CN102989044B - Biodegradable medical polymer tubing and preparation method thereof - Google Patents
Biodegradable medical polymer tubing and preparation method thereof Download PDFInfo
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- CN102989044B CN102989044B CN201210535458.8A CN201210535458A CN102989044B CN 102989044 B CN102989044 B CN 102989044B CN 201210535458 A CN201210535458 A CN 201210535458A CN 102989044 B CN102989044 B CN 102989044B
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Abstract
The invention relates to a biodegradable medical polymer tubing and a preparation method thereof. The invention provides a biodegradable medical polymer tubing with adjustable diameter and controllable wall thickness and a preparation method thereof. The tubing is made from biodegradable medical polymer material, and has inner diameter of 0.5-20 mm and thickness of 0.05-10 mm; and the biodegradable medical polymer material is one of a homopolymer, a copolymer, a star-shaped polymer and a crosslinking polymer of trimethylene carbonate, p-dioxanone, lactide, caprolactone and glycollide.
Description
Technical field:
The invention belongs to technical field of polymer materials and biomedical engineering field, more particularly, relate to a kind of biodegradable Medical high molecule pipe material and preparation method thereof.
Background technology:
Biodegradable Medical high molecule pipe material has good biological degradability and excellent biocompatibility, it can degradation in vivo be micromolecular compound by organism metabolism, absorption or excretion, when for clinical practices such as embedded type medical treatment device, medicine sustained and controlled release system and tissue engineering brackets, need not second operation, can alleviate patient's misery, simplify operative procedure, there is the therapeutic effect of raising, extend patients ' lives and improve the effects such as quality of life of patients.Therefore, biodegradable Medical high molecule pipe material has obtained application more and more widely at biomedicine field, and has effectively advanced biological medicine and clinical medical development.But, in the actual application of field of medicaments, clinical demand is high to the precision requirement of the specification of biodegradable Medical high molecule pipe material, micromorphologic homogenization degree and size, otherwise will directly have influence on actual clinical effect, to user, bring even life danger of great side effect.This just has very high requirement to the process technology of Biodegradable material, before forming end product, must strictly control biodegradable polymeric machining process and technological parameter, guarantee that the high-precision densification of tubing physical dimension and material are micromorphologic high-homogenized.The forming methods such as the method that at present, processable polymer tubing is conventional is extruded, injection, mold pressing, gas assisted injection.In above-mentioned processing method, must adopt heating, pressurization, shear and add the techniques such as solvent or additive to realize the smooth enforcement of processing, once implement to add above-mentioned technique in the course of processing of biodegradable polymers, will certainly make biodegradable polymers generation physicochemical change, as thermal degradation, shear shinning, pyrohydrolysis reaction, the side reactions such as chain transfer, destroy the initiating structure of biodegradable polymers, reduce its initial molecular weight and expand molecular weight distribution coefficient, and then the physics of polymer and/or chemical property are produced to some negative effects, be difficult to guarantee the quality of terminal tubing.Simultaneously, in the course of processing of biodegradable polymers, add other solvent or additive, be difficult to realize the zero residual of solvent and guarantee that additive is in the safety of field of medicaments, directly increasing excipient substance and declare the difficulty with new drug approval, greatly having extended product and be applied to the clinical time.Traditional polymer processing method, is difficult to biodegradable polymers to be processed into the high-accuracy tubing that can meet clinical practice requirement to a great extent.
Summary of the invention:
The present invention is exactly for the problems referred to above, and biodegradable Medical high molecule pipe material that a kind of bore is adjustable, wall thickness is controlled and preparation method thereof is provided.
In order to realize above-mentioned purpose of the present invention, the present invention adopts following technical scheme,
Tubing is made by biodegradable medical macromolecular materials, and internal diameter is 0.5～20mm, and thickness is 0.05～10mm;
Described biodegradable medical macromolecular materials are trimethylene carbonate, a kind of in the homopolymer of dioxy cyclohexanone, lactide, caprolactone, Acetic acid, hydroxy-, bimol. cyclic ester, copolymer, star-type polymer, crosslinking polymer.
Concrete preparation process is,
(1) mould with tubulose die cavity is placed in reactor, raw material is put in reactor, and closed reactor;
(2) under 80～180 ℃ of conditions, reaction 12～72h;
(3) cooling, the demoulding can obtain biodegradable Medical high molecule pipe material.
Described raw material is trimethylene carbonate, to more than one in dioxy cyclohexanone, lactide, caprolactone, Acetic acid, hydroxy-, bimol. cyclic ester.
Step adds porogen in (1), can obtain having the biodegradable polymers tubing of loose structure.
Described porogen is one or more in inorganic salt particle, protein, polysaccharide and other organic micromolecule compounds, and particle diameter is 10～1000 μ m, and the mass ratio of porogen and reaction raw materials is 10～50:100.
Step adds cross-linking agent in (1), can obtain cross-linking type biodegradation medical polymer tubing, and the mol ratio of cross-linking agent and reaction raw materials is 0.01 ~ 20mol%.
Described cross-linking agent is 2,4,8,10-spiral shell [5,5] hendecane-3 of mixing, 9-diketone, 5,5'-oxygen base dimethylene two (5-ethyl-1,3-dioxane-2-ketone), 4,4'-Dioxepane-7,7'-diketone, 5,5'-(propane-bis-base) one or more in Dioxepane-2-ketone.
In step (1), directly introduce medicine, can obtain the biodegradable polymers tubing of pastille.
More than one in politef, polyethers ether copper, glass, quartz, metal of described mould make.
The vivo degradation speed of biodegradable Medical high molecule pipe material of preparation, can be adjusted by changing classification, structure, the composition of macromolecular material according to actual needs, and degraded scope is 1 thoughtful 2.5 years.Be generally 1 month to 1 year.
Beneficial effect of the present invention:
1, the prepared biodegradable polymers tubing of the present invention, its mechanical performance can regulate and control by telomerized polymer structure or composition.
2, the prepared biodegradable polymers tubing of the present invention, adopt the Biodegradable high-molecular preparation that biocompatibility is good, the generation of side effect such as can avoiding or diminish inflammation after implanting, can meet the requirement of biological medicine, and can by body, be absorbed or drain, without second operation, take out.
3, the prepared biodegradable polymers tubing of the present invention, its vivo degradation time can regulate and control according to biological degradation polyalcohol structure or composition, degraded scope is 1 thoughtful 2.5 years, generally at 1 month to more than 1 year.
4, the prepared biodegradable polymers tubing of the present invention can directly be introduced medicine in preparation process, obtains the biodegradable polymers tubing of pastille.
5, the prepared biodegradable polymers tubing of the present invention can directly add porogen in preparation process, obtains having the biodegradable polymers tubing of loose structure.
6, the present invention adopts polymerization forming method in mould to be prepared, it is raw material monomer straight forming after polymerization in die cavity, without post-production, can prepare molding, without the process equipments such as extruder, injection machine and processing place, without later stage heating pressurization, time saving and energy saving, energy savings, in addition special environmental protection.
7, the present invention to mold material without specific (special) requirements, politef, polyethers ether copper, glass, quartz, metal and other materials all can, wide material sources, can save Mold Making cost.
8, the present invention side of operation is simple, and the demoulding can make biodegradable Medical high molecule pipe material, without biodegradable medical high polymer is carried out to purification processes, has avoided the introducing of organic solvent.
9, the present invention does not add other solvent and additive, safe and reliable in preparation process.
10, the present invention not only can prepare the tubing of stock size, also can the small precision tube of preparation size.
11, the size of gained tubing of the present invention is adjustable and precision is higher.
12, the biodegradable polymers tubing preparation method that the present invention proposes, can directly prepare cross-linking type biodegradable polymers tubing, has overcome cross linked polymer and has added the problem that is difficult to machine-shaping.
13, preparation method of the present invention, can avoid the side reactions such as biological degradation polyalcohol degradation, shear shinning, does not reduce polymer initial molecular weight, does not destroy the biological initiating structure of biological degradation polyalcohol and composition.
Accompanying drawing explanation:
Fig. 1 is the structural representation of mould.
In Fig. 1,1 shell, 2 core rods.
Fig. 2 is the degradation rate in vivo of trimethylene carbonate tubing of different crosslinking degrees.
Fig. 3 is the vitro drug release curve of trimethylene carbonate and lactide copolymer.
Fig. 4 is PTMC tubing loose structure local pictures.
The specific embodiment:
Provide the following example so that those skilled in the art are easier to understand and implement the present invention.But they should not be regarded as limiting the scope of the invention, and are only its example and representative.Improvement and adjustment about research worker is made some minute essence according to foregoing invention content to the present invention, still belong to protection scope of the present invention.
Embodiment 1
After assembling to the politef shell concentric co-axial that the politef core rod that is 2mm by external diameter and internal diameter are 3mm, be placed in reactor, add 0.1mol trimethylene carbonate simultaneously, after decompression vacuum pumping 3 times, add stannous octoate as catalyst, trimethylene carbonate and catalyst molar ratio are 1000:1, decompression vacuum pumping 3 times (vacuum <15Pa), tube sealing under vacuum condition, at 130 ℃, after bulk polymerization 24h, take out, it is 2mm that cooling and demolding can obtain internal diameter, the PTMC tubing of wall thickness 0.5mm.
Embodiment 2
After the stainless steel casing that the rustless steel core rod that is 3mm by external diameter and internal diameter are 5mm is processed with fluorine element releasing agent, fit together and be placed in to concentric co-axial reactor, add 0.1mol caprolactone simultaneously, after decompression vacuum pumping 3 times, add stannous octoate as catalyst, caprolactone and catalyst molar ratio are 3000:1, decompression vacuum pumping 3 times (vacuum <15Pa), tube sealing under vacuum condition.At 150 ℃, after polymerisation in bulk 48h, take out, it is 3mm that cooling and demolding can obtain internal diameter, the polycaprolactone tubing of wall thickness 1mm.
Embodiment 3
After the glass shell silanization that the glass core rod that is 5mm by external diameter and internal diameter are 10mm is processed, fit together and be placed in to concentric co-axial reactor, add 0.3mol trimethylene carbonate, 0.7mol caprolactone and 0.001mol cross-linking agent 5 simultaneously, 5'-(propane-bis-base) Dioxepane-2-ketone, after decompression vacuum pumping 3 times, add stannous octoate as catalyst, addition is 0.0002mol, decompression vacuum pumping 3 times (vacuum <15Pa), tube sealing under vacuum condition.At 110 ℃, after polymerisation in bulk 36h, take out, it is 5mm that cooling and demolding can obtain internal diameter, the trimethylene carbonate that wall thickness 2.5mm, crosslink density are 0.2% and caprolactone cross-linked copolymer tubing.According to the preparation method of embodiment 3, adjust TMC and the copolymerization ratio of CL and the use amount of crosslinking agent B TB, can obtain trimethylene carbonate and the caprolactone cross-linked polymer pipe of different physical characteristics.The physical property of trimethylene carbonate and caprolactone cross-linked polymer pipe can be in Table 1.
Table 1
Note: TMC=trimethylene carbonate; CL=caprolactone; BTB=55 '-(propane-bis-base) Dioxepane-2-ketone
As shown in Table 1, under identical copolymerization molar ratio (TMC:CL=100:0), content of crosslinking agent is higher, and modulus and the hot strength of copolymer tubing are higher, and elongation strain decreases.And under identical crosslink density (0.1%), caprolactone content is higher, the modulus of copolymer tubing and hot strength reduce, and elongation strain increases thereupon.Visible, in the present invention, adjust the physical property that TMC and the copolymerization ratio of CL and the use content of crosslinking agent B TB can effectively be controlled trimethylene carbonate and caprolactone cross-linked polymer pipe.Meanwhile, adjust cross-linking agent density and can effectively regulate and control cross-linked polymer pipe degradation rate in vivo.
The degradation rate of PTMC cross-linked polymer pipe in rat body is shown in Fig. 2.As shown in Figure 2, crosslink density is higher, and the degradation rate of PTMC cross-linked polymer pipe in rat body is slower.Illustrate that this method can prepare the cross-linked polymer pipe of different performance really simply and effectively, and apply it in different clinical practices and go.
Embodiment 4
After assembling to the politef shell concentric co-axial that the politef core rod that is 1mm by external diameter and internal diameter are 3mm, be placed in reactor, add 0.15mol lactide and 0.05mol Acetic acid, hydroxy-, bimol. cyclic ester simultaneously, after decompression vacuum pumping 3 times, add stannous octoate as catalyst, reaction monomers and catalyst molar ratio are 5000:1, decompression vacuum pumping 3 times (vacuum <15Pa), tube sealing under vacuum condition.At 130 ℃, after polymerisation in bulk 24h, take out, it is 1mm that cooling and demolding can obtain internal diameter, the lactide of wall thickness 1mm and glycolide copolymer tubing.
Embodiment 5
After assembling to the politef shell concentric co-axial that the politef core rod that is 4mm by external diameter and internal diameter are 7mm, be placed in reactor, add 0.1mol trimethylene carbonate, 0.1mol lactide and 0.001mol glycerol simultaneously, after decompression vacuum pumping 3 times, add stannous octoate as catalyst (reaction monomers and catalyst molar ratio are 5000:1), decompression vacuum pumping 3 times (vacuum <15Pa), tube sealing under vacuum condition.At 80 ℃, after polymerisation in bulk 24h, take out, it is 4mm that cooling and demolding can obtain internal diameter, three arm star polymer pipes of the trimethylene carbonate of wall thickness 1.5mm and lactide.
Embodiment 6
After assembling to the politef shell concentric co-axial that the politef core rod that is 1mm by external diameter and internal diameter are 3mm, be placed in reactor, add 0.15mol lactide simultaneously, 0.15mol trimethylene carbonate and 0.03mol Testosterone Propionate, after decompression vacuum pumping 3 times, add stannous octoate as catalyst, reaction monomers and catalyst molar ratio are 5000:1, decompression vacuum pumping 3 times (vacuum <15Pa), tube sealing under vacuum condition.At 130 ℃, after polymerisation in bulk 24h, take out, it is 1mm that cooling and demolding can obtain internal diameter, the lactide that wall thickness 1mm, drug loading are 10mol% and trimethylene carbonate copolymer tubing.Visible Fig. 3 of vitro drug release situation of medicine carrying trimethylene carbonate and lactide copolymer.As shown in Figure 3, medicine carrying trimethylene carbonate prepared by this method and lactide copolymer tubing, release successful, sustainable release Testosterone Propionate 100 days, and the later stage discharge and to tend to be steady, there is the performance of good sustained and controlled release medicament.
Embodiment 7
After assembling to the politef shell concentric co-axial that the politef core rod that is 4mm by external diameter and internal diameter are 7mm, be placed in reactor, add 0.1mol trimethylene carbonate and 0.05mol particle diameter is the sodium chloride particle of 200 μ m simultaneously, after decompression vacuum pumping 3 times, add stannous octoate as catalyst (reaction monomers and catalyst molar ratio are 5000:1), decompression vacuum pumping 3 times (vacuum <15Pa), tube sealing under vacuum condition.At 130 ℃, after polymerisation in bulk 24h, take out, it is 4mm that cooling and demolding can obtain internal diameter, and the trimethylene carbonate polymer pipe of wall thickness 1.5mm is put into 500ml deionized water by tubing and leached porogen particle, every 3h changes water once, until can not check white precipitate with silver nitrate aqueous solution inspection.Blot the moisture of porous tube surfaces, vacuum drying, to constant weight, finally obtains having the PTMC tubing of loose structure, the visible Fig. 4 of structure.As seen from Figure 4, the perforated biodegradable polymer pipe that space is evenly distributed can simply effectively must be prepared by this method.
Claims (1)
1. a preparation method for biodegradable Medical high molecule pipe material, is characterized in that,
After assembling to the politef shell concentric co-axial that the politef core rod that is 1mm by external diameter and internal diameter are 3mm, be placed in reactor, add 0.15mol lactide simultaneously, 0.15mol trimethylene carbonate and 0.03mol Testosterone Propionate, after decompression vacuum pumping 3 times, add stannous octoate as catalyst, reaction monomers and catalyst molar ratio are 5000:1, decompression vacuum pumping 3 times, tube sealing under vacuum <15Pa condition; At 130 ℃, after polymerisation in bulk 24h, take out, it is 1mm that cooling and demolding can obtain internal diameter, the lactide that wall thickness 1mm, drug loading are 10mol% and trimethylene carbonate copolymer tubing;
Medicine carrying trimethylene carbonate and lactide copolymer tubing, sustained release Testosterone Propionate 100 days, and the later stage discharge and to tend to be steady, there is the performance of good sustained and controlled release medicament.
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| CN105288831B (en) * | 2014-06-03 | 2019-11-08 | 辽宁省计划生育科学研究院 | A kind of biodegradation type drug delivery system of hollow tubular and preparation method thereof |
| CN106667897A (en) * | 2017-02-16 | 2017-05-17 | 辽宁省计划生育科学研究院 | Biodegradable slow/controlled-release drug delivery system and preparation method thereof |
| CN110444804B (en) * | 2018-05-04 | 2021-02-12 | 深圳新宙邦科技股份有限公司 | Lithium ion battery non-aqueous electrolyte and lithium ion battery |
| CN112472877B (en) * | 2020-12-18 | 2022-03-08 | 南京鼓楼医院 | Method for preparing lubricating oil-infused ultra-smooth porous surface for medical catheter |
| CN113288505B (en) * | 2021-04-30 | 2023-02-03 | 中国科学院大学温州研究院(温州生物材料与工程研究所) | PTMC-based intestinal anastomosis stent of bioabsorbable flexible elastomer and preparation method thereof |
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