Biocidal locks

• US 6,350,251 B1
• Filed: 01/18/2000
• Issued: 02/26/2002
• Est. Priority Date: 01/18/2000
• Status: Expired due to Term

• Current Assignee: ND Partners LLC
• Original Assignee: Biolink Corp. (Acacia Capital Corp.)
• Inventors: Prosl, Frank R., Estabrook, Brian K., Sodemann, Klaus
• Primary Examiner(s): Brown, Michael A.
• Application Number:
  US09/483,966
• Time in Patent Office: 770 Days
• Field of Search: 604/93, 604/8, 604/9, 604/94, 604/95, 514/222.5, 514/223.5
• US Class Current: 604/93.01
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61M 39/0208 Subcutaneous access sites for injecting or removing fluids transcutaneous access sites A61M39/0247; implantable infusion devices A61M5/14276
• CPC Class Codes: A61M 5/158 Needles for infusions; Accessories therefor, e.g. for inserting infusion needles, or for holding them on the body
• CPC Class Codes: A61M 5/427 Locating point where body is to be pierced, e.g. vein location means using ultrasonic waves, injection site templates

Abstract

Disclosed herein is an internal prosthetic device comprising:

(a) device for providing a continuous flowpath, crossing a patient'"'"'s skin, between an external-to-patient site and an internal-to-patient site;

(b) means for blocking the flowpath; and

(c) a biocidal lock including:

(i) an anticoagulant; and

(ii) a non-antibiotic biocide.

Claims

1. An internal prosthetic device comprising:

(a) means for providing a continuous flowpath, crossing a patient'"'"'s skin, between an external-to-patient site and an internal-to-patient site;

(b) means for blocking the flowpath; and

(c) a biocidal lock comprising;

(i) an anticoagulant; and

(ii) a non-antibiotic biocide.

2. The device of claim 1 wherein said device is a catheter.

3. The device of claim 1 wherein said device is a port.

4. An internal prosthetic device access system comprising:

(a) means for providing a continuous flowpath, crossing a patient'"'"'s skin, between an external-to-patient site and an internal-to-patient site;

(b) means for blocking the flowpath at a point under the patient'"'"'s skin;

(c) means for removing the flowpath portion crossing the patient'"'"'s skin; and

(d) a biocidal lock comprising;

(i) an anticoagulant; and

(ii) a non-antibiotic biocide.

5. The system of claim 4 wherein the system is a dialysis access system.

6. The system of claim 5 wherein the system is a hemodialysis access system.

7. A hemodialysis access system comprising:

(a) means for providing a continuous flowpath, crossing a patient'"'"'s skin, between an external-to-patient dialysis site and an internal blood vessel of the patient, the means including a flow conduit having no more than gentle changes in direction and whose internal surfaces are smooth and free of abrupt changes in flow area and define a flowpath sized for hemodialysis flow rates, and free of obstructions to provide low flow resistance and avoid any stagnation point;

(b) means for blocking the flowpath at a point under the patient'"'"'s skin;

(c) means for removing the flowpath portion crossing the patient'"'"'s skin; and

(d) a biocidal lock comprising;

(i) an anticoagulant; and

(ii) a non-antibiotic biocide.

8. The system of claim 7 further comprising a flexible seal and wherein flowpath blockage is provided by the flexible seal, the flexible seal being entirely removable from the flowpath to establish a fully open configuration thereof free of obstructions and abrupt flow diameter or flow direction changes.

9. The system of claim 7 and further comprising means for activating and inactivating the flowpath forming portion of the system.

10. The system of claim 7 and further comprising means for increasing the available skin-crossing sites used in establishing the flowpath.

11. The system of claim 10 comprising a hollow needle which is insertable percutaneously by longitudinal pushing of it to a site where it defines a portion of the flowpath, and withdrawable by longitudinal pulling of the needle, and an implanted catheter comprising another portion of the flowpath and means for establishing a smooth continuous transition between the portions.

12. The system of claim 11 further comprising means for locking the inserted needle in place wherein the locking means is constructed and arranged to lock the needle upon longitudinal withdrawal movement accompanied by a lateral twisting movement.

13. The system of claim 12 further comprising an obturator within the hollow needle wherein the obturator has a pointed end arrangeable to protrude from a hollow needle ends.

14. The system of claim 7 wherein the anticoagulant is selected from the group consisting of di-ammonium hydrogen citrate, di-ammonium tartrate, N-(2-{bis(carboxymethyl)amino}ethyl)-N-(2-hydroxyethyl)glycin salt dihydrate, citric acid, citric acid disodium salt, citric acid monopotassium salt, citric acid monosodium salt, citric acid tripotassium salt, citric acid trisodium salt, ethylenediaminetetraacetic acid (EDTA), EDTA diammonium salt, EDTA dipotassium salt, EDTA disodium salt, EDTA tetrasodium salt, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), EDTA trisodium salt, EDTA tripotassium salt, ethylene glycol-O,O′

-bis(2-aminoethyl)-N,N,N′

,N′

-tetraacetic acid, N-(2-hydroxyethyl)ethylenediamine-N,N′

,N′

-triacetic acid trisodium salt, nitrilotriacetic acid, potassium sodium tartrate, potassium hydrogen D-tartrate, L-tartaric acid dipotassium salt, L-tartaric acid disodium salt, L-tartaric acid monosodium salt, tris(carboxymethyl)amine, heparin, warfarin, acetylsalicylic acid, ibuprofen, indomethacin, prostaglandins, sulfinpyrazone, streptokinase, urokinase, tissue plasminogen activator, coumarin, protamine sulfate, anti-thrombin III, coumadin, protein C/protein S, nicoumalone, phenprocoumon, hirudin, hirulog, glycosaminoglycans, and mixtures of the foregoing.

15. The system of claim 14 wherein the anticoagulant is a mixture of citric acid and trisodium citrate.

16. The system of claim 15 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

17. The system of claim 15 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

18. The system of claim 16 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

19. The system of claim 14 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

20. The system of claim 19 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

21. The system of claim 14 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

22. The system of claim 7 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

23. The system of claim 22 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

24. The system of claim 7 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

25. A hemodialysis access system for repeated access to a patient'"'"'s vascular system, for hemodialysis repetitive blood exchange therapy, via a catheter that is subcutaneously implanted in the patient and has a distal end attached to a patient blood vessel and a proximal end near the patient'"'"'s skin, the system comprising, in combination:

(a) a subcutaneously implantable access device having an entrance region, exit region and a passage therebetween provide for introduction of a needle thereby defining together with each other and the catheter a continuous streamlined flow path having no more than gentle changes in flow direction and being essentially free of stagnation points and constructed and arranged for blood flow through the flow path at a flow rate of at least 100 milliliters per minute;

(b) a needle for defining a continuous flowpath extension relative to the catheter and with a front part of the obturator emerging from a cannula front end and removable from the cannula, the cannula being constructed and arranged as a passage, when the obturator is removed, and means for communicating from the distal end of the cannula interior to an external patient site;

(c) the needle being constructed and arranged to puncture the patient'"'"'s skin, to penetrate subcutaneous tissue and reach the entrance region of the implanted device and transit the passage of the latter to a point adjacent the exit region of the device and for withdrawal of the obturator of the needle means to thereby establish fluid communication between an external to the patient site and the catheter to provide a blood exchange path and flushing path from outside the patient to the patient'"'"'s vascular system;

(d) means located within the device'"'"'s passage at a site normally passed by needle insertion therein, for sealing the passage when the cannula/obturator is not in the passage and openable when contacted by the outer surface of the needle means, the seal and needle constructed and arranged so that the needle surface bears against the sealing material which is forced aside to an open position to permit the needle to transit the devices'"'"'s passage, but without the point thereof contacting the sealing surfaces, the cannula being sufficiently rigid to hold the seal open when the obturator is withdrawn from the inserted cannula; and

(e) a biocidal lock comprising;

(i) an anticoagulant; and

(ii) a non-antibiotic biocide.

26. The system of claim 25 wherein the passage comprises a region adjacent its exit for stopping the front end of the cannula of the inserted needle and forming a smooth walled flow path transition therewith.

27. The system of claim 25 wherein the anticoagulant is selected from the group consisting of di-ammonium hydrogen citrate, di-ammonium tartrate, N-(2-{bis(carboxymethyl)amino}ethyl)-N-(2-hydroxyethyl)glycin salt dihydrate, citric acid, citric acid disodium salt, citric acid monopotassium salt, citric acid monosodium salt, citric acid tripotassium salt, citric acid trisodium salt, ethylenediaminetetraacetic acid (EDTA), EDTA diammonium salt, EDTA dipotassium salt, EDTA disodium salt, EDTA tetrasodium salt, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), EDTA trisodium salt, EDTA tripotassium salt, ethylene glycol-O,O′

-bis(2-aminoethyl)-N,N,N′

,N′

-tetraacetic acid, N-(2-hydroxyethyl)ethylenediamine-N,N′

,N′

-triacetic acid trisodium salt, nitrilotriacetic acid, potassium sodium tartrate, potassium hydrogen D-tartrate, L-tartaric acid dipotassium salt, L-tartaric acid disodium salt, L-tartaric acid monosodium salt, tris(carboxymethyl)amine, heparin, warfarin, acetylsalicylic acid, ibuprofen, indomethacin, prostaglandins, sulfinpyrazone, streptokinase, urokinase, tissue plasminogen activator, coumarin, protamine sulfate, anti-thrombin III, coumadin, protein C/protein S, nicoumalone, phenprocoumon, hirudin, hirulog, glycosaminoglycans, and mixtures of the foregoing.

28. The system of claim 27 wherein the anticoagulant is a mixture of citric acid and trisodium citrate.

29. The system of claim 28 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

30. The system of claim 29 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

31. The system of claim 28 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

32. The system of claim 27 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium, surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

33. The system of claim 27 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrates.

34. The system of claim 32 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

35. The system of claim 25 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

36. The system of claim 35 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

37. The system of claim 25 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

38. A hemodialysis access system for access to a human or animal patient'"'"'s vascular system for high fluid flow rate exchange of blood between the vascular system and an external processing apparatus at a volumetric flow rate in excess of 100 mL/minute and having a decreased proclivity for effecting infection and blood coagulation, and comprising, in combination,

(a) a needle assembly comprising a lumen defined by an interior surface and constructed and arranged for puncturing the skin of the patient and for carrying blood therethrough at a flow rate consistent with the high blood flow requirement of the blood exchange process;

(b) a subcutaneously implantable access device permitting fluid connection to a vessel or space within a patient'"'"'s body, the device comprising

(i) a channel structure providing a flowpath having a straight or gently changing flow direction and having an interior surface and a distal end and a proximal end with reference to the patient'"'"'s skin puncture site and constructed and arranged for insertion of the needle through the proximal end of the channel and withdrawal of the needle therefrom,

(ii) a seal arranged within the channel and movable between first and second positions, where the seal, in the first position, with the needle not inserted through the seal, prevents fluids from passing the seal and, in the second position, with the needle inserted through the seal, allows fluids to pass through the needle and emerge substantially at the channel distal end, and where blood flowpath transitions between the needle interior surface and the channel interior surface are substantially continuous and smooth when the means for sealing is in the second position; and

the device further comprising structure for joining the channel distal end to a catheter that extends to an internal vessel of the patient'"'"'s body, and wherein such joining is continuous and smooth along the interior surfaces of the channel and catheter; and

(c) a biocidal lock comprising;

(i) an anticoagulant; and

(ii) a non-antibiotic biocide.

39. The the access system of claim 38 further comprising a catheter constructed and arranged for implantation between the device at a proximal cathether end and to or into a patient'"'"'s blood vessel at a distal catheter end and means for attaching the device to the surrounding patient tissue.

40. The access system of claim 38 wherein the needle has a lumen and disposed along a first axis, the needle matingly corresponding to the inner surface and having a wall thickness of approximately 0.1 mm, and an obturator that is disposed within the needle along the first axis and matingly inserted into the lumen of the needle, the needle and obturator designed to provide an assembly with a pointed end constructed for opening the means for sealing, and means defining an access channel external to the patient communicating with the lumen of the needle, when it is inserted into the patient and through the means for sealing and wherein the access channel is disposed at an acute angle from the needle first axis.

41. The access system of claim 38 for high flow rate blood exchange between a human or animal patient with simultaneous flow in and out of the patient through separate paths, comprising at least one subcutaneously implantable access devise capable of being implanted in the patient just under the skin and having at least one passage therein, each with an entrance proximal to the skin and an exit distal therefrom, for accommodating one or more hollow needles, with interior lumens, percutaneously inserted therein, the transitions between the interior lumens of the needles and passage interiors of the device having gentle changes in flow direction and streamlined flowpaths, thereby permitting fluid connection to one or two blood vessels within a patient'"'"'s body.

42. The access system of claim 41 further comprising means to secure the needles to each other and locking means to secure the needles within the device.

43. The system of claim 38 wherein the anticoagulant is selected from the group consisting of di-ammonium hydrogen citrate, di-ammonium tartrate, N-(2-{bis(carboxymethyl)amino}ethyl)-N-(2-hydroxyethyl)glycin salt dihydrate, citric acid, citric acid disodium salt, citric acid monopotassium salt, citric acid monosodium salt, citric acid tripotassium salt, citric acid trisodium salt, ethylenediaminetetraacetic acid (EDTA), EDTA diammonium salt, EDTA dipotassium salt, EDTA disodium salt, EDTA tetrasodium salt, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), EDTA trisodium salt, EDTA tripotassium salt, ethylene glycol-O,O′

-bis(2-aminoethyl)-N,N,N′

,N′

-tetraacetic acid, N-(2-hydroxyethyl)ethylenediamine-N,N′

,N′

-triacetic acid trisodium salt, nitrilotriacetic acid, potassium sodium tartrate, potassium hydrogen D-tartrate, L-tartaric acid dipotassium salt, L-tartaric acid disodium salt, L-tartaric acid monosodium salt, tris(carboxymethyl)amine, heparin, warfarin, acetylsalicylic acid, ibuprofen, indomethacin, prostaglandins, sulfinpyrazone, streptokinase, urokinase, tissue plasminogen activator, coumarin, protamine sulfate, anti-thrombin III, coumadin, protein C/protein S, nicoumalone, phenprocoumon, hirudin, hirulog, glycosaminoglycans, and mixtures of the foregoing.

44. The system of claim 43 wherein the anticoagulant is a mixture of citric acid and trisodium citrate.

45. The system of claim 44 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

46. The system of claim 44 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

47. The system of claim 45 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

48. The system of claim 38 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

49. The system of claim 48 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

50. The system of claim 38 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

51. The system of claim 43 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

52. The system of claim 51 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

53. The system of claim 43 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

54. The system of claim 53 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

61. The system of claim 54 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

55. A hemodialysis access system for use in a blood exchange therapy system, involving an extracorporeal blood processing apparatus operating at a flowrate of at least 100 milliliters per minute and being capable of allowing hundreds of such therapy cycles, the blood exchange therapy system comprising a catheter implanted in the patient and connected to a blood vessel of the patient at a distal end and having a proximal portion within the patient adjacent the patient'"'"'s skin, and the access system comprising:

(a) means forming a continuous, streamlined flowpath running from outside the patient to the catheter, essentially free of surface discontinuities and flow stagnation sites and substantial pressure drops, the means comprising a channel structure providing a flowpath having no more than gentle changes in flow direction, and the means having two elements joining at an abutment with smooth transition at such abutment and all changes in flowpath cross-section being of a gradual nature, the means comprising;

(i) a device implantable within the patient and having a passage therein;

(ii) a needle that is insertable percutaneously into the patient and into the device passage to establish a portion of the flowpath and is withdrawable from the device and the patient; and

(iii) a flexible seal in the device that automatically blocks the flowpath when the needle is not inserted and is entirely out of the flowpath when the needle is inserted and is not degraded by the repetitive therapy cycles of needles insertion, high volume blood exchange and needle withdrawal; and

(b) a biocidal lock comprising;

(i) an anticoagulant; and

(ii) a non-antibiotic biocide;

whereby a blood exchange therapy is maintainable with high resistance to blood clotting, infection, erythrocyte damage and platelet activation and with low pressure drop along the flowpath, consistent with the flow requirements of blood exchange therapy.

56. The system of claim 55 wherein the anticoagulant is selected from the group consisting of di-ammonium hydrogen citrate, di-ammonium tartrate, N-(2-{bis(carboxymethyl)amino}ethyl)-N-(2-hydroxyethyl)glycin salt dihydrate, citric acid, citric acid disodium salt, citric acid monopotassium salt, citric acid monosodium salt, citric acid tripotassium salt, citric acid trisodium salt, ethylenediaminetetraacetic acid (EDTA), EDTA diammonium salt, EDTA dipotassium salt, EDTA disodium salt, EDTA tetrasodium salt, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), EDTA trisodium salt, EDTA tripotassium salt, ethylene glycol-O,O′

-bis(2-aminoethyl)-N,N,N′

,N′

-tetraacetic acid, N-(2-hydroxyethyl)ethylenediamine-N,N′

,N′

-triacetic acid trisodium salt, nitrilotriacetic acid, potassium sodium tartrate, potassium hydrogen D-tartrate, L-tartaric acid dipotassium salt, L-tartaric acid disodium salt, L-tartaric acid monosodium salt, tris(carboxymethyl)amine, heparin, warfarin, acetylsalicylic acid, ibuprofen, indomethacin, prostaglandins, sulfinpyrazone, streptokinase, urokinase, tissue plasminogen activator, coumarin, protamine sulfate, anti-thrombin III, coumadin, protein C/protein S, nicoumalone, phenprocoumon, hirudin, hirulog, glycosaminoglycans, and mixtures of the foregoing.

57. The system of claim 56 wherein the anticoagulant is a mixture of citric acid and trisodium citrate.

58. The system of claim 57 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

59. The system of claim 58 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

60. The system of claim 57 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

62. The system of claim 56 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

63. The system of claim 55 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

64. The system of claim 63 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

65. The system of claim 55 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

66. A hemodialysis access system for repeated access to a patient'"'"'s distal vascular system in the course of long term fluid exchange therapy between the vascular system and a proximal blood processing site, via a catheter that is subcutaneously implanted in the patient and has a distal end coupled to a patient blood vessel and a proximal end, the system comprising, in combination,

(a) a needle assembly comprising an elongated thin walled rigid cannula with ends proximal toward the blood processing site and distal toward the vascular system and an obturator constructed and arranged for insertion into the cannula and passing through its full length, and with a pointed distal end of the obturator emerging from a cannula distal end and removable from the cannula, the cannula being constructed and arranged, when the obturator is removed, for blood flow through the cannula interior at a high flow rate of at least 100 milliliters per minute, the cannula being constructed at its distal end for longitudinal flow of blood at such end to enter or exit the cannula and means for communicating from the back end portion of the cannula interior to an external blood processing site,

(b) a subcutaneously implantable access device having entrance and exit regions and a passage therebetween which permits the cannula to enter the entrance end region and occupy a substantial passage length with a smooth transition between the cannula distal end and the device'"'"'s exit region, the device being arrangeable subcutaneously with its exit region attached to the proximal catheter end and its entrance region accessible to the needle assembly through the patient'"'"'s skin, the cannula interior and exit region thereby defining together a continuous streamlined flowpath having no more than gently changing flow direction and being essentially free of stagnation points or abrupt transitions and constructed and arranged for blood passage through the flow path defined thereby at a flow rate of at least 100 milliliters per minute,

(c) the needle assembly being constructed and arranged to penetrate the patient'"'"'s skin and subcutaneous tissue to reach the entrance region of the device and transit the passage of the latter to a point adjacent the exit region of the device and for withdrawal of the obturator to a point external of the patient'"'"'s skin whereby the external blood processing site can be placed in fluid communication with the cannula and catheter to establish a blood exchange path, and a flushing path, from outside the patient to the patient'"'"'s vascular system,

(d) a seal located within the device'"'"'s passage at a site normally passed by cannula/obturator insertion therein, and comprising means to close off the passage, when acted on by a biasing force, to produce a seal seating stress when the cannula/obturator is not in the passage and openable when contacted by the cannula/obturator constructed and arranged so that the external cannula/obturator surfaces bear against the means to force it aside to an open position, overcoming the bias force, to permit the cannula/obturator to transit the device'"'"'s passage, but without the obturator distal point contacting the resilient sealing material, the cannula being sufficiently rigid to hold the seal open when the obturator is withdrawn from the inserted needle, and

(e) a biocidal lock comprising:

(i) an anticoagulant; and

(ii) a non-antibiotic biocide.

67. The access system of claim 66 wherein the passage comprises a region adjacent its exit for docking with the distal end of the inserted cannula and forming a smooth walled flow path transition therewith.

68. The system of claim 66 wherein the anticoagulant is selected from the group consisting of di-ammonium hydrogen citrate, di-ammonium tartrate, N-(2-{bis(carboxymethyl)amino}ethyl)-N-(2-hydroxyethyl)glycin salt dihydrate, citric acid, citric acid disodium salt, citric acid monopotassium salt, citric acid monosodium salt, citric acid tripotassium salt, citric acid trisodium salt, ethylenediaminetetraacetic acid (EDTA), EDTA diammonium salt, EDTA dipotassium salt, EDTA disodium salt, EDTA tetrasodium salt, ethylenebis(oxyethylenenitrilo)tetraacetic acid (EGTA), EDTA trisodium salt, EDTA tripotassium salt, ethylene glycol-O,O′

-bis(2-aminoethyl)-N,N,N′

,N′

-tetraacetic acid, N-(2-hydroxyethyl)ethylenediamine-N,N′

,N′

-triacetic acid trisodium salt, nitrilotriacetic acid, potassium sodium tartrate, potassium hydrogen D-tartrate, L-tartaric acid dipotassium salt, L-tartaric acid disodium salt, L-tartaric acid monosodium salt, tris(carboxymethyl)amine, heparin, warfarin, acetylsalicylic acid, ibuprofen, indomethacin, prostaglandins, sulfinpyrazone, streptokinase, urokinase, tissue plasminogen activator, coumarin, protamine sulfate, anti-thrombin III, coumadin, protein C/protein S, nicoumalone, phenprocoumon, hirudin, hirulog, glycosaminoglyeans, and mixtures of the foregoing.

69. The system of claim 68 wherein the anticoagulant is a mixture of citric acid and trisodium citrate.

70. The system of claim 69 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

71. The system of claim 70 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

72. The system of claim 69 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

73. The system of claim 68 wherein the biocide is selected from the group consisting of a taurinamide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, arnidine, chelate and imidazoline biocides.

74. The system of claim 73 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

75. The system of claim 68 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.

76. The system of claim 66 wherein the biocide is selected from the group consisting of a taurinarnide derivative, a phenol, quaternary ammonium surfactant, chlorine-containing, quinoline, quinaldinium, lactone, dye, thiosemicarbazone, quinone, sulfa, carbamates, urea, salicylamide, carbanilide, amide, guanide, amidine, chelate and imidazoline biocides.

77. The system of claim 76 wherein the biocide is a taurinamide derivative of the formula:

wherein R¹ is hydrogen or alkyl and R² is hydrogen, alkyl, or a group of the formula;

78. The system of claim 66 wherein the biocide is selected from the group consisting of acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, esters of p-hydroxybenzoic acid, ethanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, 2-bromo-2-nitropropan-1,3-diol, formaldehyde, glutaraldehyde, calcium hypochlorite, potassium hypochlorite, sodium hypochlorite, iodine (in various solvents), povidone-iodine, hexamethylenetetramine, noxythiolin, 1-(3-choroallyl)-3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, EDTA, N(5-nitro-2-furfurylidene)-1-amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3,4,4′

-trichlorocarbanilide, 3,4′

,5-tribromosalicylanilide, salicylanilide, 3-trifluoromethyl-4,4′

-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachlorometaxylenol, 2,4,4′

-trichloro-2′

-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, and silver nitrate.