Preparation method of medical surgical alpha calcium sulfate hemihydrate
阅读说明：本技术 医用外科级α半水硫酸钙的制备方法 (Preparation method of medical surgical alpha calcium sulfate hemihydrate ) 是由 时晨 祁敏 于 2019-11-18 设计创作，主要内容包括：本发明提供了一种高强度医用外科级α半水硫酸钙的大规模制备方法,并提供了具体产品及其相应用途。在蒸压法的基础上,本发明的制备方法中使用了无机盐,特别是氯化钙或氯化镁改性硫酸钙的步骤以及使用无水乙醇蒸压前洗涤的步骤,有效提高了产品固化后的强度并保持了良好的降解性能。(The invention provides a large-scale preparation method of high-strength medical surgical alpha calcium sulfate hemihydrate, and provides a specific product and corresponding application thereof. On the basis of an autoclaved method, the preparation method disclosed by the invention uses a step of modifying calcium sulfate by inorganic salt, particularly calcium chloride or magnesium chloride, and a step of washing before autoclaving by absolute ethyl alcohol, so that the strength of the product after curing is effectively improved, and good degradation performance is kept.)
1. A preparation method of medical surgical alpha calcium sulfate hemihydrate comprises the following steps:
(1) taking calcium sulfate dihydrate at room temperature, pouring into an inorganic salt solution, heating, stirring, reacting, and performing suction filtration to obtain modified calcium sulfate dihydrate;
(2) heating and dehydrating the calcium sulfate dihydrate obtained by modification to obtain anhydrous calcium sulfate;
(3) adding the anhydrous calcium sulfate obtained in the step (2) into pure water, and soaking to obtain recrystallized calcium sulfate dihydrate;
(4) cleaning the calcium sulfate dihydrate obtained in the step (3) by using pure water, putting the cleaned calcium sulfate dihydrate into a high-pressure steam reaction kettle, and carrying out an autoclaved reaction to obtain alpha calcium sulfate hemihydrate;
(5) and (4) drying the alpha calcium sulfate hemihydrate obtained in the step (4), grinding and sieving by a 100-mesh sieve to obtain the medical surgical grade alpha calcium sulfate hemihydrate.
2. The method according to claim 1, wherein the inorganic salt solution in the step (1) is a calcium chloride or magnesium chloride solution.
3. The production method according to claim 2, wherein the inorganic salt solution in the step (1) is a 0.1mol/L magnesium chloride solution.
4. The production method according to claim 2, wherein the inorganic salt solution in the step (1) is a 0.1mol/L calcium chloride solution.
5. The production method according to any one of claims 1 to 4, wherein the steps (1) to (4) are specifically:
(1) weighing 1kg of calcium sulfate dihydrate at room temperature, pouring into 2L of inorganic salt solution with concentration, heating to 50 ℃, stirring for reaction for 12 hours, and performing suction filtration to obtain modified calcium sulfate dihydrate;
(2) placing the modified calcium sulfate dihydrate at 250 ℃, and heating and dehydrating for 36 hours to obtain anhydrous calcium sulfate;
(3) adding 2L of pure water into the anhydrous calcium sulfate obtained in the step (2), and soaking for 72 hours to obtain recrystallized calcium sulfate dihydrate;
(4) washing the calcium sulfate dihydrate obtained in the step (3) for 3 times by using pure water, then putting the calcium sulfate dihydrate into a high-pressure steam reaction kettle, and carrying out autoclaved reaction for 3 hours at 150 ℃ to obtain alpha calcium sulfate hemihydrate;
(5) and (3) drying the alpha calcium sulfate hemihydrate obtained in the step (4) at 120 ℃ for 4 hours, cooling to room temperature, grinding after cooling, and sieving with a 100-mesh sieve to obtain the medical surgical alpha calcium sulfate hemihydrate.
6. The production method according to any one of claims 1 to 5, wherein the water washing step in the step (3) is preceded by one alcohol washing.
7. The production method according to claim 7, wherein the alcohol washing is an anhydrous ethanol washing.
8. A medical surgical grade alpha calcium sulfate hemihydrate product made using the preparation process of any one of claims 1-7.
9. Use of a medical surgical grade alpha calcium sulfate hemihydrate product according to claim 8 in the preparation of an artificial bone product.
10. Use of a medical surgical grade alpha calcium sulfate hemihydrate product according to claim 8 in bone repair.
Technical Field
The invention belongs to the field of orthopedic materials, and particularly provides a large-scale preparation method of high-strength medical surgical alpha calcium sulfate hemihydrate, a specific product and corresponding application thereof.
Background
The calcium sulfate hemihydrate has good biocompatibility, can be completely degraded in vivo, has good matching between the degradation time and the bone repair time, and is an ideal bone repair material. The production method of the calcium sulfate hemihydrate is generally a hydrothermal method and an autoclaved methodThe products of the two methods are alpha calcium sulfate hemihydrate and beta calcium sulfate hemihydrate, which have great differences in crystal morphology, size, dispersity and the like. Wherein the performances of the alpha calcium sulfate hemihydrate, such as uniformity, mechanics, degradation, and the like, are obviously superior to those of the beta calcium sulfate hemihydrate, so that the alpha calcium sulfate hemihydrate is the first choice for preparing bone repair materials, and the medical calcium sulfate product commercially available at present is Wright company
At present, partial documents and patents in China report the steam-pressing preparation method of alpha calcium sulfate hemihydrate, but a large amount of crystal transformation agent is required to be added in the production process of the methods, so that the quality of the product is difficult to control; and the production scale-up of high quality alpha products is difficult (basically on the order of 100 g). In addition, there is room for improvement in the strength properties of the alpha calcium sulfate hemihydrate product due to the need for stress section repairs.
Disclosure of Invention
In view of the above problems, the applicant found that the use of an inorganic salt solution, particularly a calcium chloride/magnesium chloride solution, to modify calcium sulfate dihydrate before the preparation starts can effectively improve the density and uniformity of crystals, and further improve the compressive strength of an alpha calcium sulfate hemihydrate product, which is significantly higher than that of existing hydrothermal and autoclaved calcium sulfate hemihydrate products, and can easily and stably realize batch preparation (which can be scaled up to a 5kg scale at present). To further improve the degradation performance of the alpha calcium sulfate hemihydrate product, applicants attempted to add one more alcohol wash step prior to autoclaved dewatering, successfully adjusting the degradation time of the alpha calcium sulfate hemihydrate product to a level substantially consistent with the bone recovery time.
On one hand, the preparation method of the medical surgical grade alpha calcium sulfate hemihydrate comprises the following steps:
(1) taking calcium sulfate dihydrate at room temperature, pouring into an inorganic salt solution, heating, stirring, reacting, and performing suction filtration to obtain modified calcium sulfate dihydrate;
(2) heating and dehydrating the calcium sulfate dihydrate obtained by modification to obtain anhydrous calcium sulfate;
(3) adding the anhydrous calcium sulfate obtained in the step (2) into pure water, and soaking to obtain recrystallized calcium sulfate dihydrate;
(4) cleaning the calcium sulfate dihydrate obtained in the step (3) by using pure water, putting the cleaned calcium sulfate dihydrate into a high-pressure steam reaction kettle, and carrying out an autoclaved reaction to obtain alpha calcium sulfate hemihydrate;
(5) and (4) drying the alpha calcium sulfate hemihydrate obtained in the step (4), grinding and sieving by a 100-mesh sieve to obtain the medical surgical grade alpha calcium sulfate hemihydrate.
Further, the inorganic salt solution in the step (1) is calcium chloride or magnesium chloride solution.
Further, the inorganic salt solution in the step (1) is a 0.1mol/L magnesium chloride solution.
Further, the inorganic salt solution in the step (1) is a 0.1mol/L calcium chloride solution.
Further, the steps (1) to (4) are specifically:
(1) weighing 1kg of calcium sulfate dihydrate at room temperature, pouring into 2L of inorganic salt solution with concentration, heating to 50 ℃, stirring for reaction for 12 hours, and performing suction filtration to obtain modified calcium sulfate dihydrate;
(2) placing the modified calcium sulfate dihydrate at 250 ℃, and heating and dehydrating for 36 hours to obtain anhydrous calcium sulfate;
(3) adding 2L of pure water into the anhydrous calcium sulfate obtained in the step (2), and soaking for 72 hours to obtain recrystallized calcium sulfate dihydrate;
(4) washing the calcium sulfate dihydrate obtained in the step (3) for 3 times by using pure water, then putting the calcium sulfate dihydrate into a high-pressure steam reaction kettle, and carrying out autoclaved reaction for 3 hours at 150 ℃ to obtain alpha calcium sulfate hemihydrate;
(5) and (3) drying the alpha calcium sulfate hemihydrate obtained in the step (4) at 120 ℃ for 4 hours, cooling to room temperature, grinding after cooling, and sieving with a 100-mesh sieve to obtain the medical surgical alpha calcium sulfate hemihydrate.
Further, the water washing step in the step (3) is preceded by one alcohol washing.
Further, the alcohol washing is absolute ethyl alcohol washing.
In another aspect, the present invention provides a medical surgical grade alpha calcium sulfate hemihydrate product prepared according to the above process.
In another aspect, the invention provides the use of a medical surgical grade alpha calcium sulfate hemihydrate product prepared according to the above method in the preparation of an artificial bone product.
In another aspect, the invention provides the use of a medical surgical grade alpha calcium sulfate hemihydrate product prepared according to the above method in bone repair.
The calcium sulfate dihydrate, the calcium chloride, the magnesium chloride and the anhydrous ethanol can be imported or domestic products according to production needs, and the purity and other properties can meet the requirements.
The proportion and the parameters in the preparation method can be adjusted by the person skilled in the art according to the production conditions, the formula and the like without departing from the corresponding protection scope of the application.
The use of the products of the present application in the preparation of artificial bone products or in bone repair does not preclude the use in admixture or in combination with other products/additives/drugs including, but not limited to, hydroxyapatite, bone meal, adhesives, BMP factor, and the like.
Drawings
Fig. 1 is an SEM comparison of typical crystal structures of material 2 and material 5, with material 2 on the left and material 5 on the right.
Examples
Main reagents and instruments:
calcium sulfate dihydrate, calcium chloride, magnesium chloride, and anhydrous ethanol are obtained from SIGMA/MERCK;
the purified water is self-made by a Millipore laboratory purified water production system;
a pressure reaction kettle: a GSA-3 high pressure steam reaction kettle produced by Beijing Daisen scientific and technological development company;
a muffle furnace: CQ-10 program-controlled muffle furnace, produced by Luoyang pure blue laboratory instrument factory;
biomechanical testing machine: MACH-1 multifunctional tissue material biomechanical property, potential distribution test analysis characterization system, produced by biomolecular;
scanning electron microscope: JCM-7000 scanning electron microscope, manufactured by JEOL, Japan;
other reagents and instruments, whose source is not specified, are of conventional domestic make and model.