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EP-4735068-A1 - COMPOUNDED ACTIVE PHARMACEUTICAL AGENTS IN THERMOPLASTIC POLYMER COMPOSITIONS AND METHODS OF MANUFACTURE

EP4735068A1EP 4735068 A1EP4735068 A1EP 4735068A1EP-4735068-A1

Abstract

The present disclosure relates to articles of manufacture having an active pharmaceutical ingredient (API) integrated in a thermoplastic polymer, as well as methods of using and making such articles. For example, using the articles in medical devices and treating patients.

Inventors

  • GUPTA, NISHA
  • Sechrist, Kevin
  • MARCHESE, Eric

Assignees

  • Teleflex Medical LLC

Dates

Publication Date
20260506
Application Date
20240628

Claims (20)

  1. 1. An article of manufacture, comprising: an active pharmaceutical ingredient (API) integrated in a thermoplastic polymer, wherein: (A) the thermoplastic polymer has a water absorption capacity of about >1 to 90 % w/w of the article, preferably about 10 to 70 % w/w of the article, or most preferably about 15 to 30% w/w of the article, and/or (B) the article further comprises a hydrophilic polymer blended with the thermoplastic polymer.
  2. 2. The article of claim 1, wherein the API is present in an amount of about 100 to 5000 pg/cm of the article; preferably about 150 to 3500 pg/cm of the article; most preferably about 200 to 2000 pg/cm of the article.
  3. 3. The article of claim 1. wherein: (Al) the API is homogenously distributed throughout at least a portion of the bulk of tire thermoplastic polymer; or (Bl) the API distributed as a gradient with the API concentrated on an outer most and an inner most layers of the article.
  4. 4. The article of claim 1, wherein: (A2) the hydrophilic polymer is homogenously distributed throughout at least a portion of the bulk of the thermoplastic polymer; and/or (B2) the hydrophilic polymer distributed as a gradient with the hydrophilic polymer concentrated on an outer most and an inner most layers of the article.
  5. 5. The article of claim 1, wherein the thermoplastic polymer is about 5 to 95 % w/w of the article, preferably about 10 to 70 % w/w of the article.
  6. 6. The article of claim 1, wherein the API is about 1 to 30 % w/w of the article, preferably about 1.5 to 20 % w/w of the article, or most preferably about 2 to 15% w/w of the article.
  7. 7. The article of claim 1, wherein the hydrophilic polymer is about 1 to 60 % w/w of the article, preferably about 5 to 40 % w/w of the article, or most preferably about 10 to 35% w/w of the article.
  8. 8. The article of claim 1, wherein the thermoplastic polymer is selected from PVC, aromatic polyether polyurethane, aliphatic poly ether polyurethane, aromatic polycarbonate polyurethane, aliphatic polycarbonate polyurethane, rigid polyurethane, aromatic polycarbonate silicone polyurethane, aromatic poly ether silicone polyurethane, aliphatic polyether hydrophilic polyurethane, aromatic poly ether hydrophilic polyurethane, thermoplastic elastomer, poly ether block amide, preferably aromatic polyether polyurethane, aliphatic poly ether polyurethane, aromatic polycarbonate polyurethane, aliphatic polycarbonate polyurethane, aliphatic polyether hydrophilic polyurethane, aromatic polyether hydrophilic polyurethane, thermoplastic elastomer, polyether block amide polyurethane, or most preferably aromatic polyether polyurethane, aliphatic poly ether polyurethane, aliphatic polyether hydrophilic polyurethane, aromatic poly ether hydrophilic polyurethane.
  9. 9. The article of claim 1, wherein the contains an antimicrobial, an antithrombogenic. or an antifouling agent.
  10. 10. The article of claim 1, wherein the hydrophilic polymer is selected from aliphatic polyether hydrophilic polyurethane, aromatic polyether hydrophilic polyurethane, and polyether block amide hydrophilic; or most preferably aliphatic polyether hydrophilic polyurethane and aromatic poly ether hydrophilic polyurethane.
  11. 11. The article of claim 1, further comprising a second thermoplastic polymer.
  12. 12. The article of claim 1, further comprising a second API.
  13. 13. The article of claim 1, further comprising a second hydrophilic polymer.
  14. 14. The article of claim 1, further comprising about 10 to 40 % w/w of excipients, preferably about 15 to 35 % w/w of excipients; or most preferably about 20 to 30 % w/w of excipients.
  15. 15. The article of claim 14, wherein the excipients include a plasticizer, a stabilizer, an antioxidants, or a radio-opacifier, preferably at least an radio-opacifier which is preferably selected from barium sulfate, bismuth oxychloride, or tungsten.
  16. 16. An implantable medical device, comprising: the article of any one of claims 1-15.
  17. 17. The implantable medical device of claim 16, further comprising a lubricious overcoat on the article.
  18. 18. The implantable medical device of claim 17, wherein the lubricious overcoat comprises a lubricious agent, which is preferably a polyethylene oxide polymer or dimethyl siloxane, and an adhesive agent configured to adhere the lubricous coating to the article.
  19. 19. The implantable medical device of claim 16, wherein the article can safely remain implanted in a patient for at least 2 hours to 90 days; for example about 1 day to 7 days; preferably about 3 to 14 days; or most preferably about 7 to 30 days; alternatively at least 30 days, at least 31 days, at least 35 days up to 90 days.
  20. 20. The implantable medical device of claim 16, wherein the article has at least one property selected from: (1) antimicrobial property leading to reduction in colonization by broad spectrum microorganisms including gram positive bacteria, gram negative bacteria or fungi by at least 70%; preferably antimicrobial property leading to reduction in colonization by broad spectrum microorganisms including gram positive bacteria, gram negative bacteria or fungi by at least 80%; most preferably antimicrobial property leading to reduction in colonization by broad spectrum microorganisms including gram positive bacteria, gram negative bacteria or fungi by at least 90%, (2) antithrombogenic property leading to reduction in platelet adhesion, fibrin sheath formation, fibroblastic sleeve formation, intraluminal thrombus, extraluminal thrombus, intimal hyperplasia, or vascular thrombosis by at least 25%; preferably antithrombogenic property leading to reduction in platelet adhesion, fibrin sheath formation, fibroblastic sleeve formation, intraluminal thrombus, extraluminal thrombus, intimal hyperplasia, or vascular thrombosis by at least 50%; most preferably antithrombogenic property leading to reduction in platelet adhesion, fibrin sheath formation, fibroblastic sleeve formation, intraluminal thrombus, extraluminal thrombus, intimal hyperplasia, or vascular thrombosis by at least 75%; (3) anti-inflammatory property leading to reduction in insertion site redness, swelling, pain, phlebitis, or thrombophlebitis by at least 25%; preferably anti-inflammatory property leading to reduction in insertion site redness, swelling, pain, phlebitis, or thrombophlebitis by at least 50%; most preferably anti-inflammatory property leading to reduction in insertion site redness, swelling, pain, phlebitis, or thrombophlebitis by at least 75%, preferably at least two of the at least one property’, or most preferably at least three of the at least one property.

Description

COMPOUNDED ACTIVE PHARMACEUTICAL AGENTS IN THERMOPLASTIC POLYMER COMPOSITIONS AND METHODS OF MANUFACTURE CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Patent Application Ser. No. 63/511,102, filed June 29, 2023, the entire contents of which are incorporated by reference herein. FIELD OF THE INVENTION [0002] The present invention generally relates to compounded compositions for medical devices having antimicrobial, antithrombogenic, and/or anti-inflammatory properties. BACKGROUND OF THE INVENTION [0003] Medical devices are commonly used to facilitate care and treatment of patients undergoing surgical procedures. Examples of such devices include catheters, grafts, stents, sutures, and the like. Unfortunately, organisms such as bacteria and fungi may infiltrate and/or form biofilms on these medical devices which may be difficult to treat. Such contamination may lead to infections and cause discomfort or illness. In addition to infections, indwelling catheters can result in the problem of pathological blood clot formation, and/or catheter-induced vein thrombosis. About half of hemodialysis catheters fail within a year, and up to two thirds of the failures are due to thrombosis. [0004] The use of medical devices having antimicrobial and antithrombogenic properties may reduce the incidence of infection and thrombosis in the patient. Typically, the antimicrobial and/or antithrombogenic agent is applied as a coating on the conventional medical device or the antimicrobial agent is infused into the conventional medical device by soaking the device in a solution of the antimicrobial and antithrombogenic agent. In these and other conventional methods of incorporating the antimicrobial and antithrombogenic agent to the medical device, this extra step of coating or soaking takes time and increases costs. [0005] In addition to the added step and increased production time, soaking and coating may not achieve relatively high concentrations of antibiotic in the base material of the medical device. For relatively short procedures having a duration of a few hours, this relatively low antibiotic concentration may be sufficient. However, for longer procedures lasting several days, the antibiotic present in conventional devices may be insufficient. As such, these conventional devices must be replaced frequently as the antibiotic falls below effective levels. [0006] Accordingly, it is desirable to provide an antimicrobial and antithrombogenic medical device and/or method of incorporating an antimicrobial and antithrombogenic agent to a medical device that is capable of overcoming the disadvantages described herein at least to some extent. SUMMARY OF THE INVENTION [0007] Embodiments of the disclosure include an active pharmaceutical ingredient (API) compounded into a polymer. The API compounded into the polymer can be used in a medical device. Methods of compounding the polymer and API are provided, as well as, methods of use. [0008] Some embodiments are directed to an article of manufacture, having an API integrated in a thermoplastic polymer, wherein: the thermoplastic polymer has a water absorption capacity of about >1 to 90 % w/w of the article, preferably about 10 to 70 % w/w of the article, or most preferably about 15 to 30% w/w of the article, and/or the article further comprises a hydrophilic polymer blended with the thermoplastic polymer. [0009] Some embodiments are directed to an implantable medical device having an API integrated in a thermoplastic polymer. [0010] Embodiments of the disclosure include methods of removing or adding fluids to a patient, by implanting the medical device of having an API integrated in a thermoplastic polymer into a cavity or vein or artery of patient, wherein the medical device is a catheter; and removing or adding at least one fluid to the patient through the medical device. [0011] There has thus been outlined, rather broadly, certain embodiments of the invention in order that the detailed description thereof herein may be better understood, and in order that the present contribution to the art may be better appreciated. There are, of course, additional embodiments of the invention that will be described below and which will form the subject matter of the claims appended hereto. [0012] In this respect, before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and to the arrangements of the components set forth in the following description or illustrated in the drawings. The invention is capable of embodiments in addition to those described and of being practiced and carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein, as well as the abstract, are for the purpose of description and should not be regarded as limiting. [0013] As such, those skilled in the ar