Nanjing Medical University Second Affiliated Hospital to Transfer Novel Anticoagulant Coating Technology for Extracorporeal Circuits at RMB 100,000

Recently, the Second Affiliated Hospital of Nanjing Medical University released a public notice on the transformation of scientific and technological achievements. Through assessment-based pricing, the hospital intends to"An Anticoagulant Coating, Tubing, and Preparation Method Therefor"The relevant patents are transferred to the industry party for use, with a total transfer fee of RMBRMB 100,000. The inventor of this patented technology isLi Qingguo's Team。

The core of this technology isPreparation of Anticoagulant Coatings and Tubing Containing Such Coatings, for use in extracorporeal blood circulation devices such as CRRT, ECMO, artificial kidneys, and synthetic blood vessels.

itsForming a Coating on the Inner Wall of PVC Pipes Through Specific Steps:First, dopamine is allowed to self-polymerize to form a polydopamine layer, followed by the covalent immobilization of albumin (bovine serum albumin, BSA) and argatroban. Concurrently, albumin is adsorbed onto the inner wall of the tubing, ultimately yielding a stable, highly transparent anticoagulant coating (average transmittance: 82.60–89.74%). Compared with existing heparin-coated tubing, this coating demonstrates superior anticoagulant efficacy (prolonging activated clotting time [ACT] by approximately 117.3% and clotting time [CT] by approximately 50.3%), reduced thrombus formation, and enhanced stability. Furthermore, it reduces the dosage of anticoagulant medications required and helps control tubing costs.

Extracorporeal Blood Circulation Technology(e.g., CRRT, ECMO, artificial kidneys, and synthetic blood vessels) are critical interventions for the management of critically ill patients, with the core therapeutic requirement beingEnsures smooth blood flow in the extracorporeal circuit, prevents thrombus formation, and minimizes additional patient injury from anticoagulant medications., especially for patients with multi-organ dysfunction and a high risk of bleeding, safe and efficient anticoagulation regimens are particularly important.

Clinically, existing cardiopulmonary bypass circuits largely rely on imported heparin-coated tubing; however, these exhibit significant limitations in practical application:First, the anticoagulant effect is suboptimal and short-lived.Traditional heparin coatings are immobilized through physical blending or ionic bonding, making them prone to detachment under blood flow shear stress or protein adsorption. This can lead to thrombus formation on the inner walls of tubing, necessitating additional high-dose anticoagulant therapy. However, excessive heparin use can impair hepatic and renal function, increase the risk of bleeding, and exacerbate the patient’s physiological burden.Second, the contradiction between coating stability and functionality is prominent., Although covalently bonded heparin coatings are firmly immobilized, they tend to induce conformational changes in heparin molecules, leading to loss of anticoagulant activity and failing to balance stability with anticoagulant efficacy.

Meanwhile, existing tubing systems still suffer from two major critical pain points: on the one hand,Insufficient Light Transmittance, in clinical applications, it is necessary to observe the blood flow status and morphological changes within the tubing in real time. However, traditional coated tubing exhibits poor light transmittance (for instance, the average light transmittance of the glutathione coating in the comparative example was only 69.34%), which affects physicians' assessment of the patient's condition and adjustment of operational procedures; on the other hand,High Costs Persist, with Expensive Imported Tubing, and must be used in conjunction with other consumables, significantly increasing patients' treatment costs and medical burden.

Furthermore, existing circuits lack targeted design, making them difficult to adapt to the usage scenarios of different extracorporeal circulation devices. For patients requiring long-term extracorporeal support therapy, the risk of thrombosis increases with prolonged treatment duration, while current technologies fail to provide sustained and stable anticoagulation assurance. Meanwhile, issues such as coating delamination and thrombus formation may lead to circuit occlusion, compromising treatment continuity and even endangering patient lives.

Therefore, existing cardiopulmonary bypass anticoagulation circuits have limitations in practical applications, including limited anticoagulant efficacy, high safety risks, poor light transmission, and high costs. There is an urgent need for an improved technology with strong stability, high-efficiency anticoagulation, good light transmission, and controllable costs to meet the clinical demand for upgrading cardiopulmonary bypass therapy.

The core advantages and advanced nature of this patented technology lie in breaking through the performance limitations of traditional heparin-coated tubing, by“Innovative Coating Structure + Optimized Anticoagulation Mechanism + Upgraded Key Attributes”Triple breakthroughs have established a robust, efficient, and safe anticoagulation solution for extracorporeal circulation, comprehensively addressing the industry’s critical pain points of inadequate anticoagulation, elevated risks, and poor adaptability associated with existing technologies.

First, innovative coating structures achieve ultra-stable anticoagulant effects.Traditional heparin coatings rely on physical blending, ionic bonds, or single covalent bond attachment, presenting a dilemma of susceptibility to detachment or conformational disruption. This technologyPioneering a dual-layer structure comprising a “polydopamine underlayer + albumin-argatroban composite layer”:Leveraging the self-polymerization property of dopamine to form a polydopamine layer firmly adhered to the inner wall of PVC tubes, the anticoagulant drug argatroban is then stably immobilized via covalent bonding with bovine serum albumin (BSA); meanwhile, BSA also adheres to the tube’s inner surface to form a protective layer, thereby creating“Anchoring-Binding-Protection”triple stabilization mechanism. Validated through in vitro circulation testing, the coating maintained excellent performance after 12 hours of circulation, extending the clotting time by 2.25-fold compared to uncoated PVC tubing—significantly surpassing the 1.42-fold extension achieved by heparin coatings—and substantially reducing thrombus formation, thereby fundamentally addressing the core issues of traditional coatings, namely their propensity for delamination and short-lived anticoagulant efficacy.

Second, the synergistic anticoagulation mechanism achieves a leapfrog improvement in efficacy.Technological InnovationCombining the specific anticoagulant effect of argatroban with the biocompatibility advantages of BSA to form a synergistic and enhanced anticoagulation systemExperimental data show that the coated tubing achieves a mean activated clotting time (ACT) of 265.6 seconds, representing a 117.3% prolongation compared with conventional heparin-coated tubing; the mean clotting time (CT) is 25.1 minutes, a 50.3% increase. Meanwhile, secretion of the platelet activation marker TXB-2 is reduced by 31.4%, indicating potent inhibition of thrombus formation while minimizing impacts on platelet function. This synergistic mechanism substantially reduces the need for adjunctive clinical anticoagulants, effectively mitigating the risk of multi-organ injury associated with excessive heparin exposure, and provides a safer therapeutic option for patients at high risk of bleeding.

Third, key performance upgrades are tailored to meet actual clinical needs.Addressing the core demands for light transmittance and cost-effectiveness in cardiopulmonary bypass circuits, two key technological breakthroughs have been achieved:First, the light transmittance is significantly improved.By controlling the thickness of the polydopamine coating under acidic conditions and leveraging the adhesive properties of BSA, the average light transmittance of the coating reaches 82.60–89.74%, significantly higher than the 69.34% of traditional glutathione coatings, thereby meeting the clinical need for real-time observation of blood flow and morphological changes;2. Strong cost controllabilityBy combining a PVC substrate with domestically sourced raw materials, this approach eliminates reliance on costly imported tubing. Furthermore, the manufacturing process does not require complex equipment; scalable production can be achieved using constant-temperature shakers and ultraviolet (UV) irradiation, thereby balancing performance with cost-effectiveness. In addition, these coated tubes are broadly compatible with various extracorporeal circulation devices, including CRRT, ECMO, artificial kidneys, and vascular grafts, addressing the limited adaptability of traditional tubing and providing standardized anticoagulation solutions for diverse clinical scenarios.

In the field of anticoagulant-coated extracorporeal circuits, with the widespread adoption of critical care technologies such as CRRT and ECMO, the stability, safety, and cost-effectiveness of anticoagulant coatings have become the core of industry competition. International brands have long dominated the market, while Chinese enterprises and research institutions are accelerating technological breakthroughs, shaping a market landscape characterized by “import dominance and domestic emergence.”

Wu Gang's Team at South China University of TechnologyDeveloped byA Medical Catheter with a Hydrophilic Coating on Its Inner Wall and Its Preparation Method,Zwitterionic hydrogel coating with excellent antifouling and anticoagulant properties, reducing bacterial adhesion and thrombus formation; suitable for central venous catheters and dialysis tubing; currently in the laboratory-scale and pilot-scale process development stage.

Chongqing Tianwaitian Biotechnology Co., Ltd.R&D“Anticoagulant Coating Materials for Blood-Contacting Materials and Their Applications”, innovatively adopting a dual-layer independent packaging coating design of "base layer + top layer," breaking through the limitations of traditional anticoagulant coatings that struggle to balance stability and hydrophilicity. The base layer coating is prepared by cross-linking amino compounds (optionally polylysine, polyethyleneimine, or polydopamine) with silane coupling agents (γ-glycidoxypropyltrimethoxysilane), where unreacted amino compounds provide sufficient "anchoring sites" for the top layer reaction; the top layer coating uses phosphate compounds (such as phosphocholine or phosphoethanolamine) as biomimetic hydrophilic anticoagulants, combined with reducing agents like sodium borohydride and ascorbic acid, covalently grafted onto the base layer via phosphoramidate bonds to form a zwitterionic structure mimicking the outer layer of cell membranes.

Ordos Central Hospital (Inner Mongolia Autonomous Region Institute of Ultrasound Imaging)R&D“Anticoagulant Fusion Protein HSA-Qinghaienin(c), Its Encoding Gene, and Applications Thereof”, with the "fusion protein + polydopamine substrate" as the core technical pathway, pioneering a new "dual-function synergy" model for anticoagulant coatings. This technology first fuses the functional fragment (aa94-199) of the tick-derived anticoagulant protein Qinghaienin with human serum albumin (HSA) to construct the HSA-Qinghaienin(c) fusion protein (amino acid sequence SEQ ID NO: 1). In this construct, HSA inhibits the adsorption of plasma proteins and platelets, while Qinghaienin(c) targets Factor XII (FⅫ) in the endogenous coagulation pathway, thereby avoiding the risk of bleeding. Subsequently, the fusion protein is covalently grafted onto the material surface via a polydopamine (PDA)-polyethyleneimine (PEI) underlayer, forming a stable anticoagulant coating.

Overall, domestic anticoagulant coating technologies are breaking the import monopoly through differentiated innovation. Various technical approaches are collaboratively advancing clinical translation, providing diverse solutions for the anticoagulation upgrade of blood-contacting medical devices and facilitating the high-quality development of domestically produced medical consumables.