CN110038170A - A kind of degradable polyurethane compound and application thereof - Google Patents
A kind of degradable polyurethane compound and application thereof Download PDFInfo
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- CN110038170A CN110038170A CN201910270022.2A CN201910270022A CN110038170A CN 110038170 A CN110038170 A CN 110038170A CN 201910270022 A CN201910270022 A CN 201910270022A CN 110038170 A CN110038170 A CN 110038170A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
- A61L31/022—Metals or alloys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/02—Inorganic materials
- A61L31/028—Other inorganic materials not covered by A61L31/022 - A61L31/026
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/08—Materials for coatings
- A61L31/10—Macromolecular materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L31/127—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix containing fillers of phosphorus-containing inorganic materials
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS 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
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/16—Biologically active materials, e.g. therapeutic substances
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/64—Macromolecular compounds not provided for by groups C08G18/42 - C08G18/63
- C08G18/6484—Polysaccharides and derivatives thereof
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- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/77—Polyisocyanates or polyisothiocyanates having heteroatoms in addition to the isocyanate or isothiocyanate nitrogen and oxygen or sulfur
- C08G18/78—Nitrogen
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- A61L—METHODS 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
- A61L2420/00—Materials or methods for coatings medical devices
- A61L2420/06—Coatings containing a mixture of two or more compounds
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Abstract
The invention discloses a kind of degradable polyurethane compounds and application thereof, the degradable polyurethane compound is combined by degradable medical polyurethane and Mg-Zn based alloy, the characteristic of compound intensity with higher and induced tissue growth and degradation, is a kind of implantation material of very outstanding inducing tissue regeneration for being used to support and fixing.
Description
Technical field
This application involves a kind of degradable polyurethane compound and application thereof, the degradable polyurethane compound is by that can drop
Solution medical polyurethane and magnesium alloy are combined, and the degradable polyurethane of chain extender is made of chitosan, have preferable mechanical property
Can, high-intensitive and inducing tissue regeneration backing material can be prepared with compatibility magnesium alloy materials.
Background technique
In recent years, biodegradable implantation material has become the research hotspot of this field, and various new materials continue to bring out,
Magnesium is one of most important element and to influence to be metabolized in life entity life cycle；Magnesium ion is that content ranks the 4th in human body
Metal ion, it is known that every 300~400mg of the daily consumption magnesium of an adult, therefore the degradation of magnesium bracket or implantation material will not influence
Content of magnesium in life entity.The intensity and growth for claiming the presence of magnesium in mankind's bone structure to have beneficial to bone has been reported.Due to magnesium-based
Alloy is applied because of its corrosion resistance and bad mechanical property to be limited, and wherein Mg-Zn based alloy arranges such as: Mg-Mn-Zn, Mg-Zn-
The alloys such as Zr, Mg-Sc-Y-RE-Zr, with its superior biocompatibility and the high-intensitive blueness for receiving medical magnesium alloy researcher
It looks at.
Domestic and international more literature research report polyurethane material with good mechanical performance, biocompatibility, blood
The features such as compatibility and easy processing is very in fields such as slow releasing carrier of medication, medical surgical material, tissue engineering brackets
Promising degradable medical material is a kind of ingredient of excellent compound rest.Lot of domestic and international document all discloses preparation
The scheme of polyurethane can drop, such as with 1,6- hexamethylene diisocyanate (HDI) for hard section, polycarbonate glycol (PCDL)
The polyurethane synthesized for soft segment, ethyl ester of lysine hydrochloride (Lys-OEt) as chain extender；Using L-lysine as raw material, by L-
Converting carboxylate groups are ester group on lysine, synthesize L-lysine diisocyanate (LDI) under the action of catalyst and divide respectively from different
The polyethylene glycol (PEG) of son amount or the polyurethane that hydroxyethyl piperazine (HEP) is copolymerized；By molecular weight be 2000 it is poly-
(6-caprolactone) dihydric alcohol (PCL) is reacted with LDI generates prepolymer, then reacts synthesis with chain extender 1,4-butanediol (BDO) and gather
Urethane (PU) etc..
Chitosan is most strong to Bacteria suppression power, chitosan hexa polyose anti-tumor activity is most strong, and chitosan contains hydroxyl
Base and amino can be carried out various chemical modifications, such as grafted by quaternary ammonium group, sulfonation, phosphorylation, alkylation, hydroxyethylation, load
Natural active matter, carried metal or oxide etc. improve to change the property of chitosan such as the preparation of carboxymethyl chitosan
Water-soluble and biocidal property has good film forming.
This research team had been devoted to the research of degradable medical polyurethane, the country once applied since 2014
Patent (application number: CN201710971002), denomination of invention: degradation time is controllable, the adjustable medical degradable of elongation at break
Polyurethane) it discloses using amino acid diamine as the degradable polyurethane of chain extender and with this kind of polyurethane as magnesium alloy bracket
The preparation method of coating；The domestic patent (application number: CN201510651224) of this research team application, denomination of invention: a kind of
Biodegradable stent composition), it discloses polyurethane and the preparation method of various brackets is made in magnesium alloy combination；This research team Shen
Please domestic patent (application number: CN201811263478, denomination of invention: a kind of medical polyurethane with antibacterial activity and its
Purposes) it discloses with LDI, LTL as hard section, chitosan as the degradable polyurethane of chain extender, we continue investigation and comparison
The different performance of the polyurethane of various structures finds that various types of polyurethane have extraordinary biocompatibility, and shell is poly-
Sugar possesses intensity more higher than other types of polyurethane as the degradable polyurethane of chain extender, is more suitable for sclerous tissues
The coating of filling or bracket, but it is single use the support requirement that intensity is not able to satisfy sclerous tissues still, to further enhance the material
The Clinical practicability of material, research finds that by composite high-strength magnesium alloy materials, we are preferred after study, preferably magnesium zinc system
Composite material of the alloy as degradable medical polyurethane, can be made as follows be able to satisfy clinical use product (intravascular stent,
Prostate bracket, biliary tract rack, esophageal stents, bone plate, bone nail, spicule, bone stick, internal fixation of spine equipment, ligature, poly- kneecap
Device, bone renovating material, aneurysm clips, blood vessel anastomosis clamp (device), anastomosis ring, embolism equipment, plugging device, is clinical inspection at bone wax
Needs are tested, it is clinical convenient for detection, developer can be added during the preparation process: zirconium dioxide, nonionic diodone and pure
One of blanc fixe), wide market.
Summary of the invention
It is compound by degradable medical polyurethane and Mg-Zn based alloy the present invention provides a kind of degradable polyurethane compound
It is made, wherein the degradable medical polyurethane is chain extender by hard section, chitosan of lysine polyisocyanates.
Wherein, the range of number-average molecular weight of the degradable medical polyurethane be 50,000-30 ten thousand, soft segment by GA, LA, PDO,
One or more of the propylene glycol of CL, 1,3,1,4 butanediols, 1,5 pentanediols and PEG (200,400,600) copolymerization and
At polymer composition.
Wherein, the lysine isocyanates is selected from lysine diisocyanate or its carboxy derivatives or lysine three is different
Cyanate or its carboxy derivatives, wherein the lysine isocyanates or the preferred lysine diisocyanate of its carboxy derivatives
Three isocyanic acid aliphatic ester of aliphatic ester or lysine, wherein fatty acid carbon atoms number is 1,2,3,4,5,6,7,8, and preferably carbon is former
Subnumber be 1 or 2, specially lysine diisocyanate ethyl ester, lysine diisocyanate methyl ester, lysine triisocyanate ethyl ester or
Three methyl isocyanate of lysine；
Described chitosan or derivatives thereof viscosity average molecular weigh range be 1000-20 ten thousand, the preferred chitosan of chitosan,
More preferable deacetylation is greater than 70% chitosan, wherein chitosan or derivatives thereof chain segment containing in polyurethane molecular
Amount is 0.1%-10%；
Wherein, Mg-Zn based alloy refers specifically to Mg-Zn series, can add the microelement and good biocompatibility in human body
Rare earth element to improve the corrosion resistance and intensity of magnesium alloy, such as Mn (manganese), selenium (Se), molybdenum (Mo), chromium (Cr), cobalt
(Co), Nd (neodymium), Y (yttrium), Sr (strontium), such as: Mg-Zn based alloy refers specifically to ZK series magnesium alloy, such as Mg-Zn-Zr-RE system, Mg-
It is Zn-Mn system, Mg-Zn-Mn-Ce system, Mg-Zn-Zr-RE system (such as Mg-Zn-Zr-Y system), Mg-Zn-Mn-Se system, preferably following
The magnesium alloy of ingredient, such as international trade mark ZK40 (Zn content is 3.5-4.0%, and Zr content is 0.5%, and magnesium is surplus), ZK60
(Zn content is 5.0-6.0%, and Zr content is 0.5%, and magnesium is surplus), (Zn content is 5.0-6.0% to ZK60A, and Zr content is
0.7%, magnesium is surplus) or ZK61 (Zn content be 5.0-6.0%, Zr content be 0.6-0.8%, impurity≤0.3%, magnesium is remaining
Amount), (Zn content is 5.0-6.0% to ZK61M, and Zr content is 0.7-0.9%, and Mn content is 0.05%, and the impurity such as Cu, Ni, SI contain
For amount less than 0.1%, magnesium is surplus), (Zn content is 3.5-5.0% to magnesium-rare earth, and Zr content is 0.5-0.7%, and RE content is
0.5-0.7%, magnesium are surplus), antibacterial magnesium alloy: (Zn content is 7.5-9.0% to ZM7, and Ag0.6-1.2%, Zr content is 0.5-
1.0%, for impurity less than 0.5%, magnesium is surplus), magnesium-rare earth WE43 (Mg-4%Y-3.3%RE (Nd, Gd) -0.5Zr%)
One of.
Degradable medical polyurethane and composite material of magnesium alloy provided by the invention can be used to prepare intravascular stent, forefront
Rami glandulares frame, biliary tract rack, esophageal stents, bone plate, bone nail, spicule, bone stick, internal fixation of spine equipment, ligature, patella fracture fixator, bone
Wax, aneurysm clips, blood vessel anastomosis clamp (device), anastomosis ring, embolism equipment, plugging device, is that clinical examination needs at bone renovating material
It wants, it is not clinical convenient for detection, developer can be added during the preparation process: zirconium dioxide, nonionic diodone and bright sulfur acid
One of barium powder.
Specific preparation method is exemplified below:
1, the anchor of blood vessel blocking device is prepared the preparation method is as follows: magnesium alloy plate is rolled into bow-tie shape, is bored in several
Degradable medical polyurethane bar and film package bowknot shape magnesium alloy anchor are placed in shaping grinding apparatus, heat by outer connecting hole
After to 80-150 degree vacuum molding both.
2, for preparing alveolus bone implant, absorbable screw or bone plate, preparation method is as follows: by degradable polyurethane
Composite bar is made with porous hydroxyapatite, inserts the thin-wall tube made of high-strength magnesium alloy, being heated to 80-150 degree will
Degradable polyurethane tamps after composite bar molding is made with porous hydroxyapatite, is processed into the of various shapes of needs and inhales
Screw or bone plate are received, surface spraying or dip-coating degradable polyurethane coating both obtained.
3, for preparing absorbable orifice bracket, preparation method is as follows: thin-walled made of high-strength magnesium alloy is effective
Laser engraving go out design structure, carry out anti-corrosion polishing treatment, by the composite material of degradable polyurethane and magnesium alloy spraying or
Dip-coating polishing treatment after rack surface, heating both obtained.
Absorbable orifice bracket can also be prepared using following technique, preparation method is as follows: by high-strength magnesium alloy system
At the effective laser engraving of thin-walled go out design structure, carry out anti-corrosion polishing treatment, degradable polyurethane is passed through into electrophoretic deposition
Self-organizing is polished after heat treatment and was both obtained to magnesium alloy bracket surface.
4, for preparing absorbable hemostatic folder, preparation method is as follows: degradable polyurethane is formed by die casting
Interior card shape is made, wild card is made in degradable polyurethane composite material, uses according to commercially available similar products and both may be used.
A kind of degradable polyurethane compound provided by the invention can be with appendix drug, stem cell with, various bioactive molecules
And active medicine, such as antiproliferative, anti-migration, anti-angiogenesis, anti-inflammatory, anti-inflammatory, cell growth inhibition, cytotoxicity
And or anti-thrombosis activity agent be selected from including following substance group: sirolimus, everolimus, Elidel, growth
Chalone, tacrolimus, roxithromycin, daunomycin, ascosin, Ba Foluo mycin, Abboticine, medecamycin, angle are husky
Mycin, canavalin, Clarith, troleandomycin, folimycin, cerivastatin, Simvastatin, Lovastatin, fluorine are cut down
Statin, rosuvastatin, Atorvastatin, Pravastatin, Pitavastatin, catharanthine, vincristine, eldisine, Changchun are auspicious
Shore, Etoposide, Teniposide, Nimustine, Carmustine, Luo Mositing, cyclophosphamide, Estramustine, alkeran, different ring
Phosphamide, Chlorambucil, bendamustine, Dacarbazine, busulfan, procarbazine, Treosulfan, replaces not azoles at Trofosfamide
Amine, phosphinothioylidynetrisaziridine, Doxorubicin, Aclarubicin, epirubicin, mitoxantrone, idarubicin, bleomycin, mitomycin C, more
Mildew element, methopterin, fludarabine, fludarabine -5 '-dihydrogen orthophosphate, Cladribine, mercaptopurine, thioguanine, arabinose
One of cytidine, fluorouracil, gemcitabine, capecitabine, polyenoid taxol, carboplatin, cis-platinum, oxaliplatin or combination
Object；Developer can also be added.
Organic solvent used in the present invention is selected from toluene, paraxylene, decane, isoamyl acetate, hexane, benzene, dichloro
Methane, chloroform, cyclohexanone, ketone, dimethylformamide, heptane, dimethylamino formamide, tetrahydrofuran, petroleum ether, two
One or both of first sulfoxide, ethylene glycol terephthalate, preferably tetrahydrofuran, decane, isoamyl acetate, hexane, two
One or both of chloromethanes, chloroform, cyclohexanone, dimethylformamide and heptane, preferably methylene chloride, three chloromethanes
One or both of alkane, DMF, DMSO tetrahydrofuran or ethyl acetate.
Degradable polyurethane compound of the present invention can also add other natural or polymer materials, such as collagen
(soluble collagen), it is PVP, Sodium Hyaluronate, zinc hyaluronate, PEG series, glycerol, propylene glycol, butanediol, pentanediol, various
It can be used for the emulsifier of et al. Ke (such as: phosphatide and modified phospholipid (such as soybean lecithin, the yolk lecithin of various PC contents
Rouge), TWEEN Series (20,40,80), Families of poloxamers) polylactide, polyglycolide, polyactide and polyglycolide copolymerization
Object (PLGA (LA:GA ratio is 1-3:1), such as: the ratio of LA:GA is 75:25；65:35 and 50:50), polyethylene glycol system
Column gather and gather dioxa cyclohexanone and its copolymer (PPDO, PLA-PDO) to dioxa cyclohexanone (PPDO), polytrimethylene
Carbonic ester, polylactic acid-trimethylene carbonate copolymer, magnesium alloy-trimethylene carbonate copolymer, gather polyglycolic acid
Poly lactic coglycolic acid, polyether-ether-ketone, polyvinylpyrrolidone and/or polyethylene glycol, poly- valerolactone, in poly- ε-last of the ten Heavenly stems
Ester, poly- 6-caprolactone, polyhydroxybutyrate, poly butyric ester, poly- hydroxyl valerate, poly butyric ester-copolymerization-valerate,
Poly- (Isosorbide-5-Nitrae-dioxane -2,3- diketone), poly- (1,3- dioxane -2- ketone), poly-p-dioxanone, polyanhydride
(such as poly-maleic anhydride), poly- hydroxyl-metacrylate, fibrin, polybutylcyanoacrylate, magnesium alloy dimethyl
Acrylate, magnesium alloy butyl propyleneglycol acid esters, comes from the pure and mild oligomerization dioxa hexamethylene of few magnesium alloy two at poly- β-maleic acid
Multi-block polymer, polyethylene glycol and the polybutylene terephthalate of ketone glycol)), poly- pivalolactone, polyglycolic acid trimethyl
Carbonic ester, magnesium alloy-glycolide, poly- (γ-ethyl glutamate), poly- (DTH- iminocarbonic ester), poly- (DTE- copolymerization-DT-
Carbonic ester), poly- (bisphenol-A-iminocarbonic ester), polyorthoester, polyglycolic acid carbonate, poly- trimethyl carbonate, poly-
Iminocarbonic ester, poly- (N- vinyl)-pyrrolidones, polyvinyl alcohol, polyesteramide, dealing with alcohol polyester, polyphosphate, poly- phosphorus
Nitrile, poly- [to carboxyphenoxy) propane], poly- hydroxypentanoic acid, polyanhydride, polyethylene glycol oxide-propylene oxide, flexibel polyurethane, main chain
In with the polyurethane of amino acid residue, polyether ester (such as polyethylene glycol oxide), polyalkylene oxalate, polyorthoester and it is total
One of polymers, can also be added nontoxic plasticizer, tributyl citrate (TBC), tributyl 2-acetylcitrate (ATBC), partially
Three monooctyl ester of benzenetricarboxylic acid, tri trimellitate (810) ester, trimellitic acid glyceryl ester, tetraoctyl 1,2,4,5-benzenetetra-carboxylate, diethylene glycol (DEG) dibenzoic acid
Ester, diethylene glycol dibenzoate, dipropylene glycol dibenzoate, dioctyl terephthalate, dioctyl terephthalate, the last of the ten Heavenly stems two
One or more of sour two just own esters, epoxidized soybean oil.
Detailed description of the invention:
Fig. 1 is the schematic diagram that magnesium alloy plate rolls into bow-tie shape in the embodiment of the present invention one；
Wherein, 1, composite material of magnesium alloy；2, the hole for being connected and fixed inside and outside macromolecule；
Fig. 2 is the structural schematic diagram of the absorbable screw prepared in the embodiment of the present invention two；
Fig. 3 is the structural schematic diagram of the lockplate prepared in the embodiment of the present invention two；
Fig. 4 is the structural schematic diagram of the vertebrae mixer prepared in the embodiment of the present invention two；
Fig. 5 is the structural schematic diagram of the patella fracture fixator prepared in the embodiment of the present invention two；
Fig. 6 is the structural schematic diagram of the absorbable orifice bracket prepared in the embodiment of the present invention three；
Fig. 7 is the interior card structure schematic diagram of the absorbable hemostatic folder prepared in the embodiment of the present invention four；
Fig. 8 is the outer card structure schematic diagram of the absorbable hemostatic folder prepared in the embodiment of the present invention four.
Specific embodiment:
Embodiment 1, the anchor for preparing blood vessel blocking device
Magnesium alloy plate is rolled into bow-tie shape (such as Fig. 1), it, will if boring the hole 2 that macromolecule is connected and fixed inside and outside capable person
Degradable medical polyurethane bar and film package 1 anchor of bowknot shape composite material of magnesium alloy are placed in shaping grinding apparatus, are heated to
After 80-150 degree vacuum molding both.
Embodiment 2 prepares alveolus bone implant, absorbable screw, lockplate, vertebrae mixer, patella fracture fixator or bone plate
1, absorbable screw shown in Fig. 2 (1) and Fig. 2 (2) is prepared
Composite bar is made in degradable polyurethane and porous hydroxyapatite, is inserted by high-strength magnesium alloy (preferably Mg-
3.5%Zn-0.6%Zr-1.0%Mn-0.5%Se ingredient) thin-wall tube (wall thickness 0.1-1mm) is made, being heated to 80-150 degree will
Composite bar molding is made in degradable polyurethane and porous hydroxyapatite, is processed into the bioabsorbable interference screw of various shapes of needs
Or bone plate, surface spraying or dip-coating degradable polyurethane are made coating and both obtained.
2, lockplate, vertebrae mixer shown in Fig. 4, patella fracture fixator shown in fig. 5 or bone plate shown in Fig. 3 are prepared
Magnesium alloy plate pressure is rolled into the shape of product design, bores several inside and outside polyurethane material connecting holes, it will be degradable
Medical polyurethane film is wrapped in product surfaces externally and internally, is placed in shaping grinding apparatus, is heated to after 80-150 degree vacuum molding both obtaining；
Magnesium alloy plate pressure can also be rolled into shape of product, several inside and outside polyurethane material connecting holes are bored, by the poly- ammonia of degradable medical
Ester is dissolved in organic dissolution, and spraying or dip-coating are placed in shaping grinding apparatus in the surfaces externally and internally of product, are heated to 80-150 degree
After vacuum molding both.
Embodiment 3, preparation can absorb orifice bracket as shown in Fig. 6 (1)-Fig. 6 (3)
One of preparation method: by high-strength magnesium alloy ZK40M, ((Zn content is 3.5-4.0%, Zr content to Mg-Zn-Zr-Mn
For 0.5-0.7%, Mn content is 0.5-1.0%, and magnesium is surplus) made of the effective laser engraving of thin-walled at bracket, cleaning polishing
20min is impregnated with HF sour (20-30%) after processing, washes of absolute alcohol is used after taking-up, degradable polyurethane and magnesium are closed in drying
In rack surface, heating post-processing was both obtained for the composite material spraying or dip-coating of gold.
The two of preparation method: the effective laser engraving of thin-walled made of high-strength magnesium alloy is gone out to the structure designed, uses 3-5%
Phosphoric acid cleaning, with phytic acid or the phenolic acid containing polyhydroxy, (conversion temperature is 30-50 DEG C, treatment fluid pH=2.0-5.0, phytic acid
Or the phenolic acid concentration containing polyhydroxy is 5ml-10ml/L, and transformation time is respectively 10-30min) it handles, after washes of absolute alcohol
The chloroformic solution of degradable polyurethane and polycaprolactone material is sprayed into rack surface again, heat treatment both obtained.
The three of preparation method: the effective laser engraving of thin-walled made of high-strength magnesium alloy is gone out to the structure designed, uses 3-5%
Phosphoric acid cleaning, the phenolic acid with phytic acid or containing polyhydroxy presses open technique Passivation Treatment, and magnesium alloy sample immerses cathode and can drop
It solves in the DMF solution of polyurethane (molecular weight 3-5 ten thousand) (solid content 1-5%), is powered with plating Conventional process parameters, to magnesium alloy
Rack surface takes out after deposited the polyurethane material of 0.01-0.1mm thickness, with drying after washes of absolute alcohol both.
Embodiment 4 prepares absorbable hemostatic folder
Preparation method is as follows: interior card (Fig. 7) shape is made by die casting molding in degradable polyurethane, it can ZK60
Magnesium alloy Precision Machining at wild card (Fig. 8) shape, spraying or the degradable degradable polyurethane chloroformic solution composite material system of dip-coating
At the specification of setting, uses according to the application method of commercially available similar products and both may be used.
Embodiment 5 compares by polyurethane (molecular weight is 7-9 ten thousand) performance of the different structure of hard section of LDI
Bracket is made with the magnesium alloy materials of heterogeneity in embodiment 6, with degradable polyurethane coating treatment, tests
To the anticorrosion effect and biocompatibility of bracket
6.1, experimental method: selecting the Mg alloy thin wall pipe of heterogeneity, and metallic support is made (such as by drawing laser cutting
Structure on the right of Fig. 6, diameter 4mm, wall thickness 0.18mm), the degradable polyurethane material of the number 1 and 4 in embodiment 5 is sprayed respectively
Material, is immersed in simulated body fluid (SBF solution), 37 degree of heat preservations, observation degradation and the variation of physical performance index.
6.2, experimental result comparison is as follows:
Experimental result is shown: the support strength of B-1, B-2, C-1, C-2, E-1, E-2 can satisfy clinical use, but E-1,
E-2 (magnesium-rare earth) cytotoxicity is shown as 2 grades, does not meet the quality requirement of implantation instrument, and C-1, C-2 (ZK60) break
Split that the time is shorter, overall merit: made of the degradable polyurethane and ZK61 magnesium alloy bracket of 4 structure of number in embodiment 5
Compound rest product is ideal.
Embodiment 7, the magnesium alloy bracket degradation behavior analysis that coating preparation is done using different high molecular materials and cell
Appreciation rate research
ZK61M magnesium alloy bracket (direct 4mm, long 20mm, compression strength are greater than 5.0KPa) 12 is taken, after cleaning polishing,
First preparing phytic acid conversion film, (conversion temperature is 40 DEG C, treatment fluid pH=3.0, phytic acid concentration 7.5ml/L, transformation time difference
For 20min, the conversion film of complete fine and close flawless is obtained), then even application polymeric material coating, is immersed in simulated body fluid
In (SBF solution), surface corrosion situation is observed, while the bracket prepared being taken directly to contact with L929 l cell,
The appreciation rate of cell is measured after co-incubation 72h by mtt assay to judge the biocompatibility of the bracket of different surface treatment, knot
Fruit is as shown below:
Analysis of experimental results: since the degradable polyurethane material of material of the present invention has amphipathic, degradable polyurethane
Hydrophilic group outwardly, hydrophobic grouping is attached to Mg alloy surface and forms water blocking layer, strand in degradable polyurethane degradation process
Segmentation fracture, coating is thinning after degradation, avoids the crack of material degradation appearance and sticks up skin obscission, is before one kind has very much
The coating material on way.
The above description is only an embodiment of the present invention, is not intended to limit the scope of the invention, all to utilize this hair
Similar structures made by bright description or technique are applied directly or indirectly in other relevant technical fields, similarly
It is included within the scope of the present invention.
Claims (10)
1. a kind of degradable polyurethane compound, which is characterized in that by degradable medical polyurethane and the compound system of Mg-Zn based alloy
At, wherein the degradable medical polyurethane is chain extender by hard section, chitosan of lysine polyisocyanates.
2. a kind of degradable polyurethane compound according to claim 1, which is characterized in that the poly- ammonia of degradable medical
The range of number-average molecular weight of ester is 50,000-30 ten thousand, and the Mg-Zn based alloy refers specifically to Mg-Zn series, preferably ZK series magnesium alloy,
Such as Mg-Zn-Zr-RE system, Mg-Zn-Zr-Mn system, Mg-Zn-Zr-Se system.
3. a kind of degradable polyurethane compound according to claim 1, which is characterized in that the lysine polyisocyanic acid
Ester is selected from lysine diisocyanate or its carboxy derivatives or lysine triisocyanate or its carboxy derivatives, wherein institute
State lysine polyisocyanates or the preferred lysine diisocyanate fat acid esters of its carboxy derivatives or three carbimide of lysine
Fat acid esters, wherein fatty acid carbon atoms number is 1,2,3,4,5,6,7,8, and preferably carbon atom number is 1 or 2, specially lysine two
Ethyl isocyanate, three methyl isocyanate of lysine diisocyanate methyl ester, lysine triisocyanate ethyl ester or lysine；
The viscosity average molecular weigh range of the chitosan is 1000-20 ten thousand, and the preferred chitosan of chitosan is more preferably de-
Acetyl degree is greater than 70% chitosan, wherein content of described chitosan or derivatives thereof chain segment in polyurethane molecular be
0.1%-10%；
The Mg-Zn based alloy refers specifically to Mg-Zn series, such as: Mg-Zn-Zr-RE system, Mg-Zn-Mn system, Mg-Zn-Mn-Se system,
It is preferred that Mg-Zn-Zr is serial, wherein Zn content is 2.0-6.5%, and Zr content is 0.3-0.9%, and the control of remaining alloy impurity exists
0.5%.
4. a kind of degradable polyurethane compound according to claim 1, which is characterized in that the poly- ammonia of degradable medical
The soft segment of ester is by GA, LA, the propylene glycol of PDO, CL, 1,3,1,4 butanediols, 1,5 pentanediols and PEG (200,400,600)
Polymer made of one or more copolymerization forms.
5. a kind of degradable polyurethane compound described in any one of -4 according to claim 1, which is characterized in that can be with appendix
Drug, stem cell are with, various bioactive molecules and active medicine, for example antiproliferative, anti-migration, anti-angiogenesis, anti-inflammatory, disappear
Inflammation, cell growth inhibition, cytotoxicity and or anti-thrombosis activity agent be selected from including following substance group: Xi Luomo
Department, everolimus, Elidel, growth hormone release inhibiting hormone, tacrolimus, roxithromycin, daunomycin, ascosin, Ba Foluo mycin,
Abboticine, medecamycin, caspase, canavalin, Clarith, troleandomycin, folimycin, west, which are stood, cuts down him
Spit of fland, Simvastatin, Lovastatin, Fluvastatin, rosuvastatin, Atorvastatin, Pravastatin, Pitavastatin, catharanthine,
Vincristine, eldisine, vinorelbine, Etoposide, Teniposide, Nimustine, Carmustine, Luo Mositing, ring phosphorus
Amide, Estramustine, alkeran, ifosfamide, Trofosfamide, Chlorambucil, bendamustine, Dacarbazine, busulfan,
Procarbazine, Treosulfan, Temozolomide, phosphinothioylidynetrisaziridine, Doxorubicin, Aclarubicin, epirubicin, mitoxantrone, she reach than
Star, bleomycin, mitomycin C, dactinomycin D, methopterin, fludarabine, fludarabine -5 '-dihydrogen orthophosphate, carat
It is Qu Bin, mercaptopurine, thioguanine, cytarabine, fluorouracil, gemcitabine, capecitabine, polyenoid taxol, carboplatin, suitable
One of platinum, oxaliplatin or composition；Developer can also be added.
6. a kind of purposes such as degradable polyurethane compound of any of claims 1-4, which is characterized in that can be with
For preparing the anchor of blood vessel blocking device, preparation method is as follows: magnesium alloy plate pressure being rolled into bow-tie shape, is bored several inside and outside
Degradable medical polyurethane bar and film package bowknot shape magnesium alloy anchor are placed in shaping grinding apparatus by polyurethane material connecting hole
In, it is heated to after 80-150 degree vacuum molding both obtaining.
7. a kind of purposes such as degradable polyurethane compound of any of claims 1-4, which is characterized in that can be with
For preparing alveolus bone implant, absorbable screw, lockplate, vertebrae mixer, patella fracture fixator or bone plate；Wherein,
The absorbable screw the preparation method is as follows: composite bar is made in degradable polyurethane and porous hydroxyapatite, fill out
Enter the thin-wall tube made of high-strength magnesium alloy, is heated to 80-150 degree and degradable polyurethane and porous hydroxyapatite are made
It is tamped after composite bar molding, is processed into the bioabsorbable interference screw or bone plate of various shapes of needs, surface spraying or dip-coating can
Degradable polyurethane coating both obtained；
The lockplate, vertebrae mixer, patella fracture fixator or bone plate are the preparation method is as follows: roll into product shape for magnesium alloy plate pressure
Shape bores several inside and outside polyurethane material connecting holes, degradable medical polyurethane film is wrapped in product surfaces externally and internally, is placed in into
In type grinding tool, it is heated to after 80-150 degree vacuum molding both obtaining.
8. a kind of purposes such as degradable polyurethane compound of any of claims 1-4, which is characterized in that can be with
For preparing absorbable orifice bracket, preparation method is as follows: the effective laser engraving of thin-walled made of high-strength magnesium alloy is gone out
The structure of design carries out anti-corrosion polishing treatment, by the spraying of the composite material of degradable polyurethane and magnesium alloy or dip-coating in bracket
Surface polishes after heat treatment and both obtained.
9. a kind of purposes such as degradable polyurethane compound of any of claims 1-4, which is characterized in that can be with
For preparing absorbable orifice bracket, preparation method is as follows: the effective laser engraving of thin-walled made of high-strength magnesium alloy is gone out
The structure of design carries out anti-corrosion polishing treatment, by degradable polyurethane by electrophoretic deposition self assembly to magnesium alloy bracket surface,
It polishes after heat treatment and both obtained.
10. a kind of purposes of such as degradable polyurethane compound of any of claims 1-4, which is characterized in that can
To be used to prepare absorbable hemostatic folder, preparation method is as follows: interior card is made by die casting molding in degradable polyurethane
Wild card is made in shape, degradable polyurethane composite material, uses according to commercially available similar products and both may be used.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
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| CN201910270022.2A CN110038170A (en) | 2019-04-04 | 2019-04-04 | A kind of degradable polyurethane compound and application thereof |
| PCT/CN2019/084743 WO2020087896A1 (en) | 2018-10-28 | 2019-04-28 | Medical degradable polyurethane having antibacterial activity and application thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112210060A (en) * | 2020-07-21 | 2021-01-12 | 北京科技大学 | Self-repairing green high-toughness polyurethane elastomer and preparation method thereof |
| CN114539623A (en) * | 2022-02-24 | 2022-05-27 | 华北科技学院(中国煤矿安全技术培训中心) | Application of chitosan-based flame retardant in polyurethane |
| WO2022120902A1 (en) * | 2020-12-11 | 2022-06-16 | 深圳先进技术研究院 | Bone repair scaffold and preparation method therefor |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009097968A2 (en) * | 2008-02-05 | 2009-08-13 | Smith & Nephew Orthopaedics Ag | Open-pore biocompatible surface coating for an implant, method for producing the same, and use thereof |
| KR20110059214A (en) * | 2009-11-27 | 2011-06-02 | 한국과학기술연구원 | Coating method for stents or biomedical implants by electrospray |
| CN105169496A (en) * | 2015-09-30 | 2015-12-23 | 苏州纳晶医药技术有限公司 | Biodegradable stent composite |
| CN205569125U (en) * | 2015-09-30 | 2016-09-14 | 苏州纳晶医药技术有限公司 | Degradable urethra support composition that two sacculus catheters supported |
| CN106063949A (en) * | 2015-09-30 | 2016-11-02 | 圆容生物医药无锡有限公司 | Fixing composite material in a kind of high-strength degradable bone |
| CN107970491A (en) * | 2017-11-09 | 2018-05-01 | 四川大学 | A kind of face coat for being used to improve biological medical magnesium alloy corrosion resistance and anti-microbial property |
| CN109503797A (en) * | 2018-10-28 | 2019-03-22 | 凯斯蒂南京医疗器械有限公司 | A kind of medical degradable polyurethane and application thereof with antibacterial activity |
-
2019
- 2019-04-04 CN CN201910270022.2A patent/CN110038170A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009097968A2 (en) * | 2008-02-05 | 2009-08-13 | Smith & Nephew Orthopaedics Ag | Open-pore biocompatible surface coating for an implant, method for producing the same, and use thereof |
| KR20110059214A (en) * | 2009-11-27 | 2011-06-02 | 한국과학기술연구원 | Coating method for stents or biomedical implants by electrospray |
| CN105169496A (en) * | 2015-09-30 | 2015-12-23 | 苏州纳晶医药技术有限公司 | Biodegradable stent composite |
| CN205569125U (en) * | 2015-09-30 | 2016-09-14 | 苏州纳晶医药技术有限公司 | Degradable urethra support composition that two sacculus catheters supported |
| CN106063949A (en) * | 2015-09-30 | 2016-11-02 | 圆容生物医药无锡有限公司 | Fixing composite material in a kind of high-strength degradable bone |
| CN107970491A (en) * | 2017-11-09 | 2018-05-01 | 四川大学 | A kind of face coat for being used to improve biological medical magnesium alloy corrosion resistance and anti-microbial property |
| CN109503797A (en) * | 2018-10-28 | 2019-03-22 | 凯斯蒂南京医疗器械有限公司 | A kind of medical degradable polyurethane and application thereof with antibacterial activity |
Non-Patent Citations (2)
| Title |
|---|
| MEHDI BARIKANI 等: "Synthesis and Characterization of Polyurethane Elastomers Based on Chitosan and Poly(e-caprolactone)", 《JOURNAL OF APPLIED POLYMER SCIENCE》 * |
| 谭劲峰 编著: "《轻有色金属及其合金熔炼与铸造》", 30 April 2013, 冶金工业出版社 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112210060A (en) * | 2020-07-21 | 2021-01-12 | 北京科技大学 | Self-repairing green high-toughness polyurethane elastomer and preparation method thereof |
| CN112210060B (en) * | 2020-07-21 | 2022-04-22 | 北京科技大学 | Self-repairing green high-toughness polyurethane elastomer and preparation method thereof |
| WO2022120902A1 (en) * | 2020-12-11 | 2022-06-16 | 深圳先进技术研究院 | Bone repair scaffold and preparation method therefor |
| CN114539623A (en) * | 2022-02-24 | 2022-05-27 | 华北科技学院(中国煤矿安全技术培训中心) | Application of chitosan-based flame retardant in polyurethane |
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