CN101020085A - New-type of inorganic bone grafting material and its prepn and use - Google Patents

Abstract

The invention discloses a novel inorganic bone graft material, which belongs to the field of medical materials. A new type of inorganic bone graft material is composed of β-tricalcium phosphate particles with a mass percentage of 20%-80% and α-calcium sulfate hemihydrate powder with a mass percentage of 80%-20%. A layered structure is formed on the surface of β-tricalcium phosphate particles and/or inside their pores. The advantages of the present invention are: based on the excellent biocompatibility and in vivo degradation performance of α-calcium sulfate hemihydrate and β-tricalcium phosphate, the composite artificial bone particles with self-curing properties can repair bone defects of any shape, In-situ solidification and rapid restoration of bone mechanical strength. With the rapid degradation of calcium sulfate in the body, β-tricalcium phosphate particles with microporous structure provide an ideal scaffold for new bone growth, and can be gradually replaced by new bone crawling. The composite artificial bone has wide sources, convenient storage and use, excellent performance, simple and practical preparation process, short preparation period and low cost.

Description

A new type of inorganic bone graft material, its preparation method and application

technical field

The present invention relates to a new type of inorganic bone graft material, its preparation method and application, in particular to a self-curing and absorbable composite artificial inorganic bone cement used in medical surgery for replacing and repairing bone tissue defects, its preparation method and The invention belongs to the field of medical materials.

Background technique

Bone is composed of inorganic components and organic components, of which the inorganic components account for 60-70% of the dry weight, and the main components are hydroxyapatite (Ca ₁₀ (PO ₄ ) ₆ 5H ₂ O) and a small amount of sodium and magnesium salts etc., the organic ingredients are mainly type I collagen. The size of the hydroxyapatite crystal is about 25-50nm×40nm×200-350nm, and the direction of the long axis (c-axis) of the crystal is consistent with the direction of the type I collagen fiber, forming a porous structure material with interconnected micropores. In a state of dynamic balance, the bone resorbed by osteoclasts is gradually replaced by new bone formed by osteoblasts, and the bones in the human body are completely renewed about every 10 years. Mechanical support is one of the main physiological functions of bones, but bone defects caused by trauma, infection, tumor, surgery, etc. and operations that require bone grafting are very common. There are 6.2 million fractures in the United States every year, of which 5- Delayed union or nonunion of fractures occurs in 10% of fractures, and 800,000 spinal fusion surgeries are performed each year. The purpose of the treatment of these diseases is to restore the continuity and mechanical strength of the bone, and promote the formation of new bone and restore its physiological function through local bone grafting. Currently clinically used bone graft materials include autologous bone, allogeneic bone, bone morphogenetic protein (BMP), decalcified bone matrix (DBM), artificial bone, etc., which can be divided into organic materials with natural ingredients and synthetic inorganic materials. Two categories of materials. Autologous bone is currently the most ideal bone graft material, but due to limited sources, the donor site is prone to complications such as pain and infection. According to reports, the incidence of complications can reach 30%, which makes people start looking for other more ideal bone grafts. Bone substitute materials have led to the development of various new bone graft materials and the rapid growth of market demand. In 2005, the US bone graft material market alone reached 1.074 billion US dollars, and it is increasing at a rate of nearly 20% every year.

Various bone graft materials currently used clinically have certain shortcomings and deficiencies. Although the allogeneic bone can retain a certain amount of osteogenic activity, the source is limited, and the domestic price is 400-800 yuan/gram. At the same time, there are potential risks of immune rejection and disease transmission, and the scope of use is limited. DBM, BMP, etc. are derived from allogeneic bone, xenogeneic bone or obtained through gene protein expression. They have osteoinductive osteogenic activity but lack conductive osteogenic activity and mechanical strength. They are extremely expensive and can only be used in a small range of clinical practice. Inorganic materials mainly include calcium phosphate and calcium sulfate, which have conductive osteogenic activity and mechanical strength, but have no osteogenic activity. Although various bone graft materials have their own characteristics, autogenous bone is still the standard that various bone graft materials strive to achieve. As an ideal bone graft material, it should have the following properties: (1) osteogenic activity; (2) good biocompatibility; (3) biodegradable; (4) able to provide structural support; (5) clinical storage and easy to use; (6) cost-effective. Depending on the site where the bone graft material is used, one or a part of the above properties may be more important. For example, the bone graft material for filling metaphyseal bone defects requires a certain mechanical strength to avoid the collapse of the articular cartilage surface. Bone grafting material with osteogenic activity is needed when it is not connected. With the increasing understanding of the bone defect repair process in the body and the structure, chemical and biological properties of bone graft materials, people are more and more able to prepare or select suitable materials to imitate the characteristics of autologous bone A more ideal bone graft material is needed.

Since the artificially synthesized inorganic bone graft materials have the advantages of abundant sources, convenient storage and use, good biocompatibility and avoiding the transmission of diseases, research in this area has been increasing in recent years, especially the preparation of various calcium phosphate and calcium sulfate materials. Artificial bone has become a research hotspot. At present, artificial inorganic bone graft materials that have been commercialized abroad include ChronOS ^TM (β-tricalcium phosphate), Pro-Osteon (porous coral thermally converted hydroxyapatite), Norian SRS (calcium phosphate cement), NovaBone (bioglass), Bio-OSS (ox organic bone powder), Osteoset (calcium sulfate), etc., these artificial inorganic bone graft materials have their own characteristics, but these high-tech and high value-added artificial inorganic bone graft materials abroad are extremely expensive, and are widely used in China. The application in most areas with strict control of medical expenses is greatly restricted. Therefore, seeking and developing a more ideal artificial inorganic bone graft material with independent intellectual property rights is an important topic in the field of medical biomaterials in recent years.

The popularity of calcium phosphate artificial bone is mainly because its composition is close to the mineral phase of bone and has good biocompatibility. Therefore, its synthesis and application have attracted attention since the 1960s, mainly through wet heat method and dry method. Hydroxyapatite powder is prepared by hydrothermal method and hydrothermal method, and then high-density hydroxyapatite is produced by high-temperature calcination. Its compressive strength reaches 490.3-882.6MPa, and its bending strength reaches 196.1Mpa. It is used for bone and tooth restoration and has obtained certain effect. However, this material has high crystallinity and low solubility, Mohs hardness reaches 5, and elastic modulus is twice that of bone, making it difficult to shape and degrade in the body. Porous hydroxyapatite is an improved bone graft material with conductive osteogenic activity. It is derived from calcium carbonate in corals through thermochemical reactions and has a hydroxyapatite crystal structure similar to that of human cancellous bone. The porous space structure, new bone can grow rapidly in this hydroxyapatite. However, the application is limited to non-weight-bearing or bone defects under strong fixation protection. Once new bone grows into the pores of the material, its mechanical strength will be significantly improved, but long-term clinical observation in vivo shows that it is basically not degradable. The main disadvantage of sintered or massive calcium phosphate artificial bone is the difficulty in shaping and inconvenient operation, leading to the emergence of various calcium phosphate cements. The carbonapatite cement developed by Constanz in 1996 was hailed as a revolutionary progress in bone defect repair. This material is composed of dry powder and curing liquid. When used, the two are mixed into a paste, which can repair bone defects of any shape. It solidifies in situ and has a certain mechanical strength, forming a carbonapatite (Ca _8.8 (HPO ₄ ) _0.7 (PO ₄ ) _4.5 (CO ₃ ) _0.7 (OH) _1.3 ), chemical composition and crystal structure similar to the mineral phase of normal bone tissue, in Colles fracture, intertrochanteric fracture, tibial plateau fracture, spinal fracture, etc. Some effect has been achieved in disease treatment. However, this material degrades slowly in the body, and only a part of it is eventually absorbed and rebuilt.

The structure of β-tricalcium phosphate biological scaffold material with microporous structure is similar to that of normal cancellous bone, with a porosity of 90%, 75% of the pore diameters are between 100-1000 microns, and the remaining 24% of the pore diameters are between 1-100 microns Micron. Large pores allow bone tissue to grow in and play the role of a biological scaffold. Although small pores cannot allow bone to grow in, they can significantly improve the flow and diffusion of liquid in the bone matrix and improve the metabolism of cells in the matrix. Due to this pore structure and its own component characteristics, the absorption rate after implantation in the body is close to the normal bone healing rate, and new bone is formed within 3 weeks, 76% is absorbed at 6 weeks, and 86% is absorbed at 12 weeks. Only 2% remained at 52 weeks. However, this kind of porous material for repairing bone defects lacks mechanical strength and cannot bear early load, and has the disadvantages of difficult shaping and inconvenient use.

Calcium sulfate is commonly known as gypsum, and its name comes from a village in the north of Paris. Because calcined gypsum (calcium sulfate hemihydrate) has self-curing properties, as early as 1794, there were records of using plaster to fix fractured limbs (Eton, MedicalCommentaries). In 1892, Dreesmann used paste calcium sulfate mixed with 5% carbolic acid to fill 8 patients with bone defects, and 6 of them achieved bone healing. However, the results of clinical application of calcium sulfate are very different, mainly because the calcium sulfate used is different in size and crystal structure, resulting in too fast absorption in the body after filling bone defects, and it is completely absorbed before new bone formation, resulting in The bone defect is cavities or filled with soft tissue. The crystal structure of calcium sulfate hemihydrate is controlled through a series of special processes to form a neat and consistent α-type crystal structure, which has a relatively slow dissolution and absorption of medical grade calcium sulfate (Osteoset). It was approved by FDA for clinical use in 1996, including two specifications. The tablet granules (4.8×3.3mm, 3×2.5mm) are mainly used to fill various inclusive bone defects, but the integrity of the tablet granules must be maintained, otherwise the absorption speed and bone defect repair effect will be affected. However, its fragility and lack of mechanical strength limit its wide clinical application, and further improvement in mechanical and biological properties is needed to improve its clinical effect.

Due to the disadvantages of a single inorganic bone graft material, many studies in recent years have devoted themselves to combining several inorganic bone graft materials to make use of their respective advantages and make up for each other's shortcomings, so as to prepare a more ideal composite artificial bone repair material.

Contents of the invention

The first technical problem to be solved by the present invention is to provide a self-curing and resorbable composite inorganic bone graft material that can be solidified in situ and has certain mechanical strength.

Another technical problem to be solved by the present invention is to provide a simple, short-cycle and low-cost method for preparing the above-mentioned composite inorganic bone graft material.

In order to achieve the above object, the present invention adopts the following technical solutions:

A new type of inorganic bone graft material, composed of β-tricalcium phosphate particles with a mass percentage of 20%-80% and α-calcium sulfate hemihydrate powder with a mass percentage of 80%-20%, α-calcium sulfate hemihydrate powder The body forms a layered structure on the surface of β-TCP particles and/or inside their pores. The two components can form an inorganic bone graft material suitable for clinical use within the above mass percentage range. The content of the two components depends on the predetermined degradation rate of the bone material. The higher the content of α-calcium sulfate hemihydrate, the faster the degradation rate .

The diameter of the β-tricalcium phosphate particles is 0.2-10 mm, preferably 2-5 mm. The diameter of β-TCP particles depends on the bone graft site, and the larger the space of the bone graft site, the larger the particle size is required.

The new inorganic bone graft material can self-cure after being mixed with distilled water, blood or physiological saline at a liquid-solid ratio of 0.2-0.6ml/g.

The principle of the present invention is that: α-calcium sulfate hemihydrate and β tricalcium phosphate are similar to the composition of human bone tissue, have good tissue compatibility, and α-calcium sulfate hemihydrate has self-curing properties and has a certain mechanical strength after curing. Strength, but the degradation rate is too fast compared to the growth rate of bone tissue. Before the growth of new bone tissue, most of the implanted α-type calcium sulfate hemihydrate has been absorbed by autologous tissue, which is not conducive to the growth of bone tissue. The microporous structure of β-tricalcium phosphate particles has an ideal microporous structure, but lacks mechanical strength and self-curing properties, making it difficult to use and shape, and the degradation rate of β-tricalcium phosphate in the body is too slow, which affects new bone tissue The ingrowth of the bone is also not conducive to being replaced by its own bone tissue. In the present invention, the above two substances are compounded into a composite artificial bone, and the difference in the ratio of the two components is used to adjust the degradation speed, so as to match the growth rate of the own bone tissue, so that the composite artificial bone is gradually replaced by the own bone tissue, and at the same time Utilizing the in-situ self-curing characteristics of α-type calcium sulfate hemihydrate, the α-type calcium sulfate hemihydrate is used as a binder to prepare granular composite artificial bone particles, which are convenient for storage and use.

A preparation method of a novel inorganic bone graft material, including:

(1) preparing β-tricalcium phosphate particles with a microporous structure;

(2) prepare α-calcium sulfate hemihydrate powder;

(3) The preparation mass percentage is 20%-80% beta-tricalcium phosphate particles and mass percentage is 80%-20% alpha-calcium sulfate hemihydrate powder, on the surface of beta-tricalcium phosphate particles and/or in the void A powder layer of α-calcium sulfate hemihydrate is formed.

The (1) preparation of β-tricalcium phosphate particles with a microporous structure is to use heterogeneous or allogeneic cancellous bone to be directly calcined, and the healthy cancellous bone is taken to be calcined in a high-temperature furnace after removing the organic components. 3 hours, the heating rate is 10°C/min, the calcined bone is taken out and soaked in (NH ₄ ) ₂ HPO ₄ solution with a concentration of 1M for 24 hours, the excess liquid is removed, dried at 50°C for 4 days, and placed in the high-temperature calciner again Medium calcination, 1 hour at 1100°C, heating rate 5°C/min, slow cooling, rinsing with deionized water twice, and drying at 50°C for 4 days. The prepared calcined bone is pulverized into particles with a microporous structure.

In the (1) preparation of β-tricalcium phosphate particles with a microporous structure, 2 parts by weight of calcium hydrogen phosphate can also be converted into calcium pyrophosphate at 800°C for 3 hours, and then mixed with 1 part by weight of Calcium carbonate is mixed and pressed into tablets, cooled slowly at 1100°C for 1 hour, crushed to make β-tricalcium phosphate powder, and microporous foaming technology is used to make β-tricalcium phosphate particles with microporous structure.

The (2) preparation of α-calcium sulfate hemihydrate powder is based on analyzing pure calcium sulfate dihydrate as raw material and placing it in a closed high-pressure reactor with a steam pressure of 0.13Mpa, gradually increasing the temperature by 5°C per minute, and heating to 123 ℃, heated at a constant temperature for 7 hours, then took it out and placed it in an electric ventilation oven at 120 ℃ to dry for 4-5 hours, and crushed the obtained material with an airflow mill. Above 80MPa.

The (3) preparation mass percentage is 20%-80% beta-tricalcium phosphate particles and mass percentage is 80%-20% alpha-calcium sulfate hemihydrate powder, on the surface of beta-tricalcium phosphate particles and/or The α-calcium sulfate hemihydrate powder layer is formed in the gap, which is made into a paste by stirring with absolute ethanol and α-calcium sulfate hemihydrate, and spraying α-calcium sulfate hemihydrate directly on the surface of β-tricalcium phosphate particles by spraying method; Or put the β-tricalcium phosphate particles into the above paste mixture and stir, so that the α-calcium sulfate hemihydrate powder adheres to the surface of the β-tricalcium phosphate particles and/or the inside of the pores; 37°C naturally volatilizes to remove anhydrous ethanol.

The (3) preparation mass percentage is 20%-80% beta-tricalcium phosphate particles and mass percentage is 80%-20% alpha-calcium sulfate hemihydrate powder, on the surface of beta-tricalcium phosphate particles and/or The α-calcium sulfate hemihydrate powder layer is formed in the gap, which is to directly spray and fix the α-calcium sulfate hemihydrate powder on the surface of the β-tricalcium phosphate particle and/or in the gap by plasma method.

A large number of documents have proved that both α-type calcium sulfate hemihydrate and β-tricalcium phosphate are good carriers of antibiotics and substances with osteoinductive activity such as DBM (decalcified bone matrix), BMP (bone morphogenetic protein), and so on. Artificial bone can also be used as a carrier to compound the above materials to expand its use. For example, adding DBM and BMP with osteoinductive activity to the raw materials to repair bone defects, or compounding antibiotics and chemotherapy drugs to treat open complex war wounds, osteomyelitis or bone tumors caused by various reasons.

The method of compounding artificial bone with DBM, BMP, antibiotics or chemotherapy drugs is to mix DBM, BMP, antibiotics or chemotherapy drugs with α-calcium sulfate hemihydrate powder, and then spray and fix them on the surface of β-tricalcium phosphate particles. Or directly add DBM, BMP, antibiotics or chemotherapy drugs to the composite artificial bone. To ensure drug activity, ethanol is usually removed by lyophilization.

The advantages of the present invention are: based on the excellent biocompatibility and in vivo degradation performance of α-calcium sulfate hemihydrate and β-tricalcium phosphate, the present invention adopts a certain dose of α- Calcium sulfate hemihydrate powder is used to prepare composite artificial bone particles with self-curing properties, so as to repair bone defects of any shape, solidify in situ and quickly restore the mechanical strength of bones. With the rapid degradation of calcium sulfate in the body, β-tricalcium phosphate particles with microporous structure provide an ideal scaffold for new bone growth, and can be gradually replaced by new bone crawling. By studying its degradation and osteogenesis mechanism in vivo, adjust the spray dosage of α-calcium sulfate hemihydrate and the diameter and content of β-tricalcium phosphate particles, so that the degradation rate in the implanted body is consistent with the surrounding bone formation rate, thus To achieve a better effect of bone defect repair and bone graft fusion. The composite artificial bone has a wide range of sources, is convenient to store and use, and can quickly and effectively treat a large number of bone defects and patients who need bone grafting. The composite artificial bone provided by the invention has excellent performance, simple preparation process, short use and preparation period and low cost.

The present invention will be further described below in conjunction with specific embodiments. Embodiments of the present invention are not limited thereto. Any equivalent replacement in the field implemented according to the disclosed content or principles of the present invention shall fall within the scope of protection of the present invention.

Description of drawings

Fig. 1 Apparent structure diagram of composite artificial bone particles.

Fig. 2 Structural diagram of composite artificial bone electron microscope.

Fig. 3 Surface view of composite artificial bone after solidification.

Fig. 4 Composite artificial bone X-ray diffraction pattern.

Fig. 5a X-ray images of rabbits implanted on the supracondyle of femur to repair bone defect 1 day after operation.

Fig. 5b X-ray images at 12 weeks after implantation of rabbit femoral condyle to repair bone defect.

Fig. 6a Appearance at 4 weeks after implantation on the supracondyle of rabbit femur to repair bone defect.

Fig. 6b Appearance at 12 weeks after implantation of rabbit femoral condyle to repair bone defect.

Detailed ways

Example 1:

1. Preparation of β-tricalcium phosphate particles with a microporous structure: take healthy bovine cancellous bone and crush it into particles with a diameter of 2-3mm, rinse it and calcinate it in a high-temperature furnace at 800°C for 3 hours, take it out and soak it in a concentration of 1M (NH ₄ ) ₂ HPO ₄ solution for 24 hours, dried at 50°C for 4 days, then placed in a high-temperature calciner at 1100°C for 1 hour, with a heating rate of 5°C/min, slowly cooling down, and rinsing with deionized water twice. Dry at 50° C. for 4 days to prepare granules whose main component is β-tricalcium phosphate. The pellets have been stripped of organic matter. The diameter of the particles was 4 mm.

2. Preparation of α-calcium sulfate hemihydrate powder: put analytically pure calcium sulfate dihydrate in a closed high-pressure reactor with a steam pressure of 0.13Mpa and heat it to 123°C, heat it at a constant temperature for 7 hours, and then take out the electric heating ventilator placed at 120°C Dry in a drying oven for 4-5 hours, and use a jet mill to pulverize the obtained material into α-sulfuric acid hemihydrate powder with a diameter of 5 μm.

3. Prepare β-tricalcium phosphate and α-calcium sulfate hemihydrate in a ratio of 1:1 by weight, and form α-calcium sulfate hemihydrate powder layer on the surface of β-tricalcium phosphate particles and/or in the voids: Mix 5g of α-sulphuric acid hemihydrate powder with 10ml of absolute ethanol, then add 5g of β-tricalcium phosphate particles, mix thoroughly and place in an oven at 37°C to gradually volatilize the absolute ethanol to obtain a composite plant. Bone particles (Figure 1).

Example 2:

1. Preparation of β-tricalcium phosphate particles with a microporous structure: take healthy bovine cancellous bone and crush it into particles with a diameter of 2-3mm, rinse it and calcinate it in a high-temperature furnace at 800°C for 3 hours, take it out and soak it in a concentration of 1M (NH ₄ ) ₂ HPO ₄ solution for 24 hours, dried at 50°C for 4 days, then placed in a high-temperature calciner at 1100°C for 1 hour, with a heating rate of 5°C/min, slowly cooling down, and rinsing with deionized water twice. Dry at 50° C. for 4 days to prepare granules whose main component is β-tricalcium phosphate. The pellets have been stripped of organic matter. The diameter of the particles was 10 mm.

2. Preparation of α-calcium sulfate hemihydrate powder: put analytically pure calcium sulfate dihydrate in a closed high-pressure reactor with a steam pressure of 0.13Mpa and heat it to 123°C, heat it at a constant temperature for 7 hours, and then take out the electric heating ventilator placed at 120°C Dry in a drying oven for 4-5 hours, and use a jet mill to pulverize the obtained material into α-sulfuric acid hemihydrate powder with a diameter of 5 μm.

3. β-tricalcium phosphate and α-calcium sulfate hemihydrate are prepared in a ratio of 2:8 in parts by weight, and an α-calcium sulfate hemihydrate powder layer is formed on the surface of the β-tricalcium phosphate particles and/or in the voids: Mix 8g of α-sulphuric acid hemihydrate powder with 10ml of absolute ethanol, then spray directly onto the surface and pores of 2g of β-tricalcium phosphate particles, and place it in an oven at 37°C to gradually volatilize the absolute ethanol. Composite bone graft particles.

Example 3:

1. Preparation of β-tricalcium phosphate particles with a microporous structure: 2 parts by weight of calcium hydrogen phosphate was converted into calcium pyrophosphate at 800°C for 3 hours, then mixed with 1 part by weight of calcium carbonate and pressed into tablets, 1100 After 1 hour under the condition of ℃, cool slowly, and make β-tricalcium phosphate powder after pulverization, and adopt microporous foaming technology (conventional method) to make β-tricalcium phosphate particles with microporous structure. The diameter of the particles is 0.2 mm.

2. Preparation of α-calcium sulfate hemihydrate powder: put analytically pure calcium sulfate dihydrate in a closed high-pressure reactor with a steam pressure of 0.13Mpa and heat it to 123°C, heat it at a constant temperature for 7 hours, and then take out the electric heating ventilator placed at 120°C Dry in a drying oven for 4-5 hours, and use a jet mill to pulverize the obtained material into α-sulfuric acid hemihydrate powder with a diameter of 5 μm.

3. β-tricalcium phosphate and α-calcium sulfate hemihydrate are prepared in a ratio of 8:2 in parts by weight, and an α-calcium sulfate hemihydrate powder layer is formed on the surface of the β-tricalcium phosphate particles and/or in the voids: Mix 2g of α-sulphuric acid hemihydrate powder with 10ml of absolute ethanol, and then spray it onto the surface and pores of 8g of β-tricalcium phosphate particles by plasma spraying method. The ethanol is gradually volatilized, and the composite bone graft particles can be prepared.

Example 4:

Observing the composite bone graft particles prepared in Example 1 with a scanning electron microscope, it can be seen that the surface of the deorganized cancellous bone particles with a microporous structure is covered with α-calcium sulfate hemihydrate powder ( FIG. 2 ). This composite artificial bone can be solidified into a mass with certain mechanical strength when it encounters an aqueous solution (Fig. 3). After curing for 1 hour, the compressive strength is tested with a biomechanical testing machine (MTS 858 Mini.Bionix 2, USA). Between 10-15MPa. The X-ray diffraction pattern of the composite artificial bone particle can be seen to have peaks of both β-tricalcium phosphate and α-sulfuric acid hemihydrate (Figure 4).

Example 5:

The composite artificial bone granules produced in Example 1 are subpackaged according to appropriate weight and packaged, and can be used to repair bone defect animal models after being sterilized with Co60. Rabbits were used to make an animal model of bone defect with a diameter of 5 mm above the femoral condyle, and the bone defect was repaired with composite bone graft particles. The bone defect could be completely filled with the bone graft material on X-ray 1 day after operation (Fig. 5a). The rabbits were sacrificed 4 weeks after the operation, and the femoral condyle was cut open to see that the composite bone graft material filled the bone defect and was tightly combined with the bone interface, and no inflammatory reaction or fibrous tissue formation was seen at the interface (Fig. 6a). X-rays at 12 weeks after the operation showed that most of the bone graft material had degraded. The rabbit was killed and the femoral condyle was cut open. It can be seen that most of the composite bone graft material had degraded and was replaced by new bone crawling (Fig. 6b).

Claims (10)

1. A new type of inorganic bone graft material, composed of 20%-80% by mass percentage of β-tricalcium phosphate particles and 80%-20% by mass percentage of α-calcium sulfate hemihydrate powder, α-sulfuric acid hemihydrate The calcium powder forms a layered structure on the surface of the β-tricalcium phosphate particle and/or inside its pores. 2. A new type of inorganic bone graft material according to claim 1, characterized in that: the diameter of the β-tricalcium phosphate particles is 0.2-10mm. 3. the preparation method of the novel inorganic bone graft material described in claim 1, comprising: (1) preparing β-tricalcium phosphate particles with a microporous structure; (2) prepare α-calcium sulfate hemihydrate powder; (3) The preparation mass percentage is 20%-80% beta-tricalcium phosphate particles and mass percentage is 80%-20% alpha-calcium sulfate hemihydrate powder, on the surface of beta-tricalcium phosphate particles and/or in the void A powder layer of α-calcium sulfate hemihydrate is formed. 4. The preparation method of novel inorganic bone graft material according to claim 3, characterized in that: said (1) preparation of β-tricalcium phosphate particles with a microporous structure is to directly calcinate heterogeneous or allogeneic cancellous bone , take the healthy cancellous bone and calcined it in a high-temperature furnace after removing the organic components, at 800°C for 3 hours, with a heating rate of 10°C/min, take out the calcined bone and soak it in 1M (NH ₄ ) ₂ HPO ₄ In the solution for 24 hours, remove excess liquid, dry at 50°C for 4 days, put it in a high-temperature calciner for calcination again, under the condition of 1100°C for 1 hour, the heating rate is 5°C/min, slowly cool down, rinse with deionized water twice, 50 ℃ drying for 4 days. 5. the preparation method of novel inorganic bone graft material according to claim 3 is characterized in that: described (1) prepares the beta-tricalcium phosphate particle with microporous structure, is to adopt the calcium hydrogen phosphate of 2 parts by weight Under the condition of 800°C for 3 hours, it is converted into calcium pyrophosphate, then mixed with 1 part by weight of calcium carbonate and then pressed into tablets, then slowly cooled after 1 hour under the condition of 1100°C, and pulverized to make β-tricalcium phosphate powder. Microcellular foaming technology is used to make β-tricalcium phosphate particles with microporous structure. 6. the preparation method of novel inorganic bone grafting material according to claim 3 is characterized in that: described (2) prepares α-calcium sulfate hemihydrate powder, is to be placed in steam with analytical pure calcium sulfate dihydrate as raw material In a closed high-pressure reactor with a pressure of 0.13Mpa, gradually increase the temperature by 5°C per minute, heat to 123°C, heat at a constant temperature for 7 hours, then take it out and place it in a 120°C electric ventilation drying oven to dry for 4-5 hours, and crush the obtained material , the average particle size is less than or equal to 5μm. 7. the preparation method of novel inorganic bone graft material according to claim 3 is characterized in that: described (3) preparation mass percentage is the beta-tricalcium phosphate particle of 20%-80% and mass percentage is 80%-80%. 20% α-calcium sulfate hemihydrate powder, the α-calcium sulfate hemihydrate powder layer is formed on the surface and/or in the void of β-tricalcium phosphate particles, which is made by stirring with absolute ethanol and α-calcium sulfate hemihydrate shape, spray α-calcium sulfate hemihydrate directly on the surface of β-tricalcium phosphate particles by spraying; or put β-tricalcium phosphate particles into the above paste mixture and stir to make α-calcium sulfate hemihydrate powder adhere β-tricalcium phosphate particle surface and/or inside its pores; natural volatilization at 37°C to remove absolute ethanol. 8. The preparation method of the novel inorganic bone graft material according to claim 3, characterized in that: (3) the preparation mass percentage is 20%-80% β-tricalcium phosphate particles and the mass percentage is 80%-80%. 20% α-calcium sulfate hemihydrate powder, the α-calcium sulfate hemihydrate powder layer is formed on the surface and/or in the void of β-tricalcium phosphate particles, and the α-calcium sulfate hemihydrate powder is directly sprayed by plasma method immobilized on the surface of β-tricalcium phosphate particles. 9. The application of the novel inorganic bone grafting material according to claim 1, adding DBM, BMP etc. with osteoinductive activity in the raw material to repair bone defects, or compounding antibiotics and chemotherapeutic drugs to treat open complex war wounds and various causes. osteomyelitis or bone tumors. 10. the method for novel inorganic bone graft material composite DBM, BMP, antibiotic or chemotherapeutic drug as claimed in claim 1, is characterized in that: DBM, BMP, antibiotic or chemotherapeutic drug are mixed with α-calcium sulfate hemihydrate powder, then Spray together and fix on the surface of β-tricalcium phosphate particles, or directly add DBM, BMP, antibiotics or chemotherapy drugs to the composite artificial bone.

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