Oral joint protection composition containing ergothioneine and preparation method thereof

Abstract

The invention discloses an oral joint protection composition containing ergothioneine and a preparation method thereof, and relates to the technical field of joint protection compositions. The oral joint protection composition containing the ergothioneine is prepared from the following components in parts by mass: 0.05 to 5 parts of the ergothioneine, 20 to 50 parts of glucosamine salt, 10 to 30 parts of chondroitin sulfate, 2 to 10 parts of curcumin, 30 to 70 parts of a diluent, 1 to 10 parts of an adhesive, 0.5 to 5 parts of a lubricant, 2 to 10 parts of a disintegrating agent and 0.1 to 0.5 part of an antioxidant stabilizer. Through synergistic compatibility of active ingredients such as ergothioneine, curcumin and the like, a multi-dimensional action network of oxidation resistance, inflammation resistance and cartilage metabolism regulation is formed, the inhibition effect on joint inflammation is remarkably improved, and the limitation of a single ingredient is broken through.

Description

Technical Field

[0001] The present invention relates to the technical field of joint protection compositions, and in particular to an oral joint protection composition containing ergothioneine and a preparation method thereof. Background Art

[0002] With the development of society and the increasing aging of the population, joint diseases have become a widespread medical problem that affects people's quality of life and health. Joint diseases include degenerative arthritis, rheumatoid arthritis, osteoarthritis, and other types. Their primary pathological characteristics are the degeneration, wear, and destruction of articular cartilage, accompanied by synovial inflammation, osteophyte formation, and pathological changes in the tissues surrounding the joints. These symptoms can cause patients to experience joint pain, stiffness, and limited mobility, severely impacting their ability to carry out daily activities and reducing their quality of life.

[0003] Currently, there are various clinical methods for treating joint diseases, but they have many limitations. In terms of drug treatment, although non-steroidal anti-inflammatory drugs can relieve pain and inflammation, long-term use can easily cause gastrointestinal, cardiovascular and other adverse reactions; although glucocorticoids have significant anti-inflammatory effects, they are only suitable for short-term treatment, and long-term use may lead to further degeneration of articular cartilage; and anti-rheumatic drugs that improve the condition are slow to take effect and have limited effect on the repair of articular cartilage. Surgical treatments such as arthroscopic cleaning and artificial joint replacement can effectively improve the symptoms and functions of patients with severe joint diseases, but the surgery is high-risk, expensive, and has a long postoperative recovery period, making it only suitable for patients with severe late-stage conditions.

[0004] Against this backdrop, the development of a safe and effective oral joint protection composition is of great significance. Ergothioneine, a naturally occurring antioxidant, possesses potent antioxidant, anti-inflammatory, and cytoprotective effects. Glucosamine and chondroitin sulfate, essential precursors for the synthesis of articular cartilage, enhance the elasticity and toughness of articular cartilage. Curcumin, with its multiple antioxidant, anti-inflammatory, and immune-regulating properties, further enhances the composition's protective effects on joints. Summary of the Invention

[0005] The purpose of the present invention is to provide a safe and effective oral joint protection composition containing ergothioneine to address the problems that existing joint protection products are prone to causing adverse reactions and slow onset, and to achieve antioxidant, anti-inflammatory and joint protection functions through the synergistic effect of various ingredients, thereby improving the treatment effect of joint diseases.

[0006] To achieve the above object, the present invention provides a kind of antioxidant stabilizer for protecting thioneine, having the structure shown in Formula 1: Formula 1; The R1 is selected from any one of an alkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, and a phenyl group.

[0007] Further, the R1 is selected from: methyl, ethyl, tert-butyl, phenyl, methoxy.

[0008] Further, the antioxidant stabilizer is any one of the compounds shown in the following structure:

[0009] .

[0010] Further, the antioxidant stabilizer is used to protect ergothioneine from attack by oxygen free radicals, ultraviolet, and maintain the activity of ergothioneine.

[0011] In another aspect of the present application, there is provided a joint-protecting oral composition containing ergothioneine, comprising the following components in parts by mass: ergothioneine 0.05-5 parts, glucosamine salt 20-50 parts, chondroitin sulfate 10-30 parts, curcumin 2-10 parts, diluent 30-70 parts, binder 1-10 parts, lubricant 0.5-5 parts, disintegrant 2-10 parts, antioxidant stabilizer 0.1-0.5 parts; The composition is prepared into one of the following pharmaceutically acceptable tablets, capsules or granules; The antioxidant stabilizer is shown in the structure of formula 1.

[0012] Further, the glucosamine salt is at least one of glucosamine sulfate or glucosamine hydrochloride.

[0013] Further, the diluent is selected from at least one of starch, dextrin, microcrystalline cellulose or lactose.

[0014] Further, the binder is selected from at least one of starch paste, hypromellose, ethyl cellulose or polyethylene glycol.

[0015] Further, the lubricant is selected from at least one of magnesium stearate, microfine silica or talc.

[0016] Further, the disintegrant is selected from at least one of dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl methyl cellulose or cross-linked polyvinyl pyrrolidone.

[0017] Further, the antioxidant stabilizer is any one of the compounds shown in the following structure:

[0018] .

[0019] Further, the synthesis method of the antioxidant stabilizer is: ; First step: raw material 1 and raw material 2 are subjected to Buchwald-Hartwig aryl amination reaction to synthesize intermediate 1; Second step: intermediate 1 is subjected to boronization to synthesize intermediate 2; Third step: intermediate 2 and raw material 3 are subjected to Suzuki coupling reaction to synthesize the antioxidant stabilizer.

[0020] A preparation method of an oral joint-protecting composition containing ergothioneine, comprising the following steps: S1. The ergothioneine, glucosamine salt, chondroitin sulfate, curcumin and antioxidant stabilizer are respectively crushed through an 80-100 mesh sieve, pre-mixed for 10-30 minutes to obtain a pre-mixed material; S2. The pre-mixed material is added with the diluent and a total amount of 50%-70% of the disintegrant, mixed for 10 minutes, and then the binder is added to prepare wet granules; S3. The wet granules are dried to a moisture content of less than 5%, and then sieved through an 18 mesh sieve to obtain dry granules; S4. The remaining disintegrant and lubricant are added, and then mixed, pressed into tablets or filled into capsules to obtain an oral joint-protecting composition containing ergothioneine.

[0021] Further, the drying temperature of the wet granulation is 40-60 DEG C, and the granulation pressure is 10-15 MPa.

[0022] Further, the binder is a 5%-10% hydroxypropyl methyl cellulose aqueous solution, and the addition amount is 10%-20% of the total weight of the dry materials.

[0023] The antioxidant stabilizer according to the present application can scavenge free radicals, block the oxidation chain reaction and stabilize the easily degradable components through the active groups in the molecular structure. The structure contains multiple phenolic hydroxyl groups, which can provide hydrogen atoms to neutralize free radicals, convert into stable quinone structures and block the oxidation reaction chain; the benzoheterocyclic structure can enhance the electron ionization ability and improve the free radical capture efficiency; some derivatives (such as N and O heteroatoms) can chelate metal ions to inhibit metal-catalyzed oxidation reactions; the large steric substituents such as tert-butyl and phenyl can physically shield the active ingredients and reduce the contact with oxygen molecules.

[0024] The components form a synergistic network, and the antioxidant and anti-inflammatory are linked, such as ergothioneine and curcumin, which can reduce inflammatory factors and reduce joint oxidative damage; in terms of cartilage metabolism, glucosamine salt and chondroitin sulfate are synergistic to maintain the balance between cartilage synthesis and decomposition metabolism, and improve the joint cushioning function. The formula also overcomes the defects of the prior art, mainly uses endogenous substances, cooperates with slow-release design to improve safety and reduce side effects, and relies on the antioxidant stabilizer and multi-target coverage to ensure the stability and efficacy of the components, break through the limitations of single components, and significantly improve the joint condition.

[0025] Compared with the prior art, the present application has the following advantages: 1. Synergistic mechanism breakthrough: Through the synergistic combination of active ingredients such as ergothioneine and curcumin, a multi-dimensional action network of "antioxidation-anti-inflammation-cartilage metabolism regulation" is formed, significantly improving the inhibition effect on joint inflammation and breaking through the limitations of single components.

[0026] 2. Optimization of active ingredient stability: The antioxidant stabilizer of the present application effectively blocks the oxidative chain reaction and reduces the degradation of active ingredients through unique molecular structure design (including phenolic hydroxyl group and large steric hindering substituent), greatly improving the bioavailability of core components such as ergothioneine.

[0027] 3. Long-term safety improvement: Formulation design dominated by endogenous substances (ergothioneine, glucosamine salt, etc.), avoiding the metabolic burden of traditional drugs; combined with sustained-release technology to reduce blood drug concentration fluctuations, reduce the risk of dose-dependent side effects, and improve the safety of long-term use. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 The synthesis method of the antioxidant stabilizer described in the present application.

[0029] Figure 2 The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 1.

[0030] Figure 3 The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 2.

[0031] Figure 4 The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 3.

[0032] Figure 5 The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 4.

[0033] Figure 6 The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 5. DETAILED DESCRIPTION

[0034] The technical solutions of the present application will be described in detail below with reference to the drawings in the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, not all embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative labor fall within the scope of protection of the present application.

[0035] Synthesis Example 1 Synthesis of antioxidant stabilizer 1: ; First step: under nitrogen atmosphere, 20 g of raw material 1, 19.47 g of raw material 2 and 200 g of toluene solution were added into the reaction system, 14.78 g of sodium tert-butoxide, 0.7 g of tris (dibenzylideneacetone) dipalladium and 0.77 g of tri-tert-butyl phosphine were added into the reaction system, stirred uniformly, heated to 120℃, refluxed for 12 h; after the reaction was completed, the temperature was slightly lowered, diatomite was used for filtration to remove salt and catalyst, the filtrate was cooled to room temperature, washed with water for three times, the organic phase was reserved, then the water phase was extracted with ethyl acetate; the combined organic phase was dried with anhydrous magnesium sulfate, and the solvent was removed using a rotary evaporator; rotary evaporation, column chromatography, using petroleum ether and ethyl acetate mixture as eluent, 26.43 g of intermediate 1 was obtained. MS [MS+1]: 432.

[0036] Second step: under nitrogen atmosphere, 26.43 g of intermediate 1 and 300 g of super dry tetrahydrofuran were added into the reaction system, cooled to-70℃, 4.15 g of n-butyllithium was added dropwise, stirred for 1 h after the dropwise addition was completed, 17.24 g of triisopropyl borate was added dropwise, the temperature was naturally increased to room temperature after the dropwise addition was completed, reacted for 10 h, rotary evaporation, 18.89 g of intermediate 2 was obtained. MS [MS+1]: 398.

[0037] Third step: under nitrogen atmosphere, 18.89 g of intermediate 2, 26.01 g of raw material 3, 19.71 g of anhydrous potassium carbonate, 1.65 g of tetrakis (triphenylphosphine) palladium and 300 g of toluene solution were added into the reaction system, heated to 75℃, refluxed for 10 h, the heating was turned off, cooled to room temperature, static separation, the water phase was extracted with ethyl acetate for two times, the combined organic phase was washed with water for three times, rotary evaporation, column chromatography, using petroleum ether and ethyl acetate mixture as eluent, 27.31 g of antioxidant stabilizer 1 was obtained. MS [MS+1]: 770.

[0038] The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 1 is shown in Figure 2 , and the characterization data are as follows: 1H NMR (300 MHz, Chloroform-d) δ 8.81 (m, 1H), 7.92 - 7.82 (m, 3H), 7.76 (dd, 1H), 7.64 (d, 1H), 7.39 - 7.32 (m, 2H), 7.16 - 7.00 (m, 4H), 6.94 (m, 1), 6.63 (m, 1), 4.56 - 4.43 (m, 2H), 4.13 - 3.93 (m, 3H), 3.79 (s, 3H), 3.71 - 3.59 (m, 5H), 3.49 (m, 1H), 3.06 (t, 2H), 2.91 - 2.82 (m, 4H), 2.79 - 2.63 (m, 3H), 2.49 (m, 1H), 2.22 - 1.80 (m, 4H), 1.56 (s, 3H), 1.53 (s, 3H), 1.25 (t, 3H).

[0039] Synthesis Examples 2-5 The antioxidant stabilizers synthesized in Synthesis Examples 2-5 were synthesized according to the synthesis method of Synthesis Example 1, replacing the raw material 1 therein, and the rest was the same as Synthesis Example 1. The specific structure of raw material 1, the structure of antioxidant stabilizer and MS [MS+1] data are shown in Table 1 below.

[0040] Table 1

[0041] The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 2 is shown in Figure 3 , and the characterization data are as follows: 1H NMR (300 MHz, Chloroform-d) δ 8.20 (dd, 1H), 7.90 - 7.82 (m, 1H), 7.64 (d, 1H), 7.38 (d, 1H), 7.26 (dd, 1H), 7.14 (m, 1H), 7.08 (dd, 1H), 7.02 (m, 1H), 6.98 - 6.92 (m, 1H), 6.63 (m, 1H), 4.56 - 4.44 (m, 2H), 4.13 - 3.93 (m, 3H), 3.79 (s, 3H), 3.71 - 3.59 (m, 5H), 3.53 - 3.44 (m, 1H), 3.02 (t, 2H), 2.97 - 2.90 (m, 2H), 2.90 - 2.82 (m, 4H), 2.74 (m, 1H), 2.65 - 2.57 (m, 2H), 2.49 (m, 1H), 2.32 (m, 2H), 2.21 - 1.79 (m, 6H), 1.55 (s, 3H), 1.51 (s, 3H), 1.00 (t, 3H). The nuclear magnetic resonance (NMR) spectrum of antioxidant 3 is shown in Figure 4 and the characterization data are as follows: 1H NMR (300 MHz, Chloroform-d) δ 8.80 (m, 1H), 8.29 (m, 1H), 7.90 - 7.82 (m, 2H), 7.78 (dd, 1H), 7.64 (d, 1H), 7.49 (dd, 1H), 7.41 - 7.34 (m, 2H), 7.17 - 6.99 (m, 3H), 6.94 (m, 1H), 6.63 (m, 1H), 4.56 - 4.44 (m, 2H), 4.13 - 3.93 (m, 3H), 3.79 (s, 3H), 3.71 - 3.59 (m, 5H), 3.49 (m, 1H), 3.06 (t, 2H), 2.90 - 2.82 (m, 4H), 2.74 (m, 1H), 2.49 (m, 1H), 2.21 - 1.79 (m, 6H), 1.58 (d, 6H), 1.40 - 1.26 (m, 9H). The nuclear magnetic resonance (NMR) spectrum of antioxidant 4 is shown in Figure 5 and the characterization data are as follows: 1H NMR (300 MHz, Chloroform-d) δ 8.81 (dt, 1H), 8.09 (m, 1H), 7.90 –7.83 (m, 2H), 7.77 (dd, 1H), 7.68 – 7.32 (m, 9H), 7.17 – 6.91 (m, 4H), 6.63(m, 1H), 4.56 – 4.43 (m, 2H), 4.14 – 3.94 (m, 3H), 3.79 (s, 3H), 3.71 – 3.58(m, 5H), 3.49 (m, 1H), 3.06 (t, 2H), 2.90 – 2.81 (m, 4H), 2.74 (m, 1H), 2.49(ddt, 1H), 2.22 – 1.77 (m, 6H), 1.59 (d, 6H). NMR spectrum of the anti-oxidation stabilizer 5 is shown in Figure 6 , and the characterization data are as follows: 1H NMR (300 MHz, Chloroform-d) δ 8.82 (m, 1H), 7.89 – 7.82 (m, 2H),7.74 (dd, 1H), 7.68 – 7.61 (m, 2H), 7.48 (dd, 1H), 7.38 (d, 1H), 7.17 – 6.99(m, 3H), 6.97 – 6.84 (m, 2H), 6.63 (m, 1H), 4.56 – 4.43 (m, 2H), 4.14 – 3.92(m, 3H), 3.81 (d, 6H), 3.71 – 3.58 (m, 5H), 3.54 – 3.44 (m, 1H), 3.06 (t,2H), 2.91 – 2.82 (m, 4H), 2.74 (m, 1H), 2.49 (m, 1H), 2.22 – 1.79 (m, 6H),1.55 (d, 6H).

[0042] Example 1 Preparation of an oral joint-protecting composition containing ergothioneine: Raw material mass ratio: ergothioneine 2 parts, glucosamine sulfate 30 parts, chondroitin sulfate 20 parts, curcumin 7 parts, diluent 35 parts, adhesive 5 parts, lubricant 3 parts, disintegrant 7 parts, anti-oxidation stabilizer (product of synthesis example 1, anti-oxidation stabilizer 1) 0.3 parts.

[0043] Preparation method: S1. Ergothioneine, glucosamine sulfate, chondroitin sulfate, curcumin and antioxidant stabilizer were respectively pulverized, passed through 100 mesh sieve, and pre-mixed in a mixer for 20 minutes to obtain a pre-mixed material; S2. Microcrystalline cellulose and 4.2 parts of sodium carboxymethyl starch were added to the pre-mixed material, mixed for 10 minutes, and 8% hydroxypropyl methyl cellulose aqueous solution was slowly added to be granulated in a granulator at a pressure of 12 MPa to obtain wet granules; S3. The wet granules were dried at 50°C until the moisture content was ≤5%, and the granules were sized through an 18 mesh sieve to obtain dry granules; S4. The dry granules were added with the remaining parts of sodium carboxymethyl starch and magnesium stearate, and mixed for 10 minutes to be compressed into tablets (each tablet weighing 200 mg) by using a tablet press.

[0044] Example 2 An oral joint-protecting composition containing ergothioneine was prepared, wherein the antioxidant stabilizer 1 was replaced by the product of Synthesis Example 2, and the rest was the same as Example 1.

[0045] Example 3 An oral joint-protecting composition containing ergothioneine was prepared, wherein the antioxidant stabilizer 1 was replaced by the product of Synthesis Example 3, and the rest was the same as Example 1.

[0046] Example 4 An oral joint-protecting composition containing ergothioneine was prepared, wherein the antioxidant stabilizer 1 was replaced by the product of Synthesis Example 4, and the rest was the same as Example 1.

[0047] Example 5 An oral joint-protecting composition containing ergothioneine was prepared, wherein the antioxidant stabilizer 1 was replaced by the product of Synthesis Example 5, and the rest was the same as Example 1.

[0048] Comparative Example 1 An oral joint-protecting composition containing ergothioneine was prepared, wherein the antioxidant stabilizer was not added, and the rest was the same as Example 1.

[0049] Comparative Example 2 An oral joint-protecting composition containing ergothioneine was prepared, wherein the antioxidant stabilizer was replaced by Comparative Compound 1, and the rest was the same as Example 1.

[0050] Formula 2.

[0051] Comparative Example 3 An oral joint-protecting composition containing ergothioneine was prepared, wherein the ergothioneine was not added, and the rest was the same as Example 1.

[0052] Comparative Example 4 A preparation of oral joint-protecting composition containing ergothioneine, without adding glucosamine salt therein, and the rest being the same as Example 1.

[0053] Comparative Example 5 A preparation of oral joint-protecting composition containing ergothioneine, without adding chondroitin sulfate therein, and the rest being the same as Example 1.

[0054] Comparative Example 6 A preparation of oral joint-protecting composition containing ergothioneine, replacing the anti-oxidation stabilizer therein with vitamin C, and the rest being the same as Example 1.

[0055] Comparative Example 7 A preparation of oral joint-protecting composition containing ergothioneine, replacing the anti-oxidation stabilizer therein with citric acid, and the rest being the same as Example 1.

[0056] Performance test: 1. The sample was placed in an environment with oxygen concentration of 30%, humidity of 85% RH, UV-A light source irradiation, and 40°C for 500 hours. Then the sample was uniformly dispersed in a phosphate buffer solution with pH 6.8, filtered, and the filtrate was tested for the retention rate of ergothioneine (%) by HPLC method.

[0057] 2. Mouse biological experiment: rheumatoid arthritis mice (body weight 200±20g) were continuously administered with the sample (a preparation of oral joint-protecting composition containing ergothioneine in the examples and comparative examples, the effective ingredient of the administered medicine was converted to 200mg / kg / d) for 28 days. After 28 days, the experimental animals were fasted for 12 hours, and then the abdominal aorta was sampled (heparin sodium anticoagulation) after 12 hours. The serum was separated by centrifugation at 3500rpm for 15 minutes, and the level of inflammatory markers was detected by enzyme-linked immunosorbent assay (ELISA) according to the instructions of R&D Systems kit (TNF-α detection item number DTA00C, IL-1β detection item number DLB50): after dilution of the serum sample by 5 times, the pre-coated antibody 96-well plate was added, and incubated at 37°C for 45 minutes; after washing the plate three times with PBS buffer, biotin-labeled secondary antibody was added, and reacted at 25°C for 30 minutes; after washing the plate again, streptavidin-HRP solution was added for color development for 10 minutes, and the absorbance was measured at 450nm wavelength. The concentration value was converted according to the standard curve (the detection sensitivity of TNF-α was 5pg / mL, the detection range of IL-1β was 15.6-1000pg / mL, and the batch variation coefficient was ≤7%).

[0058] The performance test data is shown in Table 2 below: Table 2

[0059] The compositions in the examples using the antioxidant stabilizer described in the present application performed well as a whole: the ergothioneine retention rate was high, indicating that the antioxidant stabilizer effectively inhibited the degradation process; the levels of inflammatory markers TNF-a and IL-1β were low, indicating that the anti-inflammatory effect of the composition was significant; and the ergothioneine dissolution rate also remained at a good level, reflecting the release efficiency of the preparation. In contrast, the compositions in the comparative examples that lacked the antioxidant stabilizer or key ingredients (such as ergothioneine, glucosamine salt, or chondroitin sulfate) showed negative trends, such as a significant decrease in retention rate, a significant increase in the level of inflammatory markers, and a decrease in dissolution rate, especially when no antioxidant stabilizer was added or a substitute was used. The overall trends confirm the protection and synergistic effect of the antioxidant stabilizer of the present application, as well as the indispensability of the core ingredients, which together improve the joint protection performance of the composition.

[0060] Although embodiments of the present application have been shown and described, it is to be understood that various modifications, substitutions, replacements and changes can be made to these embodiments without departing from the principles and spirit of the present application, and the scope of the present application is defined by the appended claims and their equivalents.

Claims

1. An antioxidant stabilizer for protecting ergothioneine, characterized by, The antioxidant stabilizer is a compound shown in the following structure: Formula 1; The R1 is selected from any one of alkyl with carbon number 1-5, alkoxy with carbon number 1-5 or phenyl.

2. An antioxidant stabilizer for protecting ergothioneine according to claim 1, characterized in that, The antioxidant stabilizer is any one of the following compounds: 。 3. An orally administered joint protective composition comprising ergothioneine, characterized in that, The composition comprises the following mass ratio: ergothioneine 0.05-5 parts, glucosamine salt 20-50 parts, chondroitin sulfate 10-30 parts, curcumin 2-10 parts, diluent 30-70 parts, binder 1-10 parts, lubricant 0.5-5 parts, disintegrant 2-10 parts, antioxidant stabilizer 0.1-0.5 parts; The composition is prepared into one of the following pharmaceutically acceptable forms: tablet, capsule or granule; The antioxidant stabilizer is the antioxidant stabilizer according to claim 1.

4. The ergothioneine-containing oral joint protective composition according to claim 3, characterized in that, The glucosamine salt is at least one of glucosamine sulfate or glucosamine hydrochloride.

5. The ergothioneine-containing oral joint protective composition of claim 3, wherein, The diluent is at least one of starch, dextrin, microcrystalline cellulose or lactose.

6. The ergothioneine-containing oral joint protective composition of claim 3, wherein, The binder is at least one of starch paste, hypromellose, ethyl cellulose or polyethylene glycol.

7. The ergothioneine-containing oral joint protective composition of claim 3, wherein, The lubricant is at least one of magnesium stearate, microfine silica or talc.

8. An ergothioneine-containing oral joint protective composition according to claim 3, wherein The disintegrant is at least one of dry starch, sodium carboxymethyl starch, low-substituted hydroxypropyl methyl cellulose or cross-linked polyvinyl pyrrolidone.

9. A process for the preparation of the oral joint-protective ergothioneine-containing composition according to any one of claims 3 to 8, characterized in that, The method comprises the following steps: S1. The ergothioneine, glucosamine salt, chondroitin sulfate, curcumin and antioxidant stabilizer are respectively crushed through an 80-100 mesh sieve, pre-mixed for 10-30 minutes to obtain a pre-mixture; S2. The diluent and 50%-70% of the total amount of disintegrant are added to the pre-mixture, mixed for 10 minutes, and then the binder is added to obtain wet granules; S3. The wet granules are dried to a moisture content of ≤5%, sieved through an 18 mesh sieve to obtain dry granules; S4. The remaining disintegrant and lubricant are added, and the mixture is pressed into tablets or filled into capsules to obtain the oral joint protection composition containing ergothioneine.

10. The method of preparing an orally protected joint composition containing ergothioneine according to claim 9, characterized in that, The drying temperature of the wet granules is 40-60℃, the granulation pressure is 10-15 MPa; and / or the binder is added in the form of an aqueous solution, the aqueous solution is a 5%-10% hypromellose aqueous solution, and the addition amount of the aqueous solution is 10%-20% of the total weight of the dry materials.

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