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WO2017054433A1 - Composition de polyuréthane à module d'élasticité ajustable, composite d'échafaudage et son procédé de préparation - Google Patents

Composition de polyuréthane à module d'élasticité ajustable, composite d'échafaudage et son procédé de préparation Download PDF

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Publication number
WO2017054433A1
WO2017054433A1 PCT/CN2016/078430 CN2016078430W WO2017054433A1 WO 2017054433 A1 WO2017054433 A1 WO 2017054433A1 CN 2016078430 W CN2016078430 W CN 2016078430W WO 2017054433 A1 WO2017054433 A1 WO 2017054433A1
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Prior art keywords
stent
polyurethane
vacuum
degradable
polyurethane composition
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English (en)
Chinese (zh)
Inventor
张文芳
薛波新
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Yuanrong Biological Pharmaceutical Co Ltd Wuxi
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Yuanrong Biological Pharmaceutical Co Ltd Wuxi
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Priority claimed from CN201510651223.9A external-priority patent/CN105457092A/zh
Priority claimed from CN201510651224.3A external-priority patent/CN105169496A/zh
Application filed by Yuanrong Biological Pharmaceutical Co Ltd Wuxi filed Critical Yuanrong Biological Pharmaceutical Co Ltd Wuxi
Publication of WO2017054433A1 publication Critical patent/WO2017054433A1/fr
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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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • 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
    • 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
    • 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
    • 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
    • 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
    • C08G18/08—Processes
    • C08G18/10—Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
    • 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
    • C08G18/30—Low-molecular-weight compounds
    • C08G18/32—Polyhydroxy compounds; Polyamines; Hydroxyamines
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L75/00—Compositions of polyureas or polyurethanes; Compositions of derivatives of such polymers
    • C08L75/04—Polyurethanes

Definitions

  • the present invention relates to a composition having a polyurethane (PU) having an elastic modulus adjustable.
  • PU polyurethane
  • the properties of the PU can be varied over a wide range, such as PU.
  • Elasticity, modulus, strength, modulus of elasticity, wear resistance, lubricity, hydrophobicity, etc. are applied to biocompatible compatible implants for various medical products, which belong to the field of biodegradable biomaterials. .
  • Polyurethane is a generic term for polyurethanes and is a general term for macromolecular compounds containing a carbamate (-NHC00-) group in the main chain. It is formed by the addition of an organic diisocyanate or a polyisocyanate with a dihydroxy or polyhydroxy compound. As shown in the typical PU chemical structure, the polymer backbone is composed of a soft segment (soft segment) having a glass transition temperature lower than room temperature and a rigid segment (hard segment) having a glass transition temperature higher than room temperature. Generally, it is synthesized by using a polyether or a polyester diol to form a soft segment of the polymer.
  • the segment has a low glass transition temperature and a low polarity, and constitutes a continuous phase of the material, imparting PU elasticity and controlling the PU.
  • the -NH-functional group forms a large number of hydrogen bonds between the molecular chains, has strong interaction force, exists in a crystalline state, and controls properties such as PU strength and heat resistance.
  • the advantage of this material is that it can be designed in a wide range by designing different soft and hard segments of structure, length and distribution, relative proportions, and changing the relative molecular mass. Change the properties of PU, such as PU elasticity, modulus, strength, modulus of elasticity, abrasion resistance, lubricity, hydrophilicity, biocompatibility, and biostability.
  • Medical PU has good elasticity, tensile strength and elongation at break, good wear resistance and flexural resistance, easy molding, large controllable range, good tissue compatibility and blood compatibility. Excellent performance, such as sex, is widely used in medical materials.
  • Biodegradable polymers provide mechanical support when used in vivo and serve as a platform for biological tissue regeneration or repair. It degrades after a period of time, depending on biodegradability. The type of polymer and the tissue environment. Thus, biodegradable polymers are particularly useful in orthopedic applications as well as in tissue engineering products and therapies. Therefore, it is desirable for researchers in the field to prepare polyurethanes which are suitable for use in different tissue environments and which have an adjustable degradation time and can be tailored according to the properties of the products.
  • the degradable stent comprises a polymer material scaffold and a degradable metal scaffold, wherein the degradable polymer material comprises: PLLA, PLA, PGA, PDO and PCL, wherein PLLA has good rigidity, flexibility, stability and heat resistance. It has been successfully applied to the coating materials of metal stents and self-prepared into stents; the degradable metal stent materials are magnesium alloys and iron alloy materials, among which magnesium alloy materials have gradually become the mainstream of degradable stent research with its excellent processing properties.
  • Magnesium is an essential element of human metabolism. It is second only to potassium, sodium and calcium in the human body. It accounts for about half of all magnesium in the body. Studies have shown that magnesium is a cofactor for many enzymes and has a stable DNA and RNA structure; in vivo, magnesium is maintained between 0.7 and 1.05 mmol/L through the kidneys and intestines; magnesium can stimulate new bone growth with good histocompatibility .
  • the main disadvantage of magnesium is its low corrosion resistance. In the physiological environment of pH (7.4-7.6), magnesium has a strong reduction effect, which loses the mechanical integrity before the tissue is fully healed, and produces hydrogen which cannot be absorbed by the body in time.
  • magnesium-based materials in the human body causes magnesium to be unapplied to the human body. Therefore, it is very realistic to prepare a magnesium-based alloy that can be controlled to degrade, so that the hydrogen generated during the degradation of magnesium is metabolized by the tissue fluid. Significance, a variety of magnesium alloy materials with different degradation and processing properties have also become a research hotspot.
  • Degradable stents can be used in a variety of vessels in the body, including natural body passages or body lumens, but also artificial body openings and body lumens, such as bypass or ileostomy. Examples include: coronary vascular stents, intracranial vascular stents, peripheral vascular stents, splenic artery stents, intraoperative stents, heart valve stents, biliary stents, esophageal stents, intestinal stents, pancreatic duct stents, urethral stents, and tracheal stents.
  • the ureteral stent is the most mature in the research and application of clinical vascular stents.
  • polylactic acid is used as a drug-coated vascular stent. It is also useful to prepare vascular stents by using PLLA materials through 3D printing or engraving.
  • the ureteral stent and the urethral stent with controlled degradation time were prepared by PLGA.
  • the common intraurethral stents were spiral stent, polyurethane stent, bioabsorbable stent, metal mesh stent and heat sensitive stent. Due to the following five conditions after metal stent implantation: a. postoperative blood clot obstruction; b. original chronic urine Patients with retention, long-term catheterization before surgery, bladder detrusor fibrosis; c.
  • prostatic urethra proximal is not covered by stent; d. granulation tissue or epithelial hyperplasia, causing stent stenosis; e. prostate tissue continues to increase Large, more than the ends of the stent, plugged stents, etc., bioresorbable stent: a degradable stent made of pressurized polylactic acid, tissue reaction is light, can be completely absorbed within 12-14 months, in the urethra The short-term effect of stenting for benign prostatic hyperplasia is better, but its final effect remains to be seen, but it is still an effective method for patients with benign prostatic hyperplasia who are not suitable for transurethral resection of the prostate.
  • the urethral stent is divided into a permanent stent and a temporary stent according to the patient's condition.
  • the temporary stent supports the urinary tract rather than the urethral wall. It is divided into a metal stent and an absorbable biodegradable stent. It has been developed in recent years.
  • a temporary stent consisting of a polymeric glycolic acid polymer (PGA) or a lactic acid polymer (PLA) with good histocompatibility, low inflammatory response, low infection rate, no crystallization on the surface, no need to remove or Replacement and other features.
  • Prostatic hyperplasia is a benign progressive disease that increases with age and may extend beyond the range supported by the stent as it continues to increase;
  • the double-balloon degradable urethral magnesium alloy peritoneal stent designed by the invention not only can well place the stent in a suitable position, but also can achieve a good supporting effect, and the results of animal experiments in vivo show that Due to the dissolution of the coating, the tissue has no adverse reactions such as granuloma, and has very practical clinical application value.
  • the present application adjusts the softness and hardness of the product by adjusting the ratio of the two structures of polyurethane, and can be used for preparing medical sanitary materials and dressings, such as various soft tissue brackets, suture materials, and adhesives;
  • the acid triisocyanate reacts to form a network cross-linked structure.
  • the test results show that the elastic modulus of the resulting material can be higher than 500 MPa and the elongation at break is greater than 50%, which can be used to prepare polyurethane products with higher elastic modulus, such as blood vessels.
  • Stents, fracture fixation implants and other orthopedic applications such as spinal cages have a very broad clinical value.
  • the elastic modulus of the polyurethane composition can be adjusted in the range of 50 MPa to 1000 MPa, and the range can be adjusted within the range of 10% to 1000%.
  • the elongation at break of the polyurethane composition
  • a is an integer in the range of 5-50
  • b is an integer in the range of 5-50.
  • x is an integer in the range of 5 to 50
  • y is an integer in the range of 5 to 50.
  • the adjustable range is from 100% to 700%.
  • the present invention also provides a polyurethane composition comprising a polymer III having the formula C, or a polymer IV having the formula D,
  • n is an integer in the range 1-25, and R is -CH 2 - or -COOC 4 H 9 -,
  • h is an integer in the range 1-20
  • k is an integer in the range 1-25.
  • the polyurethane composition has a modulus of elasticity greater than 400 MPa and an elongation at break in the range of 30% to 300%.
  • the present invention further provides a method of preparing a polyurethane composition comprising further reacting a polyurethane with lysine triisocyanate after completion of its synthesis reaction to form a network-like crosslinked structure, the modulus of elasticity of the polyurethane composition Above 400 MPa, the elongation at break is in the range of 30% to 300%.
  • the synthesis reaction of the polyurethane is selected from the following methods:
  • diisocyanate is selected from the group consisting of: 1,6-hexamethylene diisocyanate, isophorone diisocyanate, lysine methyl ester diisocyanate, cis-cyclohexane diisocyanate, anti Formula - cyclohexane diisocyanate, 1,4-butane diisocyanate, 1,2-ethane diisocyanate, 1,3-propane diisocyanate, 4,4'-methylene-bis(cyclohexyl isocyanate), One or two of 2,4,4-trimethyl 1,6-hexane diisocyanate;
  • chain extender glycol is selected from the group consisting of ethylene glycol, diethylene glycol, tetraethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,7-g One or two of a diol, 1,8-octanediol, 1,9-nonanediol, and 1,10-decanediol;
  • the polymer diol comprises poly-(4-hydroxybutyrate) diol (P4HB diol), poly-(3-hydroxybutyrate) diol (P3HB diol), polypropylene glycol and any copolymerization thereof , including PLGA diol, P(LA/CL) diol and P(3HB/4HB) diol, polyether polyol such as poly(tetrahydrofuran), polycarbonate polyol such as poly(hexamethylene carbonate) One or two of the alcohols.
  • reaction of the polyurethane with lysine triisocyanate is selected from one of the following:
  • the polyurethane obtained in the above method is poured into a kneader or a kneader in an environment having a moisture content of less than 10 ppm, directly added with L-lysine triisocyanate, and stirred at room temperature for half an hour to obtain high a modulus of elasticity of the polyurethane composition;
  • the polyurethane obtained in the above method is added to an anhydrous organic solvent (tetrahydrofuran, dichloromethane or chloroform) to form a viscous solution, and L-lysine is directly added in an environment having a moisture content of less than 10 ppm. a triisocyanate, the reaction system is stirred or shaken, and the organic solvent is vacuum-dried after half an hour of normal temperature reaction to obtain the polyurethane composition having a high modulus of elasticity; or
  • the polyurethane obtained in the above method is directly added to L-lysine triisocyanate in an environment having a moisture content of less than 10 ppm, and the reaction system is stirred or shaken and mixed at room temperature. After half an hour of reaction, the organic solvent was vacuum dried to obtain the polyurethane composition having a high modulus of elasticity.
  • the present invention also provides a polyurethane composition prepared by the above method.
  • the invention also provides the use of the polyurethane composition in the preparation of a medical implant material selected from the group consisting of an implant device, an implantable artificial organ, a contact artificial organ, a stent, an interventional catheter, and an organ. assisting equipments.
  • the present invention further provides a degradable stent composite comprising a polyurethane composition and a degradable metal material, the weight ratio of the polyurethane composition to the degradable metal material being in the range of 0.1-99%:1%-99.9% Inside.
  • the degradable stent composite may include a stent formed of the degradable metal material, the coating formed of the polyurethane composition, and preferably the polyurethane composition and the The weight ratio of the degraded metal material is in the range of from 5 to 90%: 10% to 95%.
  • the polyurethane can be a polyurethane composition.
  • the polyurethane is selected from the group consisting of polylactic acid type polyurethane, polycaprolactone type polyurethane, and one or both of two degradable polyurethane derivatives (silicone, polyamino acid modification, polysaccharide modification), preferably Poly( ⁇ -caprolactone) diol (PCL) is a soft segment, polyurethane with L-lysine diisocyanate (LDI) and chain extender 1,4-butanediol (BDO) as hard segment (PU) )material.
  • PCL Poly( ⁇ -caprolactone) diol
  • LLI L-lysine diisocyanate
  • BDO chain extender 1,4-butanediol
  • the degradable stent composite further comprises other polymeric materials selected from the group consisting of polylactic acid, polycaprolactone, polydioxanone, and copolymers thereof (PPDO, PLA-PDO), polydioxanone (PPDO), polytrimethylene carbonate, polylactic acid-trimethylene carbonate copolymer, polycaprolactone-trimethylene carbonate copolymer, polyhydroxyl At least one of acetic acid and polylactic acid-glycolic acid copolymer, the biodegradable polymer material has a viscosity average molecular weight of 500 to 1,000,000.
  • the metal material comprises iron having a purity greater than 99.0%, a magnesium-iron alloy having a purity greater than 99.0% magnesium, and a weight percentage of 1:0.01-10,
  • a magnesium-zinc alloy having a weight percentage of 1:0.01-1 preferably Magnesium-iron alloy (weight ratio is preferably 1:0.01-0.1), magnesium-zinc alloy (weight ratio is preferably 1:0.01-0.1), for example: Mg-Nd-Zn-Zr, Mg-Zn-Mn, Mg-Zn-Mn- Se-Cu alloy, Zn content of 3.5 wt%, Mn content of 0.5-1.0 wt%, Se content of 0.4-1.0 wt%, Cu content of 0.2-0.5 wt%, Mg balance; magnesium-calcium
  • the present invention also provides a method of preparing the above-described degradable stent composite, comprising the steps of:
  • the coating material prepared in (2) is repeatedly dip-coated or uniformly sprayed on the surface of the metal stent prepared in (1) to form a composite stent with a coating having a thickness in the range of 0.001 to 1 mm. Internally, it is preferably 0.01 to 0.5 mm.
  • the method of degradable stent composites can include the following steps:
  • the degradable metal material is prepared, engraved, etched or cut into a desired pattern or strip shape, and the diameter of the pattern is 0.01-3 mm;
  • polyurethane composition according to claim 1-4 or 8 and polylactic acid are mixed and dissolved in an organic solvent in a weight ratio of 1:0.1 to 10, and are formed into a film having a thickness of 0.01- 3mm, preferably 0.1-1mm;
  • the coated stent prepared in (3) is polished to a degradable stent composite by dip coating or spraying a hydrophilic coating.
  • the method of degradable scaffold complex comprises one of the following methods:
  • the 3D printer is provided with two feeding devices, one feeding device is added with magnesium alloy powder (the powder diameter ranges from 10 nm to 1 mm), and the other feeding device is added with a degradable medical polyurethane material solution (configured with organic solvent The concentration is 20-90%), the two substances are mixed in proportion during the feeding process, and the stent of the set size and shape is printed, and the dry organic solvent is evaporated by hot air to obtain the degradable stent composite;
  • the 3D printer is equipped with two feeding devices.
  • Magnesium alloy powder (powder diameter range: 10nm-1mm) is added to one feeding device, and degradable medical polyurethane material and polylactic acid are added to the other feeding device in proportion (1:0.1).
  • the mixture is dissolved in an organic solvent and is disposed in an organic solvent to a concentration of 20-90%.
  • the two materials are mixed in proportion during the feeding process to print a stent of a set size and shape, and the hot air is dried and evaporated to dry organic a solvent to obtain the degradable stent complex;
  • the 3D printer is equipped with two feeding devices.
  • Magnesium alloy powder is added to one feeding device (the powder diameter ranges from 10 nm to 1 mm).
  • the high temperature melting prints out the bracket as needed, and the passivation treatment is used for standby; another feeding device can be added.
  • the degraded medical polyurethane material and the polylactic acid are mixed and dissolved in an organic solvent in a ratio (1:0.1-10), and are disposed in a concentration of 20-90% with an organic solvent, and the coating film is printed on the stent, and the hot air is dried and evaporated. Organic solvent, the resulting Degradable stent complex.
  • the degradable stent composite of the present invention or the degradable stent composite prepared by the method of the present invention has a structure, composition and shape suitable for blood vessels, veins, esophagus, biliary tract, trachea, bronchi, small intestine , large intestine, urethra, ureter or other segments close to the tubular passage, for example, as a vascular stent, tracheal stent, bronchial stent, urethral stent, esophageal stent, biliary stent, ureteral stent (double J tube), ureteral stricture stent, A stent for the small intestine, a stent for the large intestine, a laryngeal implant, a bypass catheter, or an ileostomy.
  • the degradable stent composite of the present invention may further comprise a contrast agent selected from the group consisting of zirconium dioxide, barium sulfate and iodine.
  • Figure 1 is a schematic view of a magnesium alloy stent
  • Figure 2 is a schematic view of a coated stent
  • Figure 3 is a schematic view of a stent graft
  • Figure 4 is a schematic view of the urethral stent placed on the double balloon
  • Figure 5 is a schematic view of the urethral stent
  • Figure 6 is a plan view showing the deployment of the ureteral stent.
  • the present invention discloses an elastic modulus tunable polyurethane composition and its use in a medical implant material, the polyurethane composition having an elastic modulus adjustable at 50-1000 MPa, fracture
  • the range of a is 5-50, and the range of b is 5-50.
  • x ranges from 5 to 50
  • y ranges from 5 to 50
  • a ranges from 10 to 20 and b ranges from 10 to 25.
  • x ranges from 10 to 20 and y ranges from 10 to 25.
  • the obtained product has an elastic modulus of 100-500 MPa and an elongation at break of 100% to 700%.
  • the polymer prepared by the invention can increase lysine triisocyanate in the late stage of the reaction to form an ultrahigh elastic polyurethane polymer having a modulus of elasticity of 400 MPa and an elongation at break of 30% to 300%, and the following molecular formula is formed:
  • n ranges from 1 to 25, and R is -CH 2 - or -COOC 4 H 9 -.
  • R 1 is The range of h is 1-20, and the range of k is 1-25.
  • a highly elastic modulus degradable polyurethane is prepared by using lysine triisocyanate, and a final product obtained by the disclosed polyurethane synthesis reaction is added with lysine triisocyanate to form a network crosslinked structure to form an ultrahigh elastic polyurethane.
  • the composition specifically includes the following polyurethane synthesis reaction:
  • diisocyanate is selected from the group consisting of: 1,6-hexamethylene diisocyanate, isophorone diisocyanate, lysine methyl ester diisocyanate, cis-cyclohexane diisocyanate, trans-cyclohexane diisocyanate, 1,4-butane diisocyanate, 1,2-ethane diisocyanate, 1,3-propane diisocyanate, 4,4'-methylene-bis(cyclohexyl isocyanate), 2,4,4-trimethyl One or two of 1,6-hexane diisocyanate;
  • chain extender glycol is selected from the group consisting of ethylene glycol, diethylene glycol, tetraethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,7-heptanediol One or two of 1,8-octanediol, 1,9-nonanediol, and 1,10-decanediol.
  • the polymer diol is selected from the group consisting of poly-(4-hydroxybutyrate) diol (P4HB diol), poly-(3-hydroxybutyrate) diol (P3HB diol), polypropylene glycol, and any copolymer thereof Including PLGA diol, P(LA/CL) diol, and P(3HB/4HB) diol.
  • a polyether polyol such as poly(tetrahydrofuran)
  • a polycarbonate polyol such as poly(hexamethylene carbonate) glycol.
  • L-lysine triisocyanate is added to the obtained product of the above method to carry out capping to prepare a polyurethane having a high elastic modulus, and the preparation method is as follows:
  • the final product obtained by the method according to claim 4 is reacted in a twin-screw extruder extruder for 20 minutes in an environment having a moisture content of less than 10 ppm, and the mixture is stirred and extruded to obtain a polyurethane having a high elastic modulus. fiber;
  • Method 2 The final product obtained by the method according to claim 4 is poured into a kneader or a kneader in an environment having a moisture content of less than 10 ppm, and directly added with L-lysine triisocyanate, and stirred at room temperature for half an hour. That is;
  • Method 3 After the reaction is completed according to the method of claim 4, an anhydrous organic solvent is added to prepare a viscous solution, and L-lysine triisocyanate is directly added in an environment having a moisture content of less than 10 ppm, and the reaction system is stirred or shaken.
  • organic solvent is selected by vacuum extraction, wherein the organic solvent is selected from the group consisting of toluene, p-xylene, decane, isoamyl acetate, hexane, benzene, dichloromethane, chloroform, 1, 4-cyclohexanone, ketone, One or two of dimethylformamide, heptane, dimethylcarbamate, tetrahydrofuran, petroleum ether, dimethyl sulfoxide, ethylene terephthalate, preferably tetrahydrofuran, dichloromethane, trichloro One or a combination of methane and 1,4 cyclohexanone;
  • Method 4 After the reaction is completed according to the method of claim 4, L-lysine triisocyanate is directly added in an environment having a moisture content of less than 10 ppm, and the reaction system is stirred or shaken, and the organic solvent is vacuum-dried after half an hour of normal temperature reaction. That is.
  • the elastic modulus adjustable polyurethane composition of the invention and the application thereof in medical implant materials include: implanted devices, implantable artificial organs, contact artificial organs, stents, interventional catheters, and organ assist devices, Specifically, it includes bone plate, bone nail, bone needle, bone rod, spinal internal fixation equipment, ligation wire, polypigment, bone wax, bone repair material, brain aneurysm clip, silver clip, vascular anastomosis clip (device), plastic material , cardiac or tissue repair materials, intraocular filling materials, birth control rings, nerve patches; implantable artificial organs include: artificial esophagus, artificial blood vessels, artificial vertebral bodies, artificial joints, artificial urethra, artificial valves, artificial kidneys, meaning Milk, artificial skull, artificial jaw, artificial heart, artificial tendon, cochlear implant, artificial anal closure; touch artificial organs include: artificial throat, artificial skin, artificial cornea; stent blood vessels specifically include: stent, prostate stent, biliary tract Stent,
  • a specific ratio of ⁇ -caprolactone and PEG is used to synthesize linear polycaprolactone diol, which is reacted with LDI and BDO, stannous octoate (0.01-0.1 wt% of the total amount) as a catalyst, and finally L- Lysine triisocyanate acts as a blocking agent to give the final product, such as Examples 34-41.
  • linear lactic acid-glycolic acid copolyol is synthesized using a specific molecular weight (molecular weight range 200-2000) of PLA, PGA, PLGA and different diols, and the product is reacted with different diisocyanates, stannous octoate (total 0.01 -0.1 wt%) as a catalyst, the reaction gives the final product, such as Examples 52-56.
  • the invention also discloses a degradable stent composition
  • the stent supporting material is a degradable metal material
  • the coating or coating material is a degradable medical polyurethane material
  • the weight percentage of the two is 1-99%: 1%-99 More preferably, the weight percentage is 5-90%: 10%-95%
  • the degradable medical polyurethane material is selected from the group consisting of polylactic acid type polyurethane, polycaprolactone type polyurethane, and two degradable polyurethane derivatives (silicone, poly One or two of amino acid modification, polysaccharide modification, wherein the polyisocyanate selected for the hard segment is preferably non-toxic and free of benzene rings, such as hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), L-lysine diisocyanate (LDI), L-lysine triisocyanate, etc., preferably poly( ⁇ -caprolactone) glycol (PCL
  • the degradation product is an amino acid-lysine in the human body
  • the range of a is 5-50, and the range of b is 5-50.
  • the range of x is 5-50, and the range of y is 5-50.
  • the degradable stent composition disclosed in the invention wherein the selected polyurethane can synthesize linear polycaprolactone diol with different ratios of ⁇ -caprolactone and PEG of different molecular weight (molecular weight 200-2000), and the products thereof are different
  • the diisocyanate reaction uses a different diol as a chain extender, and stannous octoate (0.03 wt% of the total amount) is used as a catalyst to obtain a final product.
  • the degradable stent composition disclosed in the invention, wherein the selected polyurethane can also use PLA, PGA, PLGA and different glycols with specific molecular weight (molecular weight range 200-2000).
  • a linear lactic acid-glycolic acid copolyol is reacted with a different diisocyanate, and stannous octoate (0.03 wt% of the total amount) is used as a catalyst to obtain a final product.
  • the degradable stent composition disclosed in the invention wherein the selected polyurethane can also be the above polycaprolactone type polyurethane linear molecule and the polylactic acid type polyurethane linear molecule, and the lysine triisocyanate is added to form a network crosslinked structure.
  • Forming an ultra-high elastic polyurethane composition specifically comprising the following polyurethane synthesis reaction:
  • diisocyanate is selected from the group consisting of: 1,6-hexamethylene diisocyanate, isophorone diisocyanate, lysine methyl ester diisocyanate, cis-cyclohexane diisocyanate, trans-cyclohexane diisocyanate, 1,4-butane diisocyanate, 1,2-ethane diisocyanate, 1,3-propane diisocyanate, 4,4'-methylene-bis(cyclohexyl isocyanate), 2,4,4-trimethyl One or two of 1,6-hexane diisocyanate;
  • chain extender glycol is selected from the group consisting of ethylene glycol, diethylene glycol, tetraethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,6-hexanediol, 1,7-heptanediol One or two of 1,8-octanediol, 1,9-nonanediol, and 1,10-decanediol.
  • L-lysine triisocyanate is added to the obtained product of the above method to carry out capping to prepare a polyurethane having a high elastic modulus, and the preparation method is as follows:
  • the final product obtained by the method according to claim 4 is reacted in a twin-screw extruder extruder for 20 minutes in an environment having a moisture content of less than 10 ppm, and the mixture is stirred and extruded to obtain a polyurethane having a high elastic modulus. fiber;
  • Method 2 The final product obtained by the method according to claim 4 is poured into a kneader or a kneader in an environment having a moisture content of less than 10 ppm, and directly added with L-lysine triisocyanate, and stirred at room temperature for half an hour. That is;
  • Method 3 After the reaction is completed according to the method of claim 4, an anhydrous organic solvent is added to prepare a viscous solution, and L-lysine triisocyanate is directly added in an environment having a moisture content of less than 10 ppm, and the reaction system is stirred or shaken.
  • organic solvent is selected by vacuum extraction, wherein the organic solvent is selected from the group consisting of toluene, p-xylene, decane, isoamyl acetate, hexane, benzene, dichloromethane, chloroform, 1, 4-cyclohexanone, ketone, One or two of dimethylformamide, heptane, dimethylcarbamate, tetrahydrofuran, petroleum ether, dimethyl sulfoxide, ethylene terephthalate, preferably tetrahydrofuran, dichloromethane, trichloro One or a combination of methane and 1,4 cyclohexanone.
  • the organic solvent is selected from the group consisting of toluene, p-xylene, decane, isoamyl acetate, hexane, benzene, dichloromethane, chloroform, 1, 4-cyclohexanone, ketone, One or two of dimethylformamide
  • the degradable stent composition disclosed by the invention can add other polymer materials according to the soft and hard need of the stent peritoneum, such as polylactic acid, polycaprolactone, polydioxanone and its copolymer (PPDO, PLA-PDO) polydioxanone (PPDO), polytrimethylene carbonate, polylactic acid-trimethylene carbonate copolymer, polycaprolactone-trimethylene carbonate copolymer, polyglycolic acid , polylactic acid-glycolic acid copolymer, polyetheretherketone, polyvinylpyrrolidone and/or polyethylene glycol, polyvalerolactone, poly- ⁇ -decalactone, polylactide, polyglycolide, polylactide Copolymer with polyglycolide, poly- ⁇ -caprolactone, polyhydroxybutyric acid, polyhydroxybutyrate, polyhydroxyvalerate, polyhydroxybutyrate-co-valerate, poly(1, 4-dioxane
  • Tributyl citrate TBC
  • acetyl tributyl citrate ATBC
  • trioctyl trimellitate tris(810) trimellitate
  • triglyceride trimellitate TPC
  • pyromellitic acid IV Octyl ester diethylene glycol dibenzoate, diethylene glycol dibenzoate, dipropylene glycol dibenzoate, dioctyl terephthalate, dioctyl terephthalate, sebacate
  • ester and epoxidized soybean oil TBC
  • the degradable metal material disclosed by the invention has the components of iron, copper, zinc, cobalt, manganese, chromium, selenium, iodine, nickel, fluorine, molybdenum, vanadium, tin, silicon, germanium, boron, antimony, arsenic, silver,
  • the weight percentage of the magnesium alloy material is: 0-2.0% of iron, 0-2.0% of copper, 0-2.0% of zinc, 0-2.0% of cobalt, 0-2.0% of manganese, chromium 0-2.0%, selenium 0-2.0%, iodine 0-2.0%, nickel 0-2.0%, fluorine 0-2.0%, molybdenum 0-2.0%, vanadium 0-2.0%, tin 0-2.0%, silicon 0- 2.0%, ⁇ 0-2.0%, boron 0-2.0%, ⁇ 0-2.0%, silver 0.1-4%; including: high-purity iron (purity greater than 99.0%), high
  • magnesium iron alloy weight ratio is preferably 1:0.01-0.1
  • magnesium-zinc alloy weight ratio is preferably 1:0.01-0.1
  • Mg-Nd-Zn-Zr Mg-Zn-Mn
  • Mg-Zn-Mn -Se-Cu alloy Zn content of 3.5 wt%
  • Mn content of 0.5-1.0 wt% Se content of 0.4-1.0 wt%
  • magnesium-calcium alloy weight The percentage is preferably 1:0.01-0.1)
  • magnesium aluminum alloy weight ratio is preferably 1:0.01-0.1, such as: aluminum (Al): 2.0-3.0 wt.%, zinc (Zn): 0.5-1.0 wt.% , manganese (Mn), Mg balance.
  • coated stent disclosed in the present invention is prepared as follows:
  • Dissolving polymer A a degradable medical polyurethane material in an organic solvent to prepare a coating material (material concentration: 5-50%, specifically dissolving the polyurethane in a tetrahydrofuran solution to prepare a 10-30% solution);
  • the metal stent prepared in (1) by (2) repeated dip coating, spraying or electrospinning on the surface of the stent, at least partially coating a pillar forming a grid or a grid to form a coated composite stent.
  • the thickness of the coated material is preferably between 0.01 and 3 mm, preferably between 0.01 and 0.5 mm.
  • the peritoneal stent disclosed in the present invention is prepared as follows:
  • the metal stent prepared in (1) is wound on the surface of the metal material by the film prepared in (2) to form a film stent;
  • the composite material prepared in (3) is dried, polished and polished by dip coating or spraying a hydrophilic coating (such as chitosan, hyaluronic acid, collagen, cellulose, etc.).
  • a hydrophilic coating such as chitosan, hyaluronic acid, collagen, cellulose, etc.
  • the stent disclosed in the invention is prepared by 3D printing technology:
  • magnesium alloy powder (powder diameter range: 10 nm - 1 mm, excellent 1um-100um) is mixed with a degradable medical polyurethane material solution (organic dissolved and dissolved, configured as a viscous solution of 20-90% concentration, preferably a 30-50% concentration of tetrahydrofuran or chloroform solution), and passed through 3D.
  • the printer prints a bracket that requires a diameter and a wall thickness, and the hot air is dried to evaporate the dry organic solvent;
  • Preparation method 2 3D printer is equipped with two feeding devices, one feeding device is added with magnesium alloy powder (the powder diameter ranges from 10 nm to 1 mm, preferably 1 um to 100 um), and another feeding device is added with degradable medical polyurethane. a material solution (configured in an organic solvent to a concentration of 20-90%, preferably 30-50% concentration in tetrahydrofuran or chloroform), and the two materials are mixed in proportion during the feeding process to print the set size and shape. The support, hot air drying volatile organic solvent is obtained.
  • Preparation method 3 3D printer is provided with two feeding devices, one feeding device is added with magnesium alloy powder (the powder diameter ranges from 10 nm to 1 mm, preferably 1 um to 100 um), and another feeding device is added with degradable medical polyurethane.
  • the material and the polylactic acid are mixed and dissolved in an organic solvent in a ratio (1:0.1-10), and are disposed in an organic solvent to a concentration of 20-90%, preferably 30-50% concentration of tetrahydrofuran or chloroform solution, two kinds.
  • the material is mixed in proportion during the feeding process, and the stent of the set size and shape is printed, and the hot air is dried to evaporate the dry organic solvent.
  • Preparation method 4 The 3D printer is provided with two feeding devices, and a magnesium alloy powder is added to a feeding device (the powder diameter ranges from 10 nm to 1 mm, preferably 1 um to 100 um), and the high temperature melting prints the stent as needed, and is passivated. The treatment is reserved; another defeeding device is added with a degradable medical polyurethane material and polylactic acid in a ratio (1:0.1-10) mixed and dissolved in an organic solvent, and is disposed in an organic solvent to a percentage concentration of 20-90% on the stent. The coating film is printed, and the hot air is dried to evaporate the dry organic solvent.
  • the magnesium alloy powder (the diameter of the powder is in the range of 10 nm to 1 mm, preferably 1 um to 100 um) can be passivated according to the various methods disclosed in accordance with the requirements of the degradation time of the stent.
  • a corrosion-resistant, non-toxic conversion film (the diameter of the powder is in the range of 10 nm to 1 mm, preferably 1 um to 100 um)
  • the organic solvent of the present invention is selected from the group consisting of toluene, p-xylene, decane, isoamyl acetate, hexane, benzene, dichloromethane, chloroform, cyclohexanone, ketone, dimethylformamide, One or two of heptane, dimethylcarbamate, tetrahydrofuran, petroleum ether, dimethyl sulfoxide, ethylene terephthalate, preferably tetrahydrofuran, decane, isoamyl acetate, hexane, two One or two of methyl chloride, chloroform, cyclohexanone, dimethylformamide, and heptane.
  • the double balloon design of the delivery urethral stent as shown in Figure 1, the design principle of the urethral stent: usually the diameter of the urethral stent is 4-7mm, the length is 3-5cm, and the stent is processed into a pattern that can be expanded and supported, and installed on the ball.
  • the manner of the capsule can be squeezed on the balloon by the tension of the stent tube itself, or it can be crimped and adhered to the balloon, installed in place with the expansion of the balloon, placed in the prostatic urethra, and the urethra
  • the distal end of the stent is 3-5 mm from the urethral sphincter, so that the urethral stent can both expand the urethra without damaging the sphincter.
  • the polymer material used for preparation of the balloon and the stent comprises a contrast agent, specifically one selected from the group consisting of zirconium dioxide, barium sulfate and iodine, wherein the material used for the balloon is added such as polyvinyl chloride or dry glue.
  • iodine preparations for contrast imaging in preparation of urethral stents such as diatrizoate, iodine, diazonic acid, iodine Phenylhexaol, iopromide and iupamidol.
  • the balloon design of the delivery vessel stent is consistent with commercially available products.
  • the organic solvent of the present invention is selected from the group consisting of toluene, p-xylene, decane, isoamyl acetate, hexane, benzene, dichloromethane, chloroform, cyclohexanone, ketone, dimethylformamide, One or two of heptane, dimethylcarbamate, tetrahydrofuran, petroleum ether, dimethyl sulfoxide, ethylene terephthalate, preferably tetrahydrofuran, chloroform, toluene, p-xylene, acetic acid One of amyl ester or hexane.
  • the stent of the present invention comprises a contrast agent, specifically selected from the group consisting of zirconium dioxide, barium sulfate and iodine
  • a contrast agent specifically selected from the group consisting of zirconium dioxide, barium sulfate and iodine
  • One of the preparations must be added in an amount of 1 to 20%, preferably 2 to 10% by weight based on the polymer material.
  • the anticoagulant component is cross-linked by the cross-linking agent such as glutaraldehyde on the surface of the treated bare stent, and the blood coagulation component can select hirudin, heparan sulfate and its derivative.
  • the cross-linking agent such as glutaraldehyde
  • the blood coagulation component can select hirudin, heparan sulfate and its derivative.
  • complete desulfurization and N-reacetylated heparin desulfurization and N-reacetylated heparin are prepared as anticoagulant coatings that do not activate blood coagulation.
  • a corrosion-resistant non-toxic conversion membrane can be formed on the surface of the degradable magnesium alloy, and a phosphate conversion membrane method, a phytic acid conversion membrane, a rare earth salt conversion membrane method, and an organic conversion coating film are commonly used.
  • the method, or fluorination treatment on the surface of the bare stent is specifically to polish the untreated biodegradable magnesium alloy stent, and soak for 12 to 96 hours in a mass percentage of 20-40% hydrofluoric acid.
  • the degradable stent composition of the present invention is characterized in that commercially available or already disclosed polypeptides, proteins and active ingredients, including anti-proliferation, anti-migration, anti-angiogenesis, anti-drug, can be added to the polyurethane material according to clinical needs.
  • Physiologically active drugs for inflammation, anti-inflammatory, cytostatic, cytotoxic or antithrombotic effects such as sirolimus, everolimus, pimecrolimus, melanin, ifosfamide, tromethamine, Chlorambucil, bendamustine, somatostatin, tacrolimus, roxithromycin, daunorubicin, ascomycin, bafilomycin, ramustine, cyclophosphamide, Estrostatin, dacarbazine, erythromycin, medimycin, spectabilin, concanavalin, clarithromycin, oleandomycin, vinblastine, vincristine, vindesine , vinorelbine, etoposide, teniposide, nimustine, carmustine, busulfan, procarbazine, troxulfan, temozolomide, thiotepa, doxorubicin, arou Star, epirubicin, mito
  • the raw materials used in this example were pretreated to a moisture content of less than 10 ppm for use.
  • Glycolic acid (4g), L-lactic acid (12g) and BDO (1.1g) were weighed into a vacuum reaction flask, dried at 80 ° C under high vacuum, and stopped at 150 ° C for 48 h.
  • HDI (2 g) and octanoic acid were added.
  • Tin (0.02% by weight of total) was reacted in an oil bath at 70 ° C for 6 h to obtain the final product.
  • the vacuum reaction flask was taken out and cooled to room temperature, and 0.6 g of L-lysine triisocyanate was added for blocking, shaking or stirring at room temperature. The final product was obtained in 30 min.
  • Glycolic acid (8g), DL-lactic acid (12g) and BDO (1.5g) were weighed into a vacuum reaction flask, dried at 80 ° C under high vacuum, and stopped at 170 ° C for 24 h. The reaction was stopped and IPDI (2 g) and octanoic acid were added. Tin (0.02 wt% of the total amount) was reacted in an oil bath at 70 ° C for 4 h to obtain a final product. The vacuum reaction flask was taken out and cooled to room temperature, and 1.0 g of L-lysine triisocyanate was added for blocking, and the mixture was repeatedly passed through a kneading machine. The mixture was stirred for 30 min to obtain the final product.
  • Glycolic acid (4g), DL-lactic acid (12g) and 1,6-hexanediol (1.8g) were weighed into a vacuum reaction flask, dried at 80 ° C under high vacuum, and reacted at 150 ° C for 24 h, then stopped, and added IPDI.
  • (2g) and stannous octoate (0.02wt% of total amount) were reacted in an oil bath at 70 ° C for 6 h, the vacuum reaction flask was taken out and cooled to room temperature, and the material was dissolved by adding 20 ml of tetrahydrofuran, and 1.0 g of L-lysine was added. The isocyanate was capped and stirred for 30 min to give the final product. The final product is obtained.
  • Glycolic acid (8g), L-lactic acid (12g) and BDO (0.8g) were weighed into a vacuum reaction flask, dried at 80 ° C under high vacuum, and reacted at 150 ° C for 24 h, then stopped, and added LDI (2.8 g) and octanoic acid.
  • Stannous (0.02 wt% of the total amount) was reacted in an oil bath at 70 ° C for 6 h, the vacuum reaction flask was taken out and cooled to room temperature, the material was dissolved by adding 20 ml of tetrahydrofuran, and 1.6 g of L-lysine triisocyanate was added for blocking. Stir for 30 min to give the final product. The final product is obtained.
  • glycolic acid (4g), DL-lactic acid (12g) and 1,6-hexanediol (1.8g) were weighed into a vacuum reaction flask, dried at 80 ° C under high vacuum, and reacted at 150 ° C for 24 h.
  • LDI (2 g) and stannous octoate (0.02 wt% of total) were added and reacted in an oil bath at 70 ° C for 6 h to obtain a final product.
  • the vacuum reaction flask was taken out and cooled to room temperature, and the moisture content was less than 10 ppm.
  • L-lysine triisocyanate 0.5g 1.0g 2.0g Elastic Modulus 300MPa 380MP 550MP Elongation at break 200% 120% 70%
  • Example 57 According to the product of each component in Example 57, the mixture was mixed in a high-vacuum mixer to prepare a fiber having a diameter of 0.3-0.35 mm, and the physiological saline solution at 37 ° C was changed every day to observe the degradation and determine the elongation of the fiber.
  • the rate is once a week, and the experimental results are as follows:
  • magnesium alloy compositions selected in Examples 1-9 are as follows:
  • Magnesium metal stent materials can also be selected from high purity magnesium or high purity iron depending on the degradation time.
  • Example 1 vascular stent graft
  • the preparation process is as follows:
  • a hydrophilic coating such as an aqueous solution made of chitosan, hyaluronic acid, collagen, cellulose, etc.
  • the double balloon urethral stent shown in Fig. 1 is made of silica gel material.
  • the stent is pressed or adhered to the columnar balloon, and after being placed in the urethra, the balloon is injected into the balloon, and the columnar balloon expands the stent and supports The urethra area.
  • the peritoneal urethral stent is prepared as follows:
  • the frame is 3mm in diameter and 2cm in length;
  • stent graft Drying, polishing, and polishing the composite material prepared in (3) by dip coating or spraying a hydrophilic coating (such as an aqueous solution made of chitosan, hyaluronic acid, collagen, cellulose, etc.) As a stent graft.
  • a hydrophilic coating such as an aqueous solution made of chitosan, hyaluronic acid, collagen, cellulose, etc.
  • Glycolic acid (4g), L-lactic acid (12g) and BDO (1.1g) were weighed into a vacuum reaction flask, dried at 80 ° C under high vacuum, and stopped at 150 ° C for 48 h.
  • HDI (2 g) and octanoic acid were added.
  • Tin (0.02 wt% of the total amount) was reacted in an oil bath at 70 ° C for 6 h to obtain a final product, which was capped by adding 0.6 g of L-lysine triisocyanate under vacuum, and shaken at room temperature or stirred for 30 min to obtain a final product.
  • Glycolic acid (4g), DL-lactic acid (12g) and 1,6-hexanediol (1.8g) were weighed into a vacuum reaction flask, dried at 80 ° C under high vacuum, and reacted at 150 ° C for 24 h, then stopped, and added IPDI. (2g) and stannous octoate (0.02% by weight of total) were reacted in an oil bath at 70 ° C for 6 h to obtain a final product.
  • the vacuum reaction flask was taken out and cooled to room temperature, and 1.0 g of L-lysine triisocyanate was added for sealing. At the end, the kneading machine was repeatedly kneaded and stirred for 30 minutes to obtain a final product.
  • Glycolic acid (8g), L-lactic acid (12g) and BDO (0.8g) were weighed into a vacuum reaction flask, dried at 80 ° C under high vacuum, and reacted at 150 ° C for 24 h, then stopped, and added LDI (2.8 g) and octanoic acid.
  • Stannous (0.02 wt% of the total amount) was reacted in an oil bath at 70 ° C for 6 h, the vacuum reaction flask was taken out and cooled to room temperature, the material was dissolved by adding 20 ml of tetrahydrofuran, and 1.6 g of L-lysine triisocyanate was added for blocking. Stir for 30 min to give the final product. The final product is obtained.
  • the preparation process is as follows:
  • Degradable metal materials (the alloy composition ratio is selected according to 1 in the list or 99% magnesium content, 1% Mn content)
  • Magnesium-manganese alloy is drawn into a tube with an outer diameter of 1 mm, a wall thickness of 0.2 mm and a length of 40 cm, and is engraved into a desired pattern (the schematic diagram after the tube is unfolded is shown in Fig. 6);
  • a 3D printer with two feeding devices is selected, a magnesium alloy powder (powder particle size of 30-80 um) is added to one feeding device, and a polymer material (degradable medical polyurethane material and polylactic acid are added in proportion to another feeding device) 1:1), chloroform is set to a concentration of 30% solution), ureteral stent length (15-40cm, evenly divided into 8 segments), magnesium alloy powder: polymer material weight ratio from (1:11) : 8) It is divided into 8 parts of gradient printing, and the bracket of the set size and shape is printed, and the hot air is dried to evaporate the dry organic solvent.
  • the printed bracket can be surface treated by dip coating or spraying according to product requirements.
  • a 3D printer with two feeding devices is selected, and a magnesium alloy powder (powder particle size of 30-80 um) is added to a feeding device, and the stent is printed at a high temperature and melted as needed, and passivation is used for standby, and another feeding device is used.
  • a magnesium alloy powder powder (powder particle size of 30-80 um) is added to a feeding device, and the stent is printed at a high temperature and melted as needed, and passivation is used for standby, and another feeding device is used.
  • polymer materials degradable medical polyurethane material and polylactic acid in proportion (1:3), using chloroform to form a 50% solution
  • printing the coating film and drying the volatile organic solvent by hot air Got it.
  • Example 7 Degradation of double balloon urethral stent Beagle implant
  • the double balloon urethral stent prepared in Examples 1 and 2 was sterilized with ethylene oxide.
  • Six Beagle dogs weighing about 12KG were selected and placed in the urethra of the dogs for observation, 3 in each group.
  • the degree of swelling of the urethra, serological and histological sections were observed regularly after operation.
  • the experimental results showed that the stent in Example 1 began to degrade after 2 weeks, and the degradation was complete at 6 weeks.
  • the stent in Example 2 began to degrade at 4 weeks, completely degraded at 8 weeks, and the inflammatory reaction of the urethra was light, and the tissue compatibility was good. , has a very good supporting role.

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Abstract

L'invention concerne une composition de polyuréthane à module d'élasticité ajustable, un composite d'échafaudage et son procédé de préparation. Les propriétés de PU, telles que l'élasticité, le module, la résistance, le module d'élasticité, la résistance à l'abrasion, le pouvoir lubrifiant, la propriété hydrophile-hydrophobe de PU, etc., peuvent être variées dans une large plage en ajustant les proportions de la composition et le poids moléculaire de chaque élément, et le PU peut être utilisé pour préparer une variété de produits médicaux pour l'intervention d'implantation dans le corps humain nécessitant différents degrés de souplesse et de dureté et étant biocompatibles, en particulier comprenant un dispositif implantable, un organe artificiel implantable, un organe artificiel de contact, un échafaudage, un dispositif auxiliaire d'organe, etc.
PCT/CN2016/078430 2015-09-30 2016-04-05 Composition de polyuréthane à module d'élasticité ajustable, composite d'échafaudage et son procédé de préparation Ceased WO2017054433A1 (fr)

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
CN201510638995.9 2015-09-30
CN201510638995 2015-09-30
CN201510651224.3 2015-10-12
CN201510651223.9A CN105457092A (zh) 2015-10-12 2015-10-12 一种弹性模量可调聚氨酯组合物及其在医用植入材料中的应用
CN201510651224.3A CN105169496A (zh) 2015-09-30 2015-10-12 一种可降解支架组合物
CN201510651223.9 2015-10-12

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Cited By (16)

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CN109021907A (zh) * 2018-09-03 2018-12-18 孙桂芝 一种合成革用高粘结性水性聚氨酯粘合剂的制备方法
EP3501543A1 (fr) 2017-12-19 2019-06-26 Delim Cosmetics & Pharma S.r.l. Procédé de fabrication de systèmes de distribution de médicament vaginal au moyen d'une imprimante trois dimensions
CN111714260A (zh) * 2020-07-17 2020-09-29 上海浦瑞通医疗科技有限公司 一种支架及其应用
CN111848918A (zh) * 2020-06-28 2020-10-30 梅其勇 一种血管支架用可生物降解聚氨酯及其合成方法
KR20210021056A (ko) * 2018-08-11 2021-02-24 주식회사 쿠라레 연마층용 폴리우레탄, 연마층 및 연마 패드
CN112745471A (zh) * 2020-12-29 2021-05-04 南京理工大学 室温本征自修复玻璃态聚合物材料及其制备方法
CN112979912A (zh) * 2021-02-25 2021-06-18 苏州大学 超强韧聚乳酸基聚氨酯脲及其制备方法
CN113118455A (zh) * 2021-04-23 2021-07-16 吉林大学重庆研究院 一种基于浆料直写的制备金属人工骨3d打印方法
WO2021212899A1 (fr) * 2020-04-21 2021-10-28 He Jianxiong Matériau d'impression 3d biomédicale à base de tpu et procédé de préparation associé
CN114209892A (zh) * 2021-12-01 2022-03-22 中国地质大学(北京)郑州研究院 一种颅骨固定复合材料及其制备方法
CN115253071A (zh) * 2021-04-30 2022-11-01 微创投资控股有限公司 人工耳蜗植入装置及人工耳蜗
CN115667344A (zh) * 2020-05-29 2023-01-31 马斯特里赫特大学医学中心 聚合物组合物和制造医用植入物的方法
CN116041654A (zh) * 2022-12-28 2023-05-02 四川大学 一种可自适应贴合、抗菌消炎的可吸收胰腺引流管及其制备方法
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EP3834987A4 (fr) * 2018-08-11 2022-05-04 Kuraray Co., Ltd. Polyuréthane pour couche de polissage, couche de polissage et tampon de polissage
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KR102524174B1 (ko) 2018-08-11 2023-04-20 주식회사 쿠라레 연마층용 폴리우레탄, 연마층 및 연마 패드
KR20210021056A (ko) * 2018-08-11 2021-02-24 주식회사 쿠라레 연마층용 폴리우레탄, 연마층 및 연마 패드
CN109021907A (zh) * 2018-09-03 2018-12-18 孙桂芝 一种合成革用高粘结性水性聚氨酯粘合剂的制备方法
WO2021212899A1 (fr) * 2020-04-21 2021-10-28 He Jianxiong Matériau d'impression 3d biomédicale à base de tpu et procédé de préparation associé
CN115667344B (zh) * 2020-05-29 2025-08-22 马斯特里赫特学术医院 聚合物组合物和制造医用植入物的方法
CN115667344A (zh) * 2020-05-29 2023-01-31 马斯特里赫特大学医学中心 聚合物组合物和制造医用植入物的方法
CN111848918A (zh) * 2020-06-28 2020-10-30 梅其勇 一种血管支架用可生物降解聚氨酯及其合成方法
CN111714260B (zh) * 2020-07-17 2024-05-17 上海浦瑞通医疗科技有限公司 一种支架及其应用
CN111714260A (zh) * 2020-07-17 2020-09-29 上海浦瑞通医疗科技有限公司 一种支架及其应用
CN112745471A (zh) * 2020-12-29 2021-05-04 南京理工大学 室温本征自修复玻璃态聚合物材料及其制备方法
CN112745471B (zh) * 2020-12-29 2022-08-09 南京理工大学 室温本征自修复玻璃态聚合物材料及其制备方法
CN112979912A (zh) * 2021-02-25 2021-06-18 苏州大学 超强韧聚乳酸基聚氨酯脲及其制备方法
CN113118455A (zh) * 2021-04-23 2021-07-16 吉林大学重庆研究院 一种基于浆料直写的制备金属人工骨3d打印方法
CN113118455B (zh) * 2021-04-23 2022-11-11 吉林大学重庆研究院 一种基于浆料直写的制备金属人工骨3d打印方法
CN115253071A (zh) * 2021-04-30 2022-11-01 微创投资控股有限公司 人工耳蜗植入装置及人工耳蜗
CN114209892A (zh) * 2021-12-01 2022-03-22 中国地质大学(北京)郑州研究院 一种颅骨固定复合材料及其制备方法
CN116041654B (zh) * 2022-12-28 2024-05-17 四川大学 一种可自适应贴合、抗菌消炎的可吸收胰腺引流管及其制备方法
CN116041654A (zh) * 2022-12-28 2023-05-02 四川大学 一种可自适应贴合、抗菌消炎的可吸收胰腺引流管及其制备方法
CN116102942B (zh) * 2023-02-24 2023-11-14 安徽省奥佳建材有限公司 一种防腐耐高温水性聚氨酯涂料及其制备方法
CN116102942A (zh) * 2023-02-24 2023-05-12 安徽省奥佳建材有限公司 一种防腐耐高温水性聚氨酯涂料及其制备方法
CN117143314A (zh) * 2023-10-23 2023-12-01 广东华博润材料科技有限公司 一种功能性生物基热塑性聚氨酯复合材料及其制备方法
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