CN104874090B - A new drug eluting balloon catheter - Google Patents
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- CN104874090B CN104874090B CN201510124482.6A CN201510124482A CN104874090B CN 104874090 B CN104874090 B CN 104874090B CN 201510124482 A CN201510124482 A CN 201510124482A CN 104874090 B CN104874090 B CN 104874090B
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Abstract
The invention provides a drug eluting balloon catheter, which comprises a catheter, a balloon body (1), a balloon surface (2), a hydrophilic lipophilic bottom layer (3) and a drug carrying coating (4), wherein the hydrophilic lipophilic bottom layer (3) is positioned on the balloon surface (2), the drug carrying coating (4) is positioned on the hydrophilic lipophilic bottom layer (3), and the drug carrying coating (4) consists of a polymer and a drug. The drug eluting balloon catheter has the characteristics of simple structure, simple production process, less drug loss in the conveying process and less drug residue on the balloon after interventional operation.
Description
Technical Field
The invention designs a medical instrument, in particular to a novel drug eluting balloon used for interventional therapy of cardiovascular diseases.
Background
The drug eluting balloon catheter combines the traditional balloon forming operation and the advanced drug eluting technology, the drug eluting balloon catheter releases drugs instantly during interventional therapy, avoids side effects caused by long-term retention of a metal stent and a polymer carrier, is an effective supplement of the metal stent angioplasty, has good application in the restenosis process of a blood vessel after the drug stent implantation operation, gradually shows superiority, but the drug eluting balloon also has the problems that the drug loading rate of drugs is low during pathological tissues caused by a large loss of the drugs on the drug eluting balloon during interventional therapy and partial drugs still remain to be attached to the balloon surface (about 10-20%) after interventional therapy due to the existence of surface binding force, so as to influence the drug release. Therefore, how to realize the timed and quantitative release of the drug on the drug eluting balloon at the lesion site is one of the key factors for realizing the therapeutic effect of the drug balloon.
CN101785900a discloses a drug balloon, in which the balloon is designed to have a non-planar structure with concave-convex outer surface, and the drug is coated on the groove part and the flat part of the outer surface of the balloon, and the loss of the drug in the process of delivery is reduced by the retention effect of the groove. The method adopts the mould with the groove, and the balloon is directly provided with the groove appearance in the balloon forming process, but the groove retention effect of the method also can cause higher residual quantity of the medicine on the surface of the balloon after treatment, thereby affecting the utilization efficiency of the medicine, and on the other hand, the method has higher requirements on the balloon forming process, especially on the mould processing precision.
Chinese patent CN200951251a discloses a double-layer drug eluting balloon catheter, the outer surface of the balloon is covered with a layer of microporous balloon, and the outer balloon is made of PE, PC, PEBAX and other materials. The method adopts a laser drilling or etching technology to manufacture micropores, also can increase the drug residue on the surface of the postoperative drug balloon due to the surface effect of the micropores, and the process needs expensive instruments and equipment, has complex process and is not suitable for industrial production.
In addition, chinese patent CN103990221a discloses a drug eluting balloon device, the polymer layer contains a drug or a drug and an additive, and further discloses an extractable bottom layer structure, which forms a porous structure after extraction, so that the binding force between the drug layer and the surface of the balloon can be reduced, and the drug layer can be adhered to the vessel wall after being detached in a whole or in a sheet form. However, the patent still has the problem of great loss in the intervention process, the extraction is carried out after the coating is selected and sprayed on the process, the extraction process is complex, the solvent used for extraction can damage the drug coating, the residue of the organic solvent on the balloon after the extraction is also the problem to be solved, and the flaky drug layer adhered to the vessel wall falls off, so that the risk of thrombus is caused, and even life is endangered.
Chinese patent CN204050424U discloses a drug balloon, which adopts a double-layer balloon, the outer surface of the balloon is sequentially coated with a water-soluble bottom layer and a biodegradable polymer layer containing a drug, and when the outer layer of the balloon is expanded, a solution such as physiological saline seeps from the balloon wall to dissolve the water-soluble bottom layer, thereby controlling the release of the biodegradable polymer layer containing the drug. The balloon has a complex structure, physiological saline is injected into the balloon wall, so that the production process is complex on one hand, and on the other hand, the solution is difficult to stably remain in the balloon wall for a long time, and once the solution seeps out, the integrity of the coating is seriously damaged.
Therefore, it is necessary to provide a drug eluting balloon catheter, which not only can reduce drug loss in the delivery process, reduce the residue of the postoperative drug on the surface of the balloon, and improve the drug use efficiency, but also has the advantages of simple processing technology and safe use, and is suitable for industrial production.
Disclosure of Invention
In order to solve the technical problems, the invention provides a novel drug eluting balloon catheter which has the characteristics of simple structure, simple production process, less drug loss in the conveying process and less drug residue on the balloon after interventional operation.
The drug eluting balloon catheter comprises a catheter body 1 and a balloon surface 2, and is characterized by further comprising a hydrophilic and lipophilic bottom layer 3 and a drug carrying coating 4, wherein the hydrophilic and lipophilic bottom layer 3 is positioned on the balloon surface 2, the drug carrying coating 4 is positioned on the hydrophilic and lipophilic bottom layer 3, and the drug carrying coating 4 consists of a polymer and a drug.
Wherein the bottom layer 3 is a layer of a polymer material having hydrophilic and lipophilic properties, as shown in fig. 1, the polymer material having both hydrophilic and lipophilic groups. The bottom layer forms an isolation layer between the drug-carrying coating and the balloon, and the drug of the drug-carrying coating can be prevented from contacting the surface of the balloon due to strong bonding force of the surface effect of the drug and the surface of the balloon, so that the bonding force of the drug layer is reduced, the rapid release of the drug layer is facilitated, the drug residue caused by the surface effect of the drug and the balloon can be reduced, the bottom layer material has hydrophilic and lipophilic properties, and the bottom layer material can be one or more of polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, polystearate, phospholipids and polycyanurates. The thickness of the bottom layer is preferably 0.1-2 mu m, the bottom layer cannot be too thick, the whole conveying performance of the medicine balloon is affected by the too thick bottom layer, and the effect of isolating the medicine balloon from the medicine cannot be achieved by the too thin bottom layer.
The average molecular weight of the hydrophilic and lipophilic polymer of the bottom layer is preferably Mv & gt 50K (wherein Mv is viscosity average molecular weight, K is a number of units of thousand). The hydrophilic and lipophilic polymer of the molecular weight in the range is reduced in hydrophilicity, and is not easy to fall off when being used as the bottom layer, particularly when the drug balloon coating has a multi-layer structure, the bottom layer can be ensured to be difficult to dissolve within a short time of drug balloon treatment (1 min after the balloon is opened), and can maintain better stability within a short time, and if the bottom layer falls off locally, the drug-carrying layer is easy to fall off, and the transfer of the drug to lesion tissues is influenced. Among them, 70K < Mv <150K is more preferable, because when the molecular weight is too large, the viscosity of the polymer in the blood vessel is large, the blood flow is affected, the blood vessel is easily blocked, and the life and health of the patient are endangered.
The invention has the preferential technical scheme that the invention also comprises a hydrophilic and lipophilic surface layer 5, the surface layer is a polymer material layer, the surface layer is wrapped on the surface of the medicine carrying coating, a protective layer is formed on the surface of the medicine carrying coating, the loss of medicine in the conveying process can be reduced, when the balloon is conveyed to a lesion position, the surface layer is basically completely dissolved, the medicine carrying coating is protected, the release of the medicine in the medicine carrying coating is not influenced, and the surface layer material has good lipophilic and hydrophilic properties. Because the drug eluting balloon catheter can reach a narrow position only through a long section of blood vessel in the conveying process, at the moment, a great deal of drug is always lost after the drug is flushed by blood flow, so that the drug loading rate of the drug in pathological tissues is low, toxic and side effects are easily caused, and the surface layer can play a role in protecting a drug coating in the conveying process of the drug balloon and can not influence the release of the drug when reaching the pathological position. The surface layer material can be one or more of polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, polyscleroate, phospholipids, and Polycitrate. The thickness of the surface layer is 0.1-2 mu m, the surface layer is excessive, the surface layer is difficult to dissolve and complete when the drug balloon reaches the delivery position, and the effect of protecting the drug layer is difficult to achieve when the surface layer is too thin.
The carrier material of the drug-carrying coating 4 and the material of the surface layer 5 are both hydrophilic and lipophilic polymers, the average molecular weight is preferably Mv <40K, the drug-carrying coating needs to be completely released within 1min after the balloon is opened, and the polymers are required to have better hydrophilicity, so that the polymers are required to have lower molecular weight, the surface layer plays a role in protecting the drug coating in the balloon conveying process, and simultaneously, the surface layer needs to be completely dissolved when the balloon is conveyed to a lesion position, so that the surface layer also needs to have better solubility, and the lower molecular weight is required. Of these, 1K < Mv <40K is more preferable.
The carrier material of the drug-carrying coating 4 is a mixed layer of hydrophilic lipophilic polymer and drug. The drug-carrying coating is positioned between the surface layer and the bottom layer, and the carrier material of the drug-carrying coating has hydrophilic and lipophilic properties so as to ensure that the drug can be timely and effectively released to the vessel wall after the balloon is adhered. The drug loading rate of the drug-loaded coating is preferably 1-5 mug/mm 2, the thickness of the coating is preferably 1-50 mu m, the drug loading rate and the thickness of each drug-loaded coating are all the preferred ranges of a large number of experiments, the drug loading rate of each drug-loaded coating is not too high, the drug loading rate can produce larger side effect on human body, the drug loading rate is too low to achieve the treatment effect, the thickness of each drug-loaded coating is not too high, otherwise the firmness of the combination of the coatings can be affected. In addition, the drug-loaded coating is preferably applied to the entire effective support area of the balloon after opening, and the tapers at both ends of the balloon should not be coated so as not to affect the drug content of the balloon as a whole.
The carrier material of the drug-carrying coating and one or more drugs such as paclitaxel, rapamycin and derivatives thereof, and Acximab are fully mixed, dissolved in methanol, ethanol, acetone, dichloromethane, acetonitrile and tetrahydrofuran, and the coating is carried on the surface of the saccule by adopting the modes of spraying, dip-coating, coating or flap injection. The carrier material of the drug-carrying coating is one or two of polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, polystearate, phospholipids and polycytidylate, and the average molecular weight is preferably Mv <40K, more preferably 1K < Mv <40K.
The drug-carrying coating is composed of one or more carrier materials and drugs, the carrier materials of the drug-carrying coating are preferably the same as the bottom layer, and the weight ratio of the drugs to the carrier materials is preferably 1:10-10:1. The polymer has the advantages of ensuring the safe release of the drug within 1min and the effective transfer to the vessel wall, along with the variety and content of the drug, along with the molecular weight, drug loading, components and coating thickness of the polymer.
The bottom layer is made of a higher molecular weight material, so that the hydrophilicity of the bottom layer material is reduced, and the risk of coating chipping caused by dissolution of the bottom layer local material when the balloon is opened can be reduced. The drug-carrying coating and the surface layer are required to have small molecular weight and good hydrophilicity, so that the drug can be released to the lesion position timely and effectively after the saccule is opened.
The invention further provides a preparation method of the drug eluting balloon catheter, which comprises the following steps:
firstly, pretreating the surface of the saccule by adopting a plasma cleaning technology, and then spraying a layer of bottom layer with the thickness of 0.1-2 mu m;
Spraying a drug-carrying coating with the thickness of 1-50 mu m and the drug-carrying quantity of 1 mu g/mm 2-5μg/mm2;
After the coating is dried, folding, and spraying a layer of surface layer after winding, wherein the thickness is 0.1-2 mu m.
Specifically, firstly, the surface of the sacculus is pretreated, the surface sundries of the sacculus are cleaned by adopting a plasma cleaning technology, preferably inert gas such as argon, neon and the like is adopted for the plasma cleaning, the power is 10KHz-100KHz, the pressure in a working cabin is 0.01atm-0.3atm during cleaning, and the cleaning time is 5-30min;
the preparation process of the bottom layer 3 comprises the steps of weighing a carrier material with a certain mass, dissolving the carrier material in an organic solvent, standing, obtaining a bottom layer coating liquid after the carrier material is completely dissolved, and then adopting a dip-coating or spray-coating or coating process to form a layer of carrier material coating on the surface of the balloon, and carrying out vacuum drying at a constant temperature to obtain the balloon catheter with the bottom layer.
The preparation process of the medicine carrying coating includes weighing carrier material and medicine in certain weight, dissolving in organic solvent, coating the medicine carrying spraying liquid onto the surface of the bottom layer via dip coating, spraying or coating process, and controlling the thickness of the medicine carrying coating.
After the coating is dried, the balloon is folded, coiled, and a surface layer is further prepared on the surface of the drug-carrying coating, and the preparation process of the surface layer is the same as that of the bottom layer.
The plasma cleaning technology is adopted to reduce the adhesion of the coating affected by the interface effect and the physical impact effect of the plasma, so that the surface of the balloon becomes coarser, and the bonding firmness of the coating and the surface of the balloon is improved. The adoption of the optimized technological parameters can not only ensure the complete cleaning of impurities on the surface of the balloon, but also avoid the influence of plasmas on the mechanical properties of the balloon due to long-time physical impact on the surface of the balloon.
The multi-layer drug eluting coating balloon of the present invention has the following effects:
(1) The bottom layer can reduce the direct contact between the medicine and the surface of the saccule, reduce the residue of the medicine on the surface of the saccule after interventional therapy, maximize the release of the medicine when the saccule reaches the lesion position, and optimize the therapeutic effect of the medicine;
(2) The surface layer can reduce the drug loss of the drug eluting balloon in the process of delivery, and prevent the premature release of the drug components in blood;
(3) Compared with a single-layer drug-carrying coating, the invention has the advantages of high drug bioavailability and small toxic and side effects, and has more remarkable beneficial effects when being combined with the bottom layer and the surface layer of the invention.
(4) In addition, the invention has the advantages of simple structure, convenient processing and high qualification rate, and is suitable for large-scale production.
Drawings
FIG. 1 is a schematic structural diagram of a hydrophilic lipophilic polymer
FIG. 2 is a schematic illustration of a drug eluting balloon coating structure with a primer, drug loaded coating
FIG. 3 is a schematic representation of a drug eluting balloon coating structure comprising a base layer, a drug carrying coating and a surface layer
FIG. 4 drug release profile of drug eluting balloon containing a bottom layer, drug loaded coating and top layer
Wherein 1 is the saccule body, 2 is the saccule surface, 3 is the bottom, 4 is the medicine carrying coating, and 5 is the surface layer.
Detailed Description
The invention is explained below in connection with specific embodiments and drawings, but the invention is not limited thereto.
Example 1
As shown in fig. 2, the surface of the balloon is pretreated by adopting a plasma cleaning technology, impurities on the surface of the balloon are cleaned by adopting the plasma cleaning technology, preferably, inert gas such as argon with the power of 50KHz is adopted for the plasma cleaning, the pressure in a working cabin is 0.1atmatm during cleaning, and the cleaning time is 10min. Then polyethylene glycol with good hydrophile and lipophile is used as a bottom layer material (as shown in figure 1, the polymer material has both hydrophilic groups and lipophilic groups), then a polyethylene glycol bottom layer with the molecular weight of 70K is sprayed, the thickness is 1 mu m, then a medicine carrying coating layer which is formed by mixing polyethylene glycol with the molecular weight of 15K and taxol is sprayed, the medicine carrying amount is 2.5 mu g/mm 2, the thickness is 10 mu m, and after the coating layer is dried, the folding is finally carried out.
Example 2
As shown in FIG. 3, the surface of the balloon is pretreated by a plasma cleaning technology, impurities on the surface of the balloon are cleaned by the plasma cleaning technology, preferably, inert gas such as neon is adopted for the plasma cleaning, the power is 10KHz, the pressure in a working cabin is 0.01atm during cleaning, and the cleaning time is 5min. Then taking hydrophilic and lipophilic poly-hard acid ester as a bottom material (as shown in figure 1, the polymer material has both hydrophilic groups and lipophilic groups), spraying a layer of poly-hard acid ester bottom layer with a molecular weight of 51K and a drug-loaded coating with a mixed hard acid ester with a molecular weight of 5K and taxol, wherein the drug-loaded amount is 1 mug/mm 2, the thickness is 50 mu m, and after the coating is dried, folding and winding, then spraying a layer of 2K poly-glyceride surface layer with a molecular weight of 2 mu m.
Example 3
As shown in FIG. 3, the surface of the balloon is pretreated by a plasma cleaning technology, impurities on the surface of the balloon are cleaned by the plasma cleaning technology, preferably, inert gas such as argon is adopted for the plasma cleaning, the power is 50KHz, the pressure in a working cabin is 0.1atm during cleaning, and the cleaning time is 10min. Then, taking the lipophilic and hydrophilic glucan as a bottom layer material (as shown in figure 1, the polymer material has hydrophilic groups and lipophilic groups), spraying a glucan bottom layer with the molecular weight of 150K and the thickness of 0.1 mu m, spraying a drug-carrying coating with the mixed molecular weight of 39K glucan and rapamycin and the drug-carrying amount of 2.5 mu g/mm 2 and the thickness of 1 mu m, folding after the coating is dried, and finally, spraying a surface layer of 39K poly citric acid ester with the molecular weight of 0.1 mu m after the coating is wound.
Example 4
As shown in fig. 3, the surface of the balloon is pretreated by a plasma cleaning technology, and impurities on the surface of the balloon are cleaned by the plasma cleaning technology, preferably, inert gas such as neon is adopted for the plasma cleaning, the power is 100KHz, the pressure in a working cabin is 0.3atm during cleaning, and the cleaning time is 30min. Then taking the lipophilic and hydrophilic chitosan as a bottom layer material (as shown in figure 1, the polymer material has hydrophilic groups and lipophilic groups), spraying a layer of chitosan bottom layer with the molecular weight of 200K and the thickness of 0.2 mu m, spraying a drug-loaded coating with the molecular weight of 20K and mixing the acipimab, the drug-loaded amount of 5 mu g/mm 2 and the thickness of 6 mu m, folding after the coating is dried, and finally spraying a layer of polyxylitol surface layer with the molecular weight of 10K and the thickness of 0.8 mu m after the coating is wound.
Comparative experiment 1
Firstly, the surface of the balloon is pretreated by adopting a plasma cleaning technology, sundries on the surface of the balloon are cleaned by adopting the plasma cleaning technology, preferably, inert gas such as argon is adopted for the plasma cleaning, the power is 50KHz, the pressure in a working cabin is 0.1atmatm during cleaning, and the cleaning time is 10min. Then spraying a drug-carrying coating mixed by polyglycerol ester with the molecular weight of 50K and taxol, wherein the drug-carrying amount is 2.5 mug/mm 2, the thickness is 18 mu m, and finally folding after the coating is dried.
Comparing the experimental results
To verify the drug loss of the drug eluting balloon catheter in the above embodiment during the delivery process, the folded and pressed balloon catheter was delivered to the designated abdominal aorta position of about 2.0±0.5 kg of New Zealand white rabbits, the balloon catheter was opened by full wetting and then placed at the lesion site for about 1 minute, then the balloon was removed, the residual drug residue rate on the balloon was measured, the drug content transferred in the abdominal aorta of the New Zealand rabbits was measured within a predetermined period of time, and the loss rate of the drug during the delivery process was calculated from the residue.
To verify the drug absorption by the tissue, the balloon was inflated under 16atm in iliac artery of New Zealand white rabbit implanted with the above balloon, the pressure was maintained for 1 min, the balloon was taken out under reduced pressure, and after 1 hr of blood washout, the white rabbit was quenched, and the drug concentration in the tissue and the drug residual rate on the balloon were measured.
For tissue drug absorption rate, dissecting and acquiring a blood vessel at the balloon dilatation, grinding the blood vessel to 2ml, then measuring the content of the drug in the solution by using a liquid chromatograph, and calculating the tissue drug absorption rate.
And for the medicine residual rate of the saccule, taking out the used saccule, shearing and grinding the saccule, then fixing the volume to 2ml, measuring the medicine content in the solution by using a liquid chromatograph, and calculating the medicine residual rate.
The use conditions of the detection liquid chromatograph are as follows:
A detector, an ultraviolet detector;
Column SB-Aq C 18 μm 250X 4.6mm;
mobile phase methanol acetonitrile water=23:41:36;
Column temperature is 30 ℃;
the detection wavelength is 227nm;
flow rate 1.5 ml/min;
The sample injection amount is 10 mu L.
| Examples | Drug loss rate during delivery | Tissue drug absorption rate | Residual rate of drug on balloon |
| Example 1 | 36% | 21.5% | 9% |
| Example 2 | 29% | 23.8% | 11% |
| Example 3 | 28% | 24.2% | 10% |
| Example 4 | 32% | 26.2% | 11% |
| Comparative experiment 1 | 53% | 10.3% | 15% |
Comparative experiment 2
As shown in FIG. 3, the surface of the balloon is pretreated by a plasma cleaning technology, impurities on the surface of the balloon are cleaned by the plasma cleaning technology, preferably, inert gas such as argon is adopted for the plasma cleaning, the power is 50KHz, the pressure in a working cabin is 0.1atm during cleaning, and the cleaning time is 10min. Then spraying a polyethylene glycol bottom layer with the thickness of 1 mu m, then spraying a drug-carrying coating mixed by the poly-hard acid ester and the taxol, wherein the drug-carrying quantity is 2.5 mu g/mm 2, the thickness is 15 mu m, after the coating is dried, folding, and finally spraying a polyxylitol surface layer with the thickness of 1 mu m after winding.
According to the above preparation method and the following table molecular weights, polyethylene glycol, a thermosetting acid ester and polyxylitol were respectively prepared as a bottom layer, a drug-carrying coating layer and a surface layer, and drug balloons 1 to 8 were prepared correspondingly using the following different molecular weights.
In addition, according to the above preparation method and the following table molecular weights, the bottom layer was prepared using non-hydrophilic lipophilic material PLGA, and low molecular weight PVP, and the drug-loaded coating layer and the surface layer were prepared with Polystearate and polyxylitol, respectively, to obtain balloons 9 and 10.
| Balloon numbering | Molecular weight of bottom layer (K) | Drug-loaded coating molecular weight (K) | Molecular weight of surface layer (K) |
| 1 | 31 | 0.1 | 0.1 |
| 2 | 41 | 0.5 | 0.5 |
| 3 | 51 | 1 | 1 |
| 4 | 71 | 20 | 20 |
| 5 | 101 | 30 | 30 |
| 6 | 151 | 39 | 39 |
| 7 | 201 | 50 | 50 |
| 8 | 301 | 100 | 100 |
| 9 | 101 | 30 | 30 |
| 10 | 20 | 0.1 | 0.1 |
Comparing the experimental results
In order to verify the loss of different molecular weight coatings in the conveying process of the drug eluting balloon catheter of the comparative experiment 2, the balloon catheter which is folded and pressed and held is conveyed to a designated position of abdominal aorta of about 2.0+/-0.5 kg of New Zealand white rabbits, the balloon catheter is fully wetted and then is inflated and opened, the balloon catheter is placed at a lesion position and kept for about 1 minute, then the balloon is taken out, and the weight of the corresponding polyethylene glycol, dextran and xylitol hydrophilic and lipophilic polymers in the bottom layer, the drug carrying coating and the surface layer remained on the balloon is measured.
The used balloon is taken out, soaked in an organic solvent of a soluble polymer, and then polyethylene glycol (PLGA and PVP are respectively measured on the surface of the balloon by the balloons 9 and 10), dextran and polyxylitol hydrophilic and lipophilic polymers are respectively extracted and measured, and the residual quantity and the corresponding residual rate are calculated:
| balloon numbering | Bottom layer residual ratio | Drug-loaded coating residue rate | Surface layer residual Rate |
| 1 | 61% | 8.9% | 0% |
| 2 | 72% | 9.3% | 0% |
| 3 | 80% | 9.5% | 0% |
| 4 | 91% | 10.6% | 0% |
| 5 | 93% | 12.5% | 0% |
| 6 | 95% | 14.6% | 0.9% |
| 7 | 97% | 26.3% | 8.1% |
| 8 | 98% | 72% | 46% |
| 9 | 99% | 35% | 3% |
| 10 | 48% | 5.8% | 0% |
| Example 1 | 89% | 9.2% | — |
As shown in the table above, when the molecular weight Mv of the hydrophilic and lipophilic polymer of the bottom layer is less than 50K, the bottom layer is seriously fallen off, and the bottom layer without the medicine is fallen off, so that the treatment effect is not improved, even the tail end of a tiny blood vessel is blocked, and the life and the health of a patient are endangered. When the molecular weight of the drug-carrying coating is more than 40K, the polymer residue of the drug-carrying coating is high, the drug conversion rate is low, and when the molecular weight of the drug-carrying coating is less than 1K, the loss of the drug-carrying coating dissolved into blood in the conveying process is easy to cause, and the actual transfer of the drug to the vascular wall is not much. When the molecular weight of the surface layer is more than 40K, the residual rate of the surface layer polymer is higher, which is not beneficial to drug release, and when the molecular weight of the surface layer is less than 1K, the surface layer is easy to dissolve, and the effect of protecting the drug-carrying coating can not be achieved in the process of transferring the interventional operation to the heart.
The inventors have found that when the molecular weight of the underlayer is greater than 50K, the drug-loaded coating and the surface layer are less than 40K, the loss of underlayer polymer can be reduced and the drug release of the drug-loaded coating can be improved. Moreover, similar technical effects are obtained for hydrophilic and lipophilic polymers such as polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, xylitol, polyglycerol ester, chitosan, chitin, dextran, polystearate, polycitrate.
In addition, as shown in fig. 4 and shown in the table above, the effect diagram of the drug release process of the novel drug eluting balloon catheter is shown, wherein the molecular weight of the preferable bottom hydrophilic and lipophilic polymer of the invention is 70K < Mv <150K, and the molecular weights of the preferable drug carrying coating and the surface hydrophilic and lipophilic polymer are 1K < Mv <40K, the bottom layer is obviously free from falling off locally, the falling block of the drug carrying layer is not caused, the transfer of the drug to the lesion tissue is improved, and the drug release effect is particularly remarkable.
The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.
Claims (9)
1. The utility model provides a medicine elution sacculus pipe, includes pipe, sacculus body (1) and sacculus surface (2), its characterized in that still includes hydrophilic lipophilic bottom (3) and carries medicine coating (4), hydrophilic lipophilic bottom (3) are located sacculus surface (2) top, and medicine coating (4) are located hydrophilic lipophilic bottom (3) top, medicine coating (4) are constituteed by polymer and medicine, bottom (3) are by one or more than two of following hydrophilic lipophilic polymer composition:
Polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, polystearate, phospholipids, and Polycitrate;
the average molecular weight Mv of the hydrophilic and lipophilic polymers of the bottom layer (3) meets 70K < Mv <150K;
The drug-loaded coating (4) consists of one or more than two of the following hydrophilic and lipophilic polymers:
Polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, polystearate, phospholipids, and Polycitrate;
The average molecular weight of the hydrophilic and lipophilic polymer of the drug-loaded coating (4) is 1K < Mv <40K;
The medicine is one or more than two of paclitaxel, rapamycin and derivatives thereof, and Acximab.
2. A drug eluting balloon catheter according to claim 1, further comprising a hydrophilic lipophilic skin layer (5).
3. Drug eluting balloon catheter according to claim 2, characterized in that the surface layer (5) consists of one or more of the following hydrophilic lipophilic polymers:
Polyethylene glycol, polyethylene glycol-polycaprolactone, polysorbate, polyxylitol, polyglycerol ester, chitosan, chitin, dextran, polystearate, phospholipids, and Polycitrate.
4. A drug eluting balloon catheter according to claim 3, characterized in that the hydrophilic lipophilic polymer of the skin layer (5) has an average molecular weight Mv <40K.
5. Drug eluting balloon catheter according to claim 4, characterized in that the hydrophilic lipophilic polymer of the skin layer (5) has an average molecular weight of 1k < mv <40k.
6. Drug eluting balloon catheter according to claim 1, characterized in that the bottom layer (3) has a thickness of 0.1-2 μm and the drug carrying coating (4) has a thickness of 1-50 μm.
7. Drug eluting balloon catheter according to any of the claims 2-5, wherein the skin layer (5) has a thickness of 0.1-2 μm.
8. The drug eluting balloon catheter according to claim 1, wherein the drug loading of the drug loaded coating (4) is 1-5 μg/mm 2.
9. A method for preparing a drug eluting balloon catheter according to any of claims 1-8, wherein the surface of the balloon is pretreated by plasma cleaning, a bottom layer (3) is sprayed with a thickness of 0.1-2 μm, a drug-loaded coating (4) is sprayed with a thickness of 1-50 μm and a drug loading rate of 1 μg/mm 2-5μg/mm2, the coating is dried, folded, and a surface layer (5) is sprayed with a thickness of 0.1-2 μm after winding.
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| CN104874090B true CN104874090B (en) | 2025-04-04 |
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| CN107243109B (en) * | 2016-03-29 | 2024-07-30 | 深圳信立泰医疗器械股份有限公司 | Balloon catheter without blocking blood flow |
| CN107376030B (en) * | 2017-08-09 | 2020-08-07 | 乐普（北京）医疗器械股份有限公司 | Preparation method of drug balloon, prepared drug balloon and application thereof |
| WO2019059347A1 (en) | 2017-09-21 | 2019-03-28 | テルモ株式会社 | Drug coating layer and method for forming same |
| CN109966564B (en) * | 2017-12-28 | 2022-11-18 | 先健科技(深圳)有限公司 | Drug-loaded balloon and preparation method thereof |
| US12151070B2 (en) | 2018-11-23 | 2024-11-26 | Shanghai Microport Medical (Group) Co., Ltd | Drug eluting balloon and balloon catheter |
| CN110292701B (en) * | 2019-06-27 | 2021-11-16 | 山东瑞安泰医疗技术有限公司 | Drug eluting balloon catheter and preparation method thereof |
| CN111035815A (en) * | 2020-01-10 | 2020-04-21 | 卢静 | Medical tracheal catheter, tracheal catheter coating and preparation method thereof |
| CN114146231A (en) * | 2020-09-07 | 2022-03-08 | 上海鸿脉医疗科技有限公司 | Drug balloon and preparation method thereof |
| CN112370638A (en) * | 2020-12-04 | 2021-02-19 | 上海康德莱医疗器械股份有限公司 | Medicine balloon |
| CN115337523B (en) * | 2021-05-12 | 2024-10-01 | 先健科技(深圳)有限公司 | Medicine saccule and its preparation method |
| CN116726360A (en) * | 2023-04-17 | 2023-09-12 | 浙江桐轩医疗科技有限公司 | A high-strength expansion balloon for vertebral body |
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| WO2014163097A1 (en) * | 2013-04-01 | 2014-10-09 | テルモ株式会社 | Balloon catheter for drug administration and process for producing same |
| CN103611212B (en) * | 2013-11-21 | 2015-10-28 | 先健科技(深圳)有限公司 | The preparation method of medicinal balloon |
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| CN1833734A (en) * | 2005-03-15 | 2006-09-20 | 北京扶泰敏德医药技术有限公司 | Medical coating system having double-term and/or multi-term release speed rate |
| CN204840617U (en) * | 2015-03-20 | 2015-12-09 | 深圳市信立泰生物医疗工程有限公司 | Novel medicine elution sacculus pipe |
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