Medical products Sodium alginate can treat diabetes in the future.

　　There are still many obstacles to be cleared up if sodium alginate, a marine polysaccharide material, wants to make great efforts in the field of biomedicine. Perhaps in the near future, diabetic patients can return to normal blood sugar level by taking a long-acting hypoglycemic drug without insulin injection. The latest research: the polymer formed by sodium alginate has new biological characteristics of inhibiting trypsin hydrolysis.
　

　　In recent years, with the development of marine resources, alginate, chitosan, agarose and other polysaccharide materials from marine life have gradually entered the public eye.

　　However, some marine polysaccharide materials with medical value, which are derived from natural materials and have good biocompatibility, biodegradability, plasticity and low price, have become the "hot cakes" in the field of biomedical materials.

　　The most representative is the natural polysaccharide from brown algae — — Sodium alginate.

　　"When sodium alginate molecules meet calcium ions, gelation will occur instantly." Ma Xiaojun told the China Journal of Science that sodium alginate with polyanion can be transformed by divalent or trivalent ions, and this ion-dependent gel can maintain a stable gel structure at 0℃~100℃.

　　Based on the ideal gelation performance of sodium alginate, the hydrogel formed has the characteristics of strong water retention, moderate strength and easy processing and molding, and has now become the protagonist in the manufacture of dental imprinting materials, hemostatic dressings and wound dressings.

　　After sodium alginate is processed into microspheres, it can also be used as embolic agent for interventional therapy, soft tissue enhancer, immune isolation carrier for tissue cell transplantation, tissue engineering scaffold material, etc. After modification, it can also be made into pharmaceutical excipients, drug sustained and controlled release carrier materials, etc.

　　Not long ago, a new research achievement pushed the application of sodium alginate to the peak.

　　Ma Xiaojun's research group discovered for the first time that the polymer formed by sodium alginate has a new biological characteristic of inhibiting trypsin hydrolysis. The polymer binds protease by winding and wrapping to prevent it from contacting with substrate, thus inhibiting enzymatic hydrolysis.

　　According to the staff of the research group, they took insulin, an active protein drug, as a model, and sodium alginate as a protease inhibitor. Through in vitro enzymatic hydrolysis experiments, it showed that the inhibitor could effectively prevent trypsin from enzymatic hydrolysis of oral drugs, and its enzymatic inhibition efficiency was about 400 times that of existing similar products.

　　According to Cui Fuzhai, a professor in the Department of Materials Science and Engineering in Tsinghua University, the new characteristic that sodium alginate can inhibit enzymes is also a necessary condition for developing long-term sustained-release carriers for protein and polypeptide drugs.

　　"The insulin drug test shows that the slow release rate of sodium alginate polymer is 400% higher than that of the conventional method, which may provide ideas for diabetic patients to manufacture long-acting hypoglycemic drugs, and change daily medication to weekly or even longer medication." Cui Fuzhai told the reporter of China Science News.

　　In Ma Xiaojun's view, sodium alginate materials will also provide new treatments for tumors, diabetes and other diseases from a new perspective.

　　"Based on the microcapsule technology of sodium alginate, we successfully applied SPF porcine islet cells to the blood sugar correction of patients with insulin-dependent diabetes mellitus. Patients can return to normal blood sugar levels without insulin injection and immunosuppressants."

　　Ma Xiaojun said that at present, the LCT company in Australia has started the phase II clinical trial of this technology in New Zealand and Argentina. This microcapsule technology based on sodium alginate will bring good news to the treatment of diseases such as bioartificial liver support system and Parkinson's disease because of its immune isolation function.

　　Many problems remain to be solved

　　Sodium alginate has been used as a food additive for decades, and its safety has been recognized by the public. However, if we want to apply it to demanding medical products, we still face many unsolved problems.

　　Ma Xiaojun said that the physical and chemical properties of sodium alginate materials used in vivo implantation environment, such as interventional therapy embolic agents, soft tissue enhancers, and immune isolation carriers for tissue cell transplantation, must meet the requirements of Class III medical device standards.

　　However, because sodium alginate is a material extracted from marine organisms, there are many impurities such as protein, polyphenols and endotoxin brought in by the outside world during the extraction process, which has become the main factor affecting its biocompatibility and restricting its clinical application.

　　"Protein can cause inflammatory reaction and fibrosis reaction after transplantation of marine polysaccharide biomedical products. Polyphenols can cause serious damage to the host's liver, kidney, mucosal tissue, nervous system, etc., and endotoxin can also cause fever, tissue hypoxia and even shock, and damage to liver and kidney." Ma Xiaojun told reporters frankly.

　　More importantly, the chemical structure characteristics of polysaccharide and protein, such as molecular weight, charge and charge distribution, determine that they will form polysaccharide through electrostatic interaction — Protein complex, which makes it more difficult to remove impurity protein from polysaccharide.

　　In Ma Xiaojun's view, the development of highly purified technology without changing the physicochemical properties of polysaccharide materials, and the effective removal of protein and endotoxin in the process of material purification amplification to ensure that the products meet the standards are all difficult problems in developing sodium alginate medical materials.

　　For related downstream enterprises, besides developing the drug carrier function of sodium alginate, solving the large-scale preparation process of material modification and reducing the cost of pharmaceutical excipients of sodium alginate-based materials on the premise of ensuring the quality of pharmaceutical excipients are the main problems faced by large-scale industrialization.

　　In order to promote the application of sodium alginate in the biomedical field, Ma Xiaojun's research group comprehensively considered various influencing factors, and developed the integrated separation and purification technology and pilot-scale amplification process of sodium alginate, which mainly included adsorption, membrane separation, ultracentrifugation and selective precipitation. In the future, it is expected to realize the kilogram-scale preparation and industrialization of tissue engineering-grade alginate with high purity, controllable performance and good batch repeatability.