An oral joint-protective composition containing ergothioneine and a method for its preparation

Abstract

The application 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 ergothioneine comprises the following components in a mass ratio: 0.05-5 parts of ergothioneine, 20-50 parts of glucosamine salt, 10-30 parts of chondroitin sulfate, 2-10 parts of curcumin, 30-70 parts of a diluent, 1-10 parts of a binder, 0.5-5 parts of a lubricant, 2-10 parts of a disintegrant and 0.1-0.5 parts of an antioxidant stabilizer. The application forms a multi-dimensional action network of "antioxidation-anti-inflammation-cartilage metabolism regulation" through synergistic compatibility of active ingredients such as ergothioneine and curcumin, significantly improves the inhibition effect on joint inflammation, and breaks through the limitation of single components.

Description

TECHNICAL FIELD

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

[0002] With the development of society and the aggravation of population aging, joint diseases have become a medical problem that universally affects the quality of life and health of human beings. Joint diseases include various types such as degenerative arthritis, rheumatoid arthritis, osteoarthritis, and the like. The main pathological features are the degeneration, wear and destruction of articular cartilage, accompanied by synovial inflammation, osteophyte formation and lesions of the tissues around the joint, which leads to symptoms such as joint pain, stiffness and limited activity in patients, and seriously affects the daily activity ability and reduces the quality of life.

[0003] At present, there are various methods for treating joint diseases in clinical practice, but there are many limitations. In terms of drug treatment, non-steroidal anti-inflammatory drugs can relieve pain and inflammation, but long-term use can easily cause adverse reactions in the gastrointestinal tract, cardiovascular system and the like; glucocorticoids have significant anti-inflammatory effects, but are only suitable for short-term treatment, and long-term use can lead to further degeneration of articular cartilage; and anti-rheumatic drugs for improving the condition have a slow effect and limited repair effect on 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 have high surgical risks, are expensive, and have a long postoperative rehabilitation period, and are only suitable for patients in the late stage with severe conditions.

[0004] Under this background, it is of great significance to develop a safe and effective oral joint protection composition. Ergothioneine, as a naturally occurring antioxidant, has strong antioxidant, anti-inflammatory and cell protection effects. Amino glucosamine salt and chondroitin sulfate are essential precursor substances for the synthesis of articular cartilage, which can enhance the elasticity and toughness of articular cartilage. Curcumin has multiple effects such as antioxidant, anti-inflammatory and immune regulation, which further enhances the protective effect of the composition on joints. SUMMARY

[0005] The purpose of the present application is to solve the problems of existing joint protection products, such as easy to cause adverse reactions and slow effect, and to provide a safe and effective oral joint protection composition containing ergothioneine. Through the synergistic effect of each component, the functions of antioxidant, anti-inflammatory and joint protection are realized, and the treatment effect of joint diseases is improved.

[0006] To achieve the above purpose, the present application provides an antioxidant stabilizer for protecting ergothioneine, which has a structure as shown in formula 1:

[0007] Formula 1;

[0008] 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, or a phenyl group.

[0009] Further, the R1 is selected from a methyl group, an ethyl group, a t-butyl group, a phenyl group, or a methoxy group.

[0010] Further, the antioxidant stabilizer is any one of a compound represented by the following structure:

[0011]

[0012] .

[0013] Further, the antioxidant stabilizer is used to protect ergothioneine from attack by an oxygen radical, ultraviolet, and maintain the activity of ergothioneine.

[0014] 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 to 5 parts, glucosamine salt 20 to 50 parts, chondroitin sulfate 10 to 30 parts, curcumin 2 to 10 parts, diluent 30 to 70 parts, binder 1 to 10 parts, lubricant 0.5 to 5 parts, disintegrant 2 to 10 parts, antioxidant stabilizer 0.1 to 0.5 parts;

[0015] The composition is prepared into one of a tablet, a capsule, or a granule which is pharmaceutically acceptable;

[0016] The antioxidant stabilizer is a structure represented by Formula 1.

[0017] Further, the glucosamine salt is at least one of a glucosamine sulfate salt or a glucosamine hydrochloride salt.

[0018] Further, the diluent is selected from at least one of a starch, a dextrin, a microcrystalline cellulose, or a lactose.

[0019] Further, the binder is selected from at least one of a starch paste, a hypromellose, an ethyl cellulose, or a polyethylene glycol.

[0020] Further, the lubricant is selected from at least one of a magnesium stearate, a microfine silica, or a talc.

[0021] Further, the disintegrant is selected from at least one of a dry starch, a sodium carboxymethyl starch, a low-substituted hydroxypropyl methyl cellulose, or a cross-linked polyvinyl pyrrolidone.

[0022] Further, the antioxidant stabilizer is any one of a compound represented by the following structure:

[0023]

[0024] .

[0025] Further, the synthesis method of the antioxidant stabilizer is:

[0026] ;

[0027] The first step: raw material 1 and raw material 2 are synthesized by Buchwald-Hartwig aryl amination reaction to obtain intermediate 1;

[0028] The second step: intermediate 1 is synthesized by boronization to obtain intermediate 2;

[0029] The third step: intermediate 2 and raw material 3 are synthesized by Suzuki coupling reaction to obtain the antioxidant stabilizer.

[0030] A preparation method of an oral joint protection composition containing ergothioneine, comprising the following steps:

[0031] 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 premix;

[0032] S2. Add the diluent to the premix, add 50%-70% of the total amount of disintegrant, mix for 10 minutes, and add the binder to prepare wet granules;

[0033] S3. Dry the wet granules to a moisture content of ≤5%, pass through an 18 mesh sieve to granulate, and obtain dry granules;

[0034] S4. Add the remaining disintegrant and lubricant, and mix to obtain a kind of oral joint protection composition containing ergothioneine.

[0035] Further, the drying temperature of the wet granulation is 40-60 DEG C, and the granulation pressure is 10-15 MPa.

[0036] Further, the binder is 5%-10% hydroxypropyl methyl cellulose aqueous solution, and the addition amount is 10%-20% of the total weight of dry materials.

[0037] The antioxidant stabilizer provided by the application can remove free radicals, block oxidation chain reactions and stabilize easily degradable components through active groups in the molecular structure. The structure contains multiple phenolic hydroxyl groups, which can provide hydrogen atoms to neutralize free radicals, convert to stable quinone structure, and block oxidation reaction chain; the benzoheterocyclic structure can enhance the electron ionization ability and improve the efficiency of free radical capture; some derivatives (such as N and O heteroatoms) can chelate metal ions to inhibit metal-catalyzed oxidation reaction; the large steric substituents such as tert-butyl and phenyl can physically shield active ingredients and reduce the contact of oxygen molecules.

[0038] The components form a synergistic network, and the antioxidant and anti-inflammatory are linked, such as ergothioneine and curcumin, which reduce inflammatory factors and reduce joint oxidative damage; in terms of cartilage metabolism, glucosamine salt and chondroitin sulfate are synergistic, maintain the balance of cartilage synthesis and decomposition metabolism, and improve the joint buffering function. The formula also overcomes the defects of the prior art, mainly dominated by endogenous substances, combined with slow-release design to improve safety, reduce side effects, and with antioxidant stabilizers and multi-target coverage to ensure the stability of the components and enhance the efficacy, breaking through the limitations of single components and significantly improving the joint condition.

[0039] Compared with the prior art, the beneficial effects of the present application are:

[0040] 1. Synergistic mechanism breakthrough: through the synergistic combination of active ingredients such as ergothioneine and curcumin, a multi-dimensional action network of "antioxidant-anti-inflammatory-cartilage metabolism regulation" is formed, which significantly improves the inhibition effect on joint inflammation and breaks through the limitations of single components.

[0041] 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), which greatly improves the bioavailability of core components such as ergothioneine.

[0042] 3. Long-term safety improvement: The formula design dominated by endogenous substances (ergothioneine, glucosamine salt, etc.) avoids the metabolic burden of traditional drugs; combined with slow-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

[0043] Figure 1 The synthesis method of the antioxidant stabilizer described in the present application.

[0044] Figure 2 The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 1.

[0045] Figure 3 The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 2.

[0046] Figure 4 The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 3.

[0047] Figure 5 The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 4.

[0048] Figure 6 The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 5. DETAILED DESCRIPTION

[0049] The technical solutions of the present application will be clearly and completely described below with reference to the drawings in the present application. Obviously, the described embodiments are only some of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative effort belong to the protection scope of the present application.

[0050] Synthesis Example 1

[0051] Synthesis of antioxidant stabilizer 1:

[0052] ;

[0053] First step: under the 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-butyl alcohol, 0.7 g of tris (dibenzyl ketone) palladium 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 reduced, diatomite was used for filtration to remove the 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 organic phase was combined and dried with anhydrous magnesium sulfate, and the solvent was removed by using a rotary evaporator; rotary evaporation, column chromatography, using a mixture of petroleum ether and ethyl acetate as eluent, 26.43 g of intermediate 1 was obtained. MS [MS+1]: 432.

[0054] Second step: under the 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.

[0055] Third step: under the 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, and the liquid was separated, the water phase was extracted with ethyl acetate twice, the organic phase was combined, washed with water for three times, rotary evaporation, column chromatography, using a mixture of petroleum ether and ethyl acetate as eluent, 27.31 g of antioxidant stabilizer 1 was obtained. MS [MS+1]: 770.

[0056] The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 1 is shown in Figure 2 , and the characterization data are as follows:

[0057] 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,1H),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).

[0058] Synthesis Examples 2-5

[0059] The antioxidant stabilizers synthesized in Synthesis Examples 2-5 were synthesized according to the synthesis method of Synthesis Example 1, replacing raw material 1 therein, and the rest was the same as Synthesis Example 1. The specific structure of raw material 1, the structure of the antioxidant stabilizer, and MS [MS+1] data are shown in Table 1 below.

[0060] Table 1

[0061]

[0062] The nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 2 is shown in Figure 3 , and the characterization data are as follows:

[0063] 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).

[0064] The nuclear magnetic resonance (NMR) spectrum of antioxidant 3 is shown in Figure 4 and the characterization data are as follows:

[0065] 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).

[0066] The nuclear magnetic resonance (NMR) spectrum of antioxidant 4 is shown inFigure 5 Characterization data are as follows:

[0067] 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).

[0068] Nuclear magnetic resonance (NMR) spectrum of antioxidant stabilizer 5 is shown in Figure 6 Characterization data are as follows:

[0069] 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).

[0070] Example 1

[0071] Preparation of an oral joint-protective composition containing ergothioneine:

[0072] Raw material mass ratio: ergothioneine 2 parts, glucosamine sulfate 30 parts, chondroitin sulfate 20 parts, curcumin 7 parts, diluent 35 parts, binder 5 parts, lubricant 3 parts, disintegrant 7 parts, antioxidant stabilizer (product of synthesis example 1, antioxidant stabilizer 1) 0.3 parts.

[0073] Preparation method:

[0074] S1. Ergothioneine, glucosamine sulfate, chondroitin sulfate, curcumin and antioxidant stabilizer were respectively pulverized, passed through a 100-mesh sieve, and placed in a mixer for pre-mixing for 20 minutes to obtain a pre-mixed material;

[0075] S2. To the pre-mixed material, microcrystalline cellulose and 4.2 parts of sodium carboxymethyl starch were added, mixed for 10 minutes, and 8% hydroxypropyl methylcellulose aqueous solution was slowly added to be granulated in a granulator at a pressure of 12 MPa to obtain wet granules;

[0076] 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;

[0077] S4. To the dry granules, the remaining parts of sodium carboxymethyl starch and magnesium stearate were added, and mixed for 10 minutes, and tablets were compressed using a tablet press (each tablet weighing 200 mg).

[0078] Example 2

[0079] An oral joint-protecting composition containing ergothioneine was prepared, in which the antioxidant stabilizer 1 was replaced by the product of synthesis example 2, and the rest remained the same as example 1.

[0080] Example 3

[0081] An oral joint-protecting composition containing ergothioneine was prepared, in which the antioxidant stabilizer 1 was replaced by the product of synthesis example 3, and the rest remained the same as example 1.

[0082] Example 4

[0083] An oral joint-protecting composition containing ergothioneine was prepared, in which the antioxidant stabilizer 1 was replaced by the product of synthesis example 4, and the rest remained the same as example 1.

[0084] Example 5

[0085] An oral joint-protecting composition containing ergothioneine was prepared, in which the antioxidant stabilizer 1 was replaced by the product of synthesis example 5, and the rest remained the same as example 1.

[0086] Comparative example 1

[0087] An oral joint-protecting composition containing ergothioneine was prepared, in which the antioxidant stabilizer was not added, and the rest remained the same as example 1.

[0088] Comparative Example 2

[0089] An oral joint-protective composition containing ergothioneine was prepared by replacing the antioxidant stabilizer therein with Comparative Compound 1, the structure of which is shown in Formula 2, and the rest was kept the same as in Example 1.

[0090] Formula 2.

[0091] Comparative Example 3

[0092] An oral joint-protective composition containing ergothioneine was prepared by not adding ergothioneine therein, and the rest was kept the same as in Example 1.

[0093] Comparative Example 4

[0094] An oral joint-protective composition containing ergothioneine was prepared by not adding glucosamine salt therein, and the rest was kept the same as in Example 1.

[0095] Comparative Example 5

[0096] An oral joint-protective composition containing ergothioneine was prepared by not adding chondroitin sulfate therein, and the rest was kept the same as in Example 1.

[0097] Comparative Example 6

[0098] An oral joint-protective composition containing ergothioneine was prepared by replacing the antioxidant stabilizer therein with vitamin C, and the rest was kept the same as in Example 1.

[0099] Comparative Example 7

[0100] An oral joint-protective composition containing ergothioneine was prepared by replacing the antioxidant stabilizer therein with citric acid, and the rest was kept the same as in Example 1.

[0101] Performance Test:

[0102] 1. The sample was placed in an environment with an oxygen concentration of 30%, humidity of 85% RH, UV-A light source irradiation, and 40°C for 500h, and then the sample was uniformly dispersed in a pH 6.8 phosphate buffer, filtered, and the filtrate was tested for the retention rate (%) of ergothioneine by HPLC method.

[0103] 2. Mouse biological experiment: rheumatoid arthritis mice (body weight 200±20 g) were continuously administered samples (one oral joint-protecting composition containing ergothioneine prepared in the examples and comparative examples, the administered drug was 200 mg / kg / d in terms of effective components) by gavage for 28 days, then fasted for 12 hours, and after 12 hours, abdominal aortic blood was taken from each group of experimental animals (heparin sodium anticoagulation), the serum was separated by centrifugation at 3500 rpm for 15 minutes, and the levels of inflammatory markers were detected by enzyme-linked immunosorbent assay (ELISA), according to the instructions of the R&D Systems kit (TNF-α detection item number DTA00C, IL-1β detection item number DLB50): after the serum sample was diluted 5 times, it was added to a 96-well plate pre-coated with antibody, 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 450 nm wavelength, and the concentration value was converted according to the standard curve (the detection sensitivity of TNF-α was 5 pg / mL, the detection range of IL-1β was 15.6-1000 pg / mL, and the batch variation coefficient was ≤7%).

[0104] The performance test data is shown in Table 2 below:

[0105] Table 2

[0106]

[0107] The composition using the antioxidant stabilizer described in the present application in the examples 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-α and IL-1β were low, indicating that the anti-inflammatory effect of the composition was significant; and the dissolution rate of ergothioneine was also maintained at a good level, reflecting the release efficiency of the preparation. In contrast, the compositions in the comparative examples that lacked antioxidant stabilizers or key ingredients (such as ergothioneine, glucosamine salt, or chondroitin sulfate) showed negative trends, such as significantly decreased retention rates, significantly increased levels of inflammatory markers, and decreased dissolution rates, especially when no antioxidant stabilizer was added or a substitute was used. The overall trend confirms 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.

[0108] Although embodiments of the present application have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions and alterations can be made thereto without departing from the principles and spirit of the present application, the scope of which 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 an alkyl group with 1-5 carbon atoms, an alkoxy group with 1-5 carbon atoms or a phenyl group.

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 a tablet, a capsule or a granule in pharmacy; 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 according to claim 3, wherein The diluent is selected from 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 selected from 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 selected from at least one of magnesium stearate, microfine silica or talc.

8. The ergothioneine-containing oral joint protective composition of claim 3, wherein, The disintegrant is selected from 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°C, and 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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