain alkenyl groups having 5 to 21 carbon atoms;

[0016] R1, R2, and R3 are selected from straight-chain alkyl groups with 5 to 17 carbon atoms or straight-chain alkenyl groups with 10 to 17 carbon atoms.

[0017] According to the present invention, the method for preparing the fatty acylated cleaved iridoid glycoside includes the following steps:

[0018] (1) Add secoiridinol glycoside and organic solvent A to the reaction vessel and stir until the secoiridinol glycoside is completely dispersed or dissolved;

[0019] (2) Maintain the temperature of the reactor at -10~30℃, and slowly add fatty acyl halides dropwise while stirring. After the addition is complete, add inorganic alkaline solids to neutralize the hydrogen halide produced by the reaction, continue stirring for 5~24 h, and then cool down.

[0020] (3) After cooling to room temperature, the mixture in the reactor is filtered under reduced pressure, and the filtrate is transferred to a flask for reduced pressure distillation to remove the organic solvent and obtain the mixture.

[0021] (4) Crush the mixture, place it in a vacuum filter funnel, and wash it several times with organic solvent B. During the washing process, perform vacuum filtration and collect the filter residue.

[0022] (5) Dissolve the filter residue in hot organic solvent C, filter while hot, and distill the filtrate under reduced pressure to obtain a solid powder, namely fatty acylated cyclohexene glycoside.

[0023] According to the present invention, in the method for preparing fatty acylated cleaved iridoid glycosides, the molar ratio of the cleaved iridoid glycoside in step (1) to the fatty acyl halide in step (2) is 2: (1.5~1.8).

[0024] The organic solvent A in step (1) is selected from at least one of 1,3-dimethyl-2-imidazolinone, 2,5-dimethyltetrahydrofuran, 2-methyltetrahydrofuran, N-butylpyrrolidone, N-methylpyrrolidone, N-ethylpyrrolidone, acetone, dipropylene glycol dimethyl ether, dimethyl sulfoxide, diethylene glycol dimethyl ether, diethoxyethyl succinate, sulfolane, methyl tert-butyl ether, methyl ethyl ketone, tert-butanol, tetrahydrofuran, propylene carbonate, ethylene carbonate, isopropylglycerin, ethanol, ethyl propyl ether, acetonitrile, diethyl ether, methyl acetate, ethyl acetate, isopropanol, isopropyl ether, and isosorbide dimethyl ether.

[0025] The organic solvent B in step (4) is selected from 1-hexene, 2-methylpentane, cyclohexane, cyclohexene, cyclopentane, petroleum ether, n-hexane, and n-octane.

[0026] The organic solvent C in step (5) is selected from at least one of 2-methyltetrahydrofuran, acetone, methyl tert-butyl ether, methyl ethyl ketone, tert-butanol, tetrahydrofuran, ethanol, ethyl propyl ether, methyl acetate, ethyl acetate, isopropanol, and isopropyl ether.

[0027] The inorganic alkaline solid in step (2) is selected from at least one of potassium silicate, sodium silicate, disodium hydrogen phosphate, calcium hydroxide, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, calcium bicarbonate, potassium bicarbonate, and sodium bicarbonate.

[0028] The fatty acyl halide is an alkyl acyl halide or an alkenyl acyl halide.

[0029] The fatty acyl halide is an alkyl acyl chloride, alkyl acyl bromide, or alkenyl acyl chloride, alkenyl acyl bromide.

[0030] According to the present invention, the method for preparing fatty acylated cleaved iridoid glycosides is also applicable to the preparation of fatty acylated gentian plant extracts, wherein the gentian plant extracts are water-soluble or alcohol-soluble solid powders, and the components include at least one of gentiopicrin, swertiamarin, and swertiamarin.

[0031] The Gentianaceae plants mentioned include at least *Gentiana aba*, *Gentiana adunziensis*, *Gentiana alishanensis*, *Gentiana dwarfis*, *Gentiana dwarfisyushanensis*, *Gentiana batangensis*, *Gentiana scabraensis*, *Gentiana speckula*, *Gentiana bracteata*, *Gentiana baoxingensis*, *Gentiana davidii*, *Gentiana scabraensis*, *Gentiana bomiensis*, *Gentiana scabra ... meadowensis*, *Gentiana forkedinae*, *Gentiana koreanum*, *Gentiana dentata*, *Gentiana stolonifera*, and *Gentiana scabraensis*. Gentiana sibirica, Gentiana macrophylla var. chuanxiong, Gentiana droopingensis, Gentiana semperflorens, Gentiana sibirica var. spinosa, Gentiana sibirica var. sibirica var. dauricum, Gentiana dajianlu, Gentiana macrophylla, Gentiana macrophylla var. dali, Gentiana sibirica var. dali, Gentiana sibirica var. dalicum ... Gentian, Gentiana multiflora, Gentiana multi-malebearinga, Gentiana stenoptera, Gentiana 'Emei', Gentiana auriculata, Gentiana spicata, Gentiana reflexa, Gentiana radiata, Gentiana paracrownata, Gentiana alpinea, Gentiana kaxiong, Gentiana purplish-blue, Gentiana lepidophylla, Gentiana septemlobata, Ornamental Gentiana, Gentiana tubulara, Gentiana szechuanis, Gentiana guxiong, Gentiana henryi, Gentiana serrata, Gentiana serrata purplish-blue, Gentiana septemlobata, Gentiana huensis Gentiana scabra, ... Gentian, blue and white gentian, blue and gray gentian, blue gentian, blue hosta gentian, ear-like gentian, gorgeous gentian, glossy-leaved gentian, rosette-leaved gentian, Liangshan gentian, glossy-leaved gentian, forest gentian, Linzhi gentian, scale-leaved gentian, fringe gentian, six-leaved gentian, gentian, Luding gentian, dew-stamen gentian, ovoid-calyx gentian, Rostan snow gentian, hemp-flowered gentian (hemp-flowered gentian), Ma'ershan gentian, hairy Gentiana scabra, Gentiana hairy-flowered, Gentiana hairy-stamens, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana mirin, Gentiana densely-flowered, Gentiana densely-leaved, Gentiana densely-branched, Gentiana Burmese, Gentiana Minxian, Gentiana membranacea, Gentiana moss-mountain, Gentiana medogina, Gentiana motherwort-leaf, Gentiana scapulae, Gentiana scabra, Gentiana nyalam, Gentiana ninglangensis, Gentiana scabra with twisted fruit stalk, Gentiana scabra with leafy green leaves, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra with leafy green leaves, Gentiana scabra, Gentiana sphenanthracea, Gentiana scabra, Gentiana latalis, Gentiana prostrate, Gentiana scabra, Gentiana macrophylla, Gentiana scabra, Gentiana scabra with a full calyx, Gentiana scabra with a beard, Gentiana pubescens, Gentiana scabra with soft hairs, Gentiana scabra with a soft texture, Gentiana scabra with a papillae, Gentiana scabra with a weak shape, Gentiana triflora, Gentiana trilobata, Gentiana tricolor, Gentiana trifoliata, Gentiana scabra with a trifoliate leaf, Gentiana scabra with a tricolor leaf, Gentiana scabra with a trifoliate leaf, Gentiana scabra with a trifoliate leaf, Gentiana scabra with a trifoliate leaf, Gentiana scabra with a deep stem ... Gentiana scabra, Gentiana scabra, Gentiana chinensis, Gentiana scabra, Gentiana sparsely flowered, Gentiana aquatic, Gentiana macrophylla, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana szechuanensis, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabra, Gentiana scabraGentiana linearis, Gentiana linearis, Gentiana tubularis, Gentiana capitulum, Gentiana capitulum, Gentiana elliptica, Gentiana serrata ... The following are listed: * Gentiana xinganensis*, *Gentiana xingrenensis*, *Gentiana xiuxiuensis*, *Gentiana lindracea*, *Gentiana petiolate*, *Gentiana calyx*, *Gentiana yizeshanensis*, *Gentiana yiliangensis*, *Gentiana heterophylla*, *Gentiana scalyx*, *Gentiana scalyx*, *Gentiana styracifolia*, *Gentiana yushanensis*, *Gentiana spheroides*, *Gentiana yunnanensis*, *Gentiana yunnanensis*, *Gentiana zekuensis*, *Gentiana changbaishanensis*, *Gentiana long-calyx*, *Gentiana long-stalked*, *Gentiana long-fringed*, *Gentiana long-haired*, *Gentiana long-haired*, *Gentiana variegata*, *Gentiana styracifolia*, *Gentiana styracifolia*, *Gentiana zhongdianensis*, *Gentiana zhongdianensis*, *Gentiana sinica*, *Gentiana centralis*, *Gentiana bell-shaped*, *Gentiana broom-shaped*, *Gentiana zhufengensis*, *Gentiana zhulinensis*, *Gentiana purpurea*, *Gentiana lanceolata*, *Gentiana lanceolata*.

[0032] The fatty acylated cleaved iridoid glycosides and the fatty acylated gentian plant extracts are used as raw materials in the preparation of therapeutic, soothing, redness-reducing, anti-inflammatory, antipruritic, cleansing, and antibacterial drugs, or the fatty acylated cleaved iridoid glycosides or fatty acylated gentian plant extracts are used as emulsifiers in drugs.

[0033] The aforementioned fatty acylated cleaved iridoid ether glycosides and fatty acylated gentian plant extracts are used as raw materials in the daily chemical industry, and these raw materials exert soothing, redness-reducing, anti-inflammatory, antipruritic, cleansing, emulsifying, and antibacterial effects.

[0034] The beneficial effects of this invention are:

[0035] Due to their inherent molecular structure, swertiazine glycosides (gentiopicrin, swertiazine, swertiazine) suffer from poor stability, high polarity, and poor skin absorption. The fatty acylated swertiazine glycosides of this invention modify the hydroxyl hydrogen on the hydroxymethyl group of the swertiazine glycoside into a medium- to long-chain fatty acyl group (≥6 carbon atoms). The introduction of this medium- to long-chain fatty acyl group increases the molecular weight and makes the structure more complex, which is beneficial for improving thermal stability. Furthermore, it enhances lipophilicity (reduces polarity), making the molecule both hydrophilic and lipophilic, thus facilitating skin absorption. Simultaneously, it imparts surface activity, generating additional emulsifying, cleansing, and solubilizing effects, reducing the use of surfactants in pharmaceuticals and daily chemical products.

[0036] Furthermore, the preparation method of the fatty acylated cleaved iridoid glycosides of the present invention is highly operable and easy to industrialize. It can replace cleaved iridoid glycosides and partially replace traditional surfactants, and can be widely used in the fields of medicine and daily chemicals. Detailed Implementation

[0037] The present invention will be further described below with reference to specific embodiments. It should be understood that the following embodiments are for illustrative purposes only and are not intended to limit the scope of the invention.

[0038] Unless otherwise specified, all raw materials used in the following examples are commercially available.

[0039] The performance and efficacy testing methods involved in the following embodiments are as follows:

[0040] References for stability testing methods (centrifugation test, heat and cold resistance test, room temperature sample retention observation): Chen Si, Zhang Yi. Preparation and safety study of Nocardia rubrum cell wall skeleton emulsion [J]. Daily Chemicals Science, 2023, 46(01):4-8.

[0041] References for the redness-reducing and soothing efficacy test method (redness parameter measurement): Guo Shentao, Xu Wenfeng, Cui Yujiao, et al. Application research on several cosmetic soothing efficacy evaluation methods [J]. Daily Chemical Products Science, 2023, 46(06):37-40+44.

[0042] References for emulsification and cleaning performance testing methods: Dong Shuangjian, Li Yunling. Synthesis and properties of unsaturated octadecyl betaine [J]. Dyeing and Printing Auxiliaries, 2013, 30(05):8-10.

[0043] References for testing methods of antipruritic and anti-inflammatory effects: Liu Yao, Sun Shurong. Comparative study on the soothing effects of cosmetics under three skin irritation models [J]. Science of Daily Chemical Products, 2024, 47(08):37-41.

[0044] Example 1

[0045] The structural formula of the fatty acylated cleaved iridoid ether glycoside in this embodiment is as follows:

[0046]

[0047] This refers to hexanoyl gentiopicroside, chemically named 6'-O-hexanoyl gentiopicroside, where the R1 group is n-pentyl. The preparation method of this fatty acylated cleaved cyclohexene ether glycoside is as follows:

[0048] Gentianoside (8.00 g, 0.022451 mol) and 2,5-dimethyltetrahydrofuran (180 g, 1.79711 mol) were added to a reaction vessel and stirred until gentianoside was completely dispersed. The temperature of the reaction vessel was maintained at -10℃, and hexanoyl chloride (2.40 g, 0.01783 mol) was slowly added dropwise while stirring. After the addition was complete, powdered anhydrous sodium carbonate (0.95 g, 0.00896 mol) was added, and stirring was continued for 18 h. The mixture was then cooled. After cooling to room temperature, the mixture in the reaction vessel was filtered under reduced pressure. The filtrate was transferred to a flask for vacuum distillation to remove the organic solvent, yielding a white solid. The white solid was pulverized, placed in a suction funnel, and washed repeatedly with cyclopentane. During the washing process, the mixture was filtered under reduced pressure, and the residue was collected to obtain a white powder. The white powder was dissolved in hot isopropanol (50℃, 100 g, 1.66400 mol). 0.01567 mol) was filtered while hot, and the filtrate was distilled under reduced pressure to obtain a white solid powder, namely 6'-O-hexanoyl gentiopicroside (7.12 g, 0.01567 mol), with a yield of 87.89% (the yield was calculated based on the amount of hexanoyl chloride; since more 6'-O-hexanoyl gentiopicroside was needed, gentiopicroside was in excess, and the unreacted gentiopicroside was recovered and reused).

[0049] 1 H NMR (400 MHz, DMSO-d6) δ: 7.47(s, 1H), 5.69(m, 1H), 5.50(m, 1H),5.45(m, 1H), 5.41(m, 1H), 5.02(m, 1H), 4.99(m, 1H), 4.86(m, 1H), 4.81(s, 1H),4.79(m, 2H), 4.73(s, 1H), 4.30(m, 1H), 4.21(m, 1H), 4.10(m, 1H), 3.95(m, 1H),3.74(m, 1H), 3.57(m, 1H), 3.40(m, 1H), 2.29(m, 2H), 1.70(m, 2H), 1.31(m, 2H),1.27(m, 2H), 0.89(m, 3H); 13 C NMR (100 MHz, DMSO-d6) δ: 175.2, 167.1, 151.2,135.8, 128.4, 119.6, 116.7, 110.5, 105.3, 104.9, 78.8, 77.0, 73.4, 72.7,71.4, 63.9, 47.3, 34.7, 30.6, 30.4, 23.3, 13.7; [M+H]+ m / z: 455.19.

[0050] Example 2

[0051] The structural formula of the fatty acylated cleaved iridoid ether glycoside in this embodiment is as follows:

[0052]

[0053] This refers to stearyl gentiopicroside, chemically named 6'-O-stearyl gentiopicroside, where the R1 group is n-heptadecyl. The preparation method of this fatty acylated cleaved cyclohexene ether glycoside is as follows:

[0054] Gentianoside (10.00 g, 0.02806 mol) and 1,3-dimethyl-2-imidazolinone (200 g, 1.75211 mol) were added to a reaction vessel and stirred until gentianoside was completely dispersed. The temperature of the reaction vessel was maintained at 30°C, and stearoyl chloride (7.20 g, 0.02377 mol) was slowly added dropwise while stirring. After the addition was complete, powdered anhydrous potassium carbonate (1.65 g, 0.01194 mol) was added, and stirring was continued for 24 h. The mixture was then cooled. After cooling to room temperature, the mixture in the reaction vessel was filtered under reduced pressure. The filtrate was transferred to a flask for vacuum distillation to remove the organic solvent, yielding a white solid. The white solid was pulverized, placed in a suction funnel, and washed repeatedly with cyclohexane. During the washing process, the mixture was filtered under reduced pressure, and the residue was collected to obtain a white powder. The white powder was dissolved in hot isopropanol (60°C, 100 g, 1.66400 mol). 12.14 g, 0.01949 mol), filtered while hot, and the filtrate was distilled under reduced pressure to obtain a white solid powder, namely 6'-O-stearoyl gentiopicroside (12.14 g, 0.01949 mol), with a yield of 81.99% (the yield is calculated based on the amount of stearoyl chloride. Since more 6'-O-stearoyl gentiopicroside is needed, gentiopicroside is in excess, and unreacted gentiopicroside is recovered and reused).

[0055] 1H NMR (400 MHz, DMSO-d6) δ: 7.38(s, 1H), 5.76(m, 1H), 5.60(m, 1H),5.46(m, 1H), 5.40(m, 1H), 5.04(m, 1H), 5.02(m, 1H), 4.93(m, 1H), 4.87(m, 2H),4.81(s, 1H), 4.75(s, 1H), 4.26(m, 1H), 4.12(m, 1H), 3.96(m, 1H), 3.66(m, 1H),3.59(m, 1H), 3.42(m, 1H), 2.29(m, 2H), 1.72(m, 2H), 1.37-1.23(m, 28H), 0.90(m, 3H); 13 C NMR (100 MHz, DMSO-d6) δ: 175.3, 167.3, 151.8, 135.7, 127.9,119.5, 116.8, 110.0, 105.2, 104.7, 78.5, 77.3, 73.8, 71.7, 71.2, 62.5, 47.1,34.9, 32.2, 30.1, 29.7, 28.7, 24.1, 23.1, 13.8; [M+H] + m / z: 623.37.

[0056] Example 3

[0057] The structural formula of the fatty acylated cleaved iridoid ether glycoside in this embodiment is as follows:

[0058]

[0059] This refers to swertiamarin octanoyl, chemically named 6'-O-swertiamarin, where the R2 group is n-heptyl. The preparation method of this fatty acylated cleaved iridoid glycoside is as follows:

[0060] Swertiatoside (8.00 g, 0.02239 mol) and tetrahydrofuran (180 g, 2.49630 mol) were added to a reaction vessel and stirred until swertiatoside was completely dispersed. The temperature of the reaction vessel was maintained at -5℃, and octanoyl chloride (3.20 g, 0.01967 mol) was slowly added dropwise while stirring. After the addition was complete, powdered sodium hydroxide (0.79 g, 0.01975 mol) was added, and stirring was continued for 15 h. The mixture was then cooled. After cooling to room temperature, the mixture in the reaction vessel was filtered under reduced pressure. The filtrate was transferred to a flask for vacuum distillation to remove the organic solvent, yielding a white solid. The white solid was pulverized, placed in a suction funnel, and washed repeatedly with n-hexane. During the washing process, the mixture was filtered under reduced pressure, and the residue was collected to obtain a white powder. The white powder was dissolved in hot ethyl acetate (60℃, 100 g, 1.13500 mol). 0.01707 mol), filtered while hot, and the filtrate was distilled under reduced pressure to obtain a white solid powder, namely 6'-O-octanoyl swertiamarin (8.27 g, 0.01707 mol), with a yield of 86.78% (the yield is calculated based on the amount of octanoyl chloride; since more 6'-O-octanoyl swertiamarin is needed, swertiamarin is in excess, and unreacted swertiamarin is recovered and reused).

[0061] 1 H NMR (400 MHz, DMSO-d6) δ: 7.43(s, 1H), 5.76(m, 1H), 5.66(m, 1H),5.45(m, 1H), 5.10(m, 1H), 5.00(m, 1H), 4.92(s, 1H), 4.81(s, 1H), 4.75(s, 1H),4.41(m, 1H), 4.25(m, 1H), 4.22(m, 1H), 4.13(m, 1H), 4.10(m, 1H), 3.87(m, 1H),3.73(m, 1H), 3.66(m, 1H), 2.74(m, 1H), 2.37(m, 2H), 1.89(m, 1H), 1.73(m, 1H),1.70(m, 2H), 1.48(m, 1H), 1.35-1.23(m, 8H), 0.91(m, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 175.2, 168.7, 152.4, 134.6, 121.0, 107.0, 106.7, 105.1, 78.9,77.1, 74.0, 72.4, 70.6, 62.7, 45.3, 34.4, 32.7, 29.7, 29.5, 26.5, 25.6, 23.6,14.4; [M+H] + m / z: 485.23.

[0062] Example 4

[0063] The structural formula of the fatty acylated cleaved iridoid ether glycoside in this embodiment is as follows:

[0064]

[0065] This refers to undecenoyl swertiamarin, chemically named 6'-O-(10-undecenoyl)swertiamarin, where the R2 group is 9-decenoyl. The preparation method of this fatty acylated cleaved cycloene ether glycoside is as follows:

[0066] Swertiatoside (10.00 g, 0.02798 mol) and isosorbide dimethyl ether (200 g, 1.14813 mol) were added to a reaction vessel and stirred until swertiatoside was completely dispersed. The temperature of the reaction vessel was maintained at -10℃, and 10-undecenoyl chloride (4.54 g, 0.02240 mol) was slowly added dropwise while stirring. After the addition was complete, powdered sodium bicarbonate (1.89 g, 0.022450 mol) was added, and stirring was continued for 20 h. The mixture was then cooled. After cooling to room temperature, the mixture in the reaction vessel was filtered under reduced pressure. The filtrate was transferred to a flask for vacuum distillation to remove the organic solvent, yielding a white solid. The white solid was pulverized, placed in a suction funnel, and washed repeatedly with n-hexane. During the washing process, the mixture was filtered under reduced pressure, and the residue was collected to obtain a white powder. The off-white powder was dissolved in hot ethanol (50℃, 100 g, 2.17066 mol). 10'-(1-undecenoyl) swertiamarin (10.26 g, 0.01956 mol) was filtered while hot, and the filtrate was distilled under reduced pressure to obtain a white solid powder, namely 6'-O-(1-undecenoyl) swertiamarin (10.26 g, 0.01956 mol), with a yield of 87.32% (the yield was calculated based on the amount of 10-undecenoyl chloride. Since more 6'-O-(10-undecenoyl) swertiamarin was needed, the swertiamarin was in excess, and the unreacted swertiamarin was recovered and reused).

[0067] 1H NMR (400 MHz, DMSO-d6) δ: 7.39(s, 1H), 5.87(m, 1H), 5.79(m, 1H),5.38(m, 1H), 5.12(m, 1H), 5.16(m, 1H), 5.10(m, 1H), 5.05(m, 1H), 4.94(m, 1H),4.92(m, 1H), 4.81(s, 1H), 4.75(s, 1H), 4.34(m, 1H), 4.24(m, 1H), 4.22(m, 1H),4.13(m, 1H), 4.09(m, 1H), 3.88(m, 1H), 3.68(m, 1H), 3.56(m, 1H), 2.73(s, 1H),2.29(m, 2H), 2.17(m, 2H), 1.87(m, 1H), 1.73(m, 1H), 1.70(m, 2H), 1.48(m, 1H),1.36-1.27(m, 10H) 13 C NMR (100 MHz, DMSO-d6) δ: 174.5, 168.9, 152.6, 140.2,134.4, 121.4, 116.3, 107.1, 106.7, 106.2, 79.6, 77.4, 75.3, 72.8, 70.4, 64.7,45.3, 35.0, 34.4, 30.8, 30.6, 30.3, 30.1, 29.7, 26.8, 26.2; [M+H] + m / z:525.27.

[0068] Example 5

[0069] The structural formula of the fatty acylated cleaved iridoid ether glycoside in this embodiment is as follows:

[0070]

[0071] This refers to palmitoyl swertiamarin, chemically named 6'-O-palmitoyl swertiamarin, where the R3 group is n-pentadecanyl. The preparation method of this fatty acylated cleaved cyclohexene ether glycoside is as follows:

[0072] Swertiatoside (12.00 g, 0.03206 mol) and acetonitrile (260 g, 6.33328 mol) were added to a reaction vessel and stirred until the swertiatoside was completely dispersed. The temperature of the reaction vessel was maintained at 30°C, and palmitoyl chloride (7.43 g, 0.02703 mol) was slowly added dropwise while stirring. After the addition was complete, powdered anhydrous sodium silicate (1.65 g, 0.01352 mol) was added, and stirring was continued for 15 h. The mixture was then cooled. After cooling to room temperature, the mixture in the reaction vessel was filtered under reduced pressure. The filtrate was transferred to a flask for vacuum distillation to remove the organic solvent, yielding a white solid. The white solid was pulverized, placed in a suction funnel, and washed repeatedly with cyclohexane. During the washing process, the mixture was filtered under reduced pressure, and the residue was collected to obtain a white powder. The white powder was dissolved in hot ethanol (60°C, 200 g, 4.34131 mol). 0.02304 mol), filtered while hot, and the filtrate was distilled under reduced pressure to obtain a white solid powder, namely 6'-O-palmitoyl swertiamarin (14.12 g, 0.02304 mol), with a yield of 85.24% (the yield is calculated based on the amount of palmitoyl chloride. Since more 6'-O-palmitoyl swertiamarin is needed, swertiamarin is in excess, and the unreacted swertiamarin is recovered and reused).

[0073] 1 H NMR (400 MHz, DMSO-d6) δ: 7.43(s, 1H), 5.90(m, 1H), 5.68(m, 1H),5.14(m, 1H), 5.07(m, 1H), 5.37(m, 1H), 4.91(m, 1H), 4.85(m, 1H), 4.80(m, 1H),4.67(s, 1H), 4.37(m, 1H), 4.23(m, 1H), 4.18(m, 1H), 4.12(m, 1H), 4.09(m, 1H),3.85(m, 1H), 3.64(m, 1H), 3.56(m, 1H), 2.72(m, 1H), 2.29(m, 2H), 1.88(m, 1H),1.70(m, 2H), 1.64(m, 1H), 1.36-1.22(m, 24H), 0.93(m, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 174.2, 168.9, 154.3, 134.6, 122.8, 110.8, 107.3, 79.0, 77.6,75.0, 72.4, 66.8, 65.4, 64.1, 51.4, 34.8, 32.7, 32.5, 30.7, 30.3, 28.9, 25.7,23.1, 13.9; [M+H] + m / z: 613.35.

[0074] Example 6

[0075] The structural formula of the fatty acylated cleaved iridoid ether glycoside in this embodiment is as follows:

[0076]

[0077] This refers to oleoyl swertiamarin, chemically named 6'-O-oleoyl swertiamarin, where the R3 group is an 8-heptadecenyl group. The preparation method of this fatty acylated cleaved iridoid ether glycoside is as follows:

[0078] Swertiatoside (6.00 g, 0.01603 mol) and N-methylpyrrolidone (150 g, 1.51312 mol) were added to a reaction vessel and stirred until swertiatoside was completely dispersed. The temperature of the reaction vessel was maintained at 0℃, and oleyl chloride (3.90 g, 0.01296 mol) was slowly added dropwise while stirring. After the addition was complete, powdered potassium hydroxide (0.73 g, 0.01301 mol) was added, and stirring was continued for 16 h. The mixture was then cooled. After cooling to room temperature, the mixture in the reaction vessel was filtered under reduced pressure. The filtrate was transferred to a flask for vacuum distillation to remove the organic solvent, yielding a slightly yellowish-white solid. The slightly yellowish-white solid was pulverized, placed in a suction funnel, and washed repeatedly with n-octane. During the washing process, it was filtered under reduced pressure, and the residue was collected to obtain a creamy-white powder. The creamy-white powder was dissolved in hot ethyl acetate (60℃, 120 g, 1.36200 mol). 6'-O-oleoyl swertiamarin (6.82 g, 0.01068 mol) was filtered while hot and the filtrate was distilled under reduced pressure to obtain a white solid powder, namely 6'-O-oleoyl swertiamarin (6.82 g, 0.01068 mol), with a yield of 82.41% (the yield was calculated based on the amount of oleoyl chloride. Since more 6'-O-oleoyl swertiamarin was needed, the swertiamarin was in excess, and the unreacted swertiamarin was recovered and reused).

[0079] 1H NMR (400 MHz, DMSO-d6) δ: 7.44(s, 1H), 5.85(m, 1H), 5.81(m, 1H),5.36(m, 1H), 5.28(m, 2H), 5.10(m, 1H), 5.01(m, 1H), 4.90(s, 1H), 4.80(m, 1H),4.73(m, 1H), 4.68(s, 1H), 4.30(m, 1H), 4.23(m, 1H), 4.17(m, 1H), 4.12(m, 1H),4.05(m, 1H), 3.86(m, 1H), 3.64(m, 1H), 3.56(m, 1H), 2.72(m, 1H), 2.28(m, 2H),2.21(m, 4H), 1.87(m, 1H), 1.72(m, 2H), 1.63(m, 1H), 1.35-1.21(m, 20H), 0.92(3H); 13 C NMR (100 MHz, DMSO-d6) δ: 174.2, 168.7, 154.0, 133.0, 122.4, 110.8,107.3, 106.1, 79.5, 77.8, 75.2, 72.4, 65.6, 64.3, 62.8, 53.1, 34.7, 32.7,32.5, 30.1, 29.8, 29.4, 24.6, 23.0, 13.8; [M+H] + m / z: 639.37.

[0080] Example 7

[0081] The fatty acylated gentian plant extract of this embodiment is as follows:

[0082] This refers to myristoyl blue gentian extract, chemically named tetradecyl blue gentian extract. The preparation method for this fatty acylated gentian plant extract is as follows:

[0083] Gentian extract (9.00 g, containing 2.14 g of secoiridinol glycosides) and isosorbide dimethyl ether (200 g, 1.14813 mol) were added to a reaction vessel and stirred until the gentian extract was completely dispersed. The reaction vessel temperature was maintained at 30°C, and myristoyl chloride (1.25 g, 0.00506 mol) was slowly added dropwise while stirring. After the addition was complete, powdered anhydrous sodium bicarbonate (0.38 g, 0.00452 mol) was added, and stirring was continued for 15 h. The mixture was then cooled. After cooling to room temperature, the mixture in the reaction vessel was filtered under reduced pressure. The filtrate was transferred to a flask for vacuum distillation to remove the organic solvent, yielding a pale yellow solid. The pale yellow solid was pulverized, placed in a suction funnel, and washed repeatedly with n-hexane. During the washing process, vacuum filtration was performed, and the residue was collected to obtain a pale yellow powder. The pale yellow powder was dissolved in hot ethyl acetate (60°C, 150 °C). (1.70249 mol) was filtered while hot, and the filtrate was distilled under reduced pressure to obtain a pale yellow solid powder, namely myristoyl gentian extract (2.43 g), with a yield of 84.39% (the yield was calculated based on the amount of myristoyl chloride; since more myristoyl hosta gentian extract was needed, the hosta gentian extract was in excess, and the unreacted hosta gentian extract was recovered and reused). The average molar mass of the myristoyl hosta gentian extract was 569.63 g·mol⁻¹. -1 (Perform approximate calculations).

[0084] Example 8

[0085] The fatty acylated gentian plant extract of this embodiment is as follows:

[0086] This refers to palmitoyl gentian extract, chemically known as hexadecyl gentian extract. The preparation method for this fatty acylated gentian plant extract is as follows:

[0087] Gentian extract (12.00 g, containing 2.50 g of secoiridinium glycoside) and acetonitrile (300 g, 7.30763 mol) were added to a reaction vessel and stirred until the gentian extract was completely dispersed. The reaction vessel temperature was maintained at 25°C, and palmitoyl chloride (1.74 g, 0.00633 mol) was slowly added dropwise while stirring. After the addition was complete, powdered anhydrous sodium hydroxide (0.26 g, 0.00650 mol) was added, and stirring was continued for 20 h. The mixture was then cooled. After cooling to room temperature, the mixture in the reaction vessel was filtered under reduced pressure. The filtrate was transferred to a flask for vacuum distillation to remove the organic solvent, yielding a pale yellow solid. The pale yellow solid was pulverized, placed in a suction funnel, and washed repeatedly with cyclohexane. During the washing process, vacuum filtration was performed, and the filter residue was collected to obtain a pale yellow powder. The pale yellow powder was dissolved in hot tetrahydrofuran (50°C, 100 g, 0.70405 mol). The solution was filtered while hot, and the filtrate was distilled under reduced pressure to obtain a pale yellow solid powder, namely palmitoyl gentian extract (3.15 g), with a yield of 83.57% (the yield is calculated based on the amount of palmitoyl chloride; since more palmitoyl gentian extract is needed, the gentian extract is in excess, and the unreacted gentian extract is recovered and reused). The average molar mass of the palmitoyl gentian extract is calculated as 595.50 g·mol⁻¹. -1 (Perform approximate calculations).

[0088] Example 9

[0089] The stability and anti-redness and soothing effects of the fatty acylated cleaved iridoid ether glycosides in this embodiment were investigated as follows:

[0090] The blank formulations of the gel ointment are shown in the table below. The test formulations replace the deionized water in phase B with equal masses of 6'-O-hexanoyl gentiopicroside prepared in Example 1, 6'-O-octanoyl swertiamarin in Example 3, and 6'-O-palmitoyl swertiamarin in Example 5. The control formulations replace the deionized water in phase B with equal masses of gentiopicroside, swertiamarin, and swertiamarin, respectively.

[0091]

[0092] The preparation method of the above gel ointment is as follows: Weigh each component of phase A into a beaker according to the mass fraction, heat and stir in a water bath at 75°C to obtain a uniformly dispersed phase A without visible agglomerates, cool to room temperature, weigh the corresponding mass of each component of phase B and phase C, add them to phase A, stir until the solid is completely dissolved, and obtain a uniformly dispersed gel ointment material without visible agglomerates.

[0093] The stability and soothing efficacy of the gel ointment were tested according to the methods provided in the references.

[0094] After centrifugation, no stratification or precipitation was observed in any of the gel-like ointment samples. No precipitation, stratification, or discoloration was observed within three months of storage at room temperature. After one month of cold and heat resistant treatment and subsequent return to room temperature, the samples containing gentiopicrin, swertiamarin, and swertiamarin showed slight yellowing, while the remaining samples showed no precipitation, stratification, or discoloration. After one month of high-temperature treatment and subsequent return to room temperature, the samples containing gentiopicrin, swertiamarin, and swertiamarin showed slight yellowing, while the remaining samples showed no precipitation, stratification, or discoloration. This indicates that 6'-O-hexanoyl gentiopicrin, 6'-O-octanoyl swertiamarin, and 6'-O-palmitoyl swertiamarin exhibit better thermal stability than gentiopicrin, swertiamarin, and swertiamarin, respectively.

[0095] Group 1: The initial redness scores of 30 subjects with sensitive skin were 23.13, 22.87, and 23.05, respectively. After 28 days of using the ointment containing 6'-O-hexanoyl gentiopicroside, the ointment containing gentiopicroside, and the blank ointment, the average redness scores were 21.04 (significant P < 0.01), 21.33 (significant P < 0.01), and 22.17 (significant P < 0.01), respectively. This indicates that 6'-O-hexanoyl gentiopicroside has good anti-redness and soothing effects, and is superior to gentiopicroside.

[0096] In the second group, the initial redness scores of 30 subjects with sensitive skin were 23.25, 22.94, and 23.40, respectively. After 28 days of using the ointment containing 6'-O-capryloyl swertiamarin, the ointment containing swertiamarin, and the blank ointment, the average redness scores were 21.32 (significant P < 0.01), 21.55 (significant P < 0.01), and 22.47 (significant P < 0.01), respectively. This indicates that 6'-O-capryloyl swertiamarin has good anti-redness and soothing effects, and is superior to swertiamarin.

[0097] The third group of 30 subjects with sensitive skin had initial redness values ​​of 23.07, 22.89, and 23.01, respectively. After 28 days of using the ointment containing 6'-O-palmitoyl swertiamarin, the ointment containing swertiamarin, and the blank ointment, the average redness values ​​were 20.75 (significant P < 0.01), 21.27 (significant P < 0.01), and 22.09 (significant P < 0.01), respectively. This indicates that 6'-O-palmitoyl swertiamarin has good anti-redness and soothing effects, and is superior to swertiamarin.

[0098] Example 10

[0099] The emulsifying properties of the fatty acylated cleaved iridoid ether glycosides in this embodiment were investigated as follows:

[0100] The following compounds were prepared according to the method described in Example 1: 6'-O-hexanoyl gentiopicroside, 6'-O-octanoyl gentiopicroside, 6'-O-decanoyl gentiopicroside, 6'-O-lauroyl gentiopicroside, 6'-O-myristoyl gentiopicroside, 6'-O-palmitoyl gentiopicroside, 6'-O-stearoyl gentiopicroside, 6'-O-oleoyl gentiopicroside, 6'-O-arachidoyl gentiopicroside, and 6'-O-behenoyl gentiopicroside. Their structural formulas are shown below:

[0101]

[0102]

[0103]

[0104]

[0105]

[0106]

[0107]

[0108] The emulsifying properties of the above products were tested according to the methods provided in the references. A 50 ml solution of 2.0% fatty acylated cleaved iridoid glycosides was prepared, heated to 60°C, and placed in a 100 ml stoppered graduated cylinder. 20 ml of liquid squalane (60°C) was added, the stopper was tightened, and the cylinder was shaken vigorously up and down 5 times. After standing and cooling, the time required to separate 10 ml of water at 25°C was recorded. The control sample was replaced with an equal mass of gentiopicrin, and the control sample was replaced with an equal mass of water. The test results are as follows:

[0109]

[0110] The above test results indicate that fatty acyl gentiopicroside has emulsifying or cleaning effects, and fatty acylated secoiridinol glycosides can be used as emulsifiers or cleaners. It also shows that the introduction of fatty acyl groups enhances the lipid solubility of gentiopicroside or secoiridinol glycosides.

[0111] Example 11

[0112] The anti-inflammatory and antipruritic effects of fatty acylated cleaved iridoid glycosides in this embodiment were investigated as follows:

[0113] The blank formulations of the gel ointment are shown in the table below. The test formulations replace the deionized water in phase B with equal masses of 6'-O-stearoyl gentiopicroside prepared in Example 2 and palmitoyl gentiopicroside extract prepared in Example 8. The control formulations replace the deionized water in phase B with equal masses of gentiopicroside and gentiopicroside extract.

[0114]

[0115] The preparation method of the above gel ointment is as follows: Weigh each component of phase A into a beaker according to the mass fraction, heat and stir in a water bath at 70°C to obtain a uniformly dispersed phase A without visible agglomerates, cool to 60°C, weigh the corresponding mass of each component of phase B and phase C, add them to phase A, stir until the solid is completely dissolved, cool to room temperature, and obtain a uniformly dispersed gel ointment material without visible agglomerates.

[0116] The anti-inflammatory and antipruritic effects of the gel ointment were tested according to the methods provided in the references.

[0117] Thirty subjects cleaned their arms under the supervision of an experimenter, following standard procedures, and sat quietly for 30 minutes in a temperature and humidity controlled laboratory ((21±1)℃, 50%±10%). At least five 25 mm × 25 mm areas were selected on the inner side of both forearms, marked with a ruler and skin marker. The test areas were first adhered with tape, pressed for 2 seconds, and then slowly peeled off, continuing until visible erythema appeared. Then, a 25 mm × 25 mm piece of non-woven fabric was soaked in 10 mg·mL⁻¹ water. -1 The sample was soaked in histamine solution until completely saturated, then removed and applied to the torn erythema test area. After 10 minutes, it was removed and allowed to dry completely before proceeding with subsequent tests. The severity of redness and itching was recorded as an initial score (0 - none, 1 - mild, 2 - moderate, 3 - severe). The sample area was calculated at (10.0 ± 0.1) mg / cm³. -2 Apply the gel ointment as directed. After 30 minutes, ask and record the subject's subjective feelings about the test area. Subjects self-assess and score the skin stinging and itching. Experts assess and score the degree of redness and itching at the test site (final score).

[0118] The mean initial redness and swelling scores of the 30 subjects with sensitive skin were 1.95 (significant P < 0.05), 2.19 (significant P < 0.05), 1.99 (significant P < 0.05), 1.90 (significant P < 0.05), and 2.06 (significant P < 0.05), respectively.

[0119] The mean initial pruritus scores were 1.82 (significant P < 0.05), 1.64 (significant P < 0.05), 1.75 (significant P < 0.05), 1.60 (significant P < 0.05), and 1.78 (significant P < 0.05), respectively.

[0120] After using gel ointments containing 6'-O-stearoyl gentiopicroside, palmitoyl gentiopicroside, gentiopicroside, and gentiopicroside, and a blank gel ointment, the mean final scores for redness and swelling were 1.03 (significant P < 0.05), 1.19 (significant P < 0.05), 1.35 (significant P < 0.05), 1.31 (significant P < 0.05), and 1.47 (significant P < 0.05), respectively.

[0121] The mean final scores for pruritus were 0.70 (significant P < 0.05), 0.68 (significant P < 0.05), 1.02 (significant P < 0.05), 0.94 (significant P < 0.05), and 1.56 (significant P < 0.05), respectively.

[0122] The above data indicate that 6'-O-stearoyl gentiopicroside has anti-inflammatory and antipruritic effects, and its effects are better than those of gentiopicroside. Palmitoyl gentiopicroside extract also has anti-inflammatory and antipruritic effects, and its effects are better than those of gentiopicroside extract.

[0123] Example 12

[0124] The antibacterial efficacy of the fatty acylated cleaved iridoid glycosides in this embodiment was investigated as follows:

[0125] The blank formulations of the test solutions are shown in the table below. The undecenoyl swertiamarin prepared in Example 4, the oleoyl swertiamarin prepared in Example 6, and the myristoyl Gentiana scabra extract prepared in Example 7 replace the deionized water in phase B by equal mass. The control formulation replaces the deionized water in phase B with equal mass of swertiamarin, swertiamarin, and Gentiana scabra extract.

[0126]

[0127] The preparation method of the above test solution is as follows: Weigh each component of phase A into a beaker according to the mass fraction, stir at room temperature to obtain a uniformly dispersed phase A, weigh the corresponding mass of each component of phase B and phase C, add them into phase A, stir until the solid is completely dissolved, and obtain a test solution that is uniformly dispersed and has no visible agglomerates.

[0128] The inhibitory activity of the test solution against Staphylococcus aureus and Escherichia coli was determined according to the method provided in the reference. Specifically, sterile culture medium was poured into a petri dish, cooled and solidified, and then 0.5 mL of 10... 9CFU·mL -1 The bacterial suspension was evenly spread, and sterile 10 mm circular filter paper discs were immersed in the test solution for 2 min. Then, using sterile forceps, the filter paper discs were placed at equal intervals in petri dishes, with 7 discs in each dish. Five parallel experiments were performed for each bacterial species. The petri dishes were inverted and incubated at (36±1)℃ for 48 h. The diameter of the inhibition zone was measured after incubation. The test results are as follows:

[0129]

[0130] The above test results indicate that undecenoyl swertiamarin, oleoyl swertiamarin, myristoyl gentiana extract, swertiamarin, swertiamarin, and gentiana extract all have certain antibacterial effects. Moreover, the antibacterial effect of undecenoyl swertiamarin is stronger than that of swertiamarin, the antibacterial effect of oleoyl swertiamarin is stronger than that of swertiamarin, and the antibacterial effect of myristoyl gentiana extract is stronger than that of gentiana extract.

Claims

1. A class of fatty acylated cleaved iridoid glycosides, the structures of which are represented by formulas (I), (II) or (III): in, R1, R2, and R3 are each independently selected from alkyl or alkenyl groups having 5 to 21 carbon atoms.

2. The fatty acylated cleaved cycloalkenyl glycoside according to claim 1, wherein R1, R2, and R3 are each independently selected from straight-chain alkyl or straight-chain alkenyl groups having 5 to 21 carbon atoms.

3. The fatty acylated cleaved cycloalkenyl glycoside according to claim 2, wherein R1, R2, and R3 are selected from straight-chain alkyl groups with 5 to 17 carbon atoms or straight-chain alkenyl groups with 10 to 17 carbon atoms.

4. A method for preparing the fatty acylated cleaved iridoid glycoside according to any one of claims 1 to 3, comprising the following steps: (1) Add cleaved iridoid glycosides and organic solvent A to the reactor and stir until the cleaved iridoid glycosides are completely dispersed or dissolved; (2) Maintain the temperature of the reactor at -10~30℃, and slowly add fatty acyl halides while stirring. After the addition is complete, add inorganic alkaline solid to neutralize the hydrogen halide generated by the reaction, continue stirring for 5~24 h, and then cool down; (3) After cooling to room temperature, filter the mixture in the reactor under reduced pressure, transfer the filtrate to a flask for reduced pressure distillation, remove the organic solvent, and obtain the mixture; (4) Crush the mixture, place it in a suction funnel, and wash it multiple times with organic solvent B. During the washing process, filter under reduced pressure and collect the filter residue; (5) Dissolve the filter residue in hot organic solvent C, filter it while hot, and distill the filtrate under reduced pressure to obtain a solid powder, namely fatty acylated cleaved iridoid glycosides.

5. The preparation method according to claim 4, wherein the molar ratio of the secoiridin in step (1) to the fatty acyl halide in step (2) is 2:(1.5~1.8), and the fatty acyl halide is an alkyl acyl halide or an alkenyl acyl halide.

6. The preparation method according to claim 4, wherein the organic solvent A in step (1) is selected from at least one of 1,3-dimethyl-2-imidazolinone, 2,5-dimethyltetrahydrofuran, 2-methyltetrahydrofuran, N-butylpyrrolidone, N-methylpyrrolidone, N-ethylpyrrolidone, acetone, dipropylene glycol dimethyl ether, dimethyl sulfoxide, diethylene glycol dimethyl ether, diethoxyethyl succinate, sulfolane, methyl tert-butyl ether, methyl ethyl ketone, tert-butanol, tetrahydrofuran, propylene carbonate, ethylene carbonate, isopropylglycerin, ethanol, ethyl propyl ether, acetonitrile, diethyl ether, methyl acetate, ethyl acetate, isopropanol, isopropyl ether, and isosorbide dimethyl ether; in step (4) The organic solvent B is selected from 1-hexene, 2-methylpentane, cyclohexane, cyclohexene, cyclopentane, petroleum ether, n-hexane, and n-octane; the organic solvent C in step (5) is selected from at least one of 2-methyltetrahydrofuran, acetone, methyl tert-butyl ether, methyl ethyl ketone, tert-butanol, tetrahydrofuran, ethanol, ethyl propyl ether, methyl acetate, ethyl acetate, isopropanol, and isopropyl ether; the inorganic alkaline solid in step (2) is selected from at least one of potassium silicate, sodium silicate, disodium hydrogen phosphate, calcium hydroxide, potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, calcium bicarbonate, potassium bicarbonate, and sodium bicarbonate; the fatty acyl halide is an alkyl acyl chloride, alkyl acyl bromide, or an alkenyl acyl chloride or alkenyl acyl bromide.

7. A fatty acylated gentian plant extract containing any one of the fatty acylated cleaved iridoid glycosides according to claims 1-3, wherein the gentian plant extract is a water-soluble or alcohol-soluble solid powder.

8. The gentian extract of fat-acylated plants as described in claim 7, wherein the gentian plants include *Gentiana aba*, *Gentiana datunziensis*, *Gentiana alishanensis*, *Gentiana dwarf*, *Gentiana dwarf Yushanensis*, *Gentiana batangensis*, *Gentiana scabraensis*, *Gentiana speckula*, *Gentiana bracteata*, *Gentiana baoxingensis*, *Gentiana dauricum*, *Gentiana pentaphyllum*, *Gentiana bomiensis*, *Gentiana pallida*, *Gentiana scabraensis ... Gentian, Dulongjiang Gentian, Short-stalked Gentian, Short-tubed Gentian, Folded Gentian, Multiflora Gentian, Multi-branched Gentian, Emei Gentian, Ear-folded Gentian, Chickweed Gentian, Reflexed-flowered Gentian, Radix Gentian, Cortex Gentian, Alpine Gentian, Kaohsiung Gentian, High Purple Gentian, Leather-leaved Gentian, Fringed Gentian, Ornamental Gentian, Tubular Gentian, Guangxi Gentian, He's Gentian, Riverside Gentian, black-purple gentian, thick-edged gentian, thick-leaved gentian, Hu's gentian, cauliflower gentian, lakeside gentian, gorgeous gentian, South China gentian, yellow-white gentian, yellow-eared gentian, yellow-tubed gentian, yellow-flowered gentian, yellow gentian, Huangshan gentian, yellow-striped gentian, gray-green gentian, Gyirong gentian, ridge-calyx gentian, ridge-protruding gentian, false-scaled gentian, false aquatic gentian, false broom-branch gentian, eyelash gentian, Jingdong gentian Gentiana sedum, Gentiana scabra, Gentiana scabra, Gentiana kunmingensis, Gentiana kunming dwarf gentiana, Gentiana scabra ... Gentiana scabra, Gentiana macrophylla (Gentiana macrophylla var. maculata), Gentiana scabra, Gentiana macrophylla, Gentiana macrophylla, Gentiana scabra ... Gentian, Gentiana stalkus, Gentiana scabra leaf, Gentiana macrophylla, Gentiana scabra, Gentiana scabra, Gentiana scabra (also known as creeping gentian), Gentiana scabra, Gentiana macrophylla, Gentiana scabra (also known as Tibetan gentian), Gentiana macrophylla (also known as whole-calyx gentian), Gentiana scabra (also known as bearded gentian), Gentiana scabra (also known as soft gentian), Gentiana scabra (also known as papillary gentian), Gentiana scabra (also known as weak gentian), Gentiana triflora (also known as triangular-leaved gentian), Gentiana tricolor (also known as trifoliate gentian), Gentiana trifoliate (also known as mountain gentian), Gentiana scabra (also known as southern Shaanxi gentian). Gentiana santalinus, Gentiana fan-shaped santalinus, Gentiana sparse-leaved santalinus, Gentiana stenoptera, Gentiana crimsonii, Gentiana deeply lobed, Gentiana reniformis, Gentiana caryophyllus, Gentiana scabra, Gentiana scabra, Gentiana sparsely-flowered, Gentiana aquatic, Gentiana macrocarpa, Gentiana filamentosa, Gentiana filamentosa, Gentiana filamentosa, Gentiana scabra ...Gentiana taroko, Gentiana asparagus-leaf, Gentiana azure, Gentiana tianshanensis, Gentiana striped, Gentiana stripe-leaved, Gentiana tubulara, Gentiana capitulata, Gentiana capitulata, Gentiana elliptica, Gentiana washanensis, Gentiana serrata, Gentiana serrata var. ... Gentiana macrophylla, Gentiana stellaria, Gentiana stellaria, Gentiana xinganensis, Gentiana xingrenensis, Gentiana styracifolia, Gentiana lindracea, Gentiana petiolate, Gentiana calyx, Gentiana yizeshanensis, Gentiana yiliangensis, Gentiana heterophylla, Gentiana scalyx, Gentiana scalyx, Gentiana pubescenta, Gentiana yushanensis, Gentiana spheroides, Gentiana yunnanensis, Gentiana yunnanensis, Gentiana zekuensis, Gentiana changbaishanensis, Gentiana long-calyx, Gentiana long-stalked, Gentiana long-fringed, Gentiana long-haired, Gentiana long-haired, Gentiana variegata, Gentiana tinctoria, Gentiana straight-calyx, Gentiana zhongdianensis, Gentiana zhongdianensis spoon-calyx, Gentiana sinensis, Gentiana central Asiaensis, Gentiana bell-shaped, Gentiana broom-shaped, Gentiana chinensis, Gentiana bamboo forest, Gentiana purpurea, Gentiana awl-calyx, Gentiana awl-leaf.

9. The use of the fatty acylated cleaved iridoid glycosides according to any one of claims 1 to 3, or the fatty acylated Gentiana plant extracts according to any one of claims 7 to 8, as raw materials in the preparation of therapeutic, soothing, anti-redness, anti-inflammatory, antipruritic, cleansing, and antibacterial drugs, or the use of the fatty acylated cleaved iridoid glycosides or fatty acylated Gentiana plant extracts as emulsifiers in pharmaceuticals.

10. The application of the fatty acylated cleaved iridoid glycosides according to any one of claims 1 to 3 and the fatty acylated Gentianaceae plant extracts according to any one of claims 7 to 8 as daily chemical raw materials in daily chemical products, wherein the daily chemical raw materials exert soothing, redness-reducing, anti-inflammatory, antipruritic, cleansing, emulsifying, and antibacterial effects.

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