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EP-4739363-A1 - INTRALUMINAL DEVICES COATED WITH SUBSTANCE P

EP4739363A1EP 4739363 A1EP4739363 A1EP 4739363A1EP-4739363-A1

Abstract

The present invention relates to coated metal stents, to methods for coating or producing such coated metal stents, and to their use in medicine In particular, the present invention relates to metal stents coated with Substance P., to methods for coating or producing such coated stents, and to their use as implants.

Inventors

  • JEONG, MYUNG HO
  • CHO, KYUNG HOON
  • HYUN, DAE YOUNG
  • JIN, YU JEONG
  • OH, SEOK
  • NA, MI HYANG
  • KIM, TAEHUN
  • BYEON, Daeheung
  • HERMIDA-PRIETO, Manuel
  • MARIÑAS PARDO, Luis
  • VAZQUEZ RODRIGUEZ, Jose Manuel
  • SIM, Doo Sun
  • GUTIÉRREZ-CHICO, Juan Luis
  • KEE, Seung Jung
  • AHN, YOUNGKEUN
  • KIM, JU HAN
  • HONG, YOUNG JOON
  • PARK, DAE SUNG
  • KIM, MUN KI
  • CHO, Young-Nan

Assignees

  • Industry Foundation of Chonnam National University
  • Chonnam National University Hospital
  • CG Bio Co., Ltd.
  • Universidade Da Coruña
  • Fundación Pública Galega de Investigación Biomédica INIBIC
  • Servizo Galego de Saúde (SERGAS)
  • Gutiérrez-Chico, Juan Luis

Dates

Publication Date
20260513
Application Date
20230705

Claims (14)

  1. A metal stent coated with a peptide selected from the list consisting of substance P or an analogue thereof in an amount effective for inducing mobilization of endothelial precursor cells.
  2. The metal stent of claim 1, wherein the peptide is substance P.
  3. The metal stent of claim 2, wherein the peptide is coating the stent at a concentration of between 1 to 25 μM.
  4. The metal stent of claim 3, wherein the concentration is between 1 and 10 μM.
  5. The metal stent of any of claims 1 to 4, wherein the peptide is linked to the stent through an anchor and optionally a spacer molecule.
  6. The metal stent according to claim 5, wherein the anchor is selected from the group consisting of: -W, -V-W, -V-[V-W 2 ] 2 , and -V-[V-(V-W 2 ) 2 ] 2 , wherein W represents and V represents lysine, aspartic acid or glutamic acid; m is 1, 2 or 3; and n each independently is 1, 2, 3, 4, 5, 6, 7 or 8; YY is an amino or carboxyl group.
  7. The metal stent according to claim 6, wherein the anchor is selected from the group consisting of -CO-CH=CH 2 , -CO-(CH) 1-20 -CO-CH=CH 2 , -CO-(CH2) 1-20 -SH, -CO-CH(NH 2 )-CH 2 -SH, -NH-(CH 2 ) 1-20 -CO-CH=CH 2 , -NH-(CH 2 ) 2-20 -SH, -NH-CH(CO 2 H)-CH 2 -SH.
  8. The metal stent according to any of claims 1 to 7, wherein the peptide is in combination with one or more therapeutic agents.
  9. A peptide selected from the list consisting of Substance P. or an analogue thereof characterized in that said peptide is coating a metal stent as defined in any one of claims 1 to 8, for use as an implant.
  10. A peptide selected from the list consisting of Substance P. or an analogue thereof characterized in that said peptide is coating a metal stent as defined in any one of claims 1 to 8, for use as an implant to promote blood vessel repair in an individual in need thereof.
  11. A peptide selected from the list consisting of Substance P. or an analogue thereof characterized in that said peptide is coating a metal stent as defined in any one of claims 1 to 8, for use as an implant to promote blood vessel repair in an individual in need thereof in a method that comprises the steps of introducing into a blood vessel in the individual a coated metal stent of any one of claims 1 to 8.
  12. The peptide for use according to claim 11, wherein the blood vessel is any artery or vein in the body, such as a coronary artery, a peripheral artery, an aorta, an intracerebral vessel, an aneurysm vessel, a renal vessel, a hepatic vessel, or a celiac vessel in the individual.
  13. A peptide selected from the list consisting of neurokinin, tachykinin or substance P characterized in that said peptide is coating a metal stent as defined in any one of claims 1 to 8, for use in a method of reducing restenosis in an individual in need thereof, comprising introducing into a blood vessel in the individual a coated metal stent of any one of claims 1 to 8.
  14. The peptide for use according to claim 13, wherein the blood vessel is any artery or vein in the body, such as a coronary artery, a peripheral artery, an aorta, an intracerebral vessel, an aneurysm vessel, a renal vessel, a hepatic vessel, or a celiac vessel in the individual.

Description

Intraluminal devices coated with Substance P The present invention relates to coated Intraluminal devices such as coated metal stents, to methods for coating or producing coated Intraluminal devices such as coated metal stents, and to their use in medicine. In particular, the present invention relates to metal stents coated with Substance P., to methods for coating or producing such coated stents, and to their use as implants. A living being is continuously subjected to internal or external insults that cause continuous damage to organs and tissues. Through different homeostatic mechanisms such as inflammation, once tissue damage occurs the body begins a process of repair. This process attempts the recovery of the structure and functionality of the organ, although usually this repair is not perfect, and the generation of a scar is produced. The scar is a fibrous tissue of collagen that if deposited in excess can produce a fibrosis. This fibrosis can occur in numerous organs and tissues, and in most cases, it is considered to generate secondary pathologies with the appearance of new structural and functional alterations. A second concern, in particular when vascular tissue is involved, as in the case of cardiac stents, is the thrombosis. Fibrosis and thrombosis generated in the vascular epithelia is of particular interest to the present invention. The initial insults that can trigger the aberrant repair process can have an external origin as an infectious process, an internal origin as an autoimmune pathology, but we could also define an anthropic origin. We refer to an anthropic origin when it is an exacerbated biological response to the presence of a foreign body as a medical device. In this sense, the placement of a prosthetic material after the realization of a surgical wound determines a unique tissue environment in which the normal healing sequence (coagulation, inflammation, angiogenesis, epithelialization, fibroplasty and extracellular matrix formation) is in intimate contact with the foreign material. This material will determine the initiation of an inflammatory response, where the cellular components involved include platelets, monocytes, macrophages and polymorphonuclear leukocytes. In addition, there will be other cells such as fibroblasts, endothelial cells and smooth muscle cells. When an inflammatory response occurs, it includes 4 phases: an acute inflammatory response, a chronic inflammatory response, the foreign body reaction, and finally, fibrosis. - Medical devices: fibrosis and thrombosis As already discussed, the presence of a foreign body as a medical device might initiate a fibrotic process, since the body shall attempt to encapsulate the medical device to isolate it, thus preventing it from performing its medical function properly. In this sense, joint prostheses, silicone prostheses, abdominal tights and metal stents, tend to produce such fibrosis leading to a new surgical process necessary to replace the implanted prosthesis. A special case occurs when the growth of scar and fibrotic tissue is produced in tissues that form tubular structures or internal cavities. In this case, the scar generated will act by progressively closing the interior light of the cavity, even completely blinding it. Thus, depending on the affected organ, there may be vascular, digestive, airway, urological, neurological or gynaecological stenosis. Current medical strategies to return functionality to the structure can be summarized as follows: - Surgical processes to restore light to the duct or generate an alternative duct. For example, reconstructive surgeries to eliminate intestinal stenosis, or coronary bypass surgeries. These are very aggressive procedures for the patient. - The use of balloons that, when expanded by inflating them inside the cavity, allow the light of the duct to be restored. Once the structure is recovered, and within the same surgical process, the balloon is deflated and removed. For example, the use of intestinal balloons that dilate the intestinal or oesophageal lumen, coronary balloons or tracheal balloons. Its efficiency rate is not high due to the temporary nature of the measure, requiring in some cases several expansion sessions. - The implantation of spring type medical devices, which are often metallic (and more recently of re-absorbable materials) and when expanded they press the interior walls of the cavity, thus allowing the recovery of the light from the duct. These devices are permanently implanted. For example, coronary stents or tracheal stents. Their main disadvantage is the occurrence of restenosis. On many occasions, the presence of a foreign body such as a stent and the damage it induces to expand, generates a new insult that continues to favour the deposit of scar tissue and matrix. As a result, the problem is reproduced in an even more accentuated manner. Other major concern is directly linked to the particular use of cardiac stents that often produce high rate