CN1194653C - Internal cavitary and vessel stent with medicinal coating against spinal canal restenosis and production thereof - Google Patents
Internal cavitary and vessel stent with medicinal coating against spinal canal restenosis and production thereof Download PDFInfo
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- CN1194653C CN1194653C CNB021592659A CN02159265A CN1194653C CN 1194653 C CN1194653 C CN 1194653C CN B021592659 A CNB021592659 A CN B021592659A CN 02159265 A CN02159265 A CN 02159265A CN 1194653 C CN1194653 C CN 1194653C
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- curcumin
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Abstract
The present invention relates to a therapeutic bracket for partially delivering medicines to the position of a pathological intracoelomic cavity tract by using a bracket as a skeleton and an eluting coating layer as a carrier and a method for producing the bracket of the present invention according to the characteristics of the used medicines. After being planted in the intracoelomic cavity tract, the intracoelomic cavity tract bracket can inhibit the cell proliferation of smooth muscles and the synthesis of extracellular matrixes by the sustained release of the carried medicines. The therapeutic bracket has the functions of promoting endothelialization, resisting blood coagulation, blood platelets, oxidation and inflammation, etc. Thus, the process of restenosis can be prevented in a plurality of sections. The intracoelomic cavity tract bracket of the present invention is composed of a bracket and a medicine coating layer covered on the surface of the bracket, wherein the medicine coating layer contains curcumin. The intracoelomic cavity tract bracket is particularly suitable for preventing and treating the bracket postoperative restenosis after percutaneous transluminal coronary angioplasty.
Description
Technical field
The present invention relates to a kind of support and manufacture method thereof with control restenosis medicaments coating.Specifically the present invention proposes a kind ofly by being skeleton with the support, coating is to take off to wash the treatment support of carrier to the local dispenser in pathological changes intracoelomic cavity pipe position, and the method for making support of the present invention according to the characteristic of employed medicine.
Background technology
For narrow property disease in the intracoelomic cavity pipe, adopting percutaneous tranluminal coronary angioplasty (PTCA) is a kind of main Therapeutic Method.In the method, the tubular bracket percutaneous puncture is implanted in the lumen (as blood vessel etc.), utilize the mechanical property of support that narrow sexually transmitted disease (STD) is become the position and strut required overflow section, satisfy the needs of body-internal-circulation in the human body with this.Two during the last ten years, and this technology has obtained development at full speed, and promptly promoted and be widely used.At present, the annual patient's quantity of percutaneous puncture arteria coronaria interventional therapy (PCI) that adopts in the whole world exceedes 1,500,000 routine times, and wherein about 70% case is implanted coronary artery bracket.
The major defect of percutaneous tranluminal coronary angioplasty (PTCA) is the postoperative restenosis of dispensing support portions, and its incidence rate is 20-30%.The main mechanism that produces restenosis relates to three aspect factors, and early stage elastical retraction, blood vessel is reinvented and the smooth muscle hyperplasia of stent-induced and the synthetic new intima that causes of substrate transition form.From present research, support has been eliminated the tube wall elasticity retraction basically and the negativity blood vessel is reinvented, but neointimal hyperplasia is still unsolved so far subject matter.New intima forms mainly and is made of the vascular smooth muscle and the proteoglycans substrate of breeding.Therefore, stoping vascular smooth muscle cell curing and substrate synthetic is the important target spot of the new control in-stent restenosis of exploitation.
At present, restenosis has mainly been studied the blood vessel internal radiotherapy and has been utilized Drug therapy in the treatment of vascular.The blood vessel internal radiotherapy can obviously reduce restenosis, but later stage thrombosis and edge effect have limited its clinical use.And drug treatment because many medicines, shows anti-restenosis effect as the zoopery of antiplatelet drug, anticoagulant medicine, converting enzyme inhibitor, antioxidant etc., but invalid to the mankind.The possible explanation of this contradictory phenomena is because the restriction of the toxic and side effects of medicine makes the underdosage of used medicine and pharmacologically active persistent period lack.Therefore, be that carrier discharges medicine in the pathological changes local slow with the support, both can reduce dosage significantly and avoid side effect, can form high drug level in the part again, become anti-restenosis research focus both domestic and external.
Disclose a kind of intravascular stent at Chinese patent literature CN1360951A, wherein formed by intravascular stent and the coating that is covered in rack surface with anti-restenosis coating layer.A kind of medicine eluted cardiovascular frame and preparation method thereof is further disclosed at Chinese patent literature CN1355005A, support support body is wherein uploaded and is had the multilayer medicine structure, and employed medicine with anti-restenosis function comprises one or more in rapamycin, dactinomycin, ciclosporin A or the paclitaxel.It is clear and definite that at present known coating bracket with said medicine suppresses the restenosis effect, and preliminary clinical trial shows and can significantly reduce restenosis rate that effect is encouraging.But this class medicine all can suppress the endothelialization again of blood vessel, influences the agglutination of blood vessel injury, may make the blood vessel wall attenuation, even forms hemangioma.On the other hand, the coating bracket of said medicine costs an arm and a leg, about 40,000 yuans of each piece.
Practice from clinical research, the coating drug candidate of ideal control restenosis should have multiple pharmacologically active, as suppress smooth muscle cell proliferation, suppress cellular matrix and synthesize, promote again endothelialization, anticoagulant, antiplatelet, antioxidation, antiinflammatory etc., can stop the restenosis processes in a plurality of links.
Curcumin is the natural pigment that extracts from the Chinese medicine curcuma plant.Except as the food coloring, the pharmacologically active of the curcumin concern that also induces one, its pharmacologically active has obtained proof in zoopery and human body.These activity comprise, for example, urge gall bladder emptying activity (stimulating gallbladder flesh); Lipidemia activity (reduction plasma cholesterol); [its content is referring to R Hansel, K.Keller, H.Rim pler and G.Schneider Hagers Handbuch der Pharmazeutlschen Praxis " Hager medicinal practice handbook for anti-tumor activity, Springer publishing house, the 4th volume, medicine A-D, 5 editions, the 1084-1102 page or leaf].Through discovering for many years of applicant, curcumin also has all features of the described ideal control restenosis medicaments of a last paragragh, does not have obvious toxic-side effects simultaneously.
Summary of the invention
For this reason, the objective of the invention is to propose a kind of intracoelomic cavity pipe inner support with control restenosis medicaments coating, this intracoelomic cavity pipe inner support can be by its carrier band after in the lumen that implants the lasting release of medicine suppress smooth muscle cell proliferation and extracellular matrix is synthetic, and have functions such as promoting again endothelialization, anticoagulant, antiplatelet, antioxidation, antiinflammatory, and then can stop the restenosis process in a plurality of links.
Further purpose of the present invention is to propose a kind of intracoelomic cavity pipe inner support that discharges medicine according to restenosis mechanism in the intracoelomic cavity pipe in right amount.
A further object of the present invention is to propose a kind of manufacture method of above-mentioned intracoelomic cavity pipe inner support, and the intracoelomic cavity pipe inner support that produces by this method can controllably discharge the medicine of institute's carrier band on the support.
For achieving the above object, the intracoelomic cavity pipe inner support with control restenosis medicaments coating of the present invention is made up of support and the medication coat that is covered in rack surface, it is characterized in that containing in the described medication coat curcumin (curcumin).
Wherein, described medication coat has double-layer structure at least, and its ectomesoderm synthesizes the curcumin layer that is divided into curcumin, and one deck ingredient is medicament elution carrier and the blended slow release layer of curcumin at least.The structure of described medication coat is the alternate setting with described slow release layer of described curcumin layer.
Best, described medication coat has three-decker, and wherein the one deck near described cavity inner support support body is the curcumin layer, and the intermediate layer is the slow release layer of medicament elution carrier mixing curcumin, and skin is the curcumin layer.
In the present invention, Poly-L-lactic acid (PLLA) that comparatively ideal described pharmaceutical carrier is molecular weight 30,000 dalton to 32, ten thousand dalton (30-320KD).
The invention allows for a kind of manufacture method with intracoelomic cavity pipe inner support of control restenosis medicaments coating, wherein the curcumin layer generates step:
A. curcumin and solvent are fully stirred evenly and make the curcumin drug solution;
B. use the described curcumin drug solution of support dipping;
C. from described solution, take out described support and make the curcumin drug solution drying that is bonded on the described support, form medication coat.
Further, the manufacture method with intracoelomic cavity pipe inner support of control restenosis medicaments coating of the present invention comprises that also the following slow release layer that is used alternatingly with curcumin layer generation step generates step:
-curcumin and medicament elution carrier mix homogeneously are made medicament slow release solution;
The described medicament slow release solution of-usefulness support dipping;
-take out described support and make the medicament slow release solution drying that is bonded on the described support, form medication coat.
Wherein, described solvent is dehydrated alcohol, chloroform or dichloromethane, and the proportion relation of described solvent and described curcumin is that per 1 milligram of curcumin is dissolved in 0.02 milliliter to 0.008 milliliter solution.
Described medicament elution carrier is a Poly-L-lactic acid; The proportion relation of described curcumin and Poly-L-lactic acid is per 1 milligram of curcumin and 0.2 milligram to 1.0 milligrams Poly-L-lactic acid.Described medicament elution carrier of the present invention can also be the solution of Poly-L-lactic acid and chloroform or dichloromethane; The proportion relation of described curcumin and Poly-L-lactic acid and chloroform or dichloromethane is that per 1 milligram of curcumin and 0.2 milligram to 1.0 milligrams Poly-L-lactic acid are dissolved in 0.02 milliliter to 0.008 milliliter chloroform or the dichloromethane.
Described medicament elution carrier of the present invention preferably also contains surfactant.For example a kind of ideal described surfactant is TritonX100; At this moment, the proportion relation of each composition is that per 1 milligram of curcumin and 0.1 milligram to 1.0 milligrams Poly-L-lactic acid and 0.01 milligram of TritonX100 dissolve in 0.02 milliliter to 0.008 milliliter chloroform or the dichloromethane in the described medicament elution carrier.
In the method for the invention described above, described support dipping 1 to 2 time in described curcumin drug solution, each 40 to 70 seconds; Described drying mode is for to dry up with noble gas.
A kind of alternate mode is described support dipping time in described curcumin drug solution to be about 10 minutes; Described drying mode is about 2 hours of vacuum drying.
In the method for the invention described above, described support dipping time in described medicament slow release solution is about 10 seconds; Described drying mode dried up then vacuum drying about 12 hours for adopting earlier noble gas.
Best, before with the described medicament slow release solution of support dipping, discharge dissolved gases in the described medicament slow release solution by about 30 minutes ultrasonic concussion.
In the method for the invention described above, be nitrogen or helium at the noble gas that dry run adopted.
Technique scheme of the present invention has the following advantages compared to existing technology, and the Rhizoma Curcumae Longae of being adopted have multiple pharmacologically actives such as antitumor, antiinflammatory, inhibition vascular smooth muscle cell curing, antiplatelet oxidation in the present invention.The curcumin coating to support, is formed high drug level at the pathological changes local sustained release, can suppress smooth muscle cell proliferation and platelet aggregation targetedly, promote blood vessel endothelialization again.By changing the molecular weight and the coating layer thickness of poly D-lactic acid (PLLA), the medicament elution phase of poly D-lactic acid (PLLA) eluting carrier can be controlled in for 2 thoughtful 6 weeks, and the time window that takes place with restenosis coincide.Poly-L-lactic acid pharmaceutical carrier and support biocompatibility are good, be to be widely used in clinical being implanted into property of body material, and curcumin are the extract from the Chinese medicine Rhizoma Curcumae Longae that its chemical structural formula is clear and definite, no obvious toxic and side effects, no median lethal dose(LD 50).Therefore, adopt technical scheme of the present invention, can provide efficiently for the patient, safety and effective treatment.
Description of drawings
For the easier quilt of content of the present invention is clearly understood, below according to a particular embodiment of the invention and in conjunction with the accompanying drawings, the present invention is further detailed explanation, wherein
Fig. 1 is the cross-sectional structure figure of the support element of first embodiment of the invention;
Fig. 2 is the rack making method flow diagram of first embodiment of the invention;
Fig. 3 is the cross-sectional structure figure of the support element of second embodiment of the invention;
Fig. 4 is the rack making method flow diagram of second embodiment of the invention.
Reference numeral wherein is expressed as: 1-intracoelomic cavity pipe inner support, 2-medication coat, 3-curcumin layer, the slow release layer of 4-medicament elution carrier mixing curcumin.
The specific embodiment
Referring to Fig. 1, a kind of intracoelomic cavity pipe inner support with control restenosis medicaments coating of the present invention is made up of support 1 and the medication coat 2 that is covered in support 1 surface, and wherein said medication coat is for containing the curcumin layer 3 of curcumin (curcumin).Referring to Fig. 2, the intracoelomic cavity pipe inner support of present embodiment is made in the following way: at first 150 milligrams of curcumins are poured in 1.5 milliliters the dehydrated alcohol, fully mixing is made the curcumin drug solution; Then, get an individual lumen tube inner support and insert in the described curcumin drug solution, dipping took out after 60 seconds; Dry up with nitrogen; And then this support inserted in the described curcumin drug solution, dipping took out after 20 seconds; Reuse nitrogen dries up.Make the intracoelomic cavity pipe inner support with control restenosis medicaments coating of present embodiment thus.
In the intracoelomic cavity pipe inner support manufacturing process of this embodiment, the number of times of support dipping in described curcumin drug solution also can be more than 2 times, all can in each 10 to 70 seconds; Stand-by noble gas behind the dipping for the first time after drying up as helium, carries out dipping second time again, and the reuse helium dries up at last.This production method can increase content of medicines than preceding a kind of production method.
In use, at first described support is fixed on one and carries on the sacculus, guide steel wire to place the arteria coronaria lesion through catheter guidance along arteria coronaria.To described conveying inflated, described support is strutted with 10 to 12 atmospheric pressure.After described conveying sacculus lost heart, described support was released and is left on described arteria coronaria lesion.Described curcumin on the intracoelomic cavity pipe inner support of present embodiment is fat-soluble, and therefore in described support course of conveying, the described curcumin on it loses very little in blood.And in described arteria coronaria lesion, the curcumin medicine on the described support is discharged on the outgrowth smooth muscle cell of dispensing support portions postoperative gradually.Because the fat-soluble characteristic of described curcumin medicine, medicine can enter the interior growth that suppresses this cell of the nucleus of described cell.
Referring to Fig. 3, be a kind of another embodiment of the present invention with intracoelomic cavity pipe inner support of control restenosis medicaments coating.Form by support 1 and the medication coat 2 that is covered in support 1 surface, wherein said medication coat has three-decker, one deck of the most close described cavity inner support support body is for being curcumin layer 3, and the intermediate layer is the slow release layer 4 of medicament elution carrier mixing curcumin, and skin is a curcumin layer 3.Described pharmaceutical carrier is molecular weight 30,000 dalton to 32, ten thousand dalton's (30-320KD) a Poly-L-lactic acid (PLLA).Referring to Fig. 4, the intracoelomic cavity pipe inner support of present embodiment is made in the following way: at first 150 milligrams of curcumins are poured in 1.5 milliliters the dehydrated alcohol, fully mixing is made the curcumin drug solution; Then, get an individual lumen tube inner support and inserted in the described curcumin drug solution dipping 10 minutes; In the curcumin drug solution, take out afterwards, and put into vacuum drying oven 12 hours, carry out drying; 120 milligrams of curcumins and 40 milligrams of described Poly-L-lactic acid (PLLA) and an amount of TritonX100 are mixed back and 1.5 milliliters of chloroform mix homogeneously, make medicament slow release solution; The gas that contains in the described medicament slow release solution is discharged in the ultrasonic concussion of carrying out then 30 minutes; Dipping had in curcumin drug solution and the dried intracoelomic cavity pipe insert in the described medicament slow release solution, dipping took out after 10 seconds; Dry up with helium.Repeatedly dipping and dry up three times after, described intracoelomic cavity pipe inner support is put as in the described vacuum drying oven 12 hours; And then dried intracoelomic cavity pipe inner support inserted in the described curcumin drug solution dipping 10 minutes; In the curcumin drug solution, take out afterwards, and put into vacuum drying oven 24 hours, carry out drying; Draw the intracoelomic cavity pipe inner support with control restenosis medicaments coating of present embodiment at last.
In use, same earlier described support being fixed on the conveying sacculus guides steel wire to place the arteria coronaria lesion through catheter guidance along arteria coronaria.To described conveying inflated, described support is strutted with 10 to 12 atmospheric pressure.After described conveying sacculus lost heart, described support was released and is left on described arteria coronaria lesion.
Coating and described curcumin on the intracoelomic cavity pipe inner support of the present invention are fat-soluble, and therefore in described support course of conveying, described coating and described curcumin on it lose very little in blood.Because the fat-soluble characteristic of described curcumin medicine, medicine can enter the interior growth that suppresses this cell of the nucleus of described cell.In described arteria coronaria lesion, the curcumin medicine of outer curcumin layer discharges at first gradually on the described support, utilizes its high concentration to reduce the environment that dispensing support portions postoperative causes the smooth muscle cell proliferation of neointimal hyperplasia, to restenosis its to the initial stage inhibitory action.After described outer curcumin layer release finished, the slow release layer in intermediate layer was consolidated the achievement in early stage and is kept the time of length by the release of the medicine of low concentration low dose.Thereafter, following one deck curcumin layer high concentration again discharges, to early stage contingent restenosis suppress, and destroy the environment that restenosis takes place once more.In the stage occurred frequently that restenosis takes place, eliminated the possibility that restenosis takes place basically like this.
In the miniature pig test, adopt the carrying apparatus of coating stent of medicine as medicine, selected drugs compared is the thunder handkerchief enzyme element (Rapamycin) that is used for anti-restenosis conventional in the prior art.The test pig that body weight is suitable is divided into curcumin group and thunder handkerchief enzyme element (Rapamycin) group, every group 8, insert the capable coronary angiography of conduit through carotid artery, measure anterior descending branch, circle round and prop up and the right coronary artery diameter, overdistension vascularization arteria coronaria damage model is finished described support then and is implanted.Every animal is implanted 2 pieces of same supports that scribble the relative medicine coating.Carry out the concurrent control test.1/2 of every treated animal is implanted back 1 and was put to death in 2 months and carry out histopathological examination in support, and detailed process is for taking out the heart of putting to death animal, and is fixing with the formalin perfusion.The plastic embedding of separating support artery segment, section, HE and VG dyeing.Estimate newborn interior strand and damage section branch then.Result of the test shows, the described curcumin coating bracket of present embodiment suppresses neointimal hyperplasia and reaches 70%, compare with thunder handkerchief enzyme element (Rapamycin), in the restenosis model that the tunica intima damage causes, described curcumin medicine demonstrates and equates or higher restenosis inhibition activity.
In the above-described embodiments, can also substitute with chloroform or dichloromethane as the dehydrated alcohol of described solvent, no matter the proportion relation of the sort of solvent and described curcumin is the solution that per 1 milligram of curcumin is dissolved in 0.02 milliliter to 0.008 milliliter and can both has ideal effect.
In the above-described embodiments, described medicament elution carrier is 30,000 dalton to 32, ten thousand dalton's (30-320KD) a Poly-L-lactic acid; The proportion relation of described curcumin and Poly-L-lactic acid is that per 1 milligram of curcumin is to 0.2 milligram to 1.0 milligrams Poly-L-lactic acid.The solvent of described medicament elution carrier Poly-L-lactic acid can also be replaced with dichloromethane except being the chloroform.The proportion relation of described curcumin and Poly-L-lactic acid and described solvent is that per 1 milligram of curcumin and 0.2 milligram to 1.0 milligrams Poly-L-lactic acid are dissolved in 0.02 milliliter to 0.008 milliliter chloroform or the dichloromethane.In said medicine eluting carrier, can also add an amount of TritonX100, reduce capillary effect to reach.The described field of the addition of wherein said TritonX100 medicine those of ordinary skill can obtain according to experience and simple experiment according to required tensile size.
In the above-described embodiments, the employed described noble gas of dry drug coating can also use as other indifferent gas in the periodic tables of chemical element such as helium except using nitrogen.
In the above-described embodiments, that the medicament elution carrier adopts is Poly-L-lactic acid (PLLA), but, for the those of ordinary skill in described field, it is replaced with the material that cellulose (cellulose) or PLA/PGLA copolymer or other have identical or equivalent characteristics also is conspicuous.
In the above-described embodiments, surfactant can also adopt and comprise polyoxyethylene hardened castor oil, glyceryl monostearate, monostearate Isosorbide Dinitrate, single Palmic acid Isosorbide Dinitrate, the mono laurate Isosorbide Dinitrate, polyoxyethylene-polyoxypropylene block interpolymers, polysorbate, sodium lauryl sulphate, Polyethylene Glycol, sucrose fatty acid ester etc.
By the thickness of medication coat on the resulting curcumin coating stent of medicine of the foregoing description between 10 to 80 microns, with 3 millimeters * 16 millimeters supports is example, the drug loading of every pair of support is between 100 to 800 micrograms, and the medication coat smooth surface, medication coat can not take place to break away from and crack after drawing together with sacculus.
Obviously, the above embodiment of the present invention only is for example of the present invention clearly is described, and is not to be qualification to embodiments of the present invention.For those of ordinary skill in the field, can also make other changes in different forms on the basis of the above description.Here need not also can't give exhaustive to all embodiments.And these belong to conspicuous variation or the change that spirit of the present invention extended out and still are among protection scope of the present invention.
Claims (17)
1. intracoelomic cavity pipe inner support with control restenosis medicaments coating by support (1) be covered in the surperficial medication coat (2) of support (1) and form, is characterized in that containing in the described medication coat curcumin (curcumin).
2. intracoelomic cavity pipe inner support according to claim 1, it is characterized in that described medication coat has double-layer structure at least, its ectomesoderm is that ingredient is the curcumin layer (3) of curcumin, and one deck ingredient is medicament elution carrier and the blended slow release layer of curcumin (4) at least.
3. intracoelomic cavity pipe inner support according to claim 2 is characterized in that described medication coat is the structure of described curcumin layer and the alternate setting of described slow release layer.
4. intracoelomic cavity pipe inner support according to claim 3, it is characterized in that described medication coat has three-decker, wherein the one deck near described cavity inner support support body is curcumin layer (3), the intermediate layer is curcumin layer (3) for the slow release layer (4) of medicament elution carrier mixing curcumin, skin.
5. according to claim 2,3 or 4 described intracoelomic cavity pipe inner supports, it is characterized in that described medicament elution carrier is molecular weight 30,000 dalton to 32, ten thousand dalton's (30-320KD) a Poly-L-lactic acid (PLLA).
6. manufacture method with intracoelomic cavity pipe inner support of control restenosis medicaments coating, wherein curcumin layer (3) generates step:
A. curcumin and solvent are fully stirred evenly and make the curcumin drug solution;
B. use the described curcumin drug solution of support dipping;
C. take out described support and make the curcumin drug solution drying that is bonded on the described support, form medication coat.
7. the manufacture method of intracoelomic cavity pipe inner support according to claim 6 is characterized in that further comprising with curcumin layer (3) generating slow release layer (4) the generation step that step is used alternatingly:
-curcumin and medicament elution carrier mix homogeneously are made medicament slow release solution;
The described medicament slow release solution of-usefulness support dipping;
-take out described support and make the medicament slow release solution drying that is bonded on the described support, form medication coat.
8. according to the manufacture method of claim 6 or 7 described intracoelomic cavity pipe inner supports, it is characterized in that wherein said solvent is dehydrated alcohol, chloroform or dichloromethane, the proportion relation of described solvent and described curcumin is that per 1 milligram of curcumin is dissolved in 0.02 milliliter to 0.008 milliliter solution.
9. the manufacture method of intracoelomic cavity pipe inner support according to claim 7 is characterized in that wherein said medicament elution carrier is a Poly-L-lactic acid; The proportion relation of described curcumin and Poly-L-lactic acid is per 1 milligram of curcumin and 0.2 milligram to 1.0 milligrams Poly-L-lactic acid.
10. the manufacture method of intracoelomic cavity pipe inner support according to claim 7 is characterized in that wherein said medicament elution carrier is the solution of Poly-L-lactic acid and chloroform or dichloromethane; The proportion relation of described curcumin and Poly-L-lactic acid and chloroform or dichloromethane is that per 1 milligram of curcumin and 0.2 milligram to 1.0 milligrams Poly-L-lactic acid are dissolved in 0.02 milliliter to 0.008 milliliter chloroform or the dichloromethane.
11. the manufacture method of intracoelomic cavity pipe inner support according to claim 7 is characterized in that also containing surfactant in the wherein said medicament elution carrier.
12., it is characterized in that described support dipping 1 to 2 time in described curcumin drug solution, each 10 to 60 seconds according to the manufacture method of claim 6 or 7 described intracoelomic cavity pipe inner supports; Described drying mode is for to dry up with noble gas.
13., it is characterized in that described support dipping time in described curcumin drug solution is about 10 minutes according to the manufacture method of any described intracoelomic cavity pipe inner support in the claim 7,9 to 11; Described drying mode is about 24 hours of vacuum drying.
14., it is characterized in that described support dipping time in described medicament slow release solution is about 10 seconds according to the manufacture method of any described intracoelomic cavity pipe inner support in the claim 7,9 to 11; Described drying mode dried up then vacuum drying about 24 hours for adopting earlier noble gas.
15. the manufacture method of intracoelomic cavity pipe inner support according to claim 7 is characterized in that discharging dissolved gases in the described medicament slow release solution by about 30 minutes ultrasonic concussion before using the described medicament slow release solution of support dipping.
16. the manufacture method of intracoelomic cavity pipe inner support according to claim 12 is characterized in that wherein said noble gas is nitrogen or helium.
17. the manufacture method of intracoelomic cavity pipe inner support according to claim 14 is characterized in that wherein said noble gas is nitrogen or helium.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CNB021592659A CN1194653C (en) | 2002-12-30 | 2002-12-30 | Internal cavitary and vessel stent with medicinal coating against spinal canal restenosis and production thereof |
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| Application Number | Priority Date | Filing Date | Title |
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| CNB021592659A CN1194653C (en) | 2002-12-30 | 2002-12-30 | Internal cavitary and vessel stent with medicinal coating against spinal canal restenosis and production thereof |
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| CN1424117A CN1424117A (en) | 2003-06-18 |
| CN1194653C true CN1194653C (en) | 2005-03-30 |
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| CNB021592659A Expired - Fee Related CN1194653C (en) | 2002-12-30 | 2002-12-30 | Internal cavitary and vessel stent with medicinal coating against spinal canal restenosis and production thereof |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107432956A (en) * | 2017-08-03 | 2017-12-05 | 华东理工大学 | Mesoporous calcium magnesium silicate Geniposide cross-linked wheat albumen support, carry curcumin support and preparation method and application |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100450557C (en) * | 2004-08-13 | 2009-01-14 | 重庆大学 | Medication eluting type blood vessel bracket |
| EP2352529B1 (en) * | 2008-11-04 | 2018-07-11 | inRegen | Cell-scaffold constructs |
| CN104188957B (en) * | 2014-05-28 | 2017-04-26 | 中国中医科学院西苑医院 | Medicine for preventing and curing restenosis, and preparation method and using method thereof |
| CN107519544A (en) * | 2017-08-28 | 2017-12-29 | 武汉杨森生物技术有限公司 | Compound anticoagulant heparin coating microballoon and preparation method and application |
| CN109481826A (en) * | 2018-11-05 | 2019-03-19 | 南京友德邦医疗科技有限公司 | A kind of drug coated balloon catheter and preparation method thereof |
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2002
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN107432956A (en) * | 2017-08-03 | 2017-12-05 | 华东理工大学 | Mesoporous calcium magnesium silicate Geniposide cross-linked wheat albumen support, carry curcumin support and preparation method and application |
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