Bone joint biological lubricant as well as preparation method and application thereof

Abstract

The invention relates to a biological lubricant, in particular to a bone joint biological lubricant as well as a preparation method and application thereof. The bone joint biological lubricant comprises a component A and a component B, wherein the component A comprises the following raw materials in parts by volume: 4-6 parts of a 4% (w / v) sodium alginate solution, 0.3-0.5 part of a 1M calcium nitrate tetrahydrate solution, 0.4-0.6 part of a 2M beta-sodium glycerophosphate solution and 4-4.5 parts of normal saline; wherein the component B comprises the following raw materials in parts by volume: 3-5 parts of a 1M sodium citrate solution; after an ice-cold component A solution is injected into an articular cavity through an injector, and the solution enters an in-vivo environment at 37 DEG C, the temperature triggers Ca to be slowly released from a complex, the released Ca begins to be crosslinked with a G unit on a sodium alginate molecular chain, and finally stable hydrogel is formed in the articular cavity and has a good supporting effect when a patient is static; when the patient walks, a lubricating effect is achieved; when the gel needs to be removed, the component B can be injected into the gel part to convert the gel into a liquid state.

Description

Technical Field

[0001] This invention relates to biological lubricants, and more particularly to a biological lubricant for bones and joints, its preparation method, and its application. Background Technology

[0002] Joint lubrication can decrease due to aging or disease. Therefore, injecting biological lubricants can lubricate joints and reduce wear. Biological lubricants for joints can be classified into two types based on their form: liquid and gel. Liquid lubricants are generally absorbable liquids, such as sodium hyaluronate. Gels are generally gel-like substances, such as a joint lubricant and its preparation method disclosed in Chinese patent 201811520963.9, publication number CN109481739A. The invention describes a joint lubricant, a microgel prepared from the following components in the indicated weight ratios: 13-20 parts 2-methacryloyloxyethyl phosphorylated choline; 6-10 parts methylenebisacrylamide; 170-256 parts Tween 80; 159-239 parts Span 80; 2.4-3.7 parts ammonium persulfate; 12-19 parts tetramethylethylenediamine; 4000-6000 parts deionized water; and 5238-7858 parts hexane. The joint lubricant prepared by this invention exhibits good shear-dilution properties. Its viscosity is high under no stress; under stress, its viscosity decreases with increasing shear rate. This suggests that the microgel provides good support when the patient is at rest, while exhibiting lower viscosity when the patient is walking, reducing friction and thus providing a more durable and effective lubrication. This injectable microgel can serve as a new interventional treatment option for patients with early-stage osteoarthritis.

[0003] It is generally accepted that if excessive fluid accumulation, bacterial infection, or aseptic pain occurs after the injection of a joint lubricant, the lubricant should be aspirated to prevent further damage. However, it is evident that gel-based lubricants are more difficult to remove through conventional therapeutic aspiration compared to liquid lubricants or joint effusions. Summary of the Invention

[0004] To address the shortcomings of existing technologies, one objective of this invention is to provide a bio-lubricant for bone and joints. A second objective is to provide a method for preparing the bio-lubricant for bone and joints. A third objective is to provide the use of the bio-lubricant for bone and joints in the preparation of drugs for early-stage osteoarthritis.

[0005] One of the objectives of this invention is achieved through the following technical solution: A bio-lubricant for bone and joints, comprising component A and component B; Component A comprises the following raw materials in parts by volume: 4-6 parts of 4% (w / v) sodium alginate solution, 0.3-0.5 parts of 1M calcium nitrate tetrahydrate solution, 0.4-0.6 parts of 2M β-glycerophosphate sodium solution, and 4-4.5 parts of physiological saline; Component B comprises the following raw materials in parts by volume: 3-5 parts of 1M sodium citrate solution.

[0006] Furthermore, the method for preparing the 4% (w / v) sodium alginate solution is to dilute 4g of sodium alginate to 100mL with sterile deionized water.

[0007] Furthermore, the method for preparing the 1M calcium nitrate tetrahydrate solution is to dilute 23.62g of calcium nitrate tetrahydrate to 100mL with sterile deionized water.

[0008] Furthermore, the 2M β-glycerophosphate sodium solution is prepared by diluting 43.21g of β-glycerophosphate sodium with sterile deionized water to a final volume of 100mL.

[0009] Furthermore, the 1M sodium citrate solution is prepared by diluting 25.8g of sodium citrate to 100mL with sterile deionized water.

[0010] Furthermore, component A or B also includes the following raw material in parts by volume: 0.1 parts of 1M dexamethasone solution. Used for anti-inflammatory and analgesic purposes.

[0011] The second objective of this invention is achieved through the following technical solution: A method for preparing a bio-lubricant for bone and joints includes the following steps: Step 1: Stir the 4% (w / v) sodium alginate solution at room temperature until it becomes completely clear; this step ensures that the sodium alginate is completely dissolved. Step 2: After centrifuging the 4% (w / v) sodium alginate solution to remove air bubbles, store it at 4°C for later use. Step 3: Under ice bath and stirring conditions, add sodium β-glycerophosphate solution dropwise to calcium nitrate tetrahydrate solution. During the dropwise addition process, a white turbidity will be produced, but it will gradually dissolve and become clear as the dropwise addition continues, resulting in a complex solution, which is stored at 4°C for later use. Step 4: Under ice bath and stirring conditions, the complexing solution is added dropwise to a 4% (w / v) sodium alginate solution to obtain component A. After passing through a 0.22 μm filter membrane, it is stored at 4°C for later use. Component A is the main injection solution. Before injection, it is a liquid. After being injected into the joint cavity, it is automatically triggered by the body temperature to gel. The gel acts as a gel-type biological lubricant that combines support, buffering and lubrication. Step 5: After passing component B through a 0.22μm filter membrane, store it at 4℃ for later use. Component B is an emergency component. If excessive effusion, bacterial infection, or aseptic pain occurs after injecting the joint biological lubricant, inject component B into the joint cavity. The citrate ions will form a more stable complex with Ca²⁺, and the sodium alginate gel network will disintegrate, reversing from a gel state to a liquid state. At this time, conventional therapeutic aspiration can be used to remove the biological lubricant.

[0012] Furthermore, steps one through five are all performed in a sterile environment, such as a laminar flow hood, to prevent the introduction of pathogens.

[0013] The third objective of this invention is achieved through the following technical solution: Use of a biolubricant for joints in the preparation of a drug for early osteoarthritis.

[0014] The beneficial effects of this invention are as follows: After the cold A component solution is injected into the joint cavity using a syringe, the solution enters the 37°C in vivo environment, and the temperature triggers the slow release of Ca²⁺ from the complex. The released Ca²⁺ begins to crosslink with the G units on the sodium alginate molecular chain, eventually forming a stable hydrogel in the joint cavity. This hydrogel provides good support when the patient is at rest and lubrication when the patient is walking. When it is necessary to remove the gel, component B can be injected into the gel site to convert the gel into a liquid state. Detailed Implementation

[0015] The following is a further explanation with reference to specific implementation methods: I. Source of raw materials Sodium alginate, purchased from Lianyungang Huanyu Algae Additives Co., Ltd., product name: pharmaceutical grade sodium alginate, purity: 99%; Calcium nitrate tetrahydrate, purchased from Henan Yilu Chemical Technology Co., Ltd., purity: 99%; Sodium β-glycerophosphate, purchased from Wuhan Lanabai Pharmaceutical Chemical Co., Ltd., purity: 99%; Physiological saline, purchased from Lier Medical Technology (Dongguan) Co., Ltd., concentration: 0.9% (w / v); Sterile deionized water, homemade using a medical-grade pure water machine; Sodium citrate, purchased from Shaanxi Zhengyi Pharmaceutical Excipients Co., Ltd., product name: medical grade anhydrous sodium citrate, purity: 99%.

[0016] II. Raw material pretreatment 4g of sodium alginate was diluted to 100mL with sterile deionized water to obtain a 4% (w / v) sodium alginate solution.

[0017] 23.62 g of calcium nitrate tetrahydrate was diluted to 100 mL with sterile deionized water to obtain a 1 M calcium nitrate tetrahydrate solution.

[0018] 43.21 g of sodium β-glycerophosphate was diluted to 100 mL with sterile deionized water to obtain a 2 M sodium β-glycerophosphate solution.

[0019] 25.8g of sodium citrate was diluted to 100mL with sterile deionized water to obtain a 1M sodium citrate solution.

[0020] 3. Formulations of each embodiment and comparative example Table 1 Formulation Table IV. Preparation methods of Examples 1-3 and Comparative Example 2 Step 1: Stir the 4% (w / v) sodium alginate solution at room temperature until it becomes completely clear; Step 2: After centrifuging the 4% (w / v) sodium alginate solution to remove air bubbles, store it at 4°C for later use. Step 3: Under ice bath and stirring conditions, add sodium β-glycerophosphate solution dropwise to calcium nitrate tetrahydrate solution. During the dropwise addition process, a white turbidity will be produced, but it will gradually dissolve and become clear as the dropwise addition continues, resulting in a complex solution, which is stored at 4°C for later use. Step 4: Under ice bath and stirring conditions, the complexing solution was added dropwise to a 4% (w / v) sodium alginate solution to obtain component A, which was then filtered through a 0.22 μm filter membrane and stored at 4°C for later use. Step 5: After passing component B through a 0.22μm filter membrane, store it at 4℃ for later use.

[0021] 5. Preparation method of Comparative Example 1 Mix all raw materials in an ice bath and stir for 30 minutes to obtain component A. After passing through a 0.22 μm filter membrane, store at 4°C for later use.

[0022] 6. Observation experiment on the morphology of component A after heating The A components obtained in Examples 1-3 and Comparative Examples 1-2 were injected into test tubes and placed in a constant temperature incubator at 37°C for 1 hour to observe their morphology.

[0023] Examples 1-3 and Comparative Examples 1-2 were all in a liquid state before heating (flowed smoothly when the test tube was shaken). After heating, Examples 1-3 and Comparative Example 2 were all in a gel state (did not flow when the test tube was shaken), and Comparative Example 1 was in a slightly viscous liquid state (flowed slightly when the test tube was shaken).

[0024] 7. Gel Removal Experiment Each gel obtained in Experiment (VI) was injected into its corresponding component B (using a syringe to inject component B into the center of the gel), and its morphology was observed after 3 hours.

[0025] Examples 1-2 were mostly liquid (flowed smoothly when the test tube was shaken) and contained a small amount of gel particles; Example 3 was completely liquefied (flowed smoothly when the test tube was shaken) and contained no visible gel particles; Comparative Example 2 was partially liquid (flowed slightly when the test tube was shaken) and the gel did not disintegrate.

[0026] Based on this experiment, it can be inferred that the A component (which is the main body of this bone and joint biological lubricant) obtained by the technical solution described in this invention can be activated by body temperature (37°C) to gel in the human body to provide support. When it is necessary to remove the gel, the gel can be liquefied by injecting the B component, which is convenient for removal by conventional therapeutic aspiration.

[0027] The embodiments and descriptions above are merely illustrative of the principles and preferred embodiments of the present invention. Various changes and modifications may be made to the present invention without departing from its spirit and scope, and all such changes and modifications fall within the scope of the present invention as claimed.

Claims

1. A biological lubricant for bone and joints, characterized in that, Includes component A and component B; Component A comprises the following raw materials in parts by volume: 4-6 parts of 4% (w / v) sodium alginate solution, 0.3-0.5 parts of 1M calcium nitrate tetrahydrate solution, 0.4-0.6 parts of 2M β-glycerophosphate sodium solution, and 4-4.5 parts of physiological saline; Component B comprises the following raw materials in parts by volume: 3-5 parts of 1M sodium citrate solution.

2. The bone and joint biological lubricant according to claim 1, characterized in that: The 4% (w / v) sodium alginate solution is prepared by diluting 4g of sodium alginate to 100mL with sterile deionized water.

3. The bone and joint biological lubricant according to claim 1, characterized in that: The 1M calcium nitrate tetrahydrate solution is prepared by diluting 23.62g of calcium nitrate tetrahydrate to 100mL with sterile deionized water.

4. The bone and joint biological lubricant according to claim 1, characterized in that: The 2M β-glycerophosphate sodium solution is prepared by diluting 43.21g of β-glycerophosphate sodium with sterile deionized water to a final volume of 100mL.

5. The bone and joint biological lubricant according to claim 1, characterized in that: The 1M sodium citrate solution is prepared by diluting 25.8g of sodium citrate to 100mL with sterile deionized water.

6. The bone and joint biological lubricant according to claim 1, characterized in that: The A or B component also includes the following raw materials in parts by volume: 0.1 parts of 1M dexamethasone solution.

7. A method for preparing the bone and joint biological lubricant as described in claim 1, characterized in that, Includes the following steps: Step 1: Stir the 4% (w / v) sodium alginate solution at room temperature until it becomes completely clear; this step ensures that the sodium alginate is completely dissolved. Step 2: After centrifuging the 4% (w / v) sodium alginate solution to remove air bubbles, store it at 4°C for later use. Step 3: Under ice bath and stirring conditions, add sodium β-glycerophosphate solution dropwise to calcium nitrate tetrahydrate solution. During the dropwise addition process, a white turbidity will be produced, but it will gradually dissolve and become clear as the dropwise addition continues, resulting in a complex solution, which is stored at 4°C for later use. Step 4: Under ice bath and stirring conditions, the complexing solution is added dropwise to a 4% (w / v) sodium alginate solution to obtain component A. After passing through a 0.22 μm filter membrane, it is stored at 4°C for later use. Component A is the main injection solution. Before injection, it is a liquid. After being injected into the joint cavity, it is automatically triggered by the body temperature to gel. The gel acts as a gel-type biological lubricant that combines support, buffering and lubrication. Step 5: After passing component B through a 0.22μm filter membrane, store it at 4℃ for later use.

8. The method for preparing the bone and joint biological lubricant according to claim 7, characterized in that: Steps one through five are all performed in a sterile environment.

9. Use of the bone and joint biolubricant as described in claim 1 in the preparation of a medicament for early osteoarthritis.