Nanoparticle, preparation method and application thereof, and pharmaceutical preparation

Abstract

The invention discloses a nanoparticle, a preparation method and application thereof, and a pharmaceutical preparation, and relates to the technical field of drug preparation, the nanoparticle comprises an inner core, and an ester substance and polyvinylpyrrolidone attached to the inner core; wherein the ester substance is obtained by carrying out esterification reaction on beta-1, 3-glucan and polyphenol containing carboxyl; the inner core is metal and / or metalloid nanoparticles; the inner core is connected with a hydroxyl group of phenol in the ester substance through a coordinate bond; the inner core is connected with the polyvinylpyrrolidone through a coordination bond. The nano particles have relatively strong gastrointestinal tract resistance due to the beta-1, 3-glucan, and can enter lymphatic circulation by being transferred to a Per's knot and being phagocytized by macrophages, so that inflammation parts with abundant immune cell aggregation are targeted, and the targeting effect of the nano particles is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of drug preparation, and in particular to a nanoparticle, a preparation method and application thereof, and a drug preparation. Background Art

[0002] Inflammation is the body's defense response to injury, infection or other irritation, aimed at removing harmful stimuli and initiating repair processes.

[0003] Traditional treatments for inflammation include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs, such as methotrexate (MTX)). Although these treatments can control the disease to a certain extent, they have problems such as large side effects, long-term drug resistance, and inability to effectively target the site of inflammation. Summary of the invention

[0004] The main purpose of the present invention is to provide a nanoparticle and its preparation method and application, and a pharmaceutical preparation, aiming to solve the problem that traditional drugs for treating rheumatoid arthritis cannot effectively target joints.

[0005] To achieve the above object, the present invention provides a nanoparticle, which comprises a core and an ester substance and polyvinyl pyrrolidone attached to the core;

[0006] Wherein, the ester substance is obtained by esterification reaction of β-1,3-glucan and polyphenol containing carboxyl groups;

[0007] The core is a metal and / or metal-like nanoparticle;

[0008] The core is connected to the phenolic hydroxyl group in the ester substance via a coordination bond;

[0009] The core is connected to the polyvinyl pyrrolidone via a coordination bond.

[0010] In one embodiment, the particle size of the nanoparticles is 47 to 52 nm;

[0011] The molar ratio of the polyvinyl pyrrolidone, the β-1,3-glucan, the carboxyl-containing polyphenol and the core in the nanoparticles is 1:2:2:1.

[0012] In one embodiment, the carboxyl-containing polyphenol includes gallic acid, curcumin or tannic acid;

[0013] The inner core includes at least one of iron nanoparticles, cerium nanoparticles, platinum nanoparticles, and tellurium nanoparticles.

[0014] The present invention also provides a method for preparing the aforementioned nanoparticles, comprising the following steps:

[0015] S10, mixing a carboxyl-containing polyphenol, water, and a carboxyl-activating agent to perform an activation reaction to obtain an activated carboxyl-containing polyphenol;

[0016] S20, mixing the activated carboxyl-containing polyphenol with β-1-3 glucan, and performing an esterification reaction to obtain an esterified product;

[0017] S30, mixing polyvinyl pyrrolidone with water and a coordination ion source to carry out a coordination reaction to obtain a complex containing coordination ions; the coordination ion source includes a metal ion source and / or a metalloid ion source;

[0018] S40, carrying out coordination reaction between the esterified product and the complex containing the coordinated ion to obtain the nanoparticles.

[0019] In one embodiment, in step S10:

[0020] The mass ratio of the carboxyl-containing polyphenol to the carboxyl-activating reagent is 800:71;

[0021] The activation reaction time is 1.8 to 24 hours;

[0022] The carboxyl activation reagent includes 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide or 4-dimethylaminopyridine.

[0023] In one embodiment, in step S20:

[0024] The molar ratio of the activated carboxyl-containing polyphenol to the β-1-3 glucan is 1:1;

[0025] The temperature of the esterification reaction is 20 to 50°C;

[0026] The esterification reaction time is 48h.

[0027] In one embodiment, in step S30:

[0028] The molar ratio of the polyvinyl pyrrolidone to the coordinating ion in the coordinating ion source is 1:1;

[0029] The molecular weight of the polyvinyl pyrrolidone is 3000-8000Da;

[0030] The temperature of the coordination reaction is 20-25°C;

[0031] The coordination reaction time is 50 to 70 minutes.

[0032] In one embodiment, in step S40:

[0033] The molar ratio of the esterified product to the complex containing the coordinated ion is 2:1; and / or,

[0034] The coordination reaction time is 20 to 24 hours.

[0035] The present invention also provides an application of nanoparticles in the preparation of a pharmaceutical preparation for treating rheumatoid arthritis, wherein the nanoparticles include the aforementioned nanoparticles or nanoparticles prepared by the aforementioned method for preparing the nanoparticles.

[0036] The present invention also provides a pharmaceutical preparation, comprising the aforementioned nanoparticles or nanoparticles prepared by the aforementioned method for preparing nanoparticles.

[0037] In the technical scheme of the present invention, polyvinyl pyrrolidone can prevent nanoparticles from aggregating and growing with each other, thereby maintaining the small size of the nanoparticles; the polyphenols in the ester substances have a strong antioxidant effect and can act on inflammatory cells to treat inflammation; the metal and / or metalloid nanoparticles serve as carriers of polyphenols, thereby enhancing the bioavailability and therapeutic effect of polyphenols; since the β-1,3-glucan in the nanoparticles can be transported to Peyer's patches through the phagocytic pattern recognition receptor Dectin-1 on microvilli cells (M cells), and then be phagocytosed by macrophages in the Peyer's patches, subsequently, immune cells (such as macrophages) containing β-1,3-glucan enter the lymphatic circulation, targeting inflammatory sites with abundant immune cell aggregation, thereby improving the targeting of the nanoparticles, and the β-1,3-glucan is on the outermost side of the nanoparticles, has a strong gastrointestinal resistance, and has a longer residence time in the gastrointestinal tract, thereby overcoming the problems of short residence time and low absorption rate of nanoparticles in the gastrointestinal tract, thereby achieving targeted treatment of inflammation with better efficacy. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the structures shown in these drawings without paying creative work.

[0039] Figure 1 This is a flow chart of the preparation of nanoparticles in Example 2 provided by the present invention;

[0040] Figure 2 This is a Fourier infrared analysis diagram of the nanoparticles in Example 2 provided by the present invention;

[0041] Figure 3 This is a transmission electron microscope image of the nanoparticles in Comparative Example 1 provided by the present invention;

[0042] Figure 4 This is a transmission electron microscope image of the nanoparticles in Example 2 provided by the present invention;

[0043] Figure 5 This is a particle size distribution diagram of the nanoparticles in Example 2 provided by the present invention;

[0044] Figure 6 This is a particle size distribution diagram of the nanoparticles in Comparative Example 1 provided by the present invention;

[0045] Figure 7 This is a schematic diagram of the treatment cycle of the nanoparticles in Example 2 provided by the present invention for treating ankle arthritis in mice;

[0046] Figure 8 The scoring results of the nanoparticles in Example 2 provided by the present invention for treating ankle arthritis in mice;

[0047] Fig. 9 This is a photograph of the appearance of the ankle joint of a mouse after the ankle arthritis of the mouse was treated with the nanoparticles in Example 2 provided by the present invention;

[0048] Fig.10 This is a computer tomography (CT) image of the ankle joint of a mouse after the ankle arthritis of the mouse was treated with the nanoparticles in Example 2 provided by the present invention.

[0049] The realization of the purpose, functional features and advantages of the present invention will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0050] To make the purpose, technical scheme and advantages of the embodiment of the present invention clearer, the technical scheme in the embodiment of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiment, it is carried out according to the normal conditions or the conditions recommended by the manufacturer. If the reagents or instruments used do not specify the manufacturer, they are all conventional products that can be purchased commercially. In addition, the meaning of "and / or" appearing in the full text includes three parallel schemes, taking "A and / or B" as an example, including scheme A, or scheme B, or schemes that A and B meet at the same time. In addition, the technical schemes between the various embodiments can be combined with each other, but must be based on the ability of ordinary technicians in the field to achieve. When the combination of technical solutions is contradictory or cannot be achieved, it should be considered that the combination of such technical solutions does not exist, and is not within the scope of protection required by the present invention. Based on the embodiments in the present invention, all other embodiments obtained by ordinary technicians in the field without making creative work belong to the scope of protection of the present invention.

[0051] Inflammation is the body's defense response to injury, infection or other irritation, aimed at removing harmful stimuli and initiating repair processes.

[0052] Traditional treatments for inflammation include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs, such as methotrexate). Although these treatments can control the disease to a certain extent, they have problems such as large side effects, long-term drug resistance, and inability to effectively target the site of inflammation.

[0053] In view of this, the present invention provides a nanoparticle, wherein the nanoparticle comprises a core and an ester substance and polyvinyl pyrrolidone attached to the core;

[0054] Wherein, the ester substance is obtained by esterification reaction of β-1,3-glucan and polyphenol containing carboxyl groups;

[0055] The core is a metal and / or metal-like nanoparticle;

[0056] The core is connected to the phenolic hydroxyl group in the ester substance via a coordination bond;

[0057] The core is connected to the polyvinyl pyrrolidone via a coordination bond.

[0058] In the technical scheme of the present invention, polyvinyl pyrrolidone can prevent nanoparticles from aggregating and growing with each other, thereby maintaining the small size of the nanoparticles; the polyphenols in the ester substances have a strong antioxidant effect and can act on inflammatory cells to treat inflammation; the metal and / or metalloid nanoparticles serve as carriers of polyphenols, thereby enhancing the bioavailability and therapeutic effect of polyphenols; since the β-1,3-glucan in the nanoparticles can be transported to Peyer's patches through the phagocytic pattern recognition receptor Dectin-1 on microvilli cells (M cells), and then be phagocytosed by macrophages in the Peyer's patches, immune cells (such as macrophages) containing β-1,3-glucan subsequently enter the lymphatic circulation, targeting inflammatory sites with abundant immune cell aggregation, thereby improving the targeting of the nanoparticles; and the β-1,3-glucan is on the outermost side of the nanoparticles, and its strong gastrointestinal resistance improves the problems of high gastrointestinal absorption rate and low drug utilization of conventional nanoparticles, thereby achieving targeted treatment of inflammation with better efficacy.

[0059] In some embodiments of the present invention, the particle size of the nanoparticles is 47-52 nm. The particle size of the nanoparticles within the above range can ensure that they can easily penetrate the gastrointestinal barrier and enter macrophages, thereby improving drug delivery efficiency.

[0060] In some embodiments of the present invention, the molar ratio of the polyvinyl pyrrolidone, the β-1,3-glucan, the carboxyl-containing polyphenol and the core in the nanoparticles is 1:2:2:1. The molar ratio within the above range can ensure that the nanoparticles have sufficient stability and polyphenol content. If the β-1,3-glucan content is too low, the protective effect of the nanoparticles may be small; in addition, too low a polyphenol content may result in insufficient antioxidant effect of the nanoparticles, resulting in a limited therapeutic effect on inflammation.

[0061] In some embodiments of the present invention, the polyphenols containing carboxyl groups include gallic acid, curcumin or tannic acid. The above-mentioned polyphenols containing carboxyl groups have a strong antioxidant effect and a good therapeutic effect on inflammation. The polyphenols containing carboxyl groups are preferably gallic acid. Gallic acid (GA) is a natural polyphenol present in fruits, teas and vegetables, and has strong antioxidant properties. In addition, gallic acid can reduce and prevent the toxic and side effects caused by traditional therapeutic drugs such as methotrexate (MTX).

[0062] In some embodiments of the present invention, the core includes at least one of iron nanoparticles, cerium nanoparticles, platinum nanoparticles and tellurium nanoparticles. That is, the core can be any one of iron nanoparticles, cerium nanoparticles, platinum nanoparticles and tellurium nanoparticles, or two or more of iron nanoparticles, cerium nanoparticles, platinum nanoparticles and tellurium nanoparticles, all within the scope of the present invention. The above nanoparticles have good biocompatibility, stability, targeting ability and drug release ability.

[0063] The present invention also provides a method for preparing the aforementioned nanoparticles, comprising the following steps:

[0064] S10, mixing a carboxyl-containing polyphenol, water, and a carboxyl-activating agent to perform an activation reaction to obtain an activated carboxyl-containing polyphenol;

[0065] S20, mixing the activated carboxyl-containing polyphenol with β-1-3 glucan, and performing an esterification reaction to obtain an esterified product;

[0066] S30, mixing polyvinyl pyrrolidone with water and a coordination ion source to carry out a coordination reaction to obtain a complex containing coordination ions; the coordination ion source includes a metal ion source and / or a metalloid ion source;

[0067] S40, carrying out coordination reaction between the esterified product and the complex containing the coordinated ion to obtain the nanoparticles.

[0068] In the technical scheme of the present invention, the purpose of the activation reaction in step S10 is to convert the carboxyl group (-COOH) in the carboxyl-containing polyphenol into a more active form by chemical methods, so that it is easier to undergo an esterification reaction with the hydroxyl group in β-1-3 glucan to obtain an esterified product, thereby improving the efficiency of the esterification reaction, so that the β-1-3 glucan can be tightly combined with the carboxyl-containing polyphenol. In the subsequent oral treatment process, the β-1-3 glucan can better assist the polyphenol in locating to the inflammatory site and improve the targeting effect; in step S30, the polyvinyl pyrrolidone has a repeated amide group, which can undergo a coordination reaction with the coordination ion in the coordination ion source through coordination action; in step S40, the ester The polyphenols in the esterification product react with the coordinating ions in the complex, so that the esterification product is grafted onto the coordinating ions (i.e., nanoparticles formed by the coordinating ions). At this time, polyvinyl pyrrolidone is adsorbed on the surface of the formed nanoparticles to prevent the aggregation and further growth of the particles, thereby maintaining the small size of the particles, facilitating drug delivery and release, and at the same time not affecting the therapeutic effect of the polyphenols; while the polyphenols in the esterification product are on the side close to the inner core of the nanoparticles, and the β-1-3 glucan is on the outermost side of the nanoparticles. This structure facilitates the nanoparticles to be phagocytosed by macrophages in the Peyer's patches, enter the lymphatic circulation, and target the inflammatory sites with abundant immune cell aggregation, thereby improving the targeting and therapeutic effect of the nanoparticles.

[0069] In some embodiments of the present invention, in step S10: the mass ratio of the carboxyl-containing polyphenol to the carboxyl-activating reagent is 800: 71. The mass ratio within the above range can ensure a high activation rate of the carboxyl groups in the carboxyl-containing polyphenol.

[0070] In some embodiments of the present invention, in step S10: the activation reaction time is 1.8 to 24 hours. The activation reaction time within the above range can ensure that the carboxyl group is activated more completely.

[0071] In some embodiments of the present invention, in step S10: the carboxyl activation reagent includes 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloric acid, N-hydroxysuccinimide or 4-dimethylaminopyridine. The above carboxyl activation reagents can ensure that the carboxyl activation efficiency of the polyphenol containing carboxyl groups is high.

[0072] In some embodiments of the present invention, in step S20: the molar ratio of the activated carboxyl-containing polyphenol to the β-1-3 glucan is 1: 1. The mass ratio within the above range can ensure a high binding rate of β-1-3 glucan to polyphenol, increase the retention time of nanoparticles in the gastrointestinal tract, and thus improve the efficiency of nanoparticles targeting to inflammatory sites through phagocytes.

[0073] In some embodiments of the present invention, in step S20: the temperature of the esterification reaction is 20-50° C.; and / or the time of the esterification reaction is 48 hours. The temperature and time of the esterification reaction within the above range can ensure a high esterification efficiency between the activated carboxyl-containing polyphenol and the β-1-3 glucan.

[0074] In some embodiments of the present invention, in step S30: the molar ratio of the polyvinyl pyrrolidone to the coordinating ions in the coordinating ion source is 1: 1. The molar ratio within the above range can ensure that more coordinating ions are bound to the polyvinyl pyrrolidone.

[0075] In some embodiments of the present invention, in step S30: the molecular weight of the polyvinyl pyrrolidone is 3000-8000Da. The molecular weight can be 3000Da, 5000Da or 8000Da. The molecular weight will affect the particle size of the final nanoparticles. The molecular weight within the above range can ensure that the nanoparticles are more easily phagocytosed by macrophages in Peyer's patches, enter the lymphatic circulation, and target the inflammatory site, thereby improving the targeting and utilization of the nanoparticles.

[0076] In some embodiments of the present invention, in step S30: the temperature of the coordination reaction is 20-25° C.; the time of the coordination reaction is 50-70 minutes. The temperature and time of the coordination reaction within the above range can ensure that more coordination ions are bound to polyvinyl pyrrolidone.

[0077] In some embodiments of the present invention, in step S40, the molar ratio of the esterified product to the complex containing the coordinating ion is 2: 1. The molar ratio within the above range facilitates the coordination and combination of the esterified product and the coordinating ion on the complex.

[0078] In some embodiments of the present invention, in step S40: the coordination reaction time is 20 to 24 hours. The coordination reaction time within the above range can ensure that more esters are bound to the nanoparticles, that is, the drug loading is higher.

[0079] Rheumatoid arthritis is a chronic, autoimmune disease that primarily affects the synovium of the joints, leading to inflammation, pain, joint damage and loss of function. The present invention also provides a use of a nanoparticle in the preparation of a pharmaceutical preparation for treating rheumatoid arthritis, wherein the nanoparticle comprises the aforementioned nanoparticle or the nanoparticle prepared by the aforementioned method for preparing the nanoparticle. Therefore, the aforementioned nanoparticle and the method for preparing the nanoparticle have all the beneficial effects, which will not be described one by one here.

[0080] The present invention also provides a pharmaceutical preparation, comprising the aforementioned nanoparticles or nanoparticles prepared by the aforementioned method for preparing nanoparticles. Therefore, the pharmaceutical preparation has all the beneficial effects of the aforementioned nanoparticles and the method for preparing nanoparticles, which will not be described in detail here. It should be noted that the nanoparticles prepared by the present invention are used for oral administration, which is more convenient and has better compliance than the injection route.

[0081] The technical solution of the present invention is further described in detail below in conjunction with specific embodiments and drawings. It should be understood that the following embodiments are only used to explain the present invention, and are not used to limit the present invention.

[0082] Example 1

[0083] A nanoparticle (βFeGA) comprising an iron nanoparticle core (Fe) and an ester substance and polyvinyl pyrrolidone (PVP) bound to the iron nanoparticle via a coordination bond;

[0084] Among them, ester substances are esters (βGA) formed by esterification reaction between β-1,3-glucan (β) and gallic acid;

[0085] The particle size of the nanoparticles is 47.1 to 51.49 nm;

[0086] The molar ratio of PVP, β, GA, and Fe in the nanoparticles was 1:2:2:1.

[0087] Example 2

[0088] A method for preparing nanoparticles, the preparation flow chart of which is as follows Figure 1 As shown, the following steps are included:

[0089] S10, dissolving gallic acid in pure water, adding 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and N-hydroxysuccinimide (NHS), and continuing stirring for 2 hours to activate the carboxyl group of gallic acid to obtain a mixed solution containing activated gallic acid; wherein the mass ratio of gallic acid, water, EDC and NHS is 80:144:2.5:4.6;

[0090] S20, dissolving yeast β-1-3 glucan in dimethyl sulfoxide (DMSO), and then adding the mixture to the mixed solution in step S10. After continuous stirring and heating for 48 hours, the mixed solution is dialyzed through a 14000Da dialysis bag for 24 hours, and then freeze-dried to obtain an ester, which is recorded as βGA; wherein the molar ratio of activated gallic acid to yeast β-1-3 glucan is 1:1;

[0091] S30. At room temperature, polyvinyl pyrrolidone (molecular weight 8000Da) was dissolved in pure water with vigorous stirring to a concentration of 10 mg / mL; 100 mg / mL ferric chloride (FeCl 3 ) aqueous solution, stirred for one hour to obtain a complex, recorded as Fe-PVP;

[0092] S40, slowly adding βGA to Fe-PVP, stirring overnight, dialyzing in a 14000Da dialysis bag for 24 hours to remove unreacted impurities, and obtaining nanoparticles, recorded as βFeGA; wherein the molar ratio of βGA to Fe-PVP is 2:1.

[0093] Comparative Example 1

[0094] The difference between Comparative Example 1 and Example 2 is that:

[0095] In step S20, yeast β-1,3-glucan was not added, and the prepared nanoparticles were recorded as FeGA.

[0096] Comparative Example 2

[0097] The difference between Comparative Example 2 and Example 2 is that:

[0098] No polyvinyl pyrrolidone was added in step S30.

[0099] Comparative Example 3

[0100] The difference between Comparative Example 3 and Example 2 is that:

[0101] No yeast β-1,3-glucan was added in step S20;

[0102] No polyvinyl pyrrolidone was added in step S30.

[0103] Performance Testing

[0104] The nanoparticles prepared in Example 2 were subjected to Fourier transform infrared analysis, and the results were as follows: Figure 2 As shown. It proves that its synthesis is successful.

[0105] The nanoparticles prepared in Comparative Example 1 and Example 2 were observed by transmission electron microscopy. Figure 3 and Figure 4 shown.

[0106] Depend on Figure 3 and Figure 4 It can be seen that compared with Comparative Example 1 ( Figure 3 ) compared with Example 2 ( Figure 4 ) presents a typical spherical core-shell structure, and the shell presents an uneven nanoparticle wrapping.

[0107] The particle sizes of the nanoparticles prepared in Example 2 and Comparative Example 1 were tested. Figure 5 and Figure 6 shown.

[0108] Depend on Figure 5 It can be seen that the particle size of the nanoparticles prepared in Example 2 is 47.30 nm. Figure 6 It can be seen that the particle size of the nanoparticles prepared in Comparative Example 1 is 9.14 nm.

[0109] The nanoparticles prepared in Example 2 were used for modeling experiments. The specific steps of the modeling experiment were as follows: complete Freund's adjuvant and bovine type II collagen were emulsified in a ratio of 1:1, and the first immunization was completed by subcutaneous injection into the tail of DBA / 1 mice; 21 days later, the mice were subcutaneously injected again for secondary immunization. The group without modeling was the blank group (i.e., normal mice), the group with modeling but not treated with nanoparticles (βFeGA) was the rheumatoid arthritis group, and the group with modeling and nanoparticles was the βFeGA group; the treatment cycle was from 28 to 46 days after the first immunization, once every two days (see Figure 7 During the treatment period, the ankle arthritis of the three groups of mice was scored using the clinical scoring standard. The results are shown in Figure 8 shown.

[0110] Depend on Figure 8 It can be seen that during the continuous monitoring process, the clinical score of the group treated with βFeGA was significantly lower than that of the group, proving that it can effectively treat rheumatoid arthritis.

[0111] Photos of the ankle joints of mice after the treatment period Fig. 9 The CT images of the ankle joints of mice after the treatment cycle are shown in Fig.10 shown.

[0112] Depend on Fig. 9 and Fig.10 It can be seen that the swelling of the ankle joints of mice was significantly reduced compared with that of mice with rheumatoid arthritis. And it can be observed from the CT results that the bone destruction in the joints of mice treated with βFeGA was significantly improved.

[0113] The above are only preferred embodiments of the present invention, and do not limit the patent scope of the present invention. For those skilled in the art, the present invention may have various changes and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the patent protection scope of the present invention.

Claims

1. A nanoparticle, characterized in that: The nanoparticles include a core and an ester substance and polyvinyl pyrrolidone attached to the core; Wherein, the ester substance is obtained by esterification reaction of β-1,3-glucan and polyphenol containing carboxyl groups; The core is a metal and / or metal-like nanoparticle; The core is connected to the phenolic hydroxyl group in the ester substance via a coordination bond; The core is connected to the polyvinyl pyrrolidone via a coordination bond.

2. The nanoparticle according to claim 1, characterized in that The particle size of the nanoparticles is 47 to 52 nm; The molar ratio of the polyvinyl pyrrolidone, the β-1,3-glucan, the carboxyl-containing polyphenol and the core in the nanoparticles is 1:2:2:

1.

3. The nanoparticle according to claim 1, characterized in that The carboxyl-containing polyphenols include gallic acid, curcumin or tannic acid; The inner core includes at least one of iron nanoparticles, cerium nanoparticles, platinum nanoparticles, and tellurium nanoparticles.

4. A method for preparing nanoparticles according to any one of claims 1 to 3, characterized in that: The following steps are involved: S10, mixing a carboxyl-containing polyphenol, water, and a carboxyl-activating agent to perform an activation reaction to obtain an activated carboxyl-containing polyphenol; S20, mixing the activated carboxyl-containing polyphenol with β-1-3 glucan, and performing an esterification reaction to obtain an esterified product; S30, mixing polyvinyl pyrrolidone with water and a coordination ion source to carry out a coordination reaction to obtain a complex containing coordination ions; the coordination ion source includes a metal ion source and / or a metalloid ion source; S40, carrying out coordination reaction between the esterified product and the complex containing the coordinated ion to obtain the nanoparticles.

5. The method for preparing nanoparticles according to claim 4, characterized in that: In step S10: The mass ratio of the carboxyl-containing polyphenol to the carboxyl-activating reagent is 800:71; The activation reaction time is 1.8 to 24 hours; The carboxyl activation reagent includes 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, N-hydroxysuccinimide or 4-dimethylaminopyridine.

6. The method for preparing nanoparticles according to claim 4, characterized in that: In step S20: The molar ratio of the activated carboxyl-containing polyphenol to the β-1-3 glucan is 1:1; The temperature of the esterification reaction is 20 to 50°C; The esterification reaction time is 48h.

7. The method for preparing nanoparticles according to claim 4, characterized in that: In step S30: The molar ratio of the polyvinyl pyrrolidone to the coordinating ion in the coordinating ion source is 1:1; The molecular weight of the polyvinyl pyrrolidone is 3000-8000Da; The temperature of the coordination reaction is 20-25°C; The coordination reaction time is 50 to 70 minutes.

8. The method for preparing nanoparticles according to claim 4, characterized in that: In step S40: The molar ratio of the esterified product to the complex containing the coordinated ion is 2:1; The coordination reaction time is 20 to 24 hours.

9. Use of nanoparticles in the preparation of a pharmaceutical preparation for treating rheumatoid arthritis, characterized in that: The nanoparticles include the nanoparticles according to any one of claims 1 to 3 or nanoparticles prepared by the method for preparing nanoparticles according to any one of claims 4 to 8.

10. A pharmaceutical preparation, characterized in that The invention comprises nanoparticles as claimed in any one of claims 1 to 3 or nanoparticles prepared by the method for preparing nanoparticles as claimed in any one of claims 4 to 8.

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