CN101077424B - Blood vessel bonding anastomosis sealant and kit - Google Patents

Blood vessel bonding anastomosis sealant and kit Download PDF

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Publication number
CN101077424B
CN101077424B CN2006100812207A CN200610081220A CN101077424B CN 101077424 B CN101077424 B CN 101077424B CN 2006100812207 A CN2006100812207 A CN 2006100812207A CN 200610081220 A CN200610081220 A CN 200610081220A CN 101077424 B CN101077424 B CN 101077424B
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cacl
solution
blood vessel
sodium alginate
sealant
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CN101077424A (en
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范恒华
张伯勋
伍骥
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Abstract

The present invention discloses one kind of blood vessel adhering sealant comprising 10-25 wt% concentration CaCl2 solution and 1-5 wt% concentration sodium alginate solution. The sealant of the present invention is safe and non-toxic, and can solidify fast to form water insoluble film for effective blocking. The endovascular rack with coated CaCl2 component can block medical adhere from leaking to inside the cavity.

Description

A kind of blood vessel bonding anastomosis sealant and test kit
Technical field
The present invention relates to a kind of blood vessel bonding anastomosis sealant and test kit, belong to medical biotechnology field.
Background technology
The vascular anastomosis method has a lot, and traditional identical method is identical method, i.e. " goldstandard " vascular anastomosis method of interrupted suture.But needlework cause the penetrance damage to blood vessel wall, and especially the damage to inner membrance can cause certain identical mortality, and complex operation, and is consuming time long.Therefore many scholars seek better vascular anastomosis method.As support identical method, embedding inosculating method, heat is coagulated coincide method, bonding anastomosis method and mechanical anastomosis method etc.
The blood vessel bonding anastomosis method is to use medical glue (cyano group acrylic acid ester coincide glue), and in conjunction with the method for technology anastomosis of blood vessel such as support.The medical glue that uses still has side effect such as toxic damages to vascular tissue, the colloid tube chamber that bleeds then can have the effect of strong hyperamization bolt in anastomotic stoma, thereby cause the failure that coincide.
The direct bonding anastomosis method of hollow inner support end end is a kind of bonding of former studies method of coincideing, and has Wicresoft, succinct, fast and the characteristics such as can leading to blood after finishing of coincideing.Concrete grammar is: the hollow instant bracket is inserted treat the anastomosis of blood vessel two ends, two ends are held together tightly involutory, be coated with medical identical glue then around the anastomotic stoma, colloid is a complete operation after solidifying.
Also there is weak point in this method: 1. and during blood vessel two end-to-end anastomosis, that two ends are involutory tight again, still may leave the slit, when being coated with medical glue, the tube chamber that can bleed unavoidably forms thrombosis, causing the failure that coincide; 2. for middle trunk, or the bigger anastomotic stoma of tension force, intensity may be not enough; 3. can crack during the viscose glue pyknosis, thereby easily form anastomotic leakage.
Summary of the invention
The technical problem to be solved in the present invention provides and a kind ofly can effectively stop the bleed blood vessel bonding anastomosis sealant of tube chamber of colloid.
Another technical problem that the present invention will solve provides a kind of blood vessel bonding anastomosis sealant test kit easy to use.
For achieving the above object, the present invention is by the following technical solutions:
A kind of blood vessel bonding anastomosis sealant is the CaCl of 10-25wt% by concentration 2The sodium alginate soln of solution and 1-5wt% is formed.
As better embodiment, CaCl 2The concentration of solution is 20wt%, and the concentration of sodium alginate soln is 3wt%.
Principle of the present invention: the sodium alginate soln of low concentration has certain fluidity and viscosity, meets CaCl 2Immediately at contact surface formation calcium alginate film, can't be dissolved by body fluid and wash away behind the solution, be detained original position, infiltrate tube chamber, avoid its damage and formation thrombosis, play the effect of sealing and protection blood vessel and the pipe broken ends of fractured bone and inner membrance thereby intercept medical glue.
Using method of the present invention is simple, earlier sodium alginate soln is splashed into vascular anastomosis, drips CaCl subsequently thereon 2Solution and film forming, promptly salable anastomotic stoma.
We are to sodium alginate soln and CaCl 2The concentration of solution has been carried out optimization test, chooses sodium alginate soln and 40wt%, 20wt% and the 10wt%CaCl of 1wt%, 2wt%, 3wt%, 5wt% and 10wt% respectively 2Solution is at first pressed variable concentrations sodium alginate dissolving is formed faint yellow translucent thick liquid, then with the CaCl of variable concentrations 2The solution reaction film forming is measured the indexs such as comfort level, viscosity, flowability (infiltrating time), film forming speed and film forming thickness of its dropwise operation, determines the concentration proportioning of final fluid sealant.
Discover: the sodium alginate soln for variable concentrations of (1), film forming speed and solution concentration do not have obvious relation, and film forming thickness increases with solution concentration, and mirror is observed down and is shown that the high more film forming compactness of concentration is good more.But, sodium alginate soln concentration is by 1wt% to 10%, flowability is variation gradually, flowing time increases gradually, in operation technique, requires fluid sealant to finish vascular anastomosis infiltration on every side in 1~2 second, therefore flow velocity can not be too slow, select 1wt%-5wt% better, take all factors into consideration other factors, 3wt% is an optium concentration.In addition, gel shaped good under the 5wt% concentration, be convenient to operation.(2) for the CaCl of variable concentrations 2Solution, film forming thickness increases with its concentration and slightly thickens.Film forming speed and solution concentration do not have obvious relation.
Sodium alginate soln and CaCl 2Solution reaction generates calcium alginate, it is reported that this material and body have better biocompatibility, and is nontoxic substantially, harmless to body.We select the CaCl of 40wt% and 20wt% for use 2The calcium alginate gel of 40wt% and 20wt% is made in the sodium alginate soln reaction of solution and 5wt%, heeling-in is gone in 2 groups of each 8 SD rat bodies, divide at 3 and be imbedded at both sides, back and subcutaneous abdomen, postoperative is raised, activity of observation rat and diet, drinking-water situation, and response situation such as the partial skin of heeling-in, and detect the reaction of body to calcium alginate, judge toxic reaction and other untoward reaction that experimental animal may exist after implantation.
The result shows: (1) implant faded away after 3 weeks.(2) 40wt% group SD subcutaneous rat is imbedded a local skin, has 3 redness to occur after 2 days, has 2 after the week and ulceration occurs, incrustation healing after eliminating graft and the sepage; All the other rats and 20wt% group SD rat do not see obvious adverse reaction at transplantation site, and wound healing is good.The Total Test animal activity is no abnormal, nothing is dead, and diet is normal.(3) in-vivo tissue learn to detect is found: when the 2nd thoughtful the 4th week, visible periphery has peplos and vascularization, and during to the 8th week, peplos attenuation blood vessel reduces; During to 16 weeks, peplos disappears substantially, the only surplus skim of the calcium alginate of imbedding, and the overwhelming majority absorbs (about 80%).In the identical time-histories, the group surplus that concentration is low is few.As time passes, two groups of surpluses all reduce.According to above result, there is stronger irritant reaction the calcium alginate part of 40wt%, so that the skin inflammatory is red and swollen and downright bad, but animal activity is no abnormal, does not have death, and diet is normal.CaCl is described 2Solution concentration is too high, and is only unfavorable to the part, or even destructive, but whole body is not had obvious influence.Therefore select the CaCl about 20wt% 2Solution is proper.
The present invention also provides a kind of blood vessel bonding anastomosis sealant test kit, comprises the CaCl of 10-25wt% 2The sodium alginate soln of solution and 1-5wt%.This test kit also comprises CaCl 2, sodium alginate and solvent.Wherein solvent can be distilled water, distilled water, water for injection etc., in order to dissolving CaCl 2And sodium alginate, the CaCl of preparation 10-25wt% 2The sodium alginate soln of solution and 1-5wt%.
Also prepare in this test kit endovascular stent is arranged.Endovascular stent can be present commercially available any hollow inner support that can be used for vascular anastomosis as routine techniques.
In order to obtain more excellent technique effect, the present invention has CaCl in hollow inner support surface coated 2Composition.This rack surface coating process is simple, to the CaCl of 10-25wt% 2Solution adds gelatin, and making gelatin concentration is wt2.5%, gets the gelatin CaCl of this 2.5wt% of hollow inner support dipping 2Dry behind the solution, packing is used 60The Co sterilization is standby.
The present invention also provides a kind of special endovascular stent, and it is the column structure of fusiformis for radially hollow, two ends, and outer surface is coated with CaCl 2Composition.This support is that raw material is made with the Polyethylene Glycol, and manufacture method is with reference to Liang Xiangdang, Zhang Baixun, Fan Yuwei etc. novel vascular coincide with the influence of support to tunica intima.Health care equipment .2003; 24 (7): 5-6 and 13 Sun Geng, Zhang Baixun, Liang Xiangdang etc. coincide with the research of endovascular stent dissolution mechanism.Health care equipment .2004; 25 (6): 14-15.
Surface coated has CaCl 2The endovascular stent of composition, insert tube chamber inside after, can utilize remaining moisture content in the operation medium vessels that coincide to make the CaCl of rack surface 2It is free that composition becomes solution, after touching the sodium alginate gel solution that splashes into, its at first with CaCl 2Solution reaction and, being referred to as " interior film forming " near the tube wall film forming of anastomotic stoma tube chamber inboard; After this, drip CaCl in the sodium alginate gel outside 2Solution, just side is finished film forming Monday outside the anastomotic stoma tube chamber, becomes " outer film forming ".
Beneficial effect of the present invention is: fluid sealant safety non-toxic of the present invention, film forming, curing rapidly, form water-fast membranoid substance, and be convenient to operation technique, can effectively intercept, reduce colloid toxicity; Be coated with CaCl 2The endovascular stent of composition (coating) can play the effect that the medical glue of dual obstruct leaks into tube chamber inside.
The invention will be further described below in conjunction with the drawings and specific embodiments, and all this areas of doing according to the disclosure of invention are any to be equal to replacement, all belongs to protection scope of the present invention.
Description of drawings
Fig. 1 is the structural representation of endovascular stent.
Fig. 2 is the profile of endovascular stent.
The specific embodiment
Embodiment 1. preparation fluid sealants
One. material:
Sodium alginate, CaCl 2, chemical pure, purchase in Beijing biochemical reagents company.
Two. preparation method:
With sodium alginate and CaCl 2Be dissolved in distilled water respectively, making concentration is the sodium alginate soln of 20wt% and the CaCl of 3wt% 2Solution.
Three. using method:
First method: do not use in the operation of support, sodium alginate soln is splashed into vascular anastomosis, drip CaCl subsequently thereon 2Solution is film forming immediately, can be outside blood vessel wall the side seal anastomotic stoma.After this can drip medical glue, medical glue can not leak in the vessel lumen.
Second method: at common endovascular stent surface dipping CaCl 2Solution places in the anastomotic stoma of ends of vessels, and sodium alginate soln is splashed into vascular anastomosis, drips CaCl subsequently thereon 2Solution is film forming immediately, can be from the inside and outside bilateral sealing of blood vessel wall anastomotic stoma.
The third method: use the endovascular stent of the preparation of embodiment 4, directly will prop up and be placed in the ends of vessels anastomotic stoma, the moisture content on the blood vessel wall makes the CaCl of rack surface 2Composition is free directly to splash into sodium alginate soln vascular anastomosis for solution, drips CaCl subsequently thereon 2Solution is film forming immediately, can be from the inside and outside bilateral sealing of blood vessel wall anastomotic stoma, as shown in Figure 2.
Embodiment 2. preparation fluid sealants
One. material:
Sodium alginate, CaCl 2, chemical pure, purchase in Beijing biochemical reagents company.
Two. preparation method:
With sodium alginate and CaCl 2Be dissolved in distilled water respectively, making concentration is the sodium alginate soln of 10wt% and the CaCl of 1wt% 2Solution.
Three. using method: with embodiment 1.
Embodiment 3. preparation fluid sealants
One. material:
Sodium alginate, CaCl 2, chemical pure, purchase in Beijing biochemical reagents company.
Two. preparation method:
With sodium alginate and CaCl 2Be dissolved in distilled water respectively, making concentration is the sodium alginate soln of 25wt% and the CaCl of 5wt% 2Solution.
Three. using method: with embodiment 1.
Embodiment 4. preparation endovascular stents
One. material
Polyethylene Glycol, molecular weight 20000; Gelatin is all available from Beijing chemical reagents corporation.
Two. preparation method
1. accurately take by weighing the CaCl that the 1.25g gelatin is dissolved in 50ml 20wt% 2In the solution, heat, prepare the gelatin CaCl of 2.5wt% 2Solution for standby.
2. Polyethylene Glycol is added 65~70 ℃ of thermics, dissolving forms water white thick liquid, and the control temperature utilizes mould to make the radially cylinder of hollow respectively, and taper is accomplished at the two ends of support, makes its integral body be Semen Jujubae shape outward appearance.After the oven dry, at the gelatin CaCl of rack surface dipping 2.5wt% 2Solution, oven dry once more, packing, 60The Co sterilization is standby.
The structure of endovascular stent 1 has radial hole 11 and surface C aCl as depicted in figs. 1 and 2 2 Coating 12.
Embodiment 5. preparation endovascular stents
One. material
Polyethylene Glycol, molecular weight 20000; Gelatin is all available from Beijing chemical reagents corporation.
Two. preparation method
1. accurately take by weighing the CaCl that the 1.25g gelatin is dissolved in 50ml 10wt% 2In the solution, heat, prepare the gelatin CaCl of 2.5wt% 2Solution for standby.
2. Polyethylene Glycol is added 65~70 ℃ of thermics, dissolving forms water white thick liquid, and the control temperature utilizes mould to make the radially cylinder of hollow respectively, and taper is accomplished at the two ends of support, makes its integral body be Semen Jujubae shape outward appearance.After the oven dry, at the gelatin CaCl of rack surface dipping 2.5wt% 2Solution, oven dry once more, packing, 60The Co sterilization is standby.
The structure of endovascular stent 1 has radial hole 11 and surface C aCl as depicted in figs. 1 and 2 2 Coating 12.
Embodiment 6. preparation endovascular stents
One. material
Polyethylene Glycol, molecular weight 20000; Gelatin is all available from Beijing chemical reagents corporation.
Two. preparation method
1. accurately take by weighing the CaCl that the 1.25g gelatin is dissolved in 50ml 25wt% 2In the solution, heat, prepare the gelatin CaCl of 2.5wt% 2Solution for standby.
2. Polyethylene Glycol is added 65~70 ℃ of thermics, dissolving forms water white thick liquid, and the control temperature utilizes mould to make the radially cylinder of hollow respectively, and taper is accomplished at the two ends of support, makes its integral body be Semen Jujubae shape outward appearance.After the oven dry, at the gelatin CaCl of rack surface dipping 2.5wt% 2Solution, oven dry once more, packing, 60The Co sterilization is standby.
The structure of endovascular stent 1 has radial hole 11 and surface C aCl as depicted in figs. 1 and 2 2 Coating 12.
Embodiment 7. preparation test kits
One. preparation method:
1. any method by embodiment 1 to 3 prepares fluid sealant;
2. any method by embodiment 4 to 6 prepares endovascular stent;
3. fluid sealant and endovascular stent are combined in the packing material of certain specification, promptly.
Two. using method
1. art is wild exposes: after according to the routine operation operation experimental animal (purebred New Zealand white rabbit, Chinese People's Liberation Army General Hospital experimental animal center provides) being anaesthetized, and dorsal position, cervical region preserved skin shop aseptic hole-towel.Under the aseptic condition, get the throat median incision, be about 8 centimetres, successively cut, do not have son field in the thyroid cartilage lower edge, separate and expose bilateral carotid to the open air, diameter is about 2.0 millimeters, free length 3-4 centimetre.Tremulous pulse is cut off after clipping the hemostatic clamp blocking blood flow in two ends, and blood vessel bounces back naturally, 1-1.5 centimetre damaged of having an appointment, and heparin saline flushing tube chamber, vascular anastomosis approximator are softly drawn two broken ends of fractured bone over to one's side involutoryly, prepare to coincide.
2. sealing anastomotic stoma:
Dip in hydrops in the dried art open country with meche, take out the built-in hollow stent suitable, softly insert tremulous pulse one end earlier, and then insert the tremulous pulse other end with artery diameter; After blood vessel closes up fully, sodium alginate soln is dripped in anastomotic stoma, the very fast infiltration anastomotic stoma of solution circumference dips in sodium alginate soln unnecessary on the tube wall; And then with CaCl 2Solution drips in anastomotic stoma with method, CaCl 2Solution contact sodium alginate soln is film forming rapidly, and the slit that this moment, anastomotic stoma was owed tight is sealed glued membrane sealing, dips in CaCl unnecessary on the tube wall 2Solution.
3. bonding anastomosis mouth (in the prior art for operation routine operation)
Method 1. is directly bonding:
Take out glue (the EC glue in the medical 508 serial bonding agents that coincide, provide by the medical glue company limited of Guangzhou white clouds), to drip 1-2 earlier in anastomotic stoma and drip glue, the very fast trickling of glue is soaked into around the anastomotic stoma, be coated with glue after the curing again one time, bonding anastomosis is promptly finished in very fast curing.
Method 2. tunicles (peplos) are bonding:
Take out glue (the EC glue in the medical 508 serial bonding agents that coincide, provide by the medical glue company limited of Guangzhou white clouds), drip 1-2 earlier in anastomotic stoma and drip glue, the very fast trickling of glue is soaked into around the anastomotic stoma, after the curing, be put in diaphragm under the blood vessel gently, after around vascular anastomosis, being coated with a circle glue, rapid turnup diaphragm two ends, turnup is bonding relatively, be wrapped in an outer week of anastomotic stoma, cure under pressure.
Three. result of use
Priority loose ends hemostatic clamp, visible blood flow is gradually by anastomotic stoma, and blood flow is unimpeded.The instant unimpeded rate 100% of postoperative, seal intact, seamless, do not have to leak blood, effectively prevent the medical glue tube chamber that bleeds.The support that sees through in the visible anastomotic stoma of tube wall dissolves gradually, and the anastomotic stoma section does not have narrow generation.

Claims (1)

1. blood vessel bonding anastomosis sealant test kit, it is characterized in that: described test kit is made up of the endovascular stent of fluid sealant and hollow:
Described fluid sealant is by 3% CaCl 2The sodium alginate soln of solution and 20wt% is formed;
The endovascular stent of described hollow is in hollow inner support surface coated CaCl to be arranged 2Coating is to the CaCl of 10-20wt% 2Solution adds gelatin, and making gelatin concentration is 2.5wt%, gets the gelatin CaCl of this 2.5wt% of hollow inner support dipping 2Dry behind the solution, packing is used 60The Co sterilization is standby; Described hollow inner support is the column structure of fusiformis for radially hollow, two ends, and described hollow inner support is that raw material is made with the Polyethylene Glycol.
CN2006100812207A 2006-05-25 2006-05-25 Blood vessel bonding anastomosis sealant and kit Expired - Fee Related CN101077424B (en)

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CN101077424B true CN101077424B (en) 2011-04-06

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105833361A (en) * 2016-04-15 2016-08-10 苏州大学 Flexible substrate/liquid electrolyte viscous composite material and preparation method thereof

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1106845C (en) * 2000-08-17 2003-04-30 洪宏 Process for preparing solid-state-microspherical vascular suppository of sodium alginate
CN1131074C (en) * 2001-08-10 2003-12-17 中国人民解放军总医院 Preparation method for quick-dissolving support for microtraumatic quick vascular anastomosis technique

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1106845C (en) * 2000-08-17 2003-04-30 洪宏 Process for preparing solid-state-microspherical vascular suppository of sodium alginate
CN1131074C (en) * 2001-08-10 2003-12-17 中国人民解放军总医院 Preparation method for quick-dissolving support for microtraumatic quick vascular anastomosis technique

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