T/CSBM 0045-2023
Calcium sulfate hemihydrate for surgical implants (English Version)

Standard No.

T/CSBM 0045-2023

Language

Chinese, Available in English version

Release Date

2023

Published By

Group Standards of the People's Republic of China

Latest

T/CSBM 0045-2023

Scope

Technical requirements 5.1 Appearance White solid powder, no visible foreign matter and agglomeration, the powder is uniform. 5.2 Phase composition and content 5.2.1 According to quantitative XRD analysis, the XRD spectrum of the crystal structure of calcium sulfate hemihydrate should comply with the ICDD PDF powder diffraction card No. 41-0224. The impurity phase should not have obvious other crystal phase diffraction peaks and amorphous material performance except CaSO4·2H2O or CaSO4. 5.2.2 The crystalline phase content of calcium sulfate hemihydrate measured in accordance with 6.2 should not be less than 98%. 5.3 Calcium and sulfur atomic ratio The elemental analysis of calcium and sulfur should be consistent with the theoretical stoichiometric ratio of the empirical chemical formula of calcium sulfate hemihydrate (CaSO4·1/2H2O or CaSO4·H2O·CaSO4), and the atomic ratio of calcium (Ca) and sulfur (S) should be 1.00±0.05. 5.4 Element content 5.4.1 The trace element content of arsenic, bismuth, cadmium, mercury, lead, antimony and iron should comply with the provisions of Table 1. 5.4.2 Total amount of heavy metal elements 5.4.2.1 The maximum allowable amount of total amount of heavy metal elements (in terms of Pb) is 30 mg/kg. 5.4.2.2 For metals or oxides not calculated as lead, when the content is greater than or equal to 0.1%, it is advisable to list them in the notes and attach them to the packaging. 5.5 Compression strength of hydrates The compression strength of hydrates shall comply with the indicators provided in its technical specifications. 5.6 Curing time The curing time shall comply with the indicators provided in its technical specifications. 5.7 Degradability of hydrates The degradation products of hydrates shall be qualitatively and quantitatively analyzed according to the intended use. 5.8 Biocompatibility The biocompatibility shall be evaluated according to the intended use of surgical implants. 6 Test method 6.1 Appearance Place the sample in a white container and observe it in bright light with normal or corrected vision. 6.2 Phase composition and content 6.2.1 Test equipment The test equipment is as follows: 　——X-ray diffraction analyzer; 　——Box-type resistance furnace or high-temperature sintering furnace; 　——Agate mortar; 　——Platinum or corundum crucible. 6.2.2 Calibration curve establishment 6.2.2.1 Calibration curve of calcium sulfate hemihydrate and calcium sulfate dihydrate mixture: a) Grind calcium sulfate hemihydrate and calcium sulfate dihydrate respectively with agate mortar; b) Use X-ray diffractometer to measure the diffraction spectrum of the above two powders (CuKα target, graphite monochromator), scanning speed 0.2°/min, 2θ resolution greater than 0.02°, scanning range 2θ: 10°～50°, the obtained XRD spectrum should conform to the PDF powder diffraction card No.41-0224 (CaSO4·1/2H2O) and No.33-0311 (CaSO4·2H2O) of ICDD, and there should be no other crystalline phase peaks and obvious amorphous phase peaks; c) Accurately weigh the above powders, prepare a series of mixed standard samples of CaSO4·2H2O and CaSO4·1/2H2O according to the mass percentage of CaSO4·1/2H2O of 0%, 10%, 30%, 50%, 70%, 90% and 100%, respectively, and carefully grind and mix them in an agate mortar; d) Obtain the XRD spectrum of each mixed standard sample at a scanning speed of 0.2°/min and a scanning range of 2: 10.2°～30.2°, showing that the integral area of the (400) diffraction peak (2θ=29.7°) of CaSO4·1/2H2O is CaSO4.1/2H2O and the integral area of the (021) diffraction peak (2θ=20.6°) of CaSO4·2H2O is CaSO4.2H2O, and the relative diffraction peak intensity ρ of CaSO4·1/2H2O in each mixed standard sample is calculated according to formula (1); ρ=??CaSO4·1/2H2O??CaSO4·1/2??2??+??CaSO4·2??2?? ··················································································(1) e) The XRD analysis of the mixed standard was carried out in parallel for 3 times, and ρ1, ρ2, and ρ3 were calculated respectively, and the arithmetic mean was taken. Based on the linear regression method, the X-ρ calibration curve of the mixed standard of CaSO4·2H2O and CaSO4·1/2H2O was drawn with the mass percentage X of CaSO4·1/2H2O versus the relative diffraction peak intensity ρ, as shown in Figure 1. 6.2.2.2 Calibration curve of calcium sulfate hemihydrate and anhydrous calcium sulfate mixed sample: a) Grind calcium sulfate hemihydrate with an agate mortar; heat anhydrous calcium sulfate pure powder to 800℃ at a heating rate of 5℃/min, keep it at this temperature for 2h, cool it to room temperature with the furnace, and grind it with an agate mortar; b) Same as 6.2.2.1b), the obtained XRD spectrum should conform to the PDF powder diffraction card No.41-0224 (CaSO4·1/2H2O) and No.37-1496 (CaSO4) of ICDD respectively, and there should be no other crystalline phase peaks and obvious amorphous phase peaks; c) Same as 6.2.2.1c), prepare a series of mixed standard samples of CaSO4 and CaSO4·1/2H2O; d) The XRD spectrum of each mixed standard sample is obtained in the same manner as in 6.2.2.1d), showing that the integrated area of the (400) diffraction peak (2θ=29.7°) of CaSO4·1/2H2O is ??CaSO4.1/2H2O, and the integrated area of the (020) diffraction peak (2θ=25.4°) of CaSO4 is ??CaSO4. The relative diffraction peak intensity ? of CaSO4·1/2H2O in each mixed standard sample is calculated according to formula (2); ρ=??CaSO4.1/2H2O??CaSO4.1/2H2O+??CaSO4 · ... e) Same as 6.2.2.1e), draw the X-ρ calibration curve of CaSO4 and CaSO4·1/2H2O mixed standard sample with the mass percentage X of CaSO4·1/2H2O versus the relative diffraction peak intensity ρ, as shown in Figure 1. 6.2.3 Determination procedure 6.2.3.1 Take 6g of sample and grind it with an agate mortar. Determine the XRD spectrum of the sample according to 6.2.2. The diffraction peak of the main phase in the spectrum should conform to the PDF powder diffraction card No. 41-0224 (CaSO4·1/2H2O) of ICDD. Except for CaSO4·2H2O or CaSO4, there should be no obvious other crystalline diffraction peaks and amorphous diffraction peaks of the impurity phase; 6.2.3.2 The sample is tested three times, and the CaSO4·1/2H2O content in the sample is tested: the XRD spectrum of the sample is obtained at a scanning speed of 0.2°/min, a 2θ resolution greater than 0.02°, and a scanning range of 2θ: 8.5°~30.2°. Use the operating software of the X-ray diffractometer to remove the interfering background, give the integral area of the (400) diffraction peak (2θ=29.7°) of CaSO4·1/2H2O??CaSO4.1/2H2O and the integral area of the (021) diffraction peak (2θ=20.6°) of CaSO4·2H2O??CaSO4.2H2O or the integral area of the (020) diffraction peak (2θ=25.4°) of CaSO4??CaSO4, calculate ρ1, ρ2, ρ3 respectively, take the arithmetic mean, and substitute it into the X-ρ calibration curve to obtain the mass percentage X of CaSO4·1/2H2O; 6.2.3.3 Given the integral area of the (400) diffraction peak (2θ=29.7°) of CaSO4·1/2H2O, the integral area of the (021) diffraction peak (2θ=20.6°) of CaSO4·2H2O, and the integral area of the (020) diffraction peak (2θ=25.4°) of CaSO4, substitute them into equations (1) and (2) to calculate the relative concentration of CaSO4·1/2H2O in the mixed standard compared to CaSO4·1/2H2O and CaSO4·2H2O. The relative diffraction peak intensity ρ1 of the mixed phase and the relative diffraction peak intensity ρ2 of CaSO4·1/2H2O in the mixed standard compared with the mixed phase of CaSO4·1/2H2O and CaSO4, and the mass percentage content X1 of CaSO4·1/2H2O compared with CaSO4·1/2H2O and CaSO4·2H2O and the mass percentage content X2 of CaSO4·1/2H2O compared with CaSO4·1/2H2O and CaSO4 are obtained from the corresponding X-ρ calibration curve. The mass percentage content X of CaSO4·1/2H2O in the mixture is calculated according to formula (3). ??=??1×??2/[(??1+??2)?(??1×??2)]··············(3) 6.3 Calcium and sulfur atomic ratio Dissolve 10 mg of the calcium sulfate hemihydrate sample in 50 mL of 2% dilute nitric acid. The calcium and sulfur content is determined by the inductively coupled plasma emission atomic spectrometry specified in 0411 of the General Rules of the Pharmacopoeia of the People's Republic of China (Volume IV of the 2020 Edition). The corresponding atomic number ratio is calculated from the content of the two. 6.4 Element content 6.4.1 Trace element content Dissolve 10 mg of the calcium sulfate hemihydrate sample in 50 mL of 2% dilute nitric acid and determine it by the inductively coupled plasma emission atomic spectrometry specified in 0411 of the General Rules of the Pharmacopoeia of the People's Republic of China (Volume IV of the 2020 Edition). 6.4.2 Total amount of heavy metal elements Dissolve 10 mg of the calcium sulfate hemihydrate sample in 50 mL of 2% dilute nitric acid and determine it according to the heavy metal inspection method of 0821 in the general rules of the Pharmacopoeia of the People's Republic of China (2020 Edition Part IV). 6.5 Compression strength of hydrate 6.5.1 Test apparatus The test apparatus is as follows: 　——Constant temperature and humidity chamber; 　——Moulds, end plates, demoulding rods and C-type clamps made of stainless steel or other devices that can clamp the mould and end plates together, or other devices that can make cylindrical specimens with a height of (12.0 ± 0.1) mm and a diameter of (6.0 ± 0.1) mm; 　——240 mesh emery paper; 　——A flat plate; 　——Demolding agent; 　——Container for mixing hydrates; 　——A testing machine capable of applying and measuring a pressure of at least 4 kN, with a device for recording the relationship between load and crosshead displacement; 　——Digital caliper with an accuracy of 0.01 mm. 6.5.2 Test conditions Before the test begins, the mixing container and experimental equipment should be kept at (37 ± 0.5) °C for at least 2 h, and the test should be carried out at (37 ± 0.5) °C. 6.5.3 Test steps The test should be carried out according to the following steps: a) If necessary, a small amount of release agent can be applied to the inner surface of the mold and the inner surface of the two plates; b) Place the mold on an end plate; c) Pour the weighed calcium sulfate hemihydrate into the container, add the required amount of deionized water according to the manufacturer's instructions, and mix and stir evenly to form a dough-like hydrate. d) Within 120 seconds, fill the dough-like hydrate into each hole of the mold with a slight excess, and then place the second end plate on top of the mold; e) Press the end plate and the mold together with a C-type clamp. After about 2 hours, remove the clamp and the end plate; f) Place the two end faces of the mold on a flat plate lined with corundum and grind back and forth to grind the two end faces of each cylinder of hydrate in the mold flat. Use a demoulding rod to remove the hydrate cylinder from the mold. Finally, at least 5 cylindrical specimens with a height of (12.0±0.1) mm and a diameter of (6.0±0.1) mm are obtained; g) The specimens are placed in an environment with a temperature of (37±0.5)℃ and a relative humidity of ≥90% for 24 hours, and then the compressive strength is measured; h) The diameters of at least three sections of each cylindrical specimen perpendicular to the central axis are measured with a digital caliper, and the average diameter is taken to calculate the cross-sectional area of the specimen; the specimen is placed on the sample table of the testing machine. Start the testing machine and measure the stress-strain curve of the sample at a constant compression rate within the range of 0.05mm/min to 2mm/min, and stop the machine when the specimen breaks; i) Repeat g) for each specimen. 6.5.4 Result determination 6.5.4.1 For each specimen, record the maximum stress applied before fracture, that is, the hydrate compressive strength σ, which is calculated according to formula (4). σ=??/??· ... 6.6 Curing time 6.6.1 Test equipment The penetrometer used in the test shall meet the following requirements: 　——The total weight of the rod and the needle is 300g ± 1g; 　——Scale: the scale accuracy is 0.1mm; 　——Clean and dry ring mold: made of corrosion-resistant and non-absorbent material; 　——Square glass bottom plate: 100mm×100mm; 　——Vickers needle: the needle tip is a flat circle with a cross-sectional diameter of (2±0.1)mm; 　——Ring mold: meet the test requirements of 6.6.3. 6.6.2 Test environment The test shall be carried out in an environment of (23±2)℃ and relative humidity of (50±10)%. Before the test, the test equipment and materials shall be placed in the test environment for 5h~6h. 6.6.3 Test steps When the needle touches the glass bottom plate, adjust the scale of the penetrometer so that the reading is 0 when the needle touches the bottom plate. Mix the materials according to 6.5.3c), pour them into the ring mold until they overflow slightly, and scrape the surface. When the mixture begins to solidify, lower the needle until it touches the surface of the mixture, then gently release the needle and let it penetrate into the mixture under its own weight. Repeat this operation every 15 seconds, wipe the needle clean after each penetration, and move the sample so that the penetration sites are at least 5 mm apart to prevent the same site from being penetrated twice. The penetration site is also at least 5 mm away from the edge of the mold. Start timing from the end of mixing until the indentation no longer appears, which is the curing time. 6.6.4 Result determination The test is performed 3 times. If the results of the 3 tests all meet the indicators provided in the product technical manual, it is determined to be qualified. 6.7 Hydrate degradability is carried out in accordance with the method specified in GB/T16886.14. 6.8 Biocompatibility According to the intended use of calcium sulfate hemihydrate, biological evaluation is carried out in accordance with the requirements of GB/T16886.1. 7 Marking, packaging, transportation and storage 7.1 Marking The packaging of the product shall have at least the following markings: 　——Name, address and telephone number of the manufacturer; 　——Product name, trademark and model; 　——Batch number; 　——Net weight; 　——Date of production. 7.2 Packaging 7.2.1 The product shall be packaged in a sealed, moisture-proof container. The container material shall be non-toxic, non-polluting and non-affecting the performance of the product. The packaging container shall have the performance of not being damaged or broken during normal handling or storage. 7.2.2 The packaging shall be fully marked, and the words or signs such as "moisture-proof", "shockproof" and "keep away from harmful substances" as specified in GB/T191 shall be marked on the outer packaging. 7.2.3 Each package shall be accompanied by a certificate of inspection and an instruction manual. The instruction manual shall be written in accordance with relevant national regulations and shall also include the following contents: 　——Product purpose; 　——Product performance; 　——Precautions. 7.3 Transportation and storage 7.3.1 During transportation, moisture shall be avoided, and loading and unloading shall be reasonable and handled with care. 7.3.2 Products should be stored in clean, dry rooms free of harmful substances. 8 Quality Assurance Requirements The manufacturer should have a corresponding quality assurance system that complies with the requirements of YY/T0287.

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