Injection-resistant materials and method of making same through use of nalidixic acid derivatives

An infection-resistant device for use within the interior of a human or animal body wherein at least a portion of said device comprises a polymeric substrate provided with an effective amount of at least one antimicrobial agent;

• said antimicrobial agent being a nalidixic acid derivative having the general formula:
• ##STR3## wherein X is a halogen;
• A is a carbon or nitrogen atom;
• R.sub.1 is hydrogen, a lower alkyl group or a metal;
• R.sub.2 is a lower alkyl group, a lower aralkyl group, a vinyl group, an allyl group, a lower hydroxy alkyl group or a halogenated lower alkyl group;
• R.sub.3 and R.sub.4 are hydrogen, a lower alkyl group or together, along with the nitrogen atom to which they are attached, form a 5- or 6- membered heterocyclic ring containing the nitrogen atom and additionally a second nitrogen or oxygen heteroatom.

A method of preparing infection-resistant material for use within the interior of a human or animal body comprising:

• incorporating an effective amount of at least one antimicrobial agent on a polymeric material;
• said antimicrobial agent being a nalidixic acid derivative having the general formula:
• ##STR4## wherein X is a halogen;
• A is a carbon or nitrogen atom;
• R.sub.1 is hydrogen, a lower alkyl group or a metal;
• R.sub.2 is a lower alkyl group, a lower aralkyl group, a vinyl group, an allyl group, a lower hydroxy alkyl group or a halogenated lower alkyl group;
• R.sub.3 and R.sub.4 are hydrogen, a lower alkyl group or together, along with the nitrogen atom to which they are attached, form a 5- or 6- membered heterocyclic ring containing the nitrogen atom and additionally a second nitrogen or oxygen heteroatom.

A method of preparing infection-resistant material for use within the interior of a human or animal body comprising:

• placing a polymeric substrate material in a first solution containing a soluble salt of at least one anti-microbial agent;
• said antimicrobial agent being a nalidixic acid derivative having the general formula:
• ##STR5## wherein X is a halogen;
• A is a carbon or nitrogen atom;
• R.sub.1 is hydrogen, a lower alkyl group or a metal;
• R.sub.2 is a lower alkyl group, a lower aralkyl group, a vinyl group, an allyl group, a lower hydroxy alkyl group or a halogenated lower alkyl group;
• R.sub.3 and R.sub.4 are hydrogen, a lower alkyl group or together, along with the nitrogen atom to which they are attached, form a 5- or 6- membered heterocyclic ring containing the nitrogen atom and additionally a second nitrogen or oxygen heteroatom;
• and
• placing the polymeric substrate material in a second solution of a soluble metal salt so as to cause formation of a metal salt of the nalidixic acid derivative on the substrate material.

A method for reducing the risk of infection by bacteria as a result of prosthetic vascular graft surgery, said method comprising the use of a graft comprising a polymeric material provided with an effective amount of at least one antimicrobial agent;

• said antimicrobial agent being a nalidixic acid derivative having the general formula:
• ##STR6## wherein X is a halogen;
• A is a carbon or nitrogen atom;
• R.sub.1 is hydrogen, a lower alkyl group or a metal;
• R.sub.2 is a lower alkyl group, a lower aralkyl group, a vinyl group, an allyl group, a lower hydroxy alkyl group or a halogenated lower alkyl group;
• R.sub.3 and R.sub.4 are hydrogen, a lower alkyl group or together, along with the nitrogen atom to which they are attached, form a 5- or 6- membered heterocyclic ring containing the nitrogen atom and additionally a second nitrogen or oxygen heteroatom.

A method for reducing the risk of infection by bacteria as a result of a device implanted within the interior of a human or animal body, said method comprising the use of a polymeric material provided with an effective amount of at least one antimicrobial agent for at least a portion of the implanted device;

• said antimicrobial agent being a nalidixic acid derivative having the general formula:
• ##STR7## wherein X is a halogen;
• A is a carbon or nitrogen atom;
• R.sub.1 is hydrogen, a lower alkyl group or a metal;
• R.sub.2 is a lower alkyl group, a lower aralkyl group, a vinyl group, an allyl group, a lower hydroxy alkyl group or a halogenated lower alkyl group;
• R.sub.3 and R.sub.4 are hydrogen, a lower alkyl group or together, along with the nitrogen atom to which they are attached, form a 5- or 6- membered heterocyclic ring containing the nitrogen atom and additionally a second nitrogen or oxygen heteroatom.

An infection-resistant material for use within the interior of a human or animal body, said material comprising a polymeric substrate having an effective amount of at least one antimicrobial agent complexed therewith so as to provide a long-term antimicrobial effect;

• said antimicrobial agent being a nalidixic acid derivative having the general formula:
• ##STR8## wherein X is a halogen;
• A is a carbon or nitrogen atom;
• R.sub.1 is hydrogen, a lower alkyl group or a metal;
• R.sub.2 is a lower alkyl group, a lower aralkyl group, a vinyl group, an allyl group, a lower hydroxy alkyl group or a halogenated lower alkyl group;
• R.sub.3 and R.sub.4 are hydrogen, a lower alkyl group or together, along with the nitrogen atom to which they are attached, form a 5- or 6- membered heterocyclic ring containing the nitrogen atom and additionally a second nitrogen or oxygen heteroatom.