WO2018145528A1 - Instrument médical - Google Patents

Instrument médical Download PDF

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Publication number
WO2018145528A1
WO2018145528A1 PCT/CN2017/119223 CN2017119223W WO2018145528A1 WO 2018145528 A1 WO2018145528 A1 WO 2018145528A1 CN 2017119223 W CN2017119223 W CN 2017119223W WO 2018145528 A1 WO2018145528 A1 WO 2018145528A1
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WO
WIPO (PCT)
Prior art keywords
group
ligand
acid
medical device
degradable polymer
Prior art date
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PCT/CN2017/119223
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English (en)
Chinese (zh)
Inventor
张德元
齐海萍
林文娇
Original Assignee
先健科技(深圳)有限公司
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
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Application filed by 先健科技(深圳)有限公司 filed Critical 先健科技(深圳)有限公司
Priority to CN201780062498.6A priority Critical patent/CN109803693B/zh
Priority to CN202211475122.7A priority patent/CN115845152A/zh
Publication of WO2018145528A1 publication Critical patent/WO2018145528A1/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
    • 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
    • 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
    • A61L31/14—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

Definitions

  • the invention relates to a medical device.
  • metals are particularly popular because of their superior mechanical properties such as high strength and high toughness.
  • the corrosion of metal materials may bring two disadvantages: first, the formation of solid corrosion products, which are difficult to be absorbed/metabolized in the long-term existence, such as iron-based materials; second, higher metal ion concentration may cause toxicity. For example, zinc corrosion produces zinc ions.
  • iron participates in many biochemical processes, such as the transport of oxygen.
  • Peuster M et al. used pure iron as a material to make a pure iron stent similar in shape to the clinically used metal stent by laser engraving, and implanted into the descending aorta of New Zealand rabbits.
  • the results showed that no thrombotic complications occurred during the 6- to 18-month period of pure iron stent implantation, and no adverse events occurred.
  • Pathological examination confirmed that there was no inflammatory reaction in the local blood vessel wall, and there was no obvious proliferation of smooth muscle cells, indicating that iron-based materials were produced.
  • the implanted device has a good application prospect.
  • the iron-based matrix gradually corrodes in a physiological solution to form corrosion products, including metal ions and Fe(OH) 3 , FeOOH, A solid corrosion product such as Fe 2 O 3 , Fe 3 O 4 , Fe 3 (PO 4 ) 2 or the like.
  • These solid corrosion products have low solubility, are insoluble in body fluids, and are mostly in the form of loose precipitates, which are difficult to be absorbed/metabolized by tissues, resulting in a long absorption period of medical devices and long-term retention in tissues, and iron-based medical devices are Corrosion in the body produces solid corrosion products. Although these particles can be absorbed and metabolized by the flow of intercellular fluid and macrophage phagocytosis, the process lasts for a long time and greatly prolongs the absorption cycle of implanted medical devices.
  • metal corrosion can also generate free metal ions, which can cause cytotoxicity when the concentration of metal ions is too high. It has been reported that the cytotoxicity (half lethal dose) of zinc ions on fibroblasts, smooth muscle cells and endothelial cells is 50 ⁇ mol/L, 70 ⁇ mol/L and 265 ⁇ mol/L, respectively.
  • Ligand is also called ligand and complexing agent.
  • the ligand structure contains lone pairs of electrons or ⁇ electrons as a coordination group, which can coordinate with metal ions to form water-soluble coordination compounds and reduce free metals.
  • the concentration of ions reduces the solid corrosion product (equation (1)).
  • the prior art discloses that the application of a ligand to an iron-based alloy medical device by physical mixing can complex iron corrosion products to a certain extent to form a water-soluble iron complex, which contributes to the removal of iron corrosion products.
  • complexing agents are rarely used due to factors such as the solubility and carrying capacity of the complexing agent.
  • water-soluble ligands are rapidly dissolved and lost in body fluids, and the corrosion cycle of iron is as long as one year or more.
  • it is difficult to form a ligand and it is difficult to load a large amount onto the surface of a medical device.
  • a medical device comprising a corrodible metal matrix and a ligand-degradable polymer obtained by reacting a degradable polymer with a ligand capable of degrading And releasing a coordinating group capable of coordinating reaction with the corrosion product generated by the corrodible metal matrix under a physiological environment to form a water-soluble coordination compound.
  • a medical device of an embodiment comprises a corrodible metal matrix and a ligand-degradable polymer obtained by reacting a degradable polymer with a ligand, the ligand-degradable polymer being capable of degrading and The coordination group is released, and the coordination group can coordinate with the corrosion product generated by the corrodible metal matrix to form a water-soluble coordination compound under physiological environment.
  • the material of the corrodible metal substrate is at least one selected from the group consisting of Fe, Zn, Mg, an iron alloy, a zinc alloy, and a magnesium alloy.
  • the corrodible metal substrate is an iron alloy or a zinc alloy.
  • the iron alloy is at least one of an iron carbon alloy and a nitriding iron alloy.
  • the iron alloy may also be an iron-based alloy doped with at least one of O, S, P, Mn, Pd, Si, W, Ti, Co, Cr, Cu, Re;
  • a zinc-based alloy having at least one of C, N, O, S, P, Ce, Mn, Ca, Cu, Pd, Si, W, Ti, Co, Cr, Cu, and Re.
  • the mass percentage of Fe in the iron alloy is 50% to 99.99%.
  • the mass percentage of Zn in the zinc alloy is 50% to 99.99%.
  • the corrosion product is a metal ion.
  • the metal ion includes at least one of iron ions, zinc ions, and magnesium ions.
  • the corrosion product further comprises a solid corrosion product.
  • the solid corrosion products are usually Fe(OH) 3 , FeOOH, Fe 2 O 3 , Fe 3 O 4 .
  • the volume ratio of the ligand-degradable polymer to the corrodible metal substrate is from 0.1:1 to 20:1.
  • the corrosive metal matrix is corroded to generate metal ions or solid corrosion products, and the ligand group in the ligand-degradable polymer and the metal ion or solid corrosion product occur under physiological conditions.
  • the coordination reaction produces a water-soluble coordination compound.
  • the water-soluble coordination compound can be metabolized and absorbed by the organism faster, which is beneficial to the recovery of the lesion.
  • the water-soluble coordination compound can greatly degrade the concentration of free metal ions and reduce the risk of metal ions producing cytotoxicity.
  • the medical device can be a vascular stent, a non-vascular endoluminal stent, an occluder, an orthopedic implant, a dental implant, a respiratory implant, a gynecological implant, a male implant, a suture or a bolt.
  • the non-vascular endoluminal stent can be a tracheal stent, an esophageal stent, a urethral stent, an intestinal stent, or a biliary stent.
  • the orthopedic implant can be a set screw, a fixed rivet or a bone plate.
  • other medical devices that require degradable absorption can be used as the medical device of the present embodiment.
  • both the ligand-degradable polymer and the corrodible metal matrix are capable of being biologically accepted for implantation into a living organism.
  • the ligand-degradable polymer is at least partially in contact with the corrodible metal matrix.
  • the contact manner of the ligand-degradable polymer with the corrodible metal substrate may be any one or more of the following.
  • the ligand-degradable polymer forms a coating on the surface of the corrodible metal substrate. Further, the coating is covered by spraying, dip coating, brushing or electrospinning the ligand-degradable polymer solution by disposing the ligand-degradable polymer into a ligand-degradable polymer solution. It can corrode the surface of the metal substrate. Of course, the coating may cover only the surface of the corrodible metal substrate portion or the entire surface of the corrodible metal substrate.
  • the ligand-degradable polymer solution further contains an active drug such that the resulting coating contains a ligand-degradable polymer and an active drug mixed with the ligand-degradable polymer.
  • the coating covers 5% to 100% of the surface of the metal substrate. Preferably, the coating covers 100% of the surface of the corrodible metal substrate.
  • the thickness of the coating is flexibly set according to the specific type of medical device, such as the small size of the coronary stent, the thickness of the coating does not exceed 70 microns, and the thickness of the coating in the fixed plate can reach 1 mm.
  • the corrodible metal substrate is provided with a receiving portion, and the ligand-degradable polymer is accommodated in the receiving portion.
  • the receiving portion is a groove formed on the surface of the corrodible metal substrate.
  • the receiving portion is a gap formed by the corrodible metal substrate.
  • the receiving portion is a corrodible metal substrate.
  • the medical device further comprises an active drug, and the active drug is mixed with the ligand-degradable polymer and then stored in the accommodating portion.
  • the medical device is loaded with an active drug.
  • the active drug is mixed with the ligand-degradable polymer.
  • the two methods can be used to load the corrodible metal substrate.
  • the active drug can be flexibly set according to the application scenario and specific needs of the medical device.
  • the active drug is selected from at least one of a drug for inhibiting angiogenesis, an antiplatelet drug, an antithrombotic drug, an anti-inflammatory drug, and an anti-sensitizer.
  • the drug for inhibiting vascular proliferation is selected from at least one of paclitaxel, rapamycin, and derivatives thereof.
  • the antiplatelet drug can be cilostazol.
  • the antithrombotic drug can be heparin.
  • the anti-inflammatory drug can be dexamethasone.
  • the anti-sensitizing drug is selected from at least one of calcium gluconate, chlorpheniramine and cortisone. It should be noted that the above-listed drugs are merely illustrative examples, and the selection of various drugs is not limited to the specific drugs listed above, and can be flexibly selected according to needs.
  • the ligand-degradable polymer comprises a degradable polymer and a ligand attached to the degradable polymer.
  • the ligand-degradable polymer is obtained by reacting a degradable polymer with a ligand.
  • the ligand-degradable polymer is a copolymer of a degradable polymer and a ligand. In the human environment, the ligand-degradable polymer can degrade and release a coordinating group with degradation.
  • the copolymer may be an alternating copolymer, a random copolymer, a block copolymer or a graft copolymer.
  • the degradable polymer has a weight average molecular weight of from 10,000 to 2,000,000.
  • the degradable polymer is a degradable polyester.
  • the degradable polyester is selected from the group consisting of polylactic acid, polyglycolic acid, polylactic acid glycolic acid, polycaprolactone, polyhydroxyalkanoate, polyacrylate, polysuccinate, poly( ⁇ - At least one of hydroxybutyrate), polydioxanone, and polytrimethylene carbonate.
  • the degradable polyester is selected from the group consisting of a degradable copolymer, wherein the degradable copolymer is selected from the group consisting of forming polylactic acid, polyglycolic acid, polylactic acid glycolic acid, polycaprolactone, polyhydroxy fatty acid.
  • the ligand in the ligand-degradable polymer has a mass percentage of from 5% to 80%. If the mass percentage of the ligand is less than 5%, the amount of the ligand group released by the degradation of the ligand-degradable polymer is too small, so that only a small amount of corrosion products can be complexed, and the practical significance is small; The mass percentage of the body is >80%, which may damage the structure of the degradable polymer.
  • the ligand may be reacted with a corrosion product of a corrodible metal substrate in a physiological environment to form a water-soluble coordination compound.
  • the solubility of the water soluble coordination compound in PBS buffer at 36 ° C to 38 ° C is > 10 mg / L.
  • the solubility of the water-soluble coordination compound in the PBS buffer at 36 ° C to 38 ° C is 10 mg / L to 100 mg / L.
  • this embodiment defines a coordination compound having a solubility in a physiological solution of 10 mg/L or more as a water-soluble coordination compound.
  • the coordinating group contains an amino group, a carboxyl group, a cyanide group, a thiocyanate group, an isothiocyanate group, a nitro group, a hydroxyl group, a phenolic hydroxyl group, a mercapto group (-SH), a carbonyl group, an aromatic heterocyclic group, At least one of a nitroso group, a sulfo group, a phosphoric acid group, and an organophosphine group. Further, the coordinating group contains at least one of an amino group and a carboxyl group.
  • the carbonyl group-containing ligand is at least one selected from the group consisting of a carboxylic acid, a carboxylate, an acid anhydride, an ester, an amide, a polycarboxylic acid, and a polyanhydride.
  • the aromatic heterocyclic group is selected from the group consisting of furyl, pyrrolyl, thienyl, imidazolyl, triazolyl, thiazolyl, pyridyl, pyridinyl, pyranyl, pyranone, pyrimidinyl, pyridazine
  • a pyrazine group a pyrazinyl group, a quinolyl group, an isoquinolyl group, a pyridazinyl group, an acridinyl group, a fluorenyl group, a fluorenyl group, and a phenanthroline group.
  • the ligand is a polydentate ligand containing at least two coordinating groups, and the resulting coordinating group is capable of forming a chelate with the metal ion. Further, the resulting coordinating group is capable of forming a chelate with iron ions or zinc ions under physiological conditions.
  • the polydentate ligand is a polydentate ligand comprising a hydroxyl group on a fused ring aromatic hydrocarbon, a polydentate ligand containing a thiol group, a polydentate ligand containing an amino group, a multidentate containing an aromatic heterocyclic group Ligands, nitroso-containing polydentate ligands, carbonyl-containing polydentate ligands, sulfo-containing polydentate ligands, phosphate group-containing polydentate ligands, organophosphonyl group-containing polydentate ligands And at least one of a carbonyl-containing polydentate ligand.
  • the polydentate ligand containing a hydroxyl group on the condensed aromatic hydrocarbon is selected from the group consisting of 8-hydroxyquinoline, 8-hydroxyquinaldine, sodium 4,5-dihydroxybenzene-1,3-disulfonate, and 4-[ At least one of 3,5-dihydroxyphenyl-1H-1,2,4-triazole]-benzoic acid (destasis).
  • the thiol-containing polydentate ligand is at least one selected from the group consisting of 8-mercaptoquinoline, thioglycolic acid, and methyl 5-methyl-2-mercaptobenzoate.
  • the amino group-containing polydentate ligand is selected from the group consisting of ethylenediamine, butanediamine, spermidine, spermine, triethylenetetramine, ethylenediaminetetraacetic acid, tetrasodium ethylenediaminetetraacetate, and N'-[5-[ [4-[[5-(Acetylhydroxyamino)pentyl]amino]-1,4-dioxobutyl]hydroxylamine]pentyl]-N-(5-aminopentyl)-N-hydroxysuccinamide At least one of ferric amines.
  • the polydentate ligand containing an aromatic heterocyclic group is selected from the group consisting of phenanthroline, bipyridine, porphyrin, porphin, chlorophyll, hemoglobin and 1,2-dimethyl-3-hydroxy-4-pyridone (de-iron) At least one of the ketones.
  • the nitroso-containing polydentate ligand is selected from at least one of 1-nitroso-2-naphthol and sodium 1-nitros-2-naphthol-6-sulfonate.
  • the carbonyl group-containing polydentate ligand is selected from at least one of a polyvalent carboxylic acid and a salt thereof, an acid anhydride, an ester, an amide, a polycarboxylic acid, and a polyanhydride.
  • the sulfo group-containing polydentate ligand is selected from at least one of sulfosalicylic acid and 8-hydroxyquinoline-5-sulfonic acid.
  • the polydentate ligand containing a phosphate group is at least one selected from the group consisting of pyrophosphoric acid, tripolyphosphoric acid, hexapolyphosphoric acid, polyphosphoric acid, sodium pyrophosphate, sodium hexametaphosphate, and ammonium polyphosphate.
  • the polydentate ligand containing an organophosphine group is at least one selected from the group consisting of potassium diethylenetriamine pentamethylphosphonate and sodium ethylenediaminetetramethylenephosphonate.
  • the carbonyl-containing polydentate ligand is selected from the group consisting of oxalic acid, tartaric acid, malic acid, succinic acid, oxaloacetic acid, fumaric acid, maleic acid, citric acid, ammonia triacetic acid, diethylenetriaminepentacarboxylic acid, alginic acid, glutamic acid.
  • the polydentate ligand is selected from at least one of amino or carboxyl containing amino acids, oligopeptides, polypeptides, proteins, polyamines, anhydrides, and polyanhydrides.
  • a peptide is a compound formed by peptide bonds linked after dehydration of an amino acid, a peptide consisting of 2 to 10 amino acids is called an oligopeptide, and a peptide consisting of 10 to 50 amino acids is called a polypeptide, and more than 50 are used.
  • a peptide composed of amino acids is called a protein.
  • the amino acid is selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, tyrosine, aspartic acid, asparagine, glutamic acid At least one of lysine, glutamine, methionine, serine, threonine, ornithine, cysteine, proline, histidine, and arginine.
  • the ligand is selected from the group consisting of polysaccharides containing a plurality of hydroxyl groups.
  • the polysaccharide is selected from the group consisting of dextran, chitosan, plant polysaccharide, starch, dextrin, cellulose, glycogen, chitin, chitin, inulin, agar, gum arabic, hyaluronic acid, gellan gum, Kede gum, xanthan gum, pectin, konjac glucomannan, gum arabic, seaweed lichen polysaccharide, alginate, spirulina polysaccharide, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparin and heparan sulfate At least one of them.
  • the ligand is selected from the group consisting of 2-amino-4-pentenoic acid, 2-acetamidoacrylic acid, maleic acid, flumethacic acid, allyl oxalate, octenylsuccinic acid, diethylenetriaminepentacarboxylate At least one of an acid and maleic anhydride.
  • the degradable polymer may be a general degradable polymer and can react with a ligand. Further preferably, the degradable polymer is the above-exemplified degradable polymer.
  • the base reaction gives a ligand-degradable polymer, and the specific reaction is as shown in the reaction formulas (1) and (2).
  • the wavy line represents a degradable polymer and R represents H or a hydrocarbyl group.
  • the ligand is selected from at least one of an acid, an ester, an amide, an amine, an amino acid, a peptide, and a protein.
  • the compound containing a carbon-carbon double bond is selected from at least one of vinyl isocyanate, ethylene acetic acid, vinyl acetate, vinyl sulfonic acid, vinyl versatate, ethylene sorbate, acrylic acid, methyl acrylate, and acrylamide.
  • the first reactive group graft degradable polymer can also be used as a degradable polymer intermediate, and reacted with a ligand containing the second reactive group to obtain a ligand-degradable polymer.
  • the first reactive group can react with the second reactive group.
  • At least one of the first reactive group and the second reactive group is capable of releasing a coordinating group.
  • one of the first reactive group and the second reactive group is selected from at least one of an isocyanato group, a carboxyl group, an acid chloride group and an epoxy group, and the other one is selected from the group consisting of an amino group, a hydroxyl group, a thiol group and a carboxyl group. At least one of them.
  • first reactive group and the second reactive group are not limited to the above-exemplified groups, as long as they can react with each other to obtain a ligand-degradable polymer, and can be released with metal ions or The solid corrosion product can be reacted under physiological conditions to form a coordination group of the water-soluble coordination compound.
  • one of the first reactive group and the second reactive group is an amino group, and the other is at least one of an isocyanate group, a carboxyl group, an acid chloride group and an epoxy group; the first reactive group and the second group One of the reactive groups is a hydroxyl group, and the other is at least one of an isocyanate group, a carboxyl group, an acid chloride group, and an epoxy group; one of the first reactive group and the second reactive group is a mercapto group, and the other Is at least one of an isocyanato group, a carboxyl group, an acid chloride group and an epoxy group; one of the first reactive group and the second reactive group is a carboxyl group, and the other is an isocyanate group, a carboxyl group, an acid chloride group and an epoxy group.
  • At least one of the group; one of the first reactive group and the second reactive group is an isocyanate group, and the other is at least one of an amino group, a hydroxyl group, a thiol group, and a carboxyl group; the first reactive group and the first One of the two reactive groups is a carboxyl group, and the other is at least one of an amino group, a hydroxyl group, a thiol group and a carboxyl group; one of the first reactive group and the second reactive group is an acid chloride group, and the other is an amino group or a hydroxyl group.
  • the reaction formula of the reaction of at least one of an amino group, a hydroxyl group, a thiol group and a carboxyl group with at least one of an isocyanate group, a carboxyl group, an acid chloride group and an epoxy group is represented by the following expressions (3) to (11).
  • R, R', R" each independently represent H or a hydrocarbon group.
  • the ligand contains at least one of an amino group, a hydroxyl group, a thiol group, and a carboxyl group
  • the ligand-degradable polymer is obtained by reacting a ligand with a degradable polymer intermediate.
  • the degradable polymer intermediate contains at least one of an isocyanate group, a carboxyl group, an acid chloride group, and an epoxy group.
  • the ligand is selected from the group consisting of ethylenediamine, butanediamine, spermidine, spermine, triethylenetetramine, ethylenediaminetetraacetic acid, tetrasodium ethylenediaminetetraacetate, N'-[5-[[4 -[[5-(acetylhydroxyamino)pentyl]amino]-1,4-dioxobutyl]hydroxylamine]pentyl]-N-(5-aminopentyl)-N-hydroxysuccinamide (desferramide ), 8-hydroxyquinoline, 8-hydroxyquinaldine, sodium 4,5-dihydroxybenzene-1,3-disulfonate, 4-[3,5-di-hydroxyphenyl-1H-1,2 ,4-triazole]-benzoic acid (destasis), 8-mercaptoquinoline, thioglycolic acid, methyl 5-methyl-2-mercaptobenzo
  • the degradable polymer is obtained by grafting reaction with at least one graft compound containing an isocyanate group, a carboxyl group, an acid chloride group and an epoxy group to obtain a degradable polymer intermediate.
  • the graft compound is selected from the group consisting of vinyl isocyanate, 3-isocyanate propylene, maleic anhydride, acrylic acid, methacrylic acid, decenoic acid, 9-decenoic acid undecylenic acid, acryloyl chloride, methacryloyl chloride, butyl At least one of enoyl chloride, fumaric acid chloride, undecylenyl chloride, ethylene oxide, epoxybutene, and epoxidized squalene.
  • the ligand contains at least one of an isocyanato group, a carboxyl group, an acid chloride group, and an epoxy group, and the ligand reacts with the degradable polymer intermediate to obtain a ligand-degradable polymer.
  • the degradable polymer intermediate contains at least one of an amino group, a hydroxyl group, a thiol group, and a carboxyl group.
  • the ligand is selected from the group consisting of isocyanate, oxalic acid, tartaric acid, malic acid, succinic acid, oxaloacetic acid, fumaric acid, maleic acid, citric acid, aminotriacetic acid, diethylenetriaminepentacarboxylic acid, alginic acid, glutamic acid , aspartic acid, ornithine, lysine, maleic anhydride, ethyl (acid) anhydride, maleic anhydride, succinic anhydride, maleic anhydride, phthalic anhydride, potassium citrate, citric acid Calcium, glyceryl citrate, acetylsalicylic acid, sulfosalicylamamide, polyaspartic acid, polyglutamic acid, polyornithine, polylysine, polymaleic anhydride, acetyl chloride, oxalyl chloride, Acetylsalicylic acid chloride,
  • the degradable polymer is obtained by grafting reaction with at least one graft compound containing an amino group, a hydroxyl group, a thiol group and a carboxyl group to obtain a degradable polymer intermediate.
  • the graft compound is selected from the group consisting of aminoethylene, amino propylene, tetrakis(dimethylamino)ethylene, 2-amino-4-pentenoic acid, 10-hydroxy-2-decenoic acid, p-hydroxystyrene, 1,4-dihydroxyl At least one of 2-butene, 3-buten-1-ol, mercaptopropionic acid, mercaptoacrylic acid, 3-enecarboxylic acid, cyclohexenecarboxylic acid, stilbene dicarboxylic acid, and pyrrolidone carboxylic acid .
  • the ligand is attached to the segment of the degradable polymer to obtain a chemically modified ligand-degradable polymer, and then the modified degradable polymer is mounted on the surface of the absorbable corrodible metal substrate.
  • the modified degradable polymer gradually degrades and releases the coordination group, and the coordination group reacts with the corrosion product of the corrodible metal substrate to form a water-soluble reaction under physiological environment to form a water-soluble solution.
  • Coordination compound thereby reducing the concentration of free metal ions and the corrosion-resistant solid corrosion products generated by corrosive metal matrix corrosion, reducing the risk of metal ion cytotoxicity, accelerating corrosion of metals, and allowing corrosion products to be quickly absorbed by tissues and Metabolism is beneficial to the recovery of the lesion, and reduces the possibility that the corrosion product will persist in the human body for a long time.
  • the weight average molecular weight of the ligand-degradable polymer is determined by the weight average molecular weight of the ligand-degradable polymer using a GPC-multi-angle laser light scattering instrument of Wyatt, USA.
  • the test system is tested.
  • the test system includes Agilent's liquid pump and sampler from the United States, Agilent's Agilent PL MIXED-C GPC column (size: 7.5 ⁇ 300mm, 5 microns), Wyatt's multi-angle laser light scattering instrument and Differential detector.
  • the detection conditions were: mobile phase: tetrahydrofuran; pump flow rate: 1 mL/min; injection amount: 100 ⁇ L; laser wavelength: 663.9 nm; test temperature: 35 °C.
  • the mass fraction of ligand in the ligand-degradable polymer is defined as the ratio between the molecular mass of the ligand and the total molecular mass of the ligand-degradable polymer.
  • the method for detecting the mass fraction of the ligand comprises the steps of: respectively detecting the molar ratio of the key group in the ligand and the key group of the degradable polymer molecule by a nuclear magnetic resonance spectrometer (MRI), and calculating by the ratio according to the ratio The mass fraction of the ligand.
  • MRI nuclear magnetic resonance spectrometer
  • the concentration of the water-soluble coordination compound at different stages is detected by immersing the medical device in a phosphate buffer (PBS) having a pH range of 7.4 ⁇ 0.05, and making the volume of the PBS and the volume of the medical device The ratio is 5-10:1, and the medical device needs to be completely immersed in the PBS. If the medical device has a large infusion container, the number of medical devices can be increased.
  • the physiological solution impregnated with the medical device was placed in a constant temperature water bath at 37 ⁇ 1 ° C and oscillated at a rate of 40 rpm to 80 rpm.
  • a predetermined observation time point such as 7 days, 1 month, 3 months..., filtered with an aqueous membrane having a pore size of 0.22 ⁇ m to remove insoluble substances in PBS, and then by atomic absorption spectroscopy (abbreviation) AAS)
  • AAS atomic absorption spectroscopy
  • the mass concentration of the metal element in the filtrate after filtration was measured, and the mass concentration of the water-soluble complex compound at 37 ⁇ 1° C. in PBS was further obtained by conversion.
  • the corroded medical device was placed in the same volume of PBS solution for further corrosion to the next observation time point, and the experimental procedure was as described above. If a metal element is detected in the solution after a period of liquid exchange, the coordination group is gradually released as the degradable polymer is degraded.
  • the concentration of the detected iron complex compound is detected due to the normal fluctuation of the product's own performance within the design permission range, the difference in the individual corrosion rate of the device, and the systematic error inevitably introduced by the test method. In the actual test, it will fluctuate within a certain range.
  • the medical device provided in Embodiment 1 is an absorbable nitriding iron-based stent, comprising a stent base made of a nitriding iron material, and (2-amino-4-pentenoic acid)-poly-racemic coating covering the surface of the stent substrate.
  • Lactic acid (abbreviated as mPDLLA) coating the wall thickness of the stent substrate was 50 ⁇ m, and the thickness of the coating layer was 60 ⁇ m.
  • the volume ratio of the coating to the stent substrate was 10.56:1.
  • the coating covers 100% of the surface of the stent substrate.
  • the preparation process of the absorbable nitriding iron-based stent provided in Example 1 is as follows: mPDLLA is dissolved in ethyl acetate, and the solution is sprayed onto the surface of the nitriding iron-based stent, and dried to obtain the absorbable nitriding of Example 1. Iron-based bracket.
  • the preparation method of mPDLLA comprises the following steps: dissolving poly- lactic acid (PDLLA), 2-amino-4-pentenoic acid and DCP in mass ratio of 50:50:5 in tetrahydrofuran, 60 ° C anhydrous anaerobic environment The reaction was stirred for 15 hours, and the obtained product was mPDLLA, purified by methanol-chloroform system and dried. The mPDLLA used in Example 1 was obtained. The molecular structural formula of mPDLLA is shown below.
  • the ligand 2-amino-4-pentenoic acid contains a carbon double bond, and 2-amino-4-pentenoic acid is covalently grafted on the PDLLA segment by a double bond radical reaction to form a modified PDLLA.
  • the weight average molecular weight of mPDLLA used in Example 1 was measured to be 200,000 Da.
  • the mass fraction of the ligand in mPDLLA was 46%.
  • the medical device provided in Embodiment 2 is an absorbable iron-based stent, comprising a stent base made of a pure iron material, and a salicylic acid-isocyanate-polylactic acid-glycolic acid copolymer covering the surface of the stent substrate ( Referred to as mPLGA) coating.
  • the wall thickness of the stent base was 70 ⁇ m, and the thickness of the mPLGA coating was 4 ⁇ m.
  • the volume ratio of the coating to the stent substrate was 0.17:1.
  • the coating covers 70% of the surface of the stent substrate.
  • the process for producing the absorbable iron-based stent provided in Example 2 was as follows: mPLGA was uniformly applied to the surface of the pure iron stent by spraying to obtain the absorbable iron-based stent of Example 2.
  • the preparation method of mPLGA comprises the following steps: dissolving salicylic acid and ethylene isocyanate in a molar ratio of 1:1 in chloroform and mixing uniformly, and stirring at room temperature for 12 hours, the obtained product isocyanate-salt
  • the acid is dried by vacuum drying; polylactic acid-glycolic acid copolymer (PLGA for short), vinyl isocyanate-acetylsalicylic acid and BPO are dissolved in toluene at a mass ratio of 70:30:2, and an anhydrous oxygen-free environment at 110 ° C
  • the reaction was stirred for 6 hours, and the obtained product was mPLGA, which was purified by methanol-chloroform system and dried to obtain mPLGA used in Example 1.
  • the molecular structural formula of mPLGA is shown below.
  • the isocyanate containing double bond is grafted on the ligand salicylic acid, and it participates in the radical reaction through the double bond, and grafts on the PLGA segment.
  • the weight average molecular weight of mPLGA used in Example 2 was found to be 150,000 Da, and the mass fraction of the ligand was 30%.
  • the concentration of the iron complex in PBS was 1000 mg/L.
  • the results show that by grafting salicylic acid onto polylactic acid, the ligand can exist for a long time and gradually release, and chelate with iron ions to form chelated iron, which reduces solid corrosion products.
  • the medical device provided in Example 3 is an absorbable iron-based stent comprising a stent substrate made of a pure iron material and a glycine-maleic anhydride-polycaprolactone abbreviation (mPCL) coating covering the surface of the stent substrate.
  • mPCL glycine-maleic anhydride-polycaprolactone abbreviation
  • the wall thickness of the stent base was 50 ⁇ m, and the thickness of the mPCL coating was 6 ⁇ m.
  • the volume ratio of the coating to the stent substrate was 0.54:1.
  • the coating covers 100% of the surface of the stent substrate.
  • the process for producing the absorbable iron-based stent provided in Example 3 was as follows: mPCL was uniformly applied to the surface of the pure iron stent by spraying to obtain the absorbable iron-based stent of Example 3.
  • the preparation method of mPCL comprises the steps of dissolving polycaprolactone (PCL), maleic anhydride (MAH) and benzoyl peroxide (BPO) in a mass ratio of 90:10:0.5 in chloroform and mixing. Evenly, a mixture was obtained. The mixture was dried and reacted under nitrogen atmosphere at 100 ° C for 10 hours. The obtained product was purified from methanol-chloroform system and then dried in vacuo to give a modified polycaprolactone intermediate (maleic anhydride-polycaprolactone).
  • PCL polycaprolactone
  • MAH maleic anhydride
  • BPO benzoyl peroxide
  • the obtained maleic anhydride-polycaprolactone was dissolved in tetrahydrofuran, and then added dropwise to a solution of glycine (glycine) in tetrahydrofuran to obtain a crude product of mPCL.
  • the crude product of mPCL was purified by methanol-chloroform system and dried to obtain The mPCL used in Example 3.
  • the molecular structure of mPCL is shown below.
  • a modified polycaprolactone intermediate is obtained by first grafting a maleic anhydride containing a carbon double bond on a polycaprolactone by a radical reaction, and the modified polycaprolactone intermediate contains a carboxyl group, a carboxyl group and a carboxyl group.
  • the amino group in the bulk amino acid is reacted to obtain glycine-maleic anhydride-polycaprolactone.
  • the weight average molecular weight of the mPCL used in Example 3 was found to be 100,000 Da, and the mass fraction of the ligand was 20%.
  • the concentration of the iron complex in PBS was 500 mg/L.
  • the results show that by grafting glycine onto polycaprolactone, glycine can exist for a long time and gradually release, and chelate with iron ions to form chelated iron, which reduces solid corrosion products.
  • the medical device provided in Embodiment 4 is an absorbable iron-based stent, comprising a stent base made of a nitrided iron material, and rapamycin-(8-hydroxyquinoline-2carboxylic acid) covering the surface of the stent substrate.
  • Acryl chloride-polyglycolic acid (mPGA for short) coating the substrate thickness of the stent substrate was 60 ⁇ m, and the thickness of the coating layer was 20 ⁇ m.
  • the volume ratio of the coating to the stent substrate was 1:1.
  • the coating covers 50% of the surface of the stent substrate.
  • the absorbing iron-based stent provided in Example 4 was prepared as follows: mPGA and rapamycin having a mass ratio of 5:1 were mixed and dissolved in ethyl acetate, and the solution was sprayed onto the surface of the pure iron stent, and dried. The absorbable iron-based alloy stent of Example 4 was obtained.
  • the preparation method of mPGA comprises the steps of: dissolving 8-hydroxyquinoline-2carboxylic acid having a molar ratio of 1:1 and acryloyl chloride in chloroform and mixing uniformly, and stirring at room temperature for 12 hours to obtain a product of 8-hydroxyquinoline.
  • an acryloyl chloride containing a double bond is grafted onto the ligand 8-hydroxyquinoline-2carboxylic acid, and it is subjected to a radical reaction through a double bond, and grafted onto the PGA segment.
  • (8-hydroxyquinoline-2carboxylic acid)-acryloyl chloride-polyglycolic acid will gradually degrade in vivo, while the ligand 8-hydroxyquinoline-2carboxylic acid is gradually released and chelated with iron ions to form 8-hydroxyl group. Iron of quinoline-2.
  • the weight average molecular weight of mPLA used in Example 4 was measured to be 100,000 Da, and the mass fraction of the ligand was 37%.
  • the concentration of the iron complex in PBS was 1000 mg/L.
  • the results show that by grafting the ligand onto polyglycolic acid, the ligand can exist for a long time and gradually release, and chelate with iron ions to form chelated iron, which reduces solid corrosion products.
  • the medical device provided in Embodiment 5 is an absorbable nitriding iron-based stent, comprising a stent base made of a nitrided iron material, a zinc layer covering the surface of the stent base, and ethylenediaminetetraacetic acid covering the surface of the zinc layer.
  • the volume ratio of the coating, the zinc layer to the support substrate was 1.13:0.12:1.
  • the coating covers 100% of the surface of the stent substrate.
  • the zinc layer covers 100% of the surface of the stent substrate.
  • the nitridable nitriding iron-based stent provided in Example 5 is prepared by coating a nitriding iron-based stent with a zinc layer on the surface thereof by electroplating; then dissolving mPLA in ethyl acetate and spraying the solution to The surface of the galvanized iron-based stent was dried to obtain the absorbable nitriding iron-based stent of Example 5.
  • the preparation method of mPLA comprises the steps of: dissolving ethylenediaminetetraacetic acid (EDTA) with a molar ratio of 1:1 and acryloyl chloride in chloroform and mixing uniformly, and stirring at room temperature for 12 hours to obtain the product ethylenediaminetetraacetic acid.
  • EDTA ethylenediaminetetraacetic acid
  • - acryloyl chloride was vacuum dried for use; polylactic acid (PLA for short), ethylenediaminetetraacetic acid-acryloyl chloride and di-tert-butyl peroxide (DBP) were dissolved in toluene at a mass ratio of 35:65:6, at 120 ° C.
  • the reaction was stirred under an anaerobic atmosphere for 18 hours, and the obtained product was mPLA, which was purified by methanol-chloroform system and dried to obtain mPLA used in Example 5.
  • the molecular structural formula of mPLA is shown below.
  • the acryloyl chloride containing a double bond is first grafted onto the ligand ethylenediaminetetraacetic acid, and it participates in the radical reaction through the double bond, and grafts on the PLA segment.
  • Ethylenediaminetetraacetic acid-acryloyl chloride-polylactic acid is gradually degraded in the body, and the ligand ethylenediaminetetraacetic acid is gradually released, and chelated with iron ions to form iron diamine tetraacetate.
  • the weight average molecular weight of mPLA used in Example 5 was measured to be 200,000 Da, and the mass fraction of the ligand was 60%.
  • the concentrations of zinc and iron complexes in PBS were 200 mg/L and 400 mg/L, respectively. After soaking for 3 months, the concentrations of zinc and iron complexes in PBS were 200 mg/L and 1200 mg/L, respectively.
  • the results show that by grafting the ligand onto the polyester, the ligand can exist for a long time and gradually release. The early chelation with zinc ions reduces the concentration of free zinc ions, and the chelation with iron ions in the middle and later stages reduces the corrosion products of iron solids.
  • the medical device provided in Embodiment 6 is an absorbable nitriding iron-based stent, comprising a stent base made of a nitriding iron material, and a dextran-poly linear lactic acid (mPDLLA) coating covering the surface of the stent substrate.
  • mPDLLA dextran-poly linear lactic acid
  • the wall thickness of the stent substrate was 50 ⁇ m and the thickness of the coating layer was 20 ⁇ m.
  • the volume ratio of the coating to the stent substrate was 2.24:1.
  • the coating covers 100% of the surface of the stent substrate.
  • the preparation process of the nitridable nitriding iron-based stent provided in Example 6 is as follows: the nitriding iron-based stent is coated with a zinc layer on the surface thereof by electroplating; then the dextran-poly linear lactic acid (mPDLLA) is dissolved. The solution was sprayed onto the surface of a galvanized iron-based stent and dried to obtain an absorbable nitriding iron-based stent of Example 6.
  • mPDLLA dextran-poly linear lactic acid
  • the preparation method of mPDLLA comprises the steps of dissolving dextran 5W and PDLLA in a molar ratio of 1:1 in dimethyl sulfoxide and copolymerizing under the activation of epichlorohydrin, and the obtained product glucan-PDLLA That is, mPDLLA, purified by acetone and dried to obtain mPDLLA used in Example 6.
  • the molecular structural formula of mPDLLA is shown below.
  • dextran-poly linear lactic acid gradually degrades in the body, and the dextran gradually degrades and releases, and chelate with the iron corrosion product to form a dextran iron complex.
  • the weight average molecular weight of mPLA used in Example 6 was measured to be 200,000 Da, and the mass fraction of the ligand was 50%.
  • the concentration of the iron complex in PBS was 1800 mg/L, respectively.
  • the results show that by copolymerizing the ligand with the polyester, the ligand can exist for a long time and gradually release, and chelation with iron ions reduces the iron solid corrosion product.
  • An ordinary PLA was sprayed on the surface of the pure iron stent and dried to obtain an absorbable iron-based stent of Comparative Example 1.
  • the wall thickness of the stent substrate was 50 ⁇ m, and the thickness of the PDLLA coating was 5 ⁇ m.
  • the mass ratio of the coating to the stent substrate was 0.44:1.
  • the coating covers 100% of the surface of the stent substrate.
  • the weight average molecular weight of PDLLA used in Comparative Example 1 was measured by the aforementioned detection method to be 200,000 Da.
  • the absorbable iron-based stent of Comparative Example 1 was compared with the medical device provided in Example 1, because the ordinary polylactic acid of Comparative Example 1 could not coordinate with iron ions under physiological conditions, and the iron-based matrix was in a physiological environment. A poorly soluble corrosion product is formed.
  • the polylactic acid is chemically modified to form a ligand-polylactic acid having a ligand, and the ligand-polylactic acid is combined with iron ions in a physiological environment to form a water-soluble iron coordination. Compound.
  • a common 2-amino-4-pentenoic acid coating was sprayed on the surface of the pure iron stent, and then the PDLLA coating was sprayed and dried to obtain an absorbable iron-based stent of Comparative Example 2.
  • the wall thickness of the stent substrate was 50 ⁇ m
  • the thickness of the 2-amino-4-pentenoic acid coating was 5 ⁇ m
  • the thickness of the PDLLA coating layer was 5 ⁇ m.
  • the mass ratio of the coating to the stent substrate was 0.96:1.
  • the coating covers 100% of the surface of the stent substrate.
  • the weight average molecular weight of the PLA used in Comparative Example 2 was found to be 200,000 Da, and the mass fraction of 2-amino-4-pentenoic acid was 50%.
  • the chemical modification method of Example 1 can make the ligand distribution in the ligand-degradable polyester more uniform and the binding force is stronger.
  • the large load ensures that the ligand is stable and functions, avoiding the loss of ligand due to body fluid immersion or erosion.
  • a chemically modified ligand-degradable polymer is obtained by covalently grafting a ligand on a segment of a degradable polymer, and then the ligand-degradable polymer is carried on Corrosive metal substrate surface, combined with corrosion products from corrosive metal matrix corrosion by ligands in ligand-degradable polyester to form water-soluble coordination compounds in physiological environment, thereby reducing corrosive metals
  • the poorly soluble solid corrosion products formed by the corrosion of the matrix cause the water-soluble corrosion products of the corrodible metal matrix to be quickly absorbed and metabolized by the tissue.
  • the binding between the ligand and the degradable polymer is more robust and reliable, and the ligand can be more evenly distributed in the ligand-degradable polymer. To avoid the loss of ligand caused by body fluid flushing or soaking.

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Abstract

L'invention concerne un instrument médical comprenant une matrice métallique corrodable et un polymère dégradable par un ligand. Le polymère dégradable par un ligand est obtenu par réaction d'un polymère dégradable avec un ligand. Le polymère dégradable par un ligand peut être dégradé et libérer un groupe de coordination ; le groupe de coordination peut subir une réaction de coordination avec un produit de corrosion généré par la matrice métallique corrodable dans un environnement physiologique pour générer un composé de coordination soluble dans l'eau.
PCT/CN2017/119223 2017-02-13 2017-12-28 Instrument médical WO2018145528A1 (fr)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3725339A4 (fr) * 2017-12-15 2021-08-18 Biotyx Medical (Shenzhen) Co., Ltd. Dispositif implantable à base de fer résorbable

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106798952B (zh) * 2017-02-13 2019-12-10 先健科技(深圳)有限公司 可吸收铁基骨折内固定材料

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008086369A1 (fr) * 2007-01-08 2008-07-17 Micell Technologies, Inc. Stents comportant des couches biodégradables
WO2009146209A1 (fr) * 2008-04-17 2009-12-03 Micell Technologies, Inc. Stents a couches bioabsorbables
CN104491935A (zh) * 2014-12-30 2015-04-08 马艳荣 一种生物可降解聚合物涂层载药镁合金洗脱支架
CN104587534A (zh) * 2013-10-31 2015-05-06 先健科技(深圳)有限公司 可吸收铁基合金支架
CN105797220A (zh) * 2014-12-31 2016-07-27 先健科技(深圳)有限公司 可降解铁基合金支架
CN106798952A (zh) * 2017-02-13 2017-06-06 深圳市立心科学有限公司 可吸收铁基骨折内固定材料

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6821897B2 (en) * 2001-12-05 2004-11-23 Cabot Microelectronics Corporation Method for copper CMP using polymeric complexing agents
ATE553229T1 (de) * 2003-02-25 2012-04-15 Chemetall Gmbh Verfahren zur beschichtung von metallischen oberflächen mit einer silan-reichen zusammensetzung
US20050244459A1 (en) * 2004-04-06 2005-11-03 Dewitt David M Coating compositions for bioactive agents
DE102005023728A1 (de) * 2005-05-23 2006-11-30 Basf Coatings Ag Lackschichtbildendes Korrosionsschutzmittel und Verfahren zu dessen stromfreier Applikation
CN100381182C (zh) * 2005-08-26 2008-04-16 中国科学院金属研究所 生物医用可控降解吸收高分子金属复合植入材料及其应用
US20080114096A1 (en) * 2006-11-09 2008-05-15 Hydromer, Inc. Lubricious biopolymeric network compositions and methods of making same
AU2008206954A1 (en) * 2007-01-19 2008-07-24 Cinvention Ag Partially bioabsorbable implant
WO2008122594A2 (fr) * 2007-04-05 2008-10-16 Cinvention Ag Implant thérapeutique partiellement biodégradable pour la réparation de l'os et du cartilage
GB0715376D0 (en) * 2007-08-07 2007-09-19 Smith & Nephew Coating
US20090240323A1 (en) * 2008-03-20 2009-09-24 Medtronic Vascular, Inc. Controlled Degradation of Magnesium Stents
DE102008021894A1 (de) * 2008-05-02 2009-11-05 Biotronik Vi Patent Ag Implantat umfassend eine Oberfläche mit verringerter Thrombogenität
DE102008053517A1 (de) * 2008-10-28 2010-04-29 Henkel Ag & Co. Kgaa Lackhaftung durch Polyvinylamine in sauren wässrigen polymerhaltigen Korrosionsschutzmitteln
US20110111989A1 (en) * 2009-11-12 2011-05-12 Oscar Bustos Compositions and methods to stabilize acid-in-oil emulsions
CA2812599A1 (fr) * 2010-11-12 2012-05-18 University Of Utah Research Foundation Coacervats adhesifs simples et procedes de fabrication et d'utilisation de ceux-ci
CN105597163B (zh) * 2015-12-29 2019-05-31 先健科技(深圳)有限公司 铁基合金植入医疗器械及其制备方法

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008086369A1 (fr) * 2007-01-08 2008-07-17 Micell Technologies, Inc. Stents comportant des couches biodégradables
WO2009146209A1 (fr) * 2008-04-17 2009-12-03 Micell Technologies, Inc. Stents a couches bioabsorbables
CN104587534A (zh) * 2013-10-31 2015-05-06 先健科技(深圳)有限公司 可吸收铁基合金支架
CN104491935A (zh) * 2014-12-30 2015-04-08 马艳荣 一种生物可降解聚合物涂层载药镁合金洗脱支架
CN105797220A (zh) * 2014-12-31 2016-07-27 先健科技(深圳)有限公司 可降解铁基合金支架
CN106798952A (zh) * 2017-02-13 2017-06-06 深圳市立心科学有限公司 可吸收铁基骨折内固定材料

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3725339A4 (fr) * 2017-12-15 2021-08-18 Biotyx Medical (Shenzhen) Co., Ltd. Dispositif implantable à base de fer résorbable

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