CN203802850U - Internal coating stent for blood vessel - Google Patents
Internal coating stent for blood vessel Download PDFInfo
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- CN203802850U CN203802850U CN201420191972.9U CN201420191972U CN203802850U CN 203802850 U CN203802850 U CN 203802850U CN 201420191972 U CN201420191972 U CN 201420191972U CN 203802850 U CN203802850 U CN 203802850U
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Landscapes
- Materials For Medical Uses (AREA)
- Media Introduction/Drainage Providing Device (AREA)
Abstract
The utility model discloses an internal coating stent for a blood vessel. The stent comprises a stent body and a coating layer, wherein the coating layer covers the surface of the stent body and comprises at least one TGFalpha-Saporin medicine layer and a macromolecule polymer layer covering the outmost layer of the coating layer. At least one TGFalpha-Saporin medicine layer is inserted into the coating layer of the internal coating stent for the blood vessel, so that the smooth muscle cell proliferation can be selectively inhibited and wound epithelization can also be improved at the same time.
Description
Technical field
This utility model relates to cardiovascular medical field, especially, relates to a kind of stent with coating in blood vessel.
Background technology
1987, Sigwart etc. were used for coronary artery by metal rack in blood vessel first.Coronary stent is a kind of blood vessel inner support device of being made by hard metal or alloy material, it has good plasticity and geometrical stability, can under closure state, through conduit, deliver to diseased region, after the methods such as air bag expansion are launched, can play the effect of support blood vessels.But because support cannot be avoided hamartoplasia, the thrombus source of metal itself in addition.After implanting, support still has 10%～30% probability generation vascular restenosis (ISR).Once restenosis occurs, therapeutic process is more complicated and difficult than natural coronary stricture.Therefore, ISR has become the principal element of restriction percutaneous transluminal coronary angioplasty development.Wherein coating stent of medicine is one of effective ways of greatest concern in current prevention of restenosis method.
Coating stent of medicine be by medicine directly or by suitable support coating in rack surface, make support become a local drug delivery system.At present, known bracket for eluting medicament is mainly taxol bracket for eluting medicament and drug-eluting stent, its coating medicine is all unselected cell drug toxicity, existing coating medicine is after suppressing inner film injury in smooth muscle cell hyper-proliferative, also can produce obvious cytotoxic effect to participating in endotheliocyte and the endothelial progenitor cells of endothelium reparation, suppress its migration, propagation and reparation, therefore can cause the full problem of lasting endothelial injury and endothelialization.And then cause that mortality rate is up to 45% thrombus in stents.Therefore develop a kind of selectivity and suppress smooth muscle cell proliferation, can promote again the coating medicine of injured blood vessel endothelialization to become the key of drug stent development.
Utility model content
This utility model object is to provide a kind of intravascular drug coating bracket, so that a kind of coating stent of medicine that had not only suppressed smooth muscle cell proliferation but also promoted to lose blood vessel endothelium to be provided.
For achieving the above object, according to this utility model, provide a kind of stent with coating in blood vessel, comprise rack body and coating, coating is coated on rack body surface, and coating comprises: be coated at least one deck TGF α-Saporin medicine layer on rack body and be coated on the outermost macromolecule polymer of coating layer.
Further, macromolecule polymer layer is at least one deck chitosan layer, gelatin layer or heparin layer.
Further, macromolecule polymer layer is heparin layer.
Further, coating also comprises the polymer base coat being coated between rack body surface and TGF α-Saporin medicine layer,
Polymer base coat is at least one deck chitosan layer or heparin layer.
Further, coating also comprises the layer that plugs being coated between any multilamellar TGF α-Saporin medicine layer, plugs layer and comprises
Chitosan layer or heparin layer or chitosan layer and heparin layer alternately insert between TGF α-Saporin medicine layer.
Further, in coating, the number of plies of TGF α-Saporin medicine is 14～16 layers.
Further, TGF α-Saporin medicine number of plies is 15 layers.
Further, rack body is titanium alloy support, titanium framework or stainless steel stent.
The utlity model has following beneficial effect:
In the coating of the stent with coating in blood vessel that this utility model provides, plug at least one deck TGF α-Saporin medicine layer, when making this support energy selectivity suppress smooth muscle cell proliferation, can also promote support endothelialization.The macromolecule polymer layer being simultaneously coated on TGF α-Saporin medicine layer can play to this medicine the effect of slow release, the action time of the release medicine of extending bracket in human body.
Except object described above, feature and advantage, this utility model also has other object, feature and advantage.Below with reference to figure, this utility model is described in further detail.
Accompanying drawing explanation
The accompanying drawing that forms the application's a part is used to provide further understanding of the present utility model, and schematic description and description of the present utility model is used for explaining this utility model, does not form improper restriction of the present utility model.In the accompanying drawings:
Fig. 1 is this utility model preferred embodiment coating bracket axonometric chart;
Fig. 2 is that this utility model preferred embodiment A point amplifies schematic cross section;
Fig. 3 is that this utility model preferred embodiment A point amplifies schematic cross section; And
Fig. 4 is that this utility model preferred embodiment A point amplifies schematic cross section.
Marginal data:
1, rack body; 2, TGF α-Saporin medicine layer; 3, heparin layer; 4, chitosan layer; 20, TGF α-Saporin medicine layer; 21, TGF α-Saporin medicine layer.
The specific embodiment
Below in conjunction with accompanying drawing, embodiment of the present utility model is elaborated, but the multitude of different ways that this utility model can be defined by the claims and cover is implemented.
This utility model provides a kind of stent with coating in blood vessel, and this coating bracket comprises that at least the TGFa-Saporin of one deck connects thing (transforming growth factor α-sapotoxin fibroin connects thing, is called for short TGFa-Saporin).TGFa-Saporin connection thing routinely chemical SMPT (4-succinimido oxygen carbonyl-methyl-α [2-pyridine radicals two sulfur] toluene) connecting method makes.The coating that this utility model provides can adopt conventional method to be coated on coating bracket body, such as adopting coating self assembly, immerse seasoning, multilamellar construction from part etc.Introduction for TGFa-Saporin sees Yang Jun, remaining thin brave, woods dawn, Quan Zhihua, the < < bio-guide medicine transforming growth factor a-sapotoxin fibroin Saporin that Tan little Jin is published in 62nd～65 pages of Chinese circulation magazine the 17th the 1st phases of volume of February in 2002 (total the 133rd phase) has in the article of specific growth inhibited effect > > propagation vascular smooth muscle cell.
The stereochemical structure of the coating bracket that this utility model provides as shown in Figure 1.This coating bracket comprises rack body 1 and is coated on the lip-deep coating of this rack body 1.Coating comprises at least one deck TGFa-Saporin medicine layer 2 and macromolecule polymer layer.After the coated TGFa-Saporin medicine layer 2 in stent with coating in blood vessel surface, can in the time of selectivity inhibition smooth muscle cell proliferation, can also promote support endothelialization, avoid the generation of postoperative restenosis.Macromolecule polymer layer can, for conventional support top layer macromolecule polymer layer, be preferably chitosan layer 4, gelatin layer or heparin layer 3.More preferably heparin layer 3.Heparin layer 3 can be heparin sodium (or calcium) layer or low molecular sodium heparin (or calcium) layer.A plurality of concrete materials form after single coating at rack surface, and macromolecule polymer layer can be comprised of multilamellar single coating.Preferred coating is by TGFa-Saporin medicine layer 2, chitosan layer 4, heparin layer 3 successively stacked composition.Preferred, coating using by TGFa-Saporin medicine layer 2, chitosan layer 4, heparin layer 3 successively stacked form layer as the first construction unit, repeatedly the first construction unit obtains coating bracket.Adopt the endovascular stent of this structure can make the medicine slow release after intravasation in bracket coating, the extended treatment time, promote postoperative blood vessel to recover.Macromolecule polymer layer is preferably heparin layer 3, usings heparin layer 3 during as macromolecule polymer layer, and gained coating bracket surface is more smooth, is convenient to seeking connections with of endotheliocyte, is conducive to bracket coating Chinese medicine and enters cells play effect.
Specifically can be, in Fig. 1, the amplification of A point cross section obtains Fig. 2, and as shown in Figure 2, this stent with coating in blood vessel comprises: rack body 1, TGFa-Saporin medicine layer 2 and heparin layer 3.The coating bracket body 1 coated TGFa-Saporin medicine layer 2 in surface.Coated heparin layer 3 on TGFa-Saporin medicine layer 2 outer surfaces.Preferably now coating layer thickness is 18 μ m.
Preferably, the endovascular stent that this utility model provides comprises: rack body 1 and repeat the first construction unit at least one times.The first construction unit comprises stacked successively polymer base coat, TGFa-Saporin medicine layer 2 and macromolecule polymer layer.Wherein polymer base coat is at least one deck chitosan layer 4 or heparin layer 3.When polymer base coat is multilayered shell polysaccharide layer 4 or heparin layer 3, can be by multilayered shell polysaccharide layer 4 or stacked the obtaining of heparin layer 3 intersection.This polymer base coat can be brought into play the effect of gathering, slow release TGF α-Saporin medicine layer 2 Chinese medicines, promotes the performance of support curative effect.
Fig. 3 is embodiment 2 of the present utility model.As shown in Figure 3.Coating on this coating bracket comprises successively stacked chitosan layer 4, heparin layer 3 and TGFa-Saporin medicine layer 2.It is upper that chitosan layer 4 is coated on rack body 1 surface, coated heparin layer 3 on the outer surface of chitosan layer 4, coated TGFa-Saporin medicine layer 2 on the outer surface of heparin layer 3.Increase the thickness of every layer, obtain the medicable coating bracket of tool.The endovascular stent of this structure can be determined institute's coating medicine quality by weighing weight support frame after each immersion.Make the upper dose on support be convenient to accurate control.
Preferably, the endovascular stent that this utility model provides comprises: rack body 1 and the second construction unit.The second construction unit comprises at least two-layer TGFa-Saporin medicine layer 2 and is inserted in the layer that plugs between any two-layer TGFa-Saporin medicine layer 2.Plug layer and comprise that chitosan layer 4, heparin layer 3 or chitosan layer 4 and heparin layer 3 sequentially intersect between the two-layer TGFa-Saporin medicine layer 2 of insertion.Increase and to plug layer and can protect on the one hand every layer of TGFa-Saporin medicine layer 2 to prevent from occurring in transportation loss.Can also play the effect of slow releasing pharmaceutical simultaneously.
Specific embodiment is that stent with coating in blood vessel comprises rack body 1 and coating.Coating is comprised of a plurality of the 3rd construction units.The 3rd construction unit is comprised of stacked successively heparin layer 3, TGFa-Saporin medicine layer 2, chitosan layer 4 and TGFa-Saporin medicine layer 2.
The endovascular stent that preferably this utility model provides comprises 14～16 layers of TGFa-Saporin medicine layer 2, and now the concentration of coated carrier Chinese medicine and the time graph of release just in time meet the requirement of postoperative restenosis treatment.Can guarantee that blood vessel endotheliumization is complete before drug release is complete, Restenosis does not occur again simultaneously.Most preferred is 15 layers, and now support discharges effect of drugs optimum.
Have plug layer endovascular stent embodiment as shown in Figure 4, coating bracket comprises rack body 1 and the second construction unit.The second construction unit is sequentially stacked heparin layer 3, a TGFa-Saporin medicine layer 20, chitosan layer 4, the 2nd TGFa-Saporin medicine layer 21, repeats this unit 14 times, obtains endovascular stent.
Below illustrate the preparation method of TGFa-Saporin medicine and coating bracket, the coating bracket providing when this utility model is not limited to this.
Below for illustrating TGF α-Saporin process for preparing medicine.
The TGF α preparation method of derivation
1) TGF α 20mg is dissolved in 2.67ml borate buffer.Add the SMPT (0.48mg/ml) that 267ul is dissolved in dimethyl formamide, make SMPT with TGF α mole number than excessive 2.5 times, in order to keep the dissolubility of SMPT, in reaction system, the amount of dimethyl formamide is at 10% (V/V), under room temperature, stir 1 hour, obtain the TGF α of the first derivation.
2) the first derivation TGF α uses phosphoric acid-edta buffer liquid balance after crossing SephadexG25 post (30*1.5cm), collects the first eluting peak, by nitrogen blowing, is dried concentrated or is concentrated by molecular sieve filtration, obtains the derivation TGF α after purification.
The first product preparation method of activation Saporin
10mgSaporin is dissolved in 7ml phosphoric acid-edta buffer liquid, at room temperature reacts 30 minutes with 50mmol/LDTT, obtains the first product.
TGF α-Saporin process for preparing medicine
1) the first product being crossed to SephadexG25 post, the protein peak flowing out from post is added in derivation TGF α, is that 3:1 mixes by TGF α with Saporin mol ratio.The concentrated products therefrom of molecular sieve filtration is to 10mi, and then stirring reaction 65～75 hours in logical nitrogen situation at room temperature, obtains targeted drug.
2) 0.2mmol/L cysteine solution is added in targeted drug, at room temperature stirring reaction is 5～7 hours, and passivation targeted drug obtains TGF α-Saporin medicine.
3) TGF α-Saporin medicine is at the upper purification of SephacrylS-200 post (90*2.2cm), with 0.05mol/L phosphate buffer balance eluting.Explorer protein purification system ultraviolet monitoring is collected first peak eluent, and collects post liquid and dry concentrated under nitrogen blowing environment, obtains the TGF α-Saporin medicine after purification and remains in the refrigerator of 4 ℃.
Illustrate stent with coating in blood vessel preparation method
Get 3.0mm * 20.0mm domestic Pt-Ir alloy bracket and be immersed in 60 ℃, 20%NaOH solution and soak 24 hours, fully clean, then use ultrasonic cleaning in distilled water, drying at room temperature.Get poly-D-lysine and be dissolved in PBS (phosphate buffer), obtain the said polycation solution of pH=7.2, mass concentration 2.Sg/L.Above-mentioned alloy bare bracket after NaOH surface treatment is immersed in Poly-L-Lysine Solution to 30 minutes, takes out standby.
Taking heparin sodium is dissolved in distilled water, is prepared into pH=4, the polyanion solution of mass concentration 5g/L.Chitosan is dissolved in the acetum of volume fraction 1%, is prepared into pH=4, the said polycation solution of mass concentration 5g/L.(in following examples, chitosan solution used and heparin sodium aqua are all by this preparation) gets TGF α-SAP medicine dissolution of making in embodiment 1 in ethanol.
The alloy bare bracket that soaked sodium hydroxide solution is immersed in respectively to heparin solution successively, and TGF α-SAP alcoholic solution, in chitosan solution and TGF α-SAP alcoholic solution, soak time is respectively 15,1, and 15,1 minute, each immersion finished all the support of coating to be dried afterwards; Using this as a unit, and repeatedly this unit, repeats this unit 15 times.Finally gained support is immersed in heparin sodium aqua and obtain heparin sodium layer as high molecular polymer (outermost) layer, obtain the coating containing TGF α-Saporin medicine.
The foregoing is only preferred embodiment of the present utility model, be not limited to this utility model, for a person skilled in the art, this utility model can have various modifications and variations.All within spirit of the present utility model and principle, any modification of doing, be equal to replacement, improvement etc., within all should being included in protection domain of the present utility model.
Claims (8)
1. a stent with coating in blood vessel, comprise rack body and coating, described coating is coated on described rack body surface, it is characterized in that, described coating comprises: be coated at least one deck TGF α-Saporin medicine layer on described rack body and be coated on the outermost macromolecule polymer of described coating layer.
2. support according to claim 1, is characterized in that, described macromolecule polymer layer is at least one deck chitosan layer, gelatin layer or heparin layer.
3. support according to claim 2, is characterized in that, described macromolecule polymer layer is heparin layer.
4. support according to claim 1, is characterized in that, described coating also comprises the polymer base coat being coated between described rack body surface and described TGF α-Saporin medicine layer, and described polymer base coat is at least one deck chitosan layer or heparin layer.
5. support according to claim 1, it is characterized in that, described coating also comprises the layer that plugs being coated on described in any multilamellar between TGF α-Saporin medicine layer, described in plug layer and comprise that chitosan layer or heparin layer or described chitosan layer and heparin layer alternately insert between described TGF α-Saporin medicine layer.
6. according to the support described in any one in claim 1～5, it is characterized in that, the number of plies of the α-Saporin of TGF described in described coating medicine is 14～16 layers.
7. support according to claim 6, is characterized in that, described TGF α-Saporin medicine number of plies is 15 layers.
8. support according to claim 7, is characterized in that, described rack body is titanium alloy support, titanium framework or stainless steel stent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201420191972.9U CN203802850U (en) | 2014-04-18 | 2014-04-18 | Internal coating stent for blood vessel |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201420191972.9U CN203802850U (en) | 2014-04-18 | 2014-04-18 | Internal coating stent for blood vessel |
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| Publication Number | Publication Date |
|---|---|
| CN203802850U true CN203802850U (en) | 2014-09-03 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201420191972.9U Expired - Fee Related CN203802850U (en) | 2014-04-18 | 2014-04-18 | Internal coating stent for blood vessel |
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| Country | Link |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106562838A (en) * | 2015-10-09 | 2017-04-19 | 李道远 | Novel cardiovascular stent |
| CN113616860A (en) * | 2021-06-29 | 2021-11-09 | 四川大学 | Intravascular stent coating material with drug slow release, anticoagulation and calcification resistance and preparation method thereof |
-
2014
- 2014-04-18 CN CN201420191972.9U patent/CN203802850U/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106562838A (en) * | 2015-10-09 | 2017-04-19 | 李道远 | Novel cardiovascular stent |
| CN113616860A (en) * | 2021-06-29 | 2021-11-09 | 四川大学 | Intravascular stent coating material with drug slow release, anticoagulation and calcification resistance and preparation method thereof |
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