CN102172338B - Artificial biologic valve gradient immersed chemical modification device - Google Patents

Artificial biologic valve gradient immersed chemical modification device Download PDF

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CN102172338B
CN102172338B CN 201110049733 CN201110049733A CN102172338B CN 102172338 B CN102172338 B CN 102172338B CN 201110049733 CN201110049733 CN 201110049733 CN 201110049733 A CN201110049733 A CN 201110049733A CN 102172338 B CN102172338 B CN 102172338B
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agent solution
dressing agent
liquid container
artificial
high order
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CN102172338A (en
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陈大凯
李�雨
刘翔
陈诚
陈国明
王云蕾
林韶烨
乐承筠
罗七一
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SHANGHAI MINIMALLY INVASIVE XINTONG MEDICAL TECHNOLOGY CO., LTD.
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Shanghai Microport Medical Group Co Ltd
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Abstract

The invention discloses an artificial biologic valve gradient immersed chemical modification device, which comprises a multi-stage reaction solution container, a clamp, a moving device, a rotary hanger, a machine frame and a motor. The multi-stage reaction solution container comprises a plurality of reaction solution container for accommodating different modifier solutions for chemical modification of an artificial biologic valve; the clamp clamps the artificial biologic valve and fixes the artificial biologic valve in the rotary hanger, and the rotary hanger is arranged on the moving device and can be controlled to rotate to immerse the artificial biologic valve in the different modifier solutions; the moving device is supported by the machine frame and can be controlled to move vertically to immerse different parts of the artificial biologic valve in the modifier solution; and the motor is fixed on the machine frame to provide power for the moving device and the rotary hanger. The device performs multi-stage modification of the artificial biologic valve by using a gradient immersed chemical modification method and realizes the continuous operation of the modification of the artificial biologic valve. In the artificial biologic valve prepared by the device, the inter-molecule crosslinking point distribution is reasonable, and the interval flexibility and edge rigidity are high.

Description

The device of artificial biologic valve gradient immersed chemical modification
Technical field
The invention belongs to medical instruments field, particularly relate to a kind of device of chemical modification artificial bio-prosthetic valve.
Background technology
In the preparation process of artificial bio-prosthetic valve, the chemical modification of pericardium material has influence on the maximum tension of artificial bio-prosthetic valve, elongation at break, elastic modelling quantity.The intensity of pericardium material is directly related with the framework of its collagen fiber, and because the multiformity of collagen fiber crosslinking points causes the intensity of bovine pericardium to have anisotropy.Therefore, can accomplish that the collagen fiber crosslinking points of effectively controlling the pericardium material just seems very crucial.In the preparation process of artificial bio-prosthetic valve, implant distribution and the calcification rate in formed calcification pattern and calcification district of pericardium material is different.The hydrophobicity of pericardium material is also very large on the impact of calcification.Present calcification research on mechanism shows that biomaterial can be first on elastic fibers, calcium ion and elasticity protein substrate interact and form the polymer of positively charged, thereby attracted phosphate anion electronegative in the blood, the electropositive of the calcium key substrate that neutralized, form calcium phosphate and facilitate the formation of calcification crystallization, finally can cause the calcification of artificial bio-prosthetic valve.In addition, calcium phosphorus level is also closely related with calcification in the body.Prior art adopts complete immersion technique tanning pericardium material usually.But there are a lot of problems in the durability of the pericardium material of preparing like this.Clinical practice confirms that biovalve 5-7 loses power and reaches about 50%, wherein calcification and to tear be the main cause that causes losing merit, and both and deposit reciprocal causation.Calcification mostly occurs at lobe leaf and support intersection and basilar part, tears also manyly along lobe foot through basilar part from top to bottom, and the suture place of binding foot, frame foot top is the starting point of tearing.
Jason C.Isenburg, Dan T.Simionescu, the document of Naren R.Vyavahare. " Tannic acid treatment enhances biostability and reduces calcification of glutaraldehyde fixed aortic wall " (Biomaterials.2005,26:1237-1245) adopts the process means of complete immersion to carry out the chemical modification of pericardium material.
E.Jorge-Herrero, P.Fern á ndez, J.Turnay, N.Olmo, P.Calero, R.Garc í a, I.Freile, J.L.Castillo-Olivares. document " Influence of different chemical cross-linking treatments on the properties of bovine pericardium and collagen " (Biomaterials.1999,20:539-545) adopts the process means of the complete immersion of agitating type to carry out the chemical modification of pericardium material.
But, there is the problem of excessive modification in this complete immersed chemical modification artificial bio-prosthetic valve of the prior art (after one's own heart packaging material material) technique, can't regulate and control well the multiformity of the collagen fiber crosslinking points of pericardium material, mechanical strength and the flexility of pericardium material are taken into account well, and can not be prevented the calcification of bioprosthesis valve.
Summary of the invention
The object of the present invention is to provide a kind of device of artificial biologic valve gradient immersed chemical modification, the defects that exists to overcome prior art.
The present invention has adopted the device of artificial biologic valve gradient immersed chemical modification, can carry out in order and exactly the chemical modification process of pericardium material, avoided the excessive modification in the complete immersed chemical modification process, thereby regulate and control well the multiformity of the collagen fiber crosslinking points of pericardium material, so that the mechanical strength of pericardium material and flexility are taken into account well.In addition, described device utilizes the gradient immersed chemical modification method that artificial bio-prosthetic valve is carried out multistage modification, has realized simultaneously the continuous operation of the modification of artificial bio-prosthetic valve.The intermolecular cross-linking point of the artificial bio-prosthetic valve that device according to the present invention makes distributes rationally, has excellent interval pliability and edge rigidity.
The invention provides a kind of device of artificial biologic valve gradient immersed chemical modification, it comprises reaction of high order liquid container, anchor clamps, shifter, rotary hanging rack, frame and motor.Described reaction of high order liquid container comprises a plurality of reactant liquor containers, holds respectively the different dressing agent solution that is used for the artificial bio-prosthetic valve chemical modification in described a plurality of reactant liquor containers.Described anchor clamps are used for clamping artificial bio-prosthetic valve and being fixed in described rotary hanging rack.Described rotary hanging rack is installed in described shifter and can be rotated by control, in order to artificial bio-prosthetic valve is immersed in the different dressing agent solution in described a plurality of reactant liquor container.Described shifter is by described frame support and can be controlled vertical the movement, uses so that the different parts of artificial bio-prosthetic valve immerses in the dressing agent solution.Described motor is fixed on the described frame, and being used for provides power to described shifter and rotary hanging rack.
Device of the present invention also can comprise the stirring unit, and described stirring unit is installed on the bottom of described reaction of high order liquid container, in order to stir dressing agent solution, makes its concentration keep homogeneous.Described stirring unit is optional from the mechanical agitation type assembly, magnetic stirring assembly, pressure stirring-type assembly.
Device of the present invention also can comprise fluid level detection system, detection probe, receiver, automatic liquid adding device, liquid conducting pipes and flow detector.Described detection probe is positioned in the described reaction of high order liquid container, obtains the data of the amount of dressing agent solution by contact dressing agent solution.Described fluid level detection system is associated with described detection probe, in order to the amount of Real-Time Monitoring dressing agent solution.Described receiver stores dressing agent solution and links to each other by described liquid conducting pipes with described automatic liquid adding device, described liquid conducting pipes further is connected with described reaction of high order liquid container, is less than when a certain amount of in order to the dressing agent solution in described reaction of high order liquid container dressing agent solution is added in the described reaction of high order liquid container.Described flow detector is associated with described liquid conducting pipes, enters the speed of described reaction of high order liquid container in order to regulate dressing agent solution.
Device of the present invention also can comprise the heating module assembly, and described heating module assembly is positioned at the periphery of described reaction of high order liquid container, in order to regulate the temperature of dressing agent solution.
Device of the present invention is by the control vertical movement of shifter and rotatablely moving of rotary hanging rack, and the different parts with artificial bio-prosthetic valve immerses dressing agent solution and artificial bio-prosthetic valve immersed different dressing agent solution respectively.In this way, device of the present invention is regulated and control the multiformity of the collagen fiber crosslinking points of pericardium material well, so that the mechanical strength of pericardium material and flexility are taken into account well.And device of the present invention has taked the method for plyability chemical modification to prepare artificial bio-prosthetic valve for the calcification of pericardium material and the reason of tearing, and has prevented the calcification of bioprosthesis valve, thereby has prolonged the life-span of bioprosthesis valve.
Description of drawings
Fig. 1 is the apparatus structure sketch map of artificial biologic valve gradient immersed chemical modification of the present invention.
Fig. 2 is for adopting the contrast figure that implants the calcium content of mice after 35 days according to the bovine pericardium biovalve of the technique preparation of the complete immersed chemical modification artificial bio-prosthetic valve of prior art according to device and the employing of artificial biologic valve gradient immersed chemical modification of the present invention.
The specific embodiment
Describe with reference to the accompanying drawings device of the present invention in detail.
As shown in Figure 1, the device of artificial biologic valve gradient immersed chemical modification of the present invention comprise reaction of high order liquid container 1, stir unit 2, fluid level detection system 3, detection probe 4, receiver 5, automatic liquid adding device 6, liquid conducting pipes 7, flow detector 8, anchor clamps 9, shifter 10, rotary hanging rack 11, frame 12, motor 13,13 ' and heating module assembly 14.Described reaction of high order liquid container 1 comprises a plurality of reactant liquor containers, holds respectively the different dressing agent solution that is used for the artificial bio-prosthetic valve chemical modification.Described stirring unit 2 is fixed in the bottom of each reactant liquor container; Described detection probe 4 is positioned at the afterbody of fluid level detection system 3; Described receiver 5 links to each other by liquid conducting pipes 7 with automatic liquid adding device 6; Described flow detector 8 links to each other with liquid conducting pipes 7; Described liquid conducting pipes 7 is connected with each reactant liquor container; Described anchor clamps 9 are fixed on the rotary hanging rack 11; Described rotary hanging rack 11 is installed on the described shifter 10; Described shifter 10 is supported on the frame 12; Motor 13,13 ' is fixed in frame 12, and motor 13 is positioned at and stirs unit 2 bottoms, and motor 13 ' is positioned at frame 12 tops; Heating module assembly 14 is positioned at the periphery of reaction of high order liquid container 1.In the embodiment shown in fig. 1, reaction of high order liquid container 1 comprises three reactant liquor containers.
Hold the different dressing agent solution that is used for the artificial bio-prosthetic valve chemical modification in the reaction of high order liquid container 1.The chemical modification dressing agent is selected from one or more in amino end-capping reagent, carboxyl class end-capping reagent, carbonyl class end-capping reagent, metal ion competitor, metal ion competition synergist, the free aldehyde bonding agent.Various chemical modification dressing agents and used solution all are known in those skilled in the art, are not described in detail in this.
In addition, stir unit 2 so that the concentration of dressing agent solution can keep homogeneous; The amount of dressing agent solution in each reactant liquor container of fluid level detection system 3 Real-Time Monitorings; Detection probe 4 obtains concrete amount of liquid data by contact dressing agent solution; Store various dressing agent solution in the receiver 5; Automatic liquid adding device 6 replenishes dressing agent solution when dressing agent solution is less than certain value, dressing agent solution is transported to reaction of high order liquid container 1 from receiver 5 via liquid conducting pipes 7 that is:; Flow detector 8 is regulated and control the admission velocity of dressing agent solution, anchor clamps 9 clip artificial bio-prosthetic valve, shifter 10 can vertically move, so that the different parts of artificial bio-prosthetic valve immerses in the dressing agent solution, rotary hanging rack 11 can rotate, so that artificial bio-prosthetic valve immerses in the different dressing agent solution, motor 13 is used for providing power to stirring unit 2, motor 13 ' is used for providing power to shifter 10 and rotary hanging rack 11, and heating module assembly 14 is used for the temperature of dressing agent solution.
By the control vertical movement of shifter 10 and rotatablely moving of rotary hanging rack 11, the different parts with artificial bio-prosthetic valve immerses dressing agent solution and artificial bio-prosthetic valve is immersed different dressing agent solution respectively.Orderly like this and carry out exactly the chemical modification process of pericardium material, effectively control the collagen fiber crosslinking points of pericardium material, and taked the method for plyability chemical modification to prepare artificial bio-prosthetic valve, prevented the calcification of bioprosthesis valve.
Fig. 2 has shown the complete immersion technique that adopts prior art and has adopted the contrast figure of the calcium content of bovine pericardium biovalve implantation mice after 35 days of gradient immersed device preparation of the present invention.From Fig. 2, can be clear that, adopt the calcification degree of the bovine pericardium biovalve for preparing according to gradient immersed device of the present invention significantly to reduce.
Can reduce the calcification of bioprosthesis valve according to the device of artificial biologic valve gradient immersed chemical modification of the present invention, thereby prolong the life-span of bioprosthesis valve.
It will be understood by those skilled in the art that above description is exemplary.In the situation that does not deviate from thought of the present invention and scope, those skilled in the art can make numerous modifications and variations to the present invention.
Reference numerals list:
1: the reaction of high order liquid container; 2: stir unit; 3: fluid level detection system; 4: detection probe; 5: receiver; 6: automatic liquid adding device; 7: liquid conducting pipes; 8: flow detector; 9: anchor clamps; 10: shifter; 11: rotary hanging rack; 12: frame; 13,13 ': motor; 14: the heating module assembly.

Claims (6)

1. the device of an artificial biologic valve gradient immersed chemical modification, it comprises reaction of high order liquid container (1), anchor clamps (9), shifter (10), rotary hanging rack (11), frame (12) and motor (13 '), wherein:
Described reaction of high order liquid container (1) comprises a plurality of reactant liquor containers, holds respectively the different dressing agent solution that is used for the artificial bio-prosthetic valve chemical modification in described a plurality of reactant liquor containers;
Described anchor clamps (9) are used for clamping artificial bio-prosthetic valve and being fixed in described rotary hanging rack (11);
Described rotary hanging rack (11) is installed in described shifter (10) upward and can be by the control rotation, in order to artificial bio-prosthetic valve is immersed in the different dressing agent solution in described a plurality of reactant liquor container;
Described shifter (10) is supported by described frame (12) and can be vertically mobile by control, uses so that the different parts of artificial bio-prosthetic valve immerses in the dressing agent solution;
Described motor (13 ') is fixed on the described frame (12), and being used for provides power to described shifter (10) and rotary hanging rack (11).
2. device claimed in claim 1, wherein: described device comprises also and stirs unit (2) that described stirring unit (2) is installed on the bottom of described reaction of high order liquid container (1), in order to stir dressing agent solution, makes its concentration keep homogeneous.
3. device claimed in claim 2, described stirring unit (2) is selected from mechanical agitation type assembly, magnetic stirring assembly, pressure stirring-type assembly.
4. each described device among the claim 1-3, wherein: described device also comprises fluid level detection system (3), detection probe (4), receiver (5), automatic liquid adding device (6), liquid conducting pipes (7) and flow detector (8)
Described detection probe (4) is positioned in the described reaction of high order liquid container (1), obtains the data of the amount of dressing agent solution by contact dressing agent solution;
Described fluid level detection system (3) is associated with described detection probe (4), in order to the amount of Real-Time Monitoring dressing agent solution;
Described receiver (5) stores dressing agent solution and links to each other by described liquid conducting pipes (7) with described automatic liquid adding device (6), described liquid conducting pipes (7) further is connected with described reaction of high order liquid container (1), is less than when a certain amount of in order to the dressing agent solution in described reaction of high order liquid container (1) dressing agent solution is added in the described reaction of high order liquid container (1);
Described flow detector (8) is associated with described liquid conducting pipes (7), enters the speed of described reaction of high order liquid container (1) in order to regulate dressing agent solution.
5. each described device among the claim 1-3, wherein: described device also comprises heating module assembly (14), described heating module assembly (14) is positioned at the periphery of described reaction of high order liquid container (1), in order to regulate the temperature of dressing agent solution.
6. device claimed in claim 4, wherein: described device also comprises heating module assembly (14), described heating module assembly (14) is positioned at the periphery of described reaction of high order liquid container (1), in order to regulate the temperature of dressing agent solution.
CN 201110049733 2011-02-28 2011-02-28 Artificial biologic valve gradient immersed chemical modification device Active CN102172338B (en)

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Publication number Priority date Publication date Assignee Title
CN102423505B (en) * 2011-10-27 2014-12-10 上海微创医疗器械(集团)有限公司 Method and apparatus for fixing bioprosthetic valve by membrane type pervaporation mode
CN102430150A (en) * 2011-11-04 2012-05-02 微创医疗器械(上海)有限公司 Sizing equipment and method for pulse fluid assisted fixed artificial bioprosthetic valve
CN102415919B (en) * 2011-11-15 2014-03-19 上海微创医疗器械(集团)有限公司 Steady flow field equipment for modifying artificial biologic valve and method thereof
CN109806030A (en) * 2019-03-28 2019-05-28 韦秋英 A kind of valve cleaning equipment
CN114052004A (en) * 2020-07-30 2022-02-18 赛诺心畅医疗科技有限公司 Tissue fixation treatment device and operation method thereof
CN115709153B (en) * 2022-11-01 2024-02-20 苏州心锐医疗科技有限公司 Integrated manufacturing method and device for durable artificial heart valve

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WO1996013227A1 (en) * 1994-10-21 1996-05-09 University Of Michigan Calcification-resistant bioprosthetic tissue and methods of making same
CN101128225A (en) * 2004-12-24 2008-02-20 塞尔克斯塞尔有限公司 An implantable biomaterial and a method of producing same
CN101224313A (en) * 2008-02-04 2008-07-23 中国科学院上海硅酸盐研究所 Quercetin crosslinking method for preparing artificial bioprosthesis heart valve materials
WO2010011412A2 (en) * 2008-07-24 2010-01-28 Zimmer, Inc. Reduction of free radicals in crosslinked polyethylene by infrared heating
CN101947147A (en) * 2010-06-23 2011-01-19 乐普(北京)医疗器械股份有限公司 Method for chemically treating biological tissue materials

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WO1996013227A1 (en) * 1994-10-21 1996-05-09 University Of Michigan Calcification-resistant bioprosthetic tissue and methods of making same
CN101128225A (en) * 2004-12-24 2008-02-20 塞尔克斯塞尔有限公司 An implantable biomaterial and a method of producing same
CN101224313A (en) * 2008-02-04 2008-07-23 中国科学院上海硅酸盐研究所 Quercetin crosslinking method for preparing artificial bioprosthesis heart valve materials
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