Research On The Quality Inspection Method And Industry Standard Revision Of "Crosslinked Sodium Hyaluronate Gel For Plastic Surgery"

Hyaluronic acid(HA)has good biocompatibility,hydrophilicity,viscoelasticity,and low immunogenicity.It is currently one of the most commonly used filling materials for injection microplastic surgery.The current industry standard YY/T 0962-2014 "Cross-linked Sodium Hyaluronate Gel for Plastic Surgery" has been released to the present,and some content and indicators can no longer adapt to the progress and development of the industry.For example: the standard lacks limit requirements and inspection methods for protein content in finished products,and inspection methods for items such as total heavy metals,swelling degree,free sodium hyaluronate content,syringe plunger pushing force,residual amount of crosslinking agent,etc.need to be improved,etc..The main research contents and results are as follows:1)Sample drying method for infrared identification: The influence of the drying method after ethanol precipitation,the direct drying method and the current standard sample processing method(freeze drying method)on the qualitative identification of cross-linked sodium hyaluronate gel is discussed.The experiment shows three processing methods Both are suitable for the identification of cross-linked sodium hyaluronate gel.2)Particle size distribution detection method: The microscopic method may change the particle properties and thus the particle size.The result is highly subjective,and the sample fades faster during operation,which affects the observation,so the microscope method is deleted..Make sure to use a laser particle size analyzer to directly read the D50 and D90 values of the sample from the spectrum.3)Determination of free sodium hyaluronate content: In order to solve the problem that the supernatant boundary of the cross-linked sodium hyaluronate gel single-phase product is not obvious after centrifugation,a 300 mesh screen,500 mesh screen,slow filter paper,and medium speed are added The sample pretreatment method of filter paper and 0.45 μm filter membrane filtration has determined that the slow filter paper filtration method is more suitable for the pretreatment of all products.4)Protein content determination: use acid hydrolysis method to process the sample,make sure that the sample is treated with 0.5 mol/L sulfuric acid solution and treated at(95±5)℃ for 45 min.After the sample is completely dissolved,the Coomassie brilliant blue method can be used to determine the protein in the finished product.content.5)Heavy metal determination: The cross-linked sodium hyaluronate gel is insoluble in water.The sample needs to be digested with acid,and then treated with sulfuric acid,nitric acid,and hydrochloric acid.The digestion solution is colorimetrically tested for heavy metal content.6)BDDE cross-linking agent content determination: The current standard gas chromatography analysis method and microplate reader detection technology have been appropriately revised.In order to better release BDDE from the inside of the gel,an enzymatic treatment step of the sample is added before the gas chromatography measurement,and then the BDDE is extracted,and the supernatant is centrifuged for measurement.For the detection technology of the microplate reader,the same amount of hyaluronidase is added to the standard solution as that of the enzymatically hydrolyzed sample to deduct the effect of hyaluronidase on the measurement result.7)Measurement of swelling degree: The current standard measurement method cannot effectively remove excess water,and the test operation is highly subjective.In this study,a 500-mesh screen was used to filter the sample solution,and the method to remove excess water was clarified.8)Push force measurement: Push the syringe core rod at a certain push speed to obtain the force curve.The wide fluctuation range of the pushing force indicates that the sample has uneven distribution or aggregation and concentration,which will interfere with the actual operation.Through the comparison of the pushing force at different speeds,it is finally determined that a speed of 30 mm/min is used to read the maximum,minimum and average pushing force.All the contents of this article will provide experimental and technical support for the revision of the industry standard.As a recommended standard,this standard can give enterprises a reference and guidance,and promote the healthy development of cross-linked sodium hyaluronate gel products for plastic surgery.