CN101843531A - Medicament coated thrombus filter - Google Patents
Medicament coated thrombus filter Download PDFInfo
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- CN101843531A CN101843531A CN 201010182185 CN201010182185A CN101843531A CN 101843531 A CN101843531 A CN 101843531A CN 201010182185 CN201010182185 CN 201010182185 CN 201010182185 A CN201010182185 A CN 201010182185A CN 101843531 A CN101843531 A CN 101843531A
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Materials For Medical Uses (AREA)
Abstract
The invention discloses a medicament coated thrombus filter. The medicament coated thrombus filter comprises a thrombus filter, a medicament carrier and medicaments, wherein the thrombus filter is positioned on the innermost layer; the medicament carrier is coated on the surface of the thrombus filter; and the medicaments are loaded in the medicament carrier. The provided medicament coated thrombus filter can effectively prevent local thrombus occlusion, inferior vena cava occlusion and complications thereof by taking the thrombus filter as a framework and coating a medicament carrier material containing thrombolytic anticoagulant medicaments on the surface of the thrombus filter to form a medicament coated layer.
Description
Technical field
The present invention relates to a kind of medicine coated thrombus filter, particularly a kind of is skeleton with existing thrombus filter, at its surface-coated thrombus dissolving anticoagulant, can prevent effectively that local thrombus from blocking, postcava blocks and the medicine coated thrombus filter of complication.
Background technology
Pulmonary embolism (is called for short pulmonary infarction pulmonary embolism, PE) be since around the thrombosis of deep venous thrombosis or right cardiac cavity come off and enter pulmonary circulation, stop up pulmonary artery or its branch, and then a series of clinical pathology physiological changes based on the pulmonary circulatory function obstacle that cause.It is non-specific that clinical manifestation is, and breathes hard, symptom such as chest pain, cough, spitting of blood or sudden faintness.If it is excessive that thromboembolism occurs in main pulmonary artery or blocks area, cause the PBF blocking-up to surpass 50%, severe cardiac lung failure even death can appear, its mortality rate account for clinical sudden death disease because of 5%.
Studies show that, cause that embolus that PE takes place is mainly derived from the thrombosis that limb deep vein or pelvic cavity vein come off, and accounts for 60%～90% of embolus source.And deep venous thrombosis is the main clinical commonly encountered diseases, and sickness rate rises year by year, and mortality rate is high, seriously jeopardizes patient's life.General traditional operation treatment wound face is bigger, and dangerous big; And the percutaneous IVCF to put art be the treatment of adopting the percutaneous puncture method to get involved, compare more simply, safe, effective with traditional surgical operation, be widely adopted in recent years.The vena cava filter of various ways is disclosed as Chinese patent application ZL02264778.3, ZL200420084495.2, ZL200620030819.3, ZL200720173001.1, ZL200820111457.X etc., by the variation of filter structure, can reaching not, injured blood vessel, raising stability reach purposes such as catching thrombosis better.All in all, existing filter mainly is divided into recyclable filter and not recyclable filter, and there is following shortcoming in actual applications in wherein recyclable filter:
A mistake! Do not find Reference source.Owing to reasons such as tissue adhesion, parcels, interim filter possibly can't reclaim smoothly, if reclaim complication such as may cause that caval vein is torn by force;
A mistake! Do not find Reference source.Can't play the bolt effect of catching long-term effectively.
Though and not recyclable filter can play the secular bolt effect of catching, reside in for a long time in the body as foreign body, exist following inevitable shortcoming again:
A mistake! Do not find Reference source.The thrombosis or the IVCF itself of catching from the spreading of far-end thrombosis, IVCF bring out as the human body foreign body, eventually to involving whole postcava tube chamber, cause severe complications such as local thrombus formation, postcava obstruction, this type of filter causes that having the symptom caval vein to block incidence rate is 2%～10%, and asymptomatic caval vein blocks incidence rate up to 30%;
2. take the anticoagulant medicine for a long time even throughout one's life and bring inconvenience to patient especially young patient.
Therefore, up to the present the vena cava filter on the market can not satisfy patient's demand fully.For avoiding the drawback of existing vena cava filter, be different from existing approach, the present invention proposes to adopt pharmaceutical pack to be filtered the mode of device, promptly select suitable medicine, pharmaceutical carrier and coating structure to carry out the pharmaceutical pack quilt at filter surfaces, and come the control drug release cycle by coating layer thickness and medicament contg, thereby play lasting thrombolytic, embolism extinguishing effect, reach and suppress the purpose that embolism of vena cava takes place.
Summary of the invention
Goal of the invention:, the invention provides a kind of medicine coated thrombus filter that can effectively prevent local thrombus obstruction, postcava obstruction and complication thereof in order to solve the deficiencies in the prior art.
Technical scheme: in order to realize above purpose, a kind of medicine coated thrombus filter of the present invention comprises: thrombus filter, pharmaceutical carrier and medicine; Described thrombus filter is positioned at the innermost layer, and pharmaceutical carrier is coated on the surface of thrombus filter, and drug loading is in pharmaceutical carrier.
Among the present invention, described pharmaceutical carrier is made of polymer, and described pharmaceutical carrier has several layers: one or more layers, every layer of polymer mixed by one or more forms;
Described medicine is: antithrombotic reagent, perhaps, and thrombolytic agent, perhaps, antithrombotic reagent and thrombolytic agent mix; This medicine has several layers, and every layer is made of one or more medicament mixed.
The content of the thickness of pharmaceutical carrier and the kind of used polymer and pharmaceutical units area is being controlled the rate of release of medicine simultaneously.
Wherein the polymer in the pharmaceutical carrier is: biodegradable, or nonbiodegradable synthetic polymer, or natural polymer;
Biodegradable synthetic polymer includes but not limited to: and polyamino acid, polylactic acid (PLA), copolymerization ether-ester, polyglycolic acid (PGA), poe (Polyorthester, POE), polycaprolactone (PCL), poly-anhydride (poly (anhydrides)) etc.
Nonbiodegradable synthetic polymer includes but not limited to:
1. the product of substituted olefine homopolymerization such as ethylene, propylene, styrene, vinyl chloride, acrylate or copolymerization, the preferred employing: polyethylene, polypropylene, polystyrene, polrvinyl chloride, polyacrylic acid, polymethyl acrylate, polyethyl acrylate, butyl polyacrylate, polymethyl methacrylate, polyethyl methacrylate, polybutyl methacrylate, polybutadiene, polyacrylonitrile;
2. the homopolymerization or the copolymer that contain non-carbon atom in the main chains such as polyurethane, polyester, polyethers, polyamide; The preferred employing: as poly(ether-urethane), poly terephthalic acid binaryglycol ester, poly terephthalic acid dibutylene glycol ester, poly-cyclohexyl dicarboxylic acid binaryglycol ester, poly-cyclohexyl dicarboxylic acid dipropylene glycol ester, poly-cyclohexyl dicarboxylic acid dibutylene glycol ester, polyamide 6, polyamide 66, polyamide 6 10, polyamide 1010, PTMG, polyoxyethylene, polyoxypropylene;
3. the homopolymerization of carbon-free-backbone chain such as polysiloxanes, polyphosphazene or copolymer.
Available polymer also comprises natural polymer, and is preferred: starch and derivant thereof, cellulose and derivant thereof, chitosan and derivant thereof.
Medicine described in the present invention can be made of antithrombotic reagent or thrombolytic agent, perhaps, is made of antithrombotic reagent and thrombolytic agent mixing simultaneously; Described medicine can be made of one or more medicament mixed.
Antithrombotic reagent comprises and is not limited in the described medicine: heparin class, indandione class, Coumarins, hirudin class;
Described thrombolytic agent is including but not limited to streptokinase; recombined streptokinase; urokinase; tissue-type plasminogen activator; Single-chain Urokinase-type Plasminogen Activator; acetylation plasminogen-streptokinase activator complex; alteplase; Lumbrukinase; gram bolt enzyme; anistreplase; prourokinase; Sbphylokinase; the snake venom anticoagulant enzyme; reteplase; blue for general enzyme; for Nip's enzyme; Monteplase; the K1K2Pu chimera; the coalition t-PA59D8 of antifibrin monoclonal antibody and PA.
Thrombus filter described in the present invention is including but not limited to rustless steel thrombus filter or cochrome thrombus filter or Nitinol thrombus filter or macromolecular material thrombus filter.
Thrombus filter of the present invention surface can not handled, and can also carry out modification and handle; The modification processing mode is: polishing, and perhaps roughening treatment, or add coupling agent layer, in order to the ability of sticking between raising and the drug-carrying polymer layer.
Among the present invention, described pharmaceutical carrier gross thickness is: 1 μ m～50 μ m, can constitute by one layer of polymeric, and also can comprise two-layer or two-layer above polymer; In each polymeric layer, can comprise identical or different, the medicine of equivalent or inequality.
The medicament contg that described polymeric medicine layer is last every square centimeter is: 1 μ g～500 μ g; The preferred employing: 20 μ g～200 μ g.Each drug distribution is in each polymeric layer, and the kind and the content of each layer contained drug can be the same or different.
Among the present invention, described thrombus filter can adopt the existing thrombus filter, the preferred employing: irregular olive shape, and integral body is cancellated thrombus filter; The preferred especially described thrombus filter of patent ZL022647783.3.
Beneficial effect: a kind of medicine coated thrombus filter provided by the invention, compared with prior art, advantage is: because the present invention can come the time of control drug release by the thickness of setting the drug loading layer, removed the trouble of taking medicine every day from; Because pharmaceutical carrier of the present invention is load antithrombotic reagent and thrombolytic agent simultaneously, make the present invention have the bolt of catching and thrombolytic effect simultaneously, the more effective formation that reduces local thrombus, the complication of vein obstruction etc., reduced patient's medical expense, improved patient's survival rate and guaranteed quality of life of patient.
Description of drawings
Fig. 1 is a medicine filter thrombus dissolving work sketch map of the present invention;
Fig. 2 is a structural representation of the present invention;
Fig. 3 is a kind of structural representation of thrombus filter among the present invention.
The specific embodiment:
Below in conjunction with the drawings and specific embodiments, further illustrate the present invention, should understand these embodiment only is used to the present invention is described and is not used in and limit the scope of the invention, after having read the present invention, those skilled in the art all fall within the application's claims institute restricted portion to the modification of the various equivalent form of values of the present invention.
A kind of medicine coated thrombus filter is as shown in Figure 1 inserted interception thrombosis and pulverizing in the blood vessel, discharges the thrombolytic-anticoagulant medicine simultaneously, plays the effect that continues to catch bolt and thrombolytic;
The structural representation of a kind of medicine coated thrombus filter as shown in Figures 2 and 3 comprises: thrombus filter 1, pharmaceutical carrier 2 and medicine 3; Described thrombus filter 1 is positioned at the innermost layer, and structure as shown in Figure 3; Pharmaceutical carrier 2 is made of three strata compounds, is respectively polymeric layer 21, polymeric layer 22 and polymeric layer 23; This pharmaceutical carrier 2 is coated on the surface of thrombus filter 1, and medicine 3 loads in the pharmaceutical carrier 2.
Embodiment 1
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the 316L rustless steel, and integral body is olive shape, be net distribution, the filter face coat is the vinylidene fluoride-hexafluoropropylene copolymer layer of load bearing chain mycin, and coating layer thickness is 5 μ m, and medicament contg is every square centimeter 150 μ g.The micro channel that medicine can form by polymers swell in 90 days in vitro tests progressively discharges, and plays thrombus dissolving anticoagulant effect.
Embodiment 2
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the NiTi alloy, and face coat is the vinylidene fluoride-hexafluoropropylene copolymer layer of load bearing chain mycin, and coating layer thickness is 5 μ m, and medicament contg is every square centimeter 150 μ g.The micro channel that medicine can form by polymers swell in 90 days in vitro tests progressively discharges, and plays thrombus dissolving anticoagulant effect.
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the NiTi alloy, and face coat is the vinylidene fluoride-hexafluoropropylene copolymer layer of load bearing chain mycin, and coating layer thickness is 5 μ m, and medicament contg is every square centimeter 200 μ g.The micro channel that medicine can form by polymers swell in 90 days in vitro tests progressively discharges, and plays thrombus dissolving anticoagulant effect.
Embodiment 4
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the NiTi alloy, and face coat is the copolymer layer of the methacrylic acid-beta-hydroxy ethyl ester/butyl methacrylate of load bearing chain mycin, and coating layer thickness is 3 μ m, and medicament contg is every square centimeter 130 μ g.The micro channel that medicine can form by polymers swell in 70 days in vitro tests progressively discharges, and plays thrombus dissolving anticoagulant effect.
Embodiment 5
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the NiTi alloy, and face coat is the ethyl cellulose graft polypropylene tert-butyl acrylate copolymer layer of load bearing chain mycin, and coating layer thickness is 3 μ m, and medicament contg is every square centimeter 130 μ g.The micro channel that medicine can form by polyacrylic acid tert-butyl ester swelling and cellulose degradation in 70 days in vitro tests progressively discharges, and plays thrombus dissolving anticoagulant effect.
Embodiment 6
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the NiTi alloy, and face coat is the blue polylactic acid-glycolic guanidine-acetic acid copolymer for general enzyme of load, and coating layer thickness is 6 μ m, and medicament contg is every square centimeter 160 μ g.Medicine can be realized progressively discharging from coating inside by depolymerization in 60 days in vitro tests, played thrombus dissolving anticoagulant effect.
Embodiment 7
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the NiTi alloy, and face coat is the blue polycaprolactone-copolymer of poly lactic acid for general enzyme of load, and coating layer thickness is 7 μ m, and medicament contg is every square centimeter 170 μ g.Medicine can be realized progressively discharging from coating inside by depolymerization in 70 days in vitro tests, played thrombus dissolving anticoagulant effect.
Embodiment 8
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the NiTi alloy, and face coat is polymer base coat and polymeric medicine layer.Wherein the polymer of bottom is a Parylene, and thickness is 3 μ m; Outer field polymer is a polylactic acid-glycolic guanidine-acetic acid copolymer, and thickness is 3 μ m, contains the streptomycin of every square centimeter 150 μ g.Medicine can be realized progressively discharging from coating inside by depolymerization in 50 days in vitro tests, played thrombus dissolving anticoagulant effect.
Embodiment 9
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the NiTi alloy, and face coat is polymer base coat and polymeric medicine layer.Wherein the polymer of bottom is the poly(ether-urethane) of heparinization, and thickness is 3 μ m; Outer field polymer is a polylactic acid-glycolic guanidine-acetic acid copolymer, and thickness is 3 μ m, contains the streptomycin of every square centimeter 150 μ g.Streptomycin can be realized progressively discharging from coating inside by polymer P LGA degraded in 50 days in vitro tests; Bottom medicine heparin will continue to discharge about 120 days by outer hole after a period of time, play thrombus dissolving anticoagulant effect.
Embodiment 10
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the NiTi alloy, and face coat is followed successively by polymer base coat, polymeric medicine layer and polymer surface layer from the inside to surface.Wherein the polymer of bottom is the poly(ether-urethane) of heparinization, and thickness is 3 μ m; The polymer that the polymeric medicine layer adopts is a poly lactic coglycolic acid, and thickness is 3 μ m, contains the streptomycin of every square centimeter 150 μ g; The polymer of surface layer is a poly lactic coglycolic acid, and thickness is 1 μ m.In in vitro tests, at first be that outer PLGA degrades, played the delay drug release time about 5 days, then streptomycin can progressively discharge from coating inside by realization in 90 days; Bottom medicine heparin will continue to discharge about 120 days by outer hole after a period of time, play thrombus dissolving anticoagulant effect.
Embodiment 11
A kind of thrombus filter of pharmaceutical pack quilt is a filter substrate with the NiTi alloy, and face coat is followed successively by polymer base coat, polymeric medicine layer I and polymeric medicine layer II from the inside to surface.Wherein the polymer of bottom is a Parylene, and thickness is 1 μ m; The polymer that polymeric medicine I adopts is a poly lactic coglycolic acid, and thickness is 3 μ m, contains the streptomycin of every square centimeter 100 μ g; The polymer that polymeric medicine II adopts is a poly lactic coglycolic acid, and thickness is 3 μ m, contains the streptomycin of every square centimeter 150 μ g.Streptomycin can be realized continuing afterwards to discharge about 90 days from the inner rapid release of coating by polymer P LGA degraded in 50 days in vitro tests, played the effect of thrombolytic-anticoagulant.
Claims (8)
1. medicine coated thrombus filter, it is characterized in that: this pharmaceutical pack is filtered device and comprises: thrombus filter (1), pharmaceutical carrier (2) and medicine (3); Described thrombus filter (1) is positioned at the innermost layer, and pharmaceutical carrier (2) is coated on the surface of thrombus filter (1), and medicine (3) is carried in the pharmaceutical carrier (2).
2. a kind of medicine coated thrombus filter according to claim 1 is characterized in that: described pharmaceutical carrier (2) is made of polymer, and described pharmaceutical carrier (2) has several layers, and every layer of polymer mixed by one or more forms; Described medicine (3) is: antithrombotic reagent, perhaps, and thrombolytic agent, perhaps, antithrombotic reagent and thrombolytic agent mix; This medicine (3) is distributed in the pharmaceutical carrier (2), and every layer is made of one or more medicament mixed.
3. a kind of medicine coated thrombus filter according to claim 2 is characterized in that:
The type of polymer of described formation pharmaceutical carrier (2) is: biodegradable synthetic polymer, or nonbiodegradable synthetic polymer, or natural polymer;
Described biodegradable synthetic polymer is: polyamino acid, polylactic acid, copolymerization ether-ester, polyglycolic acid, poe, polycaprolactone, poly-anhydride;
Described nonbiodegradable synthetic polymer is: the product of substituted olefine homopolymerization such as ethylene, propylene, styrene, vinyl chloride, acrylate or copolymerization, perhaps, the homopolymerization or the copolymer that contain non-carbon atom in the main chains such as polyurethane, polyester, polyethers, polyamide, perhaps, the homopolymerization of carbon-free-backbone chain such as polysiloxanes, polyphosphazene or copolymer;
Described natural polymer is: starch and derivant thereof, cellulose and derivant thereof, chitosan and derivant thereof;
In the described medicine (3),
Antithrombotic reagent is: heparin class, indandione class, Coumarins, hirudin class;
Thrombolytic agent is: streptokinase, recombined streptokinase, urokinase, tissue-type plasminogen activator, Single-chain Urokinase-type Plasminogen Activator, acetylation plasminogen-streptokinase activator complex, Lumbrukinase, gram bolt enzyme, anistreplase, prourokinase, Sbphylokinase, snake venom anticoagulant enzyme, reteplase, the blue coalition t-PA59D8 that replaces general enzyme, replaces Nip's enzyme, Monteplase, K1K2Pu chimera, antifibrin monoclonal antibody and PA.
4. a kind of medicine coated thrombus filter according to claim 1, it is characterized in that: described thrombus filter (1) is: rustless steel thrombus filter or cochrome thrombus filter or Nitinol thrombus filter, or macromolecular material thrombus filter.
5. a kind of medicine coated thrombus filter according to claim 1 is characterized in that: described thrombus filter (1) surface can be carried out modification and be handled: polishing, and perhaps roughening treatment, or add coupling agent layer.
6. a kind of medicine coated thrombus filter according to claim 1 is characterized in that: described pharmaceutical carrier (2) gross thickness is: 1 μ m～50 μ m.
7. a kind of medicine coated thrombus filter according to claim 1 is characterized in that: described medicine (3) is gone up on filter every square centimeter content and is: 1 μ g～500 μ g; And every square centimeter of preferred content is: 20 μ g～200 μ g.
8. a kind of medicine coated thrombus filter according to claim 1 is characterized in that: described thrombus filter (1) is irregular olive shape, and integral body is network structure.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 201010182185 CN101843531A (en) | 2010-05-25 | 2010-05-25 | Medicament coated thrombus filter |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 201010182185 CN101843531A (en) | 2010-05-25 | 2010-05-25 | Medicament coated thrombus filter |
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| CN103027763A (en) * | 2012-11-16 | 2013-04-10 | 北京泰杰伟业科技有限公司 | Vena cava filter coated with macromolecular coating and preparation method for macromolecular coating |
| CN103785101A (en) * | 2014-02-19 | 2014-05-14 | 东南大学 | Electric field multi-pulse drug release device and manufacturing method and application thereof |
| WO2014094543A1 (en) | 2012-12-21 | 2014-06-26 | 先健科技(深圳)有限公司 | Medical instrument coating and preparation method therefor and medical instrument comprising coating |
| CN104812336A (en) * | 2012-12-21 | 2015-07-29 | 加利福尼亚大学董事会 | In vivo positionable filtration devices and methods related thereto |
| CN105561401A (en) * | 2015-12-29 | 2016-05-11 | 深圳市昌华生物医学工程有限公司 | Composite fiber and preparation method thereof, and orthopaedic strapping line |
| CN106310392A (en) * | 2015-07-09 | 2017-01-11 | 首都医科大学附属北京世纪坛医院 | Coating solution, recoverable vena cava filter and preparation method thereof |
| CN107890381A (en) * | 2017-11-27 | 2018-04-10 | 郑州大学第附属医院 | Antiproliferative, the IVCF of antithrombotic reagent coating that can be placed for a long time |
| WO2024222834A1 (en) * | 2023-04-27 | 2024-10-31 | 北京信立泰医疗器械有限公司 | Drug coating and medical device comprising same, system, and preparation method |
| WO2024230853A1 (en) * | 2023-05-06 | 2024-11-14 | 苏州中天医疗器械科技有限公司 | Distal protection device and manufacturing method therefor |
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| CN103027763A (en) * | 2012-11-16 | 2013-04-10 | 北京泰杰伟业科技有限公司 | Vena cava filter coated with macromolecular coating and preparation method for macromolecular coating |
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| CN104812336A (en) * | 2012-12-21 | 2015-07-29 | 加利福尼亚大学董事会 | In vivo positionable filtration devices and methods related thereto |
| CN103785101A (en) * | 2014-02-19 | 2014-05-14 | 东南大学 | Electric field multi-pulse drug release device and manufacturing method and application thereof |
| CN103785101B (en) * | 2014-02-19 | 2015-08-26 | 东南大学 | A kind of electric field multiple-pulse medicament release device and its preparation method and application |
| CN106310392A (en) * | 2015-07-09 | 2017-01-11 | 首都医科大学附属北京世纪坛医院 | Coating solution, recoverable vena cava filter and preparation method thereof |
| CN105561401A (en) * | 2015-12-29 | 2016-05-11 | 深圳市昌华生物医学工程有限公司 | Composite fiber and preparation method thereof, and orthopaedic strapping line |
| CN105561401B (en) * | 2015-12-29 | 2020-06-02 | 深圳市昌华生物医学工程有限公司 | Composite fiber, manufacturing method and orthopedic binding wire |
| CN107890381A (en) * | 2017-11-27 | 2018-04-10 | 郑州大学第附属医院 | Antiproliferative, the IVCF of antithrombotic reagent coating that can be placed for a long time |
| WO2024222834A1 (en) * | 2023-04-27 | 2024-10-31 | 北京信立泰医疗器械有限公司 | Drug coating and medical device comprising same, system, and preparation method |
| WO2024230853A1 (en) * | 2023-05-06 | 2024-11-14 | 苏州中天医疗器械科技有限公司 | Distal protection device and manufacturing method therefor |
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