| Background:Since the 21 st century,the incidence and mortality of malignant tumors have risen sharply worldwide.Both developed and developing countries are facing severe challenges.The "integrated model" based on surgical resection is currently the main strategy for tumor treatment.Bleeding is inevitable during surgical resection of tumors.Conventional methods such as local compression,electrosurgical coagulation or suture ligation are usually used to effectively stop bleeding on wounds and blood vessel ends.However,there is still the possibility of bleeding after surgery.Implanting excellent hemostatic materials into the wound during the operation can significantly reduce the incidence of postoperative bleeding.In addition,during the surgery,for patients whose tumors are late in stage,large in size,local infiltration,cannot be completely removed and local tumor tissue remains.These patients need to be locally implanted with chemotherapeutic drugs during the operation to reduce the risk of local tumor recurrence and metastasis.In response to the above problems,hemostatic materials and chemotherapeutic drugs are currently implanted during surgery to prevent postoperative bleeding and reduce the risk of local tumor recurrence and metastasis.However,in the actual operation process,the chemotherapeutic drugs need to be wrapped with hemostatic materials.But,the hemostatic materials currently used in clinical practice do not have a cyst and need to be made during the operation.It not only wastes time but also makes them inappropriate,unable to carry out effective wrapping,and present problems such as improper placement.Therefore,the local hemostatic and anti-tumor effects of the combined application of biodegradable hemostatic materials and chemotherapy drugs in surgical operations have attracted great attention.Therefore,it is necessary for clinical development to prepare a hemostatic sac with excellent hemostatic properties and capable of carrying chemotherapeutic drugs.Objective:1、Preparation of a degradable hemostatic sac with excellent hemostatic properties and capable of carrying chemotherapeutic drugs;2、Research the general performance of degradable hemostatic sacs that can carry chemotherapeutic drugs;3、The hemostatic performance and biological safety of the degradable hemostatic sac that can carry chemotherapeutic drugs and the drug-loaded hemostatic sac are evaluated.Methods:1、Using hydroxyethyl cellulose as a raw material,a vacuum freeze-drying method is used to prepare a degradable hemostatic sac that can carry chemotherapeutic drugs;2、Scanning electron microscope to observe the microstructure of the material,and determine its porosity and water absorption;3、Determine the in vitro blood clotting index of the experimental group(degradable hemostatic sac that can carry chemotherapeutic drugs),drug-loaded group(add 3mg5-FU of degradable hemostatic sac that can carry chemotherapeutic drugs),gelatin sponge group,and medical gauze group,at the same time establish a rat liver hemorrhage model and a rat tail hemorrhage model,and compare the hemostatic time of different materials to evaluate the hemostatic effect;4、Observe the degradation of materials in the experimental group(degradable hemostatic sacs that can carry chemotherapeutic drugs)and the drug-loaded group(add3mg 5-FU degradable hemostatic sacs that can carry chemotherapeutic drugs),through the subcutaneous implantation experiment on the back of rats,on the 1st,3rd,7th,11 th,and 14 th days after the operation.In addition observe local inflammation by HE staining of local tissues.At the same time,on the 7th and 14 th day after the operation,the blood routine and liver function analysis of the rats were tested for hematological toxicity;5、Perform an in vitro hemolysis test to determine the hematological compatibility of the hemostatic material;6、An extract of the material was prepared for the acute systemic toxicity test in mice.Results:1、Electron microscopy observed that the degradable hemostatic sac that can carry chemotherapeutic drugs is a layered porous structure,and the layers are cross-linked to maintain connection with each other,and the layers are attached with small holes.The porosity measurement results show that they are all greater than 89%,and they have excellent water absorption performance.As the concentration of hydroxyethyl cellulose increases,the density and toughness of the material increase,but the gaps and pore diameters between the layers become smaller,and the porosity and water absorption performance decrease.Based on comprehensive analysis,a degradable hemostatic sac prepared with a concentration of 4% hydroxyethyl cellulose that can carry chemotherapeutic drugs was selected for follow-up experiments.2、The experimental group(74.76±1.46)and the drug-loaded group(74.12±1.64)had the same in vitro blood clotting index,the difference was not statistically significant(P>0.05),but both were smaller than the gelatin sponge group(80.71±1.52),the difference was statistically significant(P<0.05),it can be seen that whether the drug is loaded or not has no significant effect on the hemostatic effect of the material,and the coagulation effect is better.3、In the rat liver hemostasis experiment,the hemostasis time of the experimental group was(133±24)s,the drug-loaded group was(139±20)s,and the gelatin sponge group was(207±29)s.Compared with the drug-loaded group,the experimental group There was no statistically significant difference in hemostasis time(P>0.05).Compared with the gelatin sponge group,the hemostasis time between the experimental group and the drug-loaded group was significantly shorter,and the difference was statistically significant(P<0.05).In the rat tail docking hemostasis experiment,the hemostasis time of the experimental group(6.49±1.05)min the drug-loaded group(6.84±0.70)min and the gelatin sponge group(8.92±1.33)min was consistent with the results of the liver hemostasis experiment.4、The subcutaneous implantation test on the back of the rat shows that the implanted material has been completely degraded within 14 days,and the degradation time is reasonable.5、After material implantation,the HE staining inflammation trend of the experimental group and the blank control group was basically the same,and it was the most serious on the 3rd day,and the inflammation was reduced and disappeared in the later stage.The postoperative inflammatory reaction in the drug-loaded group was all severe.By 14 days after the operation,the inflammatory reaction was reduced with the absorption of chemotherapeutic drugs and materials.The blood routines of the experimental group and the drug-loaded group were in the normal range on the 7th and14 th day after surgery.Although the percentage of white blood cells and neutrophils in the blood routine of the drug-loaded group decreased on the 7th day after surgery,they were still at normal levels.The analysis may be due to bone marrow suppression caused by the release of 5-FU;but compared with intravenous chemotherapy,bone marrow suppression is significantly less.On the 7th day after surgery and on the 14 th day,the experimental group and the drug-loaded group have no obvious abnormalities in liver function.6、The results of the hemolysis test showed that the hemolysis rate of the degradable hemostatic sac that can carry chemotherapeutic drugs is less than 5%,and the blood compatibility is good.At the same time,it has no acute systemic toxicity and meets the requirements of the medical device GB/T 16886.11-2011 standard.Conclusion: The prepared degradable hemostatic sac that can carry chemotherapeutic drugs has good hemostatic performance and biocompatibility;in addition,the addition of chemotherapeutic drugs does not have a significant impact on its hemostatic performance and biological safety,and has broad application prospects. |
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