Uses of magnesium hydroxide in the preparation of drugs for treating joint pain
Magnesium hydroxide injections into the joint cavity address the limitations of existing OA treatments by offering sustained analgesia and improved joint health, effectively reducing pain and cartilage damage in osteoarthritis.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- XIANGYA HOSPITAL CENT SOUTH UNIV
- Filing Date
- 2024-04-12
- Publication Date
- 2026-06-08
AI Technical Summary
Current treatments for osteoarthritis (OA) joint pain, such as acetaminophen, NSAIDs, and tramadol, are ineffective or pose significant side effects, while intra-articular steroid injections have short-term analgesic effects and safety concerns, necessitating a safe and effective long-term analgesic solution.
The use of magnesium hydroxide, particularly in nano or micrometer sizes, is administered via injection into the joint cavity to provide sustained analgesia for OA-related joint pain and cartilage damage.
Magnesium hydroxide provides effective and prolonged relief of joint pain and reduces synovitis and cartilage destruction in OA models, enhancing patient compliance by minimizing administration frequency.
Smart Images
Figure 2026518426000001_ABST
Abstract
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 the priority of a Chinese patent application with application number 202310496323.3 and invention title "Magnesium Hydroxide Nanoparticles for Treating Joint Pain, Its 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 the priority of 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 the use of magnesium hydroxide in the preparation of drugs for treating joint pain.
Background Art
[0004] Osteoarthritis (OA) is a degenerative disease with joint pain as the main symptom, caused by fibrosis, cracking, ulceration and disappearance of articular cartilage induced by multiple factors. It often affects parts 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 OA, and analgesia is the most important demand for OA patients to seek medical treatment. And as the disease state progresses, OA patients often experience persistent pain, so achieving safe analgesia for a long time is 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.
[0007] The medical use of magnesium hydroxide is acid neutralization. Clinically, magnesium hydroxide is primarily used as a laxative and can be used before colonoscopy and bowel surgery, usually to promote the expulsion of feces from the intestines. However, there are currently no reports of using magnesium hydroxide as an active ingredient to provide sustained analgesia for osteoarthritis (OA). Based on this, we propose a technical solution according to the present invention. [Overview of the Initiative] [Problems that the invention aims to solve]
[0008] To address the problems present in the prior art, the present invention provides an application of magnesium hydroxide in the preparation of drugs for treating joint pain. In the course of research into the pharmacokinetics of magnesium hydroxide, the inventors discovered that injecting magnesium hydroxide into the joint cavity provides a good and sustained analgesic effect for osteoarthritis (OA). [Means for solving the problem]
[0009] The solution of the present invention provides applications for magnesium hydroxide in the preparation of drugs for treating joint pain.
[0010] One use of magnesium hydroxide is in the preparation of drugs for treating synovitis and cartilage damage.
[0011] Preferably, the magnesium hydroxide is used in the preparation of drugs that have long-lasting joint analgesic effects.
[0012] Preferably, the joint pain is joint pain associated with osteoarthritis.
[0013] Preferably, the cartilage damage is cartilage damage due to joint degenerative changes, inflammatory changes, or various traumas or chronic wear. Preferably, the magnesium hydroxide is nano-level magnesium hydroxide particles.
[0014] Preferably, the magnesium hydroxide is in the form of magnesium hydroxide particles in micrometers.
[0015] Preferably, the average particle size of the magnesium hydroxide is 50 nm to 20 μm.
[0016] Preferably, the drug is an injectable preparation.
[0017] Preferably, the drug is administered by injection into the joint cavity.
[0018] Preferably, the drug is a preparation prepared by using magnesium hydroxide as the main drug and adding pharmaceutically acceptable carriers or additives.
[0019] Preferably, the carrier or additive is selected from one or a combination of more than one of a solvent, an osmotic pressure regulator, a pH regulator, a stabilizer, a suspending agent, a surfactant or a preservative.
Advantages of the Invention
[0020] The present invention has the following beneficial effects. Verified by rat tests, the treatment with magnesium hydroxide at the nano or micrometer level can effectively and continuously relieve the joint pain of OA rats. That is, magnesium hydroxide is used in the preparation of a drug for treating joint analgesia, and the drug can significantly reduce the administration frequency, thereby improving the compliance of patients.
Brief Description of the Drawings
[0021] To more clearly explain the embodiments of the present invention or the technical solutions in the prior art, the attached drawings that need to be used in the description of the embodiments or the prior art will be briefly described below. Obviously, the attached drawings described below are only some embodiments of the present invention, and those skilled in the art can obtain other drawings based on these attached drawings without creative labor. [Figure 1] It is a data diagram of the mechanical pain threshold results of rats in each group. [Figure 2] It is a data diagram of the results of the load difference between the two hind limbs of rats in each group. [Figure 3] It is a HE staining diagram of the knee joints of rats in each group.
Modes for Carrying Out the Invention
[0022] 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, all other embodiments obtained by those skilled in the art without creative labor are included in the protection scope of the present invention.
[0023] Example 1: Pharmacological test Sodium iodoacetate was injected into the joint cavity of the knee joint of SD rats to construct an OA rat model. After swelling appeared in the rat knee joint and the pain threshold decreased significantly, an OA rat model was obtained. On the 7th day after modeling, by means of intra-articular injection, the same volume (100 μL) of physiological saline, magnesium sulfate solution with a concentration of 0.35 mmol / mL (in terms of magnesium), magnesium hydroxide nano-liquid, and magnesium hydroxide suspension were used to treat OA model rats, which were respectively denoted as the physiological saline group, magnesium sulfate solution group, nano-magnesium hydroxide group, and micro-magnesium hydroxide group.
[0024] Here, the preparation method of the magnesium sulfate solution is as follows: Magnesium sulfate heptahydrate is dissolved in physiological saline.
[0025] The preparation method of the magnesium hydroxide nano-liquid is as follows: Nano-level magnesium hydroxide (Aladdin, 99.8%) is suspended in physiological saline (the average particle size of nano-level magnesium hydroxide is 55 nm).
[0026] The preparation method of the magnesium hydroxide suspension is as follows: The magnesium hydroxide raw drug (Puli Pharmaceutical) is processed by an airflow pulverizer and then suspended in physiological saline (the average particle size of micro-meter-level magnesium hydroxide is 19.2 μm).
[0027] In addition, an equal volume of physiological saline was injected into the knee joint cavity of normal rats as a control (denoted as the normal group).
[0028] A total of one dose was administered, and the mechanical pain threshold and the difference in weight-bearing on both hind limbs of each group of rats were measured once a week starting from the first day of administration. The results are shown in Figures 1 and 2.
[0029] As can be seen from Figures 1 and 2, magnesium sulfate can alleviate joint pain in OA rats to some extent, but the effect is short-lived. Nano or micrometer-level magnesium hydroxide therapy can effectively and sustainably alleviate joint pain in OA rats. These results fully illustrate the potential use of the magnesium hydroxide of this invention in the preparation of drugs for treating joint pain.
[0030] Example 2: Pharmacological Test An OA rat model was constructed by injecting sodium iodoacetate into the joint cavity of SD rat knee joints. After swelling appeared in the rat knee joints and the pain threshold was significantly reduced, an OA rat model was obtained. On the 7th day after modeling, the OA model rats were treated by intra-articular injection with physiological saline, magnesium sulfate solution at a concentration of 0.35 mmol / mL (magnesium equivalent), magnesium hydroxide nano solution, and magnesium hydroxide suspension, respectively. These are referred to as the physiological saline group, magnesium sulfate group, nano magnesium hydroxide group, and micro magnesium hydroxide group, respectively.
[0031] The method for preparing the magnesium sulfate solution is as follows: Dissolve heptahydrated magnesium sulfate in physiological saline.
[0032] The method for preparing magnesium hydroxide nanosolution is as follows: Suspend nano-level magnesium hydroxide (Aladdin, 99.8%) in physiological saline.
[0033] The method for preparing the magnesium hydroxide suspension is as follows: The magnesium hydroxide active ingredient (Puri Pharmaceutical) is processed using an air-jet pulverizer, and then suspended in physiological saline.
[0034] Furthermore, an equal volume of physiological saline is injected into the knee joint cavity of normal rats as a control (referred to as the normal group).
[0035] A total of one dose was administered, and after 4 weeks of treatment, the knee joints were collected after administration, paraffin sections were prepared, and hematoxylin-eosin staining (HE staining) was performed. The results are shown in Figure 3. As can be seen from the results, the saline group showed significant synovitis and severe cartilage destruction. After treatment with magnesium sulfate solution, the synovitis and cartilage damage in the OA rats were alleviated to some extent. The synovitis in the OA rats treated with nano-level magnesium hydroxide and micrometer-level magnesium hydroxide was greatly improved, and cartilage damage was also effectively suppressed, bringing their condition close to that of normal rats. As can be seen from these results, magnesium hydroxide can effectively suppress synovitis and cartilage destruction.
[0036] 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. Uses of magnesium hydroxide in the preparation of drugs for treating joint pain.
2. Uses of magnesium hydroxide in the preparation of drugs for treating synovitis and cartilage damage.
3. The use according to claim 1, characterized in that the magnesium hydroxide is used for the purpose of preparing a long-term joint analgesic drug.
4. The use according to claim 1 or 3, characterized in that the joint pain is joint pain of osteoarthritis.
5. The use according to claim 2, characterized in that the cartilage damage is cartilage damage due to joint degenerative changes, inflammatory changes, various traumas, or chronic wear.
6. The use according to claim 1 or 2, characterized in that the magnesium hydroxide is nano-level magnesium hydroxide particles.
7. The use according to claim 1 or 2, characterized in that the magnesium hydroxide is in the form of magnesium hydroxide particles in micrometers.
8. The application according to claim 6 or 7, characterized in that the average particle size of the magnesium hydroxide is 50 nm to 20 μm.
9. The use according to claim 1 or 2, characterized in that the drug is an injectable preparation.
10. The use according to claim 9, characterized in that the drug is administered by injection into the joint cavity.
11. The use according to claim 10, characterized in that the drug is a preparation prepared by adding magnesium hydroxide as the main ingredient and a pharmaceutically acceptable carrier or additive.
12. The use according to claim 11, characterized in that the carrier or additive is selected from one or more combinations of solvents, osmotic pressure adjusters, pH adjusters, stabilizers, suspending agents, surfactants, or preservatives.