DESC:EVEROLIMUS - ELUTING COBALT CHROMIUM CORONARY STENT WITH ABLUMINAL BIODEGRADABLE POLYMERS
TECHNICAL FIELD
The present disclosure relates to a novel drug-eluting stent (DES) for treating coronary artery disease. Specifically, the disclosure describes a cobalt chromium coronary stent with an abluminal coating of biodegradable polymers that uniformly embed and release Everolimus drug over time.

BACKGROUND
Percutaneous coronary intervention (PCI) with stent implantation is a widely used treatment for cardiovascular diseases. In PCI, a stent is placed on a balloon catheter and delivered to the narrowed artery. The balloon is inflated, expanding the stent and restoring blood flow.

Bare metal stents (BMS) can cause complications such as neointimal hyperplasia and restenosis. Drug-eluting stents (DES) were developed to address these issues by releasing medication to prevent artery re-narrowing (restenosis). However, DES can also pose risks, such as late stent thrombosis. To mitigate these risks, there is a need for DES with biodegradable polymers that reduces systemic side effects, improves endothelial healing, enhance biocompatibility, optimise drug retention and target drug release to the bloodstream. .

SUMMARY
It is an object of the present disclosure to provide an Everolimus-eluting cobalt chromium coronary stent with a biodegradable polymers coating disposed on the abluminal surface thereof, while addressing the prior art void. This object is achieved by the features of the independent claims. Further, implementation forms are apparent from the dependent claims, the description, and the figures.

According to a first aspect, an Everolimus-eluting cobalt chromium coronary stent with a biodegradable polymer based coating disposed on the abluminal surface is provided. The coating comprises a mixture of Everolimus and two biodegradable polymers. The polymers are biodegradable ensuring controlled, monodirectional release of Everolimus drug over time.

Preferably, the coating is spray-coating technique on the abluminal surface of the stent when the stent is in crimped state.

Preferably, the length of the sent varies from 8 mm to 48 mm.

Preferably, the distribution of Everolimus within the coating is 1.20 µg/mm2.

Preferably, the polymers comprise poly L-lactide (PLLA), poly lactic-co-glycolic acid (PLGA), or a combination thereof.

Preferably, the stent adapted for deployment within arteries, the diameters of whom range between 2 mm to 4.5 mm.

Preferably, the stent is of open cell configuration. Preferably, the number of cells of the open cell configuration are one of 6, 8 and 10. Preferably, the cell diameter of a 6-cell stent ranges between 2 mm to 3 mm. Preferably, the cell diameter of an 8-cell stent ranges between 3 mm to 4.5 mm. Preferably, the cell diameter of a 10-cell stent ranges between 4 mm to 4.5 mm.

Preferably, the mixture ratio of Everolimus and the one or more polymers comprises 63.58% and 36.42% respectively.

Preferably, the thickness of the coating comprises 5 µm.

Preferably, the stent is of peak-to-peak design with intercross in the alternate cells.

To elaborate, the disclosure aims to develop a novel, biodegradable, polymer-based Everolimus-eluting stent with an asymmetric coating, delivering the drug solely to the abluminal surface. The process involves mixing Everolimus with biodegradable polymers to create a solution that is then spray-coated onto the stent when it is in crimped state. The coating is applied on the abluminal surface. This asymmetric coating strategy minimizes polymer usage, reduces interaction with the bloodstream, and improves drug retention, thereby limiting potential adverse effects associated with polymers.

Drug-eluting stents (DES) with controlled release of anti-proliferative drugs from a non-biodegradable polymer have significantly reduced the incidence of restenosis and serious cardiac events such as myocardial infarction (MI) and cardiac mortality. Abluminal coating on coronary stents offers numerous advantages, including favorable, monodirectional drug release profile, reduced systemic drug exposure, faster re-endothelialization, early neointimal healing, reduced inflammatory response, enhanced drug adherence to the stent, improved biocompatibility, improved vascular repair, and modified thrombogenicity.

These and other aspects of the present disclosure will be apparent from the implementation(s) described below.

BRIEF DESCRIPTION OF FIGURES
Implementations of the present disclosure will now be described, by way of example only, concerning the accompanying drawings, in which:

FIG. 1 is, according to an embodiment of the present disclosure, a front view of a 6-cell stent.

FIG. 2 is, according to an embodiment of the present disclosure, a front view of an 8-cell stent.

FIG. 3 is, according to an embodiment of the present disclosure, a cross section of a stent crimped over a catheter balloon.

FIG. 4 is, according to an embodiment of the present disclosure, a side view of the stent crimped over a catheter balloon.

DETAILED DESCRIPTION
Embodiments of the present disclosure are explained in detail below with reference to the various figures. In the following description, numerous specific details are set forth to provide an understanding of the embodiments and examples. However, those of ordinary skill in the art will recognize several equivalent variations of the various features provided in the description. Furthermore, the embodiments and examples may be used together in various combinations.

FIG. 1 illustrates a drug-eluting, cobalt chromium coronary stent designed for percutaneous coronary intervention (PCI). The stent features thin strut thickness and sufficient radiopacity for clear visualization during percutaneous transluminal coronary angioplasty (PTCA). The stent's abluminal surface is overlaid with a biodegradable polymer layer uniformly embedded with the antiproliferative, drug Everolimus. Upon implantation in a coronary artery, with the help of balloon catheter, contact with arterial fluids, including the bloodstream, initiates the breakdown of this layer over time. This controlled degradation results in the localized release of Everolimus, primarily through hydrolysis, directly to the surrounding tissue. The abluminal positioning of the drug minimizes direct exposure to the bloodstream, thus promoting monodirectional drug release. This targeted delivery approach offers several advantages, including reduced systemic drug exposure, faster re-endothelialization, early neointimal healing, a less pronounced inflammatory response, strong drug-stent adherence, enhanced biocompatibility, and modified thrombogenicity.

Preferably, the stent is of an open-cell configuration with a peak-to-peak design and intercrosses in alternate cells, as depicted in FIGS. 1 and 2. This open-cell design offers exceptional flexibility, crossability, and conformability. The stent is available in 6-cell (FIG. 1), 8-cell (FIG. 2), or 10-cell configurations (Figure is not given). The diameters of the corresponding cells range as follows: 2 mm to 3 mm for 6-cell stents, 3 mm to 4.5 mm for 8-cell stents, and 4 mm to 4.5 mm for 10-cell stents. More specifically, the diameter of a 6-cell stent can be 2 mm, 2.25 mm, 2.5 mm, 2.75 mm, or 3 mm. The diameter of an 8-cell stent can be 3 mm, 3.5 mm, 4 mm, or 4.5 mm. The diameter of a 10-cell stent can be either 4 mm or 4.5 mm. The length of the stent typically varies from 8 mm to 48 mm. In one embodiment, the standard length for all the cells is +/- 0.050. This stent is designed to treat coronary arteries with a diameter ranging between 2.00 mm and 4.50 mm. Studies have shown that the stent improves coronary luminal diameter in patients with symptomatic ischemic disease due to discrete de novo lesions of length = 48 mm in native coronary arteries with a reference vessel diameter of 2.00 to 4.50 mm.

Referring to FIG. 3, the biodegradable layer 12 comprises a mixture of Everolimus and one or more biodegradable polymers, such as poly L-lactide (PLLA), poly lactic-co-glycolic acid (PLGA), or a combination thereof. Everolimus is classified as a kinase inhibitor, specifically targeting mammalian target of rapamycin (mTOR). mTOR plays a crucial role in regulating cellular processes like multiplication, blood vessel formation, and nutrient utilization. By inhibiting mTOR, Everolimus reduces blood flow to tumors, hindering their growth. In the context of stent application, the hydrophobic and lipophilic nature of Everolimus allows it to attach to nearby lipid molecules and enter cells, where it arrests the cell cycle between metaphase and anaphase. This inhibition of cell division effectively prevents neointimal hyperplasia, making Everolimus a potent agent for inhibiting vascular smooth muscle cell proliferation.

As a key component of the biodegradable layer 12, PLLA exhibits desirable characteristics for stent applications. Its semi-crystalline structure contributes to favorable mechanical properties, while its biodegradability ensures gradual resorption within the body. PLLA's strong optical rotation may offer potential benefits in terms of drug delivery and interaction with surrounding tissues. By providing a smooth and biocompatible surface, PLLA coatings on stents can reduce the risk of thrombosis and inflammation. Furthermore, PLLA acts as an effective drug carrier, enabling the controlled release of Everolimus to prevent restenosis and infection.

Similarly, PLGA offers valuable properties as a component of the biodegradable layer 12. Its biocompatibility and inherent ability to degrade within the body make it well-suited for use in cardiovascular stents. PLGA coatings contribute to a smooth stent surface, which can reduce the risk of thrombosis and inflammation. Like PLLA, PLGA functions as a drug carrier, facilitating the controlled release of Everolimus to prevent restenosis and infection. The combination of PLLA and PLGA in the biodegradable layer 12 offers a synergistic effect, optimizing both the mechanical properties and drug delivery capabilities of the stent.

In one embodiment, the mixture ratio of Everolimus and the one or more polymers comprises 63.58% and 36.42% respectively, resulting in a uniform Everolimus distribution of 1.20 µg/mm2. To overlay this mixture as layer 12 atop the stent 10, the stent is first crimped on the balloon tip of delivery catheter, and then the mixture is spray-coated over it. In one embodiment, the mixture is spray-coated on the abluminal surface to achieve a uniform layer thickness of 5 µm. This coating process maintains the integrity of the coated layer even after substantial stent expansion. By confining the layer to the abluminal surface, the stent 10 limits the negative effects of polymers and improves stent retention capacity. This targeted coating strategy offers clinical benefits to patients by minimizing polymer exposure and promoting biocompatibility. Furthermore, the biodegradable nature of the polymers ensures their gradual breakdown and absorption by the body, reducing the risk of persistent inflammation.

The application of the drug-polymer mixture via spray-coating after the crimping process offers several technical advantages. This approach minimizes drug loss during the crimping process, enhancing drug retention and ensuring a consistent therapeutic dose. Additionally, coating after crimping enhances the biocompatibility of the stent by minimizing polymer exposure to the patient's vasculature. This strategy also increases flexibility in stent design, allowing for a wider range of stent geometries and configurations. Furthermore, coating after crimping simplifies the manufacturing process, reducing the need for complex coating procedures and specialized equipment.

Spray-coating in the crimped state offers further benefits in terms of coating integrity and performance. It helps reduce coating cracking or delamination, which can occur during stent expansion. This improved coating retention ensures consistent drug release and minimizes the risk of polymer particles detaching from the stent. Moreover, coating in the crimped state reduces the likelihood of stent strut deformation, as the struts are already deformed during the crimping process. This approach also minimizes coating webbing between stent struts, promoting more even drug release and preventing uneven drug distribution. In summary, coating after crimping results in improved coating retention, reduced coating cracking, and more even drug release, contributing to the overall efficacy and safety of the stent.

Notably, the improved safety profile of the stent of the present disclosure allows for a shorter duration of dual antiplatelet therapy (DAPT), which is the combination of antiplatelet medications. This reduction in DAPT duration minimizes the risk of bleeding complications and provides more flexibility for patients who cannot tolerate prolonged DAPT regimens. The one or more polymers contribute to better endothelial healing and function, promoting the overall health of the blood vessel in the long term. Additionally, the stent of the present disclosure enhances the production of extracellular matrix elements, which play a crucial role in various cellular processes, such as differentiation, migration, and wound healing.

Referring to FIGS. 3 and 4, the deployment of the stent 10 within a coronary artery involves crimping the stent over a deflated balloon 14 attached to a catheter delivery system 18. The balloon is typically positioned at the tip of the catheter. This catheter delivery system 18, aided by a catheter hub 16, facilitates the transport of the balloon-stent assembly to the targeted artery site. Upon reaching the site, the balloon 14 is inflated, expanding the stent and effectively squeezing the plaque against the arterial wall. This results in the implantation of the stent 10 at the artery site, restoring proper blood flow by removing the obstruction or restriction. Once the stent is successfully implanted, the balloon 14 is deflated and withdrawn from the artery.

Embodiments and examples are described above, and those skilled in the art will be able to make various modifications to the described embodiments and examples without departing from the scope of the embodiments and examples.

Although the processes illustrated and described herein include series of steps, it will be appreciated that the different embodiments of the present disclosure are not limited by the illustrated ordering of steps. Some steps may occur in different orders, some concurrently with other steps apart from that shown and described herein. In addition, not all illustrated steps may be required to implement a methodology in accordance with the present disclosure. Moreover, it will be appreciated that the processes may be implemented in association with the apparatus and systems illustrated and described herein as well as in association with other systems not illustrated. ,CLAIMS:We Claim:
1. An Everolimus-eluting cobalt chromium coronary stent comprising a biodegradable coating disposed on the abluminal surface thereof, said coating comprising a mixture of Everolimus and one or more polymers, said one or more polymers being biodegradable ensuring controlled, monodirectional release of Everolimus over time.

2. The stent as claimed in claim 1, wherein said coating is spray-coated on said abluminal surface when said stent is in crimped state.

3. The stent as claimed in claim 1, wherein the length thereof varies from 8 mm to 48 mm.

4. The stent as claimed in claim 1, wherein the distribution of Everolimus within said coating is 1.20 µg/mm2.

5. The stent as claimed in claim 1, wherein said one or more polymers comprising poly L-lactide, poly lactic-co-glycolic acid, or a combination thereof.

6. The stent as claimed in claim 1, wherein the stent is adapted for deployment within arteries, the diameters of which range between 2 mm to 4.5 mm.

7. The stent as claimed in claim 1 being of open cell configuration.

8. The stent as claimed in claim 7, wherein the number of cells thereof being one of 6, 8 and 10.

9. The stent as claimed in claim 8, wherein the cell diameter of a 6-cell stent ranges between 2 mm to 3 mm.

10. The stent as claimed in claim 8, wherein the cell diameter of an 8-cell stent ranges between 3 mm to 4.5 mm.

11. The stent as claimed in claim 8, wherein the cell diameter of a 10-cell stent ranges between 4 mm to 4.5 mm.

12. The stent as claimed in claim 1, wherein the mixture ratio of Everolimus and said one or more polymers comprises 63.58% and 36.42% respectively.

13. The stent as claimed in claim 1, wherein the thickness of said coating comprises 5µm.

14. The stent as claimed in claim 1 being of peak-to-peak design with intercross in the alternate cells.