Medical device comprising covalently bonded heparin coating

A covalent bonding and medical device technology, applied in medical packaging, coating, packaging, etc., can solve the problem that heparin cannot be used as an active site

Pending Publication Date: 2021-12-14
JMEDTECH XIAMEN COATING TECH CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, the hydroxyl groups of heparin cannot be used as active sites for covalent coating in aqueous solutions

Method used

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  • Medical device comprising covalently bonded heparin coating
  • Medical device comprising covalently bonded heparin coating
  • Medical device comprising covalently bonded heparin coating

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0304] Coating of heparin-TBA (40) via carbamate formation reaction (25) on PHMDI-coated polyurethane tubing (15)

[0305] To prepare the heparin-coated device (50) of the present invention, heparin-TBA (40) can be used directly in the carbamate formation reaction 25 (in acetonitrile), since the hydroxyl groups of heparin can directly interact with the PHMDI-coated tube 15 The reaction of the isocyanate group ( figure 2 ).

[0306] In a typical reaction, heparin-TBA40 (500 mg) and anhydrous acetonitrile (10 mL) were added to a 50 mL Schlenk flask in a glove box (argon protection), and a solution was obtained by shaking gently for ~5 min. The Schlenk flask was then removed from the glove box, connected to a Schlenk line (protected with nitrogen), and heated to 60°C in an oil bath.

[0307] Two freshly prepared PHMDI-coated PU tubes (prepared according to general procedure 2) were immersed in the solution and kept at 60 °C for 6 h. During the coating time of 6 h, the Schlenk...

Embodiment 2

[0310] On PHMDI or HDI coated polyurethane tubing (15), heparin-O (CHR 1 CHR 2 O) n H-TBA(60)

[0311] In addition to using heparin-TBA for direct coating onto isocyanate-coated medical devices, other modified forms of heparin-TBA can also be used (40). In one embodiment of the present invention, heparin-TBA (40 ) to modify ( image 3 ).

[0312] The ring-opening reaction of epoxides with the hydroxyl groups of heparin-TBA allows the repositioning of some of the hydroxyl groups away from the heparin carbon backbone to facilitate carbamate-forming reactions with isocyanates (25). This means that epoxy-modified heparin can be coated onto PU tubing more efficiently or more easily than heparin-TBA.

[0313] Generally, the reaction can be carried out at elevated temperature with or without a catalyst to facilitate the reaction. Examples of catalysts are triethylamine, dimethylaminopyridine (DMAP) and 1,1,3,3-tetramethylurea. The general formula of epoxide-modified heparin (...

Embodiment 3

[0321] On PHMDI-coated polyurethane tubing (15), APC cross-linked heparin-TBA (40) or APC cross-linked heparin-O (CHR 1 CHR 2 O) n H-TBA(60)

[0322] Heparin-TBA(40) or epoxy-modified heparin-O(CHR 1 CHR 2 O) n H-TBA(60) can be further modified to form intermolecular crosslinks with its respective neighboring heparin molecules. In a specific embodiment of the present invention, cross-linking can be achieved by reacting the hydroxyl group of 40 or 60 with linker 42 (i.e., adipoyl chloride (APC)) in the presence of a base (triethylamine) to obtain a cross-linked product 70 ( Figure 4 ). Alternatively, 40 or 60 can be used to react with linkers containing multiple epoxy groups to achieve intermolecular crosslinking. Intermolecular crosslinking increases the bonding density of heparin on isocyanate-coated medical devices, thereby reducing the leakage of heparin from medical devices. In this way, the lifetime of the heparin coating obtained on the device can be increased....

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Abstract

Disclosed herein is a medical device, comprising a covalently-bonded heparin coating on a substrate, where the covalently bonded heparin coating is the reaction product of (a) an isocyanate-bearing material on or covalently bonded to the substrate and (b) a heparin molecule selected from one of the formulae in the claims. The current invention also relates to a method of forming the medical device, which may be useful as heart stent or intravascular stent that is hemocompatible for preventing the formation of blood clots.

Description

technical field [0001] The present invention relates to a medical device. In particular, the medical device may comprise a covalently bonded heparin coating on a substrate (eg, polyurethane tubing). Background technique [0002] The listing or discussion of a prior published document in this specification should not be considered as an admission that the document is part of the state of the art or is common general knowledge. [0003] Heparin is one of the most effective anticoagulants and is widely used in antithrombotic coatings of medical devices such as synthetic polymer devices. This coating renders the device antithrombotic to prevent the formation of blood clots when these devices are used as cardiac stents or intravascular stents or organ stents, or in blood collection and separation applications is required (Advanced Drug Delivery Reviews 2017, 112, 12-23; US 8,501,212; US 6,953,625; US 8,101,196; US 2004 / 0142016; US 2011 / 0274821; WO 2001 / 039814). Typically, this...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L27/16A61L27/34A61L27/54A61L29/04A61L29/08A61L29/16A61L31/04A61L31/10A61L31/16A61L33/00A61L33/06
CPCA61L27/16A61L29/041A61L31/048A61L27/34A61L27/54A61L29/085A61L29/16A61L31/10A61L31/16A61L33/0011A61L33/068A61L2300/42C08L35/04A61L27/18A61L29/06A61L31/06A61L2420/02
Inventor 罗和宽王宏磊昂中燕
Owner JMEDTECH XIAMEN COATING TECH CO LTD
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