Coral hydroxyapatite and its preparation method and application

Abstract

The present invention provides a coral hydroxyapatite and its preparation method and application, wherein the coral hydroxyapatite has a pore size of 30μm-1300μm, a porosity of 50%-70%, and a conversion rate of 50% or more. The preparation method comprises: soaking the pretreated coral stone in a cutting protective agent, cutting to obtain cut coral stone, screening the cut coral stone that meets the cutting size requirements, and obtaining good cut coral stone; soaking the good cut coral stone in a phosphate solution, performing a water heat exchange reaction to obtain the coral hydroxyapatite; the cutting protective agent is a solution containing a polyol. The preparation method of the present invention can significantly improve cutting efficiency, broaden the cutting specifications and sizes, and significantly improve the product yield, especially the yield rate of small-size products, further broadening the application range of artificial bones.

Description

Technical Field

[0001] The present invention belongs to the field of medical materials, and in particular relates to coral hydroxyapatite and a preparation method and application thereof. Background Art

[0002] Coral hydroxyapatite artificial bone is a high-purity hydroxyapatite material made from natural coral. It retains the original structural properties of coral, with a porous network structure, pore sizes ranging from 100-600μm, and a porosity of 30%-70%. Under an electron microscope, this material's physical structure, crystal arrangement, and bone density closely resemble those of human bone, resulting in excellent biocompatibility and osteoconductivity. Coral hydroxyapatite artificial bone has been used clinically and demonstrated promising results, suggesting that this product holds broad application prospects.

[0003] Coral hydroxyapatite artificial bone products are mostly available in the form of bone powder (particles of varying sizes), bone strips, bone blocks, and bone flakes. However, natural corals are often irregular and large in size, and most coral hydroxyapatite artificial bone products require cutting and shaping to meet these specifications. Therefore, coral stone cutting is an essential and critical process for the preparation of coral hydroxyapatite artificial bone products. In terms of physical properties, coral stone has high hardness but is relatively fragile, making it difficult to cut. Especially when cut into small, regular shapes, coral stone is more prone to shattering, resulting in a low yield rate for coral stone products.

[0004] There are many patents on coral stone, especially the coral stone processing technology has been relatively mature. CN1055061C mainly involves a preparation method of converting natural coral into bioactive material hydroxyapatite by anion exchange reaction under hydrothermal conditions; CN1203189A mainly involves soaking coral in high-concentration phosphate solution and performing hydrothermal reaction under low and medium pressure conditions to prepare hydroxyapatite artificial bone; CN1069614C mainly introduces the chemical pore expansion technology of natural coral hydroxyapatite porous biomaterial; CN1231269C mainly prepares coral hydroxyapatite artificial bone with adjustable absorption rate. Methods for synthesizing artificial bone; CN1235645C primarily uses natural coral as material, synthesizing artificial bone through hydrothermal replacement in a diammonium hydrogen phosphate + hydrothermal system under high temperature and high pressure conditions; CN100366301C utilizes coral hydroxyapatite by immersing it in phosphoric acid, a phosphate salt, or a mixture thereof for a predetermined period of time at a certain temperature, followed by a conversion reaction by heating, to produce coral hydroxyapatite artificial bone with a surface of β-tricalcium phosphate; CN100384488C utilizes water washing, rinsing, and drying, followed by pore etching with dilute hydrochloric acid, followed by a immersion reaction in a saturated phosphate solution, to produce absorbable hydroxyapatite artificial bone, among others. Prior art focuses on the preparation of coral hydroxyapatite artificial bone, employing various processing methods but without addressing how to process natural coral stone to the desired specifications for artificial bone. The cutting process of coral stone is essential for processing, and the brittleness of coral stone makes it prone to chipping and fracture during cutting, yet this process has not been studied or reported.

[0005] In order to overcome the low cutting efficiency of existing coral stone; on the other hand, the maximum cutting size of coral stone is relatively large; thirdly, when coral hydroxyapatite is prepared into blocks, strips and other product specifications with certain shapes, it is easy to break during cutting, and the product yield is relatively low.

[0006] Therefore, it is necessary and meaningful to find a coral stone cutting protective agent and perform a pretreatment process on the coral stone to improve the yield rate of coral hydroxyapatite. Summary of the Invention

[0007] In order to solve the above technical problems, the purpose of the present invention is to provide coral hydroxyapatite and its preparation method and application.

[0008] In order to achieve the above object, the present invention provides a coral hydroxyapatite, wherein the coral hydroxyapatite has a pore size of 30 μm-1300 μm, a porosity of 50%-70%, and a conversion rate of more than 50%.

[0009] According to a specific embodiment of the present invention, the conversion rate of the coralline hydroxyapatite is above 70%.

[0010] According to a specific embodiment of the present invention, the conversion rate of the coralline hydroxyapatite is above 90%.

[0011] The pore structure of the coral hydroxyapatite of the present invention is similar to that of human cancellous bone, with pores interconnected.

[0012] The pore size of 30 μm-1300 μm mentioned in the present invention refers to the pore size distribution range.

[0013] The coral raw material of the coral hydroxyapatite product of the present invention may be natural coral stone. More preferably, the natural coral stone includes Porites coralliensis and Goniopora coralliensis.

[0014] For coral hydroxyapatite prepared from Porites as raw material, the pore size distribution range is usually 30μm-800μm; for coral hydroxyapatite prepared from Goniopora as raw material, the pore size distribution range is usually 90μm-1300μm.

[0015] The present invention also provides a method for preparing the coralline hydroxyapatite, wherein the preparation method comprises:

[0016] The pre-treated coral stone is soaked in a cutting protective agent and then cut to obtain cut coral stone, and the cut coral stone meeting the cutting size requirements is screened to obtain good cut coral stone;

[0017] The good-quality cut coral stone is fully soaked in a phosphate solution, and subjected to a water-heat exchange reaction to obtain the coral hydroxyapatite;

[0018] The cutting protection agent is a solution containing polyol.

[0019] In the above preparation method, based on the total mass of the cutting protection agent, the mass fraction of the polyol is ≥20%, preferably 30-80%, more preferably 30%-50%.

[0020] In the above preparation method, preferably, the polyol is selected from one or a combination of two or more of glycerol, ethylene glycol, sorbitol, and butylene glycol.

[0021] In the above preparation method, the soaking time of the cutting protection agent is 3-24 hours.

[0022] In the above preparation method, the pretreatment step includes:

[0023] Remove dust from the natural coral stone, soak it in sodium hypochlorite solution or hydrogen peroxide solution, clean it, and dry it for later use.

[0024] In the above preparation method, the concentration of the phosphate solution is 1-5 mol / L.

[0025] In the above preparation method, the reaction pressure of the water heat exchange is 1-3 MPa, the reaction temperature is 120-240° C., and the reaction time is 5-48 h.

[0026] In the above preparation method, the instrument used for cutting is a band saw.

[0027] In the above preparation method, preferably, the cutting speed of the cutting is 1.6-3 cm / s, preferably 1.9-2.4 cm / s.

[0028] In the above preparation method, the limit value of the cutting size is 0.1-0.5 cm, preferably 0.3-0.5 cm.

[0029] In coral stone cutting, the smaller the cutting size, the more likely it is to break. However, after being treated with the polyol cutting protective agent of the present invention, the minimum cutting size can be reduced, the yield rate of cutting small-sized products can be improved, and the integrity of the cut products can be ensured.

[0030] The cutting method of the present invention can be used to cut coral hydroxyapatite products of the following sizes: (0.1-1) cm×(0.1-1) cm×(0.1-1) cm, (1-10) cm×(1-10) cm×(1-10) cm, (5-20) cm×(5-20) cm×(5-20) cm; for example, the following sizes can be obtained: 0.1 cm×0.1 cm×0.1 cm, 0.2 cm×0.2 cm×0.2 cm, 0.1 cm×0.2 cm×0.2 cm, 0.1 cm×0.3 cm×0.3 cm, 0.1 cm×0.3 cm×0.5 cm, 0.3 cm×0.3 cm×0.5 cm, 0. .4cm×0.4cm×0.4cm, 0.4cm×0.4cm×0.5cm, 0.3cm×0.4cm×0.5cm, 0.5cm×0.5cm×0.5cm, 0.6cm×0.6cm×0.6cm, 0.7cm×0.7cm×0.7cm, 0.8cm×0.8cm ×0.8cm, 0.9cm×0.9cm×0.9cm, 1.0cm×1.0cm×1.0cm, 1.0cm×1.0cm×5.0cm, 2.0cm×2.0cm×2.0cm, 5.0cm×5.0cm×5.0cm, 10.0cm×10.0cm×10.0cm.

[0031] The coralline hydroxyapatite product of the present invention may be further cut and / or polished.

[0032] In the above preparation method, when the cutting size is ≤0.3 cm, the yield rate of the cut coral stone is 30-70%.

[0033] In the above preparation method, when the cutting size is greater than 0.3 cm, the yield rate of the cut coral stone is 30-99%.

[0034] The present invention also provides coral hydroxyapatite, which is prepared by the above preparation method.

[0035] The present invention also provides the use of the coralline hydroxyapatite in preparing products used in the field of medical materials;

[0036] According to a specific embodiment of the present invention, preferably, the product in the field of medical materials includes an artificial bone product.

[0037] According to a specific embodiment of the present invention, the method for preparing coralline hydroxyapatite comprises:

[0038] (1) The natural coral stone is ultrasonically cleaned to remove impurities and dust on the surface, then soaked in sodium hypochlorite solution or hydrogen peroxide solution, then washed with purified water, and dried for later use;

[0039] (2) soaking the coral stone in a solution containing a polyol having a concentration of not less than 20% to fully soak the coral stone for 3-24 hours;

[0040] (3) cutting and polishing the coral stone processed in step (2) to prepare it into various shapes and specifications as required, and then washing and drying it;

[0041] (4) placing the coral stone treated in step (3) in a reactor, adding 1-5 mol / L phosphate solution to fully soak it, and performing a hydrothermal reaction at a pressure of 1-3 MPa and 120-240° C. for 5-48 hours to obtain coral hydroxyapatite;

[0042] (5) The coralline hydroxyapatite obtained by the treatment in step (5) is cleaned and dried, and then packaged and irradiated for sterilization.

[0043] The present invention uses polyol to soak the coral stone, so that the coral stone is fully infiltrated and the lubricity of the coral stone is increased. In the subsequent cutting and polishing process, the coral stone is easier to cut and shape, the coral stone cutting efficiency is improved, the specifications and sizes of the coral stone artificial bone are broadened, and the yield of good coral stone artificial bone products is also improved, which can better meet the needs of bone repair. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 : are the appearance pictures of the coral stones after cutting, wherein a is the cut coral stone in Example 1, b is the cut coral stone in Comparative Example 1, c is the cut coral stone in Comparative Example 3, and d is the cut coral stone in Comparative Example 4.

[0045] Figure 2 This is a scanning electron microscope image (100×) of the coralline hydroxyapatite product in Example 1. DETAILED DESCRIPTION

[0046] In order to have a clearer understanding of the technical features, objectives and beneficial effects of the present invention, the technical solution of the present invention is now described in detail below, but it should not be understood as limiting the scope of implementation of the present invention.

[0047] In actual production, those skilled in the art will understand that some relevant process steps may be adjusted or increased or decreased, provided that qualified products can be obtained.

[0048] Example 1

[0049] Taking Porites coral as an example, the natural Porites coral stone was ultrasonically cleaned to remove impurities and powder on the surface, then soaked in 30% hydrogen peroxide solution, and then cleaned with purified water and dried;

[0050] Glycerol was mixed with water to prepare a 40% (wt) glycerol solution. The coral stone was soaked in the 40% (wt) glycerol solution to fully infiltrate the coral stone for 10 hours. The coral stone was then cut using a band saw (equipment code: JBS-260, saw blade specifications: 1710*9.5*0.35mm*14TPI). The cutting efficiency and cutting limit values ​​were compared, and the yield rate of the samples cut under the corresponding specifications was statistically analyzed. The results are shown in Table 1. The cutting of 0.5×0.5×0.5cm 3 Representative samples of specifications and sizes can be found at Figure 1 a, coral stone samples that meet the specified size are placed in a reactor, 3 mol / L diammonium hydrogen phosphate solution is added, and the reaction is carried out at 180 ° C for 24 hours, followed by washing, drying, packaging, and sterilization to obtain coral hydroxyapatite. The pore size is shown in Table 1, and the scanning electron microscope image is shown in Figure 2 The pore size distribution range is 30 μm-800 μm. According to the test, the conversion rate of the coralline hydroxyapatite product prepared in this embodiment is about 61.7%.

[0051] Example 2

[0052] Goniopora is a large-pore coral that is more prone to breaking when cut. Taking Goniopora as an example, natural Goniopora stone is ultrasonically cleaned to remove impurities and powder on the surface, then soaked in 30% hydrogen peroxide solution, rinsed with purified water, and dried.

[0053] Coralite was soaked in a 30% (wt) glycerol solution for 4 hours to ensure full infiltration. The coralite was then cut using a band saw (equipment code: JBS-260, blade specifications: 1710*9.5*0.35mm*14TPI). Cutting efficiency, cutting limits, and yield rates of samples cut to the corresponding specifications were compared (Table 1). Coralite samples meeting the specified dimensions were placed in a reactor, and a 3 mol / L diammonium hydrogen phosphate solution was added. The reaction was carried out at 180°C for 24 hours, followed by washing, drying, packaging, and sterilization. Coralite hydroxyapatite was obtained. The pore size distribution ranged from 90 μm to 1300 μm, as shown in Table 1. Testing revealed a conversion rate of approximately 66.3%.

[0054] Comparative Example 1

[0055] Taking Porites coral as an example, the natural Porites coral stone was ultrasonically cleaned to remove impurities and powder on the surface, then soaked in 30% hydrogen peroxide solution, and then cleaned with purified water and dried;

[0056] The coral stones were cut by band saw (equipment code: JBS-260, saw blade specification: 1710*9.5*0.35mm*14TPI), and the cutting efficiency, cutting limit value and yield rate of the samples under the corresponding specifications were compared. The results are shown in Table 1. 3 Representative samples of specifications and sizes can be found at Figure 1 b. Coralite samples meeting the specified size were placed in a reactor, 3 mol / L diammonium hydrogen phosphate solution was added, and the reaction was carried out at 180°C for 24 h. The samples were then cleaned, dried, packaged, and sterilized to obtain coralline hydroxyapatite. The pore sizes are shown in Table 1.

[0057] Comparative Example 2

[0058] Goniopora is a large-pore coral that is more prone to breaking when cut. Taking Goniopora as an example, natural Goniopora stone is ultrasonically cleaned to remove impurities and powder on the surface, then soaked in 30% hydrogen peroxide solution, rinsed with purified water, and dried.

[0059] The coral stones were cut using a band saw (equipment code: JBS-260, blade specifications: 1710*9.5*0.35mm*14TPI). The cutting efficiency, cutting limits, and yield rate of samples cut under the corresponding specifications were compared and statistically analyzed. The results are shown in Table 1. Coral stone samples meeting the specified size were placed in a reactor, and a 3 mol / L diammonium hydrogen phosphate solution was added. The reaction was carried out at 180°C for 24 hours. The samples were then cleaned, dried, packaged, and sterilized to obtain coralline hydroxyapatite. The pore sizes are shown in Table 1.

[0060] Comparative Example 3

[0061] Taking Porites coral as an example, the natural Porites coral stone was ultrasonically cleaned to remove impurities and powder on the surface, then soaked in 30% hydrogen peroxide solution, and then cleaned with purified water and dried;

[0062] The coral stone was soaked in 5% (wt) glycerol solution to make it fully infiltrated for 15 hours, and then cut with a band saw (equipment code: JBS-260, saw blade specifications: 1710*9.5*0.35mm*14TPI). The cutting efficiency, cutting limit value, and yield rate of the samples under the corresponding specifications were compared. The results are shown in Table 1. The cutting of 0.5×0.5×0.5cm 3 Representative samples of specifications and sizes can be found at Figure 1 Coralite samples meeting the specified size were placed in a reactor, 3 mol / L diammonium hydrogen phosphate solution was added, and the reaction was carried out at 180°C for 24 h. The samples were then cleaned, dried, packaged, and sterilized to obtain coralline hydroxyapatite. The pore sizes are shown in Table 1.

[0063] Comparative Example 4

[0064] Taking Porites coral as an example, the natural Porites coral stone was ultrasonically cleaned to remove impurities and powder on the surface, then soaked in 30% hydrogen peroxide solution, and then cleaned with purified water and dried;

[0065] Carboxymethyl cellulose (polysaccharide) was dissolved in water to prepare a 0.06% (wt) carboxymethyl cellulose solution. The coral stone was soaked in the 0.06% (wt) carboxymethyl cellulose solution to fully infiltrate the coral stone for 24 hours. The coral stone was then cut using a band saw (equipment code: JBS-260, saw blade specifications: 1710*9.5*0.35mm*14TPI). The cutting efficiency, cutting limit value, and yield rate of the samples cut under the corresponding specifications were compared. The results are shown in Table 1. 3 Representative samples of specifications and sizes can be found at Figure 1 Coralite samples meeting the specified size were placed in a reactor, 3 mol / L diammonium hydrogen phosphate solution was added, and the reaction was carried out at 180°C for 24 h. The samples were then cleaned, dried, packaged, and sterilized to obtain coralline hydroxyapatite. The pore sizes are shown in Table 1.

[0066] Table 1 Statistics of cutting results of different coral stones after different treatments

[0067]

[0068] Note: Good quality refers to coral samples cut to specifications consistent with established specifications, with an error of no more than ±1mm. Good quality rate = number of good quality coral samples cut / total number of coral samples cut × 100%. Subsequent processing after cutting has little effect on the size and appearance of the coral samples, so the good quality rate here represents the good quality rate of coral hydroxyapatite (artificial bone).

[0069] By comparison, it can be seen that when coral stone is not added with cutting protective agent or with polysaccharide substances (non-polyol protective agent) or the concentration of protective agent is too low, it is easy to break and fracture during cutting, and the cutting surface is uneven. Figure 1 b- Figure 1 The cutting speed does not exceed 1.5cm / s (this cutting speed is based on the cutting limit size, and it is almost impossible to obtain a good product if it exceeds the limit), and the cutting limit value is 0.5-1.0cm. After adding cutting protective agents and pre-treatment, the coral stone is relatively difficult to break during cutting, the cutting speed is 1.9-2.4cm / s, the cutting limit value is 0.3-0.5cm, and a good cutting morphology can be formed. Figure 1 a in .

[0070] For coral stone treated in different groups, the yield rate of products of the same specification increases with increasing product size. Adding a certain concentration of a polyol-based cutting protective agent and pretreatment significantly improves the yield rate compared to pretreatment without the addition of a protective agent. This is particularly advantageous when cutting small-sized products. After cutting, the coral stone undergoes multiple cleaning processes, and since polyols are readily soluble in water, the final coral hydroxyapatite product is tested to be free of residual protective agent. The preparation method of the present invention achieves a conversion rate of over 50% for coral hydroxyapatite of the desired size, achieving the desired degradation rate suitable for use as artificial bone.

[0071] In summary, adding a specific cutting protection agent at a certain concentration and performing pretreatment can significantly improve cutting efficiency, expand the size of cuts, and significantly increase product yield, especially for small-sized products. Therefore, this invention has great significance for the treatment of corallite and further broadens the application range of artificial bone.

Claims

1. A method for preparing coralline hydroxyapatite, wherein: The preparation method comprises: The pre-treated coral stone is soaked in a cutting protective agent and then cut to obtain cut coral stone, and the cut coral stone meeting the cutting size requirements is screened to obtain good cut coral stone; The good-quality cut coral stone is fully soaked in a phosphate solution, and subjected to a water-heat exchange reaction to obtain the coral hydroxyapatite; The cutting protection agent is a glycerol solution prepared by mixing glycerol and water; Based on the total mass of the cutting protective agent, the mass fraction of the glycerol is ≥20%.

2. The preparation method according to claim 1, wherein The soaking time of the cutting protection agent is 3-24 hours.

3. The preparation method according to claim 1, wherein The pre-processing steps include: Remove dust from the coral stone, soak it in sodium hypochlorite solution or hydrogen peroxide solution, clean it, and dry it for later use.

4. The preparation method according to claim 1, wherein The concentration of the phosphate solution is 1-5 mol / L.

5. The preparation method according to claim 1, wherein The reaction pressure of the water heat exchange is 1-3 MPa, the reaction temperature is 120-240° C., and the reaction time is 5-48 hours.

6. The preparation method according to claim 1, wherein The instrument used for the cutting is a band saw.

7. The preparation method according to claim 1, wherein The cutting speed of the cutting is 1.6-3 cm / s.

8. The preparation method according to claim 7, wherein The cutting speed of the cutting is 1.9-2.4 cm / s.

9. The preparation method according to claim 1, wherein The limit value of the cutting size is 0.1-0.5 cm.

10. The preparation method according to claim 9, wherein The limit value of the cutting size is 0.3-0.5 cm.

11. The preparation method according to any one of claims 1, 9 or 10, wherein When the cutting size is ≤0.3 cm, the yield rate of cut coral stone is 30-70%.

12. The preparation method according to any one of claims 1, 9 or 10, wherein When the cutting size is greater than 0.3 cm, the yield rate of the cut coral stone is 30-99%.

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