CN101244275A - Bone disease treatment and repair long-acting slow-release drug carrier material and preparation method thereof - Google Patents

Abstract

The invention discloses a long-acting slow-release drug carrier material for bone disease treatment and repair and a preparation method thereof. The drug carrier material mainly includes 4-8 parts by weight of strontium-doped calcium polyphosphate, 1-3 parts by weight of Chitosan drug-loaded microspheres and 1-3 parts by weight of chitosan. The preparation method is mainly as follows: preparing chitosan acetic acid solution, adding strontium-doped calcium polyphosphate powder into the chitosan acetic acid solution to make it evenly dispersed, then adding the prepared chitosan drug-loaded microspheres, and finally adding The cross-linking agent makes it cross-linked, and after being frozen at 2-6°C for 12-48 hours, it is heated and dried at 40-100°C to obtain a composite drug carrier material for treating bone diseases such as osteomyelitis. The long-acting slow-release drug carrier material used for the treatment and repair of osteomyelitis and other bone diseases provided by the present invention has bone repair function while releasing antibiotics for a long time, and has good biocompatibility and degradability. It has an ideal dual function of treatment and repair.

Description

Bone disease treatment and repair long-acting slow-release drug carrier material and preparation method thereof

a technical field

The invention relates to the technical field of biomedical material drug carriers, in particular to the technical field of long-acting slow-release drug carrier materials used for the treatment of osteomyelitis and other bone diseases and the repair of bone defects.

Two background technology

Traditional treatment of osteomyelitis usually includes surgical removal of infected tissue, washing with antiseptic solution, and 4 to 6 weeks of gastrointestinal antibiotic treatment. In order for the drug in the bone tissue to effectively kill bacteria, it is necessary to make the drug concentration in the bone tissue reach a bactericidal level, which requires prolonging the administration time and using antibiotics with high blood concentration. Due to the high incidence of disease associated with high blood levels of antibiotics, a number of topical drug delivery systems have been extensively studied and used. Carriers for topical administration of antibiotics can be classified into non-biodegradable and biodegradable types. The main representatives of the former type of sustained-release drug system for the treatment of osteomyelitis are polymethyl methacrylate (PMMA) chain beads, apatite-wollastonite glass ceramics, and hydroxyapatite. Gentamicin is often contained in PMMA chain beads, which is the earliest developed variety. The release of antibiotics from drug delivery systems is controlled by the rate of drug diffusion or dissolution in the matrix. The concentration of antibiotics locally released by these systems can generally exceed the minimum inhibitory concentration (MIC) of the most common pathogens that cause chronic osteomyelitis. At the same time, antibiotics are basically not released into the blood circulation and enter the whole body, and have little impact on other parts of the human body. At present, the gentamicin chain strain made of PMMA bone cement and gentamicin is commonly used clinically at home and abroad, which can maintain the drug effect for more than 2 months, but because the bone cement does not degrade, it needs a second operation to remove it. , causing great pain to the patient. The use of degradable biomaterials as drug carriers is a trend in the treatment of osteomyelitis.

Osteomyelitis, on the other hand, often results in bone loss and must be treated with bone repair. Current bone repair materials include polymer materials and bioceramics, among which polymer materials such as polylactic acid (PLA), polyglycolic acid (PGA) have good biocompatibility and degradability, but the lack of mechanical strength Poor, the mechanical strength loss is too fast during the degradation process. Bioceramics mainly include hydroxyapatite, tricalcium phosphate and calcium phosphate bone cement, etc. The disadvantage of hydroxyapatite is that it is brittle and difficult to degrade; the degradation rate of tricalcium phosphate is too fast, and it is difficult to control the degradation rate; calcium phosphate bone cement can Self-curing, but its degradation rate is too fast and its strength is not enough. Strontium-doped calcium polyphosphate (SCPP) is an inorganic polymer bioceramic, which has good biocompatibility, can promote vascularization, promote bone formation, and controllable degradation rate. ceramics. The laboratory of the inventor of the present invention has conducted in-depth research on strontium-doped calcium polyphosphate, and the prepared strontium-doped calcium polyphosphate has been granted a patent (patent number: ZL200410040611.5).

At present, the treatment of osteomyelitis focuses on the research of drug carrier materials on the one hand. Polymer drug carrier materials can control the time and rate of drug release, but cannot perform bone repair; on the other hand, inorganic bioceramics are also used as drug carrier materials, such as hydroxyphosphorus Limestone contains vancomycin for the treatment of osteomyelitis, but the release time of the drug is short, which cannot achieve the effect of long-acting sustained-release treatment.

Three invention content

Aiming at the deficiencies in the above-mentioned prior art, the present invention provides a long-acting slow-release drug carrier material for the treatment and repair of osteomyelitis and other bone diseases and the purpose of its preparation method is to solve the following technical problems: the prepared drug carrier material can be used in the long-term Time-released antibiotics have bone repair function at the same time, and have good biocompatibility, degradation, promotion of osteogenesis and vascularization, so as to play an ideal dual-functional role in the treatment of osteomyelitis and other bone diseases.

The basic idea of the present invention is to use chitosan with good biocompatibility as the drug carrier material to prepare chitosan-loaded antibiotic microspheres, use layer-by-layer self-assembly technology to increase different coating layers on the surface of the microspheres, and then alternately coat The drug-loaded microspheres with sodium alginate layer and chitosan layer are compounded with strontium-doped calcium polyphosphate, so that the composite carrier can release antibiotics in a gradient at different time periods, and at the same time, it can also perform bone repair to achieve a thorough treatment of osteomyelitis, etc. Osteopathic purposes.

In order to achieve the above object, the compound drug carrier material for treating and repairing bone diseases provided by the present invention mainly includes strontium-doped calcium polyphosphate (SCPP), chitosan drug-loaded microspheres and chitosan (CS). The content of each component of the carrier is mainly determined according to its influence on the release performance and mechanism of the carrier. The content of SCPP has a great influence on the mechanical strength and controllable degradation performance of the material. High SCPP content has good mechanical properties and slow degradation rate; low SCPP content has poor mechanical properties and fast degradation rate. The content of chitosan drug-loaded microspheres affects the rate, concentration and release time of drug release. If the content of chitosan drug-loaded microspheres is high, the initial drug release rate is fast, which is easy to cause a burst release effect; chitosan drug-loaded microspheres When the concentration is low, the drug release time will be shortened. Chitosan and sodium alginate self-assembled layer by layer on the surface of chitosan microspheres, the number of assembled layers is large, the drug release rate is slow, and the drug loading capacity decreases. The content of CS affects the compounding of SCPP and chitosan drug-loaded microspheres, the higher the CS content, the lower the carrier strength; the lower the CS content, the poor dispersion of SCPP and chitosan drug-loaded microspheres. In view of this, the component composition of drug carrier composite material is controlled at, the parts by weight of SCPP is 4-8 parts, the parts by weight of CS is 1-3 parts, and the parts by weight of chitosan drug-loaded microspheres is 1 part by weight. -3 servings are more appropriate.

In the above technical solution, the structure of the chitosan drug-loaded microsphere is composed of a drug-loaded microsphere core and layers of sodium alginate and chitosan alternately coated on its surface. The alternating coating layer composed of sodium alginate layer and chitosan layer coated on the outside of the drug-loaded microsphere core is at least 2 layers, and should not be more than 20 layers, usually 2 to 20 layers. Alternately coating the electrolyte chitosan layer and sodium alginate layer outside the core of the drug-loaded microspheres can further prolong the drug release time of the chitosan drug-loaded microspheres. The production and preparation components of the drug-loaded microsphere core mainly contain chitosan, antibiotics and cross-linking agents, wherein the content of chitosan is variable, usually 29wt%-69wt% (in the drug-loaded microsphere core total weight), the content of antibiotics should reach an effective amount sufficient to produce a bactericidal level in body tissues, and the specific content of antibiotic agents varies depending on different antibiotics. The general requirement is that the delivery time of effective drug concentration is at least 35 days, and its release The concentration should exceed the minimum inhibitory concentration (MIC) of the microorganism causing the infection, usually 29wt%-69wt% (in the total weight of the drug-loaded microsphere core). Antibiotics can be selected from tetracycline, vancomycin, gentamicin, tobramycin, ansefo, ceftazidime, cefotaxime, cefadroxil, etc., either one or two of them above. The cross-linking agent is selected from glutaraldehyde, glyoxal, genipin, sodium β-glycerophosphate and polyaldehyde sodium alginate, etc., and its content is relatively low. Generally, chitosan and antibiotics are removed from the drug-loaded microsphere core. remainder after.

The shape of the composite carrier material can be a specific shape required in bone disease treatment, or a general block material, which can be reprocessed into a specific shape when used by a doctor.

The above drug carrier for treating and repairing bone disease can be prepared by the following method: according to the proportion of components, chitosan is added to aqueous acetic acid solution to prepare a chitosan-acetic acid solution with a chitosan concentration of 1.0-3.0 wt%. Add strontium calcium polyphosphate powder into the chitosan acetic acid solution to make it evenly dispersed, then add the prepared chitosan drug-loaded microspheres, and finally add a cross-linking agent to make it cross-linked, freeze at 2-6°C for 12 After 48 hours, heat and dry at a temperature of 40-100°C to obtain a composite drug carrier for treating bone diseases such as osteomyelitis.

As the chitosan drug-loaded microspheres of the drug composite carrier material component, its preparation method comprises the following steps:

(1) According to the composition ratio of the components of chitosan drug-loaded microspheres, chitosan is added into aqueous acetic acid solution to be formulated with a chitosan concentration of 1.0-3.0wt% chitosan acetic acid solution, and antibiotics are added to make it completely Dissolved in chitosan acetic acid solution, used as the water phase of the water-in-oil emulsification system, adding a cross-linking agent, and performing a cross-linking reaction under stirring conditions to form a chitosan drug-loaded microsphere core. After a sufficient cross-linking reaction, separate out Chitosan drug-loaded microsphere core, after cleaning and drying, measure the particle size of the core;

(2) Disperse the chitosan drug-loaded microsphere core with particle size meeting the requirements in sodium alginate aqueous solution with sodium alginate concentration of 0.5-2.0wt%, ion concentration of 0.1-0.6M, and temperature of 50-65°C for 10 -50min for sodium alginate layer-coated self-assembly, separate and clean after self-assembly;

(3) The chitosan drug-loaded microsphere core coated with a sodium alginate layer after the self-assembly process is dispersed in a chitosan concentration of 0.5-2.0wt% and an ion concentration of 0.1-0.6M , chitosan aqueous solution at a temperature of 50-65°C for 10-50 minutes to carry out self-assembly of chitosan layer coating, and separate and clean after self-assembly;

(4) The above step (2) and step (3) are carried out for 1 to 10 times respectively to prepare the chitosan drug-loaded microspheres.

The preparation of SCPP as a component of the drug composite carrier material can refer to the patent document named "Bone tissue repair filling material and its preparation method" and the patent number is "ZL200410040611.5". The basic preparation process is that calcium dihydrogen phosphate and strontium dihydrogen phosphate are calcined at 450-630°C for at least one hour. After the polymerization reaction is completed, the SCPP sintered at the calcining temperature is rapidly cooled and quenched. , and then dried and ground into powder to obtain the strontium-doped calcium polyphosphate SCPP used in the present invention.

The present invention uses layer-by-layer self-assembly technology to alternately coat electrolyte chitosan layers and sodium alginate layers on the outside of chitosan drug-loaded microspheres, which can greatly prolong the effective time of drug release from chitosan drug-loaded microspheres, up to 35 Days or more, and the released drug concentration exceeds the minimum inhibitory concentration (MIC) of the infection-causing microorganisms (such as Staphylococcus aureus, etc.).

Some other technical measures are also disclosed in the following embodiments.

The drug carrier material for treating and repairing osteomyelitis and other bone diseases prepared by the invention is a novel composite drug carrier composed of drug-loaded microspheres and inorganic polymer SCPP. The drug-loaded microspheres in the composite drug carrier are chitosan drug-loaded microspheres, which have good biocompatibility and long drug release time. Layer-by-layer self-assembly technology is used to assemble different layers of shells on the surface of the drug-loaded microsphere core. After the polysaccharide and sodium alginate coating layer, it is not only conducive to the adhesion of the microspheres to the tissue, but also enables the drug to be released in a gradient manner, prolonging the local retention time of the drug. On the other hand, strontium-doped calcium polyphosphate in the composite drug carrier is a good bone repair material, not only its mechanical strength meets the requirements, but also its degradation is controllable, and its -P-O-P- segment can also provide cells with high-energy phosphate bonds , promote bone formation, and make up for the defects in the performance of hydroxyapatite ceramics and glass ceramics widely used at home and abroad. The drug carrier obtained by compounding drug-loaded microspheres and strontium-doped calcium polyphosphate in the present invention prolongs the degradation time. Can further prolong the time of drug release.

Compared with the existing drug carrier for treating osteomyelitis, the composite drug carrier capable of gradiently releasing antibiotic drugs for treating bone diseases such as osteomyelitis has dual functions of bactericidal and antibacterial and bone repair. The carrier material has the characteristics of combination of inorganic phase and organic phase, combination of drug-loaded microspheres and bone repair materials, combination of rigidity and flexibility, etc., so it can not only release drugs for a long time to inhibit bacterial growth, but also perform bone repair and promote osteoblast growth At the same time, it inhibits the growth of osteoclasts, promotes bone repair at the lesion site, and thoroughly treats bone diseases such as osteomyelitis. The disclosure of the present invention brings good news to patients with osteomyelitis and similar hard tissue diseases, and also provides a new idea for the research of other drug carriers.

Four specific implementation methods

The present invention will be better understood with reference to the following examples, which are given to illustrate the invention and not to limit the scope of the invention.

Examples of composite drug carrier materials for treating osteomyelitis and other bone diseases and their preparation methods are as follows:

Example 1:

Preparation of drug-loaded microspheres: adding chitosan to acetic acid aqueous solution to prepare a chitosan-acetic acid solution with a chitosan concentration of 2.0 wt%, adding tetracycline according to the chitosan and tetracycline mass ratio of 1: 1, completely dissolved as In the water phase of the W/O system, after the system is completely dispersed, add the crosslinking agent glutaraldehyde according to the volume ratio of the crosslinking agent and chitosan acetic acid solution at 1:10, the volume concentration of glutaraldehyde is 25%, and stir for about 3 hours. After fully reacting to form the chitosan drug-loaded microsphere core, after centrifugation, cleaning and drying, the particle size is measured with a laser particle size analyzer. Self-assembly of drug-loaded microsphere core coating layer: Prepare 1wt% sodium alginate aqueous solution and chitosan aqueous solution respectively, control the temperature at about 60°C, and 0.3M ion concentration, and disperse the prepared chitosan microsphere core in After about 15min in the sodium alginate aqueous solution of the above-mentioned conditions, centrifugal separation, ultrapure water cleaning, then the microspheres coated with the sodium alginate layer were dispersed in the chitosan aqueous solution of the above-mentioned conditions for about 15min, centrifugal separation, ultra-pure water Wash with pure water, repeat the self-assembly three times with sodium alginate aqueous solution and chitosan aqueous solution alternately according to this method, and assemble 6 layers in total, and obtain self-assembled chitosan drug-loaded microspheres after drying.

Preparation of composite drug carrier: Chitosan is added into acetic acid aqueous solution to prepare a chitosan acetic acid solution with a chitosan concentration of about 2wt%, and the mass ratio of SCPP powder and chitosan over 200 meshes is 8: 1. After dispersion, add it to the chitosan acetic acid solution. After complete dispersion, add the prepared self-assembled chitosan drug-loaded microspheres to the solution at a mass ratio of 1:1 to chitosan, and immediately add the crosslinking agent pentadiene Aldehyde, after about 5 minutes, transfer it to a cylindrical mold, store it in a refrigerator at about 4°C for about 24 hours, and dry it completely at about 60°C to obtain a composite drug carrier. The in vitro drug release test results of the drug carrier show that the effective release time of the tetracycline reaches more than 50 days, prolonging the drug release time.

Example 2:

Preparation of drug-loaded microspheres: adding chitosan to aqueous acetic acid solution to prepare a chitosan-acetic acid solution with a chitosan concentration of 2.0 wt%, adding vancomycin according to the mass ratio of chitosan and vancomycin at 2:1 , as the water phase of the W/O system after completely dissolving, after the system is completely dispersed, add the crosslinking agent glutaraldehyde according to the volume ratio of the crosslinking agent and chitosan acetic acid solution at 1:10, the glutaraldehyde volume concentration is 25%, After fully reacting to form the chitosan drug-loaded microsphere core, after centrifugation, cleaning and drying, the particle size is measured with a laser particle size analyzer. Self-assembly of drug-loaded microsphere core coating layer: prepare 1wt% sodium alginate aqueous solution and chitosan aqueous solution respectively, control the temperature at about 60°C, and ionic concentration of about 0.3M, and disperse the prepared chitosan microsphere core in After about 15min in the sodium alginate aqueous solution of the above-mentioned conditions, centrifugal separation, ultrapure water cleaning, then the microspheres coated with the sodium alginate layer were dispersed in the chitosan aqueous solution of the above-mentioned conditions for about 15min, centrifugal separation, ultra-pure water Wash with pure water, repeat the self-assembly twice with sodium alginate aqueous solution and chitosan aqueous solution alternately according to this method, and assemble 4 layers in total, and obtain self-assembled chitosan drug-loaded microspheres after drying

Preparation of composite drug carrier: adding chitosan to the aqueous acetic acid solution to prepare chitosan concentration is 2wt% chitosan acetic acid solution, cross 200 mesh SCPP powder and chitosan mass ratio is 8: 1, disperse with absolute ethanol After being added to the chitosan solution, after complete dispersion, the prepared self-assembled chitosan drug-loaded microspheres were added to the solution according to the chitosan mass ratio of 1:1, and the cross-linking agent glutaraldehyde was added immediately, After about 5 minutes, transfer to a cylindrical mold, store in a refrigerator at about 4°C for about 24 hours, and completely dry at about 60°C to obtain a composite drug carrier. The in vitro drug release test results of the drug carrier showed that the release time of vancomycin was more than 40 days.

Example 3:

Preparation of drug-loaded microspheres: adding chitosan to acetic acid aqueous solution to prepare a chitosan-acetic acid solution with a chitosan concentration of 2.0 wt%, adding gentamicin according to the mass ratio of chitosan and gentamicin at 1:1 As the water phase of the W/O system after complete dissolution, after the system is completely dispersed, add the cross-linking agent β-sodium glycerophosphate according to the volume ratio of the cross-linking agent and chitosan acetic acid solution 1:5, the mass of β-sodium glycerophosphate The concentration is 11%, stirred for about 3 hours, fully reacted to form the chitosan drug-loaded microsphere core, centrifuged, washed and dried, and measured with a laser particle size analyzer. Self-assembly of drug-loaded microsphere core coating layer: prepare 0.5wt% sodium alginate aqueous solution and chitosan aqueous solution respectively, control the temperature at about 40°C, and ionic concentration of about 0.5M, and disperse the prepared chitosan microsphere core After 20 minutes in the sodium alginate aqueous solution under the above conditions, centrifuge, wash with ultrapure water, repeat 3 times, and then disperse the above-mentioned microspheres coated with the sodium alginate layer in the chitosan aqueous solution under the above conditions for about 20 minutes , centrifugal separation, and ultrapure water cleaning. According to this method, sodium alginate aqueous solution and chitosan aqueous solution were used alternately to repeat the self-assembly three times, and a total of 6 layers were assembled. After drying, self-assembled chitosan drug-loaded microspheres were obtained.

Preparation of composite drug carrier: adding chitosan to the aqueous acetic acid solution to prepare chitosan concentration is 2wt% chitosan acetic acid solution, cross 200 mesh SCPP powder and chitosan mass ratio is 5: 1, disperse with absolute ethanol Finally, it was added to the chitosan acetic acid solution, and after complete dispersion, the prepared self-assembled chitosan drug-loaded microspheres were added to the solution according to the chitosan mass ratio of 1:2, and the crosslinking agent β-glycerol was added immediately Sodium phosphate, transfer it to a cylindrical mold after about 10 minutes, store it in a refrigerator at about 4°C for about 24 hours, and dry it completely at about 40°C to obtain a composite drug carrier. The in vitro drug release test results of the drug carrier show that the effective release time of gentamicin reaches more than 35 days, prolonging the drug release time.

Example 4:

Preparation of drug-loaded microspheres: adding chitosan to acetic acid aqueous solution to prepare a chitosan-acetic acid solution with a chitosan concentration of 2.0 wt%, adding Tobramycin according to the mass ratio of chitosan to tobramycin 1:1 As the water phase of the W/O system after complete dissolution, after the system is completely dispersed, add the cross-linking agent glyoxal solution according to the volume ratio of cross-linking agent and chitosan acetic acid solution of 1:10, and the volume concentration of glyoxal is 25 %, stirred for about 3 hours, fully reacted to form the chitosan drug-loaded microsphere core, centrifuged, cleaned and dried, and then measured with a laser particle size analyzer. Self-assembly of drug-loaded microsphere core coating layer: prepare 1wt% sodium alginate aqueous solution and chitosan aqueous solution respectively, control the temperature at about 60°C, and ionic concentration of about 0.3M, and disperse the prepared chitosan microsphere core in After being in the sodium alginate aqueous solution of the above-mentioned conditions for about 15 minutes, centrifuge, wash with ultrapure water, and then disperse the above-mentioned microspheres coated with the sodium alginate layer in the chitosan aqueous solution under the above-mentioned conditions for about 15 minutes, and then centrifuge. Washing with ultrapure water, using sodium alginate aqueous solution and chitosan aqueous solution alternately according to this method to repeat the self-assembly three times respectively, a total of 6 layers were assembled, and self-assembled chitosan drug-loaded microspheres were obtained after drying.

Preparation of composite drug carrier: adding chitosan to the aqueous acetic acid solution to prepare chitosan concentration is 2wt% chitosan acetic acid solution, cross 200 mesh SCPP powder and chitosan mass ratio is 5: 1, disperse with absolute ethanol Finally, it was added to the chitosan acetic acid solution, and after complete dispersion, the prepared self-assembled chitosan drug-loaded microspheres were added to the solution according to the chitosan mass ratio of 1:1, and the cross-linking agent glyoxal was added immediately. , transferred to a cylindrical mold after about 5 minutes, stored in a refrigerator at about 4°C for about 24 hours, and completely dried at about 60°C to obtain a composite drug carrier. The in vitro drug release test results of the drug carrier show that the effective release time of tobramycin reaches more than 40 days, prolonging the drug release time.

Example 5:

Preparation of drug-loaded microspheres: adding chitosan to acetic acid aqueous solution to prepare a chitosan-acetic acid solution with a chitosan concentration of 2.0 wt%, adding tetracycline according to the chitosan and tetracycline mass ratio of 1: 1, completely dissolved as The water phase of the W/O system, after the system is completely dispersed, add the crosslinking agent genipin solution according to the volume ratio of the crosslinking agent and chitosan acetic acid solution of 1:5, the mass concentration of the genipin solution is 0.625%, and stir for about 3 Hours later, after fully reacting to form the chitosan drug-loaded microsphere core, after centrifugation, cleaning and drying, the particle size is measured with a laser particle size analyzer. Self-assembly of drug-loaded microsphere core coating layer: prepare 1wt% sodium alginate aqueous solution and chitosan aqueous solution respectively, control the temperature at about 60°C, and ionic concentration of about 0.3M, and disperse the prepared chitosan microsphere core in After being in the sodium alginate aqueous solution of the above-mentioned conditions for about 15 minutes, centrifuge, wash with ultrapure water, and then disperse the above-mentioned microspheres coated with the sodium alginate layer in the chitosan aqueous solution under the above-mentioned conditions for about 15 minutes, and then centrifuge. Washing with ultrapure water, using sodium alginate aqueous solution and chitosan aqueous solution alternately according to this method to repeat the self-assembly three times respectively, a total of 6 layers were assembled, and self-assembled chitosan drug-loaded microspheres were obtained after drying.

Preparation of composite drug carrier: adding chitosan to the aqueous acetic acid solution to prepare chitosan concentration is 2wt% chitosan acetic acid solution, cross 200 mesh SCPP powder and chitosan mass ratio is 5: 1, disperse with absolute ethanol Finally, it was added to the chitosan acetic acid solution. After being completely dispersed, the prepared self-assembled chitosan drug-loaded microspheres were added to the solution according to the chitosan mass ratio of 1:1, and the cross-linking agent genipin was added immediately. The solution is transferred to a cylindrical mold after about 30 minutes, stored in a refrigerator at about 4°C for about 24 hours, and completely dried at about 60°C to obtain a composite drug carrier. The in vitro drug release test results of the drug carrier show that the effective release time of tetracycline reaches more than 40 days, prolonging the drug release time.

Claims (10)

1. A long-acting slow-release drug carrier material for bone disease treatment and repair, characterized in that the composition of the carrier composite material mainly includes 4-8 parts by weight of strontium-doped calcium polyphosphate, 1-3 parts by weight of chitosan medicine microspheres and 1-3 parts by weight of chitosan. 2. The long-acting slow-release drug carrier material for bone disease treatment and repair as claimed in claim 1, characterized in that the chitosan drug-loaded microspheres are composed of drug-loaded microsphere cores and alginic acid coated alternately on its surface Sodium layer and chitosan layer. 3. The long-acting slow-release drug carrier material for bone disease treatment and repair as claimed in claim 2, characterized in that the drug-loaded microsphere core is coated with alternating coating layers composed of sodium alginate layers and chitosan layers At least 2 layers. 4. The long-acting slow-release drug carrier material for bone disease treatment and repair as claimed in claim 3, characterized in that the alternating coating layer composed of sodium alginate layer and chitosan layer coated on the outside of the microsphere core is 2 -20 floors. 5. The long-acting slow-release drug carrier material for bone disease treatment and repair as claimed in claim 1 or 2 or 3 or 4, characterized in that the composition of the drug-loaded microsphere core mainly includes chitosan, antibiotics and A combination wherein the antibiotic is present in an effective amount sufficient to produce a bactericidal level in body tissue. 6. The long-acting slow-release drug carrier material for bone disease treatment and repair as claimed in claim 5, characterized in that the content of chitosan in the core of the drug-loaded microspheres is 29wt%-69wt%, and the content of antibiotics is 29wt%-69wt% , and the balance is the cross-linking agent. 7. The long-acting slow-release drug carrier material for bone disease treatment and repair as claimed in claim 5, characterized in that the antibiotics in the drug-loaded microsphere core are selected from tetracycline, vancomycin, gentamicin, tobramycin, Ansafefor, ceftazidime, cefotaxime, and cefadroxil. 8. The long-acting slow-release drug carrier material for bone disease treatment and repair as claimed in claim 5, characterized in that the cross-linking agent in the drug-loaded microsphere core is selected from glutaraldehyde, glyoxal, genipin, β- Sodium Glycerophosphate and Sodium Polyaldehyde Alginate. 9. The preparation method of the bone disease treatment and repair long-acting slow-release drug carrier material according to any one of claims 1 to 8, characterized in that: according to the composition ratio of the components, chitosan is added to the aqueous acetic acid solution to prepare Form a chitosan-acetic acid solution with a chitosan concentration of 1.0-3.0wt%, add strontium-doped calcium polyphosphate powder into the chitosan-acetic acid solution to make it evenly dispersed, and then add the prepared chitosan drug-loaded The microspheres are finally cross-linked by adding a cross-linking agent, frozen at 2-6°C for 12-48 hours, and then heated and dried at 40-100°C to obtain a composite drug carrier material for treating and repairing bone diseases. 10. The preparation method of long-acting slow-release drug carrier material for bone disease treatment and repair as claimed in claim 9, characterized in that the preparation of chitosan drug-loaded microspheres comprises the following steps: (1) According to the composition ratio of the components of chitosan drug-loaded microspheres, chitosan is added into aqueous acetic acid solution to be formulated with a chitosan concentration of 1.0-3.0wt% chitosan acetic acid solution, and antibiotics are added to make it completely Dissolved in chitosan acetic acid solution, as the water phase of the water-in-oil system, add a cross-linking agent, and carry out cross-linking reaction under stirring conditions to form the core of chitosan drug-loaded microspheres. After sufficient cross-linking reaction, separate the shell Glycan drug-loaded microsphere core, after washing and drying, measure the particle size; (2) Disperse the chitosan drug-loaded microsphere core with particle size meeting the requirements in sodium alginate aqueous solution with sodium alginate concentration of 0.5-2.0wt%, ion concentration of 0.1-0.6M, and temperature of 50-65°C for 10 -50min for sodium alginate layer-coated self-assembly, separate and clean after self-assembly; (3) The chitosan drug-loaded microsphere core coated with a sodium alginate layer after the self-assembly process is dispersed in a chitosan concentration of 0.5-2.0wt% and an ion concentration of 0.1-0.6M , chitosan aqueous solution at a temperature of 50-65°C for 10-50 minutes to carry out self-assembly of chitosan layer coating, and separate and clean after self-assembly; (4) The above step (2) and step (3) are carried out for 1 to 10 times respectively to prepare the chitosan drug-loaded microspheres.