Paeonol phosphate ester, preparation method therefor, and use thereof
By modifying the structure of paeonol, paeonol phosphate was synthesized, solving the problems of odor and solubility of paeonol, achieving stronger anti-inflammatory activity and enabling its wide application in anti-inflammatory drugs and cosmetics.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- SHANDONG HUAWUTANG BIOLOGICAL TECHNOLOGY CO LTD
- Filing Date
- 2024-11-14
- Publication Date
- 2026-05-07
AI Technical Summary
Paeonol, a small-molecule phenolic compound, has a distinctive odor and is irritating to the skin. Furthermore, its poor solubility in cold water limits its widespread use in anti-inflammatory drugs and cosmetics.
Paeonol phosphate was synthesized by esterifying the phenolic hydroxyl group in the paeonol structure, and then reacted with phosphite in an organic solvent to generate an intermediate. The intermediate was then debenzylated or ethylated to generate paeonol phosphate. The pharmaceutically acceptable salt form was further prepared by introducing a hydrophilic phosphate group to improve solubility and anti-inflammatory activity.
Paeonol phosphate avoids the peculiar odor and skin irritation, significantly improves solubility in cold water, and exhibits stronger anti-inflammatory activity, making it suitable for the preparation of anti-inflammatory drugs and cosmetics.
Smart Images
Figure CN2024132084_07052026_PF_FP_ABST
Abstract
Description
Paeonol phosphate, its preparation method and uses
[0001] This application claims priority to Chinese Patent Application No. 2024115604239, filed on November 4, 2024, entitled "Paeonol Phosphate and its Preparation Method and Use", the entire contents of which are incorporated herein by reference. Technical Field
[0002] This application relates to the fields of pharmaceutical and cosmetic technology, and in particular to a paeonol phosphate ester, its preparation method, and its uses. Background Technology
[0003] Paeonol is a major active ingredient extracted from the root bark of peony or the whole herb of Cynanchum paniculatum. It appears as white to slightly yellow, lustrous needle-like crystals and possesses antipyretic, analgesic, antibacterial, anti-inflammatory, and antioxidant biological activities. Paeonol is used as a major additive in cosmetics, toothpaste, soap, and other daily necessities. Tablets and topical ointments made primarily from paeonol monomers are also used clinically. Marketed paeonol preparations include paeonol tablets, paeonol anti-allergic dermatitis ointment, paeonol cyclodextrin injection, and oral solutions (Int J Nanomedicine, 2011, 6:1603-1610). However, paeonol is a small-molecule phenol compound with a distinctive odor and weak drug-resistant activity. Compared to other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and celecoxib, its clinical application is not widespread. Therefore, it is of great significance to obtain paeonol derivatives with strong anti-inflammatory activity and no special odor or skin irritation through structural optimization, using paeonol as a lead compound.
[0004] Summary of the Invention
[0005] In view of the shortcomings of the prior art, the first objective of this application is to provide a paeonol phosphate ester, its preparation method and uses.
[0006] To achieve the above objectives, the technical solution adopted in this application is as follows:
[0007] On the one hand, there is a paeonol phosphate ester, the structural formula of which is shown in formula (I):
[0008] On the other hand, a method for preparing paeonol phosphate includes the following steps:
[0009] In an organic solvent, paeonol reacts with dibenzyl phosphite or diethyl phosphite under the action of an organic base and DMAP to form an intermediate, which is then debenzylated or ethylated to form paeonol phosphate.
[0010] Furthermore, the organic solvent is selected from one or a combination of several of carbon tetrachloride, acetonitrile, tetrahydrofuran, and dioxane.
[0011] Furthermore, the amount of dibenzyl phosphite or diethyl phosphite used is 1.2 to 1.8 equivalents of paeonol.
[0012] Furthermore, the organic base is selected from any one or a combination of several of triethylamine, DBU, DIEPA, and pyridine, and the amount of the organic base used is 2.5 to 6 equivalents of paeonol.
[0013] Furthermore, the reaction temperature is 0–25°C, and the reaction time is 30–150 min.
[0014] Furthermore, the debenzylation process is carried out under the action of a catalyst / hydrogen; the catalyst is any one or a combination of two of Pd / C and PtO2.
[0015] Furthermore, the deethylation process is carried out under the action of TMSX; the TMSX is selected from any one or a combination of several of TMSCl, TMSBr, and TMSI.
[0016] On the other hand, a paeonol phosphate salt, which is any pharmaceutically acceptable salt of the paeonol phosphate shown in formula (I) above.
[0017] Furthermore, the paeonol phosphate salt includes, but is not limited to, sodium and potassium salts of paeonol phosphate.
[0018] Furthermore, the paeonol phosphate salt is prepared by paeonol phosphate as shown in formula (I) and the corresponding inorganic base.
[0019] On another aspect, the above-mentioned paeonol phosphate or paeonol phosphate salt is used in the preparation of anti-inflammatory drugs.
[0020] On the other hand, the above-mentioned use of paeonol phosphate or paeonol phosphate salt in the preparation of cosmetics.
[0021] Furthermore, the cosmetics include, but are not limited to, any one of the following: anti-inflammatory, soothing, whitening, anti-aging, and repairing cosmetics.
[0022] Compared with the prior art, this application has the following beneficial effects:
[0023] 1. The paeonol phosphate provided in this application is a novel compound. This application is the first to design and successfully synthesize paeonol phosphate.
[0024] 2. The paeonol phosphate ester provided in this application avoids the special odor and skin irritation of small molecule phenolic compounds by esterifying the phenolic hydroxyl groups in the paeonol structure. In addition, paeonol has poor solubility in cold water, with a solubility of less than 0.12g in 100mL of cold water. This application introduces a hydrophilic phosphate group into the paeonol structure, which can also solve the disadvantage of poor solubility of paeonol in cold water. The solubility of paeonol phosphate ester in 100mL of cold water increases to 7.8-8.2g, and the solubility of paeonol phosphate salt in 100mL of cold water is greater than 10g.
[0025] 3. The paeonol phosphate provided in this application has stronger anti-inflammatory activity than paeonol and can be used in the preparation of anti-inflammatory drugs or cosmetics. Attached Figure Description
[0026] The above and / or additional aspects and advantages of this application will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:
[0027] Figure 1 is a schematic diagram of the cytotoxicity test results of paeonol phosphate in this application.
[0028] Figure 2 shows the results of a single-dose anti-inflammatory activity test of paeonol phosphate in this application.
[0029] Figure 3 shows the results of the multi-dose anti-inflammatory activity test of paeonol phosphate in this application.
[0030] In the figure, P0 represents paeonol, and P8 represents paeonol phosphate. Detailed Implementation
[0031] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of this application, but do not limit this application in any way. The following content is merely an exemplary description of the scope of protection claimed in this application, and those skilled in the art can make various changes and modifications to the invention based on the disclosed content, which should also fall within the scope of protection claimed in this application.
[0032] In this application, some commonly used abbreviations have the following meanings: DBU 1,8-diazabicyclo[5.4.0]undec-7-ene; DIPEA N,N-diisopropylethylamine; DMAP 4-dimethylaminopyridine; TMSX trimethylsilane reagents; TMSCl trimethylchlorosilane; TMSBr trimethylbromosilane; TMSI trimethyliodosilane.
[0033] Unless otherwise specified, all chemical reagents used in the embodiments of this application were obtained through conventional commercial means.
[0034] The present application will be further described below by way of specific embodiments.
[0035] Example 1
[0036] Preparation of the intermediate paeonol dibenzyl phosphate
[0037] At 0℃, dibenzyl phosphite (10.4 g, 1.2 eq.) was slowly added dropwise to a mixed solution of CCl4 (30 mL) / MeCN (60 mL) containing paeonol (5.5 g, 1.0 eq.), DIPEA (19.2 g, 4.5 eq.), and DMAP (50 mg), at a rate of 1-2 drops / s. After addition, the mixture was stirred at 0℃ for 15 min, then allowed to return to room temperature and the reaction continued for 2.5 h. The mixture was evaporated by rotary evaporation, and the residual solution was wet-mounted for column chromatography with PE / EA at a ratio of 3:1 to 2:1. Paeonol dibenzyl phosphite was obtained as a colorless liquid, weighing 10.0 g, with a yield of 71%. The specific results of NMR analysis were as follows: 1 H NMR (400MHz, CDCl3) δ7.77(d,J=9.6Hz,1H),7.33-7.31(m,10H),6.93(d,J=1.2Hz,1H ), 6.74(d,J=9.6,1.2Hz,1H),5.16(dd,J=8.8,2.0Hz,4H),3.73(s,,3H),2.52(s,3H).
[0038] Example 2
[0039] Preparation of the intermediate paeonol dibenzyl phosphate
[0040] At 0℃, dibenzyl phosphite (15.6 g, 1.8 eq.) was slowly added dropwise to a mixed solution of CCl4 (30 mL) / MeCN (60 mL) containing paeonol (5.5 g, 1.0 eq.), DIPEA (19.2 g, 4.5 eq.), and DMAP (50 mg), at a rate of 1-2 drops / s. After addition, the mixture was stirred at 0℃ for 15 min, then allowed to return to room temperature and the reaction continued for 0.5 h. The mixture was evaporated by rotary evaporation, and the residual solution was wet-mounted for column chromatography with PE / EA 3:1 to 2:1 as the eluent. Paeonol dibenzyl phosphite was obtained as a colorless liquid, weighing 11.7 g, with a yield of 83%. The specific results of NMR analysis were as follows: 1H NMR (400MHz, CDCl3) δ7.77(d,J=9.6Hz,1H),7.33-7.31(m,10H),6.93(d,J=1.2Hz,1H ), 6.74(d,J=9.6,1.2Hz,1H),5.16(dd,J=8.8,2.0Hz,4H),3.73(s,,3H),2.52(s,3H).
[0041] Example 3
[0042] Preparation of the intermediate paeonol dibenzyl phosphate
[0043] At 0℃, dibenzyl phosphite (13.1 g, 1.5 eq.) was slowly added dropwise to a mixed solution of CCl4 (30 mL) / MeCN (60 mL) containing paeonol (5.5 g, 1.0 eq.), DIPEA (10.6 g, 2.5 eq.), and DMAP (50 mg), at a rate of 1-2 drops / s. After addition, the mixture was stirred at 0℃ for 15 min, then allowed to return to room temperature and the reaction continued for 0.5 h. The mixture was evaporated by rotary evaporation, and the residual solution was wet-mounted for column chromatography with PE / EA 3:1 to 2:1 as the eluent. Paeonol dibenzyl phosphite was obtained as a colorless liquid, weighing 10.3 g, with a yield of 73%. The specific results of NMR analysis were as follows: 1 H NMR (400MHz, CDCl3) δ7.77(d,J=9.6Hz,1H),7.33-7.31(m,10H),6.93(d,J=1.2Hz,1H ), 6.74(d,J=9.6,1.2Hz,1H),5.16(dd,J=8.8,2.0Hz,4H),3.73(s,,3H),2.52(s,3H).
[0044] Example 4
[0045] Preparation of the intermediate paeonol dibenzyl phosphate
[0046] At 0℃, dibenzyl phosphite (13.1 g, 1.5 eq.) was slowly added dropwise to a mixed solution of CCl4 (30 mL) / MeCN (60 mL) containing paeonol (5.5 g, 1.0 eq.), DIPEA (25.5 g, 6 eq.), and DMAP (50 mg), at a rate of 1-2 drops / s. After addition, the mixture was stirred at 0℃ for 15 min, then allowed to return to room temperature for 0.5 h. The mixture was evaporated by rotary evaporation, and the residue was wet-mounted for column chromatography with PE / EA 3:1 to 2:1 as the eluent. Paeonol dibenzyl phosphite was obtained as a colorless liquid, weighing 11.5 g, with a yield of 82%. The specific results of NMR analysis were as follows: 1H NMR (400MHz, CDCl3) δ7.77(d,J=9.6Hz,1H),7.33-7.31(m,10H),6.93(d,J=1.2Hz,1H ), 6.74(d,J=9.6,1.2Hz,1H),5.16(dd,J=8.8,2.0Hz,4H),3.73(s,,3H),2.52(s,3H).
[0047] Example 5
[0048] Preparation of the intermediate paeonol diethyl phosphate
[0049] At 0℃, diethyl phosphite (2.07 g, 1.5 eq.) was slowly added dropwise to a mixed solution of CCl4 (5 mL) / MeCN (10 mL) containing paeonol (1.66 g, 1.0 eq.), DIPEA (3.23 g, 2.5 eq.), and DMAP (12 mg), at a rate of 1-2 drops / s. After addition, the mixture was stirred at 0℃ for 15 min, then allowed to return to room temperature and the reaction continued for 1 h. The reaction solution was concentrated and then subjected to column chromatography using a wet loading method with PE / EA at a ratio of 3:1 to 2:1. Paeonol diethyl phosphate was obtained as a colorless liquid, weighing 2.48 g, with a yield of 82%. The specific results of NMR analysis were as follows: 1 H NMR (400MHz, CDCl3) δ7.76 (d, J = 8.8 Hz, 1H), 6.99 (s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 4.23 (m, 4H), 3.84 (s,, 3H), 2.59 (s, 3H), 1.34 (m, 6H).
[0050] Example 6
[0051] Preparation of the intermediate paeonol diethyl phosphate
[0052] At 0℃, diethyl phosphite (2.07 g, 1.5 eq.) was slowly added dropwise to a mixed solution of CCl4 (5 mL) / MeCN (10 mL) containing paeonol (1.66 g, 1.0 eq.), Et3N (5.06 g, 5.0 eq.), and DMAP (12 mg), at a rate of 1-2 drops / s. After addition, the mixture was stirred at 0℃ for 15 min, then allowed to return to room temperature and the reaction continued for 0.5 h. The reaction solution was concentrated and then subjected to column chromatography using a wet loading method with PE / EA 3:1 to 2:1 as the eluent. Paeonol diethyl phosphate was obtained as a colorless liquid, weighing 2.90 g, with a yield of 96%. The specific detection results after NMR analysis were as follows: 1H NMR (400MHz, CDCl3) δ7.76 (d, J = 8.8 Hz, 1H), 6.99 (s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 4.23 (m, 4H), 3.84 (s,, 3H), 2.59 (s, 3H), 1.34 (m, 6H).
[0053] Example 7
[0054] Preparation of the intermediate paeonol diethyl phosphate
[0055] At 0℃, diethyl phosphite (2.07 g, 1.5 eq.) was slowly added dropwise to a mixed solution of CCl4 (5 mL) / MeCN (10 mL) containing paeonol (1.66 g, 1.0 eq.), DIPEA (6.45 g, 5.0 eq.), and DMAP (12 mg), at a rate of 1-2 drops / s. After addition, the mixture was stirred at 0℃ for 15 min, then allowed to return to room temperature for 0.5 h. The reaction solution was concentrated and then subjected to column chromatography using a wet loading method with PE / EA at a ratio of 3:1 to 2:1. Paeonol diethyl phosphate was obtained as a colorless liquid, weighing 2.93 g, with a yield of 97%. The specific results of NMR analysis were as follows: 1 H NMR (400MHz, CDCl3) δ7.76 (d, J = 8.8 Hz, 1H), 6.99 (s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 4.23 (m, 4H), 3.84 (s,, 3H), 2.59 (s, 3H), 1.34 (m, 6H).
[0056] Example 8
[0057] Preparation of Paeonol Phosphate
[0058] Paeonol dibenzyl phosphate (10 g, 0.023 mol) was dissolved in 30 mL of methanol. After replacing the nitrogen with nitrogen, 5% Pd / C (1 g) was added, and H2 was bubbled through the solution overnight at normal pressure. The Pd / C was removed by filtration, and the filtrate was evaporated to dryness to obtain 5.48 g of paeonol phosphate, a white solid with a yield of 95% and no special odor. The specific results of NMR analysis are as follows: 1 H NMR (400MHz, DMSO-d6) δ7.68(dd,J=8.8,1.1Hz,1H),6.98 (dd,J=2.8,1.1Hz,1H),6.83(dd,J=8.5,2.8Hz,1H),3.81(s,3H),2.54(s,3H); 13C NMR (100MHz, DMSO-d6) δ196.68,163.67,152.91,131.85,123.72,110.29,106.83,56.17,31.68.
[0059] Example 9
[0060] Preparation of Paeonol Phosphate
[0061] Paeonol diethyl phosphate (10 g, 1.0 eq.) was dissolved in 250 mL of dry dichloromethane. TMSBr (250 mL) was slowly added dropwise under nitrogen. After the addition was complete, the mixture was allowed to rise naturally to room temperature and stirred for 14 h. The solution was concentrated by rotary evaporation, and then 50 mL of methanol / water (9 / 1) was added. The mixture was stirred for 1 h and then concentrated by rotary evaporation. The concentrated product was an orange-red solid. After washing with 30 mL of ethyl acetate, the solid was dissolved in anhydrous ethanol (10 mL / g crude product) / (0.2 mL / mL anhydrous ethanol) solution. 10% pharmaceutical activated carbon was added, and the mixture was heated at 50 °C for 0.5 h. The solution was filtered through a sintered glass funnel. The filtrate was colorless. After concentration, 6.84 g of a white solid was obtained, with a yield of 84%. The solid had no special odor. NMR analysis showed the following results: 1 H NMR (400MHz, DMSO-d6) δ7.68(dd,J=8.8,1.1Hz,1H),6.98(dd,J=2.8,1.1Hz,1H),6.83(dd,J=8.5,2.8Hz,1H),3.81(s,3H),2.54(s,3H); 13 C NMR (100MHz, DMSO-d6) δ196.68,163.67,152.91,131.85,123.72,110.29,106.83,56.17,31.68. 1 H NMR (400MHz, D2O) δ7.63 (d, J = 8.8, 1H), 6.90 (s, 1H), 6.74 (d, J = 8.8 1H), 3.80 (s, 3H), 2.57 (s, 3H).
[0062] Example 10
[0063] Paeonol phosphate (368 mg, 1.5 mmol) and sodium hydroxide (120 mg, 3.0 mmol) were added to a round-bottom flask. A 1:1 methanol / water mixture was added until the raw materials were completely dissolved (approximately 10 mL). The mixture was reacted at room temperature for 1 hour. After stirring was stopped, the mixture was filtered, and the solvent was recovered from the filtrate to obtain 413 mg of a white solid, with a recovery rate of 95%. Melting point > 230 °C. 1H NMR (400MHz, D2O) δ7.64 (d, J = 8.8, 1H), 7.14 (s, 1H), 6.65 (d, J = 8.8 1H), 3.84 (s, 3H), 2.65 (s, 3H).
[0064] Example 11
[0065] Paeonol phosphate (368 mg, 1.5 mmol) was dissolved in 10 mL of a 1:1 mixture of ethanol and water. Sodium hydroxide (120 mg, 3.0 mmol) was added, and the mixture was reacted at room temperature for 1 hour. After stirring was stopped, the mixture was filtered, and most of the solvent was recovered from the filtrate. Then, 15 mL of ethanol was added, and the mixture was filtered again to obtain 410 mg of a white solid, with a recovery rate of 94%. Melting point > 230 °C. 1 H NMR (400MHz, D2O) δ7.64 (d, J = 8.8, 1H), 7.14 (s, 1H), 6.65 (d, J = 8.8 1H), 3.84 (s, 3H), 2.65 (s, 3H).
[0066] Experimental Example 1
[0067] Cytotoxicity assay
[0068] RAW264.7 cells in good growth condition were seeded in 96-well plates. The experiment was divided into a blank group, a control group, a paeonol group, and a paeonol phosphate group. Five concentration gradients were set up for each drug treatment group, and three replicates were set up for each well. After 12 h of cell seeding, the drug was added according to the concentration gradient for 8 h. After 8 h of drug treatment, 10 μL of CCK-8 solution was added to each well, and the cells were incubated in a cell culture incubator for another 1 h. The absorbance was measured at 450 nm, and the results are shown in Figure 1.
[0069] As shown in Figure 1, paeonol (P0) showed significant cytotoxicity at a concentration of 400 μM (p<0.001), while paeonol phosphate (P8) only showed cytotoxicity at a concentration of 400 μM (p<0.01).
[0070] Experiment Example 2
[0071] Anti-inflammatory activity experiment
[0072] Screening for anti-inflammatory activity with a single dose: RAW264.7 cells were seeded at an appropriate density in 12-well plates. After 12 h of seeding, a single dose of paeonol and its derivatives (final concentration 50 μM) was added. After 2 h of drug treatment, LPS (final concentration 500 ng / ml) was used to stimulate cell inflammation. After 6 h of treatment, cells were collected and RNA was extracted. RT-qPCR was used to detect iNOS and IL-6 inflammatory factors. The results, as shown in Figure 2, indicate that at 50 μM, paeonol did not show significant inhibitory effects on iNOS and IL-6 inflammatory factors, while paeonol phosphate showed significant inhibitory effects on iNOS and IL-6.
[0073] Screening for anti-inflammatory activity at multiple doses: RAW264.7 cells were seeded in cell plates at an appropriate density. After 12 h of seeding, paeonol (P0) and paeonol phosphate (P8) were diluted with PBS to an appropriate concentration. The cell supernatant was discarded, and 300 μL was added to each well. Two h later, LPS (final concentration 500 ng / ml) was used to stimulate and induce cell inflammation for 24 h. Subsequently, the cell supernatant was collected, and IL-6 and iNOS were detected using an ELISA kit. iNOS was detected using a dedicated detection kit according to the kit instructions. Figure 3 shows that the expression level of the inflammatory factor IL-6 in the cell supernatant was significantly reduced by paeonol phosphate (P8) at a concentration of 25 μM (p<0.05), and showed a clear dose-dependent effect from 12.5 to 200 μM, with the lowest expression level at 200 μM. At a concentration of 200 μM, the amount of IL-6 in the supernatant after treatment with paeonol phosphate was lower than that of paeonol (P0) at the same dose. Figure 3 shows that the expression level of iNOS by paeonol phosphate (P8) was significantly reduced at a concentration of 25 μM (p<0.05), and showed a clear dose-dependent effect from 12.5 to 200 μM, with the lowest expression level at 200 μM. At a concentration of 200 μM, the amount of iNOS in the supernatant after treatment with paeonol phosphate was lower than that of the positive control drug paeonol (P0) at the same concentration.
[0074] In summary, both single-dose and multi-dose anti-inflammatory activity results show that the paeonol phosphate provided in this application has good anti-inflammatory activity.
[0075] The above description of the embodiments is provided to enable those skilled in the art to understand and use the invention. It will be apparent to those skilled in the art that various modifications can be made to these embodiments, and the general principles described herein can be applied to other embodiments without inventive effort. Therefore, this application is not limited to the above embodiments, and any improvements and modifications made by those skilled in the art based on the disclosure of this application without departing from the scope of this application should be within the protection scope of this application.
Claims
1. A paeonol phosphate ester, wherein, Its structural formula is shown in equation (I) below:
2. The method for preparing paeonol phosphate according to claim 1, wherein, Includes the following steps: In an organic solvent, paeonol reacts with dibenzyl phosphite or diethyl phosphite under the action of an organic base and DMAP to form an intermediate, which is then debenzylated or ethylated to form paeonol phosphate.
3. The method for preparing paeonol phosphate according to claim 2, wherein, The amount of dibenzyl phosphite or diethyl phosphite used is 1.2 to 1.8 equivalents of paeonol.
4. The method for preparing paeonol phosphate according to claim 2, wherein, The organic base is selected from any one or a combination of several of triethylamine, DBU, DIEPA, and pyridine, and the amount of the organic base used is 2.5 to 6 equivalents of paeonol.
5. The method for preparing paeonol phosphate according to claim 2, wherein, The reaction temperature is 0–30°C, and the reaction time is 75–90 min.
6. The method for preparing paeonol phosphate according to claim 2, wherein, The debenzylation process is carried out in the presence of a catalyst / hydrogen; the catalyst is any one or a combination of two of Pd / C and PtO2. The deethylation process is carried out under the action of TMSX; the TMSX is selected from any one or a combination of several of TMSCl, TMSBr, and TMSI.
7. A paeonol phosphate salt, wherein, It is any pharmaceutically acceptable salt of paeonol phosphate as described in claim 1; the paeonol phosphate salt comprises a sodium or potassium salt of paeonol phosphate.
8. The method for preparing paeonol phosphate salt according to claim 7, wherein, The paeonol phosphate salt is prepared by paeonol phosphate and the corresponding inorganic base.
9. The use of the paeonol phosphate ester of claim 1 or the paeonol phosphate salt of claim 7 in the preparation of anti-inflammatory drugs.
10. The use of the paeonol phosphate ester of claim 1 or the paeonol phosphate salt of claim 7 in the preparation of cosmetics.