Catechol compound calcium phosphate bone adhesive with high shear strength and free radical scavenging capacity
The bone adhesive prepared by solidifying catechol compounds with calcium phosphate and protein phosphorylation products solves the problems of low shear strength and insufficient free radical scavenging ability of calcium phosphate-based bone adhesives, achieving high shear strength and efficient free radical scavenging.
Patent Information
- Application Number
- CN202511503103.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-10-21
- Publication Date
- 2025-12-26
AI Technical Summary
Existing calcium phosphate-based bone adhesives have low shear strength and lack free radical scavenging capabilities.
A catechol compound/calcium phosphate bone adhesive was prepared by curing catechol compounds with calcium phosphate and protein phosphorylation products. The catechol compounds have free radical scavenging ability, and the shear strength of the adhesive can be improved by adjusting their ratio and curing reaction.
The prepared catechol compounds/calcium phosphate bone binder showed significantly improved shear strength, reaching 8.3 MPa, and also exhibited highly efficient free radical scavenging ability, with a scavenging rate of up to 95%.
Smart Images
Figure CN121197486A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to an adhesive and its preparation method, belonging to the technical field of calcium phosphate-based bone adhesives. Background Technology
[0002] Calcium phosphate bone adhesives exhibit good biocompatibility, osteoconductivity, and bone adhesion. Calcium phosphate bone adhesives made from tetracalcium phosphate and phosphoserine have a shear strength approaching 2.00 MPa (Liu CY, et al. Adv. Healthcare Mater, (2024) 13:2401687). However, the adhesive strength of calcium phosphate bone adhesives remains low, and they lack free radical scavenging ability. To improve the shear strength of calcium phosphate bone adhesives, polylactic acid-glycolic acid copolymer (PLGA) fibers were added, resulting in a shear strength of 3.5 MPa for the calcium phosphate / PLGA composite bone adhesive (Alina, K, et al. Adv. Healthcare Mater, (2018) 7:1800467). The addition of polyacrylic acid (PAA) resulted in a shear strength of 2.7 MPa for the calcium phosphate / polyacrylic acid composite bone adhesive (Zheng PP, et al. Journal of Materials Chemistry B, (2024) 12:8321). While PLGA fibers and PAA improved the shear strength of calcium phosphate-based bone adhesives (75% and 35%, respectively), they did not impart free radical scavenging ability. Therefore, the shear strength of calcium phosphate-based bone adhesives remained below 3.5 MPa and lacked free radical scavenging capacity. To improve the shear strength and impart free radical scavenging ability to calcium phosphate-based bone adhesives, this invention proposes for the first time the introduction of catecholaryngol compounds with free radical scavenging ability into calcium phosphate bone adhesives, preparing catecholaryngol compound / calcium phosphate bone adhesives with high shear strength and free radical scavenging ability. The catecholaryngol compounds not only improved the shear properties of the calcium phosphate bone adhesive but also endowed it with free radical scavenging ability.
[0003] Patent publication number 118453942A, filed on May 11, 2024, discloses a bone adhesive for promoting fracture healing, its preparation method, and its application. The raw materials for its preparation include: component A and a liquid phase composition; the liquid phase composition comprises a polymer and a liquid phase component; component A comprises calcium phosphate compounds, phosphoserine compounds, phenolic compounds, and magnesium ion compounds. The bone adhesive for promoting fracture healing provided by this invention exhibits strong adhesion to both hard bone and soft tissue. However, this bone adhesive suffers from low shear strength (3.5 MPa) and a lack of organic free radical scavenging ability. Summary of the Invention
[0004] To address the problems of low shear strength (3.5 MPa) and lack of free radical scavenging ability in existing calcium phosphate-based bone adhesives, this invention proposes a catechol compound / calcium phosphate bone adhesive and its preparation method.
[0005] The technical solution adopted by the present invention to solve the above problems is as follows: The catechin compound / calcium phosphate bone binder of the present invention includes calcium phosphate, protein phosphorylation products and catechin compounds with free radical scavenging ability, wherein the content of catechin compounds with free radical scavenging ability is 0.2~9.8wt%.
[0006] Furthermore, the calcium phosphate is one or more of α-tricalcium phosphate, hydroxyapatite, tetracalcium phosphate, and calcium hydrogen phosphate.
[0007] Furthermore, the protein phosphorylation product is one or more of phosphothreonine, phosphoserine, and phosphotyrosine.
[0008] The present invention discloses a method for preparing a catechol compound / calcium phosphate bone binder, wherein the catechol compound / calcium phosphate bone binder is prepared by a curing reaction of calcium phosphate, protein phosphorylation products and catechol compounds with free radical scavenging ability.
[0009] Furthermore, catechol compounds with free radical scavenging capabilities are used as curing agents to produce a curing reaction dependent on the phosphate solubility product constant with calcium phosphate and protein phosphorylation products.
[0010] Furthermore, the curing liquid is one or more of the following: caffeic acid aqueous solution, delphinidin aqueous solution, ferulic acid aqueous solution, levodopa aqueous solution, resveratrol aqueous solution, catechol aqueous solution, and gallic acid aqueous solution.
[0011] Furthermore, the curing liquid is subjected to a curing reaction with calcium phosphate and protein phosphorylation products at a solid-liquid ratio of 0.05~1.05 mL / g.
[0012] Furthermore, the curing solution is an aqueous solution of catechol compounds.
[0013] The beneficial effects of this invention are: 1. Compared with the shear strength of calcium phosphate bone adhesive, the shear strength of the catechol compound / calcium phosphate bone adhesive prepared in this invention, which has high shear strength and free radical scavenging ability, reaches 8.3 MPa. By adjusting the ratio of catechol compound (with free radical scavenging ability) to calcium phosphate and protein phosphorylation products, a catechol compound / calcium phosphate composite bone adhesive with both high shear strength and free radical scavenging ability is prepared by using a curing reaction. 2. Compared with the shear strength (2 MPa) of calcium phosphate bone adhesive prepared by existing technology, the shear strength of the catechol compound / calcium phosphate bone adhesive prepared by the present invention with high shear strength and free radical scavenging ability is increased by 3.15 times; 3. Compared with the shear strength of calcium phosphate / polyacrylic acid composite bone adhesive (2.7 MPa) and calcium phosphate / polylactic acid-glycolic acid copolymer composite bone adhesive (3.5 MPa) prepared by existing technologies, the shear strength of the catechol compound / calcium phosphate bone adhesive prepared in this invention is increased by 1.97 times and 1.29 times, respectively. 4. The catechol compounds with free radical scavenging ability in this invention enable the catechol compounds / calcium phosphate bone binder to scavenge free radicals, wherein the catechol / calcium phosphate bone binder has a DPPH scavenging rate of 95%. Attached Figure Description
[0014] Figure 1 This is a schematic diagram illustrating the shear strength of calcium phosphate bone adhesive and caffeic acid / calcium phosphate bone adhesive in the embodiments; Figure 2 This is a schematic diagram showing the shear strength of the levodopa / calcium phosphate bone adhesive in the embodiment and the calcium phosphate-based bone adhesive prepared by the prior art; Figure 3 This is a schematic diagram illustrating the effect of the impregnation time of the catechol / calcium phosphate bone adhesive on the DPPH removal rate in the examples. Detailed Implementation
[0015] Example 1 Deionized water solution was uniformly mixed with calcium phosphate and protein phosphorylation products to form a paste. The paste was pre-cured for 30 seconds and then placed in an incubator at 37°C and 100% humidity for 24 hours to cure, thus preparing calcium phosphate bone adhesive.
[0016] Example 2 A catechol compound with free radical scavenging ability (1 wt%) was uniformly mixed with calcium phosphate and protein phosphorylation products. The catechol compound solution was used as a curing agent and uniformly mixed with the calcium phosphate and protein phosphorylation products prepared in this embodiment at a liquid-to-solid ratio of 0.25 mL / g to form a paste. The paste was pre-cured for 30 s, then placed in an incubator at 37°C and 100% humidity for 24 h to prepare the catechol compound / calcium phosphate bone binder. When the catechol compound content was 1 wt%, the shear strength of the catechol compound / calcium phosphate bone binder reached 3.5–5.5 MPa. Compared with calcium phosphate bone binder, the shear strength of the catechol compound / calcium phosphate bone binder was increased by 88.7–175%.
[0017] Example 3 A 2 wt% catechol compound with free radical scavenging ability was uniformly mixed with calcium phosphate and protein phosphorylation products. The catechol compound solution was used as a curing agent and mixed uniformly with the calcium phosphate and protein phosphorylation products prepared in this embodiment at a liquid-to-solid ratio of 0.25 mL / g to form a paste. The paste was pre-cured for 30 seconds and then placed in an incubator at 37°C and 100% humidity for 24 hours to prepare a catechol compound / calcium phosphate bone binder. When the catechol compound content was 2 wt%, the shear strength of the catechol compound / calcium phosphate bone binder reached 4.5–6.5 MPa. Compared with calcium phosphate bone binder, the shear strength of the catechol compound / calcium phosphate bone binder was increased by 153.2–210%.
[0018] Example 4 A 3 wt% catechol compound with free radical scavenging ability was uniformly mixed with calcium phosphate and protein phosphorylation products. The catechol compound solution was used as a curing agent and mixed uniformly with the calcium phosphate and protein phosphorylation products prepared in this embodiment at a liquid-to-solid ratio of 0.25 mL / g to form a paste. The paste was pre-cured for 30 seconds and then placed in an incubator at 37°C and 100% humidity for 24 hours to prepare the catechol compound / calcium phosphate bone binder. When the catechol compound content was 3 wt%, the shear strength of the catechol compound / calcium phosphate bone binder reached 5.0–8.5 MPa. Compared with calcium phosphate bone binder, the shear strength of the catechol compound / calcium phosphate bone binder was increased by 174.2–304.2%.
[0019] Example 5 A catechol compound with free radical scavenging ability (4 wt%) was uniformly mixed with calcium phosphate and protein phosphorylation products. The catechol compound solution was used as a curing agent and mixed uniformly with the calcium phosphate and protein phosphorylation products prepared in this embodiment at a liquid-to-solid ratio of 0.25 mL / g to form a paste. The paste was pre-cured for 30 s, then placed in an incubator at 37°C and 100% humidity for 24 h to prepare the catechol compound / calcium phosphate bone binder. When the catechol compound content was 4 wt%, the shear strength of the catechol compound / calcium phosphate bone binder reached 5–6.5 MPa. Compared with calcium phosphate bone binder, the shear strength of the catechol compound / calcium phosphate bone binder was increased by 171–214.3%.
[0020] Example 6 A 5 wt% catechol compound with free radical scavenging ability was uniformly mixed with calcium phosphate and protein phosphorylation products. The catechol compound solution was used as a curing agent and mixed uniformly with the calcium phosphate and protein phosphorylation products prepared in this embodiment at a liquid-to-solid ratio of 0.25 mL / g to form a paste. The paste was pre-cured for 30 seconds and then placed in an incubator at 37°C and 100% humidity for 24 hours to prepare a catechol compound / calcium phosphate bone binder. When the catechol compound content was 4 wt%, the shear strength of the catechol compound / calcium phosphate bone binder reached 3.5–6.0 MPa. Compared with calcium phosphate bone binder, the shear strength of the catechol compound / calcium phosphate bone binder was increased by 83.7–195.3%.
[0021] Example 7 Catechol compounds / bone binders with free radical scavenging capabilities were prepared into thin sheets with a thickness of approximately 0.25 mm. A certain amount of these sheets was immersed in 3 ml of deionized water and incubated for 1 hour in an incubator at 37°C and 100% humidity. The supernatant was then mixed with DPPH solution, and the free radical scavenging rate was measured and calculated using a UV spectrophotometer.
[0022] The supernatant prepared in this embodiment, which was soaked for 1 h with catechol compounds that have free radical scavenging ability, achieved a 97.1% scavenging effect on DPPH free radicals.
[0023] Example 8 Catechol compounds / bone binders with free radical scavenging capabilities were prepared into thin sheets approximately 0.25 mm thick. A certain amount of these sheets was immersed in 3 ml of deionized water and incubated for 3 hours at 37°C and 100% humidity. The supernatant was then mixed with DPPH solution, and the free radical scavenging rate was measured and calculated using a UV spectrophotometer.
[0024] The supernatant prepared in this embodiment, which was soaked for 3 hours with catechol compounds that have free radical scavenging ability, achieved a 95.6% scavenging effect on DPPH free radicals.
[0025] Example 9 Catechol compounds / bone binders with free radical scavenging capabilities were prepared into thin sheets approximately 0.25 mm thick. A certain amount of these sheets was immersed in 3 ml of deionized water and incubated for 6 hours at 37°C and 100% humidity. The supernatant was then mixed with DPPH solution, and the free radical scavenging rate was measured and calculated using a UV spectrophotometer. The supernatant prepared in this embodiment, which was soaked for 6 h with catechol compounds that have free radical scavenging ability, achieved a 94.8% scavenging effect on DPPH free radicals.
[0026] Example 10 Catechol compounds / bone binders with free radical scavenging capabilities were prepared into thin sheets with a thickness of approximately 0.25 mm. A certain amount of these sheets was immersed in 3 ml of deionized water and incubated in an incubator at 37°C and 100% humidity for 12 h. The supernatant was then mixed with DPPH solution, and the free radical scavenging rate was measured and calculated using a UV spectrophotometer. The supernatant prepared in this embodiment, which was soaked for 12 h with catechol compounds that have free radical scavenging ability, achieved a 95.9% scavenging effect on DPPH free radicals.
[0027] Example 11 Catechol compounds / bone binders with free radical scavenging capabilities were prepared into thin sheets with a thickness of approximately 0.25 mm. A certain amount of these sheets was immersed in 3 ml of deionized water and incubated in an incubator at 37°C and 100% humidity for 24 h. The supernatant was then mixed with DPPH solution, and the free radical scavenging rate was measured and calculated using a UV spectrophotometer. The supernatant prepared in this embodiment, which was soaked for 24 h with catechol compounds that have free radical scavenging ability, achieved a 91.1% scavenging effect on DPPH free radicals.
[0028] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent substitutions, and improvements made to the above embodiments without departing from the scope of the present invention, based on the technical essence of the present invention and within the spirit and principles of the present invention, shall still fall within the protection scope of the present invention.
Claims
1. A catechol compound / calcium phosphate bone adhesive, characterized by, The composition comprises calcium phosphate, protein phosphorylation product, and catechol compound having DPPH radical scavenging ability, wherein the content of catechol compound having DPPH radical scavenging ability is 0.2-9.8 wt%.
2. The catechol compound / calcium phosphate bone adhesive according to claim 1, wherein The calcium phosphate is one or more of α-tricalcium phosphate, hydroxyapatite, tetracalcium phosphate, and calcium hydrogen phosphate.
3. The catechol compound / calcium phosphate bone adhesive according to claim 1, wherein The protein phosphorylation product is one or more of phosphothreonine, phosphoserine, and phosphotyrosine.
4. A method for preparing a catechol compound / calcium phosphate bone adhesive, characterized by, The catechol compound / calcium phosphate bone adhesive is prepared by a curing reaction of calcium phosphate, protein phosphorylation product, and catechol compound having DPPH radical scavenging ability.
5. The method of claim 4, wherein the catechol compound / calcium phosphate bone adhesive is prepared by the steps of: (a) mixing a catechol compound and a calcium phosphate compound; (b) adding a solvent to the mixture; and (c) drying the mixture. The catechol compound having DPPH radical scavenging ability as a curing liquid produces a curing reaction with calcium phosphate and protein phosphorylation product in a phosphate solubility product constant-dependent manner.
6. The method of claim 5, wherein the catechol compound / calcium phosphate bone adhesive is prepared by the steps of: (a) mixing a catechol compound and a calcium phosphate compound; (b) adding a solvent to the mixture; and (c) drying the mixture. The curing liquid is one or more of caffeic acid aqueous solution, cianidanol aqueous solution, ferulic acid aqueous solution, levodopa aqueous solution, resveratrol aqueous solution, catechol aqueous solution, and gallic acid aqueous solution.
7. The method of claim 5, wherein the catechol compound / calcium phosphate bone adhesive is prepared by the steps of: (a) mixing a catechol compound and a calcium phosphate compound; (b) adding a solvent to the mixture; and (c) drying the mixture. The curing liquid is subjected to a curing reaction with calcium phosphate and protein phosphorylation product at a ratio of 0.05-1.05 mL / g.
8. The method of claim 5, wherein the catechol compound / calcium phosphate bone adhesive is prepared by the steps of: (a) mixing a catechol compound and a calcium phosphate compound; (b) adding a solvent to the mixture; and (c) drying the mixture. The curing liquid is catechol compound aqueous solution.