Bone cement composite material and application thereof

Abstract

The invention relates to a bone cement composite material and application thereof. The bone cement composite material comprises the following components: solid phase powder which comprises inorganic calcium phosphate; the curing liquid comprises a water-soluble high-molecular compound and a solvent, the mass fraction of the water-soluble high-molecular compound in the curing liquid is 1%-55%, and the water-soluble high-molecular compound comprises at least one of polyacrylic acid, hydroxybutyl chitosan and polyglutamic acid. When in use, the bone cement composite material has proper initial setting time matched with ideal requirements of clinical operations, also has good injectability, collapse resistance and mechanical properties, and can better meet clinical requirements.

Description

Technical Field

[0001] The present invention relates to the technical field of bone repair materials, in particular to a bone cement composite material and applications thereof. Background Art

[0002] Clinically, the treatment of joint soft tissue injuries often requires the implantation of anchors or interference screws into the bones. However, for patients with osteoporosis, due to insufficient bone density and increased bone brittleness, drilling holes directly into the bones to implant anchors or interference screws can easily cause secondary fractures. Moreover, the fixation strength of the anchors or interference screws after implantation is low, and they are prone to loosening or even falling off, leading to surgical failure.

[0003] In addition, osteoporotic fractures are difficult to heal on their own due to insufficient bone formation activity. Clinically, bone screws are often used for internal fixation. However, direct bone screw placement can also cause secondary fractures and can easily loosen or even fall off. Therefore, before inserting bone screws, anchors, or interference screws into the bones of osteoporotic patients, surgeons pre-fill the bones with bone cement and insert the screws, anchors, or interference screws before the cement initially sets to enhance the internal fixation effect.

[0004] Calcium phosphate cement (CPC) consists of solid calcium phosphate powder and a curing liquid. The mixture of the two solidifies in a physiological environment without generating significant heat. The resulting product is hydroxyapatite, which is similar to the inorganic components of human bone. It also exhibits excellent bioactivity, osteoinduction, osteoconduction, and biodegradability, making it an ideal bone repair material. However, existing CPCs still have several issues that prevent them from meeting clinical needs. For example, they have low mechanical strength; their initial setting time is either too long or too fast, making it difficult to achieve the ideal initial setting time of 15 to 30 minutes typically used in bone screw, anchor, or interference screw implantation surgeries. This increases the risk of surgical infection due to prolonged surgery or the cement setting is too early, making it impossible to inject. CPCs also exhibit poor injectability, with solid-liquid separation likely to occur during the injection process. Furthermore, their poor anti-collapse properties can lead to their easy collapse after implantation or even failure to form. Summary of the Invention

[0005] To overcome the above-mentioned technical deficiencies in the prior art, the present invention provides a bone cement composite material and its application. The bone cement composite material, when used, has an appropriate initial setting time that matches the ideal requirements of clinical surgery, while also exhibiting good injectability, anti-collapse properties, and mechanical properties, thereby better meeting clinical needs.

[0006] A bone cement composite material, comprising:

[0007] Solid phase powder, the solid phase powder comprising inorganic calcium phosphate;

[0008] The curing liquid comprises a water-soluble polymer and a solvent, wherein the mass fraction of the water-soluble polymer in the curing liquid is 1%-55%, and the water-soluble polymer comprises at least one of polyacrylic acid, hydroxybutyl chitosan, and polyglutamic acid.

[0009] In one embodiment, when the water-soluble polymer compound is polyacrylic acid, the mass fraction of the polyacrylic acid in the curing liquid is 35%-55%;

[0010] Alternatively, when the water-soluble polymer compound is hydroxybutyl chitosan, the mass fraction of the hydroxybutyl chitosan in the solidifying liquid is 1%-5%;

[0011] Alternatively, when the water-soluble polymer compound is polyglutamic acid, the mass fraction of the polyglutamic acid in the solidifying liquid is 1%-20%;

[0012] Alternatively, when the water-soluble polymer compound is polyacrylic acid and polyglutamic acid, the mass fraction of the polyacrylic acid in the solidifying liquid is 15%-40%, and the mass fraction of the polyglutamic acid in the solidifying liquid is 1%-15%;

[0013] Alternatively, when the water-soluble polymer compound is polyacrylic acid and hydroxybutyl chitosan, the mass fraction of the polyacrylic acid in the solidifying liquid is 30%-40%, and the mass fraction of the hydroxybutyl chitosan in the solidifying liquid is 1%-5%;

[0014] Alternatively, when the water-soluble polymer compound is polyacrylic acid, polyglutamic acid and hydroxybutyl chitosan, the mass fraction of the polyacrylic acid in the solidifying liquid is 10%-30%, the mass fraction of the polyglutamic acid in the solidifying liquid is 1%-15%, and the mass fraction of the hydroxybutyl chitosan in the solidifying liquid is 1%-5%.

[0015] In one embodiment, the weight average molecular weight of the polyacrylic acid is 2000-5000.

[0016] In one embodiment, the weight average molecular weight of the hydroxybutyl chitosan is 50 kDa-200 kDa;

[0017] And / or, the degree of substitution of the hydroxybutyl chitosan is 1.0-2.0.

[0018] In one embodiment, the weight average molecular weight of the polyglutamic acid is 500 kDa-1500 kDa.

[0019] In one embodiment, the curing liquid further includes an additive, and the additive includes at least one of sodium polyacrylate, sodium alginate, phosphoric acid, and acetic acid.

[0020] In one embodiment, when the additive includes sodium alginate, the mass fraction of the sodium alginate in the solidifying liquid is 1%-15%.

[0021] In one embodiment, the median particle size of the solid phase powder is 1 μm-200 μm.

[0022] In one embodiment, the solid phase powder further comprises calcium carbonate, wherein the mass ratio of the calcium carbonate to the inorganic calcium phosphate salt is 1:9-1:4.

[0023] In one embodiment, the molar ratio of calcium to phosphorus in the solid phase powder is 0.5:1-2:1;

[0024] And / or, the inorganic calcium phosphate salt is at least one selected from α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate, and calcium dihydrogen phosphate.

[0025] A use of the bone cement composite material as described above in the preparation of bone repair materials.

[0026] In one embodiment, the solid-to-liquid ratio of the solid phase powder to the solidified liquid is 0.5 g / mL-8 g / mL.

[0027] The bone cement composite material of the present invention uses inorganic calcium phosphate as a solid phase powder, so that the bone cement composite material has good biological activity, osteoinduction, osteoconduction effect and biodegradability. At the same time, a water-soluble polymer compound with a specific mass fraction is used as the main component of the solidifying liquid, and the water-soluble polymer compound is limited to include at least one of polyacrylic acid, hydroxybutyl chitosan and polyglutamic acid. When the water-soluble polymer compound is used in combination with the inorganic calcium phosphate, the inherent properties of polyacrylic acid, hydroxybutyl chitosan and / or polyglutamic acid can be fully utilized to regulate the initial setting time of the bone cement composite material within a suitable range, while effectively improving the injectability, anti-collapse and mechanical properties of the bone cement composite material during use. In addition, by controlling the solid-to-liquid ratio of the solid phase powder and the solidifying liquid during use, not only the injectability, anti-collapse and mechanical properties of the bone cement composite material during use are further improved, but also the initial setting time of the bone cement composite material during use can be further controlled to be an optimal initial setting time, better meeting the needs of clinical surgery. Therefore, the bone cement composite material of the present invention has an appropriate initial setting time that matches the ideal requirements of clinical surgery when used, and at the same time has good injectability, anti-collapse and mechanical properties, which can better meet clinical needs. DETAILED DESCRIPTION

[0028] To facilitate understanding of the present invention, the present invention will be described in more detail below. However, it should be understood that the present invention can be implemented in many different forms and is not limited to the embodiments or examples described herein. On the contrary, the purpose of providing these embodiments or examples is to make the understanding of the disclosure of the present invention more thorough and comprehensive.

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art of the technical field of the present invention. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments or embodiments and are not intended to limit the present invention. The optional scope of the term "and / or" used herein includes any one of two or more related listed items, and also includes any and all combinations of related listed items, including any two related listed items, any more related listed items, or the combination of all related listed items.

[0030] The bone cement composite material provided by the present invention, used as an osteoporotic bone repair material in combination with bone screws, anchors, or interface screws, effectively bonds to bone tissue at the bone screw / anchor / interference screw interface, thereby avoiding the risk of secondary fractures that can occur with single-implanted bone screws, anchors, or interface screws. Specifically, the bone cement composite material comprises a solid phase powder and a curing liquid, wherein the solid phase powder comprises an inorganic calcium phosphate salt. It is understood that the bone cement composite material of the present invention is a calcium phosphate bone cement, which provides excellent osteoinduction and osteoconduction effects during use.

[0031] Calcium phosphate bone cement suffers from poor mechanical strength, poor injectability, poor anti-collapse properties, and an initial setting time that doesn't match clinical needs. This is particularly true of the initial setting time, which directly impacts surgical efficiency and safety. If the initial setting time is too short, the surgeon may not have enough time to shape and fix the cement, potentially leading to surgical failure or improper placement of the cement. Conversely, if the initial setting time is too long, it can increase surgical time and raise surgical risks, such as infection.

[0032] To this end, in the present invention, the solidifying liquid includes a water-soluble polymer compound and a solvent, the mass fraction of the water-soluble polymer compound in the solidifying liquid is 1%-55%, and the water-soluble polymer compound includes at least one of polyacrylic acid, hydroxybutyl chitosan, and polyglutamic acid.

[0033] In the present invention, polyacrylic acid contains a large number of carboxyl groups on its surface and is weakly acidic. When used as a solidifying liquid component, it can dissolve with inorganic calcium phosphate and other substances to produce Ca 2+Ionic bonds are formed to promote the hydrolysis reaction of calcium phosphate salts, thereby effectively regulating the initial setting time of bone cement composite materials during use within an appropriate range. At the same time, polyacrylic acid itself has strong viscosity, which can effectively improve the anti-collapse and mechanical properties of bone cement composite materials during use; and hydroxybutyl chitosan is a thermosensitive hydrogel material that can undergo a sol-gel phase transition at a certain temperature to form a three-dimensional network structure, thereby improving the mechanical properties and anti-collapse performance of bone cement composite materials during use. At the same time, hydroxybutyl chitosan also has good biocompatibility, biodegradability and water solubility, which can effectively regulate bone cement composite materials. The initial setting time during use is shortened, thereby improving its injectability, biocompatibility and biodegradability. Polyglutamic acid also contains a large number of carboxyl groups, which can effectively promote the hydrolysis reaction of calcium phosphate salts, thereby shortening the initial setting time of the bone cement composite material during use and regulating the initial setting time within an appropriate range. At the same time, it has good biocompatibility, biodegradability and water solubility. In addition, it is also beneficial to improve the injectability of the bone cement composite material during use. Moreover, the polyglutamic acid solution can cross-link to form a three-dimensional network structure due to its own large number of hydrogen bonds, which can effectively improve the anti-collapse and mechanical properties of the bone cement composite material during use.

[0034] It can be understood that in the present invention, a water-soluble polymer compound with a specific mass fraction is used as the main component of the solidifying liquid, and the water-soluble polymer compound is limited to include at least one of polyacrylic acid, hydroxybutyl chitosan, and polyglutamic acid. When the water-soluble polymer compound is compounded with an inorganic calcium phosphate salt, the inherent properties of polyacrylic acid, hydroxybutyl chitosan and / or polyglutamic acid can be fully utilized to regulate the initial setting time of the bone cement composite material during use within an appropriate range, while effectively improving the injectability, anti-collapse and mechanical properties of the bone cement composite material during use.

[0035] Furthermore, during use, the solid-to-liquid ratio of the solid phase powder to the solidifying liquid is controlled within a range of 0.5 g / mL to 8 g / mL, preferably 1 g / mL to 4 g / mL. By controlling the solid-to-liquid ratio of the solid phase powder to the solidifying liquid, not only can the injectability, anti-collapse, and mechanical properties of the bone cement be further improved, but the initial setting time of the bone cement composite material during use can also be better controlled to an optimal initial setting time. That is, the initial setting time of the bone cement composite material during use is 15 minutes to 30 minutes, which exactly meets the ideal initial setting time of bone cement used in bone screw, anchor, or interference screw implantation surgeries, thereby better meeting the needs of clinical surgery.

[0036] Therefore, the bone cement composite material of the present invention has an appropriate initial setting time that matches the ideal requirements of clinical surgery when used, and at the same time has good injectability, anti-collapse and mechanical properties, which can better meet clinical needs.

[0037] It should be noted that, in the present invention, the setting time of the bone cement composite material during use generally includes the initial setting time and the final setting time, wherein the initial setting time refers to the time required to reach the initial setting point, and the initial setting point refers to the state where the formed bone cement slurry has lost its fluidity and cannot be reshaped.

[0038] It can be understood that in the present invention, the water-soluble polymer compound can be any one of polyacrylic acid, hydroxybutyl chitosan or polyglutamic acid, or a combination of any two of polyacrylic acid, hydroxybutyl chitosan or polyglutamic acid, or a combination of the three.

[0039] Specifically, when the water-soluble polymer compound is polyacrylic acid, it can be understood that the solidifying liquid includes polyacrylic acid and a solvent, that is, the solidifying liquid is a polyacrylic acid solution.

[0040] Optionally, the mass fraction of the polyacrylic acid in the curing liquid is 35%-55%. Such an arrangement is conducive to better regulating the initial setting time of the bone cement composite material during use, while further improving the anti-collapse performance, mechanical properties and injectability of the bone cement composite material during use.

[0041] When the water-soluble polymer compound is hydroxybutyl chitosan, it can be understood that the solidifying liquid includes hydroxybutyl chitosan and a solvent, that is, the solidifying liquid is a hydroxybutyl chitosan solution.

[0042] Optionally, the mass fraction of the hydroxybutyl chitosan in the solidifying liquid is 1%-5%; such a setting is conducive to better regulating the initial setting time of the bone cement composite material during use, while further improving the anti-collapse performance, mechanical properties and injectability of the bone cement composite material during use.

[0043] When the water-soluble polymer compound is polyglutamic acid, it can be understood that the solidifying liquid includes polyglutamic acid and a solvent, that is, the solidifying liquid is a polyglutamic acid solution.

[0044] Optionally, the mass fraction of the polyglutamic acid in the solidifying liquid is 1%-20%; such a setting is conducive to better regulating the initial setting time of the bone cement composite material during use, while further improving the anti-collapse performance, mechanical properties and injectability of the bone cement composite material during use.

[0045] When the water-soluble polymer compound is polyacrylic acid and polyglutamic acid, the mass fraction of the polyacrylic acid in the solidifying liquid is 15%-40%, and the mass fraction of the polyglutamic acid in the solidifying liquid is 1%-15%; it can be understood that at this time, the solidifying liquid includes a solvent, polyacrylic acid and polyglutamic acid.

[0046] When the water-soluble polymer compound is polyacrylic acid and hydroxybutyl chitosan, the mass fraction of the polyacrylic acid in the solidifying liquid is 30%-40%, and the mass fraction of the hydroxybutyl chitosan in the solidifying liquid is 1%-5%; it can be understood that at this time, the solidifying liquid includes a solvent, polyacrylic acid and hydroxybutyl chitosan.

[0047] When the water-soluble polymer compound is polyacrylic acid, polyglutamic acid and hydroxybutyl chitosan, the mass fraction of the polyacrylic acid in the solidifying liquid is 10%-30%, the mass fraction of the polyglutamic acid in the solidifying liquid is 1%-15%, and the mass fraction of the hydroxybutyl chitosan in the solidifying liquid is 1%-5%; it can be understood that the solidifying liquid includes a solvent, polyacrylic acid, polyglutamic acid and hydroxybutyl chitosan.

[0048] It can be understood that in the present invention, by using polyacrylic acid, polyglutamic acid and / or hydroxybutyl chitosan together as components of the curing liquid and limiting the amount of each component, polyacrylic acid, polyglutamic acid and / or hydroxybutyl chitosan can work together to better ensure that the initial setting time of the bone cement composite material when used is the optimal initial setting time, while better improving the anti-collapse performance, mechanical properties and injectability of the bone cement composite material when used, thereby better meeting clinical needs.

[0049] Optionally, the weight average molecular weight of the polyacrylic acid is 2000-5000. This configuration is conducive to further improving the anti-collapse performance and mechanical properties of the bone cement composite material during use, while ensuring that the bone cement composite material still has good injectability during use.

[0050] Optionally, the weight average molecular weight of the polyglutamic acid is 500kDa-1500kDa. Such an arrangement is conducive to further improving the anti-collapse performance and mechanical properties of the bone cement composite material during use while ensuring that the bone cement composite material still has good injectability during use.

[0051] Optionally, the weight average molecular weight of the hydroxybutyl chitosan is 50kDa-200kDa; such a setting is conducive to further improving the anti-collapse performance and mechanical properties of the bone cement composite material during use, while ensuring that the bone cement composite material still has good injectability during use.

[0052] Furthermore, the degree of substitution of the hydroxybutyl chitosan is 1.0-2.0; such a setting is conducive to better improving the anti-collapse performance and mechanical properties of the bone cement composite material during use, while ensuring that the bone cement composite material still has good injectability during use.

[0053] Optionally, when the water-soluble polymer compound is hydroxybutyl chitosan, the pH value of the solidifying liquid is 7-7.4; such a setting can ensure that the pH value of the bone cement system is close to the pH value of human body fluids and will not cause changes in the pH value of surrounding body fluids.

[0054] Furthermore, the viscosity of the solidifying liquid is 120 cps-300 cps. Such a setting is conducive to better regulating the initial setting time of the bone cement composite material during use, and at the same time better ensuring that the bone cement composite material has good injectability during use.

[0055] In the present invention, the solidifying liquid further comprises an additive, and the additive comprises at least one of sodium polyacrylate, sodium alginate, phosphoric acid, and acetic acid.

[0056] In one embodiment, the mass fraction of the additive in the curing liquid is 0.1%-15%.

[0057] Specifically, when the solidifying liquid further includes sodium polyacrylate, the anti-collapse property of the bone cement composite material during use can be further improved by utilizing the fact that sodium polyacrylate itself is neutral to alkaline and has strong adhesiveness.

[0058] When the additive includes sodium alginate, that is, the solidifying liquid also includes sodium alginate, such an arrangement can further improve the injectability of the bone cement composite material during use.

[0059] Furthermore, the mass fraction of sodium alginate in the solidifying liquid is 1%-15%. This configuration allows the balance between injectability and anti-collapse performance of the bone cement composite material during use to be regulated by adjusting the amount of sodium alginate, thereby improving the injectability of the bone cement composite material while still ensuring good anti-collapse performance during use.

[0060] Optionally, the median particle size of the solid phase powder is 1 μm-200 μm, preferably 1 μm-70 μm. This configuration is conducive to promoting the full progress of the inorganic calcium phosphate salt hydrolysis reaction when the solid phase powder and the solidifying liquid are mixed, further improving the mechanical properties of the bone cement composite material.

[0061] Optionally, the solid phase powder further comprises calcium carbonate, wherein the mass ratio of the calcium carbonate to the inorganic calcium phosphate is 1:9-1:4. This configuration, by providing a specific amount of calcium carbonate, can, on the one hand, neutralize hydrogen ions generated during the hydrolysis reaction of the inorganic calcium phosphate, thereby adjusting the pH value of the reaction system; on the other hand, it can generate trace amounts of CO2, which regulates the pore structure of the bone cement composite material and increases the degradation rate of the bone cement composite material in the body.

[0062] Optionally, the molar ratio of calcium and phosphorus in the solid phase powder is 0.5:1-2:1, preferably 1.67:1; such a setting is conducive to promoting the self-curing reaction of inorganic calcium phosphate to generate hydroxyapatite, and makes the molar ratio of calcium and phosphorus in hydroxyapatite within an appropriate range, which is closer to the inorganic components of human bones, thereby facilitating the repair of bone tissue.

[0063] Furthermore, the inorganic calcium phosphate salt is selected from at least one of α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate, and calcium dihydrogen phosphate.

[0064] In one embodiment, in the present invention, the solvent is selected from water, physiological saline or acid-base aqueous solution.

[0065] At the same time, the present invention also provides a use of the bone cement composite material as described above in preparing bone repair materials.

[0066] Optionally, the solid-to-liquid ratio of the solid phase powder to the solidified liquid is 0.5 g / mL-8 g / mL, preferably 1 g / mL-4 g / mL.

[0067] It should be noted that when the bone cement composite material of the present invention is used, the solid phase powder and the solidifying liquid are mixed according to a specific solid-liquid ratio and continuously stirred. At the beginning, the system is in a paste state. Within a few minutes of stirring, the solid and liquid phases can be observed to gradually react, and the system gradually becomes uniform and agglomerates, at which time it is in a dough state. When the dough state is observed, it is the injection window period, at which time the system will no longer separate into phases, that is, the system will become a paste, which is the most suitable state for injection into the body, and the injection site can be the bone defect site. After entering the body, it will gradually solidify and solidify within 15min-30min, that is, it reaches the initial setting state.

[0068] In one embodiment, the bone cement composite is used as an osteoporotic bone repair material in combination with a bone screw, anchor, or interference screw. Specifically, the solid phase powder and the curing liquid are thoroughly mixed at a specific solid-to-liquid ratio to form a paste-like state, which is optimal for injection. This paste is then injected into the bone defect where the bone screw / anchor / interference screw is to be implanted, and the bone screw / anchor / interference screw is then implanted. Since the bone cement composite material of the present invention has an initial setting time of 15 minutes to 30 minutes when used, it meets the initial setting requirements in clinical / anchor / interface screw surgery and has good injectability, anti-collapse and mechanical properties. The paste formed after the two phases in the bone cement composite material are mixed can be injected into the bone defect site to fully fill it, and the surgeon is left with appropriate time to implant the bone screw / anchor / interface screw. Therefore, when used in conjunction with the bone screw / anchor / interface screw, it can effectively enhance the interface adhesion between bone tissue and the bone screw / anchor / interface screw, improve the pull-out strength of the bone screw / anchor / interface screw, and prevent the bone screw / anchor / interface screw from loosening or falling off easily, thereby providing mechanical support for the repair of osteoporotic bone defects and the repair of joint soft tissue injuries in osteoporosis patients.

[0069] Below, described bone cement composite material and application thereof will be further described by following specific examples.But those skilled in the art will appreciate that the following examples are only used to illustrate the present invention, and should not be considered as limiting the scope of the invention.Unindicated specific conditions in the embodiment, carry out according to the condition of normal condition or manufacturer's suggestion.Agents therefor or instrument are not indicated manufacturer, all are conventional products that can be obtained by commercial purchase.

[0070] Example 1

[0071] α-tricalcium phosphate, calcium carbonate, and calcium dihydrogen phosphate were ground into powder and uniformly mixed to obtain a solid phase powder with a median particle size of 70 μm, wherein the mass ratio of α-tricalcium phosphate, calcium carbonate, and calcium dihydrogen phosphate was 20:4:1; polyacrylic acid and deionized water were uniformly mixed to obtain a solidifying liquid, wherein the mass fraction of polyacrylic acid in the solidifying liquid was 40%, and the weight-average molecular weight of polyacrylic acid was 3000; at this time, a bone cement composite material was obtained.

[0072] The solid phase powder obtained above and the solidifying liquid were mixed with each other at a solid-liquid ratio of 1.25 g / mL to form a paste-like bone cement slurry.

[0073] Example 2

[0074] Tetracalcium phosphate, β-tricalcium phosphate, and monocalcium phosphate were ground into powder and uniformly mixed to obtain a solid phase powder with a median particle size of 1 μm, wherein the mass ratio of tetracalcium phosphate, β-tricalcium phosphate, and monocalcium phosphate was 146:31:25; polyacrylic acid and deionized water were uniformly mixed to obtain a solidifying liquid, wherein the mass fraction of polyacrylic acid in the solidifying liquid was 35%, and the weight-average molecular weight of polyacrylic acid was 2000; at this time, a bone cement composite material was obtained.

[0075] The solid phase powder obtained above and the solidifying liquid were mixed with each other at a solid-liquid ratio of 0.5 g / mL to form a paste-like bone cement slurry.

[0076] Example 3

[0077] Tetracalcium phosphate and calcium hydrogen phosphate were ground into powder and mixed uniformly to obtain a solid phase powder with a median particle size of 200 μm, wherein the mass ratio of tetracalcium phosphate to calcium hydrogen phosphate was 366:136; polyacrylic acid and deionized water were mixed uniformly to obtain a solidifying liquid, wherein the mass fraction of polyacrylic acid in the solidifying liquid was 55% and the weight-average molecular weight of polyacrylic acid was 5000; at this time, a bone cement composite material was obtained.

[0078] The solid phase powder obtained above and the solidifying liquid were mixed with each other at a solid-liquid ratio of 8 g / mL to form a paste-like bone cement slurry.

[0079] Example 4

[0080] The only difference between Example 4 and Example 1 is that the mass fraction of polyacrylic acid in the curing liquid is 30%, and the other conditions are the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0081] Example 5

[0082] The only difference between Example 5 and Example 1 is that the weight average molecular weight of the polyacrylic acid is 1500. Other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0083] Example 6

[0084] The only difference between Example 6 and Example 1 is that the weight average molecular weight of the polyacrylic acid is 6000. Other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0085] Example 7

[0086] Compared with Example 1, Example 7 differs only in that hydroxybutyl chitosan is used instead of polyacrylic acid, the mass fraction of hydroxybutyl chitosan in the curing liquid is 3%; the weight-average molecular weight of the hydroxybutyl chitosan is 125 kDa, and the degree of substitution is 1.5; the other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0087] Example 8

[0088] The only difference between Example 8 and Example 7 is that the mass fraction of hydroxybutyl chitosan in the curing liquid is 5%; the weight average molecular weight of the hydroxybutyl chitosan is 200 kDa, and the degree of substitution is 2.0; the other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0089] Example 9

[0090] The only difference between Example 9 and Example 7 is that the mass fraction of hydroxybutyl chitosan in the curing liquid is 1%; the weight average molecular weight of the hydroxybutyl chitosan is 50 kDa, and the degree of substitution is 1.0; the other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0091] Example 10

[0092] The only difference between Example 10 and Example 7 is that the mass fraction of hydroxybutyl chitosan in the solidifying liquid is 6%. Other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0093] Example 11

[0094] Compared with Example 7, Example 11 differs only in that the weight average molecular weight of the hydroxybutyl chitosan is 40 kDa. Other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0095] Example 12

[0096] Compared with Example 7, Example 12 differs only in that the weight average molecular weight of the hydroxybutyl chitosan is 220 kDa. Other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0097] Example 13

[0098] The only difference between Example 13 and Example 1 is that polyglutamic acid is used instead of polyacrylic acid, the mass fraction of polyglutamic acid in the curing liquid is 10%; the weight-average molecular weight of the polyglutamic acid is 1000 kDa, and the other conditions are the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0099] Example 14

[0100] The only difference between Example 14 and Example 13 is that the mass fraction of polyglutamic acid in the solidifying liquid is 20%; the weight-average molecular weight of the polyglutamic acid is 1500 kDa, and the other conditions are the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0101] Example 15

[0102] The only difference between Example 15 and Example 13 is that the mass fraction of polyglutamic acid in the solidifying liquid is 1%; the weight-average molecular weight of the polyglutamic acid is 500 kDa, and the other conditions are the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0103] Example 16

[0104] The only difference between Example 16 and Example 13 is that the mass fraction of polyglutamic acid in the solidifying liquid is 25%. The other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0105] Example 17

[0106] The only difference between Example 17 and Example 13 is that the weight-average molecular weight of the polyglutamic acid in the solidifying liquid is 400 kDa. Other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0107] Example 18

[0108] The only difference between Example 18 and Example 13 is that the weight-average molecular weight of the polyglutamic acid in the solidifying liquid is 1600 kDa. Other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0109] Example 19

[0110] Example 19 is different from Example 1 only in that polyacrylic acid, polyglutamic acid and deionized water are evenly mixed to obtain a solidifying liquid, wherein the mass fraction of polyacrylic acid is 32%, the mass fraction of polyglutamic acid is 10%, the weight average molecular weight of the polyacrylic acid is 3500, and the weight average molecular weight of the polyglutamic acid is 1000 kDa. The other conditions are the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0111] Example 20

[0112] Example 20 is different from Example 1 only in that polyacrylic acid, hydroxybutyl chitosan and deionized water are evenly mixed to obtain a solidifying liquid, wherein the mass fraction of polyacrylic acid is 40%, the mass fraction of hydroxybutyl chitosan is 3%, the weight average molecular weight of the polyacrylic acid is 3500, the weight average molecular weight of the hydroxybutyl chitosan is 125 kDa, and the degree of substitution is 1.5; the other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0113] Example 21

[0114] Example 21 is different from Example 1 only in that polyacrylic acid, polyglutamic acid, hydroxybutyl chitosan and deionized water are mixed evenly to obtain a solidifying liquid, wherein in the solidifying liquid, the mass fraction of polyacrylic acid is 30%, the mass fraction of polyglutamic acid is 10%, and the mass fraction of hydroxybutyl chitosan is 3%. The weight average molecular weight of the polyacrylic acid is 3500, the weight average molecular weight of the polyglutamic acid is 1000 kDa, the weight average molecular weight of the hydroxybutyl chitosan is 125 kDa, and the degree of substitution is 1.5; the other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0115] Example 22

[0116] The only difference between Example 22 and Example 1 is that polyacrylic acid, sodium alginate and deionized water are mixed evenly to obtain a solidifying liquid, wherein the mass fraction of sodium alginate in the solidifying liquid is 2%, and the other conditions are the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0117] Example 23

[0118] Compared with Example 22, Example 23 differs only in that the mass fraction of sodium alginate in the solidifying liquid is 14%, and the other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0119] Example 24

[0120] Compared with Example 22, Example 24 differs only in that the mass fraction of sodium alginate in the solidifying liquid is 16%, and the other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0121] Example 25

[0122] Compared with Example 22, Example 25 differs only in that the mass fraction of sodium alginate in the solidifying liquid is 0.6%, and the other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0123] Example 26

[0124] The only difference between Example 26 and Example 1 is that the solid phase powder does not contain calcium carbonate. Other conditions are the same, and the corresponding bone cement composite material and bone cement slurry are obtained.

[0125] Comparative Example 1

[0126] Comparative Example 1 is different from Example 1 only in that the mass fraction of polyacrylic acid in the curing liquid is 60%, and the other conditions are the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0127] Comparative Example 2

[0128] Comparative Example 2 is different from Example 1 only in that chitosan and acetic acid are evenly mixed to obtain a solidifying liquid, wherein the mass fraction of chitosan in the solidifying liquid is 40%, and the other conditions are the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0129] The weight average molecular weight of the chitosan is between 50 kDa and 200 kDa, and the deacetylation degree is between 85% and 100%.

[0130] Comparative Example 3

[0131] Comparative Example 3 is different from Example 1 only in that the solid-liquid ratio of the solid phase powder to the solidifying liquid is 0.4 g / mL, and other conditions are the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0132] Comparative Example 4

[0133] Comparative Example 4 is different from Example 1 only in that the solid-liquid ratio of the solid phase powder to the solidifying liquid is 9 g / mL, and other conditions are the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0134] Comparative Example 5

[0135] Comparative Example 5 Compared with Example 19, α-tricalcium phosphate, calcium carbonate, and calcium dihydrogen phosphate were ground into powder and mixed, and then polyglutamic acid powder was added and mixed evenly to obtain a solid phase powder with a median particle size of 70 μm, wherein the mass ratio of α-tricalcium phosphate, calcium carbonate, calcium dihydrogen phosphate and polyglutamic acid was 20:4:1:8, and the other conditions were the same to obtain the corresponding bone cement composite material and bone cement slurry.

[0136] The performance of the bone cement composite materials prepared in Examples 1-26 and Comparative Examples 1-5 was tested during use. The test results are shown in Table 1. The specific test method is as follows:

[0137] Initial setting time test: The prepared bone cement slurry was filled into a polytetrafluoroethylene mold with a height of 12 mm and a diameter of 6 mm. The surface was scraped flat and the slurry was cured in a 37°C water bath. The initial setting time of the bone cement slurry was then measured using a Vicat apparatus according to ISO-9597-2008E. Specifically, the initial setting time was measured as follows: the height of the initial setting needle was adjusted to contact the surface of the bone cement slurry. The screw was then loosened to allow the initial setting needle to sink naturally, and the height to which the initial setting needle descended was observed. The time was counted from the time the powder was added to the water until the depth of the initial setting needle inserted into the bone cement slurry was less than 1 mm. The time required for this process was recorded as the initial setting time of the bone cement slurry.

[0138] Syringability test: Take a 2.5mL syringe and remove the needle. Weigh its mass, recorded as m0. Then, fill the 2.5mL syringe with bone cement slurry. Weigh the total mass of the bone cement slurry and syringe, m1. Next, apply a vertical pressure of 30N to the top of the syringe piston to force the bone cement slurry out of the needle. Weigh the total mass of the syringe and the remaining bone cement slurry after extrusion, recorded as m2. Each experiment was repeated three times and the average value was obtained. The syringeability of the bone cement slurry is calculated as (m2 - m0) / (m1 - m0) × 100%.

[0139] Anti-collapse time test: After the solid phase powder and curing liquid in the bone cement composite material are blended according to the corresponding solid-liquid ratio, they are injected into a beaker containing 30mL of SBF (simulated human body fluid) using a 5mL syringe during the injectable period. The sample is then placed in a shaker at 37°C and shaken at 60rpm to observe whether the sample breaks or shatters. If there is any breakage, it means it has collapsed, and the collapse time is recorded.

[0140] Anchor mechanical performance testing: Anchor engagement was measured using osteoporotic foam blocks. The pull-out force difference between the anchors without and with bone cement was measured. After the curing period, the simulated bone blocks were fixed to the fixture of a universal testing machine, and the anchors were subjected to pull-out testing. After maintaining a preload of 1 Newton for 3 seconds, the universal testing machine applied axial tensile stress at a rate of 1 mm / min until the anchor pulled out or loosened. Pull-out strength was defined as the maximum pull-out force of the suture anchor measured by the load-displacement curve during anchor pull-out.

[0141] Table 1

[0142]

[0143] The technical features of the above-mentioned embodiments can be combined arbitrarily. In order to make the description concise, not all possible combinations of the technical features in the above-mentioned embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0144] The above-described embodiments merely represent several implementation methods of the present invention. While the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the patent. It should be noted that a person skilled in the art would be able to make various modifications and improvements without departing from the spirit of the present invention, all of which fall within the scope of protection of the present invention. Therefore, the scope of protection of the patent for this invention shall be determined by the appended claims.

Claims

1. A bone cement composite material, characterized in that: The bone cement composite material comprises: Solid phase powder, the solid phase powder comprising inorganic calcium phosphate; The curing liquid comprises a water-soluble polymer and a solvent, wherein the mass fraction of the water-soluble polymer in the curing liquid is 1%-55%, and the water-soluble polymer comprises at least one of polyacrylic acid, hydroxybutyl chitosan, and polyglutamic acid.

2. The bone cement composite material according to claim 1, characterized in that When the water-soluble polymer compound is polyacrylic acid, the mass fraction of the polyacrylic acid in the curing liquid is 35%-55%; Alternatively, when the water-soluble polymer compound is hydroxybutyl chitosan, the mass fraction of the hydroxybutyl chitosan in the solidifying liquid is 1%-5%; Alternatively, when the water-soluble polymer compound is polyglutamic acid, the mass fraction of the polyglutamic acid in the solidifying liquid is 1%-20%; Alternatively, when the water-soluble polymer compound is polyacrylic acid and polyglutamic acid, the mass fraction of the polyacrylic acid in the solidifying liquid is 15%-40%, and the mass fraction of the polyglutamic acid in the solidifying liquid is 1%-15%; Alternatively, when the water-soluble polymer compound is polyacrylic acid and hydroxybutyl chitosan, the mass fraction of the polyacrylic acid in the solidifying liquid is 30%-40%, and the mass fraction of the hydroxybutyl chitosan in the solidifying liquid is 1%-5%; Alternatively, when the water-soluble polymer compound is polyacrylic acid, polyglutamic acid and hydroxybutyl chitosan, the mass fraction of the polyacrylic acid in the solidifying liquid is 10%-30%, the mass fraction of the polyglutamic acid in the solidifying liquid is 1%-15%, and the mass fraction of the hydroxybutyl chitosan in the solidifying liquid is 1%-5%.

3. The bone cement composite material according to claim 1 or 2, characterized in that The weight average molecular weight of the polyacrylic acid is 2000-5000.

4. The bone cement composite material according to claim 1 or 2, characterized in that The weight average molecular weight of the hydroxybutyl chitosan is 50kDa-200kDa; And / or, the degree of substitution of the hydroxybutyl chitosan is 1.0-2.

0.

5. The bone cement composite material according to claim 1 or 2, characterized in that: The weight average molecular weight of the polyglutamic acid is 500 kDa-1500 kDa.

6. The bone cement composite material according to claim 1 or 2, characterized in that: The solidifying liquid further includes an additive, and the additive includes at least one of sodium polyacrylate, sodium alginate, phosphoric acid, and acetic acid.

7. The bone cement composite material according to claim 6, characterized in that: When the additive includes sodium alginate, the mass fraction of the sodium alginate in the solidifying liquid is 1%-15%.

8. The bone cement composite material according to claim 1, characterized in that The median particle size of the solid phase powder is 1 μm-200 μm.

9. The bone cement composite material according to claim 1, characterized in that The solid phase powder further comprises calcium carbonate, wherein the mass ratio of the calcium carbonate to the inorganic calcium phosphate salt is 1:9-1:

4.

10. The bone cement composite material according to claim 9, characterized in that: The molar ratio of calcium to phosphorus in the solid phase powder is 0.5:1-2:1; And / or, the inorganic calcium phosphate salt is at least one selected from α-tricalcium phosphate, β-tricalcium phosphate, tetracalcium phosphate, calcium hydrogen phosphate, and calcium dihydrogen phosphate.

11. Use of the bone cement composite material according to any one of claims 1 to 10 in preparing bone repair materials.

12. The use according to claim 11, characterized in that The solid-to-liquid ratio of the solid phase powder to the solidified liquid is 0.5 g / mL-8 g / mL.

Images