CN106214295A - A kind of it is applicable to the arterial vascular Biodegradable vascular scaffold with tapering - Google Patents
A kind of it is applicable to the arterial vascular Biodegradable vascular scaffold with tapering Download PDFInfo
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- CN106214295A CN106214295A CN201610037231.9A CN201610037231A CN106214295A CN 106214295 A CN106214295 A CN 106214295A CN 201610037231 A CN201610037231 A CN 201610037231A CN 106214295 A CN106214295 A CN 106214295A
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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
-
- 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
- A61F2002/823—Stents, different from stent-grafts, adapted to cover an aneurysm
-
- 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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00011—Metals or alloys
- A61F2310/00035—Other metals or alloys
- A61F2310/00041—Magnesium or Mg-based alloys
-
- 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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00011—Metals or alloys
- A61F2310/00035—Other metals or alloys
- A61F2310/00065—Manganese or Mn-based alloys
-
- 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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00005—The prosthesis being constructed from a particular material
- A61F2310/00011—Metals or alloys
- A61F2310/00035—Other metals or alloys
- A61F2310/00083—Zinc or Zn-based alloys
-
- 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
- A61F2310/00—Prostheses classified in A61F2/28 or A61F2/30 - A61F2/44 being constructed from or coated with a particular material
- A61F2310/00389—The prosthesis being coated or covered with a particular material
- A61F2310/0097—Coating or prosthesis-covering structure made of pharmaceutical products, e.g. antibiotics
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- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Cardiology (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Transplantation (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
The invention discloses and a kind of be applicable to the arterial vascular Biodegradable vascular scaffold with tapering.What the present invention provided is applicable to the arterial vascular Biodegradable vascular scaffold with tapering, the protective coating covering body surface including the body being made up of magnesium alloy or magnesium, being made up of polylactic acid-PTMC copolymer, polylactide-co-glycolide polymers or six phosphate ester of cyclohexanhexanol and the medication coat of the covering protection coating surface being made up of medicine；Described body is hollow round table type, and height is 40-120mm, and a diameter of 4.0-6.0mm of a bottom surface, a diameter of 3.0-5.0mm of another bottom surface, the diameter difference of two bottom surfaces is 0.5-1.5mm.The present invention will lead the revolutionary innovation of domestic medical disposable material, bring glad tidings for patient, and have high scientific meaning and potential economic benefit.
Description
Technical field
The invention belongs to implant the medical instruments field of human body, be specifically related to one and be applicable to arterial vascular there is tapering
Biodegradable vascular scaffold.
Background technology
Occlusive lower extremities disease and diabetes B lower limb arterial occlusive disease are one of most common peripheral blood vessels, 70
Crowd's sickness rate more than year is at more than 10%-20%.At present, iliac artery and femoral artery,superficial intracavitary therapy are the most increasingly mature,
Femoral artery-knee joint above tremulous pulse autologous vein Coronary Artery Bypass remains the gold mark of femoral artery,superficial length section occlusive disease treatment
Standard, with novel medicine carrying sacculus and medicine carrying metal rack, the intracavity technology as representative then becomes vascular surgery technological revolution
Focus, short-and-medium section narrow or obtains in occlusive disease and is not inferior to the curative effect of tradition bypass surgery and micro-with it
Wound, the advantage of safety become the first-selected therapeutic scheme of major part femoral artery,superficial pathological changes patient.
Tremulous pulse is the continuity that femoral artery exports at adductor canal, and position is relatively deep, after adjacent patch distal femoral surface and capsula articularis genus
To condyle of femur, portion, along the outside diagonal of semitendinosus m. outer rim, asks that nest level occupies middle part after knee joint, reaches the most vertically downward under flesh
Edge, is divided into anterior tibial artery and posterior tibial artery.Tremulous pulse can be divided into three sections, and adductor canal outlet tremulous pulse starting point is to kneecap
Bone upper limb plane is P1 section, and patella upper limb plane is P2 section to lateral condyle line plane in tibia, lateral condyle in tibia
Line plane is with down to separating at anterior tibial artery terminal for P3 section.
The pathological changes of tremulous pulse P2, P3 section below arterial disease, especially patella lower edge, either across knee joint
Autologous vein Coronary Artery Bypass, or balloon/stent intracavity forming operation, it is shallow dynamic that its therapeutic effect is still far inferior to stock
Disorders of meridian becomes.Tracing it to its cause, first tremulous pulse traveling is after human body knee joint, at knee sprung-unbending movement
In, there is multiple bending shape in tremulous pulse, and shows according to the study, and in the case of more than 75%, knee sprung is transported
The flex point of disorder of internal organs tremulous pulse bending is respectively positioned on P2 section；It is additionally, since P2 section tremulous pulse freedom maximum, and P3 section
The then free minimum because of the existence of muscle, also has the cripetura of tremulous pulse, distortion while flex point occurs in tremulous pulse bending
Deng existence.Therefore, the intravascular stent placed across knee joint bears bending diverse with other regions of anatomy, draws
Stretch, distorting stress, the severe complication incidence rate such as Acute thrombosis, support fracture is high.
The anatomical features of tremulous pulse self has more highlighted the inferior position of traditional peripheral blood vessel support.Tradition peripheral blood vessel support
Overall in isodiametric cylindricity, arteries is then in the trend gradually decreased to distal end diameter from proximal part.
At the arteries that the travelings such as aorta, iliac artery, the shallow animation of stock are longer, owing to arteries traveling is longer, relatively
For the change of local intra-arterial diameter little, the elasticity of arteries self and plasticity in addition, outside isodiametric tradition
All intravascular stents can substantially meet the needs of these blood vessels.Tremulous pulse extends to the thickest femoral artery,superficial, closes across knee joint
Being divided into rapidly anterior tibial artery and posterior tibial artery to flesh level after joint, vessel diameter change is obvious.
Summary of the invention
The invention provides and based on arteriotomy physiological characteristics a be applicable to the arterial vascular biology with tapering
Degradable blood vessel bracket.
Tremulous pulse begins from adductor tendinous opening, stops to the anterior tibial artery place of separating, and its total length is 20.2 ± 2.6cm, from adductor muscle
Tendinous hiatus is 14.0 ± 2.1cm to condyle of femur lower edge horizontal length, and separates to anterior tibial artery from condyle of femur lower edge level
Locate a length of 6.2 ± 0.8cm；And diameter change is extremely rapid, at adductor tendinous opening 5cm, artery diameter is 10.5
± 2.2mm, is kept to rapidly 8.7 ± 1.6mm to the horizontal artery diameter of condyle of femur lower edge, and separates place to anterior tibial artery
Artery diameter only 4.7 ± 0.1mm.Therefore, normal dia is the equal diameter tradition peripheral blood of 60mm-150mm
Pipe holder is difficult in adapt to the physiology of tremulous pulse and dissects.
What the present invention provided is applicable to the arterial vascular Biodegradable vascular scaffold with tapering, it is characterised in that:
Described Biodegradable vascular scaffold includes the body being made up of magnesium alloy or magnesium, by polylactic acid-polytrimethylene carbonic acid
The protection covering body surface that ester copolymer, polylactide-co-glycolide polymers or six phosphate ester of cyclohexanhexanol are made
Coating and the medication coat of covering protection coating surface being made up of medicine；Described body is hollow round table type, and height is
40-120mm, a diameter of 4.0-6.0mm of a bottom surface, a diameter of 3.0-5.0mm of another bottom surface, two bottom surfaces
Diameter difference be 0.5-1.5mm；Described arteries is arteries, the blood vessel of adductor tendinous opening to flesh lower edge,
Near three points of arterial end in middle distal section femoral artery,superficial blood vessel, anterior tibial artery blood vessel, posterior tibial artery blood vessel, peroneal artery
One of the blood vessel of length.
Described being applicable to the arterial vascular Biodegradable vascular scaffold with tapering, the height of described body specifically may be used
For 100mm, the diameter of a bottom surface concretely 5.0mm, the diameter of another bottom surface concretely 4.0mm, two
The diameter difference of bottom surface concretely 1.0mm.
Through preliminary experiment, it was found by the inventors of the present invention that the arteries support meeting Chinese's clinic needs should
A length of 40-120mm, diameter major diameter scope is 4.0,4.5,5.0,5.5,6.0mm, diameter minor axis scope is 3.0,
3.5,4.0,4.5,5.0mm, the gap of major diameter and minor axis is 0.5,1.0 or 1.5mm, to adapt on tremulous pulse
Anatomical features narrow under width, improves the compliance of arterial bracket.
Magnesium is the second important cation in human body, and content is only second to potassium, its in human normal metabolic processes not
Can or lack.Magnesium ion, is kept by kidney and small intestinal at the fluctuation of concentration of extracellular fluid between 0.7-1.05mmol/L
Its concentration is stable.But, owing to the chemical property of magnesium is extremely active (-2.36VSCE), and produce in corrosive medium
Raw oxide-film loose porous (PBR=0.8), magnesium and corrosion stability of magnesium alloy can be poor, especially containing Cl-ion
In human physiological environment all the more so.This problem is considered as the shortcoming of magnesium and magnesium alloy the most always, also becomes
For limiting it as implant in the main reason of biomedical applications.The present inventor overcomes this area to work
The technology prejudice of personnel, carries out reverse thinking, utilizes the feature that magnesium and corrosion stability of magnesium alloy can differ from, using them as life
Biodegradable materials application is to clinical medicine domain.Magnesium alloy has the performance of excellence: (density is only aluminium alloy to light weight
2/3, the 1/4 of steel)；Specific strength and specific stiffness are all higher than aluminium alloy and steel；Excellent dimensional stability is with good
Energy shock absorption；The waste recovery utilization rate of up to more than 85%；Machining is easy, welding performance is good.
Further, what the present inventor provided is applicable to the arterial vascular biodegradable vascular with tapering
Support, its shape facility, mechanical characteristics and chemical property be described below:
One, shape facility
Of the present invention be applicable to the arterial vascular Biodegradable vascular scaffold with tapering body be hollow,
Circular platform type, height is 40-120mm, a diameter of 4.0-6.0mm of a bottom surface, another bottom surface a diameter of
3.0-5.0mm, the diameter difference of two bottom surfaces is 0.5-1.5mm.
Two, radially support force
Tremulous pulse traveling P3 section is more fixing, when knee articulation by bigger radial direction support force, therefore it is required that plant
The radial direction support force entering human body fore-stock is more than or equal to 15 newton, and in (the definition of dissolution time window of dissolution time window
I.e. intravascular stent can effectively support the time of arterial wall elastical retraction) in radially support force be maintained at more than 12 newton.
Three, dissolution time window
It has been observed that the main target of arterioplasty operation is that (rest pain, ulcer are not in order to progress to critical limb ischemia
More, gangrene) patient myocardial revascularization timely is provided, it is to avoid amputation, promote ulcer healing, strive for being forged by motion
Refining is set up time of side shoot, therefore, keeps middle or short term (about 6 months) unobstructed for tremulous pulse tremulous pulse to closing weight
Want, and medium-long term comparatively speaking is whether unobstructed less for Prognostic Significance.And kneed flexing-stretch
Motion causes the intra-arterial intravascular stent at the knee joint back side to bear huge lateral buckling and axial shearing force, repeatedly
Flexing-stretch more likely causes the metal fatigue of the intravascular stent retained for a long time, induction support fracture, deformation, secondary
Acute artery thrombosis and the acute ischemia of distal limb, severe patient needs amputation to treat.The present inventor
Find after carrying out preliminary experiment that the Best Times that arteries support is retained is 6 months, therefore by the dissolving of intravascular stent
Time window is set as 150-210 days, preferably 165-195 days.
Four, maximum dissolution time
The definition of maximum dissolution time is: intravascular stent is completely dissolved (naked eyes) to support from implanting the human body moment
Time.Due to the characteristic of magnesium alloy, after self-corrosion course of dissolution, its dissolution time is quickish.
And for Biodegradable scaffold, after optimal treatment window, the quickening of dissolution time can reduce support because of the most molten
Solution fragments into little fragment and drops and cause the possibility of far-end arteriolar embolism.After the present inventor carries out preliminary experiment,
The maximum dissolution time of intravascular stent is set as 300-420 days, preferably 330-390 days.
Five, compliance
Intravascular stent compliance refers to that intravascular stent deforms maximum support cavity area and stretches shape under flecition power
The ratio of state same position submounts cavity area, deformation of timbering can use angle [alpha] simultaneously.Big situation is become at deformation angle
Under, compliance is the highest, and the tube chamber loss area representing support is the least.Application claims intravascular stent is when deforming 30 °
Support compliance is for being not less than 90%, and when deforming 60 °, support compliance is not less than 75%, and when deforming 90 °, support is complied with
Property is not less than 50%, and when deforming 120 °, support compliance is not less than 30%.
Described magnesium alloy is any one in following (1) to (8):
(1) magnesium being made up of 93.3-94.7 mass parts magnesium, 4.5-5.5 mass parts zinc and 0.8-1.2 mass parts manganese closes
Gold；
(2) by 92.1-93.9 mass parts magnesium, 4.5-5.5 mass parts zinc, 0.8-1.2 mass parts manganese and 0.8-1.2
The magnesium alloy of mass parts calcium composition；
(3) magnesium alloy being made up of 94 mass parts magnesium, 5 mass parts zinc and 1 mass parts manganese；
(4) magnesium alloy being made up of 93.3 mass parts magnesium, 5.5 mass parts zinc and 1.2 mass parts manganese；
(5) magnesium alloy being made up of 94.7 mass parts magnesium, 4.5 mass parts zinc and 0.8 mass parts manganese；
(6) magnesium alloy being made up of 93 mass parts magnesium, 5 mass parts zinc, 1 mass parts manganese and 1 mass parts calcium；
(7) magnesium being made up of 92.1 mass parts magnesium, 5.5 mass parts zinc, 1.2 mass parts manganese and 1.2 mass parts calcium
Alloy；
(8) magnesium being made up of 93.9 mass parts magnesium, 4.5 mass parts zinc, 0.8 mass parts manganese and 0.8 mass parts calcium
Alloy.
Described body is made up of tinsel, in hollow mesh.
The form of described hollow mesh is: part metals silk is some circumferential wave wave-like, the crest of each wave or trough
Connected by tinsel with crest or the trough of adjacent wave.
Described a diameter of 0.5-1.5mm wiry, preferably 1.0mm.
The processing technology of the body of described support includes but not limited to that machining or laser engraving support.
The thickness of described protective coating is 0.01-1mm, preferably 0.1mm.
The processing technology of described protective coating can be the combination of one or more in following arbitrary technique or following technique: super
Sound spraying, laser hollow out, dip-coating, spraying, thermal spraying, electrostatic coating, collosol and gel and supercritical fluid coating work
Skill.
Described polylactic acid-PTMC copolymer concretely PLA30-PTMC70。PLA30-PTMC70Weight
Average molecular weight concretely 39000, number-average molecular weight concretely 17730.
Described polylactide-co-glycolide polymers concretely LA85-GA15。LA85-GA15Weight average molecular weight specifically may be used
It is 144700, number-average molecular weight concretely 73100.
The thickness of described medication coat is 0.01-1mm, preferably 0.1mm.
The medicine of the concretely local action of the medicine in described medication coat.Medicine in described medication coat can be anti-
Neointimal hyperplasia medicine and/or antithrombotic medicine.Described anti-neointimal hyperplasia medicine includes but not limited to following medicine:
The medicine that rapamycin (Rapamycin) is similar with rapamycin structure and/or the mechanism of action is identical and/or receptor is identical
Thing, the medicine that paclitaxel (Paclitaxel) is similar with paclitaxel result and/or the mechanism of action is identical.Described anti-blood
The medicine that bolt is formed can be anticoagulant and/or antiplatelet drug.Described anticoagulant and/or antiplatelet drug include but do not limit
In following medicine: Xa factor inhibitor and thrombinogen inhibitor, Glycoprotein G P II h/ III a complex inhibitor, water
Trematodiasis element class medicine.Described Xa factor inhibitor and thrombinogen inhibitor include but not limited to heparin (Heparin),
Razaxaban (rivaroxaban).Described Glycoprotein G P II h/ III a complex inhibitor includes but not limited to chlorine pyrrole lattice
Thunder (clopidogrel).Described hirudin class medicine includes but not limited to bivalirudin (bivalirudin).
The processing technology of described medication coat can be the combination of one or more in following arbitrary technique or following technique: super
Sound spraying, laser hollow out, dip-coating, spraying, thermal spraying, electrostatic coating, collosol and gel and supercritical fluid coating work
Skill.
The introducing of Biodegradable material can alleviate some brought because metal rack forever retains Ink vessel transfusing greatly
Arrange the risk of tardy complication.But, owing to support support force rapidly disappears along with dissolving, vascular smooth muscle layer
Migrating and propagation increases therewith, support rest will face neointimal hyperplasia, tube chamber loss and restenosis for a long time
Risk.The suppression neointimal hyperplasia medicine of local action is proved to effectively to reduce the incidence rate of postoperative restenosis, reduces
Diseased region needs again the risk of myocardial revascularization.The medicine of local action is required for certain transport carrier and arrives pathological changes
Position.Biodegradable scaffold is than sacculus and conventional metals support more preferable medicine carrying carrier.Medicinal balloon faces
Big problem is owing to sacculus acts on the limited time of diseased region, in order to reach certain blood drug level must be requested that
Higher medicine carrying density, and too high medicine carrying density and relatively low effective rate of utilization can cause Systemic drug concentrations
Instantaneous blood medicine peak value, there is whole body organ injury and the tumorigenic risk of Delayed onset.Although medicine metal rack has
There are sufficient administering pharmaceutical substances time, higher drug availability and a metastable local drug concentration, but once medicine
After release, drug stent is i.e. transformed into traditional metal rack, has the various problems of conventional metals support equally.
The Biodegradable scaffold of carrying medicament has then got both, and medicinal balloon foreign is retained, drug stent is stablized and efficient office
Portion's medicine activity, such that it is able to play more preferable anti-neointimal hyperplasia effect.
The invention discloses and a kind of be primarily adapted for use in the arterial vascular Biodegradable vascular scaffold with tapering, with spy
Some character, mechanical characteristics and solubility behavior adapted to the change of the lumen diameter of tremulous pulse, physiology of exercise feature and
The myocardial revascularization requirement of arterial obliterans of lower extremity patient's arterial disease.Described Biodegradable vascular scaffold is in fall
Xie Qianneng effectively provides radially support force improve for short-term and maintain distal limb blood fortune, it is to avoid amputation, promotion ulcer
Heal and strive for the functional exercise time；The design of distinctive circular platform type agrees with human arterial's lumen diameter from the spy slightly attenuated
Point；And avoid because the long-term flexing-unbending movement of tremulous pulse causes support to become after Biodegradable vascular scaffold is degraded
The long term complications such as the fracture of shape, support, thrombosis；The medication coat being coated with outside this Biodegradable vascular scaffold relatively passes
System medicinal balloon or medicine metal rack are more beneficial for playing medicine local action.
The Biodegradable vascular scaffold with tapering that the present invention provides is used according to the conventional of intravascular stent by doctor
Method uses.
The present invention will lead the revolutionary innovation of domestic medical disposable material, bring glad tidings for patient, and have high science
Meaning and potential economic benefit.
Accompanying drawing explanation
Fig. 1 is the rip cutting sectional view of rack body.
Fig. 2 is the result (Biodegradable vascular scaffold I) of magnesium ion concentration and rapamycin concentrations.
Fig. 3 is the result (Biodegradable vascular scaffold IV) of magnesium ion concentration and rapamycin concentrations.
Detailed description of the invention
Below example facilitates a better understanding of the present invention, but does not limit the present invention.Experiment in following embodiment
Method, if no special instructions, is conventional method.Test material used in following embodiment, if no special instructions,
It is and is commercially available from routine biochemistry reagent shop.Quantitative test in following example, is respectively provided with three times and repeats in fact
Test, results averaged.
The composition of simulation blood: NaCl 8.00g/L, KCl 0.40g/L, CaCl2 0.14g/L、NaHCO3 0.35g/L、
MgSO4·7H2O 0.20g/L、Na2HPO4·12H2O 0.12g/L、KH2PO40.06g/L, surplus is water.
Human aorta vascular smooth muscle cell (HA-VSMC):CRL-1999TM。
The method of detection magnesium ion concentration: use complexometric titration magnesium ion concentration (GB Chinese standard: inorganic
The universal method compleximetry that in chemical products, content of magnesium measures；GB standard No.: GB/T 21525-2008).
Rapamycin concentrations: use current domestic general efficient liquid phase spectrographic determination rapamycin concentrations (see Liu Zhong,
Zhao Lili, Sun Qinmei, Tang Yunfeng, high effective liquid chromatography for measuring rapamycin, biological processing [J], 2013.
11 (5): 71-73).Chromatographic condition: chromatographic column Zorbax Eclipse XDB-C8 (4.6mm X 150mm, 3.5
Micron) reversed-phase column.Flowing phase: volume (acetonitrile): volume (water)=51:49.Flow velocity 1.0mL/min.Ultraviolet is examined
Survey wavelength 278nm.Column temperature 55 degrees Celsius.The rapamycin acetonitrile using rapamycin standardization product preparation variable concentrations is molten
Liquid, sample introduction under above-mentioned chromatographic condition, record chromatogram, with peak area, concentration is carried out linear regression, Criterion
Product chromatographic curve.
Polylactic acid in embodiment-PTMC copolymer refers to PLA30-PTMC70, weight average molecular weight is
39000, number-average molecular weight is 17730.
Polylactide-co-glycolide polymers in embodiment refers to LA85-GA15, weight average molecular weight is 144700, number
Average molecular weight is 73100.
Embodiment 1, preliminary experiment
It is respectively adopted various unlike material and prepares rack body (concrete material is shown in Table 1).
The rip cutting sectional view of rack body is shown in Fig. 1.The hollow round table type that is shaped as of rack body, height is 100mm,
A diameter of 5.0mm of one bottom surface, a diameter of 4.0mm of another bottom surface, the diameter difference of two bottom surfaces is 1.0mm.
Rack body is made up of the tinsel of a diameter of 1.0mm, and in hollow mesh, (form of hollow mesh is: part gold
Belonging to silk is some circumferential wave wave-like, and the crest of each wave is connected by tinsel with the crest of adjacent wave).
Table 1
At body I surface spraying polylactic acid-PTMC copolymer (polylactic acid-polytrimethylene carbonic acid
Ester copolymer forms protective coating, and the thickness of protective coating is 0.1mm), form intermediate support I.
At body II surface spraying polylactide-co-glycolide polymers, (polylactide-co-glycolide polymers forms protection
Coating, the thickness of protective coating is 0.1mm), form intermediate support II.
At body III surface spraying six phosphate ester of cyclohexanhexanol, (six phosphate ester of cyclohexanhexanol forms protective coating, and protection is coated with
The thickness of layer is 0.1mm), form intermediate support III.
At body IV surface spraying polylactic acid-PTMC copolymer (polylactic acid-polytrimethylene carbonic acid
Ester copolymer forms protective coating, and the thickness of protective coating is 0.1mm), form intermediate support IV.
At body V surface spraying polylactide-co-glycolide polymers, (polylactide-co-glycolide polymers forms protection
Coating, the thickness of protective coating is 0.1mm), form intermediate support V.
At body VI surface spraying six phosphate ester of cyclohexanhexanol, (six phosphate ester of cyclohexanhexanol forms protective coating, and protection is coated with
The thickness of layer is 0.1mm), form intermediate support VI.
The radial direction support force of each intermediate support is detected by mechanical test.The radial direction support force of intermediate support I is
17.39 newton, the radial direction support force of intermediate support II is 16.87 newton, and the radial direction support force of intermediate support III is 16.58
Newton, the radial direction support force of intermediate support IV is 18.86 newton, and the radial direction support force of intermediate support V is 16.99 newton,
The radial direction support force of intermediate support VI is 17.34 newton.
Each intermediate support is soaked (environmental condition: 37 DEG C, 3%CO in simulation blood2, humidity 99%), middle
It is 176 days that frame I radially support force is reduced to the time of 12 newton, and intermediate support II radially support force is reduced to 12 newton
Time be 172 days, it is 169 days that intermediate support III radially support force is reduced to the time of 12 newton, intermediate support IV footpath
The time being reduced to 12 newton to support force is 180 days, and intermediate support V radially support force is reduced to the time of 12 newton
Being 182 days, it is 185 days that intermediate support VI radially support force is reduced to the time of 12 newton.
Each intermediate support is soaked (environmental condition: 37 DEG C, 3%CO in simulation blood2, humidity 99%), middle
The maximum dissolution time of frame I is 355 days, and the maximum dissolution time of intermediate support II is 348 days, and intermediate support III is
Big dissolution time is 353 days, and the maximum dissolution time of intermediate support IV is 360 days, when the maximum of intermediate support V is dissolved
Between be 372 days, the maximum dissolution time of intermediate support VI is 387 days.
Embodiment 2, the preparation of Biodegradable vascular scaffold
Biodegradable vascular scaffold includes body (body IV or body I), by polylactic acid-polytrimethylene carbonic acid
The protective coating of body surface that what ester copolymer was made cover and the covering protection coating surface be made up of rapamycin
Medication coat.Body is hollow round table type, and height is 100mm, a diameter of 5.0mm of a bottom surface, another end
A diameter of 4.0mm in face, the diameter difference of two bottom surfaces is 1.0mm.Body is made up of the tinsel of a diameter of 1.0mm
, in hollow mesh, (form of hollow mesh is: part metals silk is some circumferential wave wave-like, the ripple of each wave
Peak is connected by tinsel with the crest of adjacent wave).Protective coating thickness is 0.1mm.Medication coat thickness is
0.1mm。
The material of body I is the material of the body I in the table 1 in embodiment 1.
The material of body IV is the material of the body IV in the table 1 in embodiment 1.
When using body I, the named Biodegradable vascular scaffold of Biodegradable vascular scaffold I.
When using body IV, the named Biodegradable vascular scaffold of Biodegradable vascular scaffold IV.
Embodiment 3, the performance of Biodegradable vascular scaffold
One, radially support force
Radial direction support force by the Biodegradable vascular scaffold of mechanical test detection embodiment 2 preparation.Biology can drop
The radial direction support force solving intravascular stent I is 17.39 newton, and the radial direction support force of Biodegradable vascular scaffold IV is
18.86 newton.
Two, dissolution time window
Biodegradable vascular scaffold embodiment 2 prepared soaks (environmental condition: 37 DEG C, 3%CO in simulation blood2、
Humidity 99%), it is 176 days that Biodegradable vascular scaffold I radially support force is reduced to the time of 12 newton, and biology can
It is 180 days that degraded intravascular stent IV radially support force is reduced to the time of 12 newton.
Three, maximum dissolution time
Biodegradable vascular scaffold embodiment 2 prepared soaks (environmental condition: 37 DEG C, 3%CO in simulation blood2、
Humidity 99%), the maximum dissolution time of Biodegradable vascular scaffold I is 355 days, Biodegradable vascular scaffold IV
Maximum dissolution time be 360 days.
Four, compliance
The compliance of the Biodegradable vascular scaffold of detection embodiment 2 preparation.Biodegradable vascular scaffold I,
When deforming 30 °, support compliance is 92%, and when deforming 60 °, support compliance is 76%, and when deforming 90 °, support is complied with
Property is 51%, and when deforming 120 °, support compliance is 31%.Biodegradable vascular scaffold IV, when deforming 30 °
Support compliance is 93%, and when deforming 60 °, support compliance is 77%, and when deforming 90 °, support compliance is 52%,
When deforming 120 °, support compliance is 33%.
Five, degraded situation
Biodegradable vascular scaffold prepared by embodiment 2 immersion in simulation blood (environmental condition: 37 DEG C,
3%CO2, humidity 99%), take liquid sample every day, the magnesium ion concentration in detection liquid phase sample and rapamycin concentrations.
The result of Biodegradable vascular scaffold I is shown in that Fig. 2, A are magnesium ion concentration result, and B is the result of rapamycin concentrations.
The result of Biodegradable vascular scaffold IV is shown in that Fig. 3, A are magnesium ion concentration result, and B is the result of rapamycin concentrations.
Six, the action effect to vascular smooth muscle
1st day, the 7th day, the 30th day, the 90th day and the liquid that takes for the 180th day in solution to be measured respectively step 4
Body sample.
1, take human aorta vascular smooth muscle cell, with trypsinization, then train with the DMEM containing 20% hyclone
Support base to suspend, obtain (5-10) × 104The cell suspension of individual cell/ml.
2, taking 96 orifice plates, every hole adds the cell suspension that 100 μ l steps 1 obtain, and then cultivates to cell monolayer
It is paved with at the bottom of hole.
3, after completing step 2, taking described 96 orifice plates, inhale and abandon supernatant, every hole adds 100 μ l solution to be measured,
Then cultivate 36 hours.The negative control replacing solution to be measured with equal-volume simulation blood is set.
4, after completing step 3, taking described 96 orifice plates, every hole adds 10 μ l MTT solution (5mg/ml, i.e. 0.5%MTT),
Continue to cultivate 4h.
5, after completing step 4, inhaling and abandon supernatant, every hole adds 150 μ l dimethyl sulfoxide makes crystal fully dissolve,
The light absorption value in each hole is measured at enzyme-linked immunosorbent assay instrument OD490nm.
In above-mentioned steps, cell culture condition is: 5%CO2, 37 DEG C.
Absorbance × 100% of the absorbance/negative control of cell proliferation rate=test group.
Every kind of solution to be measured arranges 5 to be repeated to process, results averaged.
The results are shown in Table 2.The degradation solution of Biodegradable vascular scaffold inhibits the increasing of human aorta vascular smooth muscle cell
Grow, say, that it achieves the effect of anti-neointimal hyperplasia.
Table 2
Claims (10)
1. one kind is applicable to arterial vascular Biodegradable vascular scaffold, it is characterised in that: described biodegradable blood
Pipe holder includes the body being made up of magnesium alloy or magnesium, by polylactic acid-PTMC copolymer, poly-third friendship
What ester-co-glycolide polymers or six phosphate ester of cyclohexanhexanol were made covers the protective coating of body surface and is made up of medicine
The medication coat of covering protection coating surface；Described body is hollow round table type, and height is 40-120mm, at the bottom of one
A diameter of 4.0-6.0mm in face, a diameter of 3.0-5.0mm of another bottom surface, the diameter difference of two bottom surfaces is
0.5-1.5mm；
Described arteries is arteries, the blood vessel of adductor tendinous opening to flesh lower edge, middle distal section femoral artery,superficial blood
The blood vessel of 1/3rd length of close arterial end in pipe, anterior tibial artery blood vessel, posterior tibial artery blood vessel or peroneal artery.
2. Biodegradable vascular scaffold as claimed in claim 1, it is characterised in that: described biodegradable vascular
The initial radial support force of support is more than 15 newton；To described Biodegradable vascular scaffold from implanting the human body moment
Radially support force is reduced to 12 newton is 150-210 days the time only, preferably 165-195 days.
3. Biodegradable vascular scaffold as claimed in claim 1 or 2, it is characterised in that: from implanting the human body moment
The time being completely dissolved playing described Biodegradable vascular scaffold is 300-420 days, preferably 330-390 days.
4. the Biodegradable vascular scaffold as described in arbitrary in claims 1 to 3, it is characterised in that: described biology
Degradable blood vessel bracket deform 30 ° time compliance be more than 90%, deform 60 ° time compliance be 75% with
On, the compliance when deforming 90 ° is more than 50%, and the compliance when deforming 120 ° is more than 30%.
5. the Biodegradable vascular scaffold as described in arbitrary in Claims 1-4, it is characterised in that: described magnesium closes
Gold is any one in following (1) to (8):
(1) magnesium being made up of 93.3-94.7 mass parts magnesium, 4.5-5.5 mass parts zinc and 0.8-1.2 mass parts manganese closes
Gold；
(2) by 92.1-93.9 mass parts magnesium, 4.5-5.5 mass parts zinc, 0.8-1.2 mass parts manganese and 0.8-1.2
The magnesium alloy of mass parts calcium composition；
(3) magnesium alloy being made up of 94 mass parts magnesium, 5 mass parts zinc and 1 mass parts manganese；
(4) magnesium alloy being made up of 93.3 mass parts magnesium, 5.5 mass parts zinc and 1.2 mass parts manganese；
(5) magnesium alloy being made up of 94.7 mass parts magnesium, 4.5 mass parts zinc and 0.8 mass parts manganese；
(6) magnesium alloy being made up of 93 mass parts magnesium, 5 mass parts zinc, 1 mass parts manganese and 1 mass parts calcium；
(7) magnesium being made up of 92.1 mass parts magnesium, 5.5 mass parts zinc, 1.2 mass parts manganese and 1.2 mass parts calcium closes
Gold；
(8) magnesium being made up of 93.9 mass parts magnesium, 4.5 mass parts zinc, 0.8 mass parts manganese and 0.8 mass parts calcium closes
Gold.
6. the Biodegradable vascular scaffold as described in arbitrary in claim 1 to 5, it is characterised in that: described medicine
For anti-neointimal hyperplasia medicine and/or antithrombotic medicine.
7. the Biodegradable vascular scaffold as described in arbitrary in claim 1 to 6, it is characterised in that: described body
It is made up of tinsel, in hollow mesh.
8. Biodegradable vascular scaffold as claimed in claim 7, it is characterised in that:
The form of described hollow mesh is: part metals silk is some circumferential wave wave-like, the crest of each wave or trough
Connected by tinsel with crest or the trough of adjacent wave；
Described a diameter of 0.5-1.5mm wiry, preferably 1.0mm.
9. the Biodegradable vascular scaffold as described in arbitrary in claim 1 to 8, it is characterised in that: described protection
The thickness of coating is 0.01-1mm, preferably 0.1mm.
10. the Biodegradable vascular scaffold as described in arbitrary in claim 1 to 9, it is characterised in that: described medicine
The thickness of thing coating is 0.01-1mm, preferably 0.1mm.
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| CN108969800A (en) * | 2017-06-05 | 2018-12-11 | 上海交通大学 | The preparation method of Wholly-degradable magnesium alloy bracket drug-carried coat with protective layer |
| CN116549744A (en) * | 2023-05-10 | 2023-08-08 | 华瑞（福建）生物科技有限公司 | Sustained-release cerebrovascular stent coating, cerebrovascular stent and preparation method thereof |
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