Antiseptic cap with thread cover

ES 2 808 632 T3

DESCRIPTION

Antiseptic cap with threaded cover

BACKGROUND OF THE INVENTION:

Technical field

The present invention relates to an antiseptic cap having a threaded cover to enhance a seal between the cap and an access site to a mammalian body. More particularly, the invention relates to an antiseptic cap for attachment to an access site of a permanent central venous catheter and having a threaded cover to enhance a closure between the cap and the access site.

Previous technique

Catheters are widely used to treat patients who require a variety of medical procedures. Catheters can be acute, or temporary, for short-term use or chronic for long-term treatment. Catheters are commonly inserted into central veins (such as the vena cava) from peripheral vein sites to provide access to a patient's vascular system. Catheters offer many benefits for patients; For example, chronic catheters provide easy access without repeated punctures or repeated vessel cannulation for the administration of large volumes of fluids, nutrients, and medications, and for intermittent blood collection. With regard to the use of catheters for fluid infusion, examples include the infusion of drugs, electrolytes or fluids used in chemotherapy. In chemotherapy, catheters are used to infuse drugs on an intermittent basis, ranging from daily to weekly. Another example includes the use of catheters in the treatment of hyperalimentation, in which catheters are typically used for the infusion of large volumes of fluids.

For hemodialysis, catheters are commonly used, usually three times a week, for the aspiration of blood for dialysis treatment and the rapid return of blood to the circulation after treatment. Although a preferred mode of vascular access for a hemodialysis patient involves the use of an arteriovenous (AV) fistula of the upper or lower extremities or an arteriovenous bypass graft (which typically uses PTFE), the use of these access devices does not it is always possible or desirable. When none of these modes of vascular access is available, for example, due to a shortage of suitable blood vessels for AV shunt creation or due to established AV shunts that do not function optimally, a large diameter line venous catheter is typically required. for hemodialysis. Catheters used for hemodialysis typically include two relatively large diameter lumens (typically molded like a catheter) for the rapid aspiration and return of blood required during the hemodialysis procedure. One lumen of said catheter is used for aspiration, or extraction, of blood, while the other lumen is used for returning the blood to the patient's bloodstream.

Catheter connections, such as, for example, catheter connections to dialysis machine tubing, IV tubing, infusion ports, and catheter caps, used to close the end of a catheter to Protecting catheter sterility and preventing fluid loss and / or particle contamination are most often made using standardized Luer cone fittings from the medical industry. These accessories, which can be either male couplings or female couplings, include a tapered end of standardized dimensions. The coupling is done by snapping the coupling parts. A threaded locking fitting or other type of locking mechanism is commonly used to ensure the integrity of the snap fit of Luer fittings.

Catheters, especially chronic venous catheters, pose challenges in their use. One of those challenges is that such catheters can become occluded by a thrombus. To prevent clotting of catheters in blood vessels between uses, such as, for example, between dialysis treatments when the catheter is essentially not working and is located within a central vein (i.e. superior vena cava, vena cava inferior, iliac, etc.), the catheter lumens are often filled with a blocking solution of a concentrated solution of the commonly used anticoagulant, heparin (up to 10,000 units of heparin per catheter lumen).

As used herein, the terms "blocking solution" or "blocking solution" refer to a solution that is injected or otherwise infused into the lumen of a catheter with the intention of allowing a substantial portion of the blocking solution remain in the lumen and not in the systemic bloodstream until access to that particular lumen is desired or required again, typically for further treatment, ie, fluid infusion or withdrawal. In addition, attention has been paid to the development of alternative blocking solutions with the aim of improving the patency rates of vascular catheters. For example, blocking solutions containing low molecular weight alcohols are under development in which the low molecular weight alcohols include ethanol, propanol, and butanol. Antimicrobial and / or anticoagulant additives can optionally be added to the blocking solution containing low weight alcohol

ES 2 808 632 T3 molecular. Preferably, the blocking solution can remain in the light for a desired amount of time lasting from about 1 hour to 3 or 4 days or more.

For the reasons stated above, great care must be taken when infusing medications, nutrients, and the like into a catheter, and when a catheter is blocked between uses, to minimize the risks associated with an indwelling catheter, including the risk of thrombosis or clotting, the risk of excessive anticoagulation and the risk of infection. Typically, syringes are used to deliver the required amount of catheter blocking solution (determined by the catheter manufacturer) into an indwelling catheter after a given use. Flushing procedures also require that care be taken to prevent backflow of blood into the catheter. Backflow in IV treatment is the term commonly used to describe fluid backing up into the catheter after a flushing procedure. The concern is that the refluxing fluid contains blood or solution that could cause the catheter to occlude. To ensure that reflux does not occur, the flushing procedures suggest two techniques: 1) at the end of the flushing solution administration, the user maintains pressure on the syringe plunger while clamping the IV line; or 2) while the last 0.5 ml of wash solution is being administered, the syringe is disconnected from the IV port or the IV is clamped Either technique maintains a positive pressure on the fluid in the catheter to prevent back flow of fluid and blood.

In view of the problems described above, there is a continuing need for advances in catheter locking techniques, devices, and procedures to improve the safety and effectiveness of catheter locking procedures and general patient care.

US5,554,135 A discloses sterile medical injection ports and covering apparatus for hospital and home use. DE89 06 628 U1 discloses a Luer nut for catheters.

SUMMARY OF THE INVENTION:

According to one aspect of the invention, a cap is provided as mentioned in claim 1. Optional features of the invention are mentioned in the dependent claims.

BRIEF DESCRIPTION OF THE DRAWINGS:

FIG. 1 is a perspective view of a syringe barrel and plunger assembly equipped with an antiseptic cap prior to connection of a syringe tip to a central venous catheter access point;

FIG. 2 is a perspective view of a syringe barrel and plunger assembly equipped with an antiseptic cap with the tip of the syringe connected to a central venous catheter access point;

FIG. 3 is a perspective view of a plunger and syringe barrel assembly equipped with an antiseptic cap prior to connection of the antiseptic cap to a central venous catheter access point;

FIG. 4 is a perspective view of a plunger and syringe barrel assembly equipped with an antiseptic cap after connection of the antiseptic cap to a central venous catheter access point;

FIG. 5 is an overall perspective view drawing of a plunger equipped with an antiseptic cap;

FIG. 6 is a perspective view of a plunger equipped with an antiseptic cap in a partially assembled state;

FIG. 7 is a perspective view of the plunger equipped with the antiseptic cap of FIG. 6 with a closure at the top;

FIG. 8 is a perspective view of a plunger equipped with an antiseptic cap of FIG. 7 mounted on a syringe barrel lumen;

FIG. 9 is a sectional side view of a syringe barrel and plunger assembly equipped with an antiseptic cap;

FIG. 10 shows an exploded view of a detail of FIG. 9 of an embodiment of the syringe barrel and plunger assembly equipped with an antiseptic cap;

FIG. 11 shows an exploded view of a detail of FIG. 9 of another embodiment of the syringe barrel and plunger assembly equipped with an antiseptic cap;

FIGS. 12-14 show various embodiments of plunger assembly grips equipped with an antiseptic cap;

ES 2 808 632 T3 FIGS. 15-17 show various views of one embodiment of the syringe barrel and plunger assembly equipped with an antiseptic cap with a barrel lock to resist rotation of the plunger assembly relative to the syringe barrel;

FIG. 18 shows another embodiment of a barrel lock to resist rotation of the plunger assembly relative to the syringe barrel;

FIGS. 19-20 show various views of another embodiment of the anti-reflux syringe barrel and plunger assembly equipped with an antiseptic cap with a barrel lock to resist rotation of the plunger assembly relative to the syringe barrel;

FIG. 21 shows a perspective view of another embodiment of the syringe barrel and plunger assembly equipped with an antiseptic cap with a barrel lock to resist rotation of the plunger assembly relative to the syringe barrel;

FIGS. 22a, b are, respectively, a perspective view of an antiseptic cap without a sponge and with a sponge;

FIGS. 23 and 24 are different embodiments of the antiseptic cap with various characteristic grip features;

FIG. 25 is a perspective view of the antiseptic cap of FIG. 22b prior to coupling with a valve;

FIG. 26 is a perspective view of the antiseptic cap of FIG. 22b coupled with a valve;

FIG. 27 is a sectional side view of the antiseptic valve and cap assembly shown in FIG. 26;

FIGS. 28-30 are sectional side views of two different embodiments of the antiseptic cap;

FIGS. 31a, b are, respectively, sectional side views showing an antiseptic cap with a centrally disposed actuating post mounted on a valve with the valve in the off and on positions;

FIGS. 32 and 33 are sectional side views showing two different embodiments of an antiseptic cap having a molded sponge;

FIG. 34 is a sectional side view showing another embodiment of an antiseptic cap having a molded sponge attached to a valve;

FIG. 35 is a sectional side view showing a step of attaching a molded sponge to an antiseptic cap;

FIG. 36 is a sectional side view showing a step of delivering an antiseptic compound to a molded sponge located within a lid;

FIG. 37 shows a sectional side view of an antiseptic cap that engages a valve with the antiseptic cap having an antiseptic coating;

FIG. 38 shows a perspective view of an antiseptic cap on a blister pack;

FIG. 39 is a cross-sectional side view of an antiseptic cap with a threaded cover;

FIG. 40 is a cross-sectional side view of an antiseptic cap with a threaded cover;

FIG. 41 is a cross-sectional side view of an antiseptic cap with a threaded cover;

FIGS. 42a, b are front and rear perspective views of an antiseptic cap with a threaded cover attached to a Cardinal SMART SITE access site;

FIGS. 43 a, b are front and rear perspective views of an antiseptic cap without a threaded cover connected to a Cardinal SMART SITE access site;

FIGS. 44 a, b are front and rear perspective views of an antiseptic cap with a threaded cover connected to a Hospira CIOOo Key Access Device (ICU);

FIGS. 45 a, b are front and rear perspective views of an antiseptic cap without a threaded cover connected to a Hospira Clave C1000 access device (ICU);

ES 2 808 632 T3 FIGS. 46 a, b are front and rear perspective views of an antiseptic cap with a threaded cover connected to a B. Braun ULTRASITE access site;

FIGS. 47 a, b are front and rear perspective views of an antiseptic cap without a threaded cover connected to a B. Braun ULTRASITE access site;

FIGS. 48 a, b are front and rear perspective views of an antiseptic cap with a threaded cover connected to a Rymed INVISION PLUS access site;

FIGS. 49 a, b are front and rear perspective views of an antiseptic cap without a threaded cover connected to a Rymed INVISION PLUS access site;

FIG. 50 is a cross-sectional side view of an antiseptic cap with a threaded cover connected to a Cardinal SMARTSITE PLUS access device ;

FIG. 51 is a cross-sectional side view of an antiseptic cap with a threaded cap connected to a Cardinal SMARTSITE PLUS access device and the threaded cap having a reduced diameter compared to the threaded cap shown in FIG. fifty;

FIG. 52 is a cross-sectional side view of an antiseptic cap with a threaded cover connected to a Hospira Clave C1000 Access Device (ICU) having a threaded cover with an alternate profile;

FIG. 53 is an assembly view of a plunger and syringe barrel system equipped with an antiseptic cap and cap holder;

FIG. 54 is an assembly view of an antiseptic cap-cap holder assembly adjoining a syringe barrel and plunger system;

FIG. 55 is a cross-sectional side view of a plunger and syringe barrel assembly equipped with an antiseptic cap and cap holder;

FIG. 56a is a perspective view of a medical access device adjoining a plunger and syringe barrel assembly equipped with an antiseptic cap with a back peeled cap material in preparation for attachment;

FIG. 56b is a perspective view of a medical access device attached to a syringe barrel and plunger assembly equipped with an antiseptic cap;

FIG. 56c is a perspective view of a medical access device attached to an antiseptic cap adjoining a syringe barrel and plunger assembly;

FIG. 57 is an enlarged view of an antiseptic cap and cap holder assembly adjoining an open and empty chamber of a syringe plunger;

FIG. 58 is an enlarged view of an antiseptic cap and cap support assembly located within a chamber of a syringe plunger;

FIG. 59 is a perspective view of an alternate embodiment of an antiseptic cap assembly adjoining a syringe barrel and plunger assembly;

FIG. 60 is a perspective view of an alternate embodiment of an antiseptic cap assembly coupled to a syringe barrel and plunger assembly; and FIG. 61 is a perspective view of an alternate embodiment of an antiseptic cap assembly coupled to a syringe barrel and plunger assembly with an outer wall that is transparent to reveal interior parts of the assembly.

DETAILED DESCRIPTION OF THE INVENTION:

While this invention is capable of embodiment in many different forms, specific embodiments thereof are shown in the drawings, and will be described herein in detail with the understanding that the present disclosure should be considered an exemplification of the principles of the invention and is not intended to limit the invention to the specific embodiments illustrated.

FIGS. 1 and 2 show a syringe barrel and plunger assembly equipped with an antiseptic cap 10 having a plunger assembly equipped with an antiseptic cap 12 and a syringe barrel 14. The barrel 14 has a side wall 16 that defines a chamber 18 and the cylinder has a proximal end 20 and a distal end 22. The proximal end 20 has an opening 23 to chamber 18 and a flange 24 extending radially outward from wall 16. The flange 24 has upper and lower surfaces 26, 28 and provides

ES 2 808 632 T3 grip for a user of assembly 10. The distal end 22 of cylinder 14 has a wall at one end 30 and an elongated tip 32 extending distally therefrom and having a conduit 34 therethrough and in fluid communication with the camera 18. The distal end wall 30, in a preferred form of the invention, is generally conical in shape and, as is well known in the art, may have a locking Luer neck 35 that concentrically surrounds the tip 32 and has a set of threads 37 on the inner surface thereof. Luer neck 35 allows a needle or cannula to be attached to barrel 14 and to attach assembly 10 to localized mating threads on other devices such as valves, injection sites, and other medical access devices well known in the art. FIG. 1 shows the syringe assembly near an access site 38 having a valve 39 that controls access to a lumen of a tube 41.

In a preferred form of the invention, chamber 18 of syringe assembly 10 will be filled with a blocking solution or a flushing solution for use with an indwelling central venous catheter. The manner of using a blocking or flushing solution with a catheter is well known in the art. Suitable blocking or flushing solutions are listed below. The flushing or blocking solution is injected into a fluid access site of the catheter to clean and disinfect the catheter and can be removed from the catheter or allowed to remain at an end portion of the catheter to serve as a barrier to entry of pathogens and pollutants.

The antiseptic cap plunger assembly 12 has an elongated shaft 40, a proximal end 42, and a distal end 44. The elongated shaft 40, in a preferred form of the invention, is generally cruciform in cross-sectional shape. A plug or piston 50 is connected to the distal end 44 of shaft 40. The piston 50 is dimensioned so that, when inserted into the syringe barrel chamber 18, an outer circumferential surface of the piston 50 is in fluid-tight engagement with an inner surface 54 of the syringe barrel. The piston assembly 14, when moved proximally (or when withdrawn), can introduce fluid into the chamber and, when moved distally (or when inserted into the syringe chamber), can expel fluid out of the chamber. FIG. 1 shows the piston assembly 14 partially inserted into the syringe chamber and FIG. 2 shows the piston assembly fully inserted into the syringe chamber to supply fluid to tube 41.

A housing 60 is located at the proximal end 42 of the plunger assembly 12 and has a wall 62 that defines a chamber 64 having an open end 66 that can be closed by any suitable structure or material, such as a cap or by a material. sheet 68. An optional annular rim 70 extends radially outward from wall 62 and provides a surface on which the closure structure can be attached.

FIG. 5 shows a cover assembly 80 near chamber 64 of housing 60 and FIG. 6 shows the cap assembly 80 located within chamber 64. In a preferred form of the invention, the cap assembly 80 has a cap 82 having a wall 83 defining a chamber 84 containing an absorbent material 86 such like a sponge. The sponge 86, in a preferred form of the invention, is moistened or soaked with an agent such as an antiseptic, anticoagulant, or antimicrobial (antiseptic solution) and can be selected from the blocking and washing solutions set out below or the solutions antiseptics listed below. Cap 82 has an interior surface 87 with a set of threads 88 for engagement with a set of threads at the access site 38.

FIGS. 7 and 8 show the lid assembly 80 closed with a sheet material or a lid material 68 that can be attached to the flange 70 by any suitable method such as by adhesives or by conductive or inductive heat sealing techniques. FIG. 7 shows the antiseptic cap piston assembly 12 and FIG. 8 shows the antiseptic cap equipped piston assembly 12 inserted into the syringe barrel chamber 14 to define the antiseptic cap equipped piston and syringe barrel assembly 10.

FIGS. 3 and 4 show a possible method of utilizing the lid assembly 80 by coupling with the access device 38. FIG. 3 shows cap material 68 peeled off flange 70 and FIG. 4 shows the attachment of the antiseptic cap assembly 80 to valve 39. The syringe barrel is rotated clockwise or counterclockwise to engage the threads 88 of the antiseptic cap assembly 80 with the threads of the access site 38. After docking, syringe barrel 14 will move away from access site 38 and antiseptic cap assembly 80 will slide out of housing 60 and remain engaged in access site 38. Antiseptic cap assembly 80 may remain coupled to valve 39 of access site 38 for any suitable period of time from a few minutes to many hours. When the antiseptic cap assembly 80 is attached to the valve 39, the tube or catheter 41 is closed to block pathogens and contaminants from entering the catheter and a portion of the access site 38 is exposed to the antiseptic material in the sponge 86 .

It is desirable that during rotation of the syringe barrel, the antiseptic cap assembly 80 does not rotate relative to the housing and / or optionally that the plunger assembly 12 does not rotate relative to the syringe barrel 14 until the threads 88 of the antiseptic cap are fully engaged with the threads of the access site 38. The present invention provides a mechanism associated with assembly 10 to prevent rotation of antiseptic cap assembly 80 relative to plunger assembly 14 and more preferably a

ES 2 808 632 T3 mechanism on either the plunger assembly or the antiseptic cap assembly 80 to prevent relative rotational movement between the antiseptic cap assembly 80 and the plunger assembly 12. In an even more preferred form of the invention, the mechanism for preventing relative rotation of the antiseptic cap assembly 80 with respect to the plunger assembly 12 has mating portions on both parts that, when assembled, cooperatively engage with each other to avoid relative rotation. It is also contemplated that a separate mechanism, device or member could be used to lock the two parts together to achieve this purpose.

If a user grasps the assembly 10 by the antiseptic cap and the plunger assembly 12, the interlocking structures between the plunger assembly 12 and the syringe barrel 14 would not inevitably be necessary. Consequently, FIGS. 5, 9-11 show exemplary structures for locking the antiseptic cap assembly 80 within the housing 60 so that these parts rotate together and one part does not rotate in one direction or at a different speed than the other part. Furthermore, FIGS. 15-18 show exemplary structures for interlocking the antiseptic cap plunger assembly 12 with the syringe barrel 14.

In a preferred form of the invention, housing 60 will have a characteristic feature or structure that forms an interference fit with an outer surface 83 of antiseptic cap 80. Even more preferably, an inner surface 63 of side wall 62 of housing 60 will have a characteristic feature or structure to form an interference fit with a portion of the antiseptic cap assembly 80. In another preferred form of the invention, the antiseptic cap assembly 80 will have a characteristic feature to form an interference fit with the housing 60 and even more preferably the outer surface 83 of the antiseptic cap 80 will have a characteristic feature for contacting. the inner surface 63 of the side wall of the housing 62.

In another preferred form of the invention, the plunger housing 60 and the cap assembly 80 will each have a characteristic feature or structure that cooperatively engage with each other to prevent relative rotation of the cap 80 assembly and the housing 60. FIG. 5 shows a preferred form of the invention having a plurality of circumferentially spaced and axially extending ribs 100 on internal surface 63 of housing side wall 62 (internal ribs 100) for engagement of wall 83 of antiseptic cap 82 to lock the cap assembly 80 in place to prevent rotation of the cap assembly 80 when positioned within the housing 60. In a preferred form of the invention, internal ribs 100 extend from a bottom wall 102 to an intermediate height of the housing side wall 62. In a preferred form of the invention, internal ribs 100 will have a height approximately equal to that of height of lid 82. A plurality of internal grooves 108 are defined between each set of contiguous internal ribs 100. The internal ribs 100, in a preferred form of the invention, will have a width that tapers inward from near the bottom wall 102 to an upper portion 104 of the internal ribs 100, so that the width of the internal ribs decreases from a lower part 106 of a rib to the upper part 104 of the rib. In addition, it is preferred that the top of the internal ribs 100 have a generally curved profile to act as an entry guide during insertion of the antiseptic cap assembly 80 into the housing 60. In a preferred form of the invention, the Internal ribs 100 will terminate near the top 113 of the housing side wall 62 to define an annular gap 111 between the top of the rib 104 and the top 113. In addition, extending radially inward from the inner surface 63 of the cap 82 is a detent 109 located near a top 113 of the side wall 62.

The antiseptic cap 82 has a plurality of circumferentially spaced and axially extending ribs 120 that extend along an outer surface 121 of the wall 83 of the cap 82 (outer ribs 120). In a preferred form of the invention, external ribs 120 extend between an annular rim 123 at a proximal end 124 of cap 82 to a position near a distal end 126 of cap 82. The outer ribs 120 are dimensioned for engagement to a portion of the surface of the inner wall 63 of the housing 62 to prevent relative rotation of the cap assembly 80 and the plunger assembly 12. The space between the outer ribs defines a plurality of external grooves 122 between each contiguous pair of external ribs 120. When cover 82 is positioned within chamber 64 (FIG. 9 and 11) each of the external ribs 120 is located within an internal slot 108 and each of the internal ribs 100 is located within an external slot 122 to lock these parts together to ensure that the lid rotates in the same direction. than the plunger rod assembly 12. FIGS. 6 and 11 also show that when cap 82 is positioned within housing 60, retainer 109 contacts annular rim 123 to hold cap assembly 80 in plunger housing chamber 64 to prevent or resist dropping. accidental cover assembly 80 from housing chamber 64 prior to engagement of cover assembly 80 with access site 38.

FIGS. 12-14 show various embodiments of gripping surfaces on housing 60 (with cap material 68 removed) to facilitate use of assembly 10 or plunger assembly 12. FIG. 12 shows circumferentially spaced axially extending protrusions 130 on an outer surface of wall 62. The protrusions 130 can have numerous different cross-sectional shapes including circular, polygonal, oval, and irregular and, in a preferred form of the invention, extend from the flange 70 to a bottom of the housing.

ES 2 808 632 T3

FIG. 13 shows a housing 60 that does not have a flange 70 and has protrusions 130 in wall 62 that extend substantially the entire height of housing 60. FIG. 14 shows a housing 60 where the outer surface of wall 62 is relatively smooth but as a series of circumferentially spaced and axially extending protrusions 130 on a circumferential edge of flange 70.

As with the characteristic features or blocking structures of the rotation of the cap and plunger assembly, the characteristic feature or blocking structure of the optional plunger assembly 12 and the syringe barrel 14 can be located only in the assembly. of the plunger 12, or only in the barrel of the syringe 14 or have cooperating structures both in the assembly of the plunger 12 with the barrel of the syringe 14. It is also contemplated that a separate mechanism, device or member could be used to lock the two parts together to achieve this purpose.

FIGS. 15-18 show various embodiments for the optional feature of locking plunger assembly 12 from rotational movement relative to syringe barrel 14. In one embodiment shown in FIGS. 15-17 and 21 a wing 150 extending axially along an outer surface of the housing side wall 62 engages a tooth 152 located on an inner surface of the syringe barrel 14 at its proximal end 20. More preferably, the plunger assembly 12 will have more than one wing 150, each wing being circumferentially spaced from the other. In an even more preferred form of the invention, the plunger assembly will have four wings 150 spaced 90 degrees from each other. Furthermore, in a more preferred form of the invention, the syringe barrel 14 will have a plurality of circumferentially spaced teeth 152. When the plunger assembly 12 is almost fully inserted into the syringe barrel 14, each of the wings 150 will extend into a tooth 152 to prevent rotation of the plunger assembly 12 relative to the syringe barrel 14.

FIG. 18 shows another embodiment of a characteristic locking feature to prevent rotation of the plunger assembly 12 with respect to the syringe barrel 14 and also prevents relative translational movement of the parts. In this embodiment, an annular protrusion 160 located on an inner surface of the syringe barrel at its proximal end 20 engages an annular retainer 162 on an outer surface of the plunger rod.

FIGS. 19 and 20 show a plunger assembly equipped with an antiseptic cap 12 and a non-reflux syringe assembly 170. Non-reflux syringes are well known in the art and there are numerous methodologies for reducing reflux while accessing the access site of a central venous catheter. In this embodiment, annular rim 70 of plunger assembly 12 abuts rim 24 of syringe barrel before plunger 50 contacts an interior surface of the distal end wall of syringe 30.

It is contemplated that the antiseptic cap assembly 80 of the present invention need not be coupled or combined with a plunger or syringe barrel. FIGS. 22a, b show a separate antiseptic cap assembly 200 having three circumferentially spaced ribs 120 for a user's hand-grip of the cap assembly. FIG. 22a shows cap 82 without absorbent material 86 and FIG. 22b shows the cap with an absorbent material. Cap 200 can be used for the same purposes as cap assembly 80 described above, but will be used by hand. All other characteristic features of cap 200 are essentially the same as described with the exception that cap 200 does not have to be sized to fit within a chamber carried by a syringe plunger. FIGS. 23 and 24 show a variable frequency of ribs 120 and variable shapes and sizes.

FIG. 25 shows cap 200 near access site 38 and FIGS. 26 and 27 show cap 200 attached to access site 38.

A suitable absorbent material 86 includes medical grade materials that can store and release an antiseptic fluid, or a liquid that serves other medical purposes, and includes materials such as sponges, breakable capsules, and other materials or devices that can serve this purpose. Suitable sponges can include any sponge suitable for use for medical purposes and can be natural or synthetic. The sponges can be punched into suitable shapes or they can be molded into the desired shape. It is desirable that the sponge 86 is attached to the antiseptic cap 82 to prevent the sponge 86 from accidentally falling off the cap 82. FIG. 28 shows that the sponge 86 is captured between an annular wall 202 and a disk 204 attached to the lid 82 by any suitable method such as ultrasonic or vibration welding or other techniques well known in the art.

FIGS. 29 and 30 show a variation on the cap assembly 200 of FIG. 28. In this embodiment, the sponge is retained in the lid 82 with a plastic sheet 206 heat welded to the lid. In a preferred form of the invention, the sponge is attached by an adhesive or other method to form an assembly which is then attached to the lid.

FIGS. 31a, b show cap 200 having a coaxially disposed and axially extending drive post 220 circumferentially surrounded by a sponge 86 having an orifice located

ES 2 808 632 T3 centrally to fit over post 220. FIG. 31a shows cap 200 in initial engagement with access site 38 and FIG. 31b shows the screw cap at the access site 38 and the actuating post opens the valve 39 and the antiseptic fluid is allowed to flow into the valve.

FIGS. 32-34 show sponges of varying shapes which, in a preferred form of the invention, were molded into various desirable shapes. The sponge of FIG. 34 has a central opening 230 to facilitate attachment of the sponge to the cap and filling of the sponge with antiseptic, anticoagulant, or other suitable fluids discussed above. FIG. 35 shows the cap having a centrally disposed energy director 231, an ultrasonic welder 232 that is brought into cooperative engagement with the sponge on a side of the sponge opposite the energy director 231. By applying ultrasonic energy, the energy director 231 melts and fixes the sponge to the lid. FIG. 36 shows a filling device 240, having a lumen 242 and a dispensing head 244 in fluid communication with a source of antiseptic, anticoagulant, or the like for dispensing a metered amount of said fluid into the interior of the sponge.

FIG. 37 shows an alternative embodiment of the antiseptic cap 200 where the sponge is replaced by an antiseptic coating on the actuation post 220.

FIG. 38 shows the antiseptic cap 200 positioned on a blister 233 prior to closing the blister.

FIG. 39 shows an antiseptic cap 300 with a threaded cap 302. The threaded cap 302 can be part of any of the antiseptic caps discussed herein. Threaded cover 302 is made of a deformable material that can flex with the application of moderate force applied by hand. In a preferred form of the invention, the threaded cover 302 is made of a polymer-containing material and more preferably a polymeric material having a modulus of elasticity of less than 20,000 psi. In another preferred form of the invention, the polymeric material will be an elastomer or plastomer or similar material. The threaded cover 302 enhances the connection between the antiseptic cap 300 and a device such as a valve or other access devices 38. The threaded cover 302 provides a physical barrier to the entry of pathogens, dust, or other contaminants through the mating threads of the antiseptic cap 300 and the access device or valve to which it is attached. The threaded cover 302 also serves to retain the antiseptic fluids from the antiseptic cap 300 from seeping through the threads. The threaded cover can be made part of the antiseptic cap 300 using techniques well known in the art, such as overmolding, or attached as a separate part using welding techniques such as heat conduction welding, heat induction welding, welding. by vibration, friction stretch fit, or using a suitable adhesive.

Threaded cover 302 can provide a universal fit to most commercially available valves, connectors, and access devices, or threaded cover 302 can be customized to fit a particular access device.

FIG. 39 shows, as described above, that the antiseptic cap 300 has an annular wall 305 having a first end 306 and a second end 320, the first end having a greater diametral dimension than the second end. The annular wall defines a central chamber 322 having an open end 323. In a preferred form of the invention, chamber 322 will have a sponge 86 positioned therein as shown in FIG. 5 and 6 above, although not shown in FIG. 39. Threaded cover 302 is shown attached by an optional tie layer 304 to first end 306 of annular wall 305. Threaded cover 302 has a first leg 308 and a second leg 310. First leg 308 extends parallel to annular wall 305 and second leg 310 extends radially inward from annular wall 305 in a direction transverse to first leg 308 and through a portion of open end 323 and defines a central opening. 312, which has a reduced diameter compared to open end 323, to chamber 322. Second leg 310 terminates at a distal end 330 with a rounded outer surface 332.

FIG. 40 shows an alternative embodiment of the antiseptic cap 300 having the threaded cover 302 having both the first and second legs 308, 310 attached to the first end 306 of the annular wall 305 through the tie layers 304 a, b . An upper surface 340 of the first end 306 is shown having the same diameter or thickness as the remainder of the first end, but it is contemplated that the upper surface could have a radially extending flange 123 as shown in FIG. 5.

FIG. 41 shows an alternative embodiment of the antiseptic cap 300 that differs from the antiseptic cap shown in FIGS. 39 and 40 for not including a counterbore 336 shown in these figures. Counterbore 336 provides a reduced diameter chamber and therefore will form a tighter fit with narrower outer diameter access devices compared to the cap shown in FIG. 41 which does not include the counterbore. This is just one example of the modifications that can be made to the geometry of the antiseptic cap to enhance the connection between the cap and an access site.

FIGS. 42 a, b show front and rear views of antiseptic cap 300 with threaded cover 302 attached to a Cardinal 350 SMART SITE access site. FIGS. 43 a, b are front and back views in

ES 2 808 632 T3 perspective of the antiseptic cap without the threaded cover 302 connected to a Cardinal SMART SITE access site.

FIGS. 44 a, b are front and rear perspective views of antiseptic cap 300 with threaded cover 302 connected to a Hospira Clave C1000 access device (ICU) 352. FIGS. 45 a, b are front and rear perspective views of the antiseptic cap, without a threaded cover 302, connected to a Hospira Clave C1000 access device (ICU).

FIGS. 46 a, b are front and rear perspective views of antiseptic cap 300 with threaded cap 302 connected to a B. Braun 354 ULTRASITE access device. FIGS. 47 a, b are front and rear perspective views of the antiseptic cap without the threaded cover 302 attached to the B. Braun ULTRASITE access device.

FIGS. 48 a, b are front and rear perspective views of the antiseptic cap with threaded cover 302 connected to a Rymed 356 INVISION PLUS access device. FIGS. 49 a, b are front and rear perspective views of the antiseptic cap without the threaded cover 302 attached to a Rymed INVISION PLUS access site.

FIGS. 50-52 show various embodiments of the threaded cover 302. FIG. 50 differs from FIG. 51 in which the second leg 310 extends further through the chamber opening in FIG. 51 shown in FIG. 50. FIG. 52 shows another embodiment of the threaded cover 302 having a second segmented leg 310a, b. This embodiment may be desirable to provide a more efficient closure for certain access devices.

FIG. 53 shows an exploded view of an alternative embodiment 400 of the syringe barrel assemblies 10, discussed above, incorporating a cap support 402 into the system of parts. Thus, the alternative assembly and system 400 has an antiseptic cap and plunger assembly equipped with cap holder 12 ', syringe barrel 14, antiseptic cap 82 (shown with optional screw cap 302), absorbent material 86 and a release lid material 68. FIG. 54 shows an exploded view of an antiseptic cap holder assembly 404 that includes the cap holder 402 with the antiseptic cap assembly 80 positioned within a chamber 406 of the cap holder 402. This embodiment 400 allows the manufacture of, the separate assembly and sterilization of the syringe barrel and plunger assembly assembly 400.

Cap support 402 has proximal and distal ends 408, 410, and an inner wall surface 412 and an outer wall surface 414, an opening 416 to chamber 406, and a radially outwardly extending rim. 418 circumferential to opening 416 and extending from proximal end 408 of cap holder 402. Cap holder 402 will also have an optional bottom wall 419.

In a preferred form of the invention, the cap holder 402 or the antiseptic cap 82 will have a structure, element or the like that prevents relative rotation of the cap holder 402 and the antiseptic cap 82 until the antiseptic cap assembly 80 is securely attached to access device 38. Furthermore, in a preferred form of the invention, the cap holder 402 or the plunger assembly 12 'will have a structure, element or the like to prevent relative rotation of the cap holder 402 and the plunger assembly 12' to the antiseptic cap assembly 80 is securely attached to access device 38. Any of the anti-rotation devices discussed above for stopping the rotation of the antiseptic cap assembly 80 with the plunger assembly 12 would be suitable for these purposes. Furthermore, it is contemplated that the devices discussed above with reference to FIGS. 15-21 to avoid relative rotation of plunger assembly 12 and syringe barrel 14 could be incorporated into this embodiment 400.

FIG. 53 shows that the surface of the inner wall 412 of the lid holder 402 carries the internal ribs 100 and the internal grooves 108 that interact with the external ribs and the external grooves 120, 122 of the lid 82 as described above with respect to FIG. 5. These structures prevent or resist the relative rotation of the cap holder 402 with respect to the antiseptic cap assembly 80. The term ribs referred to herein are structures that rise or extend outward from a surface. The term "grooves" refers to structures that extend below a surface or are defined between two ribs and are at a lower level than the ribs.

FIG. 53 also shows an interlocking structure to prevent relative rotation of the cap holder 402, or the cap holder assembly 404, with respect to the plunger assembly 12 '. The outer wall surface 414 has a plurality of circumferentially spaced and axially extending ribs 420 that define grooves 424 between each adjacent pair of ribs. In a preferred form of the invention, ribs 420 are generally triangular in shape having a base portion 426 and an apex portion 428. Grooves 424 are oppositely oriented triangular-shaped areas having groove base portions 430 that they extend between two vertex portions of a contiguous rib 428 and vertex portion of groove 432 that separate base portions of an adjacent rib 426. On the surface of the inner wall 63 of the plunger chamber 64 there are plunger ribs 434 and plunger grooves 436 similarly. The

The ribs 420 are dimensioned to fit within the grooves of the plunger 436 and the grooves 424 are dimensioned to fit therein and receive the ribs of the piston 434. Thus, when the cap holder 402 or the cap holder assembly 404 is inserted into the plunger chamber 64, the ribs on the lid holder 420 intersperse with the ribs on the plunger 434 to prevent or resist rotation. relative of cap holder 402, or cap holder assembly 404, relative to plunger assembly 12 '.

In yet another preferred form of the invention, the cap support 402, the cap support assembly 404, or the plunger assembly 12 'will have a structure, element, or the like that resists relative axial movement of these parts when the support of cap 402 or cap holder assembly 404 is fully positioned within plunger assembly 12 '. In a preferred form of the invention, the cap holder 402 has an annular protrusion 440 that is dimensioned to fit within an annular groove 442 in the surface of the inner wall 414 of the cap holder and preferably extends in line with the base portions of the ribs of the plunger 434. A second locking structure is provided having a plurality of teeth 450 that extend axially outward from the surface of the outer wall 414 of the cap holder and are located in the grooves 424. In a preferred form of the invention, the pins teeth extend axially outward to a height beyond the height of the ribs 434. The teeth 450 may be located in one or more of the grooves or in each of the grooves 424 or in alternate grooves or, as shown, circumferentially spaced 90 ° from each other. The teeth 450 are preferably located in an intermediate portion, between the base and the apex, of a slot 424. The teeth 450 are dimensioned to fit within a segmented annular groove 452 that extends circumferentially around the inner surface 412 that crosses through the ribs of the plunger 434 at an intermediate portion, between the base and the apex, of the ribs piston 434.

FIGS. 56 a, b, c show assembly 400 in a ready-to-use position, a docked position, and a used position, respectively. Assembly 400 is used in essentially the same manner as described above with respect to FIGS. 3 and 4, except that when assembly 400 is in the used position, cap holder 402 remains on plunger assembly 12 '.

The syringe barrel and plunger can be made of any material suitable for its purpose and includes glass and polymeric material. Suitable polymeric materials include, but are not limited to, homopolymers, copolymers, and terpolymers formed from monomers such as olefins, cyclic olefins, amides, esters, and ethers. The polymeric material can be a combination of more than one polymeric material and can be a monolayer structure or a multilayer structure. In a preferred form of the invention, the syringe barrel and plunger are injection molded from a polypropylene material.

FIGS. 59-61 show a third embodiment 500 of an antiseptic cap-equipped plunger and syringe barrel assembly with the antiseptic cap assembly 80 and cap material 68 removed for clarity. The third embodiment 500 provides for retrofitting of an antiseptic cap assembly 502 to a standard plunger 504. The antiseptic cap 502 has a first generally cylindrical outer wall 506 having a proximal end 508 and a distal end 510. The proximal end 508 is removably or fixedly attached to a button 512 of the plunger 504. The proximal end has an opening 514 sized to fit around button 512 and has a button attachment member. In a preferred form of the invention, the attachment member includes a plurality of circumferentially spaced, axially inwardly directed tabs 516 that extend from an inner wall surface 518 and the tabs engage a bottom surface of button 512 to secure the antiseptic cap assembly 502 to the plunger 504.

The distal end of the antiseptic cap 504 has an upper annular rim 520 that extends radially inward from the first cylindrical wall 506 and defines a generally circular opening 522. A second cylindrical wall 524 extends axially downward from the upper annular rim 520 and is coaxially disposed within the first cylindrical wall 506. When the antiseptic cap 504 is attached to the plunger button 512, a lower peripheral edge of the second cylindrical wall 524 will abut an upper surface of the plunger button 512, thereby capturing, by opposing axially directed forces, the plunger button. 512 between flanges 516 and the second cylindrical wall. However, it is contemplated that a second set of tabs spaced axially from the first set of tabs could be provided and the piston button 512 could be trapped between the two sets of tabs. Furthermore, it is contemplated that other means of fixation could be used which are well known in the art and the fixation member shown is merely exemplary.

The second cylindrical wall 524 defines a chamber as shown in greater detail in FIG. 5 above with ribs and grooves as described for engagement of the antiseptic cap assembly 80 to prevent relative rotational movement and to resist relative axial movement of the parts when the antiseptic cap assembly 80 is fully inserted into the chamber. . Furthermore, it is contemplated to adapt the plunger and syringe as described above to prevent or resist relative rotational movement of the plunger with respect to the barrel.

ES 2 808 632 T3

The piston 50 can be formed from any suitable material, including a polymeric material or a silicone material. The plug can be selected from a material with a desired durometer so that reflux is reduced when the plug engages an interior surface of the wall of the distal end of the barrel of the syringe.

Suitable blocking and washing solutions include a low molecular weight alcohol selected from ethanol, propanol, and butanol. The blocking solution can be a single low molecular weight alcohol or a combination of low molecular weight alcohols.

Suitable blocking solutions can also include a low molecular weight alcohol with an antimicrobial and / or an anticoagulant. Suitable blocking solutions may contain at least one low molecular weight alcohol in a range of 1% to 99% by volume and at least one other antimicrobial and / or anticoagulant compound in a range of 1% to 99% in volume. The low molecular weight alcohol will normally be in aqueous solution, typically 1% to 99% by volume, typically 5% to 95% by volume. The at least one other antimicrobial is selected from the group consisting of taurolidine and triclosan, and the at least one anticoagulant is selected from the group consisting of riboflavin, sodium citrate, ethylenediaminetetraacetic acid, and citric acid.

In a preferred form of the invention, the syringe assembly 10 will be pre-filled with one of the blocking solutions and will be packaged by a manufacturer and shipped to a healthcare provider. A cannula or needle will be attached to the distal end of the barrel and placed in fluid communication with the fluid access site of an indwelling central venous catheter. The flushing solution will be injected into the catheter to clean or block the catheter. Subsequently, the cap assembly 80 will be removed from the plunger 17 and the cap will engage the fluid access site of the catheter.

Antiseptic solutions containing citrate salt

In one form the antiseptic is a solution of a citrate salt and in another form of the invention the citrate salt solution is a hypertonic solution. The term hypertonic is used herein to refer to a fluid that has an osmotic concentration and density greater than the osmotic concentration and density of the patient's blood. The antiseptic solution preferably comprises a citrate salt with a concentration range, in weight percent, of from about 1.5% to about 50% with an osmolality of from about 300 to about 6400 mOsm. More preferably, the antiseptic solution comprises citrate salt in a concentration range of about 10% to about 40%, even more preferably, in a concentration range of about 20% to about 30%.

In a preferred embodiment, the antiseptic solution is prepared to have a pH lower than the pH of the patient's blood. The citrate salt solution can be prepared to have a pH of less than about 6.5, more preferably, about 4.5 to about 6.5. In addition, the citrate salt solution can include pharmaceutically acceptable agents such as sodium chloride and sodium heparin. The citrate salt solution can also include a variety of other antibacterial, antimicrobial, and anticoagulant agents such as gentamicin, vancomycin, and mixtures of these agents. Additional anticoagulant agents include, for example, heparin, urokinase, tissue plasminogen activation (tPA), and mixtures of these agents.

By pharmaceutically acceptable it is meant that the citrate salt solution and included salts and other additives are, within the scope of sound medical judgment, suitable for use in contact with human and lower animal tissues without excessive toxicity, irritation or response. allergic It is also typically necessary for a composition to be sterilized to reduce the risk of infection.

Antiseptic solutions containing an antibacterial agent

An antiseptic solution containing an antimicrobial agent of the present invention may contain at least one alcohol, at least one antimicrobial agent, and at least one chelator and / or anticoagulant. Various antimicrobial substances as disclosed herein and well known to one of ordinary skill in the art can be combined with the blocking solution to inhibit infections. The antimicrobial blocking solution of the present invention can be used to fill or wash a medical device such as a permanent device such as an implanted catheter. Other medical devices that are contemplated for use in the present invention are disclosed herein.

In another preferred form of the invention, the antiseptic agent may contain antibacterial agents such as those classified as aminoglycosides, beta-lactams, quinolones or fluoroquinolones, macrolides, sulfonamides, sulfamethaxozoles, tetracyclines, treptogramins, oxazolidinones (such as rifzolid, lincomdamicines) , glycopeptides, polymyxins, lipopeptide antibiotics, as well as pharmacologically acceptable sodium salts, pharmacologically acceptable calcium salts, pharmacologically acceptable potassium salts, lipid formulations, derivatives and / or analogs of the foregoing.

ES 2 808 632 T3

Aminoglycosides are bactericidal antibiotics that bind to the 30S ribosome and inhibit bacterial protein synthesis. Typically, they are active against aerobic gram-negative bacilli and staphylococci. Exemplary aminoglycosides that can be used in some specific aspects of the invention include amikacin, kanamycin, gentamicin, tobramycin, or netilmicin.

Suitable beta-lactams are selected from a class of antibacterials that inhibit bacterial cell wall synthesis. Most of the clinically useful beta-lactams belong to the penicillin group (penamics) or to the cephalosporin group (cefemics). Beta-lactams also include carbapenems (eg, mipenem) and monobactams (eg, aztreonam). Beta-lactamase inhibitors such as clavulanic acid and its derivatives are also included in this category.

Non-limiting examples of the group of penicillin antibiotics that can be used in the solutions of the present invention include amoxicillin, ampicillin, benzathine penicillin G, carbenicillin, cloxacillin, dicloxacillin, piperacillin or ticarcillin, etc. Examples of cephalosporins include ceftiofur, ceftiofur sodium, cefazolin, cefaclor, ceftibutenin, ceftizoxime, cefoperazone, cefuroxime, cefprozil, ceftazidime, cefotaxime, cefadroxil, cephalexin, cefamandarin, ceftibutenin, cefdinixirmafoxime, cefimethodoxin, cefithymafoxime, cefimexyprodoxin, etc. Other examples of beta-lactams include mipenem or meropenem, which are extremely active parenteral antibiotics with a spectrum against almost all gram-positive and gram-negative organisms, both aerobic and anaerobic, and to which Enterococci, B. fragilis, and P. aeruginosa are particularly susceptible.

Suitable beta-lactamase inhibitors include clavulanate, sulbactam, or tazobactam. In some aspects of the present invention, antibacterial solutions may comprise a combination of at least one beta-lactam and at least one beta-lactamase inhibitor.

Macrolide antibiotics are another class of bacteriostatic agents that bind to the 50S subunit of ribosomes and inhibit bacterial protein synthesis. These drugs are active against aerobic and anaerobic gram-positive cocci, with the exception of enterococci, and against gram-negative anaerobes. Exemplary macrolides include erythromycin, azithromycin, clarithromycin.

Quinolones and fluoroquinolones typically function by their ability to inhibit DNA gyrase activity. Examples include nalidixic acid, cinoxacin, trovafloxacin, ofloxacin, levofloxacin, grepafloxacin, trovafloxacin, sparfloxacin, norfloxacin, ciprofloxacin, moxifloxacin, and gatifloxacin.

Sulfonamides are synthetic bacteriostatic antibiotics with a broad spectrum against most gram-positive and many gram-negative organisms. These drugs inhibit the multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Examples include mafenide, sulfisoxazole, sulfamethoxazole, and sulfadiazine.

The tetracycline group of antibiotics includes tetracycline derivatives such as tigecycline, which is a new drug in clinical investigation (IND), minocycline, doxycycline, or demeclocycline, and analogs such as anhydrotetracycline, chlorotetracycline, or epioxytetracycline.

Suitable streptogramin class antibacterial agents include quinupristin, dalfopristin, or the combination of two streptogramins.

Drugs of the rifamycin class typically inhibit DNA-dependent RNA polymerase, leading to inhibition of RNA synthesis and have a very broad spectrum of activity against most gram-positive and gram-negative bacteria, including the species of Pseudomonas aeruginosa and Mycobacterium. An exemplary rifamycin is rifampin.

Other antibacterial drugs are glycopeptides, such as vancomycin, teicoplanin, and their derivatives. Still other antibacterial drugs are the polymyxins which are exemplified by colistin.

Besides these, various other antibacterial agents such as prestinomycin, chloramphenicol, trimethoprim, fusidic acid, metronidazole, bacitracin, spectinomycin, nitrofurantoin, daptomycin or other leptopeptides, oritavancin, dalbavancin, ramaplamin, ketolide, etc. they can be used in the preparation of the antiseptic solutions described herein. Of these, metronidazole is active only against protozoa, such as Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis, and strictly anaerobic bacteria. Spectinomycin is a bacteriostatic antibiotic that binds to the 30S subunit of the ribosome, thereby inhibiting bacterial protein synthesis, and nitrofurantoin is used orally for the treatment or prophylaxis of UTI, since it is active against species of Escherichia coli, Klebsiella-Enterobacter, Staphylococci, and Enterococci.

In other embodiments, the antimicrobial agent is an antifungal agent. Some exemplary classes of antifungal agents include imidazoles or triazoles such as clotrimazole, miconazole, ketoconazole, econazole, butoconazole, omoconazole, oxiconazole, terconazole, itraconazole, fluconazole, voriconazole, posaconazole, ravuconazole, or flutrimazole; polyene antifungals such as amphotericin B, liposomal amphotericin B, natamycin, nystatin and

ES 2 808 632 T3 nystatin lipid formulations; cell wall active lipopeptide antifungals, including echinocandins such as caspofungin, micafungin, anidulfungin, cilofungin; LY121019; LY303366; the allylamine group of antifungals such as terbinafine. Still other non-limiting examples of antifungal agents include naftifine, tolnaphtate, mediocidin, candicidin, trichomycin, hamycin, aurefungin, ascosin, aiphatin, azacolutin, trichomycin, levorin, heptamycin, candimycin, griseofulvin, BF-1386, BTG-1375 pradimycins (MNS 18184), benanomycin; ambisoma; nicomycin Z; flucytosine or perimycin.

In another preferred form of the invention, the antimicrobial agent is an antiviral agent. Non-limiting examples of antiviral agents include cidofovir, amantadine, rimantadine, acyclovir, ganciclovir, penciclovir, famciclovir, foscamet, ribavirin, or valciclovir. In some forms of the invention, the antimicrobial agent is an innate immune peptide or protein. Some exemplary classes of innate peptides or proteins are transferrins, lactoferrins, defensins, phospholipases, lysozyme, cathelicidins, serprocydins, proteins that increase bactericidal permeability, amphipathic alpha-helical peptides, and other synthetic antimicrobial proteins.

In other embodiments of the invention, the antimicrobial agent is an antiseptic agent. Various antiseptic agents are known in the art and these include a taurinamide derivative, a phenol, a quaternary ammonium surfactant, a chlorine-containing agent, a quinaldine, a lactone, a dye, a thiosemicarbazone, a quinone, a carbamate, urea. , salicylamide, carbanilide, a guanide, an amidine, an imidazoline biocide, acetic acid, benzoic acid, sorbic acid, propionic acid, boric acid, dehydroacetic acid, sulfurous acid, vanillic acid, p-hydroxybenzoic acid esters, 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), povidonayodate, hexamethylenetetramine, noxythioline, 1- (3-choroallyl) -3,5,7-triazo 1-azoniaadamantane chloride, taurolidine, taurultam, N (5-nitro-2-furfurylidene) -1- amino-hydantoin, 5-nitro-2-furaldehyde semicarbazone, 3, 4,4'trichlorocarbanilide, 3,4 ', 5-tribromosalicylanilide, 3-trifluoromethyl-4,4'-dichlorocarbanilide, 8-hydroxyquinoline, 1-cyclopropyl-6-fluoro-1 acid , 4-dihydro-4-oxo-7- (1-piperazinyl) -3-quinolinecarboxylic acid, 1,4-dihydro-1-ethyl-6-fluoro-4-oxo7- (1-piperazinyl) -3-quinolinecarboxylic acid, hydrogen peroxide, peracetic acid, phenol, sodium oxychlorosene, parachloromethaxylenol, 2,4,4'-trichloro-2'-hydroxydiphenol, thymol, chlorhexidine, benzalkonium chloride, cetylpyridinium chloride, silver sulfadiazine, or silver nitrate.

In another preferred form of the invention, the antiseptic solution includes a basic reagent and a dye. The basic reagent can be a guanidium compound, a biguanide, a bipyridine, a phenoxide antiseptic, an alkyl oxide, an aryl oxide, a thiol, a halide, an aliphatic amine, or an aromatic amine. In some specific aspects, the basic reagent is a guanidium compound. Non-limiting examples of guanidium compounds include chlorhexidine, alexidine, hexamidine. In other specific embodiments, the basic reagent is a bipyridine. An example of a bipyridine is octenidine. In still other aspects, the basic reagent is a phenoxide antiseptic.

The dye can be a triarylmethane dye, a monoazo dye, a diazo dye, an indigoid dye, a xanthene dye, an anthraquinone dye, a quinoline dye, an FD&C dye. Non-limiting examples of triarylmethane dye include gentian violet, crystal violet, ethyl violet, or brilliant green. Examples of monoazo dyes include FD&C Yellow # 5, or FD&C Yellow # 6. Other non-limiting examples of FD&C dyes include Blue # 1 or Green # 3. A non-limiting example of a diazo dye is D&C Red # 17. An example of an indigoid dye is FD&C Blue # 2. An example of a xanthene dye is FD&C Red # 3; of an anthraquinone dye is D&C Green # 6; and of a quinoline dye is D&C Yellow # 1.

Other examples of antiseptics that can be used for the solutions of the invention are phenoxide antiseptics such as chlorofoctol, chloroxylenol or triclosan. Still other antiseptic agents that can be used to prepare the antimicrobial solutions of the invention are gendin, genlenol, genlosan, or genfoctol.

One skilled in the art will appreciate that one or more of the antimicrobial agents can be used, including one or more antibacterial agents, and / or one or more antifungal agents, and / or one or more antiviral agents, and / or one or more agents. antiseptics, and / or combinations thereof.

A wide variety of chelating agents are contemplated as useful in the preparation of the antiseptic solutions of the invention. This includes chelators such as free acid EDTA, EDTA 2Na, EDTA 3Na, EDTA 4Na, EDTA 2K, EDTA 2Li, EDTA 2NH4, EDTA 3K, Ba (II) -EDTA, Ca (II) -EDTA, Co (II) - EDTACu (II) -EDTA, Dy (III) -EDTA, Eu (III) -EDTA, Fe (III) -EDTA, In (III-EDTA, La (III) -EDTA, CyDTA, DHEG, diethylenetriaminepentaacetic acid (DTPA) , DTPA-OH, EDDA, ​​EDDP, EDDPO, EDTA-OH, EDTPO, EGTA, HBED, HDTA, HIDA, IDA, methyl-EDTA, NTA, NTP, NTPO, O-Bistrene, TTHA, EGTA, DMSA, deferoxamine, dimercaprol , zinc citrate, a combination of bismuth and citrate, penicillamine, succimer, or etidronate. It is contemplated that any chelator that binds barium, calcium, cerium, cobalt, copper, iron, magnesium, manganese, nickel, strontium, or zinc will be acceptable for use in the present invention.

Alternatively, at least one anticoagulant such as heparin, hirudin, EGTA, EDTA, urokinase, streptokinase, hydrogen peroxide, etc. can be used in the preparation of the antimicrobial solutions of the invention.

ES 2 808 632 T3

In addition to the alcohols discussed above, a variety of alcohols are contemplated as useful in the preparation of the instant antiseptic solution and include any active antimicrobial alcohol. Non-limiting examples of alcohols include ethanol, methanol, isopropanol, propylene glycol, benzyl alcohol, chlorobutanol, phenylethyl alcohol, and the like.

One skilled in the art will appreciate that the solutions of the present invention may comprise various combinations of at least one alcohol, at least one antimicrobial agent, and at least one chelator / anticoagulant. In some specific embodiments, the solution of the invention comprises at least one alcohol, at least one tetracycline and at least one chelator / anticoagulant. In a specific aspect, said antimicrobial solution comprises ethanol, at least one tetracycline and EDTA or heparin.

In other specific aspects, said solution comprises ethanol, minocycline and EDTA or heparin. In one embodiment of this aspect, the minocycline concentration is from 0.001 mg / ml to 100 mg / ml. In another embodiment, the minocycline concentration is approximately 3 mg / ml. In another aspect, the EDTA concentration is in the range of 10-100 mg / ml. In one embodiment of this aspect, the EDTA concentration is approximately 30 mg / ml.

In another preferred form of the invention, the antiseptic solution includes a pharmacologically acceptable sodium salt, a pharmacologically acceptable calcium salt, a pharmacologically acceptable potassium salt, and about one milligram per milliliter of polyhexamethylene biguanide hydrochloride in an aqueous mixture. Additionally, the solution of the invention may also contain a pharmacologically acceptable salt of lactic acid.

Antiseptic solutions containing salt

A preferred antiseptic solution includes a pharmacologically acceptable sodium salt such as sodium chloride or the like in a concentration of between about 820 mg to about 900 mg, a pharmacologically acceptable calcium salt, such as calcium chloride dihydrate or the like in a concentration between about 30.0 mg to about 36.0 mg, a pharmacologically acceptable potassium salt, such as potassium chloride or the like in a concentration between about 28.5 to about 31.5 mg and about one milligram per milliliter of polyhexamethylene biguanide hydrochloride in an aqueous mixture with one hundred milliliters of USP Water for Injections. For particular applications, the solution of the invention can also include sodium lactate in a concentration between about 290 mg and about 330 mg in the one hundred milliliter aqueous mixture.

Photo-oxidant solutions

In another preferred form of the present invention, the antiseptic solution contains an anticoagulant and a photo-oxidant. In certain embodiments, a photo-oxidant is selected that has an antiseptic effect. As used herein, the term "photo-oxidant" is intended to refer to a compound (typically an organic dye) that has photo-oxidation properties, wherein the compound exhibits increased oxidative potential upon exposure to radiant energy such as light. The term photo-oxidant also refers to a composition that releases one or more electrons when struck by light.

In a preferred aspect of the invention, the photo-oxidant is methylene blue, which advantageously provides antibiotic and antifungal activity, and also provides a color to make the antiseptic solution clearly identifiable. In addition to methylene blue, other photo-oxidants can include rose bengal, hypericin, methylene violet, proflavin, rivanol, acriflavin, toluide blue, trypan blue, neutral red, a variety of other dyes, or mixtures thereof. Therefore, in alternative aspects of the invention, one or more alternative photo-oxidants are used, preferably a colored photo-oxidant according to the invention instead of methylene blue.

Enhanced Viscosity Solutions

In another preferred form of the invention, the antiseptic solution includes a low viscosity antibacterial agent mixed with a viscosity increasing agent. Examples of antibacterial agents that can be used, in addition to those described above, include alcohols, chlorhexidine, chlorpactin, iodine, tauroline, citric acid and soluble salts of citric acid, in particular sodium citrate, optionally mixed with water.

Suitable viscosity increasing agents include carbopol, starch, methyl cellulose, carboxypolymethylene, carboxymethyl cellulose, hydroxypropyl cellulose, or the like. Carbopol is a cross-linked polyacrylic acid-based polymer sold by Noveon, Inc. It is preferably neutralized at about pH 7 with a basic material such as tetrahydroxypropyl ethylenediamine, triethanolamine, or sodium hydroxide. Starch derivatives, such as hydroxyethyl starch, hydroxypropyl starch or starch having attached organic acid ester groups, can also be used to improve compatibility with antibacterial agents such as alcohols, for example ethanol or isopropanol. Said ester groups can be the reaction product of two to

ES 2 808 632 T3 twelve carbon organic acids with starch, for example. In addition, the high viscosity antiseptic solution can be created by using a fat emulsion or other water / alcohol dispersions of glycerol mono- or diesters of fatty acids, or fatty acid esters of other polyols such as sugars having one or more fatty acid groups attached per molecule. Analogous compounds with ether linkages can also be used.

In addition, other materials such as alginic acid, with or without calcium citrate, or polyvinyl alcohol, with or without borax, povidone, polyethylene glycol alginate, sodium alginate and / or tragacanth can be used. If desired, the fluid of the present invention may also contain an effective amount of an antithrombogenic agent such as heparin and a diluent such as water, along with other desired ingredients.

In a preferred form of the invention, the antiseptic solution contains a mixture of isopropyl alcohol and neutralized carbopol, other optional ingredients being present such as water, antithrombogenic agents such as heparin and the like. Preferably, about 0.4 to 2 weight percent carbopol is present. Citric acid can also be present as an antibacterial agent, with or as a substitute for another antibacterial agent such as isopropyl alcohol or ethanol.

In another embodiment, the antiseptic solution is a gel of an isopropyl alcohol, optionally with up to about 30 weight percent water and about 2.2 weight percent hydroxypropyl cellulose, to form a high viscosity antiseptic solution. .

In another preferred form of the invention, the antiseptic solution contains carbohydrates and / or glucose breakdown products. Suitable carbohydrates are selected from the group of glucose and / or fructose. Suitable degradation products include 3-deoxyglucosone (3-DG), acetaldehyde, formaldehyde, acetaldehyde, glyoxal, methylglyoxal, 5-hydroxymethyl-2-furaldehyde (5-HMF), 2-furaldehyde, and 3,4-dideoxyglucosone-3ene ( 3,4-DGE).

Other suitable agents to be used in this embodiment of the antiseptic solution include substances that have anticoagulant properties, i.e., inhibitors of the coagulation cascade such as standard and low molecular weight heparin, fractionated heparin, synthetic inhibitors in the coagulation cascade, futane as a broad protease inhibitor, complexing and chelating substances such as citrate, EDTA, EGTA, substances and mixtures used for the preservation of blood products (platelets or plasma), CDPA (citrate, sodium phosphate, dextrose, adenine), synthetic or natural inhibiting substances of thrombin. Other suitable additives include fucosidan, riboflavin, vitamin E, alpha-tocopherol, folic acid, and amino acids. Furthermore, anti-inflammatory compounds and drugs could also be used, for example, cortisone, mycophenolic acid (MPA) and derivatives thereof, sirolimus, tacrolimus and cyclosporine, diclofenac, etc.

Inhibitory peptides can also be used in the antiseptic solution such as defensins, (dermacidin) and others. Radicals, such as reactive oxygen species, NO or nitric oxide (NO) release systems, and peroxynitrite can also be used. A buffer composition should also be included in the antiseptic solution, and in a preferred form of the invention, the buffer contains lactate, bicarbonate, pyruvate, ethyl pyruvate, and citric acid in combination and mixtures, including pH adjustment by acetic acid. , hydrochloric acid or sulfuric acid. In addition, additives that enhance viscosity can be added, such as lipids or lipid substances (also to obtain vitamins or water-insoluble complexes in solution), nutrients in high concentration density gradient, for example fluids containing amino acids, polyglucose, icodextrin, pectin, hydroxyethyl starch (HES), alginate, hyaluronic acid, etc.

Taurolidine Antiseptic Gels and Solutions

The antiseptic solutions of the present invention can include taurolidine and / or taurultam to prevent coagulation and biofilm formation or the elements can be combined with other antimicrobial agents. One embodiment of the present invention is a gel with thixotropic properties to keep the solution inside the antiseptic cap and not spill out during the time interval between uses. This is accomplished by making a hydrogel matrix as a drug delivery vehicle that contains a biocompatible antimicrobial agent alone or with another active agent, which may be useful for particular purposes. The hydrogel matrix is ​​biocompatible and biodegradable in the bloodstream. The matrix can be a hydrogel (for example, pectin, gelatin, etc.), a protein (for example, collagen, hemoglobin, etc.), a colloidal substance (for example, serum albumin, etc.), an emulsion or other adjuvant . Preferably, the matrix will have structural integrity and will be thixotropic. Thixotropy is a property exhibited by certain gels. It is a property characterized by a solid or semi-solid substance that, when shaken, stirred or subjected to high shear forces, becomes fluid and can flow and then returns to the semi-solid state when the forces and / or movement stop. Alternatively, the gel could have properties similar to colloidal dispersion that resists movement or flow until a high shear force is imparted to the fluid and then flows easily.

Other ingredients can be added to the gel matrix to provide additional functional benefit. The preferred antimicrobial is taurolidine, which can be added to the matrix as a microparticle powder, or

ES 2 808 632 T3 encapsulate in liposomes, microspheres or nanospheres. It should be appreciated that numerous active agents and drugs can be added to the thixotropic gel, including sterilants, lysing agents (such as urokinase), imaging enhancers, catheter surface modifiers, antibiotics, and antimicrobial chemicals.

A hydrogel comprises a three-dimensional molecular network that contains large amounts of water, giving them good biocompatibility with a material consistency that is similar to a soft solid with high diffusing properties to gases, chemicals, and proteins. Suitable hydrogels include natural polymers, including serum albumin, collagen, or alginates, polyvinyl alcohol, polyethylene oxide or poly (hydroxyethylene), and polyelectrolytes, such as polyacrylic acid, polystyrene sulfonate, and carboxymethylcellulose. (CMC).

A preferred form of the antiseptic solution includes taurolidine with salicylic acid or sodium salicylate in an aqueous solvent. Salicylic acid and sodium salicylate are drugs that have been used with antibiotic blocking solutions in catheters to enhance the biocidal action of the antibiotic alone and to inhibit the attachment of microbes to surfaces. This last attribute is especially important because the onset of expression and proliferation of a biofilm requires that individual bacteria first bind to the underlying surface. By stopping fixation, biofilm formation is blocked.

Sodium salicylate has been shown to have remarkable antibacterial activity, including the ability to enhance the activities of certain antibiotics. This drug inhibits adherence, proliferation, and biofilm formation.

Antiseptic solutions containing EDTA

In a preferred antiseptic solution of the present invention, antimicrobial, antifungal, antiviral, and antiamebic properties are provided, and it can also serve as an anticoagulant. Determined Ethylenediaminetetraacetic Acid (EDTA) salts and compositions (ΟιοΗι2Ν2Ν8408) are used at specified pH levels and concentrations.

The EDTA formulations of the present invention are safe for human administration and are biocompatible and non-corrosive. They may also have anticoagulant properties and are therefore useful in preventing and / or treating a variety of catheter-related infections. In one embodiment, the antiseptic solutions of the present invention have at least four, and preferably at least five, of the following properties: anticoagulant properties; inhibitory and / or bactericidal activity against a broad spectrum of bacteria in planktonic form; inhibitory and / or fungicidal activity against a spectrum of fungal pathogens; inhibitory and / or bactericidal activity against a broad spectrum of bacteria in sessile form; inhibitory activity against protozoan infections; inhibitory activity against Acanthamoeba infections; safe and biocompatible, at least in modest volumes, in contact with a patient; safe and biocompatible, at least in modest volumes, in a patient's bloodstream; and safe and compatible with industrial objects and surfaces. The antiseptic solution may have a pH greater than physiological pH, such as a pH> 8.0, or a pH> 8.5, or a pH> 9, or a pH> 9.5.

In another preferred form of the invention, the antiseptic solution contains a sodium EDTA salt (or combination of sodium salts) in solution at a pH in the range between 8.5 and 12.5 and, in another embodiment, at a pH of between 9.5 and 11.5 and, in still another embodiment, at a pH of between 10.5 and 11.5.

When used herein, the term EDTA salt can refer to a single salt, such as a disodium or trisodium or tetrasodium salt, or other form of EDTA salt, or it can refer to a combination of such salts. . The composition of the EDTA salt (s) depends on both the EDTA salts used to formulate the composition and the pH of the composition. For the antiseptic solutions of the present invention consisting of the sodium salt (s) of EDTA, and in the desired pH ranges (specified above), the sodium salts of EDTA are predominantly present in the salt forms of both trisodium and of tetrasodium.

In one embodiment, the antiseptic solution contains a combination of at least the trisodium and tetrasodium salts of EDTA, and more preferably solutions containing at least 10% of the EDTA in the composition are present in the form of the tetrasodium salt. In yet another embodiment, at least 50%, and more preferably at least 60%, of the EDTA in the composition is present in the form of the trisodium salt.

The EDTA solutions of the present invention are preferably provided in a sterile and non-pyrogenic form and can be packaged in any convenient manner. The compositions can be prepared under sterile and aseptic conditions, or they can be sterilized after preparation and / or packaging using any of a variety of suitable sterilization techniques.

The formulation and production of antiseptic compositions of the present invention is generally straightforward. In one embodiment, the desired antiseptic solutions of the present invention are formulated by dissolving

ES 2 808 632 T3 one or more EDTA salts in an aqueous solvent, such as purified water, at the desired concentration and adjusting the pH of the EDTA salt solution to the desired pH. The antiseptic solution can then be sterilized using conventional means, such as autoclaving, UV irradiation, filtration and / or ultrafiltration, and other means. The preferred osmolarity range for EDTA solutions is 240500 mOsM / Kg, more preferably 300-420 mOsm / Kg. Solutions are preferably formulated using USP materials.

Antiseptic solutions containing EDTA sodium salts other than tri and tetrasodium salts, such as EDTa disodium, are also contemplated. For example, disodium solutions of EDTA can be used, but such solutions have a pH in solution less than the desired pH range of the compositions of the present invention but, upon adjustment of the pH to the desired range using a pH adjusting material pH, such as sodium hydroxide, sodium acetate and other known pH adjusting agents, EDTA solutions prepared using disodium salts become the preferred combination of di- and / or tri and / or tetrasodium salt solutions of EDTA of the present invention. Thus, different forms and combinations of EDTA salts can be used in the preparation of EDTA compositions of the present invention, provided that the pH of the composition is adjusted to the desired pH range prior to use. In one embodiment, antiseptic compositions consisting of a mixture of primarily EDTA tri- and tetrasodium are provided by dissolving EDTA disodium in an aqueous solution, on a 3% -5% w / v basis, and adding sodium hydroxide in a volume and / or concentration sufficient to provide the desired pH of> 8.5 and <12.0.

Antiseptic solutions containing antibacterial enzymes

Antibacterial enzyme refers to any proteolytic, pore-forming, degrading or inhibiting enzyme that destroys or damages a bacterial species or a particular strain thereof. The result can be achieved by damaging the cell wall of the bacteria, breaking the cell membranes associated with the cell wall or within the bacteria, inhibiting protein synthesis within the bacteria, breaking the carbohydrate main chain or by any other mechanism attributed to a peptide or protein that those skilled in the art consider to be an antibacterial enzyme. The enzyme can be a natural enzyme, modified by conventional techniques, conjugated with other molecules, expressed recombinantly, or synthetically constructed.

An example of an antibacterial enzyme is lysostaphin. Lysostaphin is important because it is effective in treating staphylococci and the biofilms formed from them. Lysostaphin and lysostaphin analogs are defined to include lysostaphin (wild type), any mutant or variant of lysostaphin, any recombinant or related enzyme (analog), or any synthetic version or fragment of lysostaphin (whether synthetic or otherwise) that it retains the proteolytic ability, in vivo and in vitro, to cleave the cross-linked polyglycine bridges in the peptidoglycan of the staphylococcal cell wall. Enzymes can be generated by post-translational processing of the protein (by enzymes present in a producing strain or by means of enzymes or reagents introduced at any stage of the process) or by mutation of the structural gene. Mutations can include site deletion, insertion, domain deletion, and replacement mutations.

Lysostaphin can be constructed synthetically, expressed in mammalian, insect, bacterial, yeast, reptile, or fungal cells, expressed recombinantly from a cell culture or higher recombinant species, such as a mouse, or otherwise. This would include the synthetic construct that retains the activity, including synthetic peptides and polypeptides or the recombinant expression of parts of the enzyme lysostafin responsible for its activity against staphylococci as part of a larger protein or peptide, it would include chimeric proteins, which contain the active sites of one or more other antibacterial enzymes that are effective against staphylococci or other species of biofilm-forming bacteria.

Antibacterial enzymes can also be coated on the surface of the devices described herein by immersing the device in a solution of the enzyme for a period of time sufficient to form a biofilm-inhibiting enzyme coating on the surface. susceptible. Even the smallest concentration of enzyme will confer some protection. Typically, a concentration of from about 10 pg / ml to about 100 mg / ml can be used. With device surfaces, coatings can also be formed by covalently binding the enzyme to them.

Antiseptic coatings

It is contemplated that the devices described herein may be coated with an antiseptic coating by any suitable technique such as dipping the part in an antiseptic solution, spray coating the part with the antiseptic solution, combining the antiseptic solution or material in the polymeric material used to make the device.

In a preferred form of the invention, an amount of physiological antimicrobial metal compound is added to the resin for direct molding of an article. Physiological metals and

ES 2 808 632 T3 antimicrobials include precious metals, such as silver, gold and platinum, and copper and zinc. The physiological antimicrobial metal compounds used herein include oxides and salts of preferably silver and also gold, for example: silver acetate, silver benzoate, silver carbonate, silver citrate, silver chloride, silver iodide, nitrate silver, silver oxide, silver sulfadiazine, silver sulfate, gold chloride, and gold oxide. Platinum compounds such as chloroplatinic acid or its salts (eg sodium calcium chloroplatinate) can also be used. In addition, copper and zinc compounds can be used, for example: copper and zinc oxides and salts, such as those indicated above for silver. Individual physiological antimicrobial metal compounds or combinations of physiological antimicrobial metal compounds can be used.

Preferred physiological antimicrobial metal compounds used in the present invention are silver acetate, silver oxide, silver sulfate, gold chloride, and a combination of silver oxide and gold chloride. The silver compound particles are sufficiently capable of being extracted to form a zone of inhibition to prevent and destroy the proliferation of bacteria.

In another preferred form of the invention, the devices of the present invention are impregnated with triclosan and silver compounds or triclosan and chlorhexidine.

From the foregoing, it will be appreciated that numerous variations and modifications can be made without departing from the claimed scope of the invention. It should be understood that no limitation is intended or should be inferred with respect to the specific apparatus illustrated herein. Of course, all modifications that fall within the scope of the claims are intended to be covered by the appended claims.