Magnesium hydroxide nanoparticles for treating joint pain, method of preparation thereof, and uses

Abstract

This invention belongs to the pharmaceutical field and specifically relates to magnesium hydroxide nanoparticles for treating joint pain and a method for preparing the same. The preparation method is as follows: a soluble magnesium salt is dissolved in purified water to obtain a magnesium salt solution; a soluble metal hydroxide is dissolved in purified water to obtain a metal hydroxide solution; a phospholipid is dissolved in an organic solvent to obtain a phospholipid solution; the phospholipid solution is removed by rotary vapor deposition to remove the organic reagents; after a thin film is formed, the magnesium salt solution is added to hydrate it to obtain a hydrated solution; the metal hydroxide solution is added to the hydrated solution to perform nano-processing; and the process is completed. The preparation method is simple and easy to control, and magnesium hydroxide nanoparticles can be prepared using only magnesium salt, hydroxide, and phospholipid. Verified by rat studies, after preparing magnesium salt into nano-level magnesium hydroxide using pharmaceutical formulation technology, it has joint analgesic effects, the duration of analgesia is significantly extended, the frequency of administration is greatly reduced, and thus the patient's suffering can be reduced.

Description

Technical Field

[0001] <Cross - reference to Related Applications> This application was filed with the China National Intellectual Property Administration on May 5, 2023, claiming priority to a Chinese patent application with application number 202310496323.3 and invention title "Magnesium Hydroxide Nanoparticles for Treating Joint Pain, Preparation Method and Use", and all of its contents are incorporated herein by reference.

[0002] This application was filed with the China National Intellectual Property Administration on May 5, 2023, claiming priority to a Chinese patent application with application number 202310497579.6 and invention title "Use of Magnesium Hydroxide in the Preparation of Drugs for Treating Joint Pain", and all of its contents are incorporated herein by reference.

[0003] The present invention belongs to the field of medicine, and specifically relates to magnesium hydroxide nanoparticles for treating joint pain, a preparation method thereof and uses.

Background Art

[0004] Osteoarthritis (OA) is a degenerative disease with joint pain as the main symptom, caused by fibrosis, cracks, ulcers and disappearance of articular cartilage caused by multiple factors, often involving sites such as the knee joint, hip joint, spine and hands. Its pathological features mainly include degenerative destruction of articular cartilage, sclerosis or cystic changes of subchondral bone, bone proliferation at the joint edge and synovitis, etc. OA has a profound impact on the joint function and quality of life of patients, and studies have shown that OA, especially symptomatic knee OA, can significantly increase the overall mortality risk of patients. Unfortunately, at present, there is still no safe and effective treatment method at home and abroad to delay the progression of the disease state of OA.

[0005] Joint pain is the most common clinical symptom in osteoarthritis (OA), and pain relief is the primary complaint OA patients seek medical attention for. Furthermore, as the disease progresses, OA patients often experience persistent pain, making long-term, safe pain relief extremely important for OA patients.

[0006] Currently, the primary treatment method for OA patients is joint pain relief, and while there are many types, many problems exist. For example, acetaminophen was consistently the first-line drug for treating OA pain in the past, but recent high-quality research evidence shows that it is not only ineffective in relieving OA pain compared to placebo, but also significantly increases the risk of gastrointestinal side effects. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) have a clear therapeutic effect in relieving OA pain, but there are concerns about cardiovascular and gastrointestinal side effects caused by long-term use. Oral tramadol is listed as "first-line" in both the 2013 American Academy of Orthopaedic Surgeons guidelines and the 2012 American College of Rheumatology guidelines for OA. Although it was recommended as a "first-line drug," recent studies have revealed that oral tramadol can significantly increase all-cause mortality, myocardial infarction incidence, and hip fracture incidence compared to nonsteroidal anti-inflammatory drugs (this has already been incorporated into the 2019 American College of Rheumatology OA guidelines, and tramadol is no longer recommended as a "first-line drug"). While intra-articular steroid injections are widely used and have a significant short-term analgesic effect, they have important issues that need to be addressed, such as a relatively short duration of analgesic effect, insufficient efficacy, and safety concerns. Therefore, further research is needed to find therapeutic agents that are highly effective, safe, and can be used for long-term analgesia in OA. Based on this, we propose a technical solution according to the present invention. [Overview of the project] [Problems that the invention aims to solve]

[0007] To address the problems present in the prior art, the present invention provides magnesium hydroxide nanoparticles for treating joint pain and a method for preparing the same. The preparation method is simple and easy to control, and magnesium hydroxide nanoparticles can be prepared using only magnesium salts, hydroxides, and phospholipids. Validated in rat studies, after preparing magnesium salts into nanoscale magnesium hydroxide by drug formulation technology, it exhibits joint analgesic effects, significantly extends the duration of analgesia, greatly reduces the frequency of administration, and thereby reduces patient suffering. [Means for solving the problem]

[0008] The present invention provides magnesium hydroxide nanoparticles for treating joint pain, wherein the magnesium hydroxide nanoparticles comprise magnesium hydroxide and phospholipids.

[0009] Preferably, the magnesium hydroxide nanoparticles have a "nucleus-shell" structure, where, The core layer is magnesium hydroxide, and the shell layer is phospholipid.

[0010] Preferably, the phospholipid is one of natural soybean phospholipids, natural egg yolk phospholipids, or synthetic phospholipids (e.g., hydrogenated phospholipids).

[0011] Preferably, the phospholipid is one of the phospholipids S45, S75, S100, SPC, E80, EPCS, EPG, SPC-3, PC98-T, PL-100M, HSPC, PGE, PGSH, DS-PL95E, DSPE, DPPA, DSPA, or DMPC.

[0012] Preferably, the average particle size of the magnesium hydroxide nanoparticles is 50 to 550 nm. Based on the same technical concept, the present invention further provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Dissolve the soluble magnesium salt in purified water to obtain a magnesium salt solution. (2) Dissolve the soluble metal hydroxide in purified water to obtain a metal hydroxide solution. (3) Dissolve the phospholipid in an organic solvent to obtain a phospholipid solution, (4) The phospholipid solution is removed by rotary vapor deposition to remove the organic reagent, and after a thin film is formed, the magnesium salt solution is added and hydrated to obtain a hydrated solution. (5) The metal hydroxide solution is added to the hydrated liquid to perform nanotechnology treatment, and after completion, magnesium hydroxide nanoparticles for treating joint pain are obtained.

[0013] Preferably, in step (1), the soluble magnesium salt is one or more combinations of anhydrous magnesium sulfate, monohydrated magnesium sulfate, heptahydrated magnesium sulfate, magnesium chloride, and hexahydrated magnesium chloride.

[0014] Preferably, in step (2), the metal hydroxide is one or a combination of sodium hydroxide or potassium hydroxide.

[0015] Preferably, in step (3), the organic solvent is volatile and capable of dissolving phospholipids, and is one or more combinations of ethanol, dichloromethane, or acetone.

[0016] Preferably, in step (5), the nano-processing method is one of probe ultrasonic treatment, high-pressure homogenization treatment, or ball milling treatment.

[0017] Based on the same technical concept, the present invention further provides applications of magnesium hydroxide nanoparticles for treating the aforementioned joint pain, wherein the magnesium hydroxide nanoparticles are used to prepare drugs for treating joint pain in osteoarthritis. [Effects of the Invention]

[0018] The present invention has the following beneficial effects. The preparation method described in the present invention is simple and easy to control. Magnesium hydroxide nanoparticles can be prepared only with magnesium salts, hydroxides and phospholipids. As verified by rat tests, after preparing magnesium salts into nanoscale magnesium hydroxide by pharmaceutical formulation technical means, it has an analgesic effect on joints, and the analgesic effect time is significantly prolonged, the administration frequency is greatly reduced, thereby reducing patient pain.

Brief Description of Drawings

[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings that need to be used in the description of the embodiments or the prior art will be briefly described below. Obviously, the accompanying drawings described below are only some embodiments of the present invention, and those skilled in the art can obtain other drawings based on these accompanying drawings without creative labor. [Figure 1] It is a TEM image of magnesium hydroxide nanoparticles in Test Example 1. [Figure 2] It is a result data diagram of the mechanical pain threshold of each group of rats in Test Example 2. [Figure 3] It is a result data diagram of the load difference between the two hind limbs of each group of rats in Test Example 2.

Modes for Carrying Out the Invention

[0020] To make the objectives, technical solutions and advantages of the present invention clearer, the technical solutions of the present invention will be described in detail below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative labor are all included in the protection scope of the present invention.

[0021] <Example 1> This example provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, and the preparation method includes the following steps: (1) Mix 393.6 mg of heptahydrated magnesium sulfate with 4 mL of purified water to obtain a magnesium sulfate solution. (2) Mix 8 mg of sodium hydroxide with 1 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 125 mg of egg yolk phospholipid E80 in 20 mL of dichloromethane to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask, remove the organic reagents using a rotary vapor deposition machine, form a thin film on the flask wall, then hydrate the thin film using the magnesium sulfate solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then probe ultrasonic treatment is performed at a power of 220W for 10 minutes. After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured using a laser particle size analyzer and found to be 338.5 nm.

[0022] <Example 2> This embodiment provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Mix 393.6 mg of heptahydrated magnesium sulfate with 4 mL of purified water to obtain a magnesium sulfate solution. (2) Mix 12 mg of sodium hydroxide with 1 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 125 mg of egg yolk phospholipid E80 in 30 mL of dichloromethane to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask, remove the organic reagents using a rotary vapor deposition machine, form a thin film on the flask wall, then hydrate the thin film using the magnesium sulfate solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then probe ultrasonic treatment is performed at a power of 220W for 10 minutes. After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured using a laser particle size analyzer and found to be 445.0 nm.

[0023] <Example 3> This embodiment provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Mix 393.6 mg of heptahydrated magnesium sulfate with 4 mL of purified water to obtain a magnesium sulfate solution. (2) Mix 16 mg of sodium hydroxide with 1 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 125 mg of egg yolk phospholipid E80 in 20 mL of dichloromethane to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask, remove the organic reagents using a rotary vapor deposition machine, form a thin film on the flask wall, then hydrate the thin film using the magnesium sulfate solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then probe ultrasonic treatment is performed at a power of 220W for 10 minutes. After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured using a laser particle size analyzer and found to be 539.5 nm.

[0024] <Example 4> This embodiment provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Mix 393.6 mg of heptahydrated magnesium sulfate with 4 mL of purified water to obtain a magnesium sulfate solution. (2) Mix 32 mg of sodium hydroxide with 1 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 125 mg of egg yolk phospholipid E80 in 20 mL of dichloromethane to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask and remove the organic reagents by passing it through a rotary vapor deposition machine. A thin film is formed on the flask wall, and then the thin film is hydrated using the magnesium sulfate solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then treated with a high-pressure homogenizer at 6000 psi for 5 minutes. After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured with a laser particle size analyzer and found to be 398.5 nm.

[0025] <Example 5> This embodiment provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Mix 192 mg of anhydrous magnesium sulfate with 4 mL of purified water to obtain a magnesium sulfate solution. (2) Mix 8 mg of sodium hydroxide with 1 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 125 mg of egg yolk phospholipid E80 in 20 mL of dichloromethane to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask, remove the organic reagents using a rotary vapor deposition machine, form a thin film on the flask wall, then hydrate the thin film using the magnesium sulfate solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then probe ultrasonic treatment is performed at a power of 220W for 10 minutes. After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured using a laser particle size analyzer and found to be 313.6 nm.

[0026] <Example 6> This embodiment provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Mix 1.2 g of heptahydrated magnesium sulfate with 12 mL of purified water to obtain a magnesium sulfate solution. (2) Mix 48 mg of sodium hydroxide with 3 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 350 mg of soybean phospholipid S100 in 60 mL of dichloromethane to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask and remove the organic reagents by passing it through a rotary vapor deposition machine. A thin film is formed on the flask wall, and then the thin film is hydrated using the magnesium sulfate solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then treated with a high-pressure homogenizer at 6000 psi for 5 minutes. After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured with a laser particle size analyzer and found to be 363.9 nm.

[0027] <Example 7> This embodiment provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Mix 393.6 mg of heptahydrated magnesium sulfate with 4 mL of purified water to obtain a magnesium sulfate solution. (2) Mix 8 mg of sodium hydroxide with 1 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 60 mg of egg yolk phospholipid E80 in 20 mL of dichloromethane to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask, remove the organic reagents using a rotary vapor deposition machine, form a thin film on the flask wall, then hydrate the thin film using the magnesium sulfate solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then probe ultrasonic treatment is performed at a power of 220W for 10 minutes. After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured using a laser particle size analyzer and found to be 411.7 nm.

[0028] <Example 8> This embodiment provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Mix 440 mg of monohydrated magnesium sulfate with 8 mL of purified water to obtain a magnesium sulfate solution. (2) Mix 16 mg of sodium hydroxide with 2 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 200 mg of egg yolk phospholipid PC98-T in 50 mL of anhydrous ethanol to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask, remove the organic reagents using a rotary vapor deposition machine, form a thin film on the flask wall, then hydrate the thin film using the magnesium sulfate solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then processed at 800 rpm for 2 hours using a ball mill (Retsch Emax ball mill, Germany). After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured using a laser particle size analyzer and found to be 206.5 nm.

[0029] <Example 9> This embodiment provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Mix 200 mg of anhydrous magnesium chloride (Aladdin, 99% purity) with 8 mL of purified water to obtain a magnesium chloride solution. (2) Mix 16 mg of sodium hydroxide with 2 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 200 mg of egg yolk phospholipid PC98-T in 50 mL of anhydrous ethanol to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask, remove the organic reagents using a rotary vapor deposition machine, form a thin film on the flask wall, then hydrate the thin film using the magnesium chloride solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then processed at 800 rpm for 2 hours using a ball mill (Retsch Emax type ball mill, Germany). After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured using a laser particle size analyzer and found to be 228.1 nm.

[0030] <Example 10> This embodiment provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Mix 420 mg of magnesium hexahydrate chloride (Aladdin, 99% purity) with 8 mL of purified water to obtain a magnesium chloride solution. (2) Mix 16 mg of sodium hydroxide with 2 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 200 mg of egg yolk phospholipid PC98-T in 50 mL of anhydrous ethanol to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask, remove the organic reagents using a rotary vapor deposition machine, form a thin film on the flask wall, then hydrate the thin film using the magnesium chloride solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then processed for 2 hours at 800 rpm through a ball mill (Retsch Emax ball mill, Germany). After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured using a laser particle size analyzer and found to be 235.0 nm.

[0031] <Example 11> This embodiment provides a method for preparing magnesium hydroxide nanoparticles for treating joint pain, the preparation method comprising the following steps: (1) Mix 440 mg of monohydrated magnesium sulfate with 8 mL of purified water to obtain a magnesium sulfate solution. (2) Mix 16 mg of sodium hydroxide with 2 mL of purified water to obtain a sodium hydroxide solution. (3) Dissolve 800 mg of egg yolk phospholipid PC98-T in 50 mL of anhydrous ethanol to obtain a phospholipid solution. (4) Transfer the phospholipid solution to a round-bottom flask, remove the organic reagents using a rotary vapor deposition machine, form a thin film on the flask wall, then hydrate the thin film using the magnesium sulfate solution to obtain a hydrated solution. (5) The sodium hydroxide solution is rapidly added to the hydrate solution, and then processed at 1000 rpm for 6 hours using a ball mill (Retsch Emax ball mill, Germany). After completion, magnesium hydroxide nanoparticles for treating joint pain are obtained, and the average particle size is measured using a laser particle size analyzer and found to be 65.3 nm.

[0032] <Comparative Example 1> 125 mg of egg yolk phospholipid E80 is dissolved in 20 mL of dichloromethane and transferred to a round-bottom flask. Organic reagents are removed via a rotary vapor deposition machine to form a thin film on the flask wall. The thin film is then hydrated with 5 mL of purified water and removed to form a hydrate solution. Subsequently, the solution is subjected to probe sonication at 220 W for 10 minutes to obtain blank liposomes.

[0033] <Comparative Example 2> (1) Dissolve 393.6 mg of heptahydrated magnesium sulfate in 4 mL of purified water to obtain a magnesium sulfate solution. (2) Dissolve 8 mg of sodium hydroxide in 1 mL of purified water to obtain a sodium hydroxide solution. (3) The sodium hydroxide solution is rapidly added to the magnesium sulfate solution, and then probe ultrasound is performed at a power of 220W for 10 minutes. As a result, a clear white precipitate is observed, and the particle size exceeds the measurement range of the laser particle size analyzer.

[0034] <Test Example 1> The internal structure of the magnesium hydroxide nanoparticles described in the present invention was observed. Magnesium hydroxide nanoparticles prepared in Example 1 were collected and their structure was observed using a transmission electron microscope (TEM). The results are shown in Figure 1, and the magnesium hydroxide nanoparticles prepared in this invention exhibit a ball-like shape, with the magnesium hydroxide encapsulated by phospholipids.

[0035] <Test Example 2> The effects of the magnesium hydroxide nanoparticles described in the present invention were measured. (1) OA rat model An OA rat model was constructed by injecting sodium iodoacetate into the joint cavity of the knee joint of SD rats. After swelling appeared in the rat knee joint and the pain threshold was significantly reduced, the OA rat model was obtained. (ii) Pharmacological studies OA model rats were treated via intra-articular injection using the following solutions: physiological saline (referred to as the physiological saline set), blank liposomes prepared in Comparative Example 1 (referred to as the blank liposome set), magnesium sulfate solution (magnesium sulfate heptahydrate dissolved in physiological saline, referred to as the magnesium sulfate solution set), magnesium hydroxide nanoparticle solution prepared in Example 1 (referred to as the magnesium hydroxide nanoparticle set 1), magnesium hydroxide nanoparticle solution prepared in Example 3 (referred to as the magnesium hydroxide nanoparticle set 2), and magnesium hydroxide nanoparticle solution prepared in Example 11 (referred to as the magnesium hydroxide nanoparticle set 3).

[0036] Furthermore, a symmetrical model (referred to as the "normal group") was created by injecting an equal volume (100 μL) of physiological saline into the knee joint cavity of normal rats. The administration concentration for each group was 0.4 mmol / mL (magnesium equivalent), and the dose was administered on the 7th day after modeling, for a total of one dose. From the first day of administration, the mechanical pain threshold and the difference in load on both hind limbs were measured once a week in each group of rats. The results are shown in Figures 2 and 3, respectively.

[0037] As can be seen from the results in Figures 2 and 3, the magnesium hydroxide nanoparticles prepared in this invention can effectively and sustainably relieve joint pain in OA rats, and these results also fully illustrate that the magnesium hydroxide nanoparticles of this invention can be used to prepare drugs for treating joint pain.

[0038] Although specific embodiments of the present invention have been described above, the scope of protection of the present invention is not limited thereto. Any modifications or substitutions that are easily conceivable to those skilled in the art within the technical scope disclosed by the present invention are all included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention shall be subject to the scope of protection of the claims described above.

Claims

1. Magnesium hydroxide nanoparticles for treating joint pain, characterized in that the magnesium hydroxide nanoparticles contain magnesium hydroxide and phospholipids.

2. The magnesium hydroxide nanoparticles have a "nucleus-shell" structure, Magnesium hydroxide nanoparticles for treating joint pain according to claim 1, characterized in that the core layer is magnesium hydroxide and the shell layer is phospholipid.

3. The magnesium hydroxide nanoparticles for treating joint pain according to claim 1, characterized in that the phospholipid is one or more of natural soybean phospholipids, natural egg yolk phospholipids, or synthetic phospholipids.

4. Magnesium hydroxide nanoparticles for treating joint pain according to claim 3, characterized in that the phospholipid is one or more combinations of phospholipids S45, S75, S100, SPC, E80, EPCS, EPG, SPC-3, PC98-T, PL-100M, HSPC, PGE, PGSH, DS-PL95E, DSPE, DPPA, DSPA, or DMPC.

5. The magnesium hydroxide nanoparticles for treating joint pain according to claim 4, characterized in that the average particle size of the magnesium hydroxide nanoparticles is 50 to 550 nm.

6. The above preparation method includes the following steps: (1) Dissolve the soluble magnesium salt in purified water to obtain a magnesium salt solution. (2) Dissolve the soluble metal hydroxide in purified water to obtain a metal hydroxide solution. (3) Dissolve the phospholipid in an organic solvent to obtain a phospholipid solution, (4) The phospholipid solution is removed by rotary vapor deposition to remove the organic reagent, and after a thin film is formed, the magnesium salt solution is added to hydrate it and obtain a hydrated solution. (5) A method for preparing magnesium hydroxide nanoparticles for treating joint pain according to any one of claims 1 to 5, wherein the metal hydroxide solution is added to the hydrated liquid to perform nano-processing, and after completion, magnesium hydroxide nanoparticles for treating joint pain are obtained.

7. The method for preparing magnesium hydroxide nanoparticles for treating joint pain according to claim 6, characterized in that, in step (1), the soluble magnesium salt is one or more combinations of anhydrous magnesium sulfate, monohydrated magnesium sulfate, heptahydrated magnesium sulfate, magnesium chloride, and hexahydrated magnesium chloride.

8. The method for preparing magnesium hydroxide nanoparticles for treating joint pain according to claim 6, characterized in that, in step (2), the metal hydroxide is one or a combination of two of sodium hydroxide or potassium hydroxide.

9. The method for preparing magnesium hydroxide nanoparticles for treating joint pain according to claim 6, characterized in that, in step (5), the nano-processing method is one of probe ultrasonic treatment, high-pressure homogenization treatment, or ball milling treatment.

10. An application of magnesium hydroxide nanoparticles for treating joint pain according to any one of claims 1 to 5, characterized in that the magnesium hydroxide nanoparticles are used to prepare a drug for treating joint pain in osteoarthritis.

Images