CN1446589A - Medicine controlled functional cement with calcium phosphate being as framework and its preparation method - Google Patents

Abstract

The invention discloses a drug controlled release functionally active artificial bone and its clinical application. The calcium phosphate bone cement of the present invention is mainly composed of porous calcium phosphate bone cement and therapeutically effective drug microcapsules. Compound drugs under contraindications, etc. The wall material and capsule core are prepared into drug microcapsules, which are mixed with porous calcium phosphate bone cement powder and embedded to obtain a porous drug-loaded calcium phosphate bone cement with a controlled and sustained release function. The in vitro simulation test showed that drug-loaded porous calcium phosphate bone cement released drugs in vitro to a relatively sufficient extent, the fastest release within 24 hours, and maintained an effective drug level within 6 weeks, and released nearly 80% after 8 weeks. It has the effect of filling and repairing bone defects, and also has the effect of drug sustained release therapy, and can be used for the treatment of chronic osteomyelitis, the prevention of infection at the implantation site, and the prevention of recurrence after bone tumor resection.

Description

Drug-controlled calcium phosphate bone cement and its clinical application

technical field

The invention belongs to the field of biomedical materials, and relates to a controlled-release drug-loaded calcium phosphate bone cement for hard tissue repair and drug treatment and an application thereof.

Background technique

Bone defect caused by trauma, tumor and other reasons is a difficult problem in clinical treatment. For a long time, the repair of bone defects has mainly used autologous bone grafting combined with allogeneic bone grafting, but both methods have their own disadvantages: autologous bone is limited by the number of sources, and there are at least 10% surgical complications in bone harvesting operations , It takes a long time to crawl and replace after implantation; allogeneic bone has different degrees of immune rejection and potential risk of disease transmission. The artificial synthetic substitute material can avoid the defects of biological source repair materials, and is an ideal repair material for bone defects.

The sterility of the implant site is the prerequisite and key to the success of bone grafting. Clinical studies have shown that if the site to be implanted is infected, the treatment effect will not be good, especially for large and medium-sized orthopedic operations (such as spinal surgery, etc.), once infection occurs, the harm will be catastrophic; Tumor cells may not be removed cleanly and local metastasis may occur, which makes the use of simple biomaterials for bone defect repair treatment incomplete, resulting in recurrence of old diseases. Based on this, anti-cancer or anti-inflammatory drugs are introduced into biomaterials, so that the materials also have the effect of further drug treatment while filling and repairing. Therefore, the research and application of drug-loaded biomaterials are particularly eye-catching, and have developed rapidly in recent years. At present, the following types are more involved in clinical research and application:

In 1970, Buchholz and Engelbrecht first reported the application of drug-loaded gentamicin bone cement (PMMA) to treat infection after total hipplasty and the effect was remarkable; in 1974, Klemm first reported the application of gentamicin strains to treat chronic Osteomyelitis has achieved a certain curative effect; however, it is found that the drug has a burst release effect in the body, the drug effect period is short, and it is easy to cause a series of systemic side effects. The literature (Salvati E A, Callaghen JJ, Brause B D, Klein R F, Small RD. Clin Orthop, 1986, 207: 83-94) also reported the combination of polymethylmethacrylate (PMMA) bone cement and antibiotics It has achieved obvious curative effect in the treatment of bone and deep soft tissue infection with targeted drug delivery. However, with the further deepening of basic research and the further expansion of clinical applications, it was found that there are many shortcomings in the PMMA drug-loading system: poor tissue compatibility, strong heat release during the curing process can easily cause burns and necrosis of surrounding tissues, monomers are toxic to the human body, materials Non-degradation, long-term presence of foreign bodies in the body (or one by one during treatment, the patient is very painful), incomplete drug release, etc., make the treatment result difficult and the application is limited. However, the design of this functional material is worth learning.

The literature (Sun Weizhang et al., West China Pharmaceutical Journal, 1997, vol14 (3), p172-174) reported the artificial bone prepared by porous hydroxyapatite ceramics (HAP) as a drug carrier. It has obvious drug sustained release therapeutic effect in the repairing process. However, it is found that the material is brittle, has poor elastic strength, is difficult to absorb in the body, and easily causes osteolysis. At the same time, the drug is adsorbed on the surface after soaking through the porous HAP ceramics, the adsorption amount is small, and the sustained release time in the body is not long.

To sum up, excellent drug carriers and effective compounding methods between drugs and biomaterial carriers are the key to drug-loaded biomaterials to achieve the dual purpose of bone defect repair and drug treatment, and to achieve sustained, stable and efficient sustained release of drugs.

Contents of the invention

The technical problem to be solved in the present invention is to disclose a self-curing calcium phosphate bone cement with drug controlled release function to overcome the above-mentioned defects in the prior art (such as drug carrier, drug and carrier compound method, etc.), to meet the needs of chronic osteomyelitis, treatment Prevention of site infection, prevention of tumor recurrence, etc.

The invention also relates to the clinical application of the drug-loaded artificial bone.

Design of the present invention is such:

Calcium phosphate cement (CPC) is a new type of bone repair material composed of several calcium phosphates (Chow, US 5525148, 5545254, 1996), which can self-cure, accurately shape and biodegrade under human environment and temperature, and eventually transformed into hydroxyapatite. CPC, as the only hard tissue repair material that can self-cure and produce regenerative effects, has attracted the attention of the international material and medical communities for its high biocompatibility, biodegradability and the unity of arbitrary plastic properties, and has become the current biomaterial. one of the research hotspots. In vitro experiments showed (Huang Yue, master's degree thesis of East China University of Science and Technology, 1999) that CPC is feasible as a drug carrier. The present invention uses CPC to embed microencapsulated drugs to form a solidified body of drug-loaded calcium phosphate bone cement to avoid infection at the site to be implanted or to prevent recurrence caused by incomplete debridement of tumor cells. By controlling the thickness of the microcapsule wall material and drug content , solidified body porosity, solid-liquid ratio and other parameters, to realize the fixed-point controllable slow release of anti-cancer and anti-inflammatory drugs of calcium phosphate bone cement, and endow the material with dual functions of filling repair and treatment. In the present invention, the drug-loaded calcium phosphate bone cement with a controllable slow-release function is prepared by using the microcapsule wall material of the solidified drug-loaded porous calcium phosphate bone cement in body fluid (or simulated body fluid), and the drug microcapsules are uniformly distributed. Embedded in calcium phosphate bone cement powder. When the porous calcium phosphate cement is solidified, the drug microcapsules occupy part of the space of the porous solidified body, thus forming an independent unit. The core is affected by parameters such as the thickness of the microcapsule wall material, the drug content, the porosity of the solidified body, and the solid-liquid ratio. It can be used for the treatment of chronic osteomyelitis and the prevention of infection at the implantation site.

The detailed technical scheme of the present invention is as follows:

The drug-loaded calcium phosphate bone cement with controllable slow-release function in the present invention is mainly composed of porous calcium phosphate bone cement and therapeutically effective drug microcapsules, and the preferred ratio is:

Porous calcium phosphate bone cement:medicine microcapsules=100:(0.5～20), mass ratio;

Said porous calcium phosphate bone cement is composed of calcium phosphate bone cement powder (CPC) and a pore-forming agent in a certain proportion, and can be prepared according to the method disclosed in (Liu Changsheng, ZL98110645.5). Wherein: said CPC powder is a mixture of several calcium phosphate salts mixed in a certain proportion, which can be prepared according to the method disclosed in (US5525148, US5545254), and can be tricalcium phosphate (α type or β type), tetracalcium phosphate One or a mixture of both; one or a mixture of octacalcium phosphate, calcium dihydrogen phosphate, hydroxyapatite, fluorapatite.

The pore-forming agent can be one or more of non-toxic slightly soluble salts, acid salts and basic salts, soluble non-toxic macromolecules or non-toxic surfactants.

Said drug microcapsules are embeddings that adopt pharmaceutically acceptable wall materials to embed capsule cores (medicines), wherein:

Said capsule core (medicine) includes antibacterials (such as tobramycin, vancomycin, Tylenol, Rocephine, pipemidic acid, cephalosporins, metronidazole, etc.), antitumor drugs (such as methotrexate , doxorubicin, fluorouracil, nitramide, cyclohexylnitrosourea, etc.), anti-inflammatory analgesics (such as naproxen sodium, cyclosporine, indomethacin, etc.), anti-tuberculosis drugs (such as rifampin) And the mixture of two or more drugs in the absence of incompatibility; the ratio of the wall material to the drugs is: 1:1~1:20;

Said wall material includes one of soluble starch, hydroxypropyl cellulose, ethyl cellulose, gelatin or chitosan, etc., preferably ethyl cellulose;

Said microcapsules can be prepared by interfacial coagulation method, in-situ method, polymerization method, spray drying method, solvent evaporation method, preferably solvent evaporation method.

Said bone cement of the present invention is prepared and applied according to the following method:

The wall material and the capsule core are prepared into drug microcapsules with a particle diameter of 100-400 μm by solvent evaporation method according to the ratio of wall material: capsule core=1:(1～20) and mass ratio, and then the drug microcapsules with a diameter of 5-20 μm are prepared. The porous calcium phosphate bone cement powder and the microcapsules are mixed and embedded with porous calcium phosphate bone cement: drug microcapsules = 100: (0.5-20) (mass ratio), and the porous drug-loaded phosphoric acid with controllable and sustained release function is obtained. Calcium bone cement.

Use physiological saline or other saline solutions as the solidifying solution, and mix it evenly with it according to the ratio of solid to liquid (1.5:1～5:1), and then it can be implanted in the body; said other saline solutions have a concentration of 7～25wt%. phosphate saline solution.

Said wall material includes soluble starch, hydroxypropyl cellulose, ethyl cellulose, gelatin, chitosan, etc., preferably ethyl cellulose;

Said capsule core comprises (medicine) comprises antimicrobial (such as tobramycin, vancomycin, Tylenol, Rocephine, pipemidic acid, cephalosporins, metronidazole etc.), antitumor drug (such as methotrexate) anti-inflammatory drugs (such as naproxen sodium, cyclosporine, indomethacin, etc.), anti-tuberculosis drugs (such as rifampicin ) and mixtures of two or more drugs in the absence of incompatibility;

The inventor has carried out in vitro simulation test and clinical trial to the controllable slow-release drug-loaded self-curing calcium phosphate bone cement of the present invention:

The controlled-release drug-loaded porous calcium phosphate bone cement prepared above was placed in an environment of 37°C and 100% humidity to cure for 48 hours, and then soaked in a simulated buffer solution, and samples were taken at appropriate time intervals, and the drug concentration was determined by ultraviolet spectrophotometry. It shows that drug-loaded porous calcium phosphate bone cement releases drug in vitro more fully, releases fastest within 24 hours, maintains effective drug level in 6 weeks, and releases nearly 80% after 8 weeks.

The controlled-release drug-loaded porous calcium phosphate bone cement prepared above was used in the second stage of debridement to treat chronic Pseudomonas aeruginosa osteomyelitis, and the bone defect reached 8cm×4cm. Add 0.5 g of vancomycin and 0.5 g of piperacillin to 20 g of CPC powder, respectively, to make oval particles, wrap them with warm gauze at 40°C for 15 minutes, mix and implant into the defect. Skin flap operation and drainage were performed, the proximal end was connected to a negative pressure suction device, and the distal end was injected with 80,000 units of tobramycin once a day for one week. It was found that the wound was completely healed 2 weeks after the operation, and a small amount of callus was found on X-ray film review 3 months after the operation. One year after the operation, the grafted bone healed well, and the lesion did not recur. After 1 year of follow-up, there is no sign of recurrence, which can be considered clinically cured.

The controllable slow-release drug-loaded self-curing calcium phosphate bone cement of the present invention has very significant advantages:

After the drug is microencapsulated, it is compounded heterogeneously with the porous calcium phosphate bone cement, which reduces the influence of the drug on CPC curing and prolongs the time for the drug-loaded system to release the effective drug concentration. By controlling the type and thickness of the microcapsule wall material, drug content, porosity of the solidified body, solid-liquid ratio and other parameters, the drug-loaded calcium phosphate bone cement can be controlled at a fixed point for two-stage sustained release (the degradability determined by the intrinsic structure of the wall material can achieve a Level sustained release and secondary sustained release achieved by the microporous structure of the solidified body), so that the prepared drug-loaded calcium phosphate bone cement solidified body not only has a bone repair effect, but also achieves the purpose of treatment. It is used for the treatment of chronic osteomyelitis, implantation Prevention of infection at the site of entry and prevention of recurrence after tumor resection. At the same time, the micropores formed after the sustained release of drug microcapsules are conducive to the growth of bone tissue, accelerate the degradation of materials, and promote the rapid healing of bones. It is a new generation of human hard tissue repair materials with excellent performance.

Description of drawings

Figure 1 is the drug release diagram of drug-loaded calcium phosphate bone cement.

Detailed ways

The content of the present invention will be further illustrated below in conjunction with examples, but these examples do not limit the protection scope of the present invention.

Example 1

Weigh 50 mg of ethyl cellulose, dissolve it in acetone under water bath conditions, after it is completely dissolved, add 100 mg of tobramycin, stir evenly, pour 2 g of liquid paraffin containing 8 ml of Span 80, and circulate water at 60 ° C Constant temperature, stirring, suction filtration, washing, and drying to prepare tobramycin microcapsules.

Weigh 0.1g of pore-forming agent (200～350μm), calcium hydrogen phosphate, tetracalcium phosphate, and 3g of CPC powder with a particle size less than 20μm, and add the prepared tobramycin microcapsules at the same time. Disperse evenly in the bowl, add 1.2g of normal saline, use a dental knife to mix and evenly form a mud mass, place it in a 37°C, 100% humidity environment for 48 hours, and then soak it in a simulated buffer solution, and take samples at appropriate time intervals. The concentration of tobramycin was determined by ultraviolet spectrophotometry, which indicated that the degree of drug-loaded porous calcium phosphate bone cement released drug in vitro was relatively sufficient, and the release was the fastest within 24 hours. After releasing nearly 80%.

Example 2

Weigh 50 mg of ethyl cellulose, dissolve it in acetone under water bath conditions, after it is completely dissolved, add 100 mg of naproxen sodium, stir evenly, pour 2 g of liquid paraffin containing 8 ml of Span 80, and circulate water at 60 ° C Constant temperature, stirring, suction filtration, washing, and drying to prepare naproxen sodium microcapsules. Weigh 0.1g of pore-forming agent (200～350μm), calcium hydrogen phosphate, tetracalcium phosphate, and 3g of CPC powder whose particle size is less than 20μm, and add the prepared naproxen sodium microcapsules at the same time. Disperse evenly in the bowl, add 1.2g of normal saline, use a dental knife to mix and evenly form a mud mass, place it in a 37°C, 100% humidity environment for 48 hours, and then soak it in a simulated buffer solution, and take samples at appropriate time intervals. The concentration of naproxen sodium was determined by ultraviolet spectrophotometry, which showed that the degree of drug-loaded porous calcium phosphate bone cement released drug in vitro was relatively sufficient, and the release was the fastest within 24 hours. After releasing nearly 80%.

Example 3

Weigh 50 mg of ethyl cellulose, dissolve it in acetone under the condition of water bath, after it is completely dissolved, add 100 mg of rifampicin, stir evenly, pour 2 g of liquid paraffin containing 8 ml of Span 80, and circulate water at 60°C to keep the temperature constant , stirring, suction filtration, washing, and drying to obtain rifampicin microcapsules. Weigh 0.1g of pore-forming agent (200～350μm), calcium hydrogen phosphate, tetracalcium phosphate, and 3g of CPC powder with a particle size of less than 20μm, and add the prepared rifampicin microcapsules at the same time. Disperse evenly in medium, add 1.2g of normal saline, use a dental knife to mix and evenly form a mud mass, place it in a 37°C, 100% humidity environment for 48 hours, and then soak it in a simulated buffer solution, take samples at appropriate time intervals, and use ultraviolet light The concentration of rifampicin was determined by spectrophotometry, which indicated that the release of drug-loaded porous calcium phosphate bone cement in vitro was relatively sufficient, and the release was the fastest within 24 hours, and the effective drug level was maintained within 6 weeks, and released after 8 weeks. Nearly 80%.

Example 4

Weigh 50 mg of ethyl cellulose, dissolve it in acetone under water bath conditions, after it is completely dissolved, add 100 mg of doxorubicin, stir evenly, pour 2 g of liquid paraffin containing 8 ml of Span 80, and circulate water at a constant temperature of 60 °C , stirring, suction filtration, washing, and drying to obtain doxorubicin microcapsules. Weigh 0.1 g of pore-forming agent (200-350 μm), calcium hydrogen phosphate, tetracalcium phosphate, and 3 g of CPC powder with a particle size of less than 20 μm, and add the prepared doxorubicin microcapsules at the same time. Disperse evenly in medium, add 1.2g of normal saline, use a dental knife to mix and evenly form a mud mass, place it in a 37°C, 100% humidity environment for 48 hours, and then soak it in a simulated buffer solution, take samples at appropriate time intervals, and use ultraviolet light The concentration of doxorubicin was determined by spectrophotometry, which indicated that the degree of drug-loaded porous calcium phosphate bone cement released drug in vitro was relatively sufficient, and the release was the fastest within 24 hours, and the effective drug level was maintained within 6 weeks, and released after 8 weeks Nearly 90%.

Example 5

Weigh 50 mg of ethyl cellulose, dissolve it in acetone under the condition of water bath, after it is completely dissolved, add 50 mg of tobramycin and 50 mg of vancomycin, after stirring evenly, pour 2 g of liquid paraffin containing 8 ml of Span 80, in Circulating water at constant temperature at 60°C, stirring, suction filtration, washing, and drying are used to prepare compound drug microcapsules. Weigh 0.1g of pore-forming agent (200-350μm), calcium hydrogen phosphate, tetracalcium phosphate, and 3g of CPC powder with a particle size of less than 20μm, and add the prepared composite drug microcapsules at the same time, and place in a mortar Disperse evenly, add 1.2g of normal saline, use a dental knife to reconcile and evenly form a mud mass, put it in an environment of 37°C and 100% humidity for 48 hours, and then soak it in a simulated buffer solution, take samples at appropriate time intervals, and use ultraviolet spectroscopy The concentration of the compound drug was measured by photometry, which indicated that the degree of drug-loaded porous calcium phosphate bone cement released drug in vitro was relatively sufficient, the release was the fastest within 24 hours, and the effective drug level was maintained within 6 weeks, and nearly 85% of the drug was released after 8 weeks. %.

Example 6

Weigh 30 mg of chitosan, dissolve in 0.1% glacial acetic acid, after it is completely dissolved, add 10 mg of doxorubicin, stir evenly, pour 2 g of liquid paraffin containing 8 ml of Span 80, and circulate water at 60°C to keep the temperature and stir , suction filtration, washing, and drying to obtain doxorubicin microcapsules. Weigh 0.1 g of pore-forming agent (200-350 μm), calcium hydrogen phosphate, tetracalcium phosphate, and 3 g of CPC powder with a particle size of less than 20 μm, and add the prepared doxorubicin microcapsules at the same time. Disperse evenly in medium, add 1.2g of normal saline, use a dental knife to mix and evenly form a mud mass, place it in a 37°C, 100% humidity environment for 48 hours, and then soak it in a simulated buffer solution, take samples at appropriate time intervals, and use ultraviolet light The concentration of doxorubicin was determined by spectrophotometry, which indicated that the degree of drug-loaded porous calcium phosphate bone cement released drug in vitro was relatively sufficient, and the release was the fastest within 24 hours, and the effective drug level was maintained within 6 weeks, and released after 8 weeks Nearly 80%.

Example 7

Weigh 30mg of chitosan, dissolve in 0.1% glacial acetic acid, after it is completely dissolved, add 100mg of rifampicin, stir evenly, pour 2g of liquid paraffin containing 8ml of Span 80, and circulate water at 60°C to keep the temperature and stir , suction filtration, washing, and drying to obtain rifampicin microcapsules. Weigh 0.1g of pore-forming agent (200～350μm), calcium hydrogen phosphate, tetracalcium phosphate, and 3g of CPC powder with a particle size of less than 20μm, and add the prepared rifampicin microcapsules at the same time. Disperse evenly in medium, add 1.2g of normal saline, use a dental knife to mix evenly into a mud mass, put it in a 37°C, 100% high temperature environment for curing for 48 hours, then soak in a simulated buffer bath, and take samples at appropriate time intervals. The concentration of rifampicin was determined by ultraviolet spectrophotometry, which showed that the drug-loaded porous calcium phosphate bone cement released the drug in vitro to a relatively sufficient degree, and the release was the fastest within 24 hours. After releasing nearly 80%.

Example 8

Weigh 30mg of chitosan, dissolve in 0.1% glacial acetic acid, after it is completely dissolved, add 100mg of tobramycin, stir evenly, pour 2g of liquid paraffin containing 8ml of Span 80, and circulate water at 60C to keep the temperature and stir , suction filtration, washing, and drying to obtain tobramycin microcapsules.

Weigh 0.1g of pore-forming agent (200～350μm), calcium hydrogen phosphate, tetracalcium phosphate, and 3g of CPC powder with a particle size less than 20μm, and add the prepared tobramycin microcapsules at the same time. Disperse evenly in the bowl, add 1.2g of normal saline, use a dental knife to mix and evenly form a mud mass, place it in a 37°C, 100% humidity environment for 48 hours, and then soak it in a simulated buffer solution, and take samples at appropriate time intervals. The concentration of tobramycin was determined by ultraviolet spectrophotometry, which indicated that the degree of drug-loaded porous calcium phosphate bone cement released drug in vitro was relatively sufficient, and the release was the fastest within 24 hours. After releasing nearly 80%. As shown in Figure 1.

Example 9

Weigh chitosan 30mg, dissolve in 0.1% glacial acetic acid, after it dissolves completely, add 100mg naproxen sodium, after stirring evenly, pour 2g of liquid paraffin containing 8ml Span 80, circulate water constant temperature at 60°C, Stirring, suction filtration, washing, and drying to prepare naproxen sodium microcapsules. Weigh 0.1g of pore-forming agent (200～350μm), calcium hydrogen phosphate, tetracalcium phosphate, and 3g of CPC powder whose particle size is less than 20μm, and add the prepared naproxen sodium microcapsules at the same time. Disperse evenly in the bowl, add 1.2g of normal saline, use a dental knife to mix and evenly form a mud mass, place it in a 37°C, 100% humidity environment for 48 hours, and then soak it in a simulated buffer solution, and take samples at appropriate time intervals. The concentration of naproxen sodium was determined by ultraviolet spectrophotometry, which showed that the degree of drug-loaded porous calcium phosphate bone cement released drug in vitro was relatively sufficient, and the release was the fastest within 24 hours. After releasing nearly 80%.

Example 10

Weigh chitosan 30 mg, dissolve in 0.1% glacial acetic acid, after it is completely dissolved, add 10 mg of fudoxorubicin and 50 mg of vancomycin, stir evenly, pour 2 g of liquid paraffin containing 8 ml of Span 80, and heat at 60 ° C The lower circulating water is kept at a constant temperature, stirred, suction filtered, washed, and dried to prepare the compound drug microcapsules. Weigh 0.1g of pore-forming agent (200-350μm), calcium hydrogen phosphate, tetracalcium phosphate, and 3g of CPC powder with a particle size of less than 20μm, and add the prepared composite drug microcapsules at the same time, and place in a mortar Disperse evenly, add 1.2g of normal saline, use a dental knife to reconcile and evenly form a mud mass, put it in an environment of 37°C and 100% humidity for 48 hours, and then soak it in a simulated buffer solution, take samples at appropriate time intervals, and use ultraviolet spectroscopy The concentration of the compound drug was measured by photometry, which indicated that the degree of drug-loaded porous calcium phosphate bone cement released drug in vitro was relatively sufficient, the release was the fastest within 24 hours, and the effective drug level was maintained within 6 weeks, and nearly 80% of the drug was released after 8 weeks. %.

The above examples show that the microencapsulation of the drug in self-curing calcium phosphate bone cement reduces the effect of the drug on the curing process of CPC and prolongs the release time of the drug. The prepared calcium phosphate bone cement solidified body can not only be used for filling and repairing bone defects, but also sustainably release drugs to achieve further purposes, such as the treatment of chronic osteomyelitis, the prevention of infection at the implant site, and the resection of bone tumors Post-relapse prevention. At the same time, the micropores formed by the sustained release of drug-containing microcapsules are conducive to the growth of bone tissue, accelerate the degradation of materials, and promote the rapid healing of bones. It is a new generation of human hard tissue repair materials with excellent performance.

Claims (13)

1. the active artificial bone of drug controlled-releasing function is characterized in that mainly being made up of the drug microcapsule of porous calcium phosphate bone cement and treatment effective dose.

2. artificial bone according to claim 1 is characterized in that porous calcium phosphate bone cement: drug microcapsule=100: (0.5～20), mass ratio;

3. artificial bone according to claim 2 is characterized in that said porous calcium phosphate bone cement comprises calcium phosphate bone cement powder and pore former.

4. artificial bone according to claim 3 is characterized in that said calcium phosphate bone cement powder is a kind of in tricalcium phosphate (α type or β type), the tetracalcium phosphate or both mixture; A kind of in OCP, dalcium biphosphate, hydroxyapatite, the fluor-apatite or their mixture.

5. artificial bone according to claim 3 is characterized in that said pore former is one or more in nontoxic slightly soluble salt, acid salt and basic salt, solubility non-toxic organic thing or the nontoxic surfactant.

6. according to each described artificial bone of claim 1～5, it is characterized in that said drug microcapsule is for adopting the embedding thing of pharmaceutically acceptable wall material embedding capsule-core (medicine).

7. artificial bone according to claim 6 is characterized in that the ratio of wall material and described medicine is: 1: 1～1: 20.

8. artificial bone according to claim 6 is characterized in that said capsule-core (medicine) comprises antimicrobial drug, antineoplastic agent, anti-anti-inflammatory analgesic or antitubercular agent and the mixture of two or more medicine under no incompatibility situation.

9. artificial bone according to claim 6 is characterized in that said wall material comprises a kind of in soluble starch, hydroxypropyl cellulose, ethyl cellulose, gelatin or the chitosan series.

10. artificial bone according to claim 8, it is characterized in that, antimicrobial drug is tobramycin, vancomycin, safe energy, Ceftriaxone, pipemidic acid, cephalo-type or metronidazole etc., antineoplastic agent is methotrexate, amycin, fluorouracil, flutamide or lomustine, anti-anti-inflammatory analgesic is naproxen sodium, NSC-145688 or indometacin, and antitubercular agent is a rifampicin.

11. preparation method according to the described artificial bone of claim 1～10, it is characterized in that, wall material and capsule-core are pressed the wall material: capsule-core=1: (1～20), the ratio of mass ratio, adopt solvent evaporated method to be prepared into the drug microcapsule that particle diameter is 100～400 μ m, porous calcium phosphate bone cement powder and this microcapsule of with diameter being 5～20 μ m again are with porous calcium phosphate bone cement: drug microcapsule=100: (0.5～20) (mass ratio) mixes embedding, promptly obtains the porous medicine carrying calcium phosphate bone cement with controllable sustained-release function.

12. the application according to the described artificial bone of claim 1～10 is characterized in that, as consolidation liquid, is ratio and its mix homogeneously of (1.5: 1～5: 1) in solid-to-liquid ratio with normal saline or other saline solution, can implant.

13. the application of artificial bone according to claim 12 is characterized in that, said other saline solution is that concentration is the aqueous phosphatic of 7～25wt%.