CN117180525A - Novel anti-coagulation anti-inflammatory coating and preparation method and application thereof - Google Patents
Novel anti-coagulation anti-inflammatory coating and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses an anticoagulant anti-inflammatory novel coating, a preparation method and application thereof, wherein the anticoagulant anti-inflammatory novel coating is applied to a solid hollow fiber membrane in a membrane oxygenator and an organ-shaped folding filter screen arranged in an arterial micro-thrombus filter; the novel anti-coagulation anti-inflammatory coating is a coating modified by composite polysaccharide; the complex polysaccharide is a mixture of a plurality of sulfated polysaccharides and oxidized polysaccharides. The invention adopts the novel anti-coagulation and anti-inflammatory coating and the preparation method and the application thereof, carries out blood compatibility modification on the solid hollow fiber membrane material in the membrane oxygenator and the organ-shaped folding filter screen arranged in the arterial micro-plug filter through the compound polysaccharide, and inhibits the adhesion and activation of protein and blood platelets and the formation of inflammatory factors through the formation of the functional compound coating surface on the surface of the high polymer material, thereby achieving the dual effects of anticoagulation and anti-inflammatory.
Description
Technical Field
The invention relates to the technical field of anticoagulation anti-inflammatory coating, in particular to an anticoagulation anti-inflammatory novel coating, a preparation method and application thereof.
Background
In ECMO (extracorporeal membrane oxygenation) therapeutic systems, the membrane oxygenator is a key important component, and the solid hollow fiber membrane materials in the membrane oxygenator are mainly polypropylene (PP), polydimethylsiloxane (PDMS), polymethylpentene (PMP). Among them, PMP in particular has the advantages of good thermal stability, high mechanical strength, excellent gas permeability, strong gas exchange capacity, etc. However, the surfaces of the high-molecular hollow fiber membrane materials are non-physiological, and when the high-molecular hollow fiber membrane materials are contacted with blood, severe coagulation waterfall and inflammation waterfall reactions are stimulated. At present, anticoagulation and anti-inflammatory modification of the surface of a polymer hollow fiber membrane material are important research directions for improving the blood compatibility of the polymer hollow fiber membrane material.
An arterial micro-plug filter (AF) in an extracorporeal circulation (extracorporeal circulation, ECC) treatment system is mainly used for filtering micro-emboli such as air plug, fat particle and the like, and is a key point of success and failure of extracorporeal circulation operation. The filter screen is a core component of AF and is made of Polyester fiber, polyamide fiber, nylon (PA), nylon and Polyamide fiber. A sieve material with a certain pore size is used for intercepting particles of 10-200 μm, and the pressure curve of the filter as a whole is the sum of the pressure curve of the container and the pressure curve of the sieve material. Wherein the size of the pressure curve of the filter material is determined by the open area.
The pressure profile is an important technical parameter of the micro-plug filter. If the pressure curve is large, then the pressure must be increased in order to achieve the specified flow, which is a significant damage to the red blood cells. In order to minimize the pressure curve, the filter area is increased accordingly. The filter screen is generally folded in an accordion-like manner to house the material with an increased effective filter area in a container of small starting volume. Thus, the purpose of reducing the pressure curve can be achieved without increasing the pre-charge of the filter. The accordion-shaped folding filter screen is a non-physiological surface, occupies a large contact area, can excite serious coagulation waterfall and inflammation waterfall reaction when contacting with blood, and particularly has the key problems of excessively large shearing force caused by filter screen blockage to damage blood components, reduced circulation flow, excessively high pressure at a blood inlet end and other mechanical complications to be solved urgently.
Membrane oxygenators and arterial micro-plug filters are core elements in ECMO and ECC devices, the main component of which is medical polymer membrane materials, and the blood compatibility of the polymer membrane materials is the most notable problem in clinical application. When the membrane material contacts the blood, plasma proteins are instantaneously adsorbed on the surface, the coagulation system is activated to cause coagulation, and complement and leucocytes are further activated to induce immune response and inflammatory response, so that the medical cost of frequent replacement of consumables is increased, and the death risk of a patient is increased.
The use of anticoagulants in ECMO and ECC extracorporeal circulation is a conventional measure for improving blood compatibility, which can reduce the occurrence of coagulation events, but increases the risk of bleeding, and the long-term use of heparin anticoagulants can cause adverse reactions such as lipid metabolism disorder, osteoporosis and heparin-induced thrombocytopenia, which have serious effects on the long-term survival of patients. Modification of the surface of polymeric membrane materials is another important strategy to improve the blood compatibility of membrane oxygenators and arterial micro-embolic filters. The simpler modification method is to construct a biocompatible coating on the surface of the membrane material to reduce the adsorption of plasma proteins, thereby reducing the coagulation reaction and the immune reaction.
In recent years, complications associated with membrane oxygenators and arterial micro-embolic filters have been significantly ameliorated by the use of coating materials for the imported products, but currently the imported products are expensive and limited in their use in conventional ECMO and ECC therapies. And the suppliers of the coating film type oxygenator and the arterial micro-thrombus filter are few, the coating is single, and the selection space is small. Due to the special structure of the membrane oxygenator and the arterial micro-thrombus filter, the coated membrane has good anticoagulation activity, good biocompatibility, mechanical safety and the like. However, the technology is blocked abroad, and research reports on novel coatings of membrane oxygenators and arterial micro-thrombus filters are fresh at home and abroad. The existing imported products only have anticoagulation function, and the ideal solution thinking is that the membrane oxygenator and the arterial micro-plug filter surface are subjected to bionic endothelial modification, so that the membrane oxygenator and the arterial micro-plug filter have anticoagulation and anti-inflammatory properties on the endothelial cell surface, and no ideal anticoagulation anti-inflammatory activity membrane oxygenator and arterial micro-plug filter exist at home and abroad at present.
Disclosure of Invention
The invention aims to provide an anticoagulant and anti-inflammatory novel coating, a preparation method and application thereof, wherein a solid hollow fiber membrane material in a membrane oxygenator and an organ-shaped folding filter screen arranged in an arterial micro-plug filter are subjected to blood compatibility modification through composite polysaccharide, and the surface of a functional composite coating is formed on the surface of a high polymer material to inhibit the adhesion and activation of proteins and platelets and inhibit the formation of inflammatory factors, so that the dual effects of anticoagulation and anti-inflammatory are achieved.
In order to achieve the aim, the invention provides an anticoagulant and anti-inflammatory novel coating, which is applied to a solid hollow fiber membrane in a membrane oxygenator and an organ-shaped folding filter screen arranged in an arterial micro-plug filter; the novel anti-coagulation anti-inflammatory coating is a coating modified by composite polysaccharide; the complex polysaccharide is a mixture of a plurality of sulfated polysaccharides and oxidized polysaccharides.
Preferably, the polysaccharide comprises at least one of a plant polysaccharide, an animal polysaccharide and a marine polysaccharide, preferably a plant polysaccharide and an animal polysaccharide; preferably, the plant polysaccharide comprises pueraria polysaccharide and/or bletilla striata polysaccharide and/or astragalus polysaccharide; preferably, the animal polysaccharide comprises glycosaminoglycans and/or proteoglycans; preferably, the marine polysaccharide comprises sodium alginate.
The preparation method of the novel anti-coagulation and anti-inflammatory coating of the solid hollow fiber membrane applied to the membrane oxygenator comprises the following steps:
(1) Surface pretreatment of a hollow fiber membrane material of a membrane oxygenator: weighing 40mL-60mL 98% concentrated sulfuric acid, adding into 34mL-120mL water, weighing 0.1g-0.3g KMnO 4 Preparing an acidification solution with the mass fraction of 32.83% -53.11%; immersing the solid hollow fiber membrane material into an acidification solution, acidizing for 2-5 min, washing with distilled water, and vacuum drying.
(2) Surface amination treatment of hollow fiber membrane material of membrane oxygenator:
carrying out amination reaction on the pretreated hollow fiber membrane material and an imine polymer solution with the mass fraction of 0.05% -0.12%, taking out the hollow fiber membrane material of the membrane oxygenator after the reaction is stopped, cleaning the hollow fiber membrane material with distilled water, and drying the hollow fiber membrane material in vacuum.
(3) The compound polysaccharide with the concentration of 0.8g/L-2.5g/L and the aminated hollow fiber membrane material are subjected to Schiff-base crosslinking reaction under the action of a catalyst, and react for 2-6 hours in a constant-temperature water bath at the temperature of 45-55 ℃ to complete covalent crosslinking, so that a stable anticoagulation anti-inflammatory coating is formed.
The catalyst is one or more of KCN, naSH, CH3 BNNA; the concentration of the catalyst is 0.05% -0.15%.
The compound polysaccharide comprises 38.33% of sulfated pueraria polysaccharide, 26.67% of sulfated bletilla striata polysaccharide, 20.00% of sulfated glycosaminoglycan fragments and 15.00% of oxidized proteoglycan fragments.
The preparation method of the novel anticoagulation anti-inflammatory coating applied to the organ-shaped folding filter screen arranged in the arterial micro-thrombus filter comprises the following steps of:
(1) The surface pretreatment of the filter material of the filter with the arterial micro-plug and the built-in organ-shaped folding filter screen comprises the following steps: weighing 30mL-40mL 98% concentrated sulfuric acid, adding into 48mL-110mL water, weighing 0.05g-0.1g KMnO 4 Preparing an acid solution with the mass fraction of 26.20% -37.76%; immersing the organ-shaped folding filter screen material in the arterial micro-plug filter into acidizing solutions with different concentrations, acidizing for 3-5 min, washing with distilled water, and vacuum drying.
(2) The surface amination treatment of the filter screen material with the organ-shaped folding filter screen is arranged in the arterial micro-plug filter:
carrying out amination reaction on the pretreated organ-shaped folding filter screen material in the arterial micro-plug filter and an imine polymer solution with the mass fraction of 0.05-0.08%, taking out the organ-shaped folding filter screen material in the arterial micro-plug filter after the reaction is stopped, cleaning with distilled water, and drying in vacuum.
(3) The compound polysaccharide with the concentration of 0.8g/L-2.5g/L and the aminated arterial micro-plug filter are internally provided with an organ-shaped folding filter screen material to carry out Schiff-base crosslinking reaction under the action of a catalyst, and the reaction is carried out for 2-6 hours under the constant temperature water bath of 45-55 ℃ to complete covalent crosslinking, thus forming the stable anticoagulation anti-inflammatory coating.
The catalyst is one or more of KCN, naSH, CH3 BNNA; the mass fraction of the catalyst is 0.05% -0.15%.
The compound polysaccharide comprises 38.33% of sulfated pueraria polysaccharide, 26.67% of sulfated bletilla striata polysaccharide, 20.00% of sulfated glycosaminoglycan fragments and 15.00% of oxidized proteoglycan fragments.
Preferably, the membrane oxygenator hollow fiber membrane material is one of polypropylene, polydimethylsiloxane and polymethylpentene.
Preferably, the filter with the filter is made of polyester fiber or polyamide fiber.
The natural polysaccharide can improve the anticoagulant effect of the polysaccharide after being sulfated and modified, and can improve the anti-inflammatory effect of the polysaccharide after being oxidized and modified. The invention uses the compound polysaccharide of sulfated polysaccharide and oxidized polysaccharide which are mixed in a certain proportion, has excellent anticoagulation activity and anti-inflammatory activity, and uses the compound polysaccharide as the functional substance of the coating.
The surface of the aminated medical high polymer material is rich in active amino groups through Schiff-base crosslinking reaction: r is R 2 C＝O+R'NH 2 --R 2 C＝NR'+H 2 And O, finishing covalent crosslinking to form a stable anticoagulation anti-inflammatory coating surface, and improving the blood compatibility of the medical polymer material.
Therefore, the novel anti-coagulation anti-inflammatory coating and the preparation method thereof have the following technical effects:
(1) The membrane oxygenator hollow fiber membrane material and the pulse micro-thrombus filter built-in filter screen material are subjected to anticoagulation and anti-inflammatory modification through the composite polysaccharide, so that the membrane oxygenator hollow fiber membrane material has the characteristics of resisting protein adsorption, reducing platelet adhesion and aggregation, inhibiting endogenous coagulation factor activation, inhibiting thrombosis, promoting material pseudo-intimation and the like;
(2) The membrane oxygenator hollow fiber membrane material based on covalent bond combination and anti-inflammatory modification and the pulse micro-thrombus filter are internally provided with filter screens, and the membrane oxygenator hollow fiber membrane material has the characteristics of good material safety, good blood compatibility, difficult falling and high stability;
(3) Has the dual effects of anticoagulation and anti-inflammatory, and is suitable for long-time extracorporeal circulation; is expected to reduce medical cost and generates good economic and social benefits.
Detailed Description
The technical scheme of the invention is further described below by examples.
Unless defined otherwise, technical or scientific terms used herein should be given the ordinary meaning as understood by one of ordinary skill in the art to which this invention belongs.
The novel anticoagulant and anti-inflammatory coating is applied to a solid hollow fiber membrane in a membrane oxygenator and an organ-shaped folding filter screen arranged in an arterial micro-thrombus filter, and is modified by composite polysaccharide.
The complex polysaccharide comprises: comprises 38.33 percent of sulfated pueraria polysaccharide, 26.67 percent of sulfated bletilla striata polysaccharide, 20.00 percent of sulfated glycosaminoglycan fragments and 15.00 percent of oxidized proteoglycan fragments.
Preparation of complex polysaccharide solution: and (3) respectively taking 7.3g of purified and dried polysaccharide, fully mixing and dissolving the polysaccharide in 1000g of deionized water, adding 50mg of sodium nitrite, magnetically stirring under the reaction condition of 0 ℃, carrying out light-shielding reaction for 2 hours, and regulating the PH to be neutral to terminate the reaction to obtain the anticoagulant and anti-inflammatory function compound polysaccharide solution.
Preparing composite polysaccharide powder: adding 3.0g of NaCl into the solution, fully and uniformly mixing, pouring into ethanol with the volume of 5 times, carrying out suction filtration on the precipitate, drying, dissolving in deionized water again, dialyzing by using a dialysis bag with the pore diameter of 3500Da, and carrying out low-temperature vacuum drying to obtain the anticoagulant and anti-inflammatory function compound polysaccharide powder.
Example 1
The preparation method of the novel anti-coagulation and anti-inflammatory coating comprises the following steps of:
(1) Surface pretreatment of a hollow fiber membrane material of a membrane oxygenator:
52ml of 98% concentrated sulfuric acid is weighed, added into 113ml of water, and 0.13g of KMnO is weighed 4 An acidified solution with a mass fraction of 30.96% was formulated. The solid hollow fiber membrane material is prepared by selecting polymethylpentene as a base material, immersing the base material in an acidification solution, acidizing for 5min, washing with distilled water, and vacuum drying.
(2) Surface amination treatment of hollow fiber membrane material of membrane oxygenator:
and (3) respectively carrying out amination reaction on the pretreated polymethylpentene material and an imine polymer solution with the mass fraction of 0.06%, taking out the polymethylpentene material after the reaction is stopped, cleaning with distilled water, and drying in vacuum.
(3) The compound polysaccharide with the concentration of 1.0g/L and the aminated polymethylpentene material are subjected to Schiff-base crosslinking reaction under the action of a catalyst KCN with the mass fraction of 0.05%, and the covalent crosslinking is completed after the reaction for 2 hours in a constant-temperature water bath at the temperature of 45 ℃ to form the stable anticoagulation anti-inflammatory coating.
Example two
The preparation method of the novel anti-coagulation and anti-inflammatory coating comprises the following steps of:
(1) Surface pretreatment of a hollow fiber membrane material of a membrane oxygenator:
47ml of 98% concentrated sulfuric acid was measured, added to 120ml of water, and 0.17g of KMnO was weighed 4 An acidified solution with a mass fraction of 27.68% was formulated. The solid hollow fiber membrane material is prepared by selecting polypropylene (PP) as a base material, immersing the base material in an acidification solution, acidizing for 5min, washing with distilled water, and vacuum drying.
(2) Surface amination treatment of hollow fiber membrane material of membrane oxygenator:
and (3) respectively carrying out amination reaction on the pretreated polypropylene material and an imine polymer solution with the mass fraction of 0.05%, taking out the propylene material after the reaction is stopped, cleaning with distilled water, and drying in vacuum.
(3) The compound polysaccharide with the concentration of 1.6g/L and the aminated propylene material are subjected to Schiff-base crosslinking reaction under the action of a catalyst NaSH with the mass fraction of 0.08%, and react for 3 hours in a constant-temperature water bath at 40 ℃ to complete covalent crosslinking, so that a stable anticoagulation anti-inflammatory coating is formed.
Example III
The preparation method of the novel anti-coagulation and anti-inflammatory coating comprises the following steps of:
(1) Surface pretreatment of a hollow fiber membrane material of a membrane oxygenator:
weighing 55ml 98% concentrated sulfuric acid, adding into 65ml water, weighing 0.19g KMnO 4 An acidified solution with a mass fraction of 45.08% was formulated. The solid hollow fiber membrane material is prepared by selecting polydimethylsiloxane as a base material, immersing the base material in an acidification solution, acidizing for 4min, washing with distilled water, and vacuum drying.
(2) Surface amination treatment of hollow fiber membrane material of membrane oxygenator:
and (3) respectively carrying out amination reaction on the pretreated polydimethylsiloxane material and an imine polymer solution with the mass fraction of 0.07%, taking out the polydimethylsiloxane material after the reaction is stopped, cleaning with distilled water, and drying in vacuum.
(3) Composite polysaccharide with concentration of 2.1g/L and aminated polydimethylsiloxane material are mixed with catalyst CH with mass fraction of 0.085% 3 And (3) carrying out Schiff-base crosslinking reaction under the action of BNNA, and reacting for 3 hours at the constant temperature of 48 ℃ in a water bath to complete covalent crosslinking, thereby forming the stable anticoagulation anti-inflammatory coating.
Example IV
The preparation method of the novel anti-coagulation and anti-inflammatory coating comprises the following steps of:
(1) The surface pretreatment of the filter material of the filter with the arterial micro-plug and the built-in organ-shaped folding filter screen comprises the following steps: weighing 48ml of 98% concentrated sulfuric acid, adding into 107ml of water, and weighing 0.05g of KMnO 4 An acidified solution with a mass fraction of 32.59% was formulated. The filter screen with the built-in organ type folding filter screen of the arterial micro-plug filter selects the polyester fiber asImmersing the substrate in an acidizing solution with the mass fraction of 25.71%, acidizing for 2min, washing with distilled water, and vacuum drying;
(2) The surface amination treatment of the filter screen material with the organ-shaped folding filter screen is arranged in the arterial micro-plug filter:
carrying out amination reaction on the pretreated polyester fiber and an imine polymer solution with the mass fraction of 0.08%, taking out the polyester fiber material after the reaction after terminating the reaction, cleaning with distilled water, and drying in vacuum;
(3) The compound polysaccharide with the concentration of 2.2g/L and the polyester fiber are subjected to Schiff-base crosslinking reaction under the action of a catalyst NaSH with the mass fraction of 0.06%, and the covalent crosslinking is completed after the reaction for 3 hours in a constant-temperature water bath at the temperature of 45 ℃ to form the stable anticoagulation anti-inflammatory coating.
Example five
The preparation method of the novel anti-coagulation and anti-inflammatory coating comprises the following steps of:
(1) The surface pretreatment of the filter material of the filter with the arterial micro-plug and the built-in organ-shaped folding filter screen comprises the following steps: 40ml of 98% concentrated sulfuric acid is weighed and added into 74ml of water, and 0.08g of KMnO is weighed 4 An acidified solution with a mass fraction of 42.32% was formulated. An organ-shaped folding filter screen arranged in an arterial micro-plug filter is prepared by immersing polyester fiber serving as a base material in an acidification solution with the mass fraction of 34.46%, acidizing for 4min, washing with distilled water, and vacuum drying;
(2) The surface amination treatment of the filter screen material with the organ-shaped folding filter screen is arranged in the arterial micro-plug filter:
carrying out amination reaction on the pretreated polyester fiber and an imine polymer solution with the mass fraction of 0.07%, taking out the polyester fiber material after the reaction after terminating the reaction, cleaning with distilled water, and drying in vacuum;
(3) The composite polysaccharide and polyester fiber with the concentration of 1.9g/L are subjected to Schiff-base crosslinking reaction under the action of catalyst KCN with the mass fraction of 0.10%, and react for 5 hours in a constant-temperature water bath at 45 ℃ to complete covalent crosslinking, so that a stable anticoagulation anti-inflammatory coating is formed.
Example six
The preparation method of the novel anti-coagulation and anti-inflammatory coating comprises the following steps of:
(1) The surface pretreatment of the filter material of the filter with the arterial micro-plug and the built-in organ-shaped folding filter screen comprises the following steps: 59ml of 98% concentrated sulfuric acid was weighed, added to 51ml of water, and 0.09g of KMnO was weighed 4 An acidified solution with a mass fraction of 41.43% was formulated. An organ-shaped folding filter screen arranged in an arterial micro-plug filter is prepared by immersing polyamide fibers serving as a base material in an acidification solution with the mass fraction of 42.57%, acidizing for 3min, washing with distilled water, and vacuum drying;
(2) The surface amination treatment of the filter screen material with the organ-shaped folding filter screen is arranged in the arterial micro-plug filter:
carrying out amination reaction on the pretreated polyester fiber and an imine polymer solution with the mass fraction of 0.05%, taking out the polyester fiber material after the reaction after terminating the reaction, cleaning with distilled water, and drying in vacuum;
(3) The composite polysaccharide and polyester fiber with the concentration of 1.56g/L are subjected to Schiff-base crosslinking reaction under the action of catalyst KCN with the mass fraction of 0.08%, and react for 3 hours in a constant-temperature water bath at 45 ℃ to complete covalent crosslinking, so that a stable anticoagulation anti-inflammatory coating is formed.
Test
(1) Conventional comparison of blood coagulation of sulfated pueraria polysaccharide with low molecular heparin sodium and normal plasma is shown in table 1:
table 1 comparison of coagulation convention four items
| Sulfated pueraria polysaccharide | Low molecular heparin sodium | Normal blood plasma | |
| PT | 17.85±2.04 | 16.46±2.56 | 13.46±1.21 |
| APTT | 65.36±9.39 | 61.40±7.71 | 36.49±4.11 |
| TT | 35.93±8.04 | 30.67±6.45 | 18.02±1.42 |
| FIB | 15.34±4.31 | 15.76±3.88 | 16.7±4.51 |
The result shows that the sulfated pueraria polysaccharide has good anticoagulation activity.
(2) Coating modification is carried out on hollow fiber membrane material with anticoagulation anti-inflammatory membrane oxygenator and filter screen material embedded in arterial micro-thrombus filter, and anticoagulation activity detection is carried out
Firstly, taking healthy whole blood 20m, centrifuging at 3000r/min for 10min to obtain Platelet Poor Plasma (PPP), and measuring coagulation functions ATPP, TT, PT and FT; then respectively taking materials with different coating layers of 10cm, cutting into fragments with the length of about 0.5cm multiplied by 0.5cm, and placing the fragments in a 24-hole culture plate; PPP 700 mu L and a 37C constant temperature water tank are respectively added into each coating sample hole for incubation for 2 hours; and (3) extracting the incubated plasma, adding the plasma into a centrifuge tube, shaking and mixing for 30s, measuring 4 coagulation indexes again, and calculating the coagulation time difference of each group of samples. The results are shown in Table 2.
TABLE 2 determination of clotting functions before and after coating of different materials
The results show that the APTT and TT times of each test material group are obviously prolonged and have obvious difference (P < 0.01) compared with the normal blood control group; the TT time is not obviously prolonged (P is more than 0.01), which indicates that various materials after coating modification have good anticoagulation effect.
(3) Surface hydrophilicity experiments of different material modification
At 20 ℃ or 60 ℃, the samples before and after coating modification of various materials are respectively placed in ethanol solutions with volume fractions of 0.50% and 90% for soaking for 12 hours, or are placed in Sodium Dodecyl Sulfate (SDS) solution with mass fraction of 1% for ultrasonic washing for 30 minutes. And (3) completely eluting and drying the sample by distilled water, testing the dynamic contact angle of the sample, and observing the dynamic contact angle change before and after coating modification of various polymer materials.
2 mu L of pure water is dripped on the surface of the dried sample by the microsyringe, the change of the contact angle with time is recorded by a dynamic contact angle measuring instrument, 5 points are measured each time for each sample, and the average value is measured 10 times each point. The hydrophilic character of the coating is characterized by measuring the change in contact angle of the surface of the material.
The control group is medical polymer material which is not modified by composite polysaccharide, and table 3 shows the contact angles of different modified surfaces:
TABLE 3 surface hydrophilicity experiments before and after modification of different materials
| Group of | n | Contact angle/(°) |
| Polyester fiber control group | 10 | 87.39±1.78 |
| Coated polyester fiber group | 10 | 36.75±3.29 |
| PMP control group | 10 | 89.22±1.67 |
| Coated PMP group | 10 | 31.87±3.91 |
| PP control group | 10 | 86.48±2.03 |
| Coating PP group | 10 | 33.93±3.78 |
| PDMS control group | 10 | 87.38±1.95 |
| Coated PDMS set | 10 | 46.57±1.78 |
It can be seen from table 3 that the hollow fiber membrane material with anticoagulation anti-inflammatory membrane oxygenator and the filter screen material built in arterial micro-plug filter prepared in examples one to four have good hydrophilicity and good blood compatibility.
(4) Adsorption experiment of different material modified surface proteins
The quantitative method of the surface adhesion protein adopts a BCA method, and a protein concentration standard curve is established according to a BCA kit method.
Cutting a sample to be tested into fragments of 0.25cm multiplied by 0.5cm, and adding the fragments into a 24-hole culture plate; preparing 0.2mg/ml dilutions of human serum albumin (human plasma albumin, HAS) and human fibrinogen (human protein fibriogen, HPF); preparing BCA working solution; adding 1.5mL of HSA and HPF diluent into a culture hole for placing a sample to be tested, completely immersing the material, and incubating at 37 ℃ for 1h in a constant-temperature water tank; and taking out the protein liquid after incubation, adding the protein liquid into a centrifuge tube, and shaking and uniformly mixing the protein liquid and the centrifuge tube to be tested.
Taking 100 mu L of protein liquid to be detected, adding the protein liquid into a clean centrifugal small tube, simultaneously adding 1mL of BCA working solution, and after shaking and mixing uniformly again, incubating for 30min at the constant temperature of 60 ℃; and (3) measuring Abs values of the mixed solution after incubation at a wavelength of 562nm by using an ultraviolet spectrophotometer, and calculating a protein difference value before and after reaction according to a standard curve, namely the adhesion amount of the protein on the surface of the material.
The control group is medical polymer material which is not modified by composite polysaccharide, and the results are shown in table 4:
TABLE 3 adsorption experiments of proteins on surfaces before and after modification of different materials
| Group of | n | HAS/(μg/cm 2 ) | HPF/(μg/cm 2 ) |
| Polyester fiber control group | 5 | 15.93±0.82 | 23.96±0.94 |
| Coated polyester fiber group | 5 | 4.28±0.66 | 10.15±1.91 |
| PMP control group | 5 | 14.26±0.65 | 25.12±0.76 |
| Coated PMP group | 3.93±0.73 | 11..24±1.05 | |
| PP control group | 5 | 13.45±0.45 | 23.15±0.71 |
| Coating PP group | 5 | 4.92±0.98 | 8.75±0.88 |
| PDMS control group | 5 | 15.15±0.79 | 24.01±1.04 |
| Coated PDMS set | 5 | 6.77±0.69 | 10.13±0.98 |
It can be seen from table 4 that the hollow fiber membrane material with the anticoagulation anti-inflammatory membrane oxygenator and the filter screen material built in the arterial micro-plug filter prepared in examples one to four have small adsorption amount to protein, and do not influence the quality of protein in blood.
Therefore, the novel anti-coagulation and anti-inflammatory coating and the preparation method thereof are adopted, and the composite polysaccharide is used for carrying out anti-coagulation and anti-inflammatory modification on the membrane oxygenator hollow fiber membrane material and the filter screen material arranged in the pulse micro-thrombus filter, so that the membrane oxygenator hollow fiber membrane material has the characteristics of resisting protein adsorption, reducing platelet adhesion and aggregation, inhibiting endogenous coagulation factor activation, inhibiting thrombosis, promoting material pseudo-intimation and the like; the membrane oxygenator hollow fiber membrane material based on covalent bond combination and anti-inflammatory modification and the pulse micro-thrombus filter are internally provided with filter screens, and the membrane oxygenator hollow fiber membrane material has the characteristics of good material safety, good blood compatibility, difficult falling and high stability; has the dual effects of anticoagulation and anti-inflammatory, and is suitable for long-time extracorporeal circulation; is expected to reduce medical cost and generates good economic and social benefits.
Finally, it should be noted that: the above embodiments are only for illustrating the technical solution of the present invention and not for limiting it, and although the present invention has been described in detail with reference to the preferred embodiments, it will be understood by those skilled in the art that: the technical scheme of the invention can be modified or replaced by the same, and the modified technical scheme cannot deviate from the spirit and scope of the technical scheme of the invention.
Claims (6)
1. An application of a novel anti-coagulation and anti-inflammatory coating is characterized in that: the novel anticoagulation anti-inflammatory coating is applied to a solid hollow fiber membrane in a membrane oxygenator and an organ-shaped folding filter screen arranged in an arterial micro-plug filter; the novel anti-coagulation anti-inflammatory coating is a coating modified by composite polysaccharide; the complex polysaccharide is a mixture of a plurality of sulfated polysaccharides and oxidized polysaccharides.
2. Use of a novel anti-coagulant anti-inflammatory coating according to claim 1, characterized in that: the polysaccharide comprises at least one of a plant polysaccharide, an animal polysaccharide and a marine polysaccharide, preferably comprises a plant polysaccharide and an animal polysaccharide; preferably, the plant polysaccharide comprises pueraria polysaccharide and/or bletilla striata polysaccharide and/or astragalus polysaccharide; preferably, the animal polysaccharide comprises glycosaminoglycans and/or proteoglycans; preferably, the marine polysaccharide comprises sodium alginate.
3. A method for preparing an anticoagulant anti-inflammatory novel coating, which is characterized by being applied to the solid hollow fiber membrane in the membrane oxygenator of claim 1, and comprising the following steps:
(1) Surface pretreatment of a hollow fiber membrane material of a membrane oxygenator: weighing 40mL-60mL 98% concentrated sulfuric acid, adding into 34mL-120mL water, weighing 0.1g-0.3g KMnO 4 Preparing an acidification solution with the mass fraction of 32.83% -53.11%; immersing the solid hollow fiber membrane material into an acidification solution, acidizing for 2-5 min, washing with distilled water, and vacuum drying;
(2) Surface amination treatment of hollow fiber membrane material of membrane oxygenator:
carrying out amination reaction on the pretreated hollow fiber membrane material and an imine polymer solution with the mass fraction of 0.05% -0.12%, taking out the hollow fiber membrane material of the membrane oxygenator after the reaction is stopped, cleaning the hollow fiber membrane material with distilled water, and drying the hollow fiber membrane material in vacuum;
(3) The compound polysaccharide with the concentration of 0.8g/L-2.5g/L and the aminated hollow fiber membrane material are subjected to Schiff-base crosslinking reaction under the action of a catalyst, and react for 2-6 hours in a constant-temperature water bath at the temperature of 45-55 ℃ to complete covalent crosslinking, so that a stable anticoagulation anti-inflammatory coating is formed;
the compound polysaccharide comprises 38.33 percent of sulfated pueraria polysaccharide, 26.67 percent of sulfated bletilla striata polysaccharide, 20.00 percent of sulfated glycosaminoglycan fragments and 15.00 percent of oxidized proteoglycan fragments;
the catalyst is one or more of KCN, naSH, CH3 BNNA; the concentration of the catalyst is 0.05% -0.15%.
4. A method for preparing an anticoagulant and anti-inflammatory novel coating, which is characterized by being applied to an organ-shaped folding filter screen arranged in an arterial micro-plug filter according to claim 1, comprising the following steps:
(1) The surface pretreatment of the filter material of the filter with the arterial micro-plug and the built-in organ-shaped folding filter screen comprises the following steps: weighing 30mL-40mL 98% concentrated sulfuric acid, adding into 48mL-110mL water, weighing 0.05g-0.1g KMnO 4 Preparing an acid solution with the mass fraction of 26.20% -37.76%; immersing an organ-shaped folding filter screen material in the arterial micro-plug filter into acidizing solutions with different concentrations, acidizing for 3-5 min, washing with distilled water, and vacuum drying;
(2) The surface amination treatment of the filter screen material with the organ-shaped folding filter screen is arranged in the arterial micro-plug filter:
carrying out amination reaction on the pretreated organ-shaped folding filter screen material in the arterial micro-plug filter and an imine polymer solution with the mass fraction of 0.05-0.08%, taking out the organ-shaped folding filter screen material in the arterial micro-plug filter after the reaction is stopped, cleaning with distilled water, and drying in vacuum;
(3) The compound polysaccharide with the concentration of 0.8g/L-2.5g/L and the amination arterial micro-plug filter are internally provided with an organ-shaped folding filter screen material to carry out Schiff-base crosslinking reaction under the action of a catalyst, and the reaction is carried out for 2-6 hours under the constant temperature water bath of 45-55 ℃ to complete covalent crosslinking, thus forming a stable anticoagulation anti-inflammatory coating;
the compound polysaccharide comprises 38.33 percent of sulfated pueraria polysaccharide, 26.67 percent of sulfated bletilla striata polysaccharide, 20.00 percent of sulfated glycosaminoglycan fragments and 15.00 percent of oxidized proteoglycan fragments;
the catalyst is one or more of KCN, naSH, CH3 BNNA; the concentration of the catalyst is 0.05% -0.15%.
5. Use of a novel anti-coagulant anti-inflammatory coating according to claim 3, characterized in that: the membrane type oxygenator hollow fiber membrane material is polypropylene membrane type oxygenator hollow fiber membrane material or polydimethylsiloxane and polymethylpentene membrane type oxygenator hollow fiber membrane material.
6. The use of a novel anti-coagulant anti-inflammatory coating according to claim 4, wherein: the filter is characterized in that an organ-shaped folding filter screen material is arranged in the arterial micro-plug filter and is made of polyester fiber or polyamide fiber.
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