High-absorptivity chondroitin sulfate derivative and preparation process thereof

Abstract

The invention relates to a high-absorptivity chondroitin sulfate derivative and a preparation process thereof. Chondroitin sulfate and curcumin are subjected to esterification reaction to prepare a chondroitin sulfate coupled curcumin polymer, so that the high-absorptivity chondroitin sulfate derivative is obtained. Compared with a chondroitin sulfate raw medicine, the high-absorptivity chondroitin sulfate derivative prepared by the invention has better absorptivity, enhances the biological activity of chondroitin sulfate in the aspect of resisting osteoarthritis, has good safety, and can effectively improve the bioavailability of curcumin and prolong the action time of the medicine in vivo; the compound can be used in medicines and multifunctional foods for osteoarthritis. In addition, the preparation process is simple, the synthesis method is simple, the raw material cost is low, large-scale production is easy, and good market prospects are achieved.

Description

Technical Field

[0001] The present invention relates to the technical fields of chemical synthesis and improving drug absorption performance, and mainly relates to a highly absorbable chondroitin sulfate derivative and its preparation process, providing a highly absorbable chondroitin sulfate derivative, improving its absorption performance, enhancing the efficacy of drugs, reducing drug toxicity, and prolonging the action time of drugs in the body. Background Art

[0002] Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) composed of repeating disaccharide units of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc). It is a normal component of cartilage and can bind water molecules to lubricate joints, enabling joints to move freely. Because of its low side effects, chondroitin sulfate is often used as a dietary supplement for improving knee osteoarthritis in the United States. For traditional chondroitin sulfate, most of its molecular weight is between 50 and 100 kDa. Due to its large molecular weight, it is not easy to penetrate cell membranes and belongs to class III drugs with high solubility and poor membrane permeability in the biopharmaceutics classification system. In clinical applications, it mainly faces the problem of low bioavailability. Improving oral absorption performance is an urgent problem to be solved for strengthening clinical applications.

[0003] Esterification is considered a method to improve the hydrophobicity of many polysaccharides. Curcumin is a phenolic compound and a natural herb, mainly extracted from turmeric rhizomes, with a content of about 3% - 5% of turmeric. It has low toxicity, wide sources, low price, and good hydrophobic properties. It can activate AMPK, resulting in the accumulation of phosphorylated PINK1 on the surface of damaged mitochondria. This leads to the aggregation of Parkin in the cytoplasm, followed by phosphorylation and ubiquitination. The initiation of mitophagy has a protective effect on damaged cartilage, manifested as an increase in ATP production levels and mitochondrial membrane potential, as well as a decrease in ROS and Ca 2+ concentration. In addition, it can also promote chondrocyte proliferation and increase the mitochondrial function of chondrocytes induced by IL-1β, thus alleviating the symptoms of osteoarthritis. In order to promote the absorption of chondroitin sulfate in the human intestine and improve its bioavailability, chondroitin sulfate is hydrophobically modified with curcumin as a ligand to synthesize a highly absorbable chondroitin sulfate derivative, effectively improving its absorption in the intestine and producing a positive synergistic effect, so as to be better applied to the treatment of osteoarthritis. Summary of the Invention

[0004] Based on the above facts, the present invention selects curcumin to modify the structure of chondroitin sulfate. On the basis of maintaining the original activity, the absorption performance of chondroitin sulfate has been significantly improved. And a comprehensive characterization of the highly absorbable chondroitin sulfate derivative has been carried out. The process of modifying chondroitin sulfate with curcumin has the advantages of simple operation, short preparation cycle, low raw material cost, and easy scale-up and industrialization.

[0005] The highly absorbable chondroitin sulfate derivative prepared by the present invention and its preparation process are as follows:

[0006]

[0007] Synthesis route: First, chondroitin sulfate, 4-dimethylaminopyridine (DMAP) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) are added to a solvent system in a certain molar ratio, and the carboxyl group of chondroitin sulfate is activated by stirring for a certain time. Curcumin is added to the reaction system, and under certain time and temperature conditions, the hydroxyl group in its molecule reacts with the carboxyl group in chondroitin sulfate by an esterification reaction; after the reaction is completed, another solvent is added to the reaction system, and the synthesized product is separated by anti-solvent recrystallization. The product is washed several times with the anti-solvent, and the product is dialyzed and purified in the anti-solvent and ultrapure water for a certain time respectively. After freeze-drying, a highly absorbable chondroitin sulfate derivative is obtained.

[0008] The solvent system is formamide.

[0009] The catalyst is 4-dimethylaminopyridine and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, and the preferred molar ratio is chondroitin sulfate:4-dimethylaminopyridine:1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride = 1:1:1.

[0010] The molar ratio of chondroitin sulfate to curcumin is 1:0.5 - 3.

[0011] After adding curcumin to the reaction system, the preferred reaction time is 6 - 96 h.

[0012] After adding curcumin to the reaction system, the preferred reaction temperature is 35 - 60 °C.

[0013] The anti-solvent is ethanol.

[0014] In the FTIR of the highly absorbable chondroitin sulfate derivative, there is an ester group characteristic absorption peak at 1739 cm -1 .

[0015] The highly absorbable chondroitin sulfate derivative 1 In the 1H-NMR, the methyl characteristic peaks of the acetyl group on chondroitin sulfate and the aromatic proton characteristic peaks of curcumin are at 1.89 - 1.91 ppm and 6.74 - 8.04 ppm respectively.

[0016] The described highly absorbent chondroitin sulfate derivative has an obvious absorption peak at 280 nm in UV.

[0017] In UPLC-MS of the described highly absorbent chondroitin sulfate derivative, the corresponding primary fragment ion [M-H] of curcumin standard product appears through alkaline hydrolysis, - m / z 367.12 and the secondary fragment ion peak m / z 134.04.

[0018] Advantages of the present invention:

[0019] 1. Curcumin is selected to hydrophobically modify chondroitin sulfate. While improving the hydrophobicity of chondroitin sulfate, it can also effectively enhance the water solubility of curcumin and improve the in vitro release effects of both.

[0020] 2. The highly absorbent chondroitin sulfate derivative has good cell uptake characteristics.

[0021] 3. The highly absorbent chondroitin sulfate derivative has good in vitro antioxidant characteristics.

[0022] 4. The highly absorbent chondroitin sulfate derivative has good reactive oxygen species scavenging characteristics.

[0023] 5. The highly absorbent chondroitin sulfate derivative has good in vitro anti-inflammatory characteristics.

[0024] 6. The highly absorbent chondroitin sulfate derivative has good characteristics of promoting the proliferation of rat chondrocytes.

[0025] 7. The highly absorbent chondroitin sulfate derivative has good safety.

[0026] 8. The highly absorbent chondroitin sulfate derivative can simultaneously improve the bioavailability of chondroitin sulfate and curcumin.

[0027] 9. The highly absorbent chondroitin sulfate derivative has good anti-inflammatory characteristics for rats with osteoarthritis model.

[0028] 10. The highly absorbent chondroitin sulfate derivative has good antioxidant characteristics for rats with osteoarthritis model.

[0029] 11. The synthesis process of the highly absorbent chondroitin sulfate derivative is simple and easy to scale up to industrial production. Description of the Drawings

[0030] Figure 1It is the freeze-dried powder of the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention (a), the dispersion effect of the highly absorbent chondroitin sulfate derivative prepared by the present invention in ultrapure water (b), and the Tyndall phenomenon diagram of the dispersion of the highly absorbent chondroitin sulfate derivative prepared by the present invention in ultrapure water (c).

[0031] Figure 2 FTIR detection diagrams of chondroitin sulfate raw drug, curcumin raw drug, physical mixture, and the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention.

[0032] Figure 3 Chondroitin sulfate raw drug (a), curcumin (b), physical mixture (c), and the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention (d) 1 1H-NMR detection diagram.

[0033] Figure 4 UV detection diagrams of chondroitin sulfate raw drug, curcumin, and the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention.

[0034] Figure 5 UPLC-MS detection diagrams of the primary fragment ions (a), secondary fragment ions (b) of curcumin raw drug, the primary fragment ions (c) and secondary fragment ions (d) of the alkaline hydrolysis of the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention.

[0035] Figure 6 It is the XRD detection diagrams of chondroitin sulfate raw drug, curcumin raw drug, physical mixture, the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention, and the physical mixture of chondroitin sulfate and curcumin.

[0036] Figure 7 It is the TG detection diagrams of chondroitin sulfate raw drug, curcumin raw drug, physical mixture, the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention, and the physical mixture of chondroitin sulfate and curcumin.

[0037] Figure 8 It is the DSC detection diagrams of chondroitin sulfate raw drug, curcumin raw drug, physical mixture, the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention, and the physical mixture of chondroitin sulfate and curcumin.

[0038] Figure 9 It is the SEM detection diagrams of chondroitin sulfate raw drug (a), curcumin raw material (b), and the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention (c).

[0039] Figure 10 It is the TEM detection diagram of the highly absorbent chondroitin sulfate derivative prepared by the present invention.

[0040] Figure 11 It is the graph for measuring the critical micelle concentration of the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention.

[0041] Figure 12 It is the graph of the average particle size distribution of the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention.

[0042] Figure 13 It is the stability detection graph of chondroitin sulfate raw drug, physical mixture, and the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention in simulated gastric juice (a) and simulated intestinal fluid (b), and the stability detection graph of curcumin raw drug, physical mixture, and the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention in simulated gastric juice (c) and simulated intestinal fluid (d).

[0043] Figure 14 It is the detection graph of the uptake experiment of curcumin raw drug and the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention in mouse colorectal cancer cells (CT-26).

[0044] Figure 15 It is the ABTS free radical scavenging (a) and Fe 3+ reducing power (b) detection curve graph of chondroitin sulfate raw drug, curcumin raw drug, and the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention.

[0045] Figure 16 It is the detection graph of the reactive oxygen species scavenging ability of the blank group (a), positive group (b), chondroitin sulfate raw drug (c), curcumin raw drug (d), physical mixture (e), the highly absorbent chondroitin sulfate derivative (CSC) (f) prepared by the present invention, and dexamethasone (g) in lipopolysaccharide-induced mouse monocyte macrophage leukemia cells (RAW264.7).

[0046] Figure 17 It is the detection graph of the influence of chondroitin sulfate raw drug, curcumin raw drug, physical mixture, the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention, and dexamethasone on the levels of inflammatory factors such as interleukin-1β (IL-1β) (a), tumor necrosis factor-α (TNF-α) (b), and prostaglandin E2 (PG-E2) (c) in lipopolysaccharide-induced mouse monocyte macrophage leukemia cells (RAW264.7).

[0047] Figure 18 It is the graph of the zebrafish heart rate (a), zebrafish embryo safety experiment (b), and MTT cell safety experiment (c) of the highly absorbent chondroitin sulfate derivative (CSC) prepared by the present invention.

[0048] Figure 19Detection graphs of the proliferation of chondrocytes (CP-R087) in rats by chondroitin sulfate raw drug, curcumin raw drug, physical mixture, and highly absorbable chondroitin sulfate derivative (CSC) prepared in the present invention.

[0049] Figure 20 Plasma concentration curves of chondroitin sulfate raw drug, curcumin raw drug, physical mixture, and highly absorbable chondroitin sulfate derivative (CSC) prepared in the present invention.

[0050] Figure 21 Detection graphs of the effects of chondroitin sulfate raw drug, curcumin raw drug, physical mixture, highly absorbable chondroitin sulfate derivative (CSC) prepared in the present invention, and diacerein on the levels of inflammatory factors such as interleukin-1β (IL-1β) (a), tumor necrosis factor-α (TNF-α) (b), and prostaglandin E2 (PG-E2) (c) in the blood of osteoarthritis rats.

[0051] Figure 22 Detection graphs of the effects of chondroitin sulfate raw drug, curcumin raw drug, physical mixture, highly absorbable chondroitin sulfate derivative (CSC) prepared in the present invention, and diacerein on the levels of oxidative stress factors such as malondialdehyde (MDA) (a), reduced glutathione (GSH) (b), catalase (CAT) (c), and superoxide dismutase (SOD) (d) in the blood of osteoarthritis rats. Detailed implementation manners

[0052] The specific embodiments described herein are only used to explain the present invention and provide better examples in the preparation process, but are not used to limit the present invention.

[0053] Example 1:

[0054] First, accurately weigh a certain molar ratio of chondroitin sulfate, 4-dimethylaminopyridine, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (molar ratio 1:1:1). Use formamide as the reaction solvent and stir until dissolved. Add the weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:0.5) to the reaction system and stir in the dark at 55 °C for 48 h. The obtained reaction solution is subjected to an anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. The final obtained precipitate is dialyzed and purified in absolute ethanol and ultrapure water respectively, and then freeze-dried. The yield of the prepared highly absorbable chondroitin sulfate derivative is 45.01%.

[0055] Example 2:

[0056] First, accurately weigh chondroitin sulfate, 4-dimethylaminopyridine, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in a certain molar ratio (molar ratio is 1:1:1). Use formamide as the reaction solvent and stir until dissolved. Add the weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:1) into the reaction system, and stir in the dark at 55 °C for 48 h. The obtained reaction solution is processed by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. Dialyze and purify the finally obtained precipitate in absolute ethanol and ultrapure water respectively, and perform freeze-drying treatment. The yield of the prepared highly absorbent chondroitin sulfate derivative is 52.47%.

[0057] Example 3:

[0058] First, accurately weigh chondroitin sulfate, 4-dimethylaminopyridine, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in a certain molar ratio (molar ratio is 1:1:1). Use formamide as the reaction solvent and stir until dissolved. Add the weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:1.5) into the reaction system, and stir in the dark at 55 °C for 48 h. The obtained reaction solution is processed by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. Dialyze and purify the finally obtained precipitate in absolute ethanol and ultrapure water respectively, and perform freeze-drying treatment. The yield of the prepared highly absorbent chondroitin sulfate derivative is 48.16%.

[0059] Example 4:

[0060] First, accurately weigh chondroitin sulfate, 4-dimethylaminopyridine, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in a certain molar ratio (molar ratio is 1:1:1). Use formamide as the reaction solvent and stir until dissolved. Add the weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:3) into the reaction system, and stir in the dark at 55 °C for 48 h. The obtained reaction solution is processed by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. Dialyze and purify the finally obtained precipitate in absolute ethanol and ultrapure water respectively, and perform freeze-drying treatment. The yield of the prepared highly absorbent chondroitin sulfate derivative is 40.37%.

[0061] Example 5:

[0062] First, accurately weigh chondroitin sulfate, 4-dimethylaminopyridine, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in a certain molar ratio (molar ratio is 1:1:1). Use formamide as the reaction solvent and stir until dissolved. Add the weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:1) into the reaction system, and stir in the dark at 55 °C for 6 h. The obtained reaction solution is processed by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. Dialyze and purify the finally obtained precipitate in absolute ethanol and ultrapure water respectively, and perform freeze-drying treatment. The yield of the prepared highly absorbent chondroitin sulfate derivative is 30.82%.

[0063] Example 6:

[0064] First, accurately weigh chondroitin sulfate, 4-dimethylaminopyridine, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in a certain molar ratio (molar ratio is 1:1:1). Use formamide as the reaction solvent and stir until dissolved. Add the weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:1) into the reaction system and stir in the dark at 55 °C for 24 h. The obtained reaction solution is processed by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. Dialyze and purify the finally obtained precipitate in absolute ethanol and ultrapure water respectively, and perform freeze-drying treatment. The yield of the prepared highly absorbent chondroitin sulfate derivative is 47.18%.

[0065] Example 7:

[0066] First, accurately weigh chondroitin sulfate, 4-dimethylaminopyridine, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in a certain molar ratio (molar ratio is 1:1:1). Use formamide as the reaction solvent and stir until dissolved. Add the weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:1) into the reaction system and stir in the dark at 55 °C for 48 h. The obtained reaction solution is processed by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. Dialyze and purify the finally obtained precipitate in absolute ethanol and ultrapure water respectively, and perform freeze-drying treatment. The yield of the prepared highly absorbent chondroitin sulfate derivative is 55.26%.

[0067] Example 8:

[0068] First, accurately weigh chondroitin sulfate, 4-dimethylaminopyridine, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in a certain molar ratio (molar ratio is 1:1:1). Use formamide as the reaction solvent and stir until dissolved. Add the weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:1) into the reaction system and stir in the dark at 55 °C for 96 h. The obtained reaction solution is processed by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. Dialyze and purify the finally obtained precipitate in absolute ethanol and ultrapure water respectively, and perform freeze-drying treatment. The yield of the prepared highly absorbent chondroitin sulfate derivative is 57.19%.

[0069] Example 9:

[0070] First, accurately weigh chondroitin sulfate, 4-dimethylaminopyridine, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride in a certain molar ratio (molar ratio is 1:1:1). Use formamide as the reaction solvent and stir until dissolved. Add the weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:1) into the reaction system and stir in the dark at 35 °C for 48 h. The obtained reaction solution is processed by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. Dialyze and purify the finally obtained precipitate in absolute ethanol and ultrapure water respectively, and perform freeze-drying treatment. The yield of the prepared highly absorbent chondroitin sulfate derivative is 32.66%.

[0071] Example 10:

[0072] First, chondroitin sulfate, 4-dimethylaminopyridine and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with a certain molar ratio (molar ratio 1:1:1) were accurately weighed. Using formamide as the reaction solvent, stir until dissolved. The weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:1) was added to the reaction system, and stirred in the dark at 45 °C for 48 h. The obtained reaction solution was treated by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. The final obtained precipitate was dialyzed and purified in absolute ethanol and ultrapure water respectively, and freeze-dried. The yield of the prepared highly absorbent chondroitin sulfate derivative was 45.75%.

[0073] Example 11:

[0074] First, chondroitin sulfate, 4-dimethylaminopyridine and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with a certain molar ratio (molar ratio 1:1:1) were accurately weighed. Using formamide as the reaction solvent, stir until dissolved. The weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:1) was added to the reaction system, and stirred in the dark at 55 °C for 48 h. The obtained reaction solution was treated by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. The final obtained precipitate was dialyzed and purified in absolute ethanol and ultrapure water respectively, and freeze-dried. The yield of the prepared highly absorbent chondroitin sulfate derivative was 58.66%.

[0075] Example 12:

[0076] First, chondroitin sulfate, 4-dimethylaminopyridine and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride with a certain molar ratio (molar ratio 1:1:1) were accurately weighed. Using formamide as the reaction solvent, stir until dissolved. The weighed curcumin (molar ratio, chondroitin sulfate:curcumin = 1:1) was added to the reaction system, and stirred in the dark at 60 °C for 48 h. The obtained reaction solution was treated by the anti-solvent method (ethanol as the anti-solvent) to obtain the target compound. The final obtained precipitate was dialyzed and purified in absolute ethanol and ultrapure water respectively, and freeze-dried. The yield of the prepared highly absorbent chondroitin sulfate derivative was 59.89%.

[0077] Although the above embodiments have described the present invention in detail, they are only some embodiments of the present invention, rather than all embodiments. For those of ordinary skill in the art, other embodiments can be obtained according to these embodiments without creative efforts, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A highly absorbent chondroitin sulfate derivative is as follows: Highly absorbent chondroitin sulfate derivative.

2. A preparation method of highly absorbent chondroitin sulfate as described in claim 1, characterized in that The synthesis steps are as follows: Synthesis route: First, chondroitin sulfate, catalyst 4-dimethylaminopyridine (DMAP), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) are added to a solvent in a certain molar ratio, and stirred for a certain time to activate the carboxyl group of chondroitin sulfate. Curcumin is added to the reaction system. Under certain time and temperature conditions, an esterification reaction occurs between the carboxyl group on the chondroitin sulfate molecule and the hydroxyl group in the curcumin molecule; after the reaction is completed, another solvent is added to the reaction system, and the synthetic product is separated by anti-solvent recrystallization. The product is washed several times with the anti-solvent, and the product is dialyzed and purified in the anti-solvent and ultrapure water for a certain time respectively. After freeze-drying, a highly absorbent chondroitin sulfate derivative (CSC) is obtained.

3. The preparation method of the highly absorbent chondroitin sulfate derivative according to claim 2, characterized in that, The molar ratio of chondroitin sulfate to catalyst 4-dimethylaminopyridine (DMAP) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) is 1:1:

1.

4. The preparation method of the highly absorbent chondroitin sulfate derivative according to claim 2, characterized in that, The solvent is formamide.

5. The preparation method of the highly absorbent chondroitin sulfate derivative according to claim 2, characterized in that, The molar ratio of chondroitin sulfate to curcumin is 1:0.5 - 3.

6. The preparation method of the highly absorbent chondroitin sulfate derivative according to claim 2, characterized in that, After adding curcumin to the reaction system, the reaction time is 6 - 96 h.

7. The preparation method of the highly absorbent chondroitin sulfate derivative according to claim 2, characterized in that, After adding curcumin to the reaction system, the reaction temperature is 35 - 60 °C.

8. The preparation method of the highly absorbent chondroitin sulfate derivative according to claim 2, characterized in that, The anti-solvent is ethanol.

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