Coral hydroxyapatite, its manufacturing method, and its use

Abstract

Finding a cutting protection agent for coralite and performing a pretreatment process on the coralite improves the yield of high-quality coral hydroxyapatite. [Solution] The present invention provides coral hydroxyapatite having a pore size of 30 μm to 1300 μm, a porosity of 50% to 70%, and a conversion rate of 50% or more, as well as a method for producing the same and its use. The production method includes immersing pre-treated coral stone in a cutting protective agent which is a solution containing a polyhydric alcohol, cutting it to obtain cut coral stone, selecting cut coral stone that meets the required cutting dimensions to obtain good quality cut coral stone, thoroughly immersing the good quality cut coral stone in a phosphate solution to perform a hydrothermal exchange reaction, and then obtaining the coral hydroxyapatite. The production method of the present invention significantly improves cutting efficiency, expands the standard cutting size, significantly improves the good product rate, especially the good product rate for small standard sizes, and can further expand the range of use for artificial bone.

Description

Technical Field

[0001] The present invention belongs to the field of medical materials, and specifically relates to coral hydroxyapatite, its manufacturing method and use.

Background Art

[0002] Coral hydroxyapatite artificial bone is a high-purity hydroxyapatite material manufactured from natural coral. It retains the original structural characteristics of coral, has a porous network structure, the pore diameter is between 100 and 600 μm, and the porosity is 30% to 70%. Such a material has good biocompatibility and osteoconductivity because its physical structure, crystal arrangement and bone density observed by an electron microscope are extremely similar to those of the human skeleton. Since coral hydroxyapatite artificial bone has already been clinically applied and shown good effects, coral hydroxyapatite artificial bone products have broad application possibilities.

[0003] The specifications of coral hydroxyapatite artificial bone products are numerous, such as bone powder (particles with different particle diameters), bone strips, bone blocks and bone chips. On the other hand, natural corals are mostly irregular and large in volume. Since the acquisition of many coral hydroxyapatite artificial bone product specifications must be carried out by cutting and shaping, for the manufacture of coral hydroxyapatite artificial bone products, the cutting of coral stones is an essential and important process. On the other hand, in terms of physical properties, coral stones have relatively high hardness but are relatively brittle, and there is a certain degree of difficulty during cutting. Especially when cutting into small-sized regular shapes, coral stones are more likely to crack, resulting in a low yield rate of coral stone products.

[0004] Currently, there are many patents related to coral rock, and the processing processes for coral rock are already mature. Chinese Patent No. 1055061 mainly concerns a manufacturing method for converting natural coral into hydroxyapatite, a bioactive material, by performing an anion exchange reaction under hydrothermal conditions. Chinese Patent Application Publication No. 1203189 mainly concerns the production of hydroxyapatite artificial bone by immersing coral in a high-concentration phosphate solution and performing a hydrothermal reaction under low to medium pressure conditions. Chinese Patent No. 1069614 mainly introduces a chemical hole expansion technology for porous biomaterials made from natural coral hydroxyapatite. Chinese Patent No. 1231269 mainly describes a method for producing coral hydroxyapatite artificial bone with adjustable absorption rate. Chinese Patent No. 1235645 mainly describes the synthesis of artificial bone using natural coral as a material by performing a heat-liquid exchange reaction in a diammonium hydrogen phosphate + hydrothermal liquid system under high temperature and high pressure conditions. Chinese Patent No. 100366301 describes a method for producing coral hydroxyapatite artificial bone with a surface of β-tricalcium phosphate by immersing coral hydroxyapatite in phosphoric acid, phosphate, or a mixture thereof for a predetermined time at a predetermined temperature, and then heating to carry out a conversion reaction. Chinese Patent No. 100384488 describes a method for producing absorbable hydroxyapatite artificial bone by washing with water, rinsing and drying, etching its channels with dilute hydrochloric acid, and then carrying out an immersion reaction with a saturated phosphate solution. The prior art focuses on the method of producing coral hydroxyapatite artificial bone, changing different processing methods, and does not mention the standards necessary for processing natural coral rock into artificial bone. The coral rock cutting process is one of the essential steps in coral rock processing, and the brittleness of coral rock determines that it is prone to cracking and fracturing when cut, but this has not been studied or reported.

[0005] Conventional coral stone exhibits relatively low cutting efficiency. Furthermore, coral stone has a relatively large limit to the cutting dimension. In addition, when coral hydroxyapatite is manufactured into product specifications with predetermined shapes such as massive or rod-shaped, it is prone to fracture during cutting, resulting in a relatively low yield rate of good products.

[0006] Therefore, finding a cutting protection agent for coralite and performing a pretreatment process on it is necessary and significant for improving the yield of high-quality coral hydroxyapatite. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Chinese Patent No. 1055061 Specification [Patent Document 2] Chinese Patent Application Publication No. 1203189 Specification [Patent Document 3] Chinese Patent No. 1069614 Specification [Patent Document 4] Chinese Patent No. 1231269 Specification [Patent Document 5] Chinese Patent No. 1235645 Specification [Patent Document 6] Chinese Patent No. 100366301 Specification [Patent Document 7] Chinese Patent No. 100384488 Specification [Overview of the project]

[0008] To solve the above technical problems, the present invention aims to provide coral hydroxyapatite, a method for producing the same, and a method for using the same.

[0009] To achieve the above objective, the present invention provides coral hydroxyapatite having a pore size of 30 μm to 1300 μm, a porosity of 50% to 70%, and a conversion rate of 50% or more.

[0010] According to a specific embodiment of the present invention, the conversion rate of the coral hydroxyapatite is 70% or more.

[0011] According to a specific embodiment of the present invention, the conversion rate of the coral hydroxyapatite is 90% or more.

[0012] The void structure of the coral hydroxyapatite of the present invention is similar to that of human cancellous bone, with each pore being interconnected.

[0013] The pore size range of 30 μm to 1300 μm described in this invention refers to the pore size distribution range.

[0014] The coral hydroxyapatite product of the present invention uses natural coral as the coral raw material, and more preferably, the natural coral includes Porites and Goniopora.

[0015] For coral hydroxyapatite produced using Pomazalite as a raw material, the pore size distribution range is typically 30 μm to 800 μm, while for coral hydroxyapatite produced using Goniopora coralite as a raw material, the pore size distribution range is typically 90 μm to 1300 μm.

[0016] The present invention After pre-treated coral stones are immersed in a cutting protective agent, they are cut to obtain cut coral stones, and cut coral stones that meet the required dimensions are selected to obtain high-quality cut coral stones. After thoroughly immersing good quality cut coral rock in a phosphate solution and carrying out a hydrothermal exchange reaction, the coral hydroxyapatite is obtained. The aforementioned cutting protective agent is a solution containing a polyhydric alcohol. The present invention also provides a method for producing the above-described coral hydroxyapatite, which includes the above-described method.

[0017] In the above manufacturing method, the mass fraction of the polyhydric alcohol is ≥20% of the total mass of the cutting protective agent, preferably 30-80%, and more preferably 30-50%.

[0018] In the above manufacturing method, preferably, the polyhydric alcohol is one or more selected from glycerin, ethylene glycol, sorbitol, and butanediol.

[0019] In the above manufacturing method, the dipping time of the cutting protectant is 3 to 24 h.

[0020] In the above manufacturing method, the steps of the pretreatment are

[0021] including removing dust from natural coral stones, dipping them in a sodium hypochlorite solution or a hydrogen peroxide solution, washing them, and drying them in preparation for use.

[0022] In the above manufacturing method, the concentration of the phosphate solution is 1 to 5 mol / L.

[0023] In the above manufacturing method, the reaction pressure of the hydrothermal exchange is 1 to 3 MPa, the reaction temperature is 120 to 240 °C, and the reaction time is 5 to 48 h.

[0024] In the above manufacturing method, the equipment used for cutting is a belt saw.

[0025] In the above manufacturing method, preferably, the cutting speed in the cutting is 1.6 to 3 cm / s, preferably 1.9 to 2.4 cm / s.

[0026] In the above manufacturing method, the limit value of the cutting dimension is 0.1 to 0.5 cm, preferably 0.3 to 0.5 cm.

[0027] In the cutting of coral stones, the smaller the cutting dimension, the easier it is to crack. After being treated with the polyhydric alcohol cutting protectant of the present invention, the minimum value of the standard cutting size can be reduced, the yield rate of cutting products with small standard sizes can be improved, and the integrity of the cutting products can be ensured.

[0028] The cutting method of the present invention allows for cutting of (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, 0.1cm × 0.1cm × 0.1cm, 0.2cm × 0.2cm × 0.2cm, 0.1cm × 0.2cm × 0.2cm, 0.1cm × 0.3cm × 0.3cm, 0.1cm × 0.3cm × 0.5cm, 0.3cm × 0.3cm × 0.5cm, 0.4cm × 0.4cm × 0.4cm, 0.4cm × 0.4cm × 0. Coral hydroxyapatite products with the following dimensions can be obtained by cutting them: 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, and 10.0cm×10.0cm×10.0cm.

[0029] The coral hydroxyapatite product of the present invention can be further cut and / or polished.

[0030] In the above manufacturing method, when the cutting dimension is ≤ 0.3 cm, the percentage of good quality cut coral stones is 30-70%.

[0031] In the above manufacturing method, when the cutting dimension is >0.3cm, the quality rate of the cut coral stones is 30-99%.

[0032] The present invention also provides coral hydroxyapatite produced by the above manufacturing method.

[0033] The present invention also provides the use of the above-mentioned coral hydroxyapatite in the manufacture of products in the field of medical materials.

[0034] According to specific embodiments of the present invention, preferably, the product in the field of medical materials includes an artificial bone product.

[0035] According to a specific embodiment of the present invention, the method for producing the coral hydroxyapatite includes the following steps: (1) Natural coral stones are ultrasonically cleaned to remove surface impurities and dust, then immersed in a sodium hypochlorite solution or hydrogen peroxide solution, further washed with purified water, and dried to prepare for use. (2) Immerse the coral stone in a polyhydric alcohol solution containing multiple hydroxyl groups with a concentration of 20% or more, allowing the coral stone to be thoroughly soaked, for an immersion time of 3 to 24 hours. (3) The coral stones processed in step (2) are cut, polished, manufactured into the desired shapes and specifications, and then washed and dried. (4) Place the coral rock treated in step (3) into a reaction vessel, add 1-5 mol / L of phosphate solution and immerse thoroughly, carry out a hydrothermal reaction under a pressure of 1-3 MPa and a temperature of 120-240°C for 5-48 hours to obtain coral hydroxyapatite. (5) After washing and drying the coral hydroxyapatite treated in step (5), it is packaged and sterilized by radiation.

[0036] In this invention, by immersing the coral stone in a polyhydric alcohol, the coral stone is thoroughly permeated, improving its lubricity. This makes the coral stone easier to cut and shape during the subsequent cutting and polishing processes, improving the efficiency of coral stone cutting, expanding the standard size of coral stone artificial bone, improving the yield rate of coral stone artificial bone products, and better meeting the requirements of bone repair. [Brief explanation of the drawing]

[0037] [Figure 1] This is a view of the cut coral rock, where a is the cut coral rock from Example 1, b is the cut coral rock from Comparative Example 1, c is the cut coral rock from Comparative Example 3, and d is the cut coral rock from Comparative Example 4. [Figure 2] This is a scanning electron microscope image (100×) of the coral hydroxyapatite product in Example 1. [Modes for carrying out the invention]

[0038] The following describes in detail the proposed technical aspects of the present invention in order to provide a clearer understanding of its constituent elements, objectives, and beneficial effects, but this does not limit the scope of the invention's applicability.

[0039] In actual production, a person skilled in the art will understand that, provided that good quality products can be obtained, several relevant process steps can be adjusted or increased or decreased.

[0040] Example 1 Using brain coral as an example, natural brain coral stones were ultrasonically cleaned to remove surface impurities and powder, then immersed in a 30% hydrogen peroxide solution, further washed with purified water, and dried.

[0041] Glycerin and water were mixed to prepare a 40% (wt) glycerin solution. Coral rock was immersed in the 40% (wt) glycerin solution to thoroughly immerse it for 10 hours. After that, it was cut using a band saw (equipment number: JBS-260, saw blade specifications: 1710*9.5*0.35mm*14TPI). The cutting efficiency and cutting limit were compared, and the yield rate of samples cut to the corresponding specifications was statistically calculated. The results are shown in Table 1, where 0.5×0.5×0.5cm 3 A representative sample cut to standard size is shown in Figure 1a. Coral rock samples conforming to the specified dimensions were placed in a reaction vessel, a 3 mol / L solution of diammonium hydrogen phosphate was added, and the reaction was carried out at 180°C for 24 hours. After that, the samples were washed, dried, packaged, and sterilized to obtain coral hydroxyapatite. The pore size is shown in Table 1, and a scanning electron microscope image is shown in Figure 2. The pore size distribution range was 30 μm to 800 μm. The conversion rate of the coral hydroxyapatite product produced in this example was measured to be approximately 61.7%.

[0042] Example 2 Goniopora coral is one of the corals with large holes, making it more prone to breaking when cut. Using Goniopora coral as an example, natural Goniopora coral rock was ultrasonically cleaned to remove surface impurities and powder, then immersed in a 30% hydrogen peroxide solution, further washed with purified water, and dried.

[0043] Coralite was immersed in a 30% (wt) glycerin solution to thoroughly penetrate the coralite for 4 hours. It was then cut using a band saw (equipment number: JBS-260, saw blade specifications: 1710*9.5*0.35mm*14TPI). The cutting efficiency and cutting limit were compared, and the yield rate of samples cut to the corresponding specifications was statistically calculated. The results are shown in Table 1. Coralite samples conforming to the specified dimensions were placed in a reaction vessel, a 3 mol / L diammonium hydrogen phosphate solution was added, and the reaction was carried out at 180°C for 24 hours. After that, the samples were washed, dried, packaged, and sterilized to obtain coral hydroxyapatite. The pore size is shown in Table 1, and the pore size distribution range was 90 μm to 1300 μm. The conversion rate was measured to be approximately 66.3%.

[0044] Comparative Example 1 Using brain coral as an example, natural brain coral stones were ultrasonically cleaned to remove surface impurities and powder, then immersed in a 30% hydrogen peroxide solution, further washed with purified water, and dried.

[0045] Each coral stone was cut using a band saw (equipment number: JBS-260, saw blade specifications: 1710*9.5*0.35mm*14TPI), and the cutting efficiency and cutting limit were compared. The yield rate of samples cut with the corresponding specifications was statistically calculated, and the results are shown in Table 1. Here, 0.5×0.5×0.5cm 3 A typical sample cut to standard size is shown in Figure 1b. Coral rock samples conforming to the specified dimensions are placed in a reaction vessel, a 3 mol / L solution of diammonium hydrogen phosphate is added, and the reaction is carried out at 180°C for 24 hours. After that, the samples are washed, dried, packaged, and sterilized to obtain coral hydroxyapatite, and the pore sizes are shown in Table 1.

[0046] Comparative Example 2 Goniopora coral is one of the corals with large holes, making it more prone to breaking when cut. Using Goniopora coral as an example, natural Goniopora coral rock was ultrasonically cleaned to remove surface impurities and powder, then immersed in a 30% hydrogen peroxide solution, further washed with purified water, and dried.

[0047] Each coralite sample was cut using a band saw (equipment number: JBS-260, saw blade specifications: 1710*9.5*0.35mm*14TPI). The cutting efficiency and cutting limits were compared, and the yield rate of samples cut to the corresponding specifications was statistically calculated. The results are shown in Table 1. Coralite samples that met the specified dimensions were placed in a reaction vessel, a 3 mol / L solution of diammonium hydrogen phosphate was added, and the reaction was carried out at 180°C for 24 hours. After that, the samples were washed, dried, packaged, and sterilized to obtain coral hydroxyapatite, and the pore size is shown in Table 1.

[0048] Comparative Example 3 Using brain coral as an example, natural brain coral stones were ultrasonically cleaned to remove surface impurities and powder, then immersed in a 30% hydrogen peroxide solution, further washed with purified water, and dried.

[0049] Coralite was immersed in a 5% (wt) glycerin solution to thoroughly soak it for 15 hours. Then, it was cut using a band saw (equipment number: JBS-260, saw blade specifications: 1710*9.5*0.35mm*14TPI). The cutting efficiency and cutting limits were compared, and the yield rate of samples cut to the corresponding specifications was statistically calculated. The results are shown in Table 1, where 0.5×0.5×0.5cm 3 A typical sample cut to standard size is shown in Figure 1c. Coral rock samples conforming to the specified dimensions are placed in a reaction vessel, a 3 mol / L solution of diammonium hydrogen phosphate is added, and the reaction is carried out at 180°C for 24 hours. After that, the samples are washed, dried, packaged, and sterilized to obtain coral hydroxyapatite, and the pore sizes are shown in Table 1.

[0050] Comparative Example 4 Using brain coral as an example, natural brain coral stones were ultrasonically cleaned to remove surface impurities and powder, then immersed in a 30% hydrogen peroxide solution, further washed with purified water, and dried.

[0051] Carboxymethylcellulose (polysaccharide) was dissolved in water to prepare a 0.06% (wt) carboxymethylcellulose solution. Coral rock was immersed in the 0.06% (wt) carboxymethylcellulose solution, allowing it to be thoroughly soaked for 24 hours. The rock was then cut using a band saw (equipment number: JBS-260, saw blade specifications: 1710*9.5*0.35mm*14TPI). The cutting efficiency and cutting limit were compared, and the yield rate of samples cut to the corresponding specifications was statistically calculated. The results are shown in Table 1, where 0.5×0.5×0.5cm is used. 3 A typical sample cut to standard size is shown in Figure 1d. Coral rock samples conforming to the specified dimensions are placed in a reaction vessel, a 3 mol / L solution of diammonium hydrogen phosphate is added, and the reaction is carried out at 180°C for 24 hours. After that, the samples are washed, dried, packaged, and sterilized to obtain coral hydroxyapatite, and the pore sizes are shown in Table 1.

[0052] [Table 1]

[0053] Note: A good product means that the cut coral stone sample matches the specified size requirements and the error does not exceed ±1 mm. The good product rate is calculated as: Number of good cut coral stone samples / Total number of cut coral stone samples × 100%. Since the post-cutting processing does not significantly affect the dimensions and appearance of the coral stone sample, the good product rate here represents the good product rate for coral hydroxyapatite (artificial bone).

[0054] As can be seen from the comparison, if no cutting protective agent is added to the coral stone, or if a polysaccharide substance (not a polyhydric alcohol protective agent) is added, or if the concentration of the protective agent is too low, the coral stone becomes prone to cracking and fracturing during cutting, and the cut surface is not flat, as can be seen in Figures 1b to 1d. When the cutting speed is 1.5 cm / s or less (this cutting speed is based on the limit of the cutting dimension, and if it exceeds this, almost no good products are obtained), and the limit of cutting is 0.5 to 1.0 cm, however, after pretreatment with the addition of a cutting protective agent, the coral stone becomes relatively less prone to cracking during cutting, the cutting speed is 1.9 to 2.4 cm / s, the limit of cutting is 0.3 to 0.5 cm, and a good cut shape can be formed, as can be seen in Figure 1a.

[0055] In different processing groups of coral stone, the yield rate of products of the same specifications improved with increasing product size. After pretreatment with a predetermined concentration of polyhydric alcohol cutting protective agent, the yield rate of the products improved significantly compared to when no protective agent was added. In particular, when cutting small-sized products, pretreatment with a predetermined concentration of polyhydric alcohol cutting protective agent offers significant advantages. Although the coral stone underwent multiple washing processes after cutting, polyhydric alcohols are easily soluble in water, and detection revealed that no protective agent remained in the final coral hydroxyapatite product. The coral hydroxyapatite of the desired specification size obtained by the manufacturing method of the present invention has a conversion rate of 50% or more, which allows it to be applied to artificial bone and achieve the desired decomposition rate.

[0056] As can be seen from the above, by pre-treating with a specific cutting protective agent at a predetermined concentration, cutting efficiency can be significantly improved, the standard cutting size can be expanded, and the yield rate of good products, especially for small standard sizes, can be significantly improved. Therefore, the present invention is of great significance in the treatment of coral stone and can further expand the range of applications for artificial bone.

Claims

1. Coral hydroxyapatite with a pore size of 30 μm to 1300 μm, a porosity of 50% to 70%, and a conversion rate of 50% or more.

2. Pre-treated coral stone is immersed in a cutting protective agent, which is a solution containing polyhydric alcohol, and then cut to obtain cut coral stone. Cut coral stone that meets the required dimensions is then selected to obtain high-quality cut coral stone. A method for producing coral hydroxyapatite according to claim 1, comprising thoroughly immersing good quality cut coral in a phosphate solution and carrying out a hydrothermal exchange reaction to obtain the coral hydroxyapatite.

3. The mass fraction of the polyhydric alcohol is ≥ 20% of the total mass of the cutting protective agent. The aforementioned polyhydric alcohol is one or more selected from glycerin, ethylene glycol, sorbitol, and butanediol. The manufacturing method according to claim 2, wherein the immersion time of the cutting protective agent is 3 to 24 hours.

4. The manufacturing method according to claim 2, wherein the pretreatment step includes removing dust from the coral stone, immersing it in a sodium hypochlorite solution or a hydrogen peroxide solution, washing it, and drying it to prepare it for use.

5. The concentration of the phosphate solution is 1 to 5 mol / L. The manufacturing method according to claim 2, wherein the reaction pressure for the water heat exchange is 1 to 3 MPa, the reaction temperature is 120 to 240°C, and the reaction time is 5 to 48 hours.

6. The equipment used for the aforementioned cutting is a band saw. The manufacturing method according to claim 2, wherein the cutting speed in the cutting is 1.6 to 3 cm / s.

7. The manufacturing method according to claim 2, wherein the limit value of the cutting dimension is 0.1 to 0.5 cm.

8. When the aforementioned cutting dimension is ≤ 0.3 cm, the percentage of good quality cut coral stones is 30-70%. The manufacturing method according to claim 7, wherein when the cutting dimension is > 0.3 cm, the percentage of good quality cut coral stones is 30 to 99%.

9. Coral hydroxyapatite produced by the manufacturing method described in claim 2.

10. The use of coral hydroxyapatite according to claim 9 in the manufacture of products in the field of medical materials, The aforementioned products in the medical materials field include artificial bone products.

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