CN101972176A - Artificial bile duct and preparation method thereof - Google Patents

Abstract

The invention relates to an artificial bile duct and a preparation method thereof. The artificial bile duct is a composite flexible tubular substance prepared by adopting a polytetrafluoroethylene hose serving as a liner base material, performing helium plasma surface treatment and then casting fluororubber. The preparation method comprises the following steps of: (1) winding a polytetrafluoroethylene ultrathin film on the surface of a polytetrafluoroethylene raw material tube and heating the ultrathin film to adhere the ultrathin film to the hose so as to form the liner; (2) processing the surface of the polytetrafluoroethylene liner by using the helium plasma; (3) coating the solution of the fluororubber on the outer surface of the polytetrafluoroethylene liner to obtain quasi-finished product artificial bile duct; and (4) processing the quasi-finished product artificial bile duct to obtain the artificial bile duct for clinical application. The artificial bile duct of the invention has high biocompatibility and high mechanical strength and is suitable for bile duct substitutes. The preparation method is simple in process and low in cost and has a good application prospect.

Description

A kind of artificial choledochus and preparation method thereof

Technical field

The invention belongs to the artificial choledochus field, particularly a kind of artificial choledochus and preparation method thereof.

Background technology

Medically, the reparation or the reconstruction problem of the common bile duct of pathological changes excision back biliary tract are one of main difficult problems of biliary surgery always.The gallbladder intestinal that biliary tract disease often needs to excise or cut bile duct and carry out variety of way coincide, can make bile duct, the forfeiture of Oddi sphincter function even structure disappearance like this, operating difficulty is big, and because bile duct tissue's damage back regeneration capacity is low, handle thornyly, various complication take place in postoperative easily.

Compare with technology such as artificial blood vessel, artificial sticking patch, artificial joint, cardiac valve, artificial choledochus research obviously lags behind, and does not have sophisticated bile duct succedaneum to enter clinical practice as yet.In treatments such as tumor of bile duct, bile duct injury, congenital malformation and liver transplantation, press for a kind of bile duct substitute.Along with the development of medical macromolecular materials is upgraded, biological tissue's succedaneum has progressed into clinical practice.The appearance of artificial choledochus will produce a kind of brand-new low invasive procedures mode, provide Therapeutic Method easily to the biliary tract treatment that increases day by day.

Extrahepatic biliary passages is unique path that bile is assigned, and it damages and blocks all directly influences liver function.Biliary tract surgery is often because of tumor, inborn variation, liver transplantation, multiple complicated factor such as bile duct injury need carry out the reparation and the reconstruction of extrahepatic bile ducts, that the most frequently used in the past is cholangio-jejunostomy [Leonardi MI, Ataide EC, Boin IF, etal.Role of choledochojejunostomy in liver transplantation.Transplant Proc, 2005,37 (2): 1126-1128.], but because of it is not a normal physiological routes, normal retrograde infection [the Li Cheng that takes place, grandson is equipped with. the progress of antidromicity biliary tract infection behind the bile duct jejunum Roux-en-Y anastomosis. and international surgery's magazine, 2006,133 (2): 90-93.], using substitute reconstruction extrahepatic biliary passages is the effective way [Zheng Jianwei that makes challenge trend advantages of simple, Zou Shengquan. artificial choledochus research. Chinese medicine engineering, 2005,13 (4): 385-387.].Clinically press for a kind of safe in utilization, easy, practical bile duct substitution material.

As far back as nineteen fifty-two, Voorhees etc. have used the success of polyvinyl material development artificial blood vessel, become the significant in history milestone of artificial nest [Voorhees AB, Jaretzki A, Blake A.The use of tubes constructed of Vinyon N cloth in bridging arterial defects.J.Ann.Surg, 1952,135:332-336.].In the same year, Crinis Carbonisatus such as Mccorriston are understood artificial choledochus.1962, the substitute that artificial choledochus is rebuild as congenital biliary atresia infant postoperative extrahepatic biliary passages of success such as Sterling obtained the postoperative survival rate in 4～9 years.This also is that the earliest relevant artificial choledochus is successfully applied to clinical report [Sterling JA.Infants with biliary atresia and artificial bile ducts surviving 4 to 9 years.Med.Times, 1966,94 (11): 1302-1316.].At present the artificial choledochus materials used of development mostly be greatly single macromolecular material [yellow Hua Xin, Wang Chen, Pei Fangjun etc. the real silk artificial gall duct substitutes choledoch-experimentation. Lanzhou medical college journal, 1999,20 (1): 36-38; Xu Jianheng, Guo Guanghua, Zhang Jin etc. the making of polyurethane bile duct prosthese. practical medical journal, 2000,16 (2): 104-105; Zhou Shouli etc. biliary tract Y type support and novel implantation device (CN 2899738)].There is human polyurethane (medical grade EU thermoplastic elastomer (TPE) TPE-80B) material to design a kind of bladder-type artificial choledochus prosthese, this is a kind of mechanical type bile duct prosthese, it has wearability, elasticity and the bile compatibility [Xu Jianheng preferably evidence, Guo Guanghua, Zhang Jin etc. the making of polyurethane bile duct prosthese. practical medical journal, 2000,16 (2): 104-105; Zhang Jie, Li Dong, Li Jianning. the tubulose expanded PTFE is used for the animal experiment study of tissue engineering bracket material. Chinese aesthetic medicine, 2004,13 (6): 650-651.].But the coefficient of friction of polyurethane surface is bigger, and the little condition of bile flow resistance is difficult to meet the demands.The artificial choledochus form of developing at present mainly contains simple straight pipe type structure [yellow Hua Xin, Wang Chen, Pei Fangjun etc. the real silk artificial gall duct substitutes choledoch-experimentation. Lanzhou medical college journal, 1999,20 (1): 36-38.] and gasbag-type bile duct prosthese [Xu Jianheng, bladder-type artificial choledochus (CN2242677)] two classes: simple straight pipe type bile duct can recover the biliary tract seriality, but its shortcoming is cholestasis obstruction, a retrograde infection in the short time; The research of gasbag-type bile duct prosthese can solve the cholestasis problem, but designs loaded down with trivial detailsly, lacks value for clinical application.Therefore there do not have artificial choledochus really to be applied to as yet at present to be clinical.

Polytetrafluoroethylmaterial material through experiment confirm can be used for artificial blood vessel, artificial lung, artificial valve, artificial ear, facial plasty [K L Vidur. medical macromolecular materials. international weaving Leader, 2005,2:75-78; Huang Jinghuan, Ding Jiandong. biological medical polymer material and modern medicine. Chinese medical apparatus information, 2004,10 (4): 1-5.], its histocompatibility is fully confirmed.Have Crinis Carbonisatus understand a kind of with the politef be inner bag, fluorubber be the compounded artificial choledochus of cladding material [Yang Qing etc. politef/fluorubber combined artificial bile duct and preparation (CN200910056504.4) thereof], because the chemical inertness of politef, can't directly apply fluorubber, thereby ptfe surface be carried out having carried out after naphthalene-sodium solution is handled the coating of fluorubber.The shortcoming of this bile duct is that outward appearance presents black after naphthalene-sodium is handled, and makes doctor and patient be difficult to accept.

At present domestic does not still have to adopt at ptfe surface carry out the helium plasma treatment technology to prepare the patent report of artificial choledochus.

Summary of the invention

Technical problem to be solved by this invention provides a kind of artificial choledochus and preparation method thereof, and this artificial choledochus possesses excellent biological compatibility, clinical practice convenience, time durability and mechanical strength preferably, is applicable to the bile duct substitute; Preparation method technology is simple, and cost is low, has a good application prospect.

A kind of artificial choledochus of the present invention, it is characterized in that: adopt teflon hose as the inner bag base material, its surface is the helium plasma treatment layer, and its thickness is 1～20nm, and in helium plasma treatment laminar surface coating fluorubber cast layer, the thickness of cast layer is 0.1～1mm.

A kind of preparation method that adopts the artificial choledochus of helium plasma technology preparation of the present invention comprises:

(1) twines the politef ultrathin membrane at the polytetrafluoroethylraw raw material tube-surface, place high temperature furnace then, make to produce bonding between thin film and the flexible pipe and become inner bag 320～340 ℃ of heated at constant temperature 10～40 minutes;

(2) with helium plasma the polytetrafluoroethylliner liner surface is handled, form the helium plasma treatment layer, thickness is 1～20nm; Reative cell vacuum is 15 ± 10 handkerchiefs, and discharge power is 20～300 watts, and the processing time is 5～300 seconds;

Detailed process is as follows: 1. the inner bag product of cleaning out is placed in the reative cell, guarantees to observe from form the situation of product; 2. each road needle-valve is closed in the off-response chamber, guarantees not have gas leakage air inlet state, starts vacuum pump, takes out in advance about end vacuum to 2 handkerchief; 3. open air inlet pipeline and feed helium gas, clean the residual gas of discharging in reative cell and the pipeline, regulate air pressure to 15 ± 10 handkerchiefs then; 4. start high frequency electric source, regulating discharge power is 20～300 watts, and the processing time is 5～300 seconds, according to predetermined experimental program inner bag is carried out the helium plasma surface treatment; 5. after disposing, close radio-frequency power supply earlier, and then close air inlet gas circuit and vacuum pump, reative cell is connected atmosphere, opens reative cell at last and takes out sample;

(3) fluorubber is joined in the acetone solvent, wherein the mass ratio of fluorubber and acetone is 1: 5～50, stirring makes the fluorubber dissolving, polytetrafluoroethylliner liner outer surface after the above-mentioned modification processing is carried out fluorubber solution to apply 1～10 time, thickness is 0.1～1mm, whenever be coated with once once, just obtain accurate finished product artificial choledochus after coating is finished at air drying;

(4) aim at that the finished product artificial choledochus carries out vacuum drying, packs, sterilization promptly obtains after handling can be for the artificial choledochus of clinical practice.

Polytetrafluoroethylraw raw material tube wall thickness in the described step (1) is 0.5～1 millimeter.

The present invention adopt coefficient of friction less, with water contact angle little and can anti-bile corrosive teflon hose be the artificial choledochus inner layer material, its slick inner surface can reduce the flow resistance of bile in pipeline.But under ultramicroscope, can observe, because politef itself can not fusion, flexible pipe forms by extrusion stretching, so there are a large amount of micropores in body, may cause seepage of bile, therefore need to apply fluorubber with the shutoff hole at teflon hose inner bag outer surface.Because the chemical inertness of politef, it is infeasible directly applying fluorubber.The front mention people such as Yang Qing [Yang Qing etc. politef/fluorubber combined artificial bile duct and preparation (CN200910056504.4) thereof] preparation naphthalene-sodium tetrahydrofuran solution ptfe surface is handled, though hydrophilic is greatly improved, sticking of fluorubber is also fine, but ptfe surface can become black, has influenced the outward appearance of artificial choledochus greatly.Therefore the present invention uses helium plasma instead to ptfe surface and carries out modification and handle, and ptfe surface does not have anything to change in appearance after the modification, but hydrophilicity is improved greatly, and the paintability of fluorubber is also improved greatly.By the fluorubber solution of preparation variable concentrations and intensity, permeability and the flexibility of controlling the adjustable artificial choledochus of coating number of times of fluorubber.

Beneficial effect

(1) artificial choledochus of the present invention possesses white appearance, excellent flexibility, good biocompatibility, clinical practice convenience, time durability and the characteristics of mechanical strength preferably, and is safe, simple in structure, easy to operate, is applicable to the bile duct substitute; (2) preparation method technology of the present invention is simple, and cost is low, has a good application prospect.

Description of drawings

The artificial choledochus sketch map of Fig. 1 for preparing after the helium plasma treatment.

The specific embodiment

Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after the content of having read the present invention's instruction, these equivalent form of values fall within the application's appended claims institute restricted portion equally.

Embodiment 1

Get pipe thickness and be 0.5 millimeter polytetrafluoroethylraw raw material pipe, twine one deck polytetrafluoroethylene film, put into high temperature furnace, make and produce the inner bag that is bonded to the artificial gall duct between thin film and the flexible pipe 330 ℃ of heated at constant temperature 20 minutes at the hose surface spiral.Inner bag is carried out the outer surface modification with helium plasma handle, control reative cell vacuum is 15 handkerchiefs, and discharge power is 70 watts, and the processing time is 20 seconds, records its contact angle through the video contact angle measurement and is reduced to 12.1 °.Behind the inner bag cleaning-drying after the helium plasma treatment, with fluorubber-acetone soln (fluorubber and acetone mass ratio are 1: 30) surface-coated-drying 5 times.Be placed in 55 ℃ of vacuum drying ovens heated at constant temperature 30 minutes again to extract remaining acetone solvent.After the taking-up product was cooled to ambient temperature, through scanning electron microscope and the test of water infiltration capacity, visible bile duct surface pore was by the fluorubber complete closed.Subsequently to bile duct pack, sterilization handles, the preparation of artificial choledochus finishes.This material is applicable to the bile duct substitute than ting model.

Embodiment 2

Get pipe thickness and be 0.8 millimeter polytetrafluoroethylraw raw material pipe, twine one deck polytetrafluoroethylene film, put into high temperature furnace, make and produce the inner bag that is bonded to the artificial gall duct between thin film and the flexible pipe 340 ℃ of heated at constant temperature 15 minutes at the hose surface spiral.Inner bag is carried out the outer surface modification with helium plasma handle, control reative cell vacuum is 15 handkerchiefs, and discharge power is 100 watts, and the processing time is 120 seconds, records its contact angle through the video contact angle measurement and is reduced to 35.7 °.Behind the inner bag cleaning-drying after the helium plasma treatment, with fluorubber-acetone soln (fluorubber and acetone mass ratio are 1: 30) surface-coated-drying 7 times.Be placed in 55 ℃ of vacuum drying ovens heated at constant temperature 30 minutes again to extract remaining acetone solvent.After the taking-up product was cooled to ambient temperature, through scanning electron microscope and the test of water infiltration capacity, visible bile duct surface pore was by the fluorubber complete closed.Subsequently to bile duct pack, sterilization handles, the preparation of artificial choledochus finishes.This material is applicable to the bile duct substitute of middle model.

Embodiment 3

Get pipe thickness and be 1 millimeter polytetrafluoroethylraw raw material pipe, twine one deck polytetrafluoroethylene film, put into high temperature furnace, make and produce the inner bag that is bonded to the artificial gall duct between thin film and the flexible pipe 350 ℃ of heated at constant temperature 10 minutes at the hose surface spiral.Inner bag is carried out the outer surface modification with helium plasma handle, control reative cell vacuum is 15 handkerchiefs, and discharge power is 150 watts, and the processing time is 10 seconds, records its contact angle through the video contact angle measurement and is reduced to 17.0 °.Behind the inner bag cleaning-drying after the helium plasma treatment, with fluorubber-acetone soln (fluorubber and acetone mass ratio are 1: 30) surface-coated-drying 10 times.Be placed in 55 ℃ of vacuum drying ovens heated at constant temperature 30 minutes again to extract remaining acetone solvent.After the taking-up product was cooled to ambient temperature, through scanning electron microscope and the test of water infiltration capacity, visible bile duct surface pore was by the fluorubber complete closed.Subsequently to bile duct pack, sterilization handles, the preparation of artificial choledochus finishes.This material is applicable to relatively large number bile duct substitute.

Claims (3)

1. artificial choledochus, it is characterized in that: adopt teflon hose as the inner bag base material, the inner bag substrate surface is the helium plasma treatment layer, and its thickness is 1～20nm, and in helium plasma treatment laminar surface coating fluorubber cast layer, the thickness of cast layer is 0.1～1mm.

2. method that adopts the helium plasma technology to prepare artificial choledochus comprises:

(1) twines the politef ultrathin membrane at the polytetrafluoroethylraw raw material tube-surface, place high temperature furnace then 320～340 ℃ of heated at constant temperature 10～40 minutes;

(2) with helium plasma the polytetrafluoroethylliner liner surface is handled, form the helium plasma treatment layer, thickness is 1～20nm; Reative cell vacuum is 15 ± 10 handkerchiefs, and discharge power is 20～300 watts, and the processing time is 5～300 seconds;

(3) fluorubber is joined in the acetone solvent, wherein the mass ratio of fluorubber and acetone is 1: 5～50, stirring makes the fluorubber dissolving, polytetrafluoroethylliner liner outer surface after the above-mentioned modification processing is carried out fluorubber solution to apply 1～10 time, thickness is 0.1～1mm, whenever be coated with once once, just obtain accurate finished product artificial choledochus after coating is finished at air drying;

(4) aim at that the finished product artificial choledochus carries out vacuum drying, packs, sterilization promptly obtains after handling can be for the artificial choledochus of clinical practice.

3. a kind of preparation method that adopts the artificial choledochus of helium plasma technology preparation according to claim 2, it is characterized in that: the polytetrafluoroethylraw raw material tube wall thickness in the described step (1) is 0.5～1 millimeter.