CN106983915B - Silk microfibre-gelatin-polyethylene glycol medical catheter and preparation method thereof - Google Patents

Silk microfibre-gelatin-polyethylene glycol medical catheter and preparation method thereof Download PDF

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Publication number
CN106983915B
CN106983915B CN201710373332.8A CN201710373332A CN106983915B CN 106983915 B CN106983915 B CN 106983915B CN 201710373332 A CN201710373332 A CN 201710373332A CN 106983915 B CN106983915 B CN 106983915B
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silk
microfibre
gelatin
catheter
medical catheter
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CN106983915A (en
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徐大伟
王成牛
崔志明
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Nantong First Peoples Hospital
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Nantong First Peoples Hospital
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/04Macromolecular materials
    • A61L29/06Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/18Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14Macromolecular materials
    • A61L27/22Polypeptides or derivatives thereof, e.g. degradation products
    • A61L27/222Gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/36Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3641Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
    • A61L27/3675Nerve tissue, e.g. brain, spinal cord, nerves, dura mater
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/507Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials for artificial blood vessels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/005Ingredients of undetermined constitution or reaction products thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/04Macromolecular materials
    • A61L29/044Proteins; Polypeptides; Degradation products thereof
    • A61L29/046Gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14Materials characterised by their function or physical properties, e.g. lubricating compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/14Materials characterised by their function or physical properties, e.g. lubricating compositions
    • A61L29/148Materials at least partially resorbable by the body
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00Materials or treatment for tissue regeneration
    • A61L2430/32Materials or treatment for tissue regeneration for nerve reconstruction

Abstract

The present invention provides a kind of silk microfibre-gelatin-polyethylene glycol medical catheter, and prepared by the medical catheter of every 100ml contains following component: 1 ~ 10g of silk microfibre, 10 ~ 100ml of aqueous solution, 10% 2 ~ 30ml of gelatin solution, 1 ~ 10g of polyethylene glycol 2000 in solution.The present invention prepares silk microfibre-gelatin-polyethylene glycol catheter holder material using physical mixing processes, and material price is cheap, and preparation method is simply easily operated, avoids the cellulotoxic side effect generated using crosslinking agent, good biocompatibility.Suitable for blood vessel, peripheral nerve conduit application, it is easy to be metabolized in vivo.

Description

Silk microfibre-gelatin-polyethylene glycol medical catheter and preparation method thereof
Technical field
The invention belongs to medical material tech fields, and in particular to gelatin-polyethylene glycol is medical leads for a kind of silk microfibre- Pipe and preparation method thereof.
Background technique
Medical catheter is the necessity of medical act already, it usually needs the traumatic diagnosis and treatment of implantation human body progress, such as Intravascular inlying catheter, central vein catheter use catheter, trachea cannula in the urinary tract treatment, are all in general curative The medical act of operation necessity and frequent progress.Clinically the peripheral nerve defection as caused by wound is relatively conventional, wherein growing The neurologic defect of distance cannot rely on end-to-end suture when making up neurological deficits, then to need to bridge by conduit and repair. In addition to above-mentioned conventional medical conduit, with medical technology fast development, the conduit of multitube chamber and composite pipeline form also produces successively It is raw, and set and stay in intracorporal time relative growth, also have become carry out now blood flow monitoring, infusion, haemodialysis, administration and The important tool of the medical acts such as intravenous nutrition support, it is shown that the utilization of medical catheter and demand acutely increase.
The effect harmless to the human body of silk microfibre securely and reliably has good biocompatibility, suitable for succeeding in developing Energy property material, it can be applied to the various fields such as medicine, health, food, chemical industry.
Gelatin is very important one of native biopolymer material, is the partial hydrolysate of collagen, cheap and easy to get, With good biocompatibility and degradability, food, medicine and chemical industry have been widely used in it.
Polyethylene glycol is the extremely wide polyether high molecular compound of medical application, can be applied to medicine, health, food, The various fields such as chemical industry have hydrophily, nontoxicity and immunology inertia, become internal injection macromolecule by FDA approval.Benefit With the amphipathic copolymer containing polyethylene glycol in medical macromolecular materials adsorption, retention and grafting, it can improve and be connect with blood The biocompatibility of the medical macromolecular materials of touching.
Although silk microfibre, gelatin and polyethylene glycol have above-mentioned each advantage, at present by silk microfibre, gelatin and The mixture or polymer of polyethylene glycol are used to prepare medical catheter and are rarely reported.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of silk microfibre-gelatin-polyethylene glycol medical catheter and its Preparation method, material price is cheap, and preparation method is simply easily operated, avoids the cellulotoxic side effect generated using crosslinking agent, Good biocompatibility.Suitable for blood vessel, peripheral nerve conduit application, it is easy to be metabolized in vivo.
In order to solve the above technical problems, to provide a kind of silk microfibre-gelatin-polyethylene glycol medical for the embodiment of the present invention Conduit, prepared by the medical catheter of every 100ml contains following component in solution: 1~10g of silk microfibre, aqueous solution 10~ 100ml, 10% 2~30ml of gelatin solution, 1~10g of polyethylene glycol 2000.
Wherein, prepared by the medical catheter of every 100ml contains following component: 3~7g of silk microfibre, aqueous solution 20 in solution ~80ml, 10% 10~25ml of gelatin solution, 3~8g of polyethylene glycol 2000.
Preferably, prepared by the medical catheter of every 100ml contains following component: silk microfibre 6g, aqueous solution in solution 60ml, 10% gelatin solution 20ml, polyethylene glycol 2000 5g.
Wherein, the preparation method of the silk microfibre includes following three stage:
A, degumming silk fiber is prepared from cocoon;
B, degumed silk fiber is hydrolyzed into micron order silk fiber;
C, silk fiber washs, neutralizes and be lyophilized into silk fiber powder.
Further, stage b, degumed silk fiber is hydrolyzed into the specific steps of micron order silk fiber are as follows: by sodium hydroxide plus Enter into distilled water, when 30%~40% NaOH exothermic reaction dissolution, dry degumming silk fiber is added and is stirred with scraper It mixes, is hydrolyzed, the weight ratio of the sodium hydroxide, distilled water and degumming silk fiber is 1:2.5~3.5:0.15~0.25;
Stage c, silk fiber washing, the specific steps for neutralizing and being lyophilized into silk fiber powder are as follows:
C-1, the water of 8~10 times of distilled water volumes is added in the reaction mixture of stage b, and with centrifugal force 2500 ~3000xg is centrifuged 5~8 minutes;
C-2, supernatant is abandoned, silk fiber is resuspended in the water of 8~10 times of distilled water volumes, stirs and be centrifuged;
C-3,5~8 step c-2 are repeated, removes excess base;
C-4, pH value determination, and use salt acid for adjusting pH to 7.0;
C-5, the silk fiber solution of neutralization is centrifuged 5~20min again with 3000~4000rpm and is resuspended in water, weight Multiple 3~5 times, finally fiber suspension in PBS and is lyophilized, obtains silk fiber powder.
Preferably, stage b, degumed silk fiber is hydrolyzed into the specific steps of micron order silk fiber are as follows: by the hydrogen-oxygen of 1.75g Change sodium to be added in 5mL distilled water, when about 35% NaOH exothermic reaction dissolution, the degumed silk of the drying of 0.35g is added Fiber is simultaneously stirred with scraper, is hydrolyzed.To obtain 400~500 μm and medium 150~200 μm of superfine fibres, hydrolysis Time carries out 30s and 180s respectively.In order to obtain 10~20 μm of silk fiber, by reaction mixture be placed in boiling water bath 60s with Help fast hydrolyzing;
Stage c, silk fiber washing, the specific steps for neutralizing and being lyophilized into silk fiber powder are as follows:
C-1,45ml water is added in the reaction mixture of stage b, and with centrifugal force 2800xg centrifugation 5 minutes;
C-2, supernatant is abandoned, silk fiber is resuspended in 50mL water, stirs and is centrifuged;
C-3,5~8 step c-2 are repeated, removes excess base;
C-4, pH value determination, and use salt acid for adjusting pH to 7.0;
C-5, the silk fiber solution of neutralization is centrifuged 5min again with 3500rpm and is resuspended in water, repetition 3~5 times, most Fiber suspension in PBS and is lyophilized afterwards, obtains silk fiber powder.
Wherein, 10% gelatin solution is formulated by gelatin and pure water, and the mass ratio of the gelatin and pure water is 1: 9。
The embodiment of the present invention also provides a kind of above-mentioned silk microfibre-gelatin-polyethylene glycol medical catheter, including as follows Step:
(1) it prepares silk microfibre solution: taking the silk microfibre of formula ratio to be dissolved in 10~100ml aqueous solution, add Thermal agitation makes it completely dissolved;
(2) 10% gelatin solution for weighing formula ratio, the silk that 10% gelatin solution is poured slowly into step (1) preparation are micro- In fiber solution, dissolution is sufficiently stirred in glass bar;
(3) polyethylene glycol 2000 of formula ratio is weighed, is added in mixed liquor obtained by step (2), 55~65 DEG C of ultrasonic agitations, Dissolve it sufficiently;
(4) solution is prepared using the medical catheter of 10ml syringe aspiration step (3), be injected into catheter mold, it is fixed Catheter mold early period of the good preparation solution containing medical catheter, lies in the big ware of glass, is placed in refrigerator freezing;
(5) catheter mold early period in step (4) refrigerator is taken out, the outer layer for catheter mold early period of decorporating is formed in package Later period catheter mold is sandwiched in freeze-drying bottle with tweezers, covers bottle stopper, level is put into refrigerator, freezing by the later period catheter mold of core;
(6) the freeze-drying bottle in step (5) after freezing is taken out, it is self cooling after freeze-drying bottle is lyophilized completely using freeze drier Freeze-drying bottle is removed on lyophilizer, and takes out later period catheter mold, and it is micro- to obtain silk for the inner core for later period catheter mold of carefully decorporating Fiber-gelatin-polyethylene glycol medical catheter;
(7) silk prepared microfibre-gelatin-polyethylene glycol medical catheter is put into hermetic bag, has marked name Claim and preparation time, the long-term preservation at shady and cool, drying use preceding taking-up medical catheter Co60Irradiation, disinfection, it is spare.
Preferably, the preparation method of above-mentioned silk microfibre-gelatin-polyethylene glycol medical catheter includes the following steps:
(1) ' and prepare silk microfibre solution: take 6g silk microfibre to be dissolved in 60ml aqueous solution, heating stirring makes it It is completely dissolved;
(2) 10% gelatin solution of ' weighing 20ml, the silk that 10% gelatin solution is poured slowly into step (1) preparation are micro- In fiber solution, dissolution is sufficiently stirred in glass bar;
(3) ' and 5g polyethylene glycol 2000 is weighed, it is added in mixed liquor obtained by step (2), 65 DEG C of ultrasonic agitation 2.5h make it Sufficiently dissolution;
(4) ' using 10ml syringe draw 8ml step (3) ' medical catheter prepare solution, be injected into medical catheter mould In tool, catheter mold early period of the preparation solution containing medical catheter is fixed, lies in the big ware of glass, is placed in refrigerator, -20 DEG C cold Freeze overnight;
(5) catheter mold early period in ' taking-up step (4) ' refrigerator, the outer layer for catheter mold early period of decorporating form package Later period catheter mold is sandwiched in freeze-drying bottle with tweezers, covers bottle stopper by the later period catheter mold of inner core, and level is put into refrigerator, and -20 DEG C freezing 2h;
(6) ' and freeze drier is opened, it connects freeze drier and vacuum pump, dry built-in temperature to be frozen is down to -40 DEG C Below, when vacuum is down to 0.02Pa, step (5) ' middle freeze-drying bottle is moved on in freeze drier, 12h is lyophilized, bottle to be lyophilized is complete After freeze-drying, removes freeze-drying bottle and take out later period catheter mold, the inner core for later period catheter mold of carefully decorporating obtains silk fento Dimension-gelatin-polyethylene glycol medical catheter;
(7) ' silk prepared microfibre-gelatin-polyethylene glycol medical catheter is put into hermetic bag, mark name Claim and preparation time, the long-term preservation at shady and cool, drying use preceding taking-up medical catheter Co60Irradiation, disinfection, it is spare.
Wherein, the medical catheter mold includes outer tube, inner core, lower closure and seaming chuck, and lower block is inverted T-shaped knot Structure, interior lower closure centre bore open, lower end closed equipped with upper end, the lower end of the inner core insert in lower closure centre bore, The upper end of the inner core penetrates from the lower end of outer tube and extend out to outer tube upper end, and the top of the lower closure inserts in outer tube pipe Intracavitary, lower limit is in the lower section of outer tube;
The seaming chuck is T-shaped structure, the interior seaming chuck centre bore open equipped with upper and lower side, the seaming chuck suit Between outer tube and inner core, and its underpart inserts in outer tube lumen, top is limited in above outer tube, the seaming chuck and lower closure Between gap be medical catheter prepare solution fill area.
The advantageous effects of the above technical solutions of the present invention are as follows: the present invention prepares silk fento using physical mixing processes Dimension-gelatin-polyethylene glycol catheter holder material, material price is cheap, and preparation method is simply easily operated, avoids using crosslinking agent The cellulotoxic side effect of generation, good biocompatibility.Suitable for blood vessel, peripheral nerve conduit application, it is easy to be metabolized in vivo.
Detailed description of the invention
Fig. 1 is the longitudal section scanning electron microscope (SEM) photograph of silk microfibre-gelatin-polyethylene glycol medical catheter prepared by the present invention;
Fig. 2 is the structural schematic diagram of silk microfibre-gelatin-polyethylene glycol medical catheter prepared by the present invention;
Fig. 3 is the structural exploded view for the medical catheter mold that the present invention uses.
Description of symbols:
1, outer tube;2, inner core;3, lower closure;4, seaming chuck.
Specific embodiment
To keep the technical problem to be solved in the present invention, technical solution and advantage clearer, below in conjunction with attached drawing and tool Body embodiment is described in detail.
The present invention, which provides a kind of scanning electron microscope (SEM) photograph silk microfibre-as shown in Figure 1 and Figure 2 gelatin-polyethylene glycol is medical, to be led Pipe, wherein Fig. 1 (a) is silk microfibre-gelatin-polyethylene glycol medical catheter longitudal section scanning electron microscope (SEM) photograph, and Fig. 1 (b) is Fig. 1 (a) partial enlarged view at box.Prepared by the medical catheter of every 100ml contains following component in solution: silk microfibre 1~ 10g, 10~100ml of aqueous solution, 10% 2~30ml of gelatin solution, 1~10g of polyethylene glycol 2000.
The preparation method of above-mentioned silk microfibre-gelatin-polyethylene glycol medical catheter includes the following steps:
(1) it prepares silk microfibre solution: taking the silk microfibre of formula ratio to be dissolved in 10~100ml aqueous solution, add Thermal agitation makes it completely dissolved;
(2) 10% gelatin solution for weighing formula ratio, the silk that 10% gelatin solution is poured slowly into step (1) preparation are micro- In fiber solution, dissolution is sufficiently stirred in glass bar;
(3) polyethylene glycol 2000 of formula ratio is weighed, is added in mixed liquor obtained by step (2), 55~65 DEG C of ultrasonic agitations, Dissolve it sufficiently;
(4) solution is prepared using the medical catheter of 10ml syringe aspiration step (3), be injected into catheter mold, it is fixed Catheter mold early period of the good preparation solution containing medical catheter, lies in the big ware of glass, is placed in refrigerator freezing;
(5) catheter mold early period in step (4) refrigerator is taken out, the outer layer for catheter mold early period of decorporating is formed in package Later period catheter mold is sandwiched in freeze-drying bottle with tweezers, covers bottle stopper, level is put into refrigerator, freezing by the later period catheter mold of core;
(6) the freeze-drying bottle in step (5) after freezing is taken out, it is self cooling after freeze-drying bottle is lyophilized completely using freeze drier Freeze-drying bottle is removed on lyophilizer, and takes out later period catheter mold, and it is micro- to obtain silk for the inner core for later period catheter mold of carefully decorporating Fiber-gelatin-polyethylene glycol medical catheter;
(7) silk prepared microfibre-gelatin-polyethylene glycol medical catheter is put into hermetic bag, has marked name Claim and preparation time, the long-term preservation at shady and cool, drying use preceding taking-up medical catheter Co60Irradiation, disinfection, it is spare.
Prepare medical catheter mould structure such as Fig. 3 institute used in silk microfibre-gelatin-polyethylene glycol medical catheter Show, including outer tube 1, inner core 2, it is lower block 3 and seaming chuck 4, it is described it is lower to block 3 be inverted T-shaped structure, in be equipped with upper end it is open, The lower closure centre bore of lower end closed, the lower end of the inner core 2 insert in lower closure centre bore, and the upper end of the inner core 2 is outside The lower end of pipe 1 penetrates and extend out to 1 upper end of outer tube, and the top of the lower closure 3 inserts in 1 lumen of outer tube, lower limit In the lower section of outer tube 1.
The seaming chuck 4 is T-shaped structure, the interior seaming chuck centre bore open equipped with upper and lower side, 4 sets of the seaming chuck Loaded between outer tube 1 and inner core 2, and its underpart inserts in 1 lumen of outer tube, top is limited in 1 top of outer tube, the seaming chuck 4 And the lower gap blocked between 3 is that medical catheter prepares solution fill area.
When preparing silk microfibre-gelatin-polyethylene glycol medical catheter using above-mentioned medical catheter mold, first by inner core Lower end insert into lower closure centre bore, the upper end of inner core is penetrated from the lower end of outer tube then and is extend out on outer tube upper end Side, until the top of lower closure inserts in outer tube lumen, lower limit is in the lower section of outer tube.From the upper port of outer tube to outer tube lumen Interior injection medical catheter prepares solution, then by seaming chuck through on inner core and being pressed downward medical catheter and prepare solution, until pushing The lower part of head inserts in outer tube lumen, top is limited in above outer tube, and so far, the gap between seaming chuck and lower closure forms silkworm Silk microfibre-gelatin-polyethylene glycol medical catheter.
Specifically prepare following 3 parts of samples according to above-mentioned preparation method, and porosity to 3 parts of samples and mechanical strength into Row compares, and the group score value and each experiment parameter of 3 parts of samples are the more excellent combinations under current experiment condition, but be not limit it is of the invention The unique combinations of protection scope.
The preparation of sample G1:
(1) ' and prepare silk microfibre solution: take 6g silk microfibre to be dissolved in 60ml aqueous solution, heating stirring makes it It is completely dissolved;
(2) 10% gelatin solution of ' weighing 20ml, the silk that 10% gelatin solution is poured slowly into step (1) preparation are micro- In fiber solution, dissolution is sufficiently stirred in glass bar;
(3) ' and 5g polyethylene glycol 2000 is weighed, it is added in mixed liquor obtained by step (2), 65 DEG C of ultrasonic agitation 2.5h make it Sufficiently dissolution;
(4) ' using 10ml syringe draw 8ml step (3) ' medical catheter prepare solution, be injected into medical catheter mould In tool, catheter mold early period of the preparation solution containing medical catheter is fixed, lies in the big ware of glass, is placed in refrigerator, -20 DEG C cold Freeze overnight;
(5) catheter mold early period in ' taking-up step (4) ' refrigerator, the outer layer for catheter mold early period of decorporating form package Later period catheter mold is sandwiched in freeze-drying bottle with tweezers, covers bottle stopper by the later period catheter mold of inner core, and level is put into refrigerator, and -20 DEG C freezing 2h;
(6) ' and freeze drier is opened, it connects freeze drier and vacuum pump, dry built-in temperature to be frozen is down to -40 DEG C Below, when vacuum is down to 0.02Pa, step (5) ' middle freeze-drying bottle is moved on in freeze drier, 12h is lyophilized, bottle to be lyophilized is complete After freeze-drying, removes freeze-drying bottle and take out later period catheter mold, the inner core for later period catheter mold of carefully decorporating obtains silk fento Dimension-gelatin-polyethylene glycol medical catheter;
(7) ' silk prepared microfibre-gelatin-polyethylene glycol medical catheter is put into hermetic bag, mark name Claim and preparation time, the long-term preservation at shady and cool, drying use preceding taking-up medical catheter Co60Irradiation, disinfection, it is spare.
Sample G2 and G3 except constituent part content Bu Tong in addition to, remaining implementation process is the same as sample G1, the prescription of sample G2 and G3 Content such as following table one.
Table one:
Formula G2 G3
Silk microfibre 2g 4g
Aqueous solution 80mL 40mL
10% gelatin solution 20mL 8mL
Polyethylene glycol 2000 1g 3g
Porosity is carried out to sample G1, G2, G3 respectively and pulling force loading detects, as a result such as table two.
Table two:
Sample Porosity Maximum loading
G1 > 45% 4.102N
G2 It forms bad 1.892N
G3 < 40% 3.981N
As shown in Table 2, the medical catheter of sample G1 prescription preparation has good porosity and mechanical strength, preferably The requirement for meeting cell culture and cellular products research field is the good medical catheter for studying organizational project.
The advantageous effects of the above technical solutions of the present invention are as follows:
(1) formula material of the present invention is from a wealth of sources, cheap, have medical macromolecular materials adsorption, Retention and grafting functional.
(2) medical catheter nontoxicity and immunology inertia prepared by formula of the present invention, improvement and contacting blood Medical macromolecular materials biocompatibility.
(3) formula of the present invention has three-dimensional structure abundant by medical catheter prepared by mold, can be nerve The conveying of nutriment needed for cell growth process provides necessary approach, for nerve cell growth provide it is necessary Inducing action and necessary growing space.
(4) medical catheter that preparation method of the present invention obtains has good mechanical strength, and maximum loading is 4.102N。
The above is a preferred embodiment of the present invention, it is noted that for those skilled in the art For, without departing from the principles of the present invention, it can also make several improvements and retouch, these improvements and modifications It should be regarded as protection scope of the present invention.

Claims (7)

1. a kind of silk microfibre-gelatin-polyethylene glycol medical catheter, the medical catheter of every 100ml is prepared in solution containing such as Lower component: 1~10g of silk microfibre, 10~100ml of aqueous solution, 10% 2~30ml of gelatin solution, polyethylene glycol 2000 1~ 10g;
The preparation method of the silk microfibre includes following three stage:
A, degumming silk fiber is prepared from cocoon;
B, degumed silk fiber is hydrolyzed into micron order silk fiber;
C, silk fiber washs, neutralizes and be lyophilized into silk fiber powder;
It is characterized in that, stage b, degumed silk fiber to be hydrolyzed into the specific steps of micron order silk fiber are as follows: by sodium hydroxide plus Enter into distilled water, when 30%~40% NaOH exothermic reaction dissolution, dry degumming silk fiber is added and is stirred with scraper It mixes, is hydrolyzed, the weight ratio of the sodium hydroxide, distilled water and degumming silk fiber is 1:2.5~3.5:0.15~0.25;
Stage c, silk fiber washing, the specific steps for neutralizing and being lyophilized into silk fiber powder are as follows:
C-1, the water of 8~10 times of distilled water volumes is added in the reaction mixture of stage b, and with centrifugal force 2500~ 3000xg is centrifuged 5~8 minutes;
C-2, supernatant is abandoned, silk fiber is resuspended in the water of 8~10 times of distilled water volumes, stirs and be centrifuged;
C-3,5~8 step c-2 are repeated, removes excess base;
C-4, pH value determination, and use salt acid for adjusting pH to 7.0;
C-5, the silk fiber solution of neutralization is centrifuged 5~20min again with 3000~4000rpm and is resuspended in water, repetition 3~ 5 times, finally fiber suspension in PBS and is lyophilized, obtains silk fiber powder.
2. silk microfibre-gelatin-polyethylene glycol medical catheter according to claim 1, which is characterized in that every 100ml Medical catheter prepare in solution containing following component: 3~7g of silk microfibre, 20~80ml of aqueous solution, 10% gelatin solution 10~25ml, 3~8g of polyethylene glycol 2000.
3. silk microfibre-gelatin-polyethylene glycol medical catheter according to claim 1, which is characterized in that every 100ml Medical catheter prepare in solution containing following component: it is silk microfibre 6g, aqueous solution 60ml, 10% gelatin solution 20ml, poly- 2000 5g of ethylene glycol.
4. silk microfibre-gelatin-polyethylene glycol medical catheter described in any one of claim 1 to 3, feature exist In 10% gelatin solution is formulated by gelatin and pure water, and the mass ratio of the gelatin and pure water is 1:9.
5. a kind of preparation of silk microfibre-gelatin-polyethylene glycol medical catheter according to any one of claims 1 to 3 Method, which comprises the steps of:
(1) it prepares silk microfibre solution: taking the silk microfibre of formula ratio to be dissolved in 10~100ml aqueous solution, heating is stirred It mixes and makes it completely dissolved;
(2) 10% gelatin solution is poured slowly into the silk microfibre of step (1) preparation by 10% gelatin solution for weighing formula ratio In solution, dissolution is sufficiently stirred in glass bar;
(3) polyethylene glycol 2000 of formula ratio is weighed, is added in mixed liquor obtained by step (2), 55~65 DEG C of ultrasonic agitations make it Sufficiently dissolution;
(4) solution is prepared using the medical catheter of 10ml syringe aspiration step (3), is injected into catheter mold, fixes and contain Catheter mold early period of medical catheter preparation solution lies in the big ware of glass, is placed in refrigerator freezing;
(5) catheter mold early period in step (4) refrigerator is taken out, the outer layer for catheter mold early period of decorporating forms package inner core Later period catheter mold is sandwiched in freeze-drying bottle with tweezers, covers bottle stopper, level is put into refrigerator, freezing by later period catheter mold;
(6) the freeze-drying bottle in step (5) after freezing is taken out, after freeze-drying bottle is lyophilized completely using freeze drier, self cooling freeze-drying Freeze-drying bottle is removed on dry machine, and takes out later period catheter mold, and the inner core for later period catheter mold of carefully decorporating obtains silk fento Dimension-gelatin-polyethylene glycol medical catheter;
(7) silk prepared microfibre-gelatin-polyethylene glycol medical catheter is put into hermetic bag, marked title and Preparation time, the long-term preservation at shady and cool, drying, uses preceding taking-up medical catheter Co60Irradiation, disinfection, it is spare.
6. the preparation method of silk microfibre-gelatin-polyethylene glycol medical catheter according to claim 5, feature exist In including the following steps:
(1) ' and prepare silk microfibre solution: take 6g silk microfibre to be dissolved in 60ml aqueous solution, heating stirring makes it completely Dissolution;
(2) 10% gelatin solution, is poured slowly into the silk microfibre of step (1) preparation by 10% gelatin solution of ' weighing 20ml In solution, dissolution is sufficiently stirred in glass bar;
(3) ' and 5g polyethylene glycol 2000 is weighed, it is added in mixed liquor obtained by step (2), 65 DEG C of ultrasonic agitation 2.5h, makes it sufficiently Dissolution;
(4) ' using 10ml syringe draw 8ml step (3) ' medical catheter prepare solution, be injected into medical catheter mold, Catheter mold early period for fixing the preparation solution containing medical catheter, lies in the big ware of glass, is placed in refrigerator, -20 DEG C freezed Night;
(5) catheter mold early period in ' taking-up step (4) ' refrigerator, the outer layer for catheter mold early period of decorporating form package inner core Later period catheter mold, by later period catheter mold with tweezers sandwich freeze-drying bottle in, cover bottle stopper, level is put into refrigerator, and -20 DEG C are cold Freeze 2h;
(6) ' open freeze drier, connect freeze drier and vacuum pump, dry built-in temperature to be frozen be down to -40 DEG C with Under, vacuum is when being down to 0.02Pa, step (5) ' middle freeze-drying bottle is moved on in freeze drier, 12h is lyophilized, bottle to be lyophilized freezes completely After dry, remove freeze-drying bottle and take out later period catheter mold, the inner core for later period catheter mold of carefully decorporating obtains silk microfibre- Gelatin-polyethylene glycol medical catheter;
(7) ' silk prepared microfibre-gelatin-polyethylene glycol medical catheter is put into hermetic bag, marked title and Preparation time, the long-term preservation at shady and cool, drying, uses preceding taking-up medical catheter Co60Irradiation, disinfection, it is spare.
7. the preparation method of silk microfibre-gelatin-polyethylene glycol medical catheter according to claim 5, feature exist In the medical catheter mold includes outer tube, inner core, lower closure and seaming chuck, and lower block is inverted T-shaped structure, is inside set There is the lower closure centre bore of upper end opening, lower end closed, the lower end of the inner core inserts in lower closure centre bore, the inner core Upper end penetrates from the lower end of outer tube and extend out to outer tube upper end, and the top of the lower closure inserts in outer tube lumen, lower part It is limited in the lower section of outer tube;
The seaming chuck is T-shaped structure, and the interior seaming chuck centre bore open equipped with upper and lower side, the seaming chuck is set in outer Between pipe and inner core, and its underpart inserts in outer tube lumen, top is limited in above outer tube, between the seaming chuck and lower closure Gap be medical catheter prepare solution fill area.
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CN101036802A (en) * 2006-12-30 2007-09-19 苏州大学 Antheraea pernyi silk fibrion biology medicine material and the preparation method
CN101579246A (en) * 2009-05-31 2009-11-18 苏州大学 Artificial silk fibroin nano-fiber nerve repair conduit and preparation method thereof
WO2011019211A2 (en) * 2009-08-12 2011-02-17 서울대학교 산학협력단 Silk nanofiber nerve conduit and method for producing thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101036802A (en) * 2006-12-30 2007-09-19 苏州大学 Antheraea pernyi silk fibrion biology medicine material and the preparation method
CN101579246A (en) * 2009-05-31 2009-11-18 苏州大学 Artificial silk fibroin nano-fiber nerve repair conduit and preparation method thereof
WO2011019211A2 (en) * 2009-08-12 2011-02-17 서울대학교 산학협력단 Silk nanofiber nerve conduit and method for producing thereof

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