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Application of anticoagulant materials?
Application of anticoagulant materials

Study on the application of plasma deposited polymer film in medical anticoagulant materials

Plasma deposition; Polymer film; Anticoagulant material

Study on polymer membrane for blood anticoagulant materials

Liu Zhijing

(Associate Professor, Department of Astronomy and Applied Physics, China University of Science and Technology, Hefei 230026)

Keywords plasma deposition, polymer membrane, blood anticoagulant material

This paper introduces the medical application of blood-contacting polymers and the definition of blood-compatible materials, and discusses the characteristics and applications of plasma deposition of polymer films, especially in anticoagulant materials.

I. Introduction

Some plasma processing methods, such as deposition, polymerization, sputtering, ion implantation, cleaning and disinfection, are practical high-tech and widely used in microelectronics, thin films, material processing and other fields. Plasma chemical vapor deposition and polymerization can modify and coat the surface of materials to improve the blood compatibility of biomaterials. These methods are not only applicable to inorganic materials such as metals, ceramics and carbon, but also to organic polymer materials. Polymer materials are widely used in medicine, but there are also some unfavorable factors, such as coagulation, inflammation and allergic reaction. Therefore, how to improve the properties of materials (such as blood compatibility and anticoagulation) to overcome these shortcomings is still a key issue in basic research and material preparation. In the manufacture of heart valves and extracorporeal blood circulation devices, it is urgent to use anticoagulant materials in artificial blood vessels and other medical devices in contact with blood. The research of anticoagulant materials is considered as an important symbol of the research level of biomaterials. Strengthening the research in this field is of great significance to improve biomaterial science's academic status and influence in the world [1]. This paper introduces the application of blood contact polymer, the definition of blood soluble polymer, the characteristics and application of polymer membrane, and the properties of anticoagulant materials.

Second, the characteristics of polymer films deposited by plasma

Since 1950s, polymers have been widely used in the medical field. Polymer equipment in contact with blood includes: extracorporeal blood circulation equipment, catheters, blood bags and catheters for blood transfusion, renal dialysis equipment, plasma removal and detoxification equipment, heart valves and blood vessel transplantation. The application of these devices is increasing at an annual rate of 65,438+00% ~ 20%. In short-term equipment, polyvinyl chloride (PVC) is the most widely used. Followed by silicone rubber and polyethylene. In dialysis equipment, cellulose and its transformants, polyamide, polypropylene, polyacrylonitrile, polyester, etc. Both are basic membrane materials and fiber tube materials. Commercial vascular grafts and heart valves are mainly polyester, mainly polyethylene terephthalate (Dacron) and polytetrafluoroethylene (Teflon). In the early 1990s, polyurethane ionomers (polyurethane) and biopolymer materials were developed. From 1980 to 1990, the main improvement of polymer is to use medical-grade polymer, which does not release toxic components and carcinogens, and its degradation products are non-toxic and carcinogenic, and do not accumulate in organisms. Permeability and mechanical strength of membranes and fiber tubes in dialysis devices, as well as mechanical strength and pore characteristics of vascular grafts.

Although polymers are widely used, they are still unsatisfactory. First, the mechanical plasticity (flexibility) of some polymers is worse than that of naturally occurring blood vessel walls, which leads to turbulence and reduces dialysis, platelet activity and aggregation [2, 3]. Second, some polymers will release some additives, stabilizers and plastic particles, which will cause damage to the blood. Third, some polymer degradation products can cause blood coagulation. Stimulate immune response, cell response, etc. In order to overcome the above shortcomings, on the one hand, long-term anticoagulant auxiliary drugs, such as coumarin (anti-vitamin K), are used in medical practice, on the other hand, new materials that do not cause coagulation and immune response are devoted to research. Polymer film materials obtained by plasma deposition and polymerization technology have special advantages. This film can be uniformly deposited and formed in materials with complex geometries and even fiber gaps. It can be combined with almost all substrate materials, such as metal, glass, ceramics, semiconductors and so on. , and has good adhesion and high crosslinking, which is difficult to synthesize by general chemical methods [4-6]. This kind of polymer can be used as isolation film and protective film, which can effectively isolate components harmful to organisms. With the rapid development of microelectronics industry, plasma processing technology is becoming more and more mature. Therefore, the preparation and detection of polymer films have become relatively perfect. The properties of this film can be further determined by infrared radiation, nuclear magnetic resonance (NMR) and electronic spectrum for chemical analysis. Because plasma itself has sterilization and disinfection performance, the cost of medical equipment is reduced

There are two basic requirements for biomaterials: (1) the biomaterial must be able to successfully perform the expected functions, and (2) the biomaterial will not produce side effects. Therefore, it is required that the chemical properties, physical properties, mechanical properties, permeability, degradation ability, strength and flexibility of biomaterials must be consistent with the expected functions. Medical materials must be tested reliably and carefully, and strict production standards must be established.

Third, the performance of anticoagulant materials.

An important requirement of the material implanted in living body is that it can be compatible with blood and does not cause coagulation, toxicity and immune response. This material is called blood compatibility material. An ideal blood-compatible polymer material should not have the following characteristics:

(1) polymers release some components or their degradation products into the blood, causing blood coagulation, inflammation, carcinogenesis and toxic reactions;

(2) The polymer lacks mechanical elasticity, which leads to turbulent blood flow, platelet activity, inflammatory reaction and blood embolism;

(3) Polymers can cause inflammatory reaction and delay infection.

It can be seen that blood compatibility is a multi-parameter function of polymer properties. In this sense, the ideal blood-compatible polymers have almost never been obtained, and only some polymers that meet the requirements of blood compatibility can be obtained. For example, by using medical-grade polymers, the released components and degradation products of polymers are non-toxic.

The main ways of blood coagulation are related to platelets, hemoglobin and fibrinogen [7, 8]. The anticoagulant properties of artificial materials mainly refer to: (1) affinity for blood; (2) inhibition of platelet adhesion and aggregation; (3) biological fusion reaction; (4) forming a surface [9] simulating biological tissues. Most of the blood components are water, and the blood compatibility of the material is hydrophilic to a great extent. Plasma deposition of thin films shows unique advantages. In the process of plasma action, a specific chemical reaction occurs to form a polymer film, and its hydrophilic genes (such as -OH, -—COOH, etc.). ) often exposed, so that the film shows good hydrophilicity. This characteristic is inherent in movies.

In normal blood vessels, the aggregation and release of platelets are in a dynamic balance, so thrombosis is generally not formed. If the aggregation is greater than the release, a thrombus will form. When the polymer film is deposited by plasma, the blood flows over the surface of the film, the laminar flow is accelerated, the eddy current is less, and the stagnation flow is rarely observed. Compared with materials without plasma treatment, the chance of thrombosis is greatly reduced. The experiment of implantation in the great vein ring of experimental dogs shows that the intensity and duration of rejection caused by it are also reduced.

The blood compatibility of polymer membrane includes non-toxic effects on living body, such as non-toxic effects on blood cells, no increase in platelet consumption and short-term decline of platelets. The experiment using the vein-free branching system of baboon has obtained meaningful results. The vein-free branching model of baboon is a cluster of small-caliber blood vessels, which travel almost parallel. In the experiment, an artificial blood vessel made of PTFE was implanted between two adjacent blood vessels. Form a u-shaped artificial blood vessel ring. The decay rate of labeled platelets in natural blood vessels and artificial blood vessels can be determined by radioisotope tracer method. The results show that the implanted artificial blood vessel has little effect on the decay of normal platelets in baboons, and the platelet consumption rate on the surface of the material has nothing to do with the blood flow rate and the total number of platelets, but only has a linear relationship with the length of the artificial blood vessel. Similar results have been obtained in animal and human experiments.

Four. Anticoagulant material

Artificial biomaterials should not activate the coagulation process, but the surface of materials in contact with blood should inhibit the coagulation process and prevent the formation of coagulants. Therefore, an appropriate anticoagulant material should be a catalyst to inhibit the coagulation reaction. During the 20 years from 1970 to 1990, different kinds of anticoagulant tablets were developed and widely used. An anticoagulant tablet can release a substance, PGI2, which can prevent platelet aggregation and release, thus controlling the coagulation process. However, it is expensive and unstable. Under biological conditions, its life after hydrolysis is only 1 min. Therefore, this biomaterial has no practical use. Another anticoagulant material can be prepared by adding an anticoagulant tablet dippridamole to the surface of a polymer in contact with blood. For example, pyridine [10] can be added to fibers, cellulose diacetate, nylon and terephthalic acid polymers.

When the material was implanted in dogs, it was proved that the material had effective anticoagulant performance. Anticoagulants with strong anionic properties were bound to the surface of polycationic polymers by ionic bonds to prepare anticoagulant materials [1 1]. Polycationic polymers can be prepared from styrene and its transformants, cellulose, silicone rubber, epoxy resin, polyurethane or the transformants of acrylonitrile and acrylate. Biomaterials release ion-bonded anticoagulants into the bloodstream. The concentration of anticoagulant near the surface is high enough to prevent the formation of coagulant within a few days. Then the concentration of the coagulant decreases. So this kind of material is only suitable for short-term use. Polymer gel can also be used to prepare anticoagulant materials. The anticoagulant ion coating trapped in the gel can prevent the formation of blood clots [12, 13]. Spraying prothrombin kinase and kinase on the surface of PVC and silicone rubber can greatly improve the blood compatibility of the materials. However, the immobilized enzyme will also dissociate on the blood surface, which hinders the long-term use of this material. Anticoagulant materials can be prepared by combining anticoagulant with polymer surface. For example, the hydrogel obtained by polyvinyl alcohol is combined with an anticoagulant fixed by acetal [14], and the anticoagulant is combined with agarose [15]. The common way is to activate the polymer chemically or by radiation, and then react with the anticoagulant chemically. For example, isocyanate groups are immobilized on polystyrene. The formed polymer then reacts with an anticoagulant. An anticoagulant is bonded to a modified polyvinyl alcohol hydrogel, an elastomer, a glycidyl poly -2- hydroxyethyl methacrylate polymer or a cellulose membrane by a similar method. Chemical or radiation chemical treatment leads to the formation of large groups, which in turn leads to the polymerization of monomers, and then the anticoagulant is bonded to the polymer with a valence of * * *. In the document [16], the surface properties and anticoagulant gene activity of anticoagulant combined with * * * valence are described.

Activated carbon has been used in hemodialysis for nearly 30 years, but its disadvantage is that the released pure carbon will lead to blood coagulation and blood cell damage. But after plasma treatment, activated carbon can enhance blood compatibility. After coating a layer of HMDS film on the surface of activated carbon particles by plasma deposition, it was confirmed by solid column experiments of dog blood and sheep blood infiltration activated carbon. HMDS membrane can effectively reduce blood cell damage and platelet decline [20]. Amorphous hydride carbon films containing different amounts of fluorine and silicon atoms can be prepared by plasma deposition, which has good compatibility. Cell fusion layer [2 1] can be observed within 2 days. When the film is coated on polyethylene and other plastic substrates, it can be used as a tissue culture material. Medical polyurethane and antibiotics can be made into composite materials with drug controlled release function. If it is prepared by plasma surface modification technology, the drug release rate of this composite will decrease, thus prolonging the antibacterial time. It will not affect the mechanical strength and flexibility of the material [22]. As early as 1940s, polymethyl methacrylate (PMMA) was used as the material of contact lenses. However, the defects of poor hydrophilicity and poor oxygen permeability of PMMA cause the wearer to feel uncomfortable. Coating the lens surface with a plasma polymer film made of acetylene, nitrogen and water can improve the hydrophilicity of the material and reduce the adhesion between the lens and corneal epithelial cells. After oxygen plasma treatment, the oxygen-containing functional groups in the membrane increased, and the affinity with oxygen increased, thus improving the permeability. In addition, porous polypropylene membrane is used as drug transdermal absorption carrier, and the surface hydrophilicity and blood compatibility can be improved after plasma surface modification [23].

Plasma deposition, polymerization and treatment technology are not only applied to anticoagulant materials, but also to surface cleaning, disinfection and sterilization of ophthalmic materials (such as intraocular lens), orthopedic materials, oral materials, drug delivery systems, biosensor materials and materials and devices. In a word, plasma deposition and treatment technology shows broad application prospects in the field of biomedical materials.

Finally, we briefly discuss some limitations in the application of polymer materials. In the 1970s, the main manifestation was coagulation, and in the 1990s, the main frontier problem was the immune response caused by polymer implantation and long-term use. That is, delayed infection, allergic reaction, inflammatory reaction and device calcification. Rough and porous surface implantation has a high risk of infection. Inflammation is related to the shape, mechanical properties and chemical properties of the implanted device. Allergic reaction is the main research field at present. Polymethyl methacrylate, metal wire, clip, nylon suture and catheter can cause allergic reaction and cell reaction [24]. Dextran and fibroglucan can cause allergic reactions. The basic research in the field of coagulation system needs the cooperation of many experts such as chemistry, physical chemistry, biochemistry, biology, physics, internal medicine and surgery.

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also

/Abstract.aspx? A=swyxgcx20050205 1

Must be a member, is a paid website, the following brief introduction:

A good anticoagulant biomaterial should not only have good surface chemical properties and mechanical properties, but also have good biocompatibility (including histocompatibility and blood compatibility). In order to understand the above properties, it is necessary to describe them. This paper discusses the characterization of anticoagulant biomaterials from three aspects, namely, the characterization of surface chemical composition and structure, mechanical properties and biocompatibility.