CN-122013526-A - Zwitterionic modified PMP membrane based on dopamine mediation and application of membrane in ECMO

Abstract

The invention relates to the technical field of biomedical materials, in particular to a surface modification method of a poly-4-methylpentene (PMP) hollow fiber membrane, which improves the blood compatibility of the material by the cooperation of a Polydopamine (PDA) coating and a zwitterionic grafting technology and is suitable for blood contact devices such as external membrane pulmonary oxygenation (ECMO). The invention provides a modified PMP membrane based on dopamine mediated zwitter ions, which comprises a PMP membrane and a modified layer on the surface of the PMP membrane, wherein the modified layer comprises a polydopamine interlayer formed on the surface of the PMP membrane through dopamine in-situ oxidation self-polymerization, and a zwitterionic polymer brush grafted on the polydopamine interlayer.

Inventors

• CUI CHAOLIANG
• Lv xing
• WANG XIAOYUN
• ZHOU YUE
• CHENG YANGMING
• XING WEIHONG

Assignees

• 南京工业大学
• 江苏爱科膜高科技有限公司
• 南京工业大学苏州未来膜技术创新中心
• 南京工大膜应用技术研究所有限公司

Dates

Publication Date

20260512

Application Date

20250620

Claims (9)

1. 1. The modified PMP membrane based on the dopamine-mediated zwitter ions is characterized by comprising a PMP membrane and a modified layer on the surface of the PMP membrane, wherein the modified layer comprises a poly-dopamine intermediate layer formed on the surface of the PMP membrane through dopamine in-situ oxidation self-polymerization, and a zwitterionic polymer brush grafted on the poly-dopamine intermediate layer.
2. 2. The dopamine-mediated zwitterionic-based modified PMP membrane according to claim 1, wherein said zwitterion is a Phosphobetaine (PBMA) monomer.
3. 3. The dopamine-mediated zwitterionic-based modified PMP membrane according to claim 1, wherein said PMP membrane is a hollow fiber membrane.
4. 4. The method for producing a modified PMP film according to claim 1, comprising the steps of: (1) Cu 2+ /H 2 O 2 catalyzes dopamine polymerization Immersing the PMP membrane in Tris buffer solution containing dopamine, cuSO 4 ·5H 2 O and H 2 O 2 , and reacting for 4-8H; (2) Grafting modification of PBMA Taking out and cleaning the PMP film treated in the step (1), and then putting the PMP film into PBS buffer solution (pH=5.6) of PBMA (10 wt%) for reaction for 12h; (3) Drying And cleaning and drying the PMP film grafted with the zwitterion to obtain the modified PMP film.
5. 5. The method of claim 4, wherein the Tris buffer of step (1) has a dopamine concentration of 1-5mg/mL, a CuSO 4 ·5H 2 O concentration of 0.2-1mM, a H 2 O 2 concentration of 1-3wt%, and a pH of 8-10.
6. 6. A method according to claim 3, wherein in step (2) the PBS buffer has a pH = 5-7 and the pbma concentration is 5-15wt%.
7. 7. A method according to claim 3, wherein in step (3), the zwitterionic grafted PMP film is rinsed with ultra pure water and dried by hanging.
8. 8. ECMO oxygenator characterized by the use of a dopamine-based mediated zwitterionic modified PMP membrane according to any one of claims 1 to 3 as gas exchange site.
9. 9. The modified membrane of claim 1 for ECMO, wherein said dopamine-based zwitterionic modified PMP membrane is used in ECMO membrane lung to oxygenate excess CO 2 .

Description

Zwitterionic modified PMP membrane based on dopamine mediation and application of membrane in ECMO Technical Field The invention relates to the technical field of biomedical materials, in particular to a surface modification method of a poly-4-methylpentene (PMP) hollow fiber membrane, which improves the blood compatibility of the material by the cooperation of a Polydopamine (PDA) coating and a zwitterionic grafting technology and is suitable for blood contact devices such as external membrane pulmonary oxygenation (ECMO). Background Extracorporeal membrane oxygenation (Extracorporeal Membrane Oxygenation, ECMO) is a technique that temporarily replaces or assists cardiopulmonary function in a patient by extracorporeal circulation equipment. ECMO is used as a high-end life support device, and the blood compatibility and stability of the core membrane lung material directly determine the clinical effect. In the prior art, the hydrophobic defect of the PMP hollow fiber membrane and the limitation of the traditional modification method are urgent to realize breakthrough through the surface chemical modification and functional collaborative design. However, the existing modification technology still has some defects, such as easy falling and poor stability of physical coating (such as heparinization), possibility of damaging the PMP bulk structure by chemical grafting (such as plasma treatment) to influence the air permeability, and difficulty in combining anticoagulation and anti-fouling performance by a single modification strategy. The prior art has disclosed the use of amphiphilic polymers as hydrophilic coatings such as Phosphatidylcholine (PC), carboxybetaines (CB) and Sulfobetaines (SB). In the early work of the inventors, the zwitterionic polymer, poly (sulfobetaine methacrylate) (PSBMA) and dopamine, were co-deposited on the surface of PMP hollow fiber membranes to construct an antithrombotic coating to reduce protein adsorption and improve the blood compatibility of the original PMP membrane. However, the modified PMP hollow fiber membrane formed by the above method does not meet the requirement of high pollution resistance, and further improvement of the above technology is needed. As a novel zwitterionic monomer, phosphobetaine (PBMA) gradually becomes a research hot spot for improving the blood compatibility of materials due to the unique chemical structure and performance advantages. The anticoagulant property of the phosphobetaine is derived from electronegativity of a phosphate group in the molecule, and can inhibit platelet adhesion and activation of a coagulation factor through electrostatic repulsion. The blocking effect of the phosphate groups on the coagulation cascade is more pronounced than in the case of conventional Sulfobetaines (SBMA) or Carboxybetaines (CBAA), and in particular performs better under high shear conditions, such as ECMO blood circulation. The phosphobetaine can keep solubility in acidic, neutral and alkaline mediums, and can not generate precipitation due to the change of environmental pH, and the property makes the phosphobetaine suitable for the surface modification of medical instruments under different physiological conditions. The phosphate group and the quaternary ammonium group in the chemical structure form a stable zwitterionic structure, and the coating can still keep the contact angle change less than 5% even in long-term blood contact or PBS soaking experiments, so that the coating has no shedding phenomenon. The inventor tries to form a hydrophilic coating on a PMP hollow fiber membrane by codeposition of Phosphobetaine (PBMA) and dopamine, but the codeposition method has difficulty in ensuring the uniformity and poor stability of PBMA grafting. Thus, there is a need for improvements in existing dopamine-mediated zwitterionic modified PMP membranes and methods for their preparation to meet the increased demand. Disclosure of Invention Aiming at the problems, the invention provides a modified PMP membrane based on dopamine mediated amphoteric ions, a preparation method and application thereof, and long-acting stable blood compatibility improvement is realized through the synergistic effect of dopamine self-polymerization and specific amphoteric ion grafting, and meanwhile, the gas exchange performance of the membrane is maintained. Firstly, the invention provides a modified PMP membrane based on dopamine mediated zwitterion, which comprises a PMP membrane and a modified layer on the surface of the PMP membrane, wherein the modified layer comprises a polydopamine interlayer formed on the surface of the PMP membrane through dopamine in-situ oxidation self-polymerization, and a zwitterionic polymer brush grafted on the polydopamine interlayer. Preferably, the zwitterionic is a Phosphobetaine (PBMA) monomer. Preferably, the PMP membrane is a hollow fiber membrane. Secondly, the invention also provides a preparation method of the modified PMP membrane based on d