Bone repair gel and preparation method thereof

Abstract

The present application discloses a bone repair gel, which includes, by mass, 5 to 15 parts of biodegradable polymer materials, 1 to 5 parts of calcium supplements, 0.01 to 0.05 parts of growth factors, and 0.05 to 0.2 parts of non-steroidal anti-inflammatory drugs; the biodegradable polymer material is polylactic-co-glycolic acid copolymer. The present application adjusts the local effective concentration of non-steroidal anti-inflammatory drugs to 0.05-0.2 mg / mL to achieve a balance between anti-inflammatory and osteogenesis; combines growth factors and calcium supplements to significantly improve bone regeneration and mineralization capacity; constructs a gel matrix through biodegradable materials, provides a sustained release function, prolongs the drug action time, avoids the situation where the drug effect is too strong during the peak period or the drug disappears quickly, and the drug effect is prolonged, thereby enhancing the repair effect.

Description

Technical Field

[0001] The present application relates to the field of bone repair and tissue engineering, and in particular to a bone repair gel and a preparation method thereof. Background Art

[0002] In the process of bone repair, inflammatory response is an important stage in initiating bone regeneration, but excessive or persistent inflammation may inhibit the osteogenesis process and lead to bone resorption. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to control postoperative inflammation due to their good anti-inflammatory effects, but traditional oral or injection methods may cause systemic side effects (such as gastrointestinal damage).

[0003] Bone repair gel can improve the side effects caused by traditional oral or injection methods. However, many traditional NSAIDs, such as ibuprofen and naproxen, although the incidence of toxic reactions is very low, still have many less serious side effects. Long-term high-dose administration can lead to gastrointestinal reactions, liver, kidney and blood system damage, etc.

[0004] Therefore, developing a bone repair gel that can ensure long-term anti-inflammatory and bone repair effects and prolong drug action and calcium release time is an urgent problem to be solved by those skilled in the art. Summary of the invention

[0005] In view of this, the present application provides a bone repair gel that can reduce postoperative inflammatory response, reduce the possibility of bone resorption, thereby promoting bone repair, and provide a sustained release function to prolong the time of drug action and calcium release.

[0006] The present application provides a bone repair gel, which comprises, by mass, 5 to 15 parts of a biodegradable polymer material, 1 to 5 parts of a calcium supplement, 0.01 to 0.05 parts of a growth factor, and 0.05 to 0.2 parts of a non-steroidal anti-inflammatory drug; the biodegradable polymer material is a polylactic acid-glycolic acid copolymer.

[0007] The present application uses 5 to 15 parts of biodegradable polymer materials, 1 to 5 parts of calcium supplements, 0.01 to 0.05 parts of growth factors and 0.05 to 0.2 parts of non-steroidal anti-inflammatory drugs. The bone repair gel prepared can achieve bone defect repair, bone regeneration promotion and inflammation inhibition, has excellent fixation ability, anti-inflammatory properties and bone regeneration effects, provides an efficient and safe solution for bone defect repair and postoperative inflammation management, and has good sustained release properties, which can release continuously for more than 48 hours.

[0008] The bone repair gel described in the present application includes a biodegradable polymer material. In some specific implementations, the biodegradable polymer material is polylactic acid-glycolic acid copolymer (PLGA). The biodegradable polymer material can slowly release the active ingredients in the gel by constructing a gel matrix, thereby ensuring the sustained release of the drug and avoiding the situation where the drug effect is too strong or the drug disappears rapidly during the peak period. Through the sustained-release characteristics of PLGA, the effect of the drug is prolonged, thereby enhancing the repair effect.

[0009] In some specific implementations, the mass percentage of the biodegradable polymer material is 5 to 15 parts, which can be 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 parts, and is preferably 8 to 12 parts.

[0010] The bone repair gel described in the present application includes a calcium supplement. In some specific implementations, the calcium supplement includes but is not limited to hydroxyapatite and / or calcium phosphate, and the present application has no special requirements for the selection of calcium supplements. In some specific implementations, the calcium supplement is hydroxyapatite and calcium phosphate, and the mass ratio of hydroxyapatite to calcium phosphate is 1:1 to 4:1, preferably 2:1. Calcium supplements provide the required minerals for bone tissue and promote the formation and mineralization of bone matrix. Calcium provides support for bone cells during the repair process, and meloxicam helps calcium supplements better participate in bone repair by reducing inflammation and avoiding excessive bone absorption.

[0011] In some specific implementations, the mass percentage of the calcium supplement is 1 to 5 parts, and can be 1 part, 1.5 parts, 2 parts, 2.5 parts, 3 parts, 3.5 parts, 4 parts, 4.5 parts, 5 parts, and is preferably 2 to 4 parts.

[0012] The bone repair gel described in the present application includes growth factors. In some specific implementations, the growth factors include but are not limited to one or more of bone morphogenetic protein, vascular endothelial growth factor or fibroblast growth factor, and the present application has no special requirements for the selection of growth factors. Bone morphogenetic protein (BMP-2) as a bone morphogenetic protein can significantly promote the proliferation and differentiation of osteoblasts, thereby accelerating the regeneration and mineralization of bone tissue. When inflammation is effectively controlled, the effect of BMP-2 is more significant.

[0013] In some specific implementations, the mass fraction of the growth factor is 0.01 to 0.05, and can be 0.02, 0.03, 0.04, or 0.05.

[0014] The bone repair gel described in the present application includes non-steroidal anti-inflammatory drugs. In some specific implementations, the non-steroidal anti-inflammatory drugs include but are not limited to nano-scale meloxicam, and the present application has no special requirements for the selection of non-steroidal anti-inflammatory drugs. Meloxicam inhibits inflammation through local sustained release, helps BMP-2 to play its role, and improves the effect of bone repair. While inflammation is controlled, calcium supplements can work together with BMP-2 to further promote the deposition and mineralization of bone matrix. The anti-inflammatory effect of meloxicam and the mineralization effect of calcium supplements promote each other and enhance the overall effect of bone repair. In some specific implementations, the nano-scale meloxicam includes meloxicam nanocrystals and / or meloxicam solid dispersions; the particle size of the non-steroidal anti-inflammatory drug is 100nm to 200nm, preferably 120nm to 180nm. In the bone repair gel, meloxicam (Meloxicam) has multiple significant advantages as a non-steroidal anti-inflammatory drug (NSAID) compared with other traditional NSAIDs. First, meloxicam is a selective COX-2 inhibitor that can effectively inhibit the COX-2 enzyme activity associated with inflammation and pain, while having a weaker inhibitory effect on COX-1, which makes it better at reducing gastrointestinal side effects. Compared with many traditional NSAIDs, such as ibuprofen and naproxen, it is less irritating to the gastrointestinal tract and suitable for long-term use. Secondly, meloxicam has significant advantages in anti-inflammatory and analgesic effects, especially in the treatment of inflammation after osteoarthritis and soft tissue injuries, which can effectively relieve inflammation and pain while reducing the negative impact on bone healing.

[0015] In addition, meloxicam has a long half-life (about 20 hours), which allows it to maintain its efficacy for a longer period of time during bone repair, reducing the need for patients to take medication frequently and improving medication compliance. Compared with traditional NSAIDs, meloxicam has fewer side effects, especially in the gastrointestinal tract, which can reduce the risk of gastric ulcers and bleeding caused by long-term use. Through local administration, meloxicam can act directly on the damaged area, further reducing local inflammation and promoting recovery.

[0016] The bone repair gel described in the present application forms a synergistic effect by combining meloxicam with growth factors (such as BMP-2) and calcium supplements (such as hydroxyapatite), thereby achieving a balance among bone repair, inflammation inhibition and osteogenesis.

[0017] Meloxicam has a selective COX-2 inhibitory effect, which promotes bone repair by reducing postoperative inflammatory response and reducing the possibility of bone resorption. The local sustained-release properties of meloxicam ensure long-term anti-inflammatory effects and provide a favorable growth environment for bone tissue.

[0018] In some specific implementations, the concentration of the non-steroidal anti-inflammatory drug is 0.05 parts to 0.2 parts, and can be 0.05 parts, 0.1 parts, 0.15 parts, or 0.2 parts.

[0019] In some specific implementations, the preparation method of the meloxicam nanocrystals includes: mixing meloxicam, a solvent and a stabilizer, performing wet grinding, setting the grinding speed between 1000-3000rpm, and the grinding time is usually set to 30min to 50min, to obtain meloxicam nanocrystals. In some specific implementations, the preparation method of the meloxicam solid dispersion includes: dissolving 1 times the weight of meloxicam in ethanol, and dissolving 2 times the weight of hydroxypropyl methylcellulose (HMPC) in the same volume of water as ethanol. The drug solution is mixed with the HMPC solution, and the solvent is gradually removed by rotary evaporation or the like, so that the drug is evenly dispersed in the matrix to form a solid dispersion.

[0020] The present application also provides a method for preparing a bone repair gel, comprising:

[0021] The biodegradable polymer material, the organic solvent and the calcium supplement are mixed and ultrasonically dispersed to obtain a gel matrix;

[0022] The nonsteroidal anti-inflammatory drug, buffer, gel matrix and growth factor are mixed and emulsified, and the solvent is evaporated and freeze-dried to obtain the bone repair gel.

[0023] The present application first needs to prepare meloxicam nanocrystals or meloxicam solid dispersions. In some specific implementations, the preparation method of the meloxicam nanocrystals includes: mixing meloxicam and a solvent, performing wet grinding, and obtaining meloxicam nanocrystals. In some specific implementations, the step of wet grinding includes: adding a premixed liquid to a grinding device, and performing wet grinding. Depending on the type of equipment (ball mill, bead mill or high-pressure homogenizer, etc.), the grinding speed is usually set between 1000-3000rpm, and the grinding time is usually set to 30min to 50min. In some specific implementations, the preparation method of the meloxicam solid dispersion includes: dissolving meloxicam in ethanol and HPMC in water. The drug solution is mixed with the HPMC solution, and the solvent is gradually removed by rotary evaporation or the like, so that the drug is evenly dispersed in the matrix to form a solid dispersion. The present application then dissolves the biodegradable polymer material in an organic solvent to obtain a PLGA solution. In some specific implementations, the organic solvent includes but is not limited to dichloromethane, and the present application has no special requirements for the selection of the organic solvent. In some specific implementations, the mass percentage of PLGA in the PLGA solution is 8% to 15%, preferably 10%.

[0024] The present application then adds a calcium supplement to the PLGA solution and performs ultrasonic dispersion to obtain a gel matrix. In some specific implementations, the calcium supplement includes but is not limited to hydroxyapatite and / or calcium phosphate; the calcium supplement is hydroxyapatite and calcium phosphate, and the mass ratio of hydroxyapatite to calcium phosphate is 1:1 to 4:1. In some specific implementations, the ultrasonic dispersion time is 10 min to 40 min.

[0025] The present application then disperses the meloxicam nanocrystals or meloxicam solid dispersion in a buffer solution, stirs, and then adds growth factors to mix and emulsify to obtain a suspension. In some specific implementations, the growth factors include but are not limited to one or more of bone morphogenetic protein, vascular endothelial growth factor or fibroblast growth factor, and the present application has no special requirements for the selection of growth factors. In some specific implementations, the buffer solution includes but is not limited to phosphate buffer, and the present application has no special requirements for the selection of buffer solution. In some specific implementations, the volume of the buffer solution is 75% to 90% of the total volume of the non-steroidal anti-inflammatory drug, buffer solution, gel matrix and growth factor.

[0026] The present application then performs solvent volatilization, freeze drying and inactivation on the suspension to obtain bone repair gel. In some specific implementations, the specific step of solvent volatilization includes: adding the drug solution to a rotary evaporator at 30°C-40°C and vacuum drying.

[0027] The present application achieves a balance between anti-inflammatory and osteogenic effects by adjusting the local effective concentration of non-steroidal anti-inflammatory drugs to 0.05-0.2 mg / mL; combines growth factors and calcium supplements to significantly improve bone regeneration and mineralization capabilities; constructs a gel matrix with biodegradable materials to provide a sustained release function, prolong the drug action time, avoid the situation where the drug effect is too strong at the peak or the drug disappears quickly, and the drug effect is prolonged, thereby enhancing the repair effect, and can be released continuously for more than 48 hours; the 6-day release rate of calcium release can reach more than 90%. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 This is a drug release diagram of the bone repair gel provided in Example 1 of the present application;

[0029] Figure 2 This is a calcium release diagram of the bone repair gel provided in Example 1 of the present application;

[0030] Figure 3 This is a drug release diagram of the bone repair gel provided in Example 2 of the present application;

[0031] Figure 4 This is a calcium release diagram of the bone repair gel provided in Example 2 of the present application;

[0032] Figure 5 This is a drug release diagram of the bone repair gel provided in Example 3 of the present application;

[0033] Figure 6 This is a calcium release diagram of the bone repair gel provided in Example 3 of the present application;

[0034] Figure 7 This is a drug release diagram of the bone repair gel provided in Example 4 of the present application;

[0035] Figure 8 This is a calcium release diagram of the bone repair gel provided in Example 4 of the present application;

[0036] Fig. 9 This is a drug release diagram of the bone repair gel provided in Example 5 of the present application;

[0037] Fig.10 This is a calcium release diagram of the bone repair gel provided in Example 5 of the present application;

[0038] Fig.11 This is a drug release diagram of the bone repair gel provided in Comparative Example 1 of the present application;

[0039] Fig.12 This is a calcium release diagram of the bone repair gel provided in Comparative Example 1 of the present application;

[0040] Fig.13 This is a drug release diagram of the bone repair gel provided in Comparative Example 2 of the present application;

[0041] Fig.14 This is the calcium release diagram of the bone repair gel provided in Comparative Example 2 of the present application. DETAILED DESCRIPTION

[0042] It should be understood that the expression "one or more of..." includes each of the items recited after the expression individually and in various different combinations of two or more of the recited items, unless otherwise understood from the context and usage. The expression "and / or" in combination with three or more recited items should be understood to have the same meaning, unless otherwise understood from the context.

[0043] The use of the terms "comprising", "having" or "containing", including their grammatical synonyms, should generally be understood as open and non-restrictive, for example not excluding other unrecited elements or steps, unless otherwise specifically stated or otherwise understood from the context.

[0044] It should be understood that the order of steps or the order in which certain actions are performed is not important as long as the application is still operable. In addition, two or more steps or actions can be performed simultaneously.

[0045] The use of any and all examples or exemplary language, such as "for example" or "including", herein is intended only to better illustrate the present application and does not limit the scope of the present application unless the claims are set forth. No language in this specification should be construed as indicating that any non-claimed element is essential to the practice of the present application.

[0046] In addition, the numerical ranges and parameters used to define the present application are approximate values, and the relevant values ​​in the specific embodiments have been presented as accurately as possible. However, any numerical value inherently inevitably contains standard deviations due to individual test methods. Therefore, unless otherwise expressly stated, it should be understood that all ranges, quantities, values ​​and percentages used in this disclosure are modified by "about". Here, "about" generally means that the actual value is within plus or minus 10%, 5%, 1% or 0.5% of a specific value or range.

[0047] The present application provides a bone repair gel, which comprises, by mass, 5 to 15 parts of a biodegradable polymer material, 1 to 5 parts of a calcium supplement, 0.01 to 0.05 parts of a growth factor, and 0.05 to 0.2 parts of a non-steroidal anti-inflammatory drug; the biodegradable polymer material is a polylactic acid-glycolic acid copolymer.

[0048] The present application achieves a balance between anti-inflammatory and osteogenic effects by adjusting the local effective concentration of non-steroidal anti-inflammatory drugs to 0.05-0.2 mg / mL; combines growth factors and calcium supplements to significantly improve bone regeneration and mineralization capabilities; constructs a gel matrix with biodegradable materials to provide a sustained release function, prolong the drug action time, avoid the situation where the drug effect is too strong at the peak or the drug disappears quickly, and the drug effect is prolonged, thereby enhancing the repair effect, and can be released continuously for more than 48 hours; the 6-day release rate of calcium release can reach more than 90%.

[0049] The present application is further described below in conjunction with the following embodiments. The protection scope of the present application is not limited by the following embodiments.

[0050] Example 1

[0051] This embodiment provides a bone repair gel, comprising:

[0052] Biodegradable material: PLGA 1000mg;

[0053] Meloxicam nanocrystals: 10 mg (particle size 100-200 nm);

[0054] Growth factors: BMP-2, 3 mg;

[0055] Calcium supplement: Hydroxyapatite 200mg.

[0056] Prepare the raw material also including buffer: add phosphate buffered saline (PBS) to 100 mL.

[0057] The preparation method of the meloxicam nanocrystal comprises: dissolving 1 times of meloxicam in 1 times of ethanol, adding 1 times of stabilizer (Poloxamer 188), high-speed shear mixing, adopting wet grinding technology, adding the premixed liquid into a grinding device, and performing wet grinding. According to the equipment type (ball mill, bead mill or high-pressure homogenizer, etc.), the grinding speed is usually set between 1000-3000rpm, and the grinding time is usually set to 30min to 50min. The crystal particle size is controlled to 100-200nm, and the meloxicam nanocrystal is obtained after freeze-drying.

[0058] The bone repair gel preparation method comprises:

[0059] Dissolving PLGA in dichloromethane to obtain a PLGA solution, adding hydroxyapatite and calcium phosphate particles to the PLGA solution, and uniformly dispersing by ultrasonication to obtain a gel matrix;

[0060] adding meloxicam nanocrystals into a buffer solution and stirring to obtain a meloxicam nanocrystal suspension;

[0061] Add bone repair matrix to meloxicam nanocrystal suspension and stir evenly; add BMP-2 and mix evenly; mix with gel matrix and form gel by emulsification-solvent evaporation method: dissolve gel matrix meloxicam and bone repair matrix in dichloromethane to form oil phase. Slowly add oil phase to water phase containing emulsifier and stir to form stable oil-in-water (O / W) emulsion. Remove solvent by rotary evaporation to promote drug and matrix aggregation to form gel. Sterilize after freeze drying to obtain bone repair gel.

[0062] Example 2

[0063] This embodiment provides a bone repair gel, comprising:

[0064] Biodegradable material: PLGA 1200mg;

[0065] Meloxicam solid dispersion: 10 mg (particle size 100-200 nm);

[0066] Growth factors: BMP-2, 2 mg;

[0067] Calcium supplement: 300 mg hydroxyapatite, 100 mg calcium phosphate.

[0068] Prepare the raw material also including buffer: add phosphate buffered saline (PBS) to 100 mL.

[0069] The preparation method of the meloxicam solid dispersion comprises: dissolving meloxicam in ethanol and HPMC in water, mixing the drug solution with the HPMC solution, and gradually removing the solvent by rotary evaporation or the like, so that the drug is evenly dispersed in the matrix to form a solid dispersion.

[0070] The preparation method of the bone repair gel is the same as that in Example 1.

[0071] Example 3

[0072] This embodiment provides a bone repair gel, comprising:

[0073] Biodegradable material: PLGA 1500mg;

[0074] Meloxicam nanocrystals: 15 mg (particle size 100-200 nm);

[0075] Growth factors: BMP-2, 4 mg;

[0076] Calcium supplement: Hydroxyapatite 200mg.

[0077] Prepare the raw material also including buffer: add phosphate buffered saline (PBS) to 100 mL.

[0078] The preparation method of the meloxicam nanocrystals is the same as that in Example 1.

[0079] The preparation method of the bone repair gel is the same as that in Example 1.

[0080] Example 4

[0081] This embodiment provides a bone repair gel, comprising:

[0082] Biodegradable material: PLGA 1000mg;

[0083] Meloxicam solid dispersion: 5 mg (particle size 100-200 nm);

[0084] Growth factors: BMP-2, 2.5 mg;

[0085] Calcium supplement: 400 mg hydroxyapatite, 200 mg calcium phosphate.

[0086] Prepare the raw material also including buffer: add phosphate buffered saline (PBS) to 100 mL.

[0087] The preparation method of the meloxicam solid dispersion is the same as that in Example 2.

[0088] The preparation method of the bone repair gel is the same as that of Example 2.

[0089] Example 5

[0090] This embodiment provides a bone repair gel, comprising:

[0091] Biodegradable material: PLGA 1000mg;

[0092] Meloxicam nanocrystals: 10 mg (particle size 100-200 nm);

[0093] Growth factors: BMP-2, 3 mg, VEGF (vascular endothelial growth factor) 2 mg;

[0094] Calcium supplement: Hydroxyapatite 200mg.

[0095] Prepare the raw material also including buffer: add phosphate buffered saline (PBS) to 100 mL.

[0096] The preparation method of the meloxicam nanocrystals is the same as that in Example 1.

[0097] The bone repair gel preparation method comprises:

[0098] Dissolving PLGA in dichloromethane to obtain a PLGA solution, adding hydroxyapatite and calcium phosphate particles to the PLGA solution, and uniformly dispersing by ultrasonication to obtain a gel matrix;

[0099] adding meloxicam nanocrystals into a buffer solution and stirring to obtain a meloxicam nanocrystal suspension;

[0100] Add bone repair matrix to meloxicam nanocrystal suspension and stir evenly; add BMP-2 and VEGF and mix evenly; mix with gel matrix and form gel by emulsification-solvent evaporation method: dissolve gel matrix meloxicam and bone repair matrix in dichloromethane to form oil phase. Slowly add oil phase to water phase containing emulsifier and stir to form stable oil-in-water (O / W) emulsion. Remove solvent by rotary evaporation to promote drug and matrix aggregation to form gel, freeze-dry and sterilize to obtain bone repair gel.

[0101] Comparative Example 1

[0102] This comparative example provides a bone repair gel, comprising:

[0103] Biodegradable material: PVA 1000mg;

[0104] Meloxicam nanocrystals: 10 mg (particle size 100-200 nm);

[0105] Growth factors: BMP-2, 3 mg, VEGF (vascular endothelial growth factor) 2 mg;

[0106] Calcium supplement: Hydroxyapatite 200mg.

[0107] Prepare the raw material also including buffer: add phosphate buffered saline (PBS) to 100 mL.

[0108] The preparation method of the meloxicam nanocrystals is the same as that in Example 5.

[0109] The preparation method of the bone repair gel is the same as that of Example 5.

[0110] Comparative Example 2

[0111] The only difference between this comparative example and comparative example 1 is that PVA is replaced with sodium alginate.

[0112] The preparation method of the meloxicam nanocrystals is the same as that in Example 1.

[0113] The preparation method of the bone repair gel is the same as that in Example 1.

[0114] The performance of the bone repair gel provided in Examples 1-5 and Comparative Examples 1-2 was tested, and the testing method was as follows:

[0115] Calcium release detection: ICP-OES was used to measure the calcium ion release;

[0116] Drug release assay: Meloxicam concentration-time curve was analyzed using HPLC.

[0117] The drug release diagram of the bone repair gel provided in Example 1 is as follows Figure 1 As shown; the calcium release diagram of the bone repair gel provided in Example 1 is as shown Figure 2 As shown; the drug release diagram of the bone repair gel provided in Example 2 is as shown Figure 3 As shown; the calcium release diagram of the bone repair gel provided in Example 2 is as shown Figure 4 As shown; the drug release diagram of the bone repair gel provided in Example 3 is as shown Figure 5 As shown; the calcium release diagram of the bone repair gel provided in Example 3 is as shown Figure 6 As shown; the drug release diagram of the bone repair gel provided in Example 4 is as shown Figure 7 As shown; the calcium release diagram of the bone repair gel provided in Example 4 is as shown Figure 8 As shown; the drug release diagram of the bone repair gel provided in Example 5 is as shown Fig. 9 As shown; the calcium release diagram of the bone repair gel provided in Example 5 is as shown Fig.10 As shown; the drug release diagram of the bone repair gel provided in Comparative Example 1 is as shown Fig.11 As shown; Comparative Example 1 provides a calcium release diagram of the bone repair gel as shown Fig.12 As shown; the drug release diagram of the bone repair gel provided in Comparative Example 2 is as shown Fig.13 As shown; Comparative Example 2 provides a calcium release diagram of the bone repair gel as shown Fig.14 shown.

[0118] The drug release of the bone repair gel described in Examples 1-5 can be sustained for more than 48 hours, and the release rate in 6 days can reach more than 90%, while that in Comparative Example 1 is only 85%. After 2 days, the release rate of the embodiment can be controlled below 40%, while Comparative Example 1 has reached 60%, and Comparative Example 2 has reached 89%, and the sustained-release effect of the embodiment is obvious; the bone repair gel calcium release described in Examples 1-5 can be controlled below 50% when the embodiment is released for 2 days, while Comparative Example 1 has reached 55%, and Comparative Example 2 has reached 85%, and the sustained-release effect of the embodiment is obvious.

[0119] The above is only a preferred specific implementation manner of the present application, but the protection scope of the present application is not limited thereto. Any technician familiar with the technical field can make equivalent substitutions or changes within the technical scope disclosed in the present application according to the technical solution and application concept of the present application, which should be covered by the protection scope of the present application.

Claims

1. A bone repair gel, characterized in that: The composition comprises, by weight: 5 to 15 parts of biodegradable polymer materials, 1 to 5 parts of calcium supplements, 0.01 to 0.05 parts of growth factors and 0.05 to 0.2 parts of non-steroidal anti-inflammatory drugs; the biodegradable polymer material is a polylactic acid-glycolic acid copolymer.

2. The bone repair gel according to claim 1, characterized in that: The calcium supplement includes hydroxyapatite and / or calcium phosphate.

3. The bone repair gel according to claim 2, characterized in that: The calcium supplement is hydroxyapatite and calcium phosphate, and the mass ratio of hydroxyapatite to calcium phosphate is 1:1 to 4:

1.

4. The bone repair gel according to claim 1, characterized in that: The growth factor comprises one or more of bone morphogenetic protein, vascular endothelial growth factor or fibroblast growth factor.

5. The bone repair gel according to claim 1, characterized in that: The non-steroidal anti-inflammatory drug comprises nano-scale meloxicam; the particle size of the non-steroidal anti-inflammatory drug is 100nm to 200nm.

6. The bone repair gel according to claim 1, characterized in that: The nano-scale meloxicam includes meloxicam nanocrystals and / or meloxicam solid dispersions.

7. A method for preparing the bone repair gel according to any one of claims 1 to 6, characterized in that: include: The biodegradable polymer material, the organic solvent and the calcium supplement are mixed and ultrasonically dispersed to obtain a gel matrix; The nonsteroidal anti-inflammatory drug, buffer, gel matrix and growth factor are mixed and emulsified, the solvent is evaporated and freeze-dried to obtain the bone repair gel.

8. The preparation method according to claim 7, characterized in that: The buffer comprises a phosphate buffer.

9. The preparation method according to claim 7, characterized in that: The volume of the buffer is 75% to 90% of the total volume of the nonsteroidal anti-inflammatory drug, the buffer, the gel matrix and the growth factor.

10. The preparation method according to claim 7, characterized in that: The ultrasonic dispersion time is 10 min to 40 min.

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