CN104027844A - Novel method for coating artificial blood vessel with Astragalus polysaccharide - Google Patents

Novel method for coating artificial blood vessel with Astragalus polysaccharide Download PDF

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CN104027844A
CN104027844A CN201410138204.1A CN201410138204A CN104027844A CN 104027844 A CN104027844 A CN 104027844A CN 201410138204 A CN201410138204 A CN 201410138204A CN 104027844 A CN104027844 A CN 104027844A
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coating
blood vessel
artificial
vascular prosthesis
prosthesis
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CN201410138204.1A
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张志辉
张梅
俞晓立
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张志辉
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Abstract

The invention provides a novel method for coating an artificial blood vessel with Astragalus polysaccharide. The artificial blood vessel is prepared by coating a terylene (with a chemical name of polyethylene terephthalate) woven or knitted elastic porous tube-shaped or Y-shaped synthesized blood vessel prosthesis with an Astragalus polysaccharide mixed solution 3 to 10 times; the mixed solution mainly comprises Astragalus polysaccharide and a plasticizer and is uniformly distributed on the whole layer of the blood vessel prosthesis through infiltration; and the coated blood vessel prosthesis is placed in a drying box containing carbodiimide steam for cross-linking and fixation.

Description

一种用黄芪多糖涂层人工血管的新方法 Astragalus Polysaccharide new coating method for use in artificial blood vessels

所属技术领域 Those of skill

[0001] 本发明涉及一种可用于置换病变人体血管的人工血管假体的预凝涂层方法,尤其是使用混合有塑化剂的黄芪多糖溶液涂层人血管假体,使其不漏血和促进血管组织再生,从而免除手术过程中预凝血操作和促进血管组织再生的方法。 [0001] relates to an artificial vascular prosthesis used to replace diseased blood vessels in the coating process of the present invention, the pre-condensate, especially the use of plasticizer mixed with a solution of polysaccharides were coated vascular prosthesis, so as not to Louxue and promoting vascular tissue regeneration, thereby eliminating the surgical procedure and operating method of pre-coagulation promoting vascular tissue regeneration.

背景技术 Background technique

[0002]目前,使用人工血管置换人体病变血管是一项重要的外科操作技术。 [0002] Currently, the use of human disease vascular graft replacement is a major surgical operation techniques. 人工血管有多种类型并且有多种材质。 There are many types of artificial blood vessels and there are a variety of materials. 涤纶(学名聚对苯二甲酸乙二酯)材质的人工血管在现代血管置换手术中使用最为普遍,由涤纶编织的人工血管管壁通常有不同程度的孔隙,便于受体组织侵入生长、包裹人工血管假体并促其愈合。 Polyester (polyethylene terephthalate scientific name) material in modern vascular grafts in the replacement procedure using the most common, woven Dacron artificial blood vessel walls typically have different degrees of porosity to facilitate tissue growth receptors invasive, artificial parcel vascular prosthesis and promote healing. 但同时,人工血管的孔隙亦有其不利的一面,即植入时会导致大量血液通过管壁渗漏到体腔中,明显增加手术风险。 But at the same time, the porosity of the graft has its downside, can cause a lot of blood leaking through the wall into the body cavity, significantly increasing the risk of surgery that is implanted.

[0003] 预凝涂层是指在目前使用的涤纶材质人工血管置换机体病变血管时,由于涤纶材质的人工血管本身具有多渗漏性,同时缺乏组织生长的引导性,若涂上适合的生物组织相容性化学物质作为涤纶材质人工血管的涂层(此过程称为预凝),即可防止血液的渗漏,同时还可促进血管平滑肌细胞和成纤维细胞迁移再生的物质,即预凝涂层。 [0003] presetting means when the polyester coating material of the currently used artificial blood vessel lesion displacement body, since the polyester graft material having a plurality of leaky itself, while the lack of guided tissue growth, if coated with a suitable biological histocompatibility chemical polyester coating material as an artificial blood vessel (a process known as pre-condensate), to prevent leakage of blood, but can also promote vascular smooth muscle cells and fibroblast migration regeneration material, i.e., pregelatinized coating. 在目前临床上通常使用的预凝涂层主要是可降解的生物材料,包括自体血浆、白蛋白、胶原、丝素蛋白和明胶等(沈宗林.介绍一种涤纶血管预凝方法.中国循环杂志.1990 ;冯慕贤.马凡综合征心血管病的手术配合.岭南心血管病杂志.1998 ;黄福华.丝素蛋白涂层人工血管的研制.中国医学科学院博士论文;Kuijpers et al, Journal of B1materials Science:PolymerEdit1n,11,225,2000 ;Folk JE.Transglutaminases.B1chemistry1980,49:517 ~531 ;Falcone P,Serafini D,Del Duca S.Comparative studies of transglutaminase activityand substrates in different organs of helianthus tuverosus.Plant Phys1ll993,142:263 ~273 ;Yasueda II,Kumazawa Y,Motoki M.Purificat1n and characterizat1nof a tissue-type transglutaminase from red sea bream.B1science B1technologyB1chemistryl994,58:2041~2045)。 In the main clinical pregelatinized coating are commonly used biodegradable materials, including autologous plasma, albumin, collagen, gelatin and fibroin (Chenzong Lin. Introduction of a polyester vessel presetting method. Chinese Journal of cycle . 1990;.. Pingmu Xian surgery with Marfan syndrome, cardiovascular disease journal cardiovascular diseases. 1998; Huang Fuhua silk fibroin coating developed artificial blood vessels doctoral thesis Chinese Academy of Medical Sciences;.. Kuijpers et al, Journal of B1materials Science : PolymerEdit1n, 11,225,2000; Folk JE.Transglutaminases.B1chemistry1980,49: 517 ~ 531; Falcone P, Serafini D, Del Duca S.Comparative studies of transglutaminase activityand substrates in different organs of helianthus tuverosus.Plant Phys1ll993,142: 263 ~ 273; Yasueda II, Kumazawa Y, Motoki M.Purificat1n and characterizat1nof a tissue-type transglutaminase from red sea bream.B1science B1technologyB1chemistryl994,58: 2041 ~ 2045). 但以上所述涂层材料不稳定,提取和提纯困难,同时价格昂贵(JHLee, WGKim, and SSKim, “Development and characterizat1nok an alginate impregnated polyester vascular graft,”J B1med Mater Res36,200-208(1997)) o But unstable above the coating material, the extraction and purification difficult, and expensive (JHLee, WGKim, and SSKim, "Development and characterizat1nok an alginate impregnated polyester vascular graft," J B1med Mater Res36,200-208 (1997)) o

发明内容 SUMMARY

[0004] 为克服涂层材料不稳定,提取和提纯困难,同时价格昂贵的困难,本发明釆用可降解的生物材料黄芪多糖混合溶液涂层人工血管假体,同样达到免除手术过程中预凝血操作,减少漏血,同时促进血管组织重塑的目的。 [0004] To overcome the instability of the coating material, the extraction and purification difficult, and expensive problem, the present invention is a mixed solution coating Bian prosthetic graft degradable biomaterials APS, to achieve the same pre-coagulation procedure exempt operations, reduce blood leak, while the purpose of promoting vascular tissue remodeling. 该人工血管由具有生物相容材料构成的多孔隙管状或Y状合成血管假体与混合有塑化剂的黄芪多糖溶液交联而成,使得人工血管假体不漏血,从而免除手术过程中的预凝操作。 The artificial blood vessel made of a biocompatible material having a tubular or Y-shaped porous synthetic vascular prosthesis with a mixed solution of Astragalus Polysaccharide crosslinking plasticizer, such that no artificial vascular prosthesis endoleak, eliminating the surgical procedure the presetting operation. 该多孔隙人工血管假体由涤纶材质机织或针织rfo )¾。 The artificial porous woven Dacron vascular prosthesis material knitting machine or rfo) ¾. [0005] 从中药黄芪提炼并通过微波辅助和沉淀等方法得到高纯度的黄芪多糖原粉后,通过配比制成悬浮液。 [0005] After the extract of astragalus root and astragalus polysaccharide obtained raw powder by microwave assisted high purity and precipitation methods, by the ratio to prepare a suspension. 将高纯度的黄芪多糖溶液均匀涂于合成血管假体的内外面,使人工血管结构上充满弹性而且具备较好的操控性和纵向伸展能力。 The high purity polysaccharide solution evenly Astragalus inner and outer surfaces of the synthetic vascular prosthesis, so that full flexibility and with good handling ability and extending longitudinally vascular prosthesis structure. 使用黄芪多糖蛋白混合溶液涂层3到10遍,干燥后将其暴露于炭化二亚胺蒸汽的干燥箱中交联固定。 Astragalus Polysaccharide protein using a mixed solution of 3 to 10 times the coating, after drying, exposed to steam drying oven carbonization carbodiimide crosslinking fixed.

[0006]为保持人工血管假体在干燥状态下保持柔软不塌陷而具有弹性,在使用黄芪多糖溶液涂层人工血管假体前需要阿拉伯胶或其他生物相容性的塑化剂。 [0006] In order to maintain an artificial vascular prosthesis remains soft and does not collapse in the dry state has an elastic, biocompatible need acacia or other plasticizer prior to use in the coating solution Astragalus polysaccharides artificial vascular prosthesis. 混合涂层材料中黄芪多糖浓度为20μ g / ml,塑化剂浓度为20-25% (重量百分比)。 Astragalus Polysaccharide hybrid coating material at a concentration of 20μ g / ml, the concentration of plasticizer is 20-25% (by weight).

[0007] 合成针织或机织型的人工血管依照本发明的方法使用黄芪多糖和塑化剂的混合液涂层后获得最重要的特征是使原来多孔隙结构的血管基质的渗水率约降至零,并且有利于血管组织的生长。 The most important feature is obtained after the coating mixture [0007] Synthetic knitted or woven vascular prosthesis type using Astragalan and plasticizer according to the method of the present invention is a water-permeability of the blood vessel so that the original porous structure of the matrix is ​​reduced to approximately zero, and is conducive to the growth of vascular tissue. 作为对照实验,随机取未涂层的10根合成机织型的涤纶血管,平均渗水率为:357.9±20.4ml / min*cnT2,按照本发明涂层后渗水率降至零。 As a control experiment, randomly selected 10 uncoated woven synthetic vascular polyester type, average seepage rate: 357.9 ± 20.4ml / min * cnT2, according to the present invention, the water-permeability of the coating to zero. 同时取未涂层的5根合成机织型的涤纶血管植入实验动物体内6小时后,病理组织学检验显示并无血管组织生长,按照本发明涂层后有血管组织生长。 At the same time taking 5 uncoated woven synthetic vascular implant type polyester experimental animals 6 hours, histopathological examination showed no growth of vascular tissue, according to the present invention, after the coating vascular tissue growth.

[0008] 由此,本发明目的是提供一种制备不漏血和促进血管组织再生的人工血管假体的方法。 [0008] Accordingly, an object of the present invention to provide a method of preparation does not promote vascular leakage of blood and tissue regeneration in artificial vascular prosthesis.

[0009] 本发明进一步的目的是提供一种制备黄芪多糖溶液涂层合成血管假体使其不漏血并且可促进血管组织再生的方法。 A further object of the [0009] present invention is to provide a process for preparing the coating solution Astragalus polysaccharides synthetic vascular prosthesis and method of leakage of blood vessel so as not to promote tissue regeneration.

[0010] 本发明其他的目的和益处将在以下的实例说明中得到清晰的显示。 Other objects and advantages of the invention will be obtained in the following description, examples clearly show the [0010] present.

[0011] 本发明包含的特征、性质以及相关原理和操作步骤和各步骤之间的关系将在以下具体实例中的细节逐一阐述,而本发明的范围将在权利要求中说明。 [0011] The invention comprises the features, properties and the relation between the steps and the related principles and operation of the various steps in the following specific details given in each example, and the scope of the present invention will be described in the claims.

附图说明 BRIEF DESCRIPTION

[0012] 为更好的理解本发明,须参考说明书附图及说明: [0012] For better understanding of the present invention shall be described with reference to the description and the accompanying drawings:

[0013] 图1是按照本发明的方法制备的黄芪多糖溶液涂层的直线型人工血管假体部分的横截面; [0013] FIG. 1 is a cross-sectional linear portion artificial vascular prosthesis was coated polysaccharides were prepared according to the method of the present invention;

[0014] 图2是按照本发明的方法制备的黄芪多糖溶液涂层的Y型人工血管假体部分的横截面; [0014] FIG. 2 is a cross-sectional Y-graft prosthesis portion polysaccharides were prepared by a solution coating method according to the present invention;

[0015] 图3表示人工血管假体的渗水率随着按照本发明的方法运用黄芪多糖溶液涂层次数增多逐步降低; [0015] FIG. 3 shows a water-permeability of the artificial blood vessel prosthesis with the use of the number of coating solution Astragalus Polysaccharide method according to the present invention increased gradually decreased;

[0016] 图4表示运用本发明的方法黄芪多糖涂层人工血管上血管组织生长表现。 [0016] FIG. 4 shows the use of the present invention is a coating method of Astragalus Polysaccharide graft vascular tissue growth performance.

图5表示不同浓度黄芪多糖对细胞增殖的影响。 FIG 5 shows the effect of different concentrations of Astragalus Polysaccharide on cell proliferation.

具体实施方式 Detailed ways

[0017] 按照本发明制备的合成人下血管假体如图1所示:包括管型结构主体01,它是由具生物相容性的纤维合成材料,尤其是聚对苯二甲酸乙酯(即涤纶)针织或机织而成的基质02构成的多孔隙结构体.基质02具有内外侧两层绒面04。 [0017] FIG vascular prosthesis according to the present invention, synthetic human prepared 1: structure comprises a tubular body 01, which is made of fibrous composite material with a biocompatible, especially polyethylene terephthalate ( i.e. polyester porous structure) knitted or woven from a matrix configuration 02 the matrix 02 having inner and outer layers 04 suede. 涤纶构成管型结构主体01,并且使其具备多孔隙的结构允许受体的血管组织侵入生长,同时保持开放的管腔结构允许血液顺畅通过。 Polyester constituting the tubular body structure 01, and it includes a porous structure allows the growth of blood vessels invade tissue receptors, while maintaining an open lumen through the structure allows smooth blood. 在绒面04内侧面覆盖有黄芪多糖溶液涂层06,黄芪多糖溶液涂层06需要运用黄芪多糖和塑化剂的混合液体材料涂层3-10遍并通过暴露在炭化二亚胺蒸汽中交联ίίϋ 。 In the pile 04 is covered with the side surface 06 Astragalus polysaccharides coating solution, the coating solution was 06 Astragalus polysaccharides requires the use of a mixed liquid coating material Astragalan and plasticizer and 3-10 times by exposure to vapor deposit carbonization diimine United ίίϋ.

[0018] 图2演示一Y字形黄芪多糖溶液涂层的人工血管假体12,血管假体12包括主管状结构体14和两个分枝管状体16。 [0018] 12, vascular prosthesis graft prosthesis of FIG. 2 illustrates a Y-shaped coating solution Astragalus Polysaccharide 12 includes a main body structure 14 and the two branches of the tubular body 16. 主管状结构体14和分枝管状体16由漆纟仑针织或机织而成的基质18构成,基质18内侧绒面覆盖有黄芪多糖溶液涂层20,需要运用黄芪多糖溶液涂层3-10遍。 Main tubular structure 14 and the tubular body 16 woven by the branched paint Hyland knitted or made of Si substrate 18 constituting the matrix 18 is covered with the textured inner Astragalus polysaccharides coating solution 20, it requires the use of a coating solution Astragalus polysaccharides 3-10 all over.

[0019] 依据本发明多孔隙结构的人工血管假体基质由涤纶通过针织或机织而成最优。 [0019] The artificial vascular prosthesis according to the matrix of the porous structure of the present invention is woven by a machine or by knitting the best polyester. 通常通过涤纶机织编织而成的人工血管假体渗水率范围在357.9±20.4ml / min*cm~20交联黄芪多糖溶液的方法是将黄芪多糖和塑化剂的混合液均匀涂在人工血管假体基质内,去除多余的涂层材料并放置干燥后暴露于炭化二亚胺蒸汽中交联,后在干燥箱内干燥脱水。 Usually by weaving woven Dacron vascular prosthesis machine artificial water permeability in the range of 357.9 ± 20.4ml / min * cm ~ 20. The method of crosslinking the polysaccharide solution is Astragalus mixture Astragalan and plasticizer uniformly coated grafts endoprosthesis matrix to remove excess coating material after drying and left exposed to the steam charring carbodiimide crosslinking, dehydrated and dried in an oven. 按照本发明制备的黄芪多糖溶液涂层的人工血管的渗水率(单位:ml / min*cm~2)接近于零。 Water permeability of the artificial blood vessel in accordance with the coating solution of polysaccharides were prepared in the present invention (unit: ml / min * cm ~ 2) close to zero. 通常通过涤纶基质编织而成的人工血管假体植入到实验动物体内,在6小时内人工血管假体上血管组织基本不生长。 Dacron is usually woven by a matrix graft prosthesis is implanted into experimental animals, the graft prosthesis within 6 hours of vascular tissue does not grow substantially. 通过本发明制成的含有黄芪多糖涂层的人工血管假体植入实验动物体内,6小时后人工血管假体上血管组织有明显生长。 Artificial vascular prosthesis comprising Astragalus Polysaccharide coatings produced by the present invention implanted in experimental animals, six hours after the artificial blood vessel prosthesis significant growth of vascular tissue.

[0020] 以下实例将说明黄芪多糖从植物黄芪中提取和纯化以及根据发明制备黄芪多糖溶液涂层人工血管假体的过程。 [0020] The following examples will be described tragacanth Astragalus polysaccharides extracted from plants and purification, and prepared according to the process of the invention the polysaccharide solution coating Astragalus graft prosthesis. 列举实例的目的是阐述专利而不是来限制它的范围。 Lists of examples are illustrative purposes and not to limit its patent scope.

[0021] 实例1:黄芪多糖提取方法 [0021] Example 1: Methodology for the Extraction

[0022] 把黄芪在磨粉机中磨成粗细均匀的粉末状,然后取10g黄芪粉末加入适量蒸馏水溶解搅拌形成溶液,后将溶液在70°C恒温中回流提取3次,每次提取3h,加纯化水量40ml和95%乙醇至终浓度90%进行醇沉静置4h,收集沉淀物。 [0022] The pulverized in a mill Astragalus uniform thickness of powder, and then take 10g of astragalus powder was added an appropriate amount of distilled water was stirred to form a solution, the solution was extracted three times under reflux for 70 ° C at constant temperature, each extraction 3h, add 40ml purified water and 95% ethanol to a final concentration of 90% alcohol for quiet set 4h, the precipitate was collected. 收集到的沉淀物在干燥箱中干燥24h后形成粉末状黄芪多糖,此时所得黄芪多糖原粉浓度为70-80% (重量百分比),最后加入适当的蒸馏水调配成实验所需的浓度。 The precipitate was collected and dried in a drying oven 24h powdered form APS, the concentration of the original powder obtained at this time Astragalus polysaccharides 70-80% (by weight), distilled water was added to the appropriate final formulated to a desired concentration in the experiment.

[0023] 实例2:黄芪多糖溶液涂层人工血管 [0023] Example 2: Astragalus Polysaccharide graft coating solution

[0024] 将含有黄芪多糖(按照实例I从黄芪中提取)浓度为20μ g / ml的黄芪多糖混合液注满50ml的注射器内,该黄芪多糖混合液含有20%的阿拉伯胶和蒸馏水,粘度为30000-37000厘泊。 [0024] Polysaccharide containing Astragalus (Astragalus membranaceus extract from according to Example I) at a concentration of syringe 20μ g / ml polysaccharides were filled with 50ml of a mixture, the mixture was Astragalus polysaccharides containing gum arabic and 20% distilled water, viscosity 30000-37000 cps. 注射器与人工血管假体一端相连,黄芪多糖混合液被推注入人工血管腔并使涂层液均匀涂布在管腔内壁,多余的黄芪多糖混合液在人工血管假体另外一端流出。 Syringe connected to an end of the artificial vascular prosthesis, APS implanted artificial blood vessel lumen mixture was pressed and the coating was uniformly applied to the inner wall of the lumen, the excess mixture Astragalus Polysaccharide graft prosthesis in the other end of the outflow. 涂层后人工血管在50摄氏度的干燥箱中干燥I小时,涂层干燥需要反复操作3-10次。 After the coating was dried artificial blood vessel I hour, drying the coating operation requires repeated 3-10 times at 50 degrees C in the oven.

[0025] 涂层3-10次后,使人工血管暴露于炭化二亚胺蒸汽中交联交联后置于50摄氏度干燥箱中干燥24小时。 After [0025] 3-10 coating the artificial blood vessel is exposed to steam carbonization carbodiimide cross-linking the cross-linking oven dried at 50 ° C for 24 hours.

[0026] 实例3:涂层前后人工血管假体血液渗透率比较 [0026] Example 3: Comparison of artificial blood vascular prosthesis permeability before and after coating

[0027] 按照实例2的方法制备的黄芪多糖溶液涂层的人工血管检测如下,随机取10根直径为8mm,长度为1cm涂层后的合成机织人工血管并与储血器相连,在120mmHg压力下,使肝素化的血液在人工血管内通过,收集渗漏的血液并计量(单位/ min*cnT2)。 [0027] The graft coating was detected polysaccharides were prepared following the method of Example 2, having a diameter of 10 randomly selected 8mm, a length of 1cm after coating a woven synthetic vascular prosthesis connected with the blood reservoir and is at 120mmHg under pressure, heparinized blood in the artificial blood vessels by collecting blood leakage and measurement (unit / min * cnT2). 检测结果10根人工血管的血液渗出率分别为:0.10,0.05,0.01,0.04,0.05,0.01,0.0,0.01, 10 the detection result of the artificial blood vessel bleeding rates were: 0.10,0.05,0.01,0.04,0.05,0.01,0.0,0.01,

0.03,0.02,平均血液渗出率为0.032ml / min*cnT2,接近于零。 0.03,0.02, oozing average rate of 0.032ml / min * cnT2, close to zero.

[0028] 为与未涂层的机织人工血管比较,选取未涂层的人工血管重复上述实验操作,测得平均血液渗出率为30.1ml / min*cm'2o [0028] The uncoated knitting machine with artificial blood vessels compared to uncoated selected above experiment was repeated artificial blood vessel operation, bleeding was measured mean blood 30.1ml / min * cm'2o

[0029] 实例4:涂层次数前后人工血管假体渗水率比较 [0029] Example 4: Comparison of an artificial vascular prosthesis times seepage rate before coating

[0030] 人工血管经过黄芪多糖混合液涂层3次后渗水率降至6%以下,涂层10次后渗水率降至IV0以下。 [0030] After the artificial blood vessel Astragalus Polysaccharide coating mixture after 3 to 6% or less water-permeability, water permeability of the coating after 10 IV0 less reduced. 标准的渗水率实验测定为在120mmHg的水柱压力下通过2.44cm~2面积的圆孔,将人工血管假体的样品固定在圆孔上lmin,收集并且测定渗水量。 Standard water permeability experiment was measured by 2.44cm ~ 2 circular area of ​​the sample artificial blood vessel prosthesis is fixed on the circular hole lmin at water pressure of 120mmHg, collected and measured seepage. 每个样品分别测定数次,测定结果如下表示:渗水率=ml / (min*cnT2)。 Each sample were measured several times, the measurement results are shown as follows: water permeability = ml / (min * cnT2). 机织人工血管的渗水率为600ml /min*cnT2经过不同次数涂层后的渗水率。 Woven vascular prosthesis water-permeability of 600ml / min * cnT2 different times after the water permeability of the coating.

[0031] 变化如下: [0031] change as follows:

[0032] [0032]

Figure CN104027844AD00061

[0033] 在上述实验的每一次涂层使用的黄芪多糖溶液均从黄芪按照实例I描述提取,涂层方法均按照实例2描述操作。 [0033] Astragalus polysaccharides are described extraction solution used in each coating layer from the above experiment Astragalus according to Example I, were coated according to the method of operation described in Example 2. 结果如附图3所示。 The results are shown in Figure 3. 结果黄芪多糖涂层后的人工血管渗水率大幅下降,接近于零。 Results graft seepage rate after coating polysaccharides were dropped close to zero.

[0034] 与未涂层的人工血管相比,黄芪多糖溶液涂层的人工血管不仅降低了渗水率,而且促进血管组织生长。 [0034] Compared with uncoated artificial blood vessel, artificial blood vessel Astragalus Polysaccharide coating solution not only reduces water-permeability and promote the growth of vascular tissue. 以下的实例证明与对照组相比黄芪多糖溶液涂层人工血管假体显著的促进血管组织生长。 The following examples demonstrate significant role in promoting the growth of vascular tissue Astragalus Polysaccharide coating artificial vascular prosthesis was compared with the control group.

[0035] 实例5:涂层前后人工血管上血管组织生长比较实验(体内实验) [0035] Example 5: before and after the coating on growth of vascular tissue graft comparative experiment (in vivo experiment)

[0036] 黄芪多糖涂层人工血管假体体内(实验用新西兰大白兔)实验如下。 [0036] Astragalus Polysaccharide coatings of artificial vascular prosthesis in vivo (experiment New Zealand white rabbits) following experiment. 动物术前称重安定,后用浓度为20%的乌拉坦3ml / kg静脉麻醉。 Animals were weighed before stable operation, after 20% of the concentration of urethane 3ml / kg intravenous. 每个动物植入人工血管前经静脉给予10ug / kg肝素避免血管内血栓形成。 Each animal before implantation of an artificial blood vessel administered 10ug / kg avoiding intravascular thrombosis heparin intravenously. 腹部正中切口,游离约肾动脉开口以下Icm的腹主动脉3-6cm,以主动脉阻断钳上下阻断并切除1-2腹主动脉,以6-0 Prolene线采用端端吻合植入黄芪多糖涂层血管假体,术毕以鱼精蛋白中和肝素(I: D防止术后出血。术中给予抗生素头抱唑啉10mg静推,术后相同剂量肌注3天,处死前常规喂养。 Abdominal incision, opening the free about the renal artery of the abdominal aorta Icm 3-6cm, in order to block the vertical and clamp aortic occlusion of the abdominal aorta excised 1-2 to 6-0 Prolene line using anastomosis implant Astragalus polysaccharide coatings vascular prosthesis, surgery to protamine and heparin (I: D surgery to prevent postoperative bleeding cephalosporin antibiotics oxazoline 10mg bolus intramuscular injection at the same dose after 3 days before sacrifice regular feeding. .

[0037] 按照以上述操作重复为5只实验动物进行手术。 [0037] In accordance with the above-described surgical operations are repeated for the five experimental animals. 并分别在6小时、I天、I周、I个月、3个月共5个时间点取出体内的黄芪多糖涂层人工血管进行组织学切片,并按一下方式评估人工血管上血管组织的生长情况。 And 6 hours, respectively, the I day, the I weeks, the I months, 3 months, 5 time points were taken Astragalus Polysaccharide coatings of artificial blood vessel body of histological sections, and click on the assessed growth of vascular tissue graft Happening.

[0038] 按预定时间取出移植物,纵行切开血管假体,以PBS液细心冲洗,拍摄照片观察血管外形,显微镜分析血管假体近端吻合口、血管中段和远端吻合口约Icm长的标本。 [0038] The graft taken at a predetermined time, the longitudinal incision vascular prosthesis, was carefully rinsed with PBS and photographed blood vessel shape observation, microscopic analysis of the proximal anastomosis vascular prosthesis, vascular middle and distal anastomotic length approximately Icm specimens. 标本用2%的甲醛固定2h,冷冻干燥后石蜡块包埋,10pm厚度切片,同定在玻片上后以苏木精一伊红染色,染色标本的愈合特征通过光学显微镜观察炎症,异物巨细胞反应,内膜纤维化的程度。 Specimens were fixed with 2% formaldehyde 2h, embedded in paraffin blocks after lyophilization, 10 pM slice thickness, with the slide in the fixed hematoxylin eosin, characterized in healing inflammation stained specimen was observed by an optical microscope, foreign body giant cell response the degree of intimal fibrosis. 简单说将反应程度分为三个等级,以参数从O到2表示相应的等级,炎症的等级依据移植血管周围浆细胞,淋巴细胞和多形核细胞的多少进行估计,0=无到轻度;1=轻度到中度;2=中度到重度。 The extent of reaction simply divided into three levels, represented by a parameter corresponding grade 2, grade inflammation based graft perivascular plasma cells, lymphocytes, and polymorphonuclear cells number is estimated, from 0 to mild = O to ; 1 = mild to moderate; 2 = moderate to severe. 异物巨细胞反应则依据多核巨细胞和组织细胞(巨嗜细胞)在血管织物周围的情况进行估计:0=极轻微的反应从中线延伸到移植物不到I / 3的厚度,1=异物反应从中线到达移植物达2 / 3的厚度;2 二异物反应达到整个移植物壁的厚度"血管假体纤维化的分析依据内膜表面纤维化的程度:0 =绝大部分的纤维蛋白和红细胞;1= 一些成纤维细胞和纤维蛋白;2=绝大部分是成纤维细胞和胶原。血管假体内壁的新内膜形成通过光学显微镜和扫描电子显微镜观察评价。 Giant cell foreign body reaction were based on the tissue cells and multinucleated giant cells (macrophages) in the case of a fabric around a vascular estimation: 0 = a very mild reactions extends from the centerline to a thickness of less than implant I / 3, the foreign body reaction 1 = midline graft reaching up to 2/3 of the thickness; 2 reaches two foreign body response analysis "fibrosis vascular prosthesis graft wall thickness of the entire endocardial surface based on the degree of fibrosis: 0 = most of fibrin and erythrocytes ; 1 = number of fibroblasts and fibrous proteins; 2 = mostly of fibroblasts and collagen prosthesis wall neointima formation of blood vessels was observed by an optical microscope and scanning electron microscopic evaluation.

[0039] 具体结果如下: [0039] The results were as follows:

[0040] [0040]

Figure CN104027844AD00071

[0041 ] 为与未涂层的机织人工血管比较,选取未涂层的人工血管重复上述实验操作。 [0041] The comparison with the uncoated weaving machine artificial blood vessels, artificial blood vessel selected uncoated above experiment was repeated operation.

[0042] 具体结果如下: [0042] The results were as follows:

[0043] [0043]

Figure CN104027844AD00072

[0044] 基于上述实验结果,黄芪多糖涂层的涤纶人工血管显著促进血管组织生长,并且显著多于未预凝组,这可能与黄芪多糖可促进血管组织生长有关。 [0044] Based on the above experimental results, Astragalus Polysaccharide graft polyester coating significantly promote the growth of vascular tissue, and not significantly more than the pre-coagulation group, which may be relevant Astragalus polysaccharides can promote the growth of vascular tissue.

[0045] 实例6:不同浓度黄芪多糖促进人脐静脉血管内皮细胞实验(体外实验) [0045] Example 6: Different concentrations of Astragalus polysaccharides promote human umbilical vein endothelial cell assay (in vitro)

[0046] 人脐静脉血管内皮细胞增殖实验如下。 [0046] The human umbilical vein endothelial cell proliferation assay as follows. 取对数生长期细胞,常规消化制成细胞悬液。 Cells in logarithmic growth phase, regular digested cell suspension. 重悬细胞,以约IX 10~4个细胞每200 μ g接种于96孔板。 Cells were resuspended at about IX 10 ~ 4 cells per 200 μ g were seeded in 96-well plates. 24h后,待细胞贴壁后分别给予生物膜4处理,并设置空白培养液组作为比色时的空白对照,每个浓度设置3个复孔。 After 24h, cells were administered until biofilm adherent 4, and sets a blank incubation time of the control group as compared to the color, each provided with three wells concentration. 继续培养24h。 Cultured for 24h. 每孔加入CCK820LL,置5% C02孵箱继续培养24h。 Added to each well CCK820LL, 5% C02 incubator set cultured 24h. 用酶标仪检测450nm处的光密度值(0D值)。 Detecting the optical density (0D value) using a microplate reader at 450nm.

[0047] 黄芪多糖不同浓度对细胞增殖的影响:黄芪多糖浓度分别为0、10、20、40、80、120Lg / ml处理人脐静脉血管内皮细胞24小时后加入CCK820LL,37e,lh后490nm检测其OD值结果。 [0047] Effect of different concentrations of Astragalus Polysaccharide on cell proliferation: Astragalus Polysaccharide concentrations of 0,10,20,40,80,120Lg / ml treatment of human umbilical vein endothelial cells were added CCK820LL After 24 hours, 37e, after lh 490nm Detection OD values ​​result. 重复3次(n=3)取均值与标准差。 Was repeated 3 times (n = 3) taking the mean and standard deviation. 黄芪多糖浓度在20ug / ml时促进细胞生长作用最明显,此后随着浓度的升高,促生长的作用逐渐降低,但均显著高于控制组(P<0.01);黄芪多糖在20ug / ml时内皮细胞增殖率几乎达到控制组2倍,且显著高于其他各组(P〈0.01)。 Astragalus Polysaccharide concentration of the accelerator at 20ug / ml most significant effect of cell growth, then with increasing concentration of the growth-promoting effect gradually decreased, but were significantly higher than control group (P <0.01); astragalus polysaccharide 20ug / ml endothelial cell proliferation rate of almost 2 times the control group, and significantly higher than the other groups (P <0.01).

[0048] 具体结果如图5所示。 [0048] In particular the results shown in FIG.

[0049] [0049]

[0050] [0050]

[0051] 综上所有实例,黄芪多糖和塑化剂的混合溶液涂层合成机织具多孔隙结构的人工血管假体免除了手术过程中的预凝血操作,同时提供了理想的基质便于血管组织的侵入和包裹生长。 [0051] The mixed solution coating Synthesizer all instances, APS and a plasticizer having a porous structure woven artificial vascular prosthesis fully eliminates the pre-coagulation operations during surgery, while over vascular tissue matrix to facilitate invasive growth and parcels. 合成的针织或机织涤纶人工血管按照本发明使用黄芪多糖溶液涂层后使其柔软有弹性具备好的操作性。 After synthetic knitted or woven Dacron vascular prosthesis was coated Astragalus polysaccharides used according to the present invention includes a soft and flexible so good operability.

[0052] 由此依据以上阐述的方法操作,本发明目的能客观有效实现。 [0052] Thus according to the method of operation set forth above, object of the present invention can be effective to achieve the objective. 但在不背离本发明精神和范围情况下,上述的操作具体步骤和某些条款可以有一定改变,因此上述实例描述和附图描述所涉及的方法和使用的某些物质材料是用来演示阐述发明,而不应该理解为限制发明所涵盖的范围。 However, without departing from the spirit and scope of the present invention, the above-described specific operation steps and certain provisions may have a change, so the method described in the above example description and drawings of certain substances involved and the materials used are set forth to demonstrate the invention should not be construed as limiting the scope covered by the invention.

Claims (6)

1.一种制备预凝涂层的人工血管假体的方法,所述具有涂层的人工血管假体包括人工血管假体和涂在人工血管假体上的涂层,其特征在于所述涂层含有黄芪多糖和塑化剂。 CLAIMS 1. An artificial vascular prosthesis pregelatinized coating prepared with the coating artificial vascular prosthesis comprising an artificial vascular prosthesis and coated on the coating artificial vascular prosthesis, characterized in that the coating Astragalus polysaccharide containing layer and a plasticizer.
2.根据权利要求1所述的制备人工血管的方法,特征在于将含有黄芪多糖和塑化剂的混合溶液均匀涂覆在人工血管全层,然后在含有炭化二亚胺蒸汽的干燥箱中进行交联固定,最终获得所述的人工血管假体。 The method for preparing an artificial blood vessel according to claim 1, wherein the mixed solution containing a uniform coating Astragalan and plasticizer in full-thickness graft, comprising a drying oven and then carbonized vapor carried diimine cross fixing finally obtained artificial blood vessel prosthesis.
3.根据权利要求1或2所述的制备人工血管假体的方法,其特征在于塑化剂选自阿拉伯胶。 The method according to claim 1 or 2 Preparation of artificial vascular prosthesis as claimed in claim, wherein the plasticizer is selected from acacia.
4.根据权利要求1或2所述的制备人工血管假体的方法,其特征在于人工血管假体由生物相容性材料制成,其为涤纶材质(学名聚对苯二甲酸乙二酯)并具有弹性多孔隙管型或Y字型结构的合成编织物,可以是机织型或针织型。 The method of producing an artificial vascular prosthesis of claim 1 or claim 2, characterized in that the artificial blood vessel prosthesis is made of biocompatible material, which is made of polyester (polyethylene terephthalate scientific name) and multiple synthetic elastic tubular knitted fabric or pores of the Y-shaped structure can be woven or knitted type type.
5.根据权利要求1或2所述的制备人工血管假体的方法,其特征在于黄芪多糖的浓度为20μ g / mL,塑化剂浓度为20-25% (重量百分比)。 5. The method of claim 1 or 2 Preparation of artificial vascular prosthesis as claimed in claim, characterized in that the concentration of APS was 20μ g / mL, the concentration of plasticizer of 20-25% (by weight).
6.根据权利要求1或2所述的制备人工血管假体的方法,其中涂覆涂层溶液一般要.3-10 层。 The method according to claim 1 or 2 Preparation of artificial vascular prosthesis as claimed in claim, wherein the coating solution generally .3-10 layer.
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