US4563485A
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US
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Injection-resistant materials and method of making same through use of nalidixic acid derivatives
Assignee: Columbia University
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Filing: 1984-04-30
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Granted: 1986-01-07
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Expires: 2004-04-30
Abstract
Abstract Infection-resistant materials, and methods of preparing same, suitable for use within the interior of a human or animal body in such forms as vascular grafts prostheses, or other implanted devices. The material is rendered infection-resistant by incorporating therein antimicrobial agents, such as nalidixic acid derivatives or metal salts of nalidixic acid derivatives. In particular illustrative embodiments, silver norfloxacin and silver pefloxacin, are complexed with natural or synthetic polymeric materials such as silk, polyester (e.g., Dacron), polyurethane, polytetrafluoroethylene, or silicone-based material, to provide long-term prevention of infections which may otherwise result during or after surgery or implantation of a device.
Inventors
- 👤 Charles L. Fox, Jr.
- 👤 Shanta Modak
- 👤 Keith Reemtsma
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-22 22:59
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/495; A61K31/435; A61K31/47; A61K31/505; A61L; A61L17/00; A61L17/005; A61L27/00; A61L27/50; A61L27/54; A61L29/00; A61L29/14; A61L29/16; A61L2300/00; A61L2300/10; A61L2300/102; A61L2300/104; A61L2300/20; A61L2300/21; A61L2300/224; A61L2300/40; A61L2300/404
Claims Analysis
Total Claims: 39
Claim 1
Independent Claim
134 words
Infection-resistant material for use within the interior of a human or animal body comprising a polymeric substrate provided with an effective amount of at least one antimicrobial agent; said antimicrobial agent bearing a nalidixic acid derivative having the general formula: ##STR2## wherein X is a halogen; A is a carbon or nitrogen atom; R 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 2
Dependent Claim
134 words
Infection-resistant material for use within the interior of a human or animal body comprising a polymeric substrate provided with an effective amount of at least one antimicrobial agent; said antimicrobial agent bearing a nalidixic acid derivative having the general formula: ##STR2## wherein X is a halogen; A is a carbon or nitrogen atom; R 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 3
Dependent Claim
15 words
The infection-resistant material of claim 1 wherein said polymeric substrate comprises a synthetic polymeric material.
Claim 4
Dependent Claim
23 words
The infection-resistant material of claim 2 wherein said synthetic polymeric material is selected from the group consisting of polyester, polytetrafluoroethylene, polyurethane, and polyamide.
Claim 5
Dependent Claim
13 words
The infection-resistant material of claim 3 wherein said synthetic polymeric material is polyester.
Claim 6
Dependent Claim
12 words
The infection-resistant material of claim 2 wherein said polymeric material contains silicone.
Claim 7
Dependent Claim
15 words
The infection-resistant material of claim 1 wherein said polymeric material comprises a natural polymeric material.
Claim 8
Dependent Claim
24 words
The infection-resistant material of claim 6 wherein said natural polymeric material is selected from the group consisting of biological tissues, collagenous substances, and silk.
Claim 9
Dependent Claim
28 words
The infection-resistant material of claim 1 wherein said nalidixic acid derivative is selected from the group consisting of norfloxacin, pefloxacin, enoxacin, 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-7-(4-methyl-1-piperazinyl)-quinoline-3-carboxylic acid, piromidic acid, and pipemidic acid.
Claim 10
Dependent Claim
11 words
The infection-resistant material of claim 8 wherein said metal is silver.
Claim 11
Dependent Claim
144 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 12
Dependent Claim
144 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 13
Dependent Claim
14 words
The infection-resistant device of claim 10 wherein said device is a vascular graft prosthesis.
Claim 14
Dependent Claim
12 words
The infection-resistant device of claim 10 wherein said device is a catheter.
Claim 15
Dependent Claim
14 words
The infection-resistant device of claim 10 wherein said device is an internal contraceptive device.
Claim 16
Dependent Claim
15 words
The infection-resistant device of claim 10 wherein said device is an internal feminine hygiene device.
Claim 17
Dependent Claim
13 words
The infection-resistant device of claim 10 wherein said device is a surgical suture.
Claim 18
Independent Claim
139 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 19
Independent Claim
139 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 20
Dependent Claim
23 words
The method of claim 16 wherein said incorporating step comprises placing said material in a solution containing said at least one antimicrobial agent.
Claim 21
Dependent Claim
10 words
The method of claim 17 wherein said solution contains ammonia.
Claim 22
Dependent Claim
18 words
The method of claim 18 wherein said ammoniacal solution contains about 4% by weight of said antimicrobial agent.
Claim 23
Dependent Claim
24 words
The method of claim 16 wherein said incorporating step comprises placing said material in an aqueous suspension of said at least one antimicrobial agent.
Claim 24
Dependent Claim
18 words
The method of claim 20 wherein said aqueous suspension contains 20 micromoles of silver pefloxacin per ml water.
Claim 25
Dependent Claim
26 words
The method of claim 16 wherein said incorporating step comprises forming a metal salt of the nalidixic acid derivative in the presence of the substrate material.
Claim 26
Independent Claim
177 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 27
Independent Claim
177 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 28
Dependent Claim
34 words
The method of claim 23 wherein said first solution comprises an aqueous solution of a non-metal salt of a nalidixic acid derivative and said second solution comprises an aqueous solution of a silver salt.
Claim 29
Dependent Claim
16 words
The method of claim 24 wherein said second solution is an aqueous solution of silver nitrate.
Claim 30
Dependent Claim
22 words
The method of claim 24 wherein said first solution is an aqueous solution of the ammonium salt of a nalidixic acid derivative.
Claim 31
Dependent Claim
27 words
The method of claim 24 wherein said nalidixic acid derivative is selected from the group consisting of norfloxacin, pefloxacin, enoxacin, 6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-4-oxo-7-(4-methyl-1-piperazinyl)-quinoline-3-carboxylic acid, piromidic acid, and pipemidic acid.
Claim 32
Independent Claim
148 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 33
Independent Claim
148 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 34
Independent Claim
24 words
A method for reducing the risk of infection by silver sulfadiazine resistant bacteria said method comprising the use of silver pefloxacin incorporated graft materials.
Claim 35
Independent Claim
24 words
A method for reducing the risk of infection by silver sulfadiazine resistant bacteria said method comprising the use of silver pefloxacin incorporated graft materials.
Claim 36
Independent Claim
162 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 37
Independent Claim
162 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 38
Dependent Claim
147 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
Claim 39
Dependent Claim
147 words
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 1 is hydrogen, a lower alkyl group or a metal; R 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 3 and R 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.
References Cited (Backward Citations)
US4049802A
Cited
US4353996A
Cited
US4455146A
Cited
US4271070A
Cited
US4404197A
Cited
US4462981A
Cited
US4401712A
Cited
US4446124A
Cited
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