Coral hydroxyapatite as well as preparation method and application thereof

Abstract

The invention provides coral hydroxyapatite as well as a preparation method and application thereof, the aperture of the coral hydroxyapatite is 30-1300 microns, the porosity is 50-70%, and the conversion rate is more than 50%. The preparation method comprises the following steps: soaking pretreated corallite in a cutting protective agent, cutting to obtain cut corallite, and screening the cut corallite meeting the cutting size requirement to obtain a cut corallite good product; and fully soaking the cut corallite good product with a phosphate solution, and carrying out a water heat exchange reaction to obtain the coral hydroxyapatite, the cutting protective agent is a solution containing polyol. According to the preparation method disclosed by the invention, the cutting efficiency can be obviously improved, the cutting specification and dimension can be widened, the product yield, particularly the yield of small-specification and dimension products, can be obviously improved, and the application range of the artificial bone is further widened.

Description

Technical Field

[0001] The 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 characteristics of coral and has a porous mesh structure with a pore size between 100-600μm and a porosity of 30%-70%. The physical structure, crystal arrangement and bone density of this material under an electron microscope are very similar to those of human bones, so it has good biocompatibility and osteoconductivity. Coral hydroxyapatite artificial bone has been used clinically and has shown good results, so coral hydroxyapatite artificial bone products have broad application prospects.

[0003] The specifications of coral hydroxyapatite artificial bone products are mostly bone powder (particles of different sizes), bone strips, bone blocks and bone slices, etc., while natural corals are mostly irregular and large in size. Most specifications of coral hydroxyapatite artificial bone products must be obtained through cutting and shaping. Therefore, the cutting of coral stone is an essential and key process for the preparation of coral hydroxyapatite artificial bone products. In terms of physical properties, coral stone has high hardness, but is relatively fragile, and there is a certain degree of difficulty in cutting, especially when it is cut into small regular shapes, coral stone is more likely to break, so the yield of coral stone products is low.

[0004] There are many patents about coral stone, especially the processing technology of coral stone has been relatively mature. CN1055061C mainly involves a preparation method of using natural coral to carry out anion exchange reaction under hydrothermal conditions to convert it into bioactive material hydroxyapatite; CN1203189A mainly involves soaking coral in high-concentration phosphate solution and carrying out 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 biomaterials; CN1231269C mainly introduces the preparation of coral hydroxyapatite artificial bone with adjustable absorption rate. The method of preparing artificial bone; CN1235645C mainly uses natural coral as material, and performs hydrothermal replacement in diammonium hydrogen phosphate + hydrothermal system under high temperature and high pressure conditions to synthesize artificial bone; CN100366301C adopts a method of soaking coral hydroxyapatite in phosphoric acid, phosphate or their mixed solution for a certain time at a certain temperature, and then heating for conversion reaction to prepare coral hydroxyapatite artificial bone with β-type tricalcium phosphate on the surface; CN100384488C etches its pores with dilute hydrochloric acid after washing, rinsing and drying, and then soaks and reacts with saturated phosphate solution to prepare absorbable hydroxyapatite artificial bone, etc. The existing technology focuses on the preparation method of coral hydroxyapatite artificial bone, changes different processing methods, and does not mention how to process natural coral stone into the required specifications of artificial bone. The cutting process of coral stone is an essential process for coral stone processing, and the brittleness of coral stone determines that coral stone is prone to breakage during cutting, but there is no research and report.

[0005] In order to overcome the low efficiency of existing coral stone when cutting; 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 yield of the product 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 a coral hydroxyapatite and a preparation method and application thereof.

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

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

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

[0011] The pore structure of the coral hydroxyapatite of the present invention is similar to that of human cancellous bone, and the pores are 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 coral hydroxyapatite, wherein the preparation method comprises:

[0016] The pretreated coral stone is soaked in a cutting protective agent, and then cut to obtain cut coral stone, and the cut coral stone that meets 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 a water-heat exchange reaction is performed 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%, and 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 butanediol.

[0021] In the above preparation method, the cutting protection agent is immersed for 3-24 hours.

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

[0023] Remove dust from the natural coral stone, soak and clean it with sodium hypochlorite solution or hydrogen peroxide solution, 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 easier it is to break. After being treated with the polyol cutting protective agent of the present invention, the minimum value of the cutting size can be reduced, the yield rate of cutting small size 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, 0.5 ...1 cm×0.1 cm×0.1 cm .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 coral 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 artificial bone products.

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

[0038] (1) The natural coral stone is ultrasonically cleaned to remove impurities, dust, etc. on the surface, then soaked in a sodium hypochlorite solution or a hydrogen peroxide solution, then cleaned 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 grinding 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 reaction kettle, 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 coral hydroxyapatite obtained through the treatment in step (5) is cleaned and dried, and then packaged and sterilized by irradiation.

[0043] The present invention uses polyol to soak the coral stone, so that the coral stone is fully infiltrated, the lubricity of the coral stone is increased, and in the subsequent cutting and grinding process, the coral stone is easier to cut and shape, the coral stone cutting efficiency is improved, the specification size of the coral stone artificial bone is 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 coral hydroxyapatite product in Example 1. DETAILED DESCRIPTION

[0046] In order to have a clearer understanding of the technical features, purposes 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 construed as limiting the applicable scope 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 as an example, the natural Porites stone is ultrasonically cleaned to remove impurities and powder on the surface, then soaked in 30% hydrogen peroxide solution, 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 soak the coral stone for 10 hours. Then it was cut with a band saw (equipment code: JBS-260, saw blade specification: 1710*9.5*0.35mm*14TPI). The cutting efficiency and cutting limit were compared. The yield rate of the samples cut under the corresponding specifications was statistically analyzed. The results are shown in Table 1. The cutting efficiency of 0.5×0.5×0.5cm 3 For representative samples of specifications and dimensions, see Figure 1 a, place a coral stone sample of the specified size in a reactor, add 3 mol / L diammonium hydrogen phosphate solution, react at 180°C for 24 h, then wash, dry, package and sterilize to obtain coral hydroxyapatite, the pore size of which 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 coral hydroxyapatite product prepared in this embodiment is about 61.7%.

[0051] Example 2

[0052] Goniopora is a large-pore coral that is more likely to break 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, then cleaned with purified water and dried;

[0053] The coral stone was soaked in 30% (wt) glycerol solution to fully infiltrate the coral stone. The soaking time was 4 hours. The coral stone was cut with a band saw (equipment code: JBS-260, saw blade specification: 1710*9.5*0.35mm*14TPI), and the cutting efficiency, cutting limit value, and the yield rate of the cut samples under the corresponding specifications were compared. The results are shown in Table 1. The 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, and then washed, dried, packaged, and sterilized to obtain coral hydroxyapatite. The pore size is shown in Table 1, and the pore size distribution range is 90μm-1300μm. After testing, the conversion rate is about 66.3%.

[0054] Comparative Example 1

[0055] Taking Porites as an example, the natural Porites stone is ultrasonically cleaned to remove impurities and powder on the surface, then soaked in 30% hydrogen peroxide solution, 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 cut under the corresponding specifications were compared. The results are shown in Table 1. 3 For representative samples of specifications and dimensions, see Figure 1 b. Place the coral stone sample of the specified size in a reactor, add 3 mol / L diammonium hydrogen phosphate solution, react at 180°C for 24 hours, then wash, dry, package and sterilize to obtain coral hydroxyapatite, the pore size of which is shown in Table 1.

[0057] Comparative Example 2

[0058] Goniopora is a large-pore coral that is more likely to break 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, then cleaned with purified water and dried;

[0059] The coral stones were cut by band saws (equipment code: JBS-260, saw blade specifications: 1710*9.5*0.35mm*14TPI), and the cutting efficiency, cutting limit value, and yield rate of the cut samples under the corresponding specifications were compared, and the results are shown in Table 1. The 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, and then washed, dried, packaged, and sterilized to obtain coral hydroxyapatite, the pore size of which is shown in Table 1.

[0060] Comparative Example 3

[0061] Taking Porites as an example, the natural Porites stone is ultrasonically cleaned to remove impurities and powder on the surface, then soaked in 30% hydrogen peroxide solution, 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 specification: 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. The cutting 0.5×0.5×0.5cm 3 For representative samples of specifications and dimensions, see Figure 1 c. The coral stone sample meeting the specified size was 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, followed by washing, drying, packaging, and sterilization to obtain coral hydroxyapatite, the pore size of which is shown in Table 1.

[0063] Comparative Example 4

[0064] Taking Porites as an example, the natural Porites stone is ultrasonically cleaned to remove impurities and powder on the surface, then soaked in 30% hydrogen peroxide solution, 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 with a band saw (equipment code: JBS-260, saw blade specification: 1710*9.5*0.35mm*14TPI). The cutting efficiency, cutting limit value, and the yield rate of the cut samples under the corresponding specifications were compared. The results are shown in Table 1. 3 For representative samples of specifications and dimensions, see Figure 1 The coral stone sample meeting the specified size was 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, followed by washing, drying, packaging, and sterilization to obtain coral hydroxyapatite, the pore size of which is 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 the cut coral stone samples whose specifications and dimensions are consistent with the established requirements and the error does not exceed ±1mm. Good quality rate = the number of good quality cut coral stones / the total number of cut coral stone samples × 100%. The size and appearance of the coral stone samples are not greatly affected in the subsequent processing after cutting, so the good quality rate here represents the good quality rate of coral hydroxyapatite (artificial bone).

[0069] By comparison, it can be seen that coral stone is easy to break and fracture during cutting without adding cutting protective agent or adding polysaccharide substances (non-polyol protective agent) or the concentration of protective agent is too low, 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 get a good product if it exceeds the limit size), and the cutting limit value is 0.5-1.0cm. After adding the cutting protection agent 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] In the different treatment groups of coral stone, for the product yield rate under the same specification, as the product size increases, the product yield rate will also increase. After adding a certain concentration of polyol cutting protective agent and pretreatment, the product yield rate will be significantly improved compared with when no protective agent is added. Especially when cutting small-sized products, adding a certain concentration of polyol cutting protective agent and pretreatment has great advantages. After the coral stone is cut, it undergoes multiple cleaning processes, and polyols are easily soluble in water. The coral hydroxyapatite final product has no protective agent residue after testing. The conversion rate of the coral hydroxyapatite of the required specification size obtained by the preparation method of the present invention is more than 50%, so that it is suitable for its application performance as artificial bone and achieves the required degradation rate.

[0071] In summary, by adding a certain concentration of a specific cutting protective agent and performing pretreatment, the cutting efficiency can be significantly improved, the cutting specifications can be widened, and the product yield rate can be significantly improved, especially the yield rate of small-size products. Therefore, the present invention has great significance for the treatment of coral stone and further broadens the application range of artificial bones.

Claims

1. 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%.

2. A method for preparing coralline hydroxyapatite according to claim 1, wherein: The preparation method comprises: The pretreated coral stone is soaked in a cutting protective agent, and then cut to obtain cut coral stone, and the cut coral stone that meets 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 a water-heat exchange reaction is performed to obtain the coral hydroxyapatite; The cutting protection agent is a solution containing polyol.

3. The preparation method according to claim 2, wherein Based on the total mass of the cutting protection agent, the mass fraction of the polyol is ≥20%; Preferably, the polyol is selected from one or a combination of two or more of glycerol, ethylene glycol, sorbitol, and butanediol; Preferably, the cutting protection agent is soaked for 3-24 hours.

4. The preparation method according to claim 2, wherein The pre-processing steps include: Remove dust from the coral stone, soak and clean it with sodium hypochlorite solution or hydrogen peroxide solution, and dry it for later use.

5. The preparation method according to claim 2, wherein: The concentration of the phosphate solution is 1-5 mol / L; Preferably, 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.

6. The preparation method according to claim 2, wherein: The instrument used for cutting is a band saw; Preferably, the cutting speed of the cutting is 1.6-3 cm / s, preferably 1.9-2.4 cm / s.

7. The preparation method according to claim 2, wherein: The limit value of the cutting size is 0.1-0.5 cm, more preferably 0.3-0.5 cm.

8. The preparation method according to claim 2 or 7, wherein: When the cutting size is ≤0.3 cm, the yield rate of cut coral stone is 30-70%; Preferably, when the cutting size is greater than 0.3 cm, the yield rate of the cut coral stone is 30-99%.

9. Coral hydroxyapatite, prepared by the preparation method according to any one of claims 2 to 8.

10. Use of the coral hydroxyapatite according to claim 9 in preparing products in the field of medical materials; Preferably, the products in the field of medical materials include artificial bone products.

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