CN1876926A - Biodegradable nanofiber nonwoven fabric capable of preventing postoperative adhesion and preparation thereof - Google Patents

Abstract

The invention provides a biodegradable textile fiber adhesive-bonded fabric to prevent adhesion after the operation and its preparing method, which belongs to the domain of medical article, and relates to the preparation of a nanometre-sized fiber adhesive-bonded fabric and the application as the anti-block film after the operation. The said adhesive-bonded fabric is prepared by adopting electrostatic spinning method, which includes preparing spin dope, dissolving the aliphatic polyester in the flux and mixing intimately to prepare the aliphatic polyester spin dope. The used flux of the spin dope can be one or compound system of two of carrene, chloroform, acetone, acetylene tetrachloride,acetic acid dimethylamide. Secondarily on the electrostatic spinning machine, by filling spin dope, electrostatic spinning and collecting superfine fibre, the aliphatic polyester superfine fibre is prepared, which carries out the adhesive-bonded fabric of electronic spinning nanometre-grade fiber and which can be used as blocking agent after the operation by the decontamination and biocidal treatment. The cloth has good flexibility and toughness, which can overcome the defect of anti-block film reported in the past. Because the degradable materials are selected, the adhesive-bonded fabric begins to degrade after about one month and completely degrade finally, which comes up to the anti-block function.

Description

A kind of biodegradable nanofiber nonwoven fabric and preparation that prevents post-operation adhesion

Technical field:

The present invention's " a kind of biodegradable nanofiber nonwoven fabric and preparation that prevents post-operation adhesion " belongs to field of medical products, relates to a kind of preparation of nano-scale fiber bondedfibre fabric, reaches the application as the post-operation adhesion preventing film.

Background technology:

Post-operation adhesion is that one of unsolved important topic has still been arranged since the history of operation both at home and abroad.There are nearly various types of operation cases of ten million in the whole nation every year, and nearly all operation all relates to anti and local anti-inflammatory problem between the tissue.It not only can cause severe complication, as: can cause adhesive ileus after belly, the operation on pelvis, can cause postoperative epilepsy after the operation of opening cranium, the thyroid gland postoperative can cause Secondary cases only stimulate the menstrual flow the damage etc., and be the main reason that complication obviously increases when performing the operation once more, as the damage of enteron aisle glandular tube, only logical nerve and parathyroid injury etc.Past only limits to abdominal operation prevention adhesive ileus in the research of prevention of postoperative adhesion.Once put silicone oil, before the middle molecule dextrose and method such as streptokinase, but all do not have positive effect with the abdominal cavity inner face.Silicone oil can not be absorbed by the body, although little to the body excitant, is stranded in for a long time in the abdominal cavity, will produce to stimulate can to cause and ooze out, and cause adhesion.In the molecule dextrose join owing to be that height oozes body fluid, tissue is had excitant, make and organize congestion and edema, oozing out increases and causes adhesion.Streptokinase is to inject in Intraabdominal micropore tubule from being detained, in the hope of solution fibrin, but owing to can only inject in a small amount, pore can get clogged and tubule transposition etc. all multifactor, curative effect is not remarkable yet.Begin to adopt biological absorbable medical film to prevent post-operation adhesion at present as physical barriers, polylactic acid membrane is arranged, hyaluronic acid membrane, chitosan film and oxycellulose film are several, and commercially available polylactic acid membrane is PLA and ethanol copolymer, or the film of PLA homopolymers, matter is crisp, pliability, and draftability is poor, be difficult to well fit together with tissue, can not satisfy clinical requirement fully even if add plasticizer.Hyaluronic acid membrane, chitosan film and oxycellulose membrane degradation time are too short, can not keep the physical barriers effect in the time that requires, thereby can not finish the anti function preferably.Therefore, wait in expectation for a long time clinically new material of a kind of convenience, safe and effective anti and new method come out.

Summary of the invention:

The purpose of this invention is to provide a kind of novel biodegradable nanofiber nonwoven fabric that prevents post-operation adhesion.The present invention is mixed with spinning solution with aliphatic polyester, and electrospinning becomes the bondedfibre fabric of nano-scale fiber, and thickness is the 0.01-1 millimeter, and by sterilization, the back anti is used to perform the operation.This fabric has splendid pliability, the shortcoming of the Antiadhesive film that can overcome in the past to be reported.

This purpose realizes by the following technical solutions.

At first prepare spinning solution, this stoste contains raw material and solvent, raw material is dissolved in solvent, it is characterized in that, described raw material is that the aliphatic poly ester material mainly comprises poly-DL lactic acid (PDLLA), poly-L-lactic acid (PLLA), in polyglycolic acid (PGA), polycaprolactone (PCL), the polydioxanone (polydioxanone) any one uses or uses the blend and the copolymer of two kinds and two or more materials separately, and copolymerization, the blend of PLA and polyethylene glycol.The spinning solution solvent for use is a carrene, chloroform, acetone, tetrachloroethanes, one or both compound system such as dimethylacetylamide.Properties of materials viscosity (Ubbelohde viscometer, chloroform solvent, 25 ℃) scope is at 0.1-5.0dl/g, and wherein the best is 0.5-4.0dl/g, and molecular weight ranges is (10000-1000000), and the best is (50000-400000).

Be dissolved in solvent by raw material, stirring makes the aliphatic polyester spinning solution.

Now describe the preparation of spinning solution of the present invention in detail.The preparation of described aliphatic polyester spinning solution is characterized in that, operating procedure:

First step raw material is dissolved in solvent

Take by weighing 1～50wt% raw material and 50～99wt% solvent, raw material is that the aliphatic poly ester material mainly comprises poly-DL lactic acid (PDLLA), poly-L-lactic acid (PLLA), in polyglycolic acid (PGA), polycaprolactone (PCL), the polydioxanone (polydioxanone) any one uses or uses the blend and the copolymer of two kinds and two or more materials separately, and copolymerization, the blend of PLA and polyethylene glycol.Solvent is a carrene, chloroform, acetone, tetrachloroethanes, one or both compound system such as dimethylacetylamide.

Second step stirred

At normal temperatures, to the airtight stirring of solution that the last step makes, speed of agitator obtains uniform solution between 75～150rpm.The viscosity of spinning solution is between 40～4000 centipoises.

Next utilizes the aliphatic polyester spinning solution on electrostatic spinning machine, goes on foot by spinning solution dress notes, electrostatic spinning and collection superfine fibre two and makes the aliphatic polyester superfine fibre, realizes that electrospinning becomes the bondedfibre fabric of nano-scale fiber to use.Now in conjunction with the accompanying drawings 1, describe application of the present invention in detail.The application of described aliphatic polyester spinning solution, all operations is implemented on electrostatic spinning machine, described electrostatic spinning machine equipment comprises: a main bucket 1 of containing spray silk material is used for storing electrospinning silk material, ameasuring pump 2 is used to calculate the consumption and the control charging rate of spinning material,nozzle block 5 is made up of a large amount of syringe needles, can make the discharge of electrospinning silk material be fibrous, one is being lower than thepotential plate 7 that is used for collecting spinning fibre ofnozzle block 5 least significant ends, onehigh voltage generators 8 is used to produce a high voltage, voltage conductive bar 4 is used for conducting at voltage that high pressure generator produces to abovenozzle block 5 ends, also has an electrospinning silk material Liqiud-gas mixing device 3 betweenmeasuring pump 2 and nozzle block 5.Here for the formation that promotes fiber by applying electric field force, it is 50KV that the voltage that produces inhigh pressure generator 8 surpasses 1KV only, is transferred on the voltage conduit 4, collectingboard 6 is installed in the below ofnozzle block 5 ends.As being fit to use conveyer belt in collectingboard 6 productions.

Operating procedure:

First step spinning solution dress is annotated

The aliphatic polyester spinning solution is put into thebucket 2 of containing spray silk material;

The second step electrostatic spinning

1. the aliphatic polyester spinning solution is measured by measuringpump 2, and the control amount offers spinning material Liqiud-gas mixing device 3.

2. when the spinning material offered Liqiud-gas mixing device 3 and process Liqiud-gas mixing device 3, the spinning material fully mixed with gas, and is as described above the same.Be supplied tonozzle block 5 by a higher voltage spinning material subsequently.

3. the adjusting nozzle is 5～30cm to the distance of gathering-device; Gathering-device is installed: endlessbelt collecting board 6 is installed in the below ofnozzle block 5 ends.Below injection apparatus, open high voltage source, regulation voltage carries out spinning to 10kV～80kV.

4.nozzle block 5 is injected into a kind of single fibre morphology with the spinning material by nozzle.

5. the non-woven fabrics fabric net that forms on collectingboard 6 is spirally wound on cylinder, thereby has finished the process of preparation non-woven fabrics fabric.

By the prepared Antiadhesive film of electrostatic spinning, thickness is the 0.01-1 millimeter, vacuumizes the removal residual solvent at last, sterilization, anti after packing is used to perform the operation.

The invention has the beneficial effects as follows:

1. the electrospinning film made from aliphatic polyester, prove from the safety evaluatio and the zoopery of material, this electrospinning film has splendid pliability, and is biodegradable, has absorbability favorable tissue compatibility and blood compatibility, this film is fixed in the anti position surface of a wound, to prevent itself and peripheral organization's adhesion, not only can prevent intestinal adhesion in the abdominal cavity, and can prevent the liver visceral surface, the hepatic portal liver, duodenum, the adhesion of ligament, the esophagus adhesion of thyroid gland art, the cavum subarachnoidale adhesion of operation of opening cranium. the adhesion (fallopian tube of pelvic cavity viscera, the pleaural adhesion in ovary people thoracic cavity, uterus etc.), can reduce postoperative complication effectively, avoid operation once more, improved operative effect, reduced patient's misery, saved medical expense, this a kind of really convenience, safety, the effectively method of post-operation adhesion preventing.

2. this electrospinning silk equipment can be realized mass production.

3. by the diameter of adjustment process parameter controlling fiber, electrospinning silk technology gained fibre diameter is generally at 3nm-5 μ m.The little several magnitude of fibre diameter that makes than conventional method.

Description of drawings:

Figure l: electrospinning silk apparatus figure, number in the figure is respectively:

1, storage tank

2, measuring pump

3, Liqiud-gas mixing device

4, voltage conductive bar

5, nozzle block territory

6, collecting board

7, potential plate

8, high pressure generator

The specific embodiment:

Following example will the present invention is further elaborated, but do not limit content of the present invention.

Embodiment 1

The preparation of PLLA spinning solution:

Solvent is a carrene, PLLA raw material (viscosity average molecular weigh is 450000): carrene=5wt%: 95wt%; Stir at normal temperatures.

PLLA spinning solution electrostatic spinning:

The spinning material is stored in the storage tank 1, by measuringpump 2 quantitative measurments, and offers spinning material Liqiud-gas mixing device 3, changes flowing of spinning material thereby be interrupted.After that, the spinning material is supplied tonozzle block territory 5, under the voltage of 50kv, and is woven into the shape of fiber by nozzle.The fiber of weaving is collected on collectingboard 6, and is prepared into the non-woven fabrics fiber net.Each nozzle block all has 400 syringe needles, and is made of 20 nozzle retardance arrangements.Use high-voltage generator.The output speed of a syringe needle is 0.0026g/min, thereby total productive capacity is 20.8g/min.A nozzle block territory is divided into 10, and per 20 syringe needles are installed a spinning material Liqiud-gas mixing device 3.The non-woven fabrics fiber net is transmitted with the speed of 4m/min.

Spin to certain thickness, stop, taking off, vacuumize the removal residual solvent, cutting, packing, sterilization.The back anti is used to perform the operation.

Embodiment 2

The preparation of PLGA copolymer (50: 50) spinning solution:

Solvent is a carrene, PLGA copolymer (50: 50) raw material (viscosity average molecular weigh is 250000): carrene=10wt%: 90wt%; Stir at normal temperatures.

PLGA copolymer (50: 50) spinning solution electrostatic spinning:

The spinning material is stored in the storage tank 1, by measuringpump 2 quantitative measurments, and offers spinning material Liqiud-gas mixing device 3, changes flowing of spinning material thereby be interrupted.After that, the spinning material is supplied tonozzle block territory 5 under the voltage of 50kv, and is woven into the shape of a fiber by nozzle.The fiber of weaving is collected on collectingboard 6, and prepares preparation non-woven fabrics fiber net.Here, each nozzle block all has 400 syringe needles, and is that formation is arranged in 20 nozzle retardances.Use high-voltage generator.The output speed of a syringe needle is 0.0032g/min (the injection total amount of a nozzle block is 1.28g/min), thereby total productive capacity is 25.6g/min.A nozzle block territory is divided into 10, and per 40 syringe needles are installed a spinning material Liqiud-gas mixing device 3.The non-woven fabrics fiber net is transmitted with the speed of 3m/min.

Spin to certain thickness, stop, taking off, vacuumize the removal residual solvent, cutting, packing, sterilization.The back anti is used to perform the operation.

Embodiment 3

The preparation of PDLLA spinning solution:

Solvent is a carrene, PLLA raw material (viscosity average molecular weigh is 350000): carrene=8wt%: 92wt%; Stir at normal temperatures.

PDLLA spinning solution electrostatic spinning:

The spinning material is stored in the storage tank 1, by measuringpump 2 quantitative measurments, and offers spinning material Liqiud-gas mixing device 3, changes flowing of spinning material thereby be interrupted.The spinning material is supplied tonozzle block territory 5 afterwards, under the voltage of 50kv, and is woven into the shape of fiber by nozzle.The fiber of weaving is collected on collectingboard 6, and is prepared into the non-woven fabrics fiber net.Each nozzle block all has 400 syringe needles, and is that formation is arranged in 20 nozzle retardances.Use high-voltage generator.The output speed of a syringe needle is 0.0026g/min, thereby total productive capacity is 20.8g/min.A nozzle block territory is divided into 10, and per 40 syringe needles are installed a spinning material Liqiud-gas mixing device 3.The non-woven fabrics fiber net is transmitted with the speed of 3m/min.

Spin to certain thickness, stop, taking off, vacuumize the removal residual solvent, cutting, packing, sterilization.The back anti is used to perform the operation.

Claims (7)

1, a kind ofly biodegradablely prevents the nanofiber nonwoven fabric of post-operation adhesion and preparation from is characterized in that with biodegradable aliphatic poly ester material being that raw material is dissolved in solvent, stir and make spinning solution, on electrostatic spinning machine, make superfine fibre by spinning solution dress notes, electrostatic spinning and two steps of collection superfine fibre, form the bondedfibre fabric of nano-scale fiber, after sterilization is handled, be used for post-operation adhesion preventing.

2, it is characterized in that poly-DL lactic acid (PDLLA), poly-L-lactic acid (PLLA) according to claims 1 described biodegradable aliphatic poly ester material, any one in polyglycolic acid (PGA), polycaprolactone (PCL), polydioxanone (PDO), the PTMC uses or uses the blend of two kinds and two or more materials and copolymer or PLA and polyethylene glycol copolymerization, blend separately; Properties of materials viscosity (dark type viscometer, chloroform solvent, 25 ℃) scope is at 0.1-5.0dl/g, and wherein the best is 0.5-4.0dl/g, and molecular weight ranges is 10000～1000000, and the best is 50000-400000.

3, it is characterized in that according to claims 1 described nanofiber nonwoven fabric the electrostatic spinning solvent for use is a carrene, chloroform, acetone, tetrachloroethanes, one or both compound system such as dimethylacetylamide.

4, it is characterized in that according to claims 1 described nanofiber nonwoven fabric the viscosity of described spinning solution is between 40～4000 centipoises.

5, prepare the device of Antiadhesive film according to claims 1 described electrostatic spinning, it is characterized by: electrospinning silk equipment comprises: a main holding vessel; A measuring pump; A nozzle block, and the spinning material is ejected on the fiber; A voltage transmission bar is positioned at the lower end of nozzle block; Can produce a voltage generator of high voltage; And a spinning material Liqiud-gas mixing device is placed between measuring pump and the nozzle retardance; A receiving system, transport tape or rotary drum receive.

6, according to claims 1 described electrostatic spinning operating procedure:

First step spinning solution dress is annotated

The aliphatic polyester spinning solution is put into the bucket 2 of containing spray silk material;

The second step electrostatic spinning

(1) the aliphatic polyester spinning solution is measured by measuring pump 2, and the control amount offers spinning material Liqiud-gas mixing device 3;

(2) when the spinning material offered Liqiud-gas mixing device 3 and process Liqiud-gas mixing device 3, the spinning material fully mixed with gas, and is as described above the same, has been supplied to nozzle block 5 by a higher voltage spinning material subsequently;

(3) the adjusting nozzle is 5～30cm to the distance of gathering-device; Gathering-device is installed: endless belt collecting board 6 is installed in the below of nozzle block 5 ends, below injection apparatus, opens high voltage source, and regulation voltage carries out spinning to 10kV～80kv;

(4) nozzle block 5 is injected into a kind of single fibre morphology with the spinning material by nozzle;

(5) the non-woven fabrics fabric net that forms on collecting board 6 is spirally wound on cylinder, thereby has finished the process of preparation non-woven fabrics fabric.

7, it is characterized in that according to claims 1 described nanofiber nonwoven fabric electrospinning becomes the thick film of 0.01-1mm, after sterilization is handled, be used for post-operation adhesion preventing.

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