WO2020228629A1 - 可降解载药支架及其制作方法 - Google Patents

可降解载药支架及其制作方法 Download PDF

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Publication number
WO2020228629A1
WO2020228629A1 PCT/CN2020/089349 CN2020089349W WO2020228629A1 WO 2020228629 A1 WO2020228629 A1 WO 2020228629A1 CN 2020089349 W CN2020089349 W CN 2020089349W WO 2020228629 A1 WO2020228629 A1 WO 2020228629A1
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Prior art keywords
drug
groove
stent
degradable
loaded
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PCT/CN2020/089349
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English (en)
French (fr)
Inventor
刘伟
王雪琴
高雅琴
祁凡
Original Assignee
上海微创医疗器械（集团）有限公司
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Application filed by 上海微创医疗器械（集团）有限公司 filed Critical 上海微创医疗器械（集团）有限公司
Priority to EP20806423.8A priority Critical patent/EP3967279A4/en
Priority to JP2022514032A priority patent/JP7334338B2/ja
Priority to US17/595,131 priority patent/US20220079786A1/en
Publication of WO2020228629A1 publication Critical patent/WO2020228629A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B23—MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23K—SOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K26/00—Working by laser beam, e.g. welding, cutting or boring
    • B23K26/36—Removing material
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B23—MACHINE TOOLS; METAL-WORKING NOT OTHERWISE PROVIDED FOR
    • B23K—SOLDERING OR UNSOLDERING; WELDING; CLADDING OR PLATING BY SOLDERING OR WELDING; CUTTING BY APPLYING HEAT LOCALLY, e.g. FLAME CUTTING; WORKING BY LASER BEAM
    • B23K26/00—Working by laser beam, e.g. welding, cutting or boring
    • B23K26/36—Removing material
    • B23K26/38—Removing material by boring or cutting
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/91533—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other characterised by the phase between adjacent bands
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A61F2002/9155—Adjacent bands being connected to each other
    • A61F2002/91558—Adjacent bands being connected to each other connected peak to peak
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2240/00—Manufacturing or designing of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2240/001—Designing or manufacturing processes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
    • A61F2250/0068—Means for introducing or releasing pharmaceutical products into the body the pharmaceutical product being in a reservoir

Definitions

  • This application relates to the technical field of medical devices, in particular to a degradable drug-carrying stent and a manufacturing method thereof.
  • Cardiovascular diseases have become one of the main diseases threatening human health.
  • the most common diseases in cardiovascular diseases include coronary atherosclerotic heart disease, which is also often referred to as coronary heart disease.
  • Coronary heart disease is caused by abnormal lipid metabolism. The lipids in the blood deposit on the smooth intima of the artery, forming atheroma-like white plaques (called coronary atherosclerotic lesions), causing vascular lumen to narrow or block , Resulting in heart disease caused by myocardial ischemia and hypoxia.
  • Percutaneous arterial interventional stent surgery has become an important treatment for coronary heart disease.
  • the types of stents mainly include bare metal stents and drug-eluting stents. The biggest problem with bare metal stents is the possibility of intimal hyperplasia and restenosis. The application of drug-eluting stents reduces the restenosis rate from 30% of bare stents to less than 10%.
  • degradable stents have been widely used in drug-eluting stents due to their superior degradability. They can be degraded and absorbed after being implanted in the body for a period of time.
  • degradable stents also have some problems.
  • the sprayed drug droplets are prone to overflow, resulting in inconsistent thickness and uneven distribution of the drug coating on the surface of the stent.
  • the uneven distribution of the drug coating may cause uneven release of the drug or partial shedding of the drug overflow, which may easily cause thrombosis.
  • the material used in the degradable stent is weaker than the metal stent. Based on this, the industry urgently needs to overcome the practical technical problem of how to improve the adhesion of the drug on the stent while providing sufficient support.
  • the present application provides a degradable drug-loaded stent and a manufacturing method of the degradable drug-loaded stent, which can improve the adhesion ability of drugs on the degradable stent while providing sufficient support force.
  • a degradable drug-loaded stent wherein the degradable drug-loaded stent includes a stent body, and the outer surface of the stent body is provided with a drug-loading groove; the stent body has a contracted state and an expanded state, and the stent body can Switching from the contracted state to the expanded state by radial expansion, the stent body has a mesh columnar structure in the expanded state, and the depth of the drug-carrying groove is 10% of the wall thickness of the mesh columnar structure ⁇ 60%.
  • the stent body is made of biodegradable polymer.
  • the depth of the drug-carrying groove is 25%-45% of the wall thickness of the mesh columnar structure.
  • the stent body includes a plurality of support unit rings and connecting rods, the support unit rings are connected by the connecting rods to form the net column structure, and the drug-carrying groove is provided at least in at least one of the Support the outer surface of the unit ring.
  • the cumulative groove length of the drug-loading groove on at least one of the support unit rings is 0.9 to 5 times the length of the support unit ring where it is located.
  • the groove width of the drug-carrying groove on at least one of the support unit rings is 10% to 80% of the width of the support unit ring where it is located.
  • At least one drug-carrying groove on at least one of the support unit rings is made by a continuous groove.
  • At least one of the two support unit rings located at the end of the stent body is provided with a plurality of drug-carrying grooves, and the plurality of drug-carrying grooves are arranged at intervals in the circumferential direction.
  • At least one support unit ring located between the ends of the stent body is provided with a closed drug-carrying groove.
  • At least one of the support unit rings is provided with a plurality of the drug-carrying grooves, and the plurality of the drug-carrying grooves are arranged at intervals along the axial direction of the support unit ring and do not intersect each other.
  • the groove line of the drug-carrying groove is a curved or wavy line extending in the circumferential direction of the supporting unit.
  • the drug-carrying groove on at least one of the support unit rings includes a plurality of convoluted groove segments and a plurality of connecting groove segments, and two adjacent convoluted groove segments are connected by one of the connecting groove segments.
  • the drug-carrying groove on at least one of the support unit rings includes a plurality of sub-slots, each of the sub-slots respectively having a main body section and a circuitous section extending from the end of the main body section to the main body section.
  • the main body section extends in the circumferential direction of the at least one supporting unit, and the partial structure of the circuitous section and the partial structure of the main body section are arranged side by side at intervals.
  • a manufacturing method of a degradable drug-loaded stent wherein the manufacturing method of the degradable drug-loaded stent includes the following steps:
  • a medicine-carrying groove is opened on the outer surface of the net columnar structure, and the depth of the medicine-carrying groove is 10% to 60% of the wall thickness of the net columnar structure.
  • the moving speed S of the focal point of the femtosecond laser on the outer surface of the mesh columnar structure meets the following conditions:
  • V is the moving speed of the femtosecond laser's focal point relative to the forming tube or stent parison when the femtosecond laser processes the formed tube or stent parison.
  • the medicine is filled into the medicine loading tank.
  • the surface of the stent body filled with medicine is polished.
  • This application provides a degradable drug-loaded stent and a manufacturing method thereof.
  • the stent body of the degradable drug-loaded stent is made of biodegradable polymer to realize the biodegradation of the material-loaded stent.
  • the depth of the drug-carrying trough can be controlled to be 10% to 60% of the wall thickness of the net columnar structure, so as to meet the physical performance requirements of the degradable drug-carrying stent while providing better adhesion effects for the drugs.
  • FIG. 1 is a schematic diagram of the main body structure of the degradable drug-loaded stent in one embodiment
  • Fig. 2 is a schematic front view of the stent body of the degradable drug-loaded stent shown in Fig. 1 along the axial direction;
  • Fig. 3 is a schematic diagram of the deployment of the stent body of the degradable drug-loaded stent shown in Fig. 1;
  • FIG. 4 is a schematic diagram of a partial structure of the stent body of the degradable drug-loaded stent shown in FIG. 3;
  • FIG. 5 is a schematic cross-sectional view of the stent body of the degradable drug-loaded stent shown in FIG. 4 along the line I-I;
  • FIG. 6 is a schematic cross-sectional view of another embodiment when the stent body of the degradable drug-loaded stent shown in FIG. 4 is cross-sectionally viewed along the line I-I;
  • FIG. 7 is a schematic cross-sectional view of another embodiment when the stent body of the degradable drug-loaded stent shown in FIG. 4 is cross-sectionally viewed along the line I-I;
  • Fig. 8 is a schematic cross-sectional view of another embodiment when the stent body of the degradable drug-loaded stent shown in Fig. 4 is cross-sectionally viewed along the line I-I;
  • Fig. 9 is a partial structural schematic diagram of the stent body of the degradable drug-loaded stent according to another embodiment when it is deployed;
  • Fig. 10 is a partial enlarged schematic diagram of the circle F in Fig. 9;
  • Fig. 11 is a partial structural diagram of the stent body of the degradable drug-loaded stent according to another embodiment when it is deployed;
  • FIG. 12 is a schematic diagram of the shape of the drug-loading groove on the ring of the support unit of the stent body in the degradable drug-loaded stent of another embodiment
  • Fig. 13 is a partial structural diagram of the stent body of the degradable drug-loaded stent according to another embodiment when it is deployed;
  • Fig. 14 is a partial enlarged schematic diagram of the dotted frame in Fig. 13;
  • 15 is a schematic diagram of electron microscopy on the outer surface side of the degradable drug-loaded stent in an embodiment when a continuous drug-loading groove is provided on the ring of the support unit of the stent body;
  • FIG. 16 is a schematic diagram of electron microscopy of the inner surface of the stent body when a continuous drug-carrying groove is opened on the support unit ring of the stent body shown in FIG. 15;
  • FIG. 17 is a schematic diagram of electron microscopy of a drug-carrying groove opened on the support unit ring of the stent body of an embodiment. The figure shows that the groove depth of the energy gathering point of the drug-carrying groove is relatively deep;
  • 18 is a schematic diagram of electron microscopy of the inner surface of the stent body when the support unit ring of the stent body is provided with a drug-carrying groove, wherein the energy of the drug-carrying groove is gathered to penetrate the inner surface of the support unit ring;
  • Fig. 19 is a schematic flow chart of the steps of a method for manufacturing a degradable drug-loaded stent according to an embodiment.
  • connection also includes a detachable connection.
  • inner, outer, outer, left, “right” and similar expressions used herein are for illustrative purposes only and do not mean that they are the only embodiments.
  • a degradable drug-loaded stent in an embodiment includes a stent body 10 made of biodegradable polymer.
  • the stent body 10 is made of a biodegradable polymer, which can be degraded and absorbed after being put into the body, avoiding the problem of negative effects caused by the traditional metal stent that needs to be removed through a second operation.
  • the stent body 10 is a structure that can expand and contract radially, and has a contracted state and an expanded state.
  • the stent body 10 is in a contracted state when it is pressed on the outer surface of the balloon catheter, and changes to an expanded state after being expanded by the balloon catheter.
  • the mesh columnar structure has opposite inner and outer surfaces 10a and 10b, wherein the outer surface 10b of the mesh columnar structure is provided with a drug-carrying groove 13, and the depth of the drug-carrying groove 13 is 10%-60% of the wall thickness of the mesh columnar structure.
  • the wall thickness h of the net columnar structure is the distance between the inner surface 10a and the outer surface 10b.
  • a drug-carrying groove 13 is provided on the outer surface 10b of the net column structure, and the drug can be contained in the drug-carrying groove 13, which can improve the adhesion of the drug to the degradable drug-carrying stent, thereby reducing the probability of drug shedding, and thus The uneven distribution of the medicine on the outer surface of the stent body 10 is avoided.
  • the degradable drug-carrying stent can also meet certain physical performance requirements, for example, the radial anti-extrusion performance of the degradable drug-carrying stent , Over-expansion (referred to as over-expansion) performance or axial retraction ability needs to meet the corresponding medical device standards. If the depth of the drug-carrying trough 13 accounts for more of the wall thickness of the net columnar structure, the wall thickness of the degradable drug-carrying stent will become thinner at the drug-carrying trough 13 and easily break.
  • the stent body of the degradable drug-carrying stent can not only meet the physical performance requirements, provide sufficient supporting force, but also provide better adhesion conditions for the drug and improve the adhesion effect of the drug.
  • multiple stent bodies of the degradable drug-loaded stent as shown in FIG. 1 are selected for physical performance testing.
  • the stent bodies of the multiple degradable drug-loaded stents used in the test are roughly divided into four in Table 1.
  • the structure design and size of the stent body of different types of degradable drug-loaded stents are basically the same. The difference is that the depth of the drug-loading groove 13 is changed. Specifically, the test results are shown in Table 1.
  • the wall thickness of the mesh columnar structure of each degradable drug-loaded stent is 125um.
  • the corresponding groove depth ratios of different types of degradable drug-loaded stents are 31.07 respectively. %, 36.21%, 60.02% and 67.64%.
  • the ratio of groove depth refers to the ratio of the depth of the drug-carrying groove 13 to the wall thickness h of the net columnar structure.
  • the stent body of the degradable drug-loaded stents with the groove depth ratios of 31.07%, 36.21%, 60.02% and 67.64% were tested for supporting force and overexpansion, and the corresponding average value was obtained through multiple tests, and the groove depth ratio was found
  • the support force of 31.07%, 36.21%, and 60.02% of the degradable drug-loaded stents are all not less than 50Kpa, which meets the standards for supporting biodegradable drug-loaded stents in vivo.
  • the measured support force of the biodegradable drug-carrying stent with a groove depth of 67.64% is 49.6Kpa, which is slightly less than the specified 50Kpa.
  • Table 1 also shows that when the proportion of groove depth changes at 31.07%, 36.21%, 60.02%, and 67.64%, the mean overexpansion of the corresponding degradable drug-loaded stents (over-expansion of the stent body of multiple degradable drug-loaded stents) After the test, the change of the average size of the over-expansion is very small, and all are above 4.5mm, which meets the expansion performance standard of the degradable drug-loaded stent.
  • Table 1 shows the test results of supporting force and overexpansion performance of the stent body of multiple degradable drug-loaded stents with groove depths of 31.07%, 36.21%, 60.02% and 67.64%, respectively. It reflects that the proportion of groove depth has a greater impact on the supporting force of the degradable drug-loaded stent, but has a small impact on the overexpansion performance. Further, in order to make the drug loading tanks 13 of different types of degradable drug-loading stents substantially the same, that is, to make the volumes of the drug loading tanks 13 of different types substantially the same, it needs to be changed according to the depth of the drug loading tanks 13 The groove width of the medicine-loading groove 13 is changed adaptively.
  • the groove depth In order to increase the area ratio of the grooved area occupying the outer surface 10b of the net columnar structure. In other words, while maintaining the drug loading of the drug loading tank 13 so that the drug is well attached to the drug loading tank 13, the groove depth cannot be infinitely small, and too much urine will cause the slotted area to occupy the net columnar structure. If the ratio of the area of the outer surface 10b is too large, it is easy to cause the edge structure of the drug-carrying groove 13 to be thinner and lower in strength, and cracks are likely to occur.
  • the inventor found that when the proportion of groove depth is reduced to less than 10%, the width of the groove is widened in order to ensure sufficient drug loading space, resulting in the edge structure of the drug loading slot It becomes thinner, and cracks are likely to occur during the expansion test. At this time, the overall mechanical performance of the stent body of the degradable drug-loaded stent decreases. Based on this, through experimental verification, taking into account that the degradable drug-loaded stent provides sufficient support and the ability of the drug to adhere to the stent body, the depth of the drug-loading groove 13 is controlled to be 10% of the wall thickness of the net columnar structure. % ⁇ 60% is reasonable and safe.
  • the depth of the drug-loading trough 13 can be controlled to account for 25% to 45% of the wall thickness h of the net columnar structure. After experimental verification, this range corresponds to the same drug-loaded amount.
  • the depth and width of the drug-carrying tank 13 can better meet the processing needs. For example, when the laser beam emitted by a femtosecond laser is used to process the drug-carrying groove 13 on the outer surface 10b of the net columnar structure, the processing width of the laser beam in a single scan is ⁇ , so when the width of the drug-carrying groove 13 is roughly controlled at ⁇ , Can avoid repetitive laser processing. At this time, only the laser beam is required to move along the processing path to form the drug-carrying groove 13 adapted to the processing path.
  • the biodegradable polymer used in the stent body 10 can have many choices.
  • the biodegradable polymer includes one or more of the following substances: polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolide or polyglycolic acid, PGA, polycyanoacrylate (PACA), polycaprolactone (PCL), polyanhydrides, polylactic acid copolymer (PLGA), polypentyl hydroxybutyrate (PHBV), polyacetylglutamic acid (PAGA), polyorthoester (POE) , Polyoxyethylene/polybutylene copolymer (PEO/PBTP), polyorthoester, polycaprolactone, polyglycolic acid, polyoxyethylene/polybutylene terephthalate copolymer, methacrylate or ester , Methacrylate or ester, polyurethane, silicone resin, polyvinyl alcohol, vinyl alcohol, polyglycolic acid, polyphosphoesterase, and copolymers formed by at least two of the monomers of the above-mentioned poly
  • the medicine filled in the medicine tank 13 includes one or more of the following substances: anti-inflammatory drugs, antiplatelet drugs, anticoagulants, anticancer drugs, immunosuppressants and/or hormones. , Inhibitor of intimal cell proliferation.
  • the medicine filled in the medicine-loading tank 13 is preferably rapamycin and its derivatives, paclitaxel and its derivatives, probucol and its derivatives, dexamethasone and its derivatives, asiaticoside, heparin, aspirin, One or more of cilostazol, ticlopidine, triptolide, cyclosporine, tacrolimus, or estradiol.
  • the medicine filled in the medicine-loading tank 13 is more preferably rapamycin.
  • the stent body 10 includes a plurality of support unit rings 11 and connecting rods 12.
  • the support unit rings 11 are connected by the connecting rods 12 to form a net column structure.
  • the drug-carrying groove 13 is preferably located in the support unit ring. 11 on.
  • At least one drug-carrying groove 13 on at least one supporting unit ring 11 is made by continuous grooving.
  • each drug-carrying groove 13 on each supporting unit ring 11 is a continuous groove made by a continuous groove.
  • the drug-carrying groove 13 formed by continuous grooving can be understood as, for example, that the grooving tool (such as laser) is not interrupted or stopped during the grooving process, so that there is no groove section between the two ends of the drug-carrying groove 13 Energy concentration point (for example, if the laser focus point pauses during processing, energy will be concentrated and superimposed at the pause point, and then a deeper energy concentration point with a deeper groove is formed).
  • each drug-carrying groove 13 on the support unit ring 11 at both ends of the stent body 10 has two ends, one of which corresponds to the starting position of the groove, and the other end corresponds to the ending position of the groove.
  • the drug-loading tank 13 is formed by laser processing as an example.
  • the laser continuously emits light, and the focus point of the laser moves from the starting position of the slot to the end position at a constant speed according to the set cutting speed, making the drug-loading tank 13
  • one-time processing and forming can reduce the number of energy accumulation points left by the drug-carrying groove 13 on the support unit ring 11 as much as possible under the same groove length, that is, reduce the energy accumulation points Where the laser energy is concentrated, there is a chance of material breakdown.
  • This structural form can not only provide a larger drug load, but also reduce material loss due to breakdown, and prevent the stent body 10 from generating local stress due to the lack of material, thereby reducing the risk of fracture of the stent body 10.
  • the two ends of the medicine-carrying groove 13 overlap so that the groove line of the medicine-carrying groove 13 is closed.
  • the starting position of the slot and the end position of the slot 13 coincide with each other, so that the slot 13 forms a closed loop (for example, in Figure 3, the slot 13 on the support unit ring 11 in the middle may be a closed ring slot).
  • the medicine-carrying groove 13 is a continuous groove, and the continuous groove may be formed by one-time continuous processing instead of multiple processing and shaping in sections, so as to minimize the number of energy gathering points of the medicine-carrying groove 13 on the support unit ring 11 .
  • the continuous grooved Processing the drug-loaded trough 13 in this way can reduce the breakdown probability of the stent body 10 and minimize the number of stress points of the stent body 10 to maintain good physical properties of the degradable drug-loaded stent.
  • FIG. 15 shows the groove section at the non-end position of the drug-carrying groove 13 formed by continuous grooving
  • FIG. 16 shows that there is no breakdown point on the side of the inner surface 10a.
  • the energy concentration point 13c of the drug-carrying tank 13 for example, the laser energy is superimposed due to a pause.
  • the energy concentration point 13c is deeper than the non-pause of the continuously processed drug-loading tank 13
  • the point is deep, and breakdown is likely to occur at the energy concentration point (see Figure 18), and it is easy to form a breakdown point on the side of the inner surface 10a, where local material stress is formed, which is not conducive to the structure of the stent body 10. strength.
  • the two adjacent ends of two adjacent drug-carrying troughs 13 are arranged at intervals, so as to further avoid that when the drug-carrying trough 13 is processed by laser, the laser energy is superimposed on the two overlapping ends to easily penetrate Support unit ring 11.
  • the risk of the support unit ring 11 being penetrated is reduced, thereby preventing the stent body 10 from being broken due to stress concentration at the penetrated position when the stent body 10 contracts or expands.
  • each support unit ring 11 is provided with a plurality of drug loading grooves 13 to increase the drug loading.
  • the structure of the support unit ring 11 has multiple possibilities.
  • the support unit ring 11 may be a ring structure formed by a support rod.
  • the support unit ring 11 may be a net ring structure formed by a plurality of struts.
  • the structure of the support unit ring is not limited here.
  • the extending direction and the arrangement form of the medicine-carrying groove 13 can be adaptively adjusted according to the struts constituting the supporting unit ring 11.
  • the support unit ring 11 is composed of struts.
  • the multiple drug-loading grooves 13 are arranged at intervals along the axial direction of the support unit ring 11, and the multiple drug-loading grooves 13 do not intersect each other, so as to avoid the superposition of laser energy at the intersection and cause the stent body 10 to easily produce breakdown points. As shown in FIG.
  • each support unit ring 11 is provided with two drug-loading grooves 13, and each of the two drug-loading grooves 13 has substantially the same profile in the extending direction, that is, the two drug-loading grooves 13 are in the extending direction.
  • the intervals on each part of the upper part are roughly equal and extend roughly parallel to each other, so that the two drug-carrying grooves 13 are evenly distributed on the surface of the support unit ring 11.
  • the physical properties of the materials of the support unit ring 11 are equivalent, and the forces are more balanced. The overall structural strength is better.
  • the drug-carrying grooves 13 provided on the plurality of struts are made in a form of continuous grooves and disjoint to obtain the whole degradable drug-carrying stent.
  • it can also be slotted according to the extension direction of each support rod.
  • the direction of the groove line of the drug-carrying groove 13 on each strut is roughly the same as that of the strut, so that after the strut is slotted, the force on each part is equivalent, which avoids local stress and easy breakage.
  • the groove line of the drug-loading groove 13 may also be a curved or wavy line extending in the circumferential direction of the support unit ring 11 to increase the unit length along the extension direction of the support unit ring 11. The cumulative groove length on the upper side, thereby increasing the drug load.
  • the cross-sectional shape of the drug-carrying tank 13 may have various possibilities.
  • the cross-sectional shape of the medicine-carrying tank 13 is V-shaped.
  • the cross-sectional shape of the medicine-carrying tank 13 is U-shaped.
  • the cross-sectional shape of the drug-carrying tank 13 is trapezoidal.
  • the depth d (equivalent to the depth Y of the front groove) and the width a (equivalent to the width X of the front groove) of the drug-loading tank 13 can be adjusted adaptively to meet the requirements of different drug-loading amounts. It only needs to satisfy that the depth d of the drug-carrying tank 13 is 10%-60% of the wall thickness h of the net columnar structure.
  • the width a of the medicine-loading groove 13 is 10% to 80% of the width W of the support unit ring 11.
  • the cumulative groove length of the medicine-loading groove 13 is 0.9 to 5 times the length of the supporting unit ring 11 where it is located. Therefore, the drug loading capacity can be increased by the arrangement of the longer drug loading tank 13.
  • the cumulative groove length of the medicine-carrying groove 13 can be 0.9 to 5 times the length of the supporting unit ring 11 where it is located by means of winding grooves or spiral grooves.
  • the overall extension direction of the drug-carrying groove 13 is consistent with the extension direction of the support unit ring 11.
  • the slotting paths of the drug-carrying slot 13 do not intersect and the continuous slot is formed by continuous slotting as far as possible to avoid At the intersection or the pause, energy gathers to produce a breakdown point.
  • the cumulative length of the drug-carrying groove 13 is less limited by the length of the support unit ring 11, and can be 5 times the length of the support unit ring 11 where it is located to increase the drug-carrying capacity.
  • the phenomenon of material breakdown is less, so that the better physical properties of the degradable drug-loaded stent can be maintained to meet the needs of use.
  • the medicine-carrying tank 13 includes a convoluted groove section 13a and a connecting groove section 13b.
  • the cumulative groove length of the convolution groove section 13a is greater than the length of the connecting groove section 13b, and the groove lines of the convolution groove section 13a do not intersect each other.
  • the convolute groove section 13a has a denser groove line relative to the connecting groove section 13b, so that the convolute groove section 13a can be used to increase the local drug loading, so as to perform fixed-point drug application.
  • the cumulative groove length of the convolution groove section 13a is greater than the length of the connecting groove section 13b. Therefore, after the degradable drug-loaded stent is loaded with drugs and implanted in the body, the amount of drug loaded in the convolute groove section 13a is relatively large, which can prolong the drug effect of the corresponding position of the convolute groove section 13a.
  • the medicine-carrying tank 13 includes a plurality of swirling groove sections 13a and a plurality of connecting groove sections 13b, and the plurality of swirling groove sections 13a are connected in series through a plurality of connecting groove sections 13b respectively, so that the medicine carrying groove 13 can pass through as continuous as possible.
  • the slotting method minimizes the possibility of breakdown at a local location due to energy concentration, thereby improving the overall structural strength of the degradable drug-loaded stent, so as to maintain good physical properties of the stent body 10.
  • the distance between the multiple convolute groove segments 13a can be equal, in other words, the multiple convolute groove segments 13a can be evenly distributed on the corresponding support unit ring 11, so that the force on the support unit ring 11 is balanced and maintains a relatively stable Structural strength.
  • the medicine-loading groove 13 may also adopt a circuitous manner to increase the cumulative groove length per unit length on the support unit ring 11 so as to load more medicine.
  • the drug-carrying tank 13 includes a plurality of sub-slots 131.
  • the sub-slots 131 have a main body section 131a and a circuitous section 131b extending from the end of the main body section 131a to the opposite direction relative to the main body section 131a.
  • the main body section 131a runs along the supporting unit.
  • the ring 11 extends in the circumferential direction, and the partial structure of the detour section 131b and the partial structure of the main section 131a are arranged side by side at intervals. The use of this detour arrangement increases the cumulative groove length per unit length in the extension direction of the support unit ring 11 to meet more loading requirements. The need for medication.
  • adjacent sub-slots 131 are nested together through their respective winding sections 131b, and the groove lines of multiple sub-slots 131 do not intersect each other, so as to avoid laser processing the drug-carrying groove 13
  • the intersection of slot lines may cause breakdown due to energy concentration.
  • the present application also provides a method for manufacturing a degradable drug-loaded stent.
  • the manufacturing method of the degradable drug-loaded stent includes the following steps:
  • step S102 the pipe or stent parison is processed and formed by the biodegradable polymer.
  • the biodegradable polymer includes one or more of the following substances: polylactic acid (PLA), poly-L-lactic acid (PLLA), polyglycolide or polyglycolic acid, PGA, polycyanoacrylate (PACA), Polycaprolactone (PCL), polyanhydrides, polylactic acid copolymer (PLGA), polypentyl hydroxybutyrate (PHBV), polyacetylglutamic acid (PAGA), polyorthoester (POE), polyethylene oxide /Polybutene copolymer (PEO/PBTP), polyorthoester, polycaprolactone, polyglycolic acid, polyoxyethylene/polybutylene terephthalate copolymer, methacrylate or methacrylic acid Salt or ester, polyurethane, silicone resin, polyvinyl alcohol, vinyl alcohol, polyglycolic acid, polyphosphoesterase, and a copolymer of at least two of the monomers of the above-mentioned polymers.
  • PHA
  • step S104 a femtosecond laser is used to process the molded tube or stent parison to form the stent body 10 with a net column structure, and the stent body 10 can expand and contract radially.
  • a femtosecond laser is used to process and remove part of the material, and a hollow groove C is opened to form a radially expandable mesh columnar structure, that is, the stent body 10.
  • Step S106 using a femtosecond laser to open a drug-carrying groove 13 on the outer surface 10b of the net columnar structure, and the depth of the drug-carrying groove 13 is 10% to 60% of the wall thickness of the net columnar structure.
  • the laser when processing the drug-loaded groove 13, the laser continuously emits light, and the focal point of the laser moves from the starting position of the groove to the ending position.
  • the starting position and end position preferably correspond to one end and the other end of a continuous medicine-carrying tank 13, so that it can be as long as possible with the same groove length. It is possible to reduce the number of energy concentration points left by the drug-carrying groove 13 on the support unit ring 11, that is, to reduce the phenomenon of material breakdown due to laser energy concentration at a local location. Under this structure, it can provide more drug load and reduce the breakdown point, thereby preventing the stent body 10 from generating local stress due to the lack of material, and reducing the risk of rupture of the stent body 10.
  • the moving speed S of the focal point of the femtosecond laser on the outer surface 10b of the mesh columnar structure meets the following conditions:
  • V is the moving speed of the femtosecond laser's focal point relative to the forming tube or stent parison when the femtosecond laser processes the formed tube or stent parison.
  • the focal point of the femtosecond laser moves faster on the outer surface 10b of the net columnar structure That is, the laser cutting speed for opening the drug-loading groove 13 is faster than the laser cutting speed for opening the hollow groove C, so as to reduce the laser energy absorbed per unit cutting length and reduce the risk of the stent body 10 being broken down.
  • the drug is filled into the drug loading tank 13 in a micron-level or nano-level spraying manner.
  • the surface of the stent body can be polished to remove the drug overflowing the surface of the stent.
  • the thickness of the medicine contained in the medicine loading tank 13 is basically uniform, and the medicine can be uniformly released.
  • the drug-loading slot 13 can improve the adhesion ability of the drug on the degradable drug-loaded stent, and the drug is loaded
  • the influence of the groove 13 on the physical properties of the degradable drug-loaded stent is controlled within the scope of the medical device standard.
  • the degradable drug-loaded stent shown in Figure 3 was selected for physical performance testing, and stents with diameters of 2.5 mm, 3.0 mm, and 4.0 mm were used for group control experiments.
  • the diameter of the stent refers to the diameter of the mesh columnar structure in an expanded state. That is, the diameters of the selected mesh columnar structures corresponding to the multiple degradable drug-loaded stent samples provided with the drug-loading trough 13 include 2.5 mm, 3.0 mm, and 4.0 mm.
  • a degradable stent with the same specifications and no drug-loading tank was used as a reference sample for physical performance testing for reference.
  • the serial numbers 1, 2, 3, and 4 in Table 2-Table 10 represent the No. 1, 2, 3, and 4 brackets of the specification model.
  • the wall thickness of the mesh column structure of the stents 1-4 is about 125 ⁇ m
  • the stents 1 and 2 are ungrooved stents
  • the stents 3 and 4 are the degradable drug-loading stents with the drug-loading trough 13.
  • the depth of 13 is controlled to be 40 ⁇ m-60 ⁇ m
  • the groove width of the medicine-loading groove 13 on the outer surface 10b is controlled to be 30 ⁇ 10 ⁇ m
  • the groove line of the medicine-loading groove 13 is continuously made one round along the circumferential direction of the support unit ring 11.
  • Table 2 to Table 4 respectively list the radial anti-extrusion data of the stents with diameters of 2.5mm, 3.0mm and 4.0mm. From Table 2-4, we can see that the samples 3 and 4 with the drug loading tank 13 are relative to the reference samples. The anti-extrusion performances of 1 and 2 are equivalent, that is, after opening the drug-carrying groove 13 on the outer surface 10b of the net columnar structure, it still has a relatively good radial anti-extrusion performance.
  • the fracture diameter is used as an indicator to measure the over-expansion performance.
  • the fracture diameter refers to the stent being processed, stored, and aging under certain conditions, and the stent is gradually expanded in 37°C water using a balloon until support appears. The diameter corresponding to the bracket when the unit ring 11 is broken.
  • the fracture diameters of the samples 3 and 4 with the drug-loading tank 13 are equivalent to those of the reference samples 1 and 2, that is, after the drug-loading tank 13 is opened on the outer surface 10b of the net columnar structure, There is little difference in the over-expansion performance of the stent, and it still has a good over-expansion performance.

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Abstract

一种可降解载药支架及其制作方法。其中，可降解载药支架包括支架主体（10），支架主体的外表面设置有载药槽（13）；支架主体具有收缩状态及扩张状态，支架主体能够通过径向扩展从所述收缩状态切换到所述扩张状态，支架主体在扩张状态下为网柱状结构，载药槽（13）的深度为网柱状结构的壁厚的10％～60％。

Description

可降解载药支架及其制作方法 技术领域
本申请涉及医疗器械技术领域，特别是涉及一种可降解载药支架及其制作方法。
背景技术
心血管疾病已成为威胁人类健康的主要疾病之一，心血管疾病中最常见的疾病包括冠状动脉粥样硬化性心脏病，也常被称为冠心病。冠心病是由于脂质代谢不正常，血液中的脂质沉着在原本光滑的动脉内膜上，形成类似粥样的白色斑块(称为冠状动脉粥样硬化病变)，引起血管腔狭窄或阻塞，造成心肌缺血、缺氧而导致的心脏病。经皮动脉介入支架手术已然成为用于治疗冠心病的重要的治疗手段。目前，支架类型主要包括金属裸支架和药物洗脱支架两种。金属裸支架存在的最大问题是可能发生内膜增生而导致再狭窄。药物洗脱支架的应用使再狭窄率由裸支架的30％下降到10％以下。
随着支架材料技术的发展，可降解支架以其优越的降解性在药物洗脱支架中得到广泛的应用，其能够在植入体内一段时期后被降解吸收。
然而，可降解支架也存在一些问题。例如，在将药物涂覆在支架表面上的涂层过程中，喷涂的药物液滴容易发生溢出，导致药物涂层在支架表面上厚度不一致，分布不均。当支架植入体内后，药物涂层的不均匀分布可能造成药物释放不均匀或药物溢出部分脱落的问题，容易引起血栓。此外，可降解支架所采用的材料相比金属支架而言较为脆弱。基于此，业界急需攻克如何在提供足够的支撑力的情况下改善药物在支架上的附着能力这一现实性技术难题。
发明内容
基于此，本申请提供一种可降解载药支架以及该可降解载药支架的制作方法，在提供足够的支撑力的情况下改善药物在可降解支架上的附着能力。
一种可降解载药支架，其中，所述可降解载药支架包括支架主体，所述支架主体的外表面设置有载药槽；所述支架主体具有收缩状态及扩张状态，所述支架主体能够通过径向扩展从所述收缩状态切换到所述扩张状态，所述支架主体在所述扩张状态下为网柱状结构，所述载药槽的深度为所述网柱状结构的壁厚的10％～60％。
进一步地，所述支架主体由生物可降解聚合物制成。
进一步地，所述载药槽的深度为所述网柱状结构的壁厚的25％～45％。
进一步地，所述载药槽的深度与宽度满足如下条件：Y＝120-2X；其中，Y为所述载药槽的深度，X为所述载药槽的宽度，Y的取值范围为小于等于80微米。
进一步地，所述支架主体包括多个支撑单元环和连接杆，所述支撑单元环之间通过所述连接杆相连以形成所述网柱状结构，所述载药槽至少设置于至少一个所述支撑单元环的外表面上。
进一步地，至少一个所述支撑单元环上的所述载药槽的累计槽长为其所在的所述支撑单元环的长度的0.9倍～5倍。
进一步地，至少一个所述支撑单元环上的所述载药槽的槽宽为其所在的所述支撑单元环的宽度的10％～80％。
进一步地，至少一个所述支撑单元环上的至少一个载药槽通过连续开槽方式制成。
进一步地，位于所述支架主体的端部的两个支撑单元环中的至少一个上设置有多个载药槽，所述多个载药槽在周向上间隔布置。
进一步地，位于所述支架主体的端部之间的至少一个支撑单元环上设置有闭合的载药槽。
进一步地，至少一个所述支撑单元环上设置有多个所述载药槽，多个所述载药槽沿所述支撑单元环的轴向间隔设置且互不相交。
进一步地，所述载药槽的槽线为沿所述支撑单元环周向延伸的曲线或波浪线。
进一步地，至少一个所述支撑单元环上的所述载药槽包括多个回旋槽段和多个连接槽段，相邻的两个所述回旋槽段通过一个所述连接槽段连接。
进一步地，至少一个所述支撑单元环上的所述载药槽包括多个子槽，各所述子槽分别具有主体段和由所述主体段的端部相对所述主体段迂回延伸的迂回段，所述主体段沿所述至少一个支撑单元环周向延伸，所述迂回段的部分结构与所述主体段的部分结构间隔地并排在一起。
一种可降解载药支架的制作方法，其中，所述可降解载药支架的制作方法包括以下步骤：
采用生物可降解聚合物加工成型管材或支架型坯；
对成型管材或支架型坯进行加工，以形成网柱状结构的支架主体，所述支架主体可径向扩展和收缩；
在所述网柱状结构的外表面开设载药槽，所述载药槽的深度为所述网柱状结构的壁厚的10％～60％。
进一步地，开设载药槽时，飞秒激光器的聚焦点在网柱状结构的外表面移动速度S满足如下条件：
V＜S≤10V，
其中，V为飞秒激光器对成型管材或支架型坯进行加工时，飞秒激光器的聚焦点相对成型管材或支架型坯的移动速度。
进一步地，开设载药槽后将药物填充至所述载药槽内部。
进一步地，对已填充药物的支架主体的表面进行打磨处理。
本申请提供了可降解载药支架及其制作方法，可降解载药支架的支架主体采用生物可降解聚合物制成，以实现载料支架的生物降解。通过在支架的外表面开设载药槽，使药物填充到载药槽中的方式，改善了药物在支架主体上的附着能力，避免了药物以涂层方式附着在支架主体上时容易造成厚度分布不均匀的问题。此外，可以将载药槽的深度控制在网柱状结构的壁厚的10％～60％，以在满足可降解载药支架的物理性能要求的同时为药物提供较好的附着效果。
附图说明
图1为一实施方式中可降解载药支架的支架主体结构示意图；
图2为图1示出的可降解载药支架的支架主体沿轴向的正视示意图；
图3为图1示出的可降解载药支架的支架主体的展开示意图；
图4为图3示出的可降解载药支架的支架主体的局部结构示意图；
图5为图4示出的可降解载药支架的支架主体沿I-I线的剖视示意图；
图6为图4示出的可降解载药支架的支架主体沿I-I线进行剖视时，另一实施方式的剖视示意图；
图7为图4示出的可降解载药支架的支架主体沿I-I线进行剖视时，又一实施方式的剖视示意图；
图8为图4示出的可降解载药支架的支架主体沿I-I线进行剖视时，再一实施方式的剖视示意图；
图9为另一实施方式的可降解载药支架的支架主体展开时的局部结构示意图；
图10为图9中圆圈F部分的局部放大示意图；
图11为另一实施方式的可降解载药支架的支架主体展开时的局部结构示意图；
图12为另一实施方式的可降解载药支架中，支架主体的支撑单元环上的载药槽形态示意图；
图13为另一实施方式的可降解载药支架的支架主体展开时的局部结构示意图；
图14为图13中虚线框处的局部放大示意图；
图15为一实施方式中的可降解载药支架中，支架主体的支撑单元环上开设连续的载药槽时，外表面一侧的电子显微示意图；
图16为图15示出的支架主体的支撑单元环上开设连续的载药槽时，支架主体的内表面一侧的电子显微示意图；
图17为一实施方式的支架主体的支撑单元环上开设的载药槽的电子显微示意图，图中示出，载药槽的能量聚集点的槽深比较深；
图18为支架主体的支撑单元环上开设有载药槽时，支架主体的内表面的电子显微示意图，其中，载药槽的能量聚集点击穿支撑单元环的内表面；
图19为一实施方式的可降解载药支架的制作方法的步骤流程示意图。
具体实施方式
为了便于理解本申请，下面将参照相关附图对本申请进行更全面的描述。附图中给出了本申请的较佳实施方式。但是，本申请可以以许多不同的形式来实现，并不限于本文所描述的实施方式。相反地，提供这些实施方式的目的是使对本申请的公开内容理解的更加透彻全面。
需要说明的是，当元件被称为“固定于”另一个元件，它可以直接在另一个元件上或者也可以存在居中的元件。当一个元件被认为是“连接”另一个元件，它可以是直接连接到另一个元件或者可能同时存在居中元件，所述“连接”也包括可拆卸的连接。本文所使用的术语“内”、“外”、“左”、“右”以及类似的表述只是为了说明的目的，并不表示是唯一的实施方式。
结合图1和图2所示，一实施例中的一种可降解载药支架，包括生物可降解聚合物制成的支架主体10。支架主体10采用生物可降解聚合物制成，在放入体内后，可以被降解吸收，避免传统的金属支架需要通过二次手术取出而引起负面效果的问题。该实施例中，支架主体10为可径向扩展和收缩的结构，具有收缩状态及扩张状态。例如，支架主体10压握于球囊导管的外表面时处于收缩状态，经球囊导管膨胀后改变为扩张状态。网柱状结构具有相对的内表面10a和外表面10b，其中，网柱状结构的外表面10b开设有载药槽13，载药槽13的深度为网柱状结构的壁厚的10％～60％。如图2所示，网柱状结构的壁厚h即为内表面10a与外表面10b之间的距离。
该实施方式中，在网柱状结构的外表面10b开设载药槽13，药物能够容纳在载药槽13中，能够改善药物在可降解载药支架上的附着能力，从而降低药物脱落机率，进而避免药物在支架主体10外表面上的不均匀分布。当载药槽13的深度为网柱状结构的壁厚的10％～60％时，可降解载药支架也能够满足一定的物理性能要求，例如，可降解载药支架的径向抗挤压性能、过度扩张(简称过扩)性能或轴向回缩能力需要满足相应的医疗器械标准。如果载药槽13的深 度占网柱状结构的壁厚较多，将会导致可降解载药支架的壁厚在载药槽13处变薄而容易出现断裂。通过对载药槽13的深度进行合理设置，使得可降解载药支架的支架主体既能够满足物理性能要求，提供足够支撑力，又能够为药物提供较好的附着条件，改善药物的附着效果。
在一些实施方式中，选取多个如图1示出的可降解载药支架的支架主体进行物理性能测试，测试所采用的多个可降解载药支架的支架主体大体分为表1中的四类，不同类别的可降解载药支架的支架主体的结构设计、尺寸基本一致，区别在于载药槽13的深度有所变化。具体地，测试结果参照表1所示。
表1
Figure PCTCN2020089349-appb-000001
表1中，各可降解载药支架的网柱状结构的壁厚均为125um，通过仅调整载药槽13的深度，使得不同类别的可降解载药支架的相应的槽深占比分别为31.07％、36.21％、60.02％和67.64％。其中，槽深占比指的是载药槽13的深度与网柱状结构的壁厚h的比值。分别对槽深占比为31.07％、36.21％、60.02％和67.64％的可降解载药支架的支架主体进行支撑力及过扩测试，通过多次测试并求得相应均值，发现槽深占比为31.07％、36.21％、60.02％的可降解载药支架的支撑力均值均不低于50Kpa，符合可降解载药支架类医疗器械在体内支撑的标准。相应地，槽深占比为67.64％的可降解载药支架所测得的支撑力均值为49.6Kpa，略小于规定的50Kpa，由于支撑力不够而存在体内坍缩风险，被认定为不合格。表1还表明，槽深占比在31.07％、36.21％、60.02％和67.64％变化时，相应的可降解载药支架的过扩均值(对多个可降解载药支架的支架主体进行过度扩张测试后的过扩尺寸平均值)变化很小，且都在4.5mm以上，符合可降解载药支架的扩张性能标准。
需要说明的是，表1示出了对槽深占比分别为31.07％、36.21％、60.02％和67.64％的多个可降解载药支架的支架主体进行支撑力及过扩性能测试的结果，其反应出槽深占比对可降解载药支架的支撑力影响较大，而对过扩性能影响较小。进一步地，为了使不同类别的可降解载药支架的载药槽13的载药量大体相同，即，使不同类别的载药槽13的容积大体相同，需要根据载药槽13的深度改变而使载药槽13的槽宽做适应性的改变。其中，载药槽13相对网柱状结构的槽深占比越小，表明载药槽13的越浅，继而此时需要扩宽载药槽13的槽宽或者提高载药槽13的开槽数量，以提高开槽面积占据网柱状结构的外表面10b的面积比。也就是说，在维持载药槽13的载药量，使得药物良好地附着在载药槽13中的同时，槽深占比不可能无限的小，过小便会导致开槽面积占据网柱状结构的外表面10b的面积的比值过大，容易导致载药槽13的边缘结构较薄而强度较低，进而容易出现裂纹。
发明人在减小槽深占比的研究过程中发现，当槽深占比减小到低于10％时，为了确保足够的载药空间而扩宽槽的宽度，导致载药槽的边缘结构变薄，进而在进行扩张测试时容易出现裂纹，此时，可降解载药支架的支架主体的整体力学性能下降。基于此，通过实验验证，在考虑可降解载药支架提供足够的支撑力以及药物在支架主体上的附着能力的情况下，将载药槽13的深度控制在占网柱状结构的壁厚的10％～60％是合理安全的。
在一些实施方式中，可以将载药槽13的深度控制在占网柱状结构的壁厚h的25％～45％，经过实验验证，在维持同等载药量的情况下，这一范围所对应的载药槽13的深度和宽度能够更好的适应加工需要。例如，采取飞秒激光器发出的激光束在网柱状结构的外表面10b加工载药槽13时，激光束单次扫描的加工宽度为φ，那么将载药槽13的宽度大致控制在φ时，可以避免激光重复加工。此时，只需要激光束沿着加工路径移动便可以形成与加工路径相适应的载药槽13。
在一些实施方式中，为了满足载药量的要求，载药槽13的深度与宽度例如满足如下条件：Y＝120-2X，其中，Y为槽深，X为槽宽，Y的取值范围为小于等于80微米，显然，Y大于零。当槽深与槽宽满足上述条件时，既可以避免槽深过大影响生物可降解聚合物支架的力学性能，也可以满足医用支架的载药需求。
支架主体10所采用的生物可降解聚合物可以有多种选择。
在一些实施方式中，生物可降解聚合物包括下述一种或多种物质：聚乳酸(PLA)、聚左旋乳酸(PLLA)、聚乙交酯或聚羟基乙酸，PGA、聚氰基丙烯酸酯(PACA)，聚己酸内酯(PCL)、聚酸酐类、聚乳酸共聚物(PLGA)、聚羟基丁酸戊酯(PHBV)、聚乙酰谷氨酸(PAGA)、聚正酯(POE)、聚氧化乙烯/聚丁烯共聚物(PEO/PBTP)，聚原酸酯、聚己内酯、聚羟基乙酸、聚氧化乙烯/聚对苯二甲酸丁二酯共聚物、异丁烯酸盐或酯、甲基丙烯酸盐或酯、聚亚安酯、硅树脂、聚乙烯乙醇、乙烯基乙醇、聚羟基乙酸、聚磷酸酯酶，以及上述聚合物的单体中的至少两种形成的共聚物或共混物。
在一些实施方式中，载药槽13中所填充的药物包括下述一种或多种物质：抗炎症类药物、抗血小板药物、抗凝血剂、抗癌药物、免疫抑制剂和/或激素、内膜细胞增生抑制剂。载药槽13中填充的药物优选为雷帕霉素及其衍生物、紫杉醇及其衍生物、普罗布考及其衍生物、地塞米松及其衍生物、积雪草苷、肝素、阿司匹林、西洛他唑、噻氯匹定、雷公藤内酯、环孢霉素、他克莫斯或雌二醇的一种或多种。载药槽13中填充的药物更优选为雷帕霉素。
继续参阅图1所示，支架主体10包括多个支撑单元环11和连接杆12，支撑单元环11之间通过连接杆12相连，以形成网柱状结构，载药槽13优选地位于支撑单元环11上。
结合图3和图4所示，在一些优选方式中，至少一个支撑单元环11上的至少一个载药槽13是通过连续开槽方式制成的。优选地，每一支撑单元环11上的各个载药槽13均为通过连续开槽方式制成的连续槽。通过连续开槽方式形成的载药槽13例如可以理解为开槽工具(例如激光)在开槽过程中没有中断或停顿，使得载药槽13的位于两个端部之间的槽段上没有能量聚集点(例如，若激光聚焦点在加工过程中发生停顿，能量将在该停顿点处聚集叠加，继而形成槽深较深的能量聚集点)。例如图3中，支架主体10两端的支撑单元环11上的各个载药槽13分别具有两个端部，其中一个端部对应于开槽起点位置，另一个端部对应于开槽终点位置。载药槽13以激光加工成型为例，在加工载药槽13时，激光器持续出光，激光的聚焦点从开槽的起点位置按照设定的切割速度匀速移至终点位置，使得载药槽13通过连续开槽的方式一次加工成型，这样可以在同等槽长的情况下，尽可能的减少载药槽13在支撑单元环11上留下的能量聚集点数量，也即减少了因能量聚集点处激光能量集中而出现材料击穿的几率。这种结构形式，既能够提供较多载药量，又能够减少因击穿而造成的材料缺失，防止支架主体10因材料缺失而产生局部应力，从而降低了支架主体10断裂风险。
在一些实施方式中，载药槽13的两端部重合以使得载药槽13的槽线闭合。例如，载药槽13的开槽起点位置和开槽终点位置重合，使得载药槽13形成闭环(例如图3中，居于中间的 支撑单元环11上的载药槽13可以为闭环槽)。该实施方式中，载药槽13为连续槽，该连续槽可以是一次连续加工成型而不是分区段多次加工成型，从而尽可能减少载药槽13在支撑单元环11上的能量聚集点数量。如上所述，由于采用激光加工载药槽13时，激光能量容易在停顿位置或者中断位置产生叠加效应而击穿由生物可降解聚合物制成的支架主体10，因此通过这种连续开槽的方式加工载药槽13，可以减少支架主体10的击穿几率，尽可能减少支架主体10应力点的数量，以保持可降解载药支架良好的物理性能。
结合图15和图16所示，图15示出了连续开槽加工形成的载药槽13的非端部位置的槽段，图16示出了内表面10a所在一侧没有出现击穿点。结合图17和图18所示，在载药槽13的能量聚集点13c处，例如是由于停顿所导致的激光能量叠加，能量聚集点13c处的深度比连续加工的载药槽13的非停顿点处深，在能量聚集点处容易产生击穿现象(参阅图18所示)，容易在内表面10a所在一侧形成击穿点，此处形成局部的材料应力，不利于支架主体10的结构强度。通过上述实施方式可以看出，利用激光连续开槽来形成槽线连续的载药槽13可以减少这种击穿现象，可以保持可降解载药支架良好的物理性能。
在一些实施方式中，相邻两个载药槽13的相邻两个端部间隔设置，从而进一步避免利用激光加工载药槽13时，激光能量在重合的两个端部叠加而容易穿透支撑单元环11。通过这种结构形式，减少支撑单元环11被穿透的风险，从而避免支架主体10在收缩或扩张时，被穿透的位置产生应力集中而发生断裂。
在一些实施方式中，每一支撑单元环11上开设有多个载药槽13，以提高载药量。
需要说明的是，支撑单元环11结构形态具有多种可能，例如，在一些实施方式中，支撑单元环11可以是由一个支杆形成的环状结构。再如，在一些实施方式中，支撑单元环11可以是多个支杆形成的网环状结构。对于支撑单元环的结构形态，在此不作限定。
此外，在支撑单元环11的表面开设载药槽13时，载药槽13的延伸方向以及布置形式可以根据构成支撑单元环11的支杆作适应性调整。例如，在一些实施方式中，支撑单元环11由支杆构成，在设置多个载药槽13时，多个载药槽13沿支撑单元环11的轴向间隔布置，且多个载药槽13互不相交，从而避免相交的地方出现激光能量叠加而导致支架主体10容易产生击穿点。结合图11所示，每一支撑单元环11上开设有2个载药槽13，2个载药槽13在延伸方向上的每一处轮廓大体相同，即2个载药槽13在延伸方向上的每处间隔大体相等，大体相平行地延伸，进而使得2个载药槽13在支撑单元环11的表面呈均匀分布，支撑单元环11各处的材料物理性能相当，受力较为均衡，整体结构强度较好。
在此基础上，在支撑单元环11为多个支杆构成时，多个支杆上开设的载药槽13除了采用连续开槽且不相交的形式来制成以获得可降解载药支架整体上较佳的物理力学性能之外，还可以根据各支杆的延伸方向进行开槽。例如，各支杆上的载药槽13的槽线的走向与支杆的走向形态大体一致，从而使得支杆在开槽后，各处的受力相当，避免了产生局部应力而容易断裂。
结合图12所示，在一些实施方式中，载药槽13的槽线还可以是沿支撑单元环11周向延伸的曲线或波浪线，以提高在沿支撑单元环11延伸方向上的单位长度上的累计槽长，进而提高载药量。
载药槽13的截面形状可以具有多种可能。例如，如图5所示，载药槽13的截面形状为V形。如图6所示，载药槽13的截面形状为U形。再如图7和图8所示，载药槽13的截面形状为梯形。结合图5至图8所示，载药槽13的深度d(相当于前面的槽深Y)以及宽度a(相当于前面的槽宽X)可以适应性调整，以满足不同载药量需求，只需满足载药槽13的深度d 为网柱状结构的壁厚h的10％～60％即可。
在一些实施方式中，载药槽13的宽度a为支撑单元环11的宽度W的10％～80％。在维持载药量不变的情况下，载药槽13的宽度a越大，载药槽13的深度d越小，也就是说，在设计载药槽13的开设尺寸时，为适应预定的载药量需求，载药槽13的宽度a设计的越宽，载药槽13的深度越浅。
在一些实施方式中，载药槽13的累计槽长为其所在的支撑单元环11的长度的0.9倍～5倍。从而通过较长载药槽13的设置提高载药量。在载药槽13为连续槽的情况下，可以通过迂回开槽或螺旋开槽的方式使得载药槽13的累计槽长为其所在的支撑单元环11的长度的0.9倍～5倍。例如图9所示，载药槽13的整体延伸方向与支撑单元环11的延伸方向一致，载药槽13的开槽路径不相交并尽可能通过连续开槽的方式形成连续槽，以避免因交集位置或停顿位置能量聚集而产生击穿点。通过螺旋或迂回的开槽方式，使得载药槽13的累计长度受支撑单元环11的长度限制较少，能够做到其所在的支撑单元环11的长度的5倍，以提高载药量。采用连续开槽方式，材料被击穿的现象较少，从而能够维持可降解载药支架较好的物理性能以满足使用需要。
结合图9和图10所示，载药槽13包括回旋槽段13a和连接槽段13b。优选地，在同一个支撑单元环11上，回旋槽段13a的累计槽长大于连接槽段13b的长度，且回旋槽段13a的槽线互不相交。该实施方式中，回旋槽段13a相对于连接槽段13b，具有更为密集的槽线，从而可以利用回旋槽段13a加大局部载药量，从而进行定点施药。确切的说，由于在同一个支撑单元环11上，回旋槽段13a的累计槽长大于连接槽段13b的长度。从而在可降解载药支架装载药物植入体内后，回旋槽段13a装载的药量相对较多，能够延长回旋槽段13a对应位置的药效。
载药槽13包括多个回旋槽段13a和多个连接槽段13b，多个回旋槽段13a之间分别通过多个连接槽段13b串接在一起，以使得载药槽13能够尽量通过连续开槽的方式获得，尽可能降低局部位置因能量集中而被击穿的可能性，进而提高可降解载药支架的整体结构强度，以维持支架主体10较好的物理性能。
多个回旋槽段13a之间的距离可以相等，换言之，多个回旋槽段13a可以均匀的分布在相应的支撑单元环11上，使得支撑单元环11的各处受力均衡，维持较稳定的结构强度。
结合图13和图14所示，在一些实施方式中，载药槽13也可以采用迂回的方式，提高支撑单元环11上单位长度的累计槽长，以便装载更多的药量。
具体地，载药槽13包括多个子槽131，子槽131具有主体段131a和由所述主体段131a的端部相对主体段131a朝相反方向迂回延伸的迂回段131b，主体段131a沿支撑单元环11周向延伸，迂回段131b的部分结构与主体段131a的部分结构间隔地并排在一起，利用这种迂回设置提高支撑单元环11延伸方向上单位长度的累计槽长，以满足装载更多药量的需要。需要指出的是，该实施方式中，相邻的子槽131通过各自的迂回段131b嵌套在一起，且多个子槽131的槽线互不相交，从而避免利用激光加工载药槽13时，槽线交点处因能量汇聚而可能导致击穿。
另一方面，结合图19所示，本申请还提供了一种可降解载药支架的制作方法，可降解载药支架的制作方法包括以下步骤：
步骤S102，采用生物可降解聚合物加工成型管材或支架型坯。
其中，生物可降解聚合物包括下述一种或多种物质：聚乳酸(PLA)、聚左旋乳酸(PLLA)、聚乙交酯或聚羟基乙酸，PGA、聚氰基丙烯酸酯(PACA)，聚己酸内酯(PCL)、聚酸酐类、聚乳 酸共聚物(PLGA)、聚羟基丁酸戊酯(PHBV)、聚乙酰谷氨酸(PAGA)、聚正酯(POE)、聚氧化乙烯/聚丁烯共聚物(PEO/PBTP)，聚原酸酯、聚己内酯、聚羟基乙酸、聚氧化乙烯/聚对苯二甲酸丁二酯共聚物、异丁烯酸盐或酯、甲基丙烯酸盐或酯、聚亚安酯、硅树脂、聚乙烯乙醇、乙烯基乙醇、聚羟基乙酸、聚磷酸酯酶，以及上述聚合物的单体中的至少两种形成的共聚物。利用生物可降解聚合物加工成型管材或支架型坯，能够进行体内降解，无需通过手术取出。
步骤S104，利用飞秒激光器对成型管材或支架型坯进行加工，以形成网柱状结构的支架主体10，支架主体10可径向扩展和收缩。
结合图1和图3所示，对于成型管材或支架型坯而言，通过飞秒激光器进行加工去除部分材料，开设镂空槽C，以形成径向可扩展的网柱状结构，即支架主体10。
步骤S106，利用飞秒激光器在网柱状结构的外表面10b开设载药槽13，载药槽13的深度为网柱状结构的壁厚的10％～60％。
在一些实施方式中，在加工载药槽13时，激光器持续出光，激光的聚焦点从开槽的起点位置移至终点位置。对于不封闭的载药槽13而言，该起点位置和终点位置优选地对应于一个连续的载药槽13的一个端部和另一个端部，这样便可以在同等槽长的情况下，尽可能的减少载药槽13在支撑单元环11上留下的能量聚集点数量，也即减少了局部位置因激光能量集中而出现材料击穿的现象。这种结构形式下，既能够提供较多载药量，又能够减少击穿点，从而防止支架主体10因材料缺失而产生局部应力，降低了支架主体10断裂风险。
在一些实施方式中，飞秒激光器开设载药槽13时，飞秒激光器的聚焦点在网柱状结构的外表面10b移动速度S满足如下条件：
V＜S≤10V，
其中，V为飞秒激光器对成型管材或支架型坯进行加工时，飞秒激光器的聚焦点相对成型管材或支架型坯的移动速度。
该实施方式中，相对于在成型管材或支架型坯加工镂空槽时的切割速度，飞秒激光器开设载药槽13时，飞秒激光器的聚焦点在网柱状结构的外表面10b移动速度更快，即开载药槽13的激光切割速度比开镂空槽C的激光切割速度更快，以减少单位切割长度所吸收的激光能量，降低支架主体10被击穿的风险。
完成载药槽加工后，将药物以微米级或纳米级喷滴的方式填充至载药槽13内部。完成药物填充后可以对支架主体的表面进行打磨处理，去除溢出支架表面的药物。容纳在载药槽13内部的药物厚度基本均匀一致，药物能够均匀释放。
本申请的可降解载药支架，在生物可降解聚合物制成的支架主体10上开设载药槽13后，载药槽13能够改善药物在可降解载药支架上的附着能力，且载药槽13对可降解载药支架物理性能的影响控制在医疗器械标准范围内。
具体地，参照表2-表10，选用图3示出的可降解载药支架进行物理性能测试，以直径为2.5mm、3.0mm、4.0mm规格的支架进行分组对照实验。需要说明的是，支架的直径指的是呈扩展状态的网柱状结构的直径。即，选用的开设有载药槽13的多个可降解载药支架样品对应的网柱状结构的直径包括2.5mm、3.0mm、4.0mm。同时，采用同等规格支架且没有开设载药槽的可降解支架作为参照样品进行物理性能测试，以供参照。
表2-表10中的序号1、2、3、4代表的是该规格型号下的第1、2、3、4号支架。其中1-4号支架的网柱状结构的壁厚约为125μm,1、2号支架为未挖槽支架，3、4号支架为设置有载药槽13的可降解载药支架，载药槽13的深度控制在40μm-60μm，载药槽13在外表面10b 的槽宽控制在30±10μm，载药槽13的槽线沿支撑单元环11周向连续绕一周。
径向抗挤压测试的结果参见下表：
表2
Figure PCTCN2020089349-appb-000002
表3
Figure PCTCN2020089349-appb-000003
表4
Figure PCTCN2020089349-appb-000004
表2-表4分别列出了直径为2.5mm、3.0mm、4.0mm规格支架的径向抗挤压数据，由表2-4可知，设置有载药槽13的样品3、4相对参照样品1、2的抗挤压性能相当，也就是说，在网柱状结构的外表面10b开设载药槽13后，仍具有较良好的径向抗挤压性能。
支架过度扩张测试的结果参见下表：
支架过度扩张测试时，采用断裂直径作为衡量过度扩张性能的指标，其中，断裂直径是指支架经过一定的条件加工、存储、老化后，在37℃水域中使用球囊逐渐扩张支架，直至出现支撑单元环11断裂时支架所对应的直径。
表5
Figure PCTCN2020089349-appb-000005
表6
Figure PCTCN2020089349-appb-000006
表7
Figure PCTCN2020089349-appb-000007
由表5-表7所示，设置有载药槽13的样品3、4相对参照样品1、2的断裂直径相当，也就是说，在网柱状结构的外表面10b开设载药槽13后，支架过度扩张性能的差异不大，仍具有较良好的支架过度扩张性能。
轴向回缩测试的结果参见下表：
表8
Figure PCTCN2020089349-appb-000008
表9
Figure PCTCN2020089349-appb-000009
表10
Figure PCTCN2020089349-appb-000010
由表8-10所示，同等规格的支架，参照样品1、2和设置有载药槽13的样品3、4的轴向回缩差异不大，且轴向回缩都在5％以内，符合支架类医疗器械的使用标准。
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本申请的几种实施方式，其描述较为具体和详细，但并不能因此而理解为对申请专利范围的限制。应当指出的是，对于本领域的普通技术人员来说，在不脱离本申请构思的前提下，还可以做出若干变形和改进，这些都属于本申请的保护范围。因此，本申请专利的保护范围应以所附权利要求为准。

Claims (18)

  1. 一种可降解载药支架，其中，所述可降解载药支架包括支架主体，所述支架主体的外表面设置有载药槽；所述支架主体具有收缩状态及扩张状态，所述支架主体能够通过径向扩展从所述收缩状态切换到所述扩张状态，所述支架主体在所述扩张状态下为网柱状结构，所述载药槽的深度为所述网柱状结构的壁厚的10％～60％。
  2. 根据权利要求1所述的可降解载药支架，其中，所述支架主体由生物可降解聚合物制成。
  3. 根据权利要求1所述的可降解载药支架，其中，所述载药槽的深度为所述网柱状结构的壁厚的25％～45％。
  4. 根据权利要求1所述的可降解载药支架，其中，所述载药槽的深度与宽度满足如下条件：Y＝120-2X；
    其中，Y为所述载药槽的深度，X为所述载药槽的宽度，Y的取值范围为小于等于80微米。
  5. 根据权利要求1-4中任一项所述的可降解载药支架，其中，所述支架主体包括多个支撑单元环和连接杆，所述支撑单元环之间通过所述连接杆相连以形成所述网柱状结构，所述载药槽至少设置于至少一个所述支撑单元环的外表面上。
  6. 根据权利要求5所述的可降解载药支架，其中，至少一个所述支撑单元环上的所述载药槽的累计槽长为其所在的所述支撑单元环的长度的0.9倍～5倍。
  7. 根据权利要求5所述的可降解载药支架，其中，至少一个所述支撑单元环上的所述载药槽的槽宽为其所在的所述支撑单元环的宽度的10％～80％。
  8. 根据权利要求5所述的可降解载药支架，其中，至少一个所述支撑单元环上的至少一个载药槽通过连续开槽方式制成。
  9. 根据权利要求5-8中任一项所述的可降解载药支架，其中，位于所述支架主体的端部的两个支撑单元环中的至少一个上设置有多个载药槽，所述多个载药槽在周向上间隔布置。
  10. 根据权利要求5-8中任一项所述的可降解载药支架，其中，位于所述支架主体的端部之间的至少一个支撑单元环上设置有闭合的载药槽。
  11. 根据权利要求5-8中任一项所述的可降解载药支架，其中，至少一个所述支撑单元环上设置有多个所述载药槽，多个所述载药槽沿所述支撑单元环的轴向间隔设置且互不相交。
  12. 根据权利要求5-8中任一项所述的可降解载药支架，其中，所述载药槽的槽线为沿所述支撑单元环周向延伸的曲线或波浪线。
  13. 根据权利要求5-8中任一项所述的可降解载药支架，其中，至少一个所述支撑单元环上的所述载药槽包括多个回旋槽段和多个连接槽段，相邻的两个所述回旋槽段通过一个所述连接槽段连接。
  14. 根据权利要求5-8中任一项所述的可降解载药支架，其中，至少一个所述支撑单元环上的所述载药槽包括多个子槽，各所述子槽分别具有主体段和由所述主体段的端部相对所述主体段迂回延伸的迂回段，所述主体段沿所述至少一个支撑单元环周向延伸，所述迂回段的部分结构与所述主体段的部分结构间隔地并排在一起。
  15. 一种可降解载药支架的制作方法，其中，所述可降解载药支架的制作方法包括以下步骤：
    采用生物可降解聚合物加工成型管材或支架型坯；
    对成型管材或支架型坯进行加工，以形成网柱状结构的支架主体，所述支架主体可径向扩展和收缩；
    在所述网柱状结构的外表面开设载药槽，所述载药槽的深度为所述网柱状结构的壁厚的10％～60％。
  16. 根据权利要求15所述的可降解载药支架的制作方法，其中，开设载药槽时，飞秒激光器的聚焦点在网柱状结构的外表面移动速度S满足如下条件：
    V＜S≤10V，
    其中，V为飞秒激光器对成型管材或支架型坯进行加工时，飞秒激光器的聚焦点相对成型管材或支架型坯的移动速度。
  17. 根据权利要求15所述的可降解载药支架的制作方法，其中，开设载药槽后将药物填充至所述载药槽内部。
  18. 根据权利要求17所述的可降解载药支架的制作方法，其中，对已填充药物的支架主体的表面进行打磨处理。
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