Medical fluid connectors and methods for providing additives in medical fluid lines

Information

  • Patent Grant
  • 11517733
  • Patent Number
    11,517,733
  • Date Filed
    Wednesday, October 30, 2019
    5 years ago
  • Date Issued
    Tuesday, December 6, 2022
    2 years ago
Abstract
Disclosed is a medical fluid connector configured to receive and dispense medical liquid. The medical connector can be structured to include an initial stage in which medical liquid is infused into the connector and dispensed out of the connector essentially unchanged. The medical connector also can be structured to include a subsequent stage in which medical liquid is not infused into the connector and a volume of therapeutic liquid is dispensed out of the connector. The therapeutic liquid can include a portion of the volume of the medical liquid that was infused into the connector in the initial stage plus a therapeutic additive.
Description
BACKGROUND
Field

This disclosure relates generally to medical fluid connectors, and specifically to medical fluid connectors for providing additives in medical fluid lines.


Description of the Related Art

In healthcare settings where an intravenous (IV) catheter is inserted into a patient, there is an ever-present risk of microbial invasion into the catheter, which can lead to a catheter-related bloodstream infection (CRBSI) in the patient. There are many negative effects of CRBSI's, including serious health risks and increased costs for additional patient treatment. It is common practice in situations where the risk of contracting a CRBSI is particularly high, such as in long-term uses of central venous catheters, to utilize an anti-microbial lock procedure to provide a static anti-microbial solution in the catheter when fluid is not being transferring to or from the patient through the catheter.


SUMMARY

Disclosed are embodiments of medical fluid connectors and/or fluid-modifying devices configured to receive, convey, and/or dispense medical liquid, methods of making the same, and methods of using the same. In some embodiments, the medical connector or fluid-modifying device can be structured to include an initial stage in which medical liquid is infused into the connector and at least a portion of the medical liquid (or all of the medical liquid) is dispensed out of the connector essentially unchanged. The medical connector or fluid-modifying device also can be structured to include a subsequent or final stage in which medical liquid is not infused into the connector and a volume of therapeutic liquid is dispensed out of the connector. In some embodiments, as illustrated, the connector or fluid-modifying device transitions automatically from the initial stage to the subsequent or final stage (e.g., without mechanical actuation or manipulation by a user of a switch or product setting or device configuration), such as by operation of fluid flow only and/or by one or more changes in a force propagated in or through a fluid. In some embodiments, the connector transitions from the initial stage to the subsequent stage by manual actuation by a user, such as by moving or changing a fluid pathway and/or opening a valve within or on the connector. The therapeutic liquid can include a portion of the volume of the medical liquid that was infused into the connector in the initial stage plus a therapeutic additive.


Some embodiments disclosed or claimed in this specification, or in any applications that claim priority to this specification, will overcome one or more of the identified shortcomings in the prior art. However, not all embodiments disclosed or claimed in this specification, or in any applications that claim priority to this specification, will overcome any or all of the identified shortcomings of the prior art, but can be useful for one or more other purposes.





BRIEF DESCRIPTION OF THE DRAWINGS


FIG. 1 is a schematic illustration of a medical fluid connector;



FIG. 2A is a front view of an example of a medical fluid connector of FIG. 1;



FIG. 2B is a front view of another example of a medical fluid connector of FIG. 1;



FIG. 2C is a front view of another example of a medical fluid connector of FIG. 1;



FIG. 3A is an example cross-sectional view of the medical fluid connector of FIG. 2A, taken along the line 3A-3A of FIG. 2A;



FIG. 3B is a cross-sectional view of the medical fluid connector of FIG. 2B, taken along the line 3B-3B of FIG. 2B;



FIG. 3C is a cross-sectional view of the medical fluid connector of FIG. 2C, taken along line 3C-3C of FIG. 2C;



FIG. 3D is another example cross-sectional view of the medical fluid connector of FIG. 2A, taken along the line 3A-3A of FIG. 2A.



FIG. 3E is another example cross-sectional view of the medical fluid connector of FIG. 2A, taken along the line 3A-3A of FIG. 2A.



FIG. 3F is a cross-sectional view of the medical fluid connector of FIG. 3E, taken along the line 3F-3F of FIG. 3E.



FIG. 4 is a front view of an internal fluid guide from the medical fluid connector of FIG. 2A;



FIG. 5 is a front view of a fluid modifier from the medical fluid connector of FIG. 2A;



FIG. 6A is an example cross-sectional view of the medical fluid connector of FIG. 3A with a cross-sectional view of a distal end of a syringe attached to an inlet end of the connector in a first stage of fluid flow;



FIG. 6B is another example cross-sectional view of the medical fluid connector of FIG. 3D in a first stage of fluid flow;



FIG. 6C is another example cross-sectional view of the medical fluid connector of FIGS. 3E-F in a first stage of fluid flow;



FIGS. 7 and 8 are example cross-sectional views of the medical fluid connector of FIG. 3A with a cross-sectional view of a distal end of a syringe attached to an inlet end of the connection in a second stage of fluid flow;



FIG. 9 is an example cross-sectional view of the medical fluid connector of FIG. 3A with a cross-sectional view of a distal end of a syringe attached to an inlet end of the connection in a third stage of fluid flow;



FIG. 10 is a cross-sectional view of the medical fluid connector of FIG. 2C with a cross-sectional view of a distal end of a syringe attached to an inlet end of the connector in a first stage of fluid flow;



FIGS. 11 and 12 are cross-sectional views of the medical fluid connector of FIG. 2C with a cross-sectional view of a distal end of a syringe attached to an inlet end of the connector in a second stage of fluid flow;



FIG. 13 is a cross-sectional view of the medical fluid connector of FIG. 2C with a cross-sectional view of a distal end of a syringe attached to an inlet end of the connector in a third stage of fluid flow;



FIG. 14 is a graph showing an example of an infusion of liquid through a connector of FIG. 2A, that illustrates a relationship between the concentration of additive as compared to infused volume; and



FIG. 15 is a graph showing an example of an infusion of liquid through a connector of FIG. 2C, that illustrates a relationship between the concentration of additive as compared to infused volume.





DETAILED DESCRIPTION

Some embodiments disclosed herein pertain to medical connectors, fluid dispensers, and/or fluid modifiers. In some embodiments, the medical connectors include fluid modifiers that infuse a medical fluid with one or more additives, or permit the addition of one or more additives into a medical fluid, or modify a medical fluid in some other way, as the medical fluid passes through or is dispensed from the connector. In some embodiments, methods of making and/or using the disclosed connectors are provided. The following description provides context and examples, but should not be interpreted to limit the scope of the inventions covered by the claims that follow in this specification or in any other application that claims priority to this specification. No single component or collection of components is essential or indispensable. For example, some embodiments may not include a fluid modifier. Any feature, structure, component, material, step, or method that is described and/or illustrated in any embodiment in this specification can be used with or instead of any feature, structure, component, material, step, or method that is described and/or illustrated in any other embodiment in this specification. The relative sizes and dimensions of components shown in the drawings are not limiting if not present in a claim, but are intended to form part of the supporting disclosure in this specification when claimed.


While conventional procedures for achieving anti-microbial locks exist, those procedures are time-consuming, require the acquisition, storage, and use of multiple liquids, may be highly dependent on the techniques employed by healthcare providers for successful outcomes (subject to human error or variation), and may not deliver the anti-microbial solution in an effective dosage or in a useful timing sequence. Some embodiments disclosed herein address one or more of these issues and/or other issues that can occur when using a catheter or while performing a conventional antimicrobial lock method with conventional equipment. In some embodiments, a medical fluid connector configured to provide an additive (e.g., an antimicrobial compound, etc.) to the catheter as a locking solution is provided. In some embodiments, as a medical fluid is passed through the connector, an initial volume of the medical fluid is unchanged or substantially unchanged, having little or no additive added to it, such that there is no clinically significant effect. In some embodiments, after the initial volume of medical fluid passes through the medical connector, the connector is configured to then permit removal of or distribute or expel (automatically, in some devices) an additive-infused or otherwise modified or different portion of medical fluid out of the connector and into the catheter. In some embodiments, a delayed release of additive into the medical fluid locks the catheter without infusing any (or substantially any or any clinically significant amount) of the locking solution (e.g., the additive-infused medical fluid) into the patient. For example, the initial liquid volume can be sufficient to flush the liquid container within the catheter into the patient (e.g., at least about 5 mL, or at least about 3 mL, or at least about 2 mL, etc.), and the volume of additive-infused liquid can be approximately equal to or less than the volume of liquid that is inside of the catheter in communication with the patient's blood flow (e.g., less than or equal to about 5 ml, or less than or equal to about 3 mL, or less than or equal to about 2 mL, etc.), or approximately equal to or less than the volume of liquid that is configured to be inside of the portion of the patient's catheter that is outside of the patient.


As illustrated in FIG. 1, in some embodiments, a medical fluid connector 100 can comprise a housing 120, a fluid inlet or upstream connector 102, a fluid entry region 106, a main fluid pathway 108, a secondary fluid pathway 110, an additive 112, a fluid exit region 114, and a fluid outlet or downstream connector 104. As with all embodiments in this specification, any component(s) can be omitted. For example, a medical fluid connector 100 can omit the fluid entry region 106 and/or fluid exit region 114 (e.g., the fluid can enter or exit directly into or from another part of the connector 100. In the example illustrated, the connector 100 can be configured to: (a) receive a medical liquid in the inlet 102, such as saline or water or another medical liquid (e.g., a glucose solution, a dextrose solution, a nutrient solution, a medicated or pharmaceutical solution, etc.); (b) permit a portion of the medical liquid to travel in the main fluid pathway 108 through to the fluid exit region 114 and out of the fluid outlet 104 without a clinically significant change to the liquid; and (c) permit another portion of the liquid to travel in the secondary fluid pathway 110 where it becomes mixed with an additive 112 and then moves into the fluid exit region 114 and out of the fluid outlet 104. In some embodiments, the medical liquid travelling through the secondary fluid pathway 110 can be offset in time, or out of phase, or delayed or advanced as compared to the medical liquid travelling through the main fluid pathway 108. In some embodiments, all or essentially all of the medical liquid infused into the connector is modified to include an additive, such as by first passing through a region of the connector containing a fluid modifier before exiting the connector. For example, in some embodiments, the main fluid pathway 108 and the secondary fluid pathway 110 are the same or overlap or are positioned in series flow rather than in parallel flow (as illustrated), such that all or essentially all of the medical liquid that is infused into the connector includes at least one additive before exiting the connector.


The main fluid pathway 108 and the secondary fluid pathway 110 can be separated by one or more physical barriers, or can constitute different portions of a single liquid flow being transported through the connector 100, or can represent a single liquid pathway in one or more different phases or configurations. In some embodiments, as shown, liquid that flows directly through the main fluid pathway 108, without deviating into the secondary fluid pathway 100, can be isolated or separated from the additive 112 or from a carrier, such as a matrix or substrate or other holder, of additive 112, during one or more phases, stages, or configurations of use. As illustrated, in some embodiments, the main fluid pathway 108 is essentially straight and/or is essentially co-linear or co-axial with the main central axis or longitude of the connector 200, while the secondary fluid pathway 110 can comprise at least a portion that is offset or spaced laterally from the main central axis or longitude of the connector 200, and/or non-parallel with the main central axis or longitude of the connector 200, and/or can include one or more turns or can follow a tortuous pathway through the connector 200. As shown, the secondary fluid pathway 110 can create more turbulence during fluid flow than the main fluid pathway 108, and/or can be configured to direct fluid through at least a portion of the secondary fluid pathway 110 in a direction that is different from or generally or completely opposite from the direction of fluid flow through the main fluid pathway 108. In situations where the main fluid pathway 108 and the secondary fluid pathway 110 are separated by one or more physical barriers, a first diversion region 111 can be a location or a structure where the pathways 108, 110 separate or are caused to separate; and a second diversion region 113 can be a location or a structure where the separate pathways 108, 110 recombine or are caused to recombine. In many embodiments, either or both of the first and second diversion regions 111, 113 are omitted. In some embodiments, as shown in FIGS. 2A-3F and 6A-13, the first and second diversion regions 111, 113 can be positioned in the same location or substantially the same location (e.g., in or around a transitional region 274, 274A, 274B, 274C, 274D), and/or can exist or take effect at different times, depending on fluid-flow dynamics or changing configurations or positions of the structure of the connector 100. In some embodiments, as shown in FIG. 1, the first and second diversion regions are not at the same location. In some embodiments, including those illustrated in FIG. 2A, a carrier of the additive 112 or the additive 112 itself does not block or clog or impede the flow of fluid through the main fluid pathway 108 and/or the secondary fluid pathway 110 in a manner that would otherwise significantly diminish the fluid flow volume or rate.


Any of these steps and/or structures can be omitted. For example, in some embodiments, the connector 100 can be configured to permit all of the liquid to flow through a fluid pathway that includes one or more additives (e.g., if the additive is provided in the main fluid pathway and there is no secondary fluid pathway). In some embodiments, the one or more additives can be antimicrobial additives. As also described elsewhere herein, any other type of one or more additives can be used for any other type of patient therapy, with or without one or more antimicrobial additives.


As illustrated, in some embodiments, the connector 100 can comprise a fluid modifier 116 to alter one or more qualities of the liquid flow through the connector 100, such as by modifying the direction or size or shape of the liquid pathway through the connector 100 (e.g., in the secondary fluid pathway 110 and/or in the main fluid pathway 108), and/or by modifying the composition of the liquid flowing through the connector 100, such as by adding one or more additives 112 to the liquid flowing through the connector 100. A fluid modifier 116 may perform a single function or multiple functions. For example, in some embodiments, the fluid modifier 116 can: (a) permit the secondary fluid pathway to temporarily increase in size or volume or length; and/or (b) the fluid modifier 116 can affect the timing or sequence of the passage of liquid through the secondary fluid pathway, such as by delaying the passage of liquid that enters and/or that travels through the secondary fluid pathway 110 as compared to the passage of liquid through the main fluid pathway 108 (e.g., liquid that passes by and/or does not travel through the secondary fluid pathway 110); and/or (c) the fluid modifier 116 can include a coating or a dusting or an impregnation or any other suitable application or placement or attachment of one or more additives on or in or underneath or covered by or surrounded by the fluid modifier 116 that can be dispersed from or by the fluid modifier 116 into the liquid passing through or around the fluid modifier 116 in a dosage, timing, and/or sequence that is clinically effective for a therapeutic use, such as for providing an anti-microbial lock.


For example, in some embodiments, the connector 100 can be configured to receive through the fluid inlet 102 a first medical liquid, such as saline or water or some other medical liquid, and to deliver out of the fluid outlet 104 a pre-determined initial volume of saline or water or some other medical liquid that has the same or essentially or substantially the same composition or the same or substantially the same clinical effect as the first medical liquid, and then subsequently to deliver out of the fluid outlet 104 a pre-determined secondary volume of a second medical liquid that is comprised of the first medical liquid plus a clinically significant concentration of one or more additives 112 that can be used to provide an effective therapy to a patient, such as an anti-microbial lock in a catheter line. Any other desired liquid delivery profile can be accomplished, such as an additional or alternative fluid delivery concentration or composition or sequence. For example, the first medical liquid can include a clinically significant concentration of one or more additives, followed by a second medical liquid that does not include a clinically significant concentration of one or more additives or that includes a different clinically significant concentration of one or more additives (e.g., if the main fluid pathway 108 and the secondary fluid pathway 110 both include one or more additives, or if there is an additional fluid pathway or if there are layers of additives positioned within the pathway); or a generally uniform concentration of one or more additives can be provided through substantially the entire period of infusion of liquid through the connector 100. In some embodiments, the fluid modifier 116 or the connector 100 does not include any additive 112, but may accomplish one or more other purposes, such as performing a delay in the delivery of fluid or a pre-determine liquid-delivery sequence.


In some embodiments, as also described elsewhere herein, the secondary pathway 110 can fill as a result of, for example, a threshold volume and/or threshold rate of liquid passing into and/or through the main fluid pathway 108.


In some embodiments, the connector 100 comprises one or more additional fluid pathways (not shown) that fill before or after or while the secondary fluid pathway fills or is filled. In some embodiments, as described elsewhere herein, the additional pathways can fill as a result of, for example, a specific (e.g., threshold) volume and/or rate of liquid passing through the main fluid pathway and/or as a result of a specific (e.g., threshold) volume and/or rate of liquid passing through or into the secondary fluid pathway. In some embodiments, using a multistage configuration allows multiple infusion profiles or infusion profiles with multiple stages or changes to be obtained. In some embodiments, multiple connectors can be used (e.g., connected) serially or in any other way to achieve any of various clinically significant infusion profiles.


In some embodiments, there can be a boundary 118 that is in contact with or surrounding either or both of the main fluid pathway 108 and the secondary fluid pathway 110 or that is positioned between the main fluid pathway 108 and the secondary fluid pathway 100. The boundary can be configured to move, thereby changing either or both of the volumes or path lengths of the main fluid pathway 108 and the secondary fluid pathway 110, such as in a generally inverse relationship. In some embodiments, one or more valves can be provided between the main fluid pathway 108 and the secondary fluid pathway 110. For example, either or both of diversion regions 111, 113 can comprise a valve for selectively permitting or impeding fluid flow from the fluid entry region 106 and/or into the fluid exit region 114. The valve can transition between open and closed positions manually by a user or automatically (e.g., based upon a quantity of fluid flow or volume or a change in fluid pressure, or in some other way). In some embodiments, the valve or valves are responsive to a certain volume or force achieved in the main fluid pathway and/or in the secondary fluid pathway. In some embodiments, the connector 100 is configured to provide a desired dosage or concentration of one or more additives after a pre-determined period of time or after a pre-determined volume of liquid has passed through the connector 100, and/or during a pre-determined period of time or while a pre-determined volume of liquid is passing through the connector, in the medical liquid that flows out of the fluid outlet 104 of the connector 100.


In some embodiments, the fluid modifier 116 can be omitted or can be configured to have no effect on the size, shape, and/or length of the fluid pathway. For example, in some embodiments, the size and/or length of the secondary fluid pathway 110 and the main fluid pathway 108 are both static, and/or the size and/or length of the secondary fluid pathway 110 can be greater than the main fluid pathway 108, thereby delaying the delivery of liquid through the secondary fluid pathway 110 as compared to the main fluid pathway 108. The secondary fluid pathway 110 can include one or more additives that can be dispersed into the liquid flowing through the connector 100, with or without a fluid modifier 116 to disperse the one or more additives into the liquid.


In some embodiments, the connector 100 is configured to deliver or to infuse a specific and/or adjustable volume of medical fluid with the additive. In some embodiments, as also described elsewhere herein, this volume is controllable depending on the length, volume, or other dimensions of the secondary fluid pathway 110. In some embodiments, the connector is configured to distribute sufficient additive-infused liquid to fill or substantially fill the catheter to which it is attached. In some embodiments, the connector is selected and/or configured to provide a volume of additive-infused liquid that fills only a portion of the catheter (e.g., a portion of tubing external to the patient's body) and/or a volume insufficient to overflow out of the catheter into the patient. For example, the volume of additive-infused liquid to be emitted from the connector 100 can be configured to be less than or approximately equal to the interior fluid-carrying volume of the patient's catheter or less than or approximately equal to a portion of the patient's catheter that is configured to be positioned outside of the patient's body during use. In some embodiments, the volume of additive-infused liquid is less than or equal to about: 0.25 mL, 0.5 mL, 2 mL, 5 mL, 10 mL, 25 mL, values between the aforementioned values, ranges spanning those values, or otherwise. In some configurations, the connector can be configured to receive a volume sufficient to fill or overfill the catheter and/or to deliver a small amount of additive or the entire volume of additive infused liquid into the patient (e.g., when the additive is a medicament, etc.). In some embodiments, in a multistage configuration or other configuration, a volume of additive-infused liquid can be delivered from the connector, followed by an additive-free (or substantially additive-free) volume of medical fluid. In some embodiments, for example, where a therapeutic agent and locking agent are provided in a connector (or a series of connectors), the connector (or series) can be configured to deliver the therapeutic additive into the patient completely and to lock the catheter with the locking agent, which is retained or substantially retained in the catheter.


In some embodiments, the connector is configured to achieve one or more of the above-referenced volume distributions to the catheter when using any commercial catheter, including those selected from the group consisting of Hickman, Broviac, or Leonard tunneled catheters, including at least about 9 Fr or at least about 10 Fr Single or Double Lumen catheters, Double or Triple (e.g., red, blue, or white) Lumen catheters, at least about 12 Fr Double Lumen catheters, or at least about 12.5 Triple Lumen catheters. In some embodiments, the volume of additive-infused medical fluid distributed from (e.g., delivered out of) the connector is greater than or equal to about: 0.25 mL, 0.5 mL, 2 mL, 5 mL, values between the aforementioned values, ranges spanning those values, or otherwise. In some embodiments, the volume of additive-free medical fluid distributed from (e.g., delivered out of) the connector is greater than or equal to about: 0.25 mL, 0.5 mL, 2 mL, 5 mL, 10 mL, 25 mL, values between the aforementioned values, ranges spanning those values, or otherwise.


As also described in detail elsewhere herein, in some embodiments, at or near the termination of an infusion of medical liquid into the patient through the connector 100 (e.g., approximately at the point that the volume to be injected is achieved, the volume at which a plunger of a syringe used to infuse the fluid nears or reaches the terminal end of a syringe or bottoms out, at a point where the infusion is halted, etc.), the medical liquid in the secondary fluid pathway 110 exits the secondary fluid pathway 110 and passes through the fluid outlet 104. In some embodiments, this distribution of liquid from the secondary fluid pathway occurs automatically and/or without active manipulation of the connector by the user. In some embodiments, the medical fluid (e.g., the medical liquid without additive) and the additive-containing fluid (e.g., additive-infused liquid) mix at a location and/or time near or substantially at the end of the infusion of medical liquid through the connector 100 and/or form a locking solution at the fluid exit region 114 of the connector 100.


It is contemplated that any other embodiment that follows can include any feature, structure, component, material, step, or method of the connector 100 of FIG. 1, whether or not explicitly described and/or illustrated in such other embodiment for purposes of brevity. Nothing described or illustrated in connection with the connector 100 of FIG. 1 is required or essential or indispensable in connector 100 or in any other embodiment in this specification.


As illustrated in FIG. 2A, a connector 200 can include a fluid inlet 102 in the form of a first fluid-line attachment 202. The connector 200 can also include a cover cap 203, a housing 220, an air port 222, and a fluid outlet 104 in the form of a second fluid-line attachment 204. In some embodiments, the housing 220 can be formed of a rigid or substantially rigid material, such as polycarbonate. Either or both of the first or second fluid-line attachments can be closeable or resealable male or female connectors, such as a resealable female luer connector as the fluid inlet 202 and a resealable male luer connector with a male protrusion 205 as the fluid outlet 204, as shown. Any or all of the housing 220, the fluid guide 224, and/or the flexible carrier 232, and/or any other component or collection of components of the connector 200 can be made of, or can comprise a portion that is made of, a transparent or clear material to permit viewing of movement inside of the housing 220 or to permit viewing of liquid passing through the housing 220 or mixing with one or more additives inside of the housing 220. Any or all of the first fluid-line attachment 202, the housing 220, and the second fluid-line attachment 204 can be made of one or more rigid materials, such as polycarbonate or another form of plastic.



FIGS. 2B and 2C show other embodiments of medical connectors 200A, 200B. The embodiments of FIGS. 2B and 2C can include features that are the same as or that are different from features of the embodiment of FIG. 2A. FIG. 3A illustrates an example cross-section of the connector 200. FIGS. 3D-3E illustrate other example cross-sections of medical connectors 200C, 200D, although the connector 200C, 200D can have the same or substantially the same outer appearance as the connector 200 shown in FIG. 2A. The embodiments of FIGS. 3D-3F can include features that are the same as or that are different from features of the embodiment of FIGS. 2A and 3A. Any feature, structure, component, material, step, or method that is described and/or illustrated in one of FIGS. 2A-2C and 3A-3F can be used with or instead of any feature, structure, component, material, step, or method that is described and/or illustrated in any other embodiment in this specification. Similar features (e.g., fluid guides, internal fluid pathways, etc.) for different embodiments of the connectors are shown with coinciding numerical values but labeled with either a letter or a different letter (e.g., no letter for connector 200, the letter “A” for connector 200A, and the letter “B” for connector 200B, the letter “C” for connector 200C, and the letter “D” for connector 200D). For example, comparing the embodiment of FIG. 2A to the embodiment of FIG. 2B, the housing 220 of the connector 200 in FIG. 2A coincides to the housing 220A of the connector 200A in FIG. 2B. Likewise, comparing the embodiment of FIG. 2A or 2B to the embodiment of FIG. 2C, the housing 220 of the connector 200 in FIG. 2A or the housing 220A of the connector 200A in FIG. 2B coincides to the housing 220B of the connector 200B in FIG. 2C.


For brevity, not every feature of the connector 200A of FIG. 3B, the connector 200B of FIG. 3C, the connector 200C of FIG. 3D, or the connector 200D of FIGS. 3E-3F are numerically indicated, though certain features of the connector 200A, 200B, 200C, or 200D are apparent by comparing it with the connector 200 of FIG. 3A and such features form part of the disclosure of FIGS. 3B-3F. In addition, just as the embodiments of FIGS. 3A-3F can have features that are the same or substantially the same, those embodiments can include one or more features that are different, as shown or otherwise. It should be appreciated that different features of the embodiments of FIGS. 3A-3F are for illustration only, and as disclosed elsewhere herein, any feature, structure, or component that is described and/or illustrated in one embodiment in this specification can be used with or instead of any feature, structure, or component that is described and/or illustrated in any other embodiment in this specification. Additionally, one or more of the features described for the illustrative embodiments herein can be excluded from other embodiments.


As illustrated in FIG. 3A, an interior region of the connector 200 can comprise multiple components, including a fluid guide 224 with a proximal fluid port 228, a proximal cover region 256 (e.g., with a vent 225 (see also FIG. 4)), an internal fluid pathway 226, a distal fluid port 230 (see also FIG. 4), and a distal attachment region 250 (see also FIG. 4); and a fluid modifying region 254 and a fluid modifier 116 in the form of a flexible carrier 232 with an internal region 248. In some embodiments, as shown, the fluid modifier 116 can be held in place at a plurality of points or regions inside of the connector 100. For example, a proximal edge 258 of the flexible carrier 232 can be securely held between an upper region 260 (e.g., forming a lip, a projection, a barb, etc.) of the housing 220 and an underside of the outer edge of the cover region 256 of the fluid guide 224; and a distal end region 262 of the flexible carrier 232 can be securely held circumferentially in a fluid-tight manner in the distal attachment region 250 of the fluid guide 224, such as by forming a distal opening in the flexible carrier 232 that is slightly smaller than the outer circumference of the distal attachment region 250, causing the distal opening to exert a radially inwardly directed restoring force which tightly grips the distal attachment region 250 of the fluid guide 224. As shown, each of the connectors 200, 200A, 200B, 200C, 200D can be formed as a single integrated connector with any combination or all of the parts illustrated in the figures or described in the text permanently and non-removably attached to each other, and not configured to be attached together or removed from each other by a user in the normal course of use. Of course, in some embodiments, any components or combinations of components can be removable or attachable from each other by a user in suitable configurations, such as in modular configurations with different types of fluid modifiers that can be combined with different types of connector components. As illustrated in some embodiments, each of the connectors 200, 200A, 200B, 200C, 200D can be needle-free or needle-less or spike-less, without requiring an exposed metal or plastic needle or spike to pierce or penetrate a septum or seal or other structure to enable fluid flow.


As shown in FIGS. 3A, 3D, and 3E, the first fluid-line attachment 202, 202C, 202D can comprise an internal fluid channel 236, 236C, 236D that comprises a proximal female end 238, 238C, 238D (which in some embodiments can include an ISO 594-compliant luer taper) with a male-receiving region 234, 234C, 234D, and a male end 240, 240C, 240D that is coupled to the proximal fluid port 228, 228C, 228D of the fluid guide 224, 224C, 224D. In some embodiments, as shown in FIGS. 3A, 3D, and 3E, the proximal female end 238, 238C, 238D can be threaded. In some embodiments, the proximal female end is not threaded. The second fluid-line attachment 204, 204C, 204D can comprise an internal fluid channel 244, 244C, 244D, an internally threaded shroud 242, 242C, 242D, and a male luer protrusion 205, 205C, 205D (which in some embodiments can include an ISO 594-compliant luer taper). In some embodiments, the internal fluid pathway 226, 226C, 226D can have an internal diameter that is smaller than an internal diameter of the proximal internal fluid channel 236, 236C, 236D and/or an internal diameter of the internal fluid channel 244, 244C, 244D. In some embodiments, as shown in FIG. 3C, any shroud provided herein can lack threading or, as shown in FIG. 3B, any shroud provided herein can include threading. In some embodiments, any of the inlet or outlet adaptors (male or female) and shrouds disclosed herein can include threading or lack threading. In some embodiments, as shown in the connector 200, 200C, 200D, the main fluid pathway 108 can be provided in the form of the combination of the internal fluid channel 236, 236C, 236D of the first fluid-line attachment and the internal fluid pathway 226, 226C, 226D of the fluid guide 224, 224C, 224D. In some embodiments, either or both of the first or second fluid-line attachments 202, 202C, 202D, 204, 204C, 204D can comprise closeable, resealable, and/or swabbable medical fluid connectors.


As shown in FIG. 3B, in some embodiments, instead of a male connection, the connector 200A can include a fluid inlet 102 comprising a first fluid-line attachment 202A and a female luer connector 206A. In some embodiments, as shown in FIG. 3B, the female luer connector 206A can include a male-receiving region 236A configured to receive a male protrusion (which in some embodiments can include an ISO 594-compliant luer taper). In some embodiments, the fluid inlet 102 is recessed as shown in FIG. 3B. As shown, a recessed fluid-line attachment 202A can be disposed wholly within the connector and/or not protruding from the connector. In some embodiments, not shown, the fluid line attachment can be partially disposed in and/or partially protruding or exposed from the connector. Having a recessed fluid inlet 102 makes the connector 200A advantageously compact while still offering ease of manipulation by a user (e.g., providing a large area on the side of the connector for grasping between a finger and the thumb, allowing rotation and manipulation of the connector, for instance). In some embodiments, the recessed configuration facilitates bulk storage and/or transport of the connectors. In some embodiments, for example, the connectors 200A can be connected serially (e.g., end-to-end) and stored. As also disclosed elsewhere herein, serial connection or other connection of multiple connectors can advantageously be used to infuse more than one additive at a time. For instance, in some embodiments, where connectors are attached serially, each connector 200A in a series can comprise a different therapeutic and/or chemical agent. In some embodiments, during infusion of a medical fluid through serially linked connectors, different agents can be infused at once (e.g., with one infusion of medical fluid). In some embodiments, different connector configurations can be connected serially, in parallel, or in any other way to provide a desired additive infusion profile. The recessed configuration is also less bulky when in use, lowering chances that the connector is inadvertently contacted after insertion of the catheter into a patient, increasing the comfort level of the patient.


In some embodiments, as shown in FIG. 3B, the recessed fluid inlet provides a receptacle 261A configured to receive a shroud of, for example, a syringe or another connector having a male luer fitting. In some embodiments, the receptacle 261A is configured to snuggly receive an interfacing shroud (e.g., is snug-fit). In some embodiments, the snug fitting within the receptacle provides added strength and/or stability to the connection between the coupling features. In some embodiments, this strength and/or stability can beneficially prevent movement, bending, or breakage of the coupled components. In some embodiments, interaction between the receptacle 261A and a shroud of a coupled device also provides stability in configurations where multiple connectors are attached serially by, for instance, preventing or substantially lowering the amount of movement between attached components (e.g., reducing bending, etc.).


In some embodiments, the connector has a length measured generally from a first end (e.g., from the inlet 102) to a second end (e.g., to the outlet 104) along the direction of fluid flow. In some embodiments, the connector also has a diameter measured across the connector transverse to the direction of fluid flow from a first side of the connector to a second side laterally (e.g., extending radially outward from the fluid pathway). In some embodiments, this diameter of the connector can be greater than an outer diameter of the fluid inlet and/or the fluid outlet. In some embodiments, this diameter can improve ease of gripping of the connector between fingers of a user.


As shown in FIGS. 3A, 3B, 3D, and 3E, in some embodiments, the length of the connector can be greater than the diameter (or equal to or greater than the diameter). As shown in FIG. 3C, in some embodiments, the diameter can be greater than the length of the connector (or greater than or equal to the length).


In some embodiments, as also described elsewhere herein, having a length greater than the width of the connector also allows the user to easily grasp the connector and align it with the catheter during placement, replacement, or manipulation of the connector. In some embodiments, having a diameter greater than or equal to the length facilitates bulk storage and/or transport of the connectors. For example, as also described elsewhere herein, the connectors can be connected serially and stored or used (e.g., to infuse more than one additive or to infuse a greater quantity of additive). In some embodiments, in configurations where the diameter is greater than or equal to the length of the connector, serial or parallel connection and disconnection of the connectors is facilitated because the lateral sides of the connector protrude from the inlet and outlet portions of the connector, allowing easier access to and manipulation of individual connectors.


As shown in FIG. 3C, in some embodiments, any of the connectors disclosed herein can comprise traction features 221B to facilitate manipulation (e.g., placement, twisting, movement, etc.) of the connectors. For example, as shown in FIG. 3C, the connector 200B can comprise grips 221B (e.g., roughenings, knurlings, traction pads, dimples, protrusions, ribs, etc.) around the periphery or portion of the periphery of the exterior of the connector 200B.


As shown in FIG. 3C, in some embodiments, the connector 200B can include a fluid inlet 102 comprising a first fluid-line attachment 202B and a female luer connector 206B. As shown, the fluid inlet can lack a shroud. In some embodiments, as shown in FIG. 3C, the female luer connector 206B can include a male-receiving region 236B configured to receive a male protrusion (which in some embodiments can include an ISO 594-compliant luer taper). In some embodiments, the fluid outlet of the connector 200B comprises a second fluid-line attachment 204B. In some embodiments, the second fluid-line attachment comprises one or more of an internal fluid channel 244B, a shroud 242 (e.g., a non-threaded shroud), and a male luer protrusion 205B (which in some embodiments can include an ISO 594-compliant luer taper). In some embodiments, the fluid outlet 104 lacks a shroud.


In some embodiments, the flexible carrier can be placed in an orientation that allows it to deform towards different portions of the connector 200, 200A, 200B, 200C, 200D. For example, in the embodiments of FIGS. 3A, 3B, 3D, and 3E, the flexible carrier 232, 232A, 232C, 232D is configured to deform upwardly and in a lateral direction that is towards the internal fluid pathway 226, 226A, 226C, 226D. In FIG. 3C, the flexible carrier 232B configured to deform downwardly and laterally in a direction that is towards the housing 220B. In other embodiments, not shown, the flexible carrier can be placed in a position to deform in a direction towards the proximal end of the connector, or otherwise.


In some embodiments, such as shown in the embodiments of FIGS. 3A, 3D-3F, and 6A-9, the upwardly deforming configuration can advantageously utilize gravity as an additional restoring force when expelling the additive-infused liquid into the catheter. In other words, gravity (in addition to or instead of the elastic force of the fluid modifier) can provide a restoring force, pushing the additive-infused fluid out of the fluid modifying region. In some embodiments, as shown in FIGS. 3C and 10-13, a downwardly deforming configuration (e.g., where the fluid contacting the flexible carrier enters at an upper portion of the flexible carrier and pushes the flexible carrier downward as the flexible carrier is deformed) can advantageously utilize gravity as an additional deforming force when infusing the medical liquid into the catheter. In other words, gravity (in addition to flow force of the fluid) can push against the flexible carrier, deforming it, and allowing infusion of the medical fluid with the additive. In some embodiments, during infusion, the user can manipulate the orientation of the connector (e.g., by holding it so the outlet faces upwardly or downwardly) to allow gravity to either or both aid in the deformation or restoration of the flexible carrier.


In some embodiments, such as shown in the embodiment of FIG. 3C, the flexible carrier can be shaped in a manner that itself resists deformation. For example, the flexible carrier 232B of the embodiment of FIG. 3C is cross-sectionally arch-shaped or substantially arch-shaped. The restorative force of one or more resiliently-shaped configurations (arch-shaped, arc-shaped, semi-circular, etc.) can advantageously provide additional restorative force to expel the additive-infused liquid from the fluid modifying region 254B.


As illustrated, in some embodiments, the first diversion region 111 of the embodiment of FIG. 1 can be provided in the connector 200, 200A, 200B, 200D in the form of a plurality of alternative fluid pathways in the region between a distal end of the fluid guide 224, 224A, 224B, 224D and a constriction or diverter or divider 246, 246A, 246B, 246D, or near a distal end of the fluid guide 224C, with a diverter or divider 246C located proximal to the transitional region 274C. In some embodiments, the diverter or divider 246, 246A, 246B, 246C, 246D can comprise an opening that is narrower than the fluid pathway 226, 226A, 226B, 226C, 226D within the fluid guide 224, 224A, 224B, 224C, 224D. In some embodiments, the diverter or divider 246, 246A, 246B, 246C, 246D can include a constriction (such as shown in FIG. 3A-3E), a manifold, a valve, or any other structure that can allow some but not all of the fluid from the fluid pathway 226, 226A, 226B, 226C, 226D to pass to the internal flow channel 244, 244A, 244B, 244C, 244D. The change in cross-sectional width between the fluid pathway 226, 226A, 226B, 226C, 226D within the fluid guide 224, 224A, 224B, 224C, 224D and the opening in the diverter or divider 246, 246A, 246B, 246C, 246D can cause some of the liquid that is passing through connector 200, 200A, 200B, 200C, 200D to be diverted laterally into a lateral fluid region 252, 252A, 252B, 252C, 252D and then upwardly or downwardly into a fluid-modifying region 254, 254A, 254B, 254C, 254D such as a variable-volume fluid-modifying region 254, 254A, 254B, 254C, 254D between an interior wall 268, 268A, 268B, 268C, 268D of the housing 220, 220A, 220B, 220C, 220D and an exterior wall 264, 264A, 264B, 264C, 264D of the fluid modifier 116.


As shown in FIGS. 3A-3C, the transitional region 274, 274A, 274B can be located distal to the distal fluid port 230, 230A, 230B. The transitional region 274, 274A, 274B can include a gap separating a proximal end of the diverter or divider 246, 246A, 246B and a distal end 272, 272A, 272B of the fluid guide 224, 224A, 224B. The diverter or divider 246, 246A, 246B can be located distal to the transitional region 274, 274A, 274B. The transitional region 274, 274B in FIGS. 6A and 10 respectively can include the proximal opening of the diverter or divider 246, 246B and the lateral opening where the portion of the medical liquid 266, 266B is diverted laterally, and/or the space or volume located between these locations or structures. The lateral fluid region 252, 252A, 252B can extend radially and/or generally transverse to the fluid pathway 226, 226A, 226B.


As shown in FIG. 3D, the diverter or divider 246C can be proximal to the transitional region 274C and can extend distally from the distal fluid port 230C to the transitional region 274C. The fluid guide 224C can have an outer surface 280C near the distal end 272C of the fluid guide 224C to interface with an inner surface 282C of the housing 220C near a proximal end of the second fluid-line attachment 204C. The interface can be impermeable to liquid such that liquid cannot pass through between the outer surface 280C and the inner surface 282C (for example, via a tight fit at the interface). The lateral fluid region 252C can be located near or at the distal fluid port 230C. The lateral fluid region 252C can extend generally transversely from the fluid pathway 226C to the variable-volume fluid-modifying region 254C and can comprise a generally uniform cross-section. In some embodiments, the cross-section of the lateral fluid region 252C can be generally circular.


The opening in the diverter or divider 246C can have a greater cross-sectional area than the lateral fluid region 252C. In some embodiments, the cross-sectional area of the opening in the diverter or divider 246C can be about four times that of the lateral fluid region 252C. In some embodiments, the opening in the diverter or divider 246C can have a greater internal diameter or width than the lateral fluid region 252C. In some embodiments, the internal diameter of the opening in the diverter or divider 246C can be at least about two times that of the lateral fluid region 252C. In some embodiments, the internal diameter of the opening in the diverter or divider 246C can be about 0.032″ and the internal diameter of the lateral fluid region 252C can be about 0.016″.


As shown in FIG. 3E, the diverter or divider 246D can be located distal to the transitional region 274D so that the internal flow channel 244D extends distally from the diverter or divider 246D. The fluid guide 224D can have an outer surface 280D near the distal end 272D of the fluid guide 224D to interface with an inner surface 282D of the housing 220D near or at the proximal end of the second fluid-line attachment 204D. The interface can be liquid impermeable such that liquid cannot pass through between the outer surface 280D and the inner surface 282D (for example, via a tight fit at the interface). As shown in FIGS. 3E and 3F, the lateral fluid region 252D can be located to a lateral side of the transitional region 274D. The lateral fluid region 252D can be in fluid communication with the transitional region 274D at a distal end of the fluid region 252D, and can extend generally parallel to the fluid pathway 226D from the transitional region 274D to the variable-volume fluid-modifying region 254D. As shown in FIG. 3E, the variable-volume fluid-modifying region 254D can include a portion between a distal end 286D of the fluid-modifying region 254D and a shoulder 284D of the fluid guide 224D. The lateral fluid region 252D can be in fluid communication with fluid-modifying region 254D at a location within this portion. In some embodiments, such as shown in FIGS. 3E and 3F, the lateral fluid region 252D can be adjacent the outer surface 280D near the distal end 272D of the fluid guide 224D. In other embodiments, the lateral fluid region can be located more laterally, with a tunnel connecting the lateral fluid region and the transitional region 274D.


The lateral fluid region 252D can have a generally uniform cross-section. As shown in FIG. 3F, the lateral fluid region 252D can have a generally rectangular cross-section. In other embodiments, the cross section of the lateral fluid region 252D can have other shapes, such as semicircular, triangular, or others. The diverter or divider 246D can have an opening with a greater cross-sectional area than the lateral fluid region 252D. In some embodiments, the cross-sectional area of the opening in the diverter or divider 246D can be about four times that of the lateral fluid region 252D. In some embodiments, the opening in the diverter or divider 246D can have a greater internal dimension than the lateral fluid region 252D. In some embodiments, the internal diameter of the opening in the diverter or divider 246D can be greater than a width of the cross-section of the lateral fluid region 252D. In some embodiments, the internal diameter of the opening in the diverter or divider 246D can be about 0.032″ (resulting in a cross-sectional area of about 0.0008 square inch) and the lateral fluid region 252C can have cross-sectional dimensions such as 0.020″×0.010″, or any other dimensions resulting in a cross-sectional area of about 0.0002 square inch.


In some embodiments, such as shown in FIG. 3A, at least a portion of the fluid modifying region 254 can be created by a separation or by an increase in distance between the flexible carrier 232 and another component of the connector 200, such as an inner wall 268 of the connector 200, producing a variable volume into which liquid can flow. The secondary fluid pathway 110 of the embodiment of FIG. 1 can be provided in the connector 200, 200A, 200B, 200C, 200D of FIGS. 3A-3F in the form of the lateral fluid region 252, 252A, 252B, 252C, 252D and the fluid-modifying region 254, 254A, 254B, 254C, 254D, such as describedelsewhere herein. As illustrated in FIGS. 7-9 and FIGS. 11-13, the size or volume of the secondary fluid pathway 110 in the connector 200 (or 200C, 200D), 200B (or connector 200A, not shown) can be variable over time or variable as a function of the volume of fluid that has been infused into and/or out of the connector 200 (or 200C, 200D), 200B. In some embodiments, as shown in FIGS. 3A-3E and 6-13, the fluid modifier 116 is a flexible carrier. In some embodiments, the fluid modifier 116 is a structure or device that does not significantly bend or flex to change the volume or direction of the fluid flow path, but instead merely permits an additive to be emitted or eluted or leached out into the fluid flow path, such as by dissolving into the fluid or releasing into the fluid or permitting the fluid to flow in, through, or around the fluid modifier 116 while the fluid modifier 116 itself remains essentially or entirely static.


In some embodiments, the connector comprises a fluid pathway with at least a portion that has a completely or at least substantially unobstructed pathway (e.g., through the entirety of the connector). For instance, while the constriction or diverter or divider 246, 246A, 246B, 246C, 246D can divert a portion of the medical fluid from the primary fluid path, a portion of fluid can travel directly through the opening in the diverter or divider or constriction unimpeded 266 (or 266C, 266D), 266B (as shown in FIGS. 6A-13). In some embodiments, the medical connector is configured to allow at least a portion of the medical fluid to travel through it uninterrupted in a straight or substantially straight pathway and devoid (or substantially devoid) of additive. In some embodiments, as shown in FIGS. 3A-3E, the variable-volume fluid-modifying region 254, 254A, 254B, 254C, 254D is in fluidic communication with the fluid guide 224, 224A, 224B, 224C, 224D, the opening in the constriction or diverter or divider 246, 246A, 246B, 246C, 246D, and/or the internal fluid channel 244, 244A, 244B, 244C, 244D. Thus, while some embodiments can achieve certain objectives disclosed herein using a valve (e.g., to divert at least a portion of fluid into, for instance, a secondary fluid pathway of FIG. 1), in other embodiments, the connector lacks a valve. In some embodiments, the infusion of additive containing fluid into the catheter happens by virtue of the elasticity of the flexible carrier, automatically and without additional infusion steps taken by a user.


As shown in FIG. 5, in some embodiments, the flexible carrier 232 can be formed with a generally paraboloid shape, in which the exterior wall 264 comprises a wider proximal cross-sectional width and a narrower distal cross-sectional width. Any other suitable shape can be used (as shown in, for example, FIG. 3C). In some embodiments, as shown, the flexible carrier 232 can be made of a flexible, resilient, deformable, and/or compressible material, such as silicone or another polymeric material. In some embodiments, the compressible material is porous or adherent to allow temporary uptake or reception of a therapeutic or antibacterial agent that can be subsequently released into the medical fluid. As shown, in some situations, the additive 112 can be provided on only one side of the flexible carrier 232 (or on any other carrier of additive 112), especially in situations when the medical fluid only contacts the flexible carrier 232 on one side. Of course, in many embodiments, the additive 112 can be provided on multiple sides of the flexible carrier 232 or the flexible carrier 232 can be provided with additive 112 embedded within and/or throughout its structure, such as when the flexible carrier 232 is a matrix or otherwise has passages through which the medical fluid passes or in which the medical fluid is temporarily absorbed. In some embodiments, the flexible carrier 232, 232A, 232B, 232C, 232D can be molded or otherwise made in a natural or native shape as shown in FIGS. 3A-3E and 5. In some embodiments, the flexible carrier is woven or otherwise formed. In some situations, when the flexible carrier 232, 232A, 232B, 232C, 232D is deformed or compressed or moved in some way that is different from its natural or native shape, it can be configured to exert a restoring force to return resiliently to its natural or native shape. In some embodiments, the carrier can be formed of the additive 112 such that the carrier itself is partially or totally consumed or partially or totally dissolved away or leached into the medical fluid.


The flexible carrier 232, 232A, 232B, 232C, 232D can be configured to carry one or more additives 112 and to transfer the one or more additives 112 into the liquid that flows around or contacts the flexible carrier 232, 232A, 232B, 232C, 232D. In some embodiments, the one or more additives 112 can comprise any one or more of the following: an antimicrobial, an antibiotic, an antiseptic, an analgesic, an anesthetic, a blood-thinner, a chemotherapy drug, an immunosuppressive drug, a nutritional supplement, or any other therapeutic substance that is combinable with a liquid flowing through the connector 200, 200A, 200B, 200C, 200D. An example of an antimicrobial additive is chlorhexidine gluconate, which can be provided in powdered form and coated or dusted or positioned or otherwise placed around the outer surface of the exterior wall 264, 264A, 264B, 264C, 264D of the flexible carrier 232, 232A, 232B, 232C, 232D. In some embodiments, the one or more additives 112 can be temporarily adhered or bound or attached to the exterior wall 264, 264A, 264B, 264C, 264D of the flexible carrier 232, 232A, 232B, 232C, 232D, such as by electrostatic forces or in surface recesses or by a water-soluble or saline-soluble binder, such as glycerol. In some embodiments, the one or more additives 112 can be formed or trapped or bound to or into the structure of the exterior wall 264, 264A, 264B, 264C, 264D of the flexible carrier 232, 232A, 232B, 232C, 232D such as by being captured within a cross-linked matrix of the exterior wall 264, 264A, 264B, 264C, 264D in a manner that permits leaching out or eluting of the one or more additives into the liquid as the liquid flows around or through the flexible carrier.


In some embodiments, a degradable (e.g., biodegradable, water dissolvable, etc.) matrix is deposited on the exterior wall 264, 264A, 264B, 264C, 264D and/or on the flexible carrier 232, 232A, 232B, 232C, 232D. In some embodiments, the flexible carrier 232, 232A, 232B, 232C, 232D is a degradable matrix. In some embodiments, a portion of the degradable matrix dissolves upon exposure to medical fluid. In some embodiments, as the matrix degrades, sufficient additive is released into the medical fluid to permit locking of the catheter. In some embodiments, the degradable matrix can have a tailored or adjustable degradation rate and/or additive concentration such that the degradation rate and/or delivery concentration is sufficient to deliver an appropriate locking concentration throughout the estimated lifetime of the catheter or the connector. For example, if a catheter is estimated to require locking about 15 times over its lifetime, the flexible carrier 232, 232A, 232B, 232C, 232D can be tailored to allow 1, 2, 10, 15 or more locks of the catheter line with sufficient therapeutic agent to, for example, avoid microbial growth in the catheter during the average lifetime use of the catheter.


In some embodiments, the additive (e.g. as disposed in, around, or near the variable-volume fluid-modifying region 254, 254A, 254B, 254C, 254D or elsewhere in the connector) comprises antibiotic. In some embodiments, the antibiotic is a gram-positive antibacterial, a gram negative antibacterial, or a combination thereof. In some embodiments, the additive comprises one or more of chlorhexidine, chlorhexidine gluconate, vancomycin, cefazolin, ceftazidime, ciprofloxacin, gentamicin, and/or ampicillin.


In some embodiments, the additive comprises an anti-coagulant. In some embodiments, the anti-coagulent is heparin. The anti-coagulant can be provided as the only additive or as an additive in combination with other additives described elsewhere herein. In some embodiments, the anti-coagulant is provided at a concentration of at least about: 100 units/mL, 2500 units/mL, 5000 units/mL, values between the aforementioned values, ranges spanning those values, or otherwise.


In some embodiments, the connector is configured to provide an additive infused solution with a concentration of equal to or at least about 0.2 mg/mL, 0.5 mg/mL, 1.0 mg/mL, 2.5 mg/mL, 5.0 mg/mL, 10 mg/mL, values between the aforementioned values, ranges spanning those values, or otherwise.


As illustrated in FIGS. 6A-9 (for the embodiment shown in FIGS. 2A, 3A, and 3D-3F) and FIGS. 10-13 (for the embodiment shown in FIGS. 2C and 3C), some embodiments of the connector 200, 200C, 200D, 200B can provide fluid flow in a plurality of different stages with different fluid flow characteristics and/or different liquid compositions. For example, in a first stage of the connector 200, 200C, 200D, 200B, as illustrated in FIGS. 6A-6C and 10, the flexible carrier 232, 232C, 232D, 232B can be in a first or initial phase in which its shape, orientation, and/or location is in a default or natural or native position. When moved or modified away from this position to a second or modified phase, the flexible carrier 232, 232C, 232D, 232B can be configured to exert one or more restoring forces to return to the first or initial phase. As shown, in the first or initial phase, the outer exterior wall 264, 264C, 264D, 264B of the flexible carrier 232, 232C, 232D, 232B can be in contact with, cover, and/or overlay at least a portion of, or nearly entirely, or all of, an interior wall of the region of the housing 220, 220C, 220D, 220B of the connector 200, 200C, 200D, 200B in which the flexible carrier 232, 232C, 232D, 232B is disposed.


As shown in FIGS. 6A-6C and 10, as a medical liquid 266, 266C, 266D, 266B (e.g., saline) is infused into the proximal end of the connector 200, 200C, 200D, 200B, such as from a syringe 270 (not shown in FIGS. 6B and 6C), 270B or other medical implement, the medical liquid passes through the first fluid-line attachment 202, 202C, 202D, 202B, into the internal pathway 226, 226C, 226D, 226B of the fluid guide 224, 224C, 224D, 224B, and then to the transitional region 274, 274C, 274D, 274B. The transitional region 274, 274D, 274B can be between the distal end 272, 274D, 272B of the fluid guide 224, 224D, 224B and the diverter or divider 246, 246D, 246B. The transitional region 274C can be distal of the distal end 272C of the fluid guide 224C and the diverter or divider 246C. As shown, the cross-sectional width or diameter of the constriction or opening in the diverter or divider 246, 246C, 246D, 246B is smaller than the cross-sectional width or diameter of the internal pathway 226, 226C, 226D, 226B of the fluid guide 224, 224C, 224D, 224B.


Some of the medical liquid 266, 266C, 266D, 266B passes from the transitional region 274, 274D, 274B directly through the constriction or opening in the diverter or divider 246, 246D, 246B, or from the internal fluid pathway 226C directly through the opening in the diverter or diverter 246C, into the interior of the male protrusion 205, 205C, 205D, 205B. In some embodiments, as illustrated, the portion of the medical liquid 266, 266C, 266D, 266B that passes directly through can be essentially unchanged; that is, it can have the same or essentially the same composition as before it entered the connector 200, 200C, 200D, 200B, and/or it can be therapeutically or clinically the same (e.g., the medical liquid can have no concentration of additive or clinically insignificant concentration, which can be a low enough concentration of additive dissolved in the medical liquid such that the medical fluid can be infused directly into a patient or otherwise be used as though it were completely additive-free). This essentially unchanged medical liquid 266, 266C, 266D, 266B passes very quickly through the connector 200, 200C, 200D, 200B, without a clinically significant delay, and emerges from and continues to be emitted from the second fluid-line attachment 204, 204C, 204D, 204B during an initial time period or over a period during which an initial volume of liquid is dispensed from the connector 200, 200C, 200D, 200B.


Generally simultaneously, another portion of the medical liquid 266, 266C, 266D, 266B is diverted laterally because the opening in the diverter or divider 246, 246C, 246D, 246B creates a lower flow rate (volume/time) of medical liquid 266, 266C, 266D, 266B entering from the wider internal fluid pathway 226, 226C, 226D, 226B of the fluid guide 224, 224C, 224D, 224B (and the transitional region 274, 274D, 274B) into the opening in the diverter or divider 246, 246C, 246D, 246B. As described above, the transitional region 274, 274D, 274B in FIGS. 6A, 6C, and 10 respectively can include the proximal opening of the diverter or divider 246, 246D, 246B and the lateral opening where the portion of the medical liquid 266, 266D, 266B is diverted laterally, and/or the space or volume located between these locations or structures. As described above, the lateral fluid region 252C and the diverter or divider 246C in FIG. 6B can both be located proximal to the transitional region 274C. A ratio of the flow rate of medical fluid, and hence a volume of medical fluid, entering into the opening in the diverter or divider and into the lateral fluid region can be proportional to a ratio of the cross-sectional areas of the opening in the diverter or divider and the lateral fluid region. In some embodiments, such as shown in FIGS. 6B and 6C, the cross-sectional area of the opening in the diverter or divider 246C, 246D can be at least about three times or at least about four times that of the lateral fluid region 252C, 252D. When a volume of the medical fluid 266C, 266D enters the fluid pathway 226C, 226D, at least about 70% or at least about 80% of the volume of the medical fluid 266C, 266D enters the opening in the diverter or divider 246C, 246D, and less than or equal to about 30% or less than or equal to about 20% of the volume of the medical fluid 266C, 266D enters the lateral fluid region 252C, 252D. The ratio of the volume of medical fluid entering into the opening in the diverter or divider and into the lateral fluid region can be adjusted by adjusting the ratio of the cross-sectional areas of the opening in the diverter or divider and the lateral fluid region. In some embodiments, such as shown in FIGS. 6B and 6C, the ratio of the cross-sectional areas of the opening in the diverter or divider and the lateral fluid region can be adjusted by changing the size of the opening in the diverter or divider 246C, 246D, and/or the size of the lateral fluid region 252C, 252D.


In some embodiments, the diverted or laterally flowing liquid 276, 276C, 276D, 276B moves into the variable-volume fluid-modifying region 254, 254C, 254D, 254B and begins to: (a) exert a modifying force on the flexible carrier 232, 232C, 232D, 232B; and/or (b) contacts the exterior wall 264, 264C, 264D, 264B of the flexible carrier 232, 232C, 232D, 232B. In some embodiments of the connector 200, 200C, 200D, 200B, where the fluid modifier 116 is a flexible member but not a flexible carrier 232, 232C, 232D, 232B (e.g., because the fluid modifier 116 does not carry an additive 112), the variable-volume fluid-modifying region 254, 254C, 254D, 254B can contain the additive 112 or some other region or structure of the connector 200, 200C, 200D, 200B can contain or hold the additive 112 (e.g., a portion of a fluid-contacting inner wall 268, 268C, 268D, 268B of the housing 220, 200C, 200D, 220B or a portion of the fluid guide 224, 224C, 224D, 224B or one or more of any other structures or components of the connector 200, 200C, 200D, 200B, or any combination of structures or components). In some embodiments, the additive 112 can be omitted.


As shown in FIGS. 7-8 and 11-12, in a second stage of the connector 200, 200B, as more medical liquid 266, 266B is infused into the connector 200, 200B (such as by distally advancing and/or depressing a syringe plunger 277, 277B in the syringe 270, 270B), more medical liquid 266, 266B continues to pass through the diverter or divider 246, 246B and more liquid is forced into the variable-volume fluid-modifying region 254, 254B. The connector 200C, 200D can also have a second stage that can have substantially the same features as disclosed herein with reference to FIGS. 7 and 8 and that is not repeated for brevity. The additional liquid in the variable-volume fluid-modifying region 254, 254B causes the liquid to exert a force against the flexible carrier 232, 232B which causes at least a portion of the flexible carrier 232, 232B, such as a wall of the flexible carrier, to flex, bend, contract, collapse, deform, or otherwise move away from its default or natural or native position. The fluid-modifying region 254, or any component thereof, including the flexible carrier 232, 232B, can comprise a material that is softer, more pliable, more resilient, and/or more flexible than the material of the housing 220 of the connector 200. In some embodiments, at the same time, air contained within the internal region 248, 248B of the flexible carrier 232, 232B can be forced outside of the flexible carrier and through the vent 225, 225B and air port 222, 222B into the atmosphere. As shown, this escaping air can be sealed off from the flow of liquid through the connector 200, 200B. In some embodiments, the connector 200, 200B lacks a vent 225, 225B and the internal region 248, 248B is closed. In the illustrated embodiments, the mixing and emitting of additive into the medical liquid, and the fluid flow within the connector 200, are not accomplished through erosion or dissolving or washing away of one or more layers that are configured to initially block mixing or emitting of the additive, but rather by a dynamic movement of one or more components of the connector that changes the direction, position, orientation, and/or volume of one or more fluid flow paths within the connector 200. Some embodiments can include one or more processes of mixing or emitting that include eroding or dissolving or washing away of one or more layers into the surrounding fluid.


As illustrated, in some embodiments, the movement of the flexible carrier 232, 232B can create a void between the exterior wall 264, 264B of the flexible carrier 232, 232B and the interior wall 268, 268B of the connector 200, 200B, which can increase the size of the variable-volume fluid-modifying region 254, 254B and temporarily store or retain liquid within the increasingly large fluid-modifying region 254, 254B. Once the flexible carrier 232, 232B begins to deform, it exerts a restoring force in opposition to the force of the entering liquid. In some embodiments, the force of the entering liquid is greater than the restoring force of the flexible carrier 232, 232B during the infusion stage. Simultaneously, the liquid in the fluid-modifying region 254, 254B can come into contact with and mix with one or more additives 112 on the flexible carrier 232, 232B or otherwise, transforming the liquid into a therapeutic liquid 278, 278B (e.g., an additive-containing liquid). In some embodiments, the therapeutic liquid 278, 278B can flow or swirl generally circumferentially around the interior of the housing 220, 220B of the connector 200, 220B in a general vortex pathway as medical liquid is infused into the connector 200, 200B, between the interior wall 268, 268B of the housing 220, 220B and the exterior wall 264, 264B of the flexible carrier 232, 232B, providing thorough mixing and consistency of concentration of additive 112 in the therapeutic liquid 278, 278B.


As shown in FIGS. 8 and 12, the second stage of the connector 200, 200B can end when the infusion of medical liquid 266, 266B into the connector 200, 200B ends, such as when the plunger 278, 278B of the syringe 270, 270B stops or bottoms out or moves to its distal end point within the syringe barrel. At this point, the fluid pressure within the main fluid pathway can decrease, and medical liquid 266, 266B can stop flowing from the first fluid-line attachment 202, 202B through the connector 200, 200B to the second fluid-line attachment 204, 204B.


As illustrated in FIGS. 9 and 13, a third stage of the connector 200, 200B can begin upon completion of the second stage, or at any other suitable time (such as after a delay after completion of the second stage). The connector 200C, 200D can also have a third stage that can have substantially the same features as disclosed herein with reference to FIG. 9 and that is not repeated for brevity. In the third stage, the therapeutic liquid 278, 278B stored in the fluid-modifying region 254, 254B is no longer under pressure from the medical liquid 266, 266B that was previously being infused into the connector 200, 200B during stage two of the connector 200, 200B, and the restoring force exerted by the flexible carrier 232, 232B can then move the flexible carrier 232, 232B back toward its default or native or natural position in its first or initial phase. As the flexible carrier 232, 232B moves back toward its first or initial phase, the fluid modifying region 254, 254B shrinks or contracts or otherwise moves to decrease in size, and the therapeutic liquid 278, 278B in the fluid-modifying region 254, 254B is forced out, passing through the transitional region 274, 274B and the diverter or divider 246, 246B, into the male protrusion 205, 205B, and out of the connector 200, 200B. Thus, in some embodiments, the third stage can begin after infusion from the source (e.g., the syringe 270, 270B) of medical liquid 266, 266B stops, at which point a volume of therapeutic fluid 278, 278B is then dispensed from the distal end of the connector 200, 200B. In embodiments where the internal region of the connector is closed (e.g., in embodiments that lack a vent 225, 225B), the internal region increases in pressure upon deformation of the flexible carrier during depression of the syringe plunger. This pressure increase can be used to aid in forcing the additive-infused fluid out of the connector by exerting pressure on the flexible carrier, forcing the flexible carrier back into its original position.


Any of the first or second or third or other stages can be combined or eliminated. Any steps or methods that are described and/or illustrated in any particular stage can be performed additionally or alternatively in another stage. The descriptions and/or illustrations of stages are not intended to be exhaustive or limiting. In some embodiments, as illustrated, any transition from any stage to any other stage can be automatic. For example, one or more transitions between any stages can be governed by fluid-flow and/or fluid pressure parameters, not by one or more intentional or direct user adjustments or modifications of the connector. In some embodiments, one or more connector features can be manipulated and used collectively and/or singularly to adjust and/or manipulate the ratio of medical fluid that remains substantially additive-free versus the amount of medical fluid infused with an additive (or additives). In some embodiments, multiple connector types with various features can be mixed and matched and attached serially for the infusion of multiple additives and/or to achieve multiple infusion profiles. As shown, in some embodiments, any of the connectors 200, 200A, 200B, 200C, 200D can be different from long-term medical pumps (e.g., bladder pumps or ambulatory pumps) in that the fluid-flow emitted from the downstream or outflow end or region of the connectors 200, 200A, 200B, 200C, 200D can terminate or stop generally simultaneously with or shortly after the fluid-flow infused or inserted into the upstream or inflow end or region of the connectors 200, 200A, 200B, 200C, 200D. For example, in some embodiments, as illustrated, the time between the beginning of fluid-flow infused or inserted into the upstream or inflow end or region of the connectors 200, 200A, 200B, 200C, 200D and the end of fluid-flow infused or inserted into the upstream or inflow end or region of the connectors 200, 200A, 200B, 200C, 200D can be generally equal to or greater than the time between the end of fluid-flow infused or inserted into the upstream or inflow end or region of the connectors 200, 200A, 200B, 200C, 200D and the end of fluid-flow emitted from the downstream or outflow end or region of the connectors 200, 200A, 200B, 200C, 200D, such that the connectors 200, 200A, 200B, 200C, 200D do not provide a long-term pumping function. Of course, in some embodiments, one or more structures, methods, functions, and/or components that are illustrated in the accompanying figures and/or described anywhere in this specification can be used in or with medical pumps or can be used as medical pumps with appropriate modifications.


In some embodiments, the cross-sectional area (e.g., diameter) of the internal fluid pathway is larger than the cross-sectional area of the fluid pathway through (or the opening in) the constriction or diverter or divider. In some embodiments, the diverter or divider can be a constriction. In some embodiments, the ratio of the cross-sectional area of the internal fluid pathway 226, 226A, 226B, 226C, 226D and the cross-sectional area of the opening in the diverter or divider or constriction 246, 246A, 246B, 246C, 246D can be changed from connector to connector to divert more or less liquid into the fluid modifying region. For example, if only a small volume of liquid is being infused, it may be advantageous to divert a larger volume of liquid into the fluid modifying region to allow sufficient additive to be infused into the medical fluid. As the cross-sectional area of the internal fluid pathway becomes larger relative to the cross-sectional area of the fluid pathway at the diverter or divider or constriction, more fluid pressure builds at the diverter or divider or constriction diverting more fluid into the fluid modifying region. In some embodiments, the ratio of a cross-sectional area of the internal fluid pathway to the cross-sectional area of the fluid pathway through the diverter or divider or constriction is equal to or less than about: 5:4, 4:3, 2:1, 5:1, values between the aforementioned ratios, ranges spanning those ratios, or otherwise.


Alternatively or additionally, in some embodiments, the cross-sectional area of the entrance (e.g., the lateral fluid region) to the fluid modifying region is larger than the cross-sectional area of the fluid pathway through the diverter or divider or constriction. In some embodiments, the ratio of the cross-sectional area of the entrance of the fluid modifying region to the cross-sectional area of the opening in the diverter or divider or constriction can be different among a plurality of connectors to divert more or less liquid into the fluid modifying region, depending upon clinical needs. When the cross-sectional area of the entrance to the fluid modifying region is larger than the cross-sectional area of the fluid pathway at the diverter or divider or constriction, more fluid can be diverted into the fluid modifying region. In some embodiments, the ratio of a cross-sectional area of the entrance to fluid modifying region to the cross-sectional area of the fluid pathway through the diverter or divider or constriction is equal to or less than about: 2:1, 5:1, 10:1 values between the aforementioned ratios, ranges spanning those ratios, or otherwise.


In some embodiments, the volume of the secondary pathway can be adjusted and/or the volume of the primary fluid pathway can be adjusted. In some embodiments, the capacity of the secondary fluid pathway (e.g., the volume of liquid the secondary pathway can hold when filled) is equal to or at least about: 0.125 mL, 0.25 mL, 0.5 mL, 2 mL, 5 mL, values between the aforementioned values, ranges spanning those values, or otherwise. In some embodiments, capacity of the primary fluid pathway is equal to or at least about: 0.1 mL, 0.2 mL, 0.5 mL, 1 mL, values between the aforementioned values, ranges spanning those values, or otherwise. In some embodiments, by making the volume of the secondary fluid pathway 110 larger than the volume of the main fluid pathway 108, a larger volume of additive-infused medical liquid can be infused into the catheter. As shown in FIGS. 14 and 15, differing volume ratios of the main fluid pathway and secondary fluid pathway can be used to achieve different release profiles. In some embodiments, the ratio of the volume of the secondary fluid pathway to the volume of the main fluid pathway is equal to or greater than about: 0.5:1, 1:1, 2:1, 4:1, ratios between the aforementioned ratios, ranges spanning those ratios, or otherwise. In some embodiments, the ratio of the length of the secondary fluid pathway to the length of the main fluid pathway can be adjusted. In some embodiments, the ratio of the length of the secondary fluid pathway to the length of the main fluid pathway is equal to or greater than about: 0.5:1, 1:1, 2:1, 4:1, ratios between the aforementioned ratios, ranges spanning those ratios, or otherwise. In some embodiments, the connector can be configured to have a low retained volume of fluid after the third stage is complete. In some embodiments, the retained volume of fluid in the connector after the third stage is less than or equal to about: 0.5 mL, 0.2 mL, 0.1 mL, values between the aforementioned values, ranges spanning those values, or otherwise.


In some embodiments, as discussed elsewhere herein, the medical fluid can enter the secondary fluid pathway 110 (or an additional fluid pathway) based in part on the rate and/or the volume of medical fluid injected into the connector 100. In some embodiments, for example, the amount of deformation of the flexible carrier and/or the amount of fluid that enters the secondary pathway depends on the rate at which a fluid is passed through main fluid pathway of the connector. In some embodiments, the secondary fluid pathway 110 is filled with medical fluid and/or the flexible carrier deforms when an infusion from, for example, a syringe into the connector reaches a rate of equal to, or at least, about: 0.25 mL/sec, 0.5 mL/sec, 2 mL/sec, 5 mL/sec, values between the aforementioned values, ranges spanning those values, or otherwise. In some embodiments, the additive can be completely or substantially distributed into the medical fluid with an infusion rate from a syringe (or other infusion device) of equal to, or at least, about: 0.25 mL/sec, 0.5 mL/sec, 2 mL/sec, 5 mL/sec, values between the aforementioned values, ranges spanning those values, or otherwise.


In some embodiments, the amount of deformation of the flexible carrier and/or the amount of fluid that enters the secondary pathway depends on the volume of fluid that is passed through the connector. In some embodiments, the secondary fluid pathway 110 is filled with medical fluid when an infusion volume is equal to or at least about: 2.5 mL, 5 mL, 10 mL, values between the aforementioned values, ranges spanning those values, or otherwise. In some embodiments, the additive can be completely or substantially completely distributed into the medical fluid using an infusion volume of equal to or at least about: 2.5 mL, 5 mL, 10 mL, values between the aforementioned values, ranges spanning those values, or otherwise.


In some embodiments, the resiliency and/or the modulus of the flexible carrier can be selected to provide different release characteristics. In some embodiments, stiff materials deform less and result in less additive being added to the medical fluid but can expel the additive at a greater pressure and in less time. In some embodiments, the resilience of the flexible carrier is at least about: 0.1 J/m3, 1 J/m3, 10 J/m3, 100 J/m3, values between the aforementioned values, ranges spanning those values, or otherwise. In some embodiments, the modulus of the flexible carrier is greater than or equal to about: 0.01 GPa, 0.1 GPa, 1 GPa, 2 GPa, values between the aforementioned values, ranges spanning those values, or otherwise.


In some embodiments, a portion of the flexible carrier can comprise an indicator, for instance, a colored, luminescent, or fluorescent dye (not shown). In some embodiments, the indicator dissolves into the medical fluid with the additive. In some embodiments, the indicator is located on a portion of the flexible carrier that is away from or distal to the transitional region so that the indicator is only infused into the medical fluid after all or substantially all the additive is infused into the medical fluid. In some embodiments, where the indicator is present, the indicator only enters into the medical fluid when an appropriate rate and/or volume of medical fluid enters the variable-volume fluid-modifying region 254, 254A, 254B, 254C, 254D. In some embodiments, the indicator can be used to visually demonstrate that the additive has been appropriately infused into the medical fluid. In some embodiments, the indicator may also be used to visualize the distance that the lock solution (or any other therapeutic solution) has traveled in the catheter line.


In some embodiments, as shown in at least FIGS. 6A-9 and FIGS. 10-13, the connector 200, 200C, 200D, 200B can be structured and/or configured to: (a) initially direct liquid into the secondary fluid pathway 110 (e.g., the lateral fluid region 252, 252C, 252D, 252B and the variable-volume fluid-modifying region 254, 254C, 254D, 254B) in an entrance direction and then subsequently direct that same liquid, in a modified form, back out of the secondary fluid pathway 110, in a substantially or primarily opposite exit direction; (b) simultaneously provide a first fluid pathway through an interior or central region of the connector 200, 200C, 200D, 200B (e.g., internal fluid pathway 226, 226C, 226D, 226B) and a second fluid region or pathway (e.g., the lateral fluid region 252, 252C, 252D, 252B and the variable-volume fluid-modifying region 254, 254C, 254D, 254B) through or around or into a peripheral or outer region of the connector 200, 200C, 200D, 200B; (c) simultaneously permit some portion of fluid conveyed within the connector 200, 200C, 200D, 200B to move primarily in a distal direction (e.g., in the fluid guide 224, 224C, 224D, 224B) and some portion of fluid conveyed within the connector 200, 200C, 200D, 200B to move primarily in a proximal direction (e.g., into the variable-volume fluid-modifying region 254, 254C, 254D, 254B); (d) provide a single fluid exit (e.g., diverter or divider or constriction 246, 246C, 246D, 246B) for both the main fluid pathway 108 and the secondary fluid pathway 110; (e) automatically continue emitting fluid out of the fluid exit region 114 (e.g., out of the male protrusion 205, 205C, 205D, 205B) for a clinically significant period of time after infusion of fluid into the fluid entry region 106 has stopped and/or produce an automatic delay in stopping the flow of fluid or permit a continuation in delivering or emitting a substantial or clinically significant amount of fluid (e.g., at least about 20% of the fluid-holding capacity of the overall connector 200, 200C, 200D, 200B or at least about 5 mL or at least about 10 mL) out of the fluid exit region 114 (e.g., male protrusion 205, 205C, 205D, 205B) after the infusion of fluid into the fluid entry region 106 (e.g., the first fluid-line attachment 202, 202C, 202D, 202B) has stopped; (f) provide an internal fluid pathway 226, 226C, 226D, 226B that does not move with respect to the housing 220, 220C, 220D, 220B of the connector 200, 200C, 200D, 200B; (g) provide a rigid internal fluid pathway (e.g., internal fluid pathway 226, 2226C, 226D, 226B) that extends across and/or within a flexible member (e.g., flexible carrier 232, 232C, 232D, 232B); (h) provide fluid flow both inside and outside of a flexible member (e.g., flexible carrier 232, 232C, 232D, 232B); (i) provide fluid contact and/or fluid flow across or around or on an outside surface of a flexible member; and/or (j) provide a rigid internal fluid pathway (e.g., internal fluid pathway 226, 226C, 226D, 226B) that extends across and/or within a flexible member (e.g., flexible carrier 232, 232C, 232D, 232B), the internal fluid pathway being longitudinally stationary with respect to the flexible member. Any of these features can be included in or omitted from any embodiment in this application.



FIGS. 14 and 15 provide examples of liquid dispensing profiles created by liquid flowing through and/or out of a fluid source, such as connector 200 (or connector 200C, 200D) and connector 200B, respectively. In the first stage, which in some embodiments can correspond to the condition of the connector 200, 200B shown in FIGS. 6A and 10, medical fluid 266, 266B can pass into and out of the connector 200, 200B in an unchanged or essentially unchanged state such that the concentration of additive 112 is essentially non-existent or essentially zero or clinically insignificant. In the second stage, which in some embodiments can correspond to the condition of the connector 200, 200B shown in FIGS. 7-8 and 11-12, medical fluid 266, 266B can pass into and out of the connector with very little, if any change (e.g., not clinically significant), but some of the medical fluid can be internally mixing with additive 112 and can be temporarily retained or stored inside of the connector 200, 200B. In the second stage, medical fluid 266, 266B can also pass into and out of the connector in an unchanged or essentially unchanged state. Finally, in the third stage, which in some embodiments can correspond to the condition of the connector 200, 200B shown in FIGS. 9 and 13, medical fluid 266, 266B can stop being infused into the connector 200, 200B, and/or therapeutic fluid 278, 278B can be expelled or dispensed or emitted from a liquid storage or liquid retaining region inside of the connector 200, 200B with a high concentration of additive 112 in the therapeutic fluid 278, 278B, which is clinically significant (e.g., for an antimicrobial product, the concentration of antimicrobial additive can be sufficient to provide antimicrobial protection in a catheter that diminishes the risk of microbial invasion into the catheter to a level that is clinically acceptable according to one or more applicable industry standard practices or guidelines). For example, during the third or final stage, in some embodiments, the maximum concentration of additive can be at least about 3% or at least about 10% or at least about 30% of the total liquid volume or weight, and/or no more than about 5% or no more than about 12% or no more than about 40% of the total liquid volume or weight, depending upon the particular type of additive used and the therapeutic purposes of the treatment. As illustrated in FIGS. 14 and 15, the concentration of the additive can rapidly increase from essentially none (or a clinically insignificant amount) to any of the foregoing clinically significant concentrations (or any other clinically significant concentration) in a short time or while a small amount of liquid passes through the connector, such as within less than or equal to about 0.25 second or less than or equal to about 1.0 second at an average fluid flow rate through a medical connector, or while less than or equal to about 1, 2, or 5 mL of liquid passes through the connector. In some embodiments, the percentage of concentration of additive, such as an antimicrobial additive and/or an antibiotic additive, can rise from essentially zero in the first stage to at least about 0.2% or at least about 1.5% in a subsequent stage (e.g., the third stage). Many other different types and stages and concentrations of fluid-dispensing profiles can be provided, depending upon therapeutic needs. In some embodiments, the volume of liquid that is dispensed or expelled out of the connector during the first stage and/or the second stage (or any other initial or intermediate stage) can be greater than or equal to about the volume of liquid capacity of a catheter to which the connector is intended to be attached, such that the liquid dispensed or expelled out of the connector during the first stage and/or the second stage can provide a flush of basic, standard, non-therapeutic, non-pharmaceutical, or inert medical liquid (such as medical liquid without an additive, e.g. saline or other medical liquid without an additive) from the connector into the patient catheter to flush essentially the entire patient catheter before subsequent use. In some embodiments, the volume of liquid that is dispensed or expelled out of the connector during the third stage (or during any other intermediate or final stage or any stage that is subsequent to the first stage or to the second stage) can be less than or equal to about the volume of liquid capacity of the patient catheter to which the connector is intended to be attached, such that the liquid dispensed or expelled out of the connector during this stage does not become infused into the patient or does not become infused into the patient in any clinically significant volume, but rather is configured to remain in the catheter during a locking or antimicrobial phase. Many other different configurations can be used, including configurations that do not provide a locking or antimicrobial phase. The volumes in each stage can be designed or configured to fit a variety of different clinical needs or therapeutic purposes.


Some embodiments pertain to methods of using medical fluid connectors as disclosed herein. Any device or structure illustrated or described in this specification can be used with any method in this specification. In some embodiments, a method includes the step of obtaining a connector. In some embodiments, a method includes the step of attaching the connector to a catheter. In some embodiments, a method includes the step of obtaining a syringe or device capable of holding a medical fluid. In some embodiments, a method includes the step of attaching the syringe or other device to the connector. In some embodiments, a method includes the step of introducing medical fluid into the connector and/or the catheter using the syringe or other medical fluid carrying device. In some embodiments, a method includes the step of introducing an additive to the fluid as it passes through the connector. In some embodiments, a first portion of fluid that is substantially additive-free is introduced to the catheter. In some embodiments, a second portion of fluid that contains additive is introduced to the catheter. In some embodiments, a first portion of fluid that contains additive (e.g., a therapeutic) is introduced to the catheter and/or passed through the catheter to the patient. In some embodiments, a second portion of fluid that is contains additive is introduced to the catheter. In some embodiments, the method includes the step of locking the catheter with an antimicrobial-containing medical fluid.


Some embodiments pertain to methods of preparing medical fluid connectors. In some embodiments, a method includes the step of obtaining one or more of a fluid guide, a proximal cover region (e.g., with a vent), and/or a distal fluid port. In some embodiments, a method includes the step of attaching a fluid modifier in place at a plurality of points or regions inside of the connector. In some embodiments, a method includes the step of affixing a proximal edge of the flexible carrier securely between an upper region (e.g., forming a lip, a projection, a barb, etc.) of the housing and an underside of the outer edge of a region of the fluid guide (e.g., a cover region). In some embodiments, a distal end region of the flexible carrier is fastened circumferentially (e.g., securely and/or in a fluid-tight manner) at the distal attachment region of the fluid guide, such as by affixing a distal opening in the flexible carrier that is slightly smaller than the outer circumference of the distal attachment region, causing the distal opening to exert a radially inwardly directed restoring force which tightly grips the distal attachment region of the fluid guide. In some embodiments, the fluid guide and/or the flexible carrier can be placed into the housing of the connector. In some embodiments, a cap can be placed over the fluid guide, securing it in place. In some embodiments, a first fluid line attachment can be affixed or placed on the fluid guide.


Certain features that are described in this disclosure in the context of separate implementations can also be implemented in combination in a single implementation. Conversely, various features that are described in the context of a single implementation also can be implemented in multiple implementations separately or in any suitable subcombination. Moreover, although features may be described above as acting in certain combinations, one or more features from a claimed combination can in some cases be excised from the combination, and the combination may be claimed as a subcombination or variation of a sub combination.


Any portion of any of the steps, processes, structures, and/or devices disclosed or illustrated in one embodiment, flowchart, or example in this disclosure can be combined or used with (or instead of) any other portion of any of the steps, processes, structures, and/or devices disclosed or illustrated in a different embodiment, flowchart, or example. The embodiments and examples described herein are not intended to be discrete and separate from each other. Combinations, variations, and other implementations of the disclosed features are within the scope of this disclosure.


Some embodiments have been described in connection with the accompanying drawings. Moreover, while operations may be depicted in the drawings or described in the specification in a particular order, such operations need not be performed in the particular order shown or in sequential order, and/or one or more of the operations may be omitted entirely, to achieve desirable results. Other operations that are not depicted or described can be incorporated in the example methods and processes. For example, one or more additional operations can be performed before, after, simultaneously, or between any of the described operations. Additionally, the operations may be rearranged or reordered in other implementations. Also, the separation of various components in the implementations described above should not be understood as requiring such separation in all implementations, and it should be understood that the described components and systems can generally be integrated together in a single product or packaged into multiple products. Additionally, other implementations are within the scope of this disclosure.

Claims
  • 1. A medical fluid-modifying device configured to modify a medical fluid by inserting an additive into the medical fluid, the medical fluid-modifying device comprising: an upstream connector;a downstream connector;a main fluid pathway; anda secondary fluid pathway that is different from the main fluid pathway, the secondary fluid pathway including a carrier of additive, the carrier of additive being flexible, wherein at a diversion region between the main fluid pathway and the secondary fluid pathway, the main fluid pathway stays open to a flow of the medical fluid;wherein the main fluid pathway is configured to convey unchanged a portion of the medical fluid that is inserted into the fluid-modifying device from the upstream connector to the downstream connector,wherein the secondary fluid pathway is configured to add an additive into a portion of the medical fluid that is inserted into the fluid-modifying device, andwherein the unchanged portion of the medical fluid is configured to be conveyed through the medical fluid-modifying device before the portion of the medical fluid in which the additive is added.
  • 2. The medical fluid-modifying device of claim 1, wherein the unchanged portion of the medical fluid is configured to have a sufficient volume to flush out a patient catheter to be used with the medical fluid-modifying device before a clinically significant amount of additive is added to the medical fluid by the medical fluid-modifying device.
  • 3. The combination of the medical fluid-modifying device of claim 2 and the patient catheter.
  • 4. The fluid-modifying device of claim 1, wherein the flexible carrier of additive is configured to change the volume within the secondary fluid pathway.
  • 5. The medical fluid-modifying device of claim 1, wherein at the diversion region between the main fluid pathway and the secondary fluid pathway, the main fluid pathway has a first cross-sectional area and the secondary fluid pathway has a second cross-sectional area, the first cross-sectional area being greater than the second cross-sectional area.
  • 6. The medical fluid-modifying device of claim 5, wherein the first cross-sectional area is at least about four times larger than the second cross-sectional area.
  • 7. A medical fluid connector configured to receive and dispense medical fluid, the medical fluid connector comprising: an initial stage in which the connector is configured to permit at least a portion of a medical fluid that is infused into the connector to be dispensed out of the connector essentially unchanged; anda subsequent stage in which the connector is configured to dispense a therapeutic liquid out of the connector after infusion of the medical fluid into the connector has stopped such that the therapeutic liquid comprises a portion of the medical fluid that was infused into the connector in the initial stage plus a therapeutic additive;wherein the connector is configured to automatically transition from the initial stage to the subsequent stage initiated by stopping of infusion of the medical fluid into the connector.
  • 8. The medical fluid connector of claim 7 comprising a fluid modifier.
  • 9. The medical fluid connector of claim 8 in which the fluid modifier is a flexible carrier.
  • 10. The medical fluid connector of claim 9 in which the flexible carrier comprises one or more additives.
  • 11. The medical fluid connector of claim 10 in which the one or more additives comprise an antimicrobial agent.
  • 12. The medical fluid connector of claim 11 in which the antimicrobial agent is chlorhexidine.
  • 13. A medical fluid connector configured to receive and dispense medical fluid, the medical fluid connector comprising: an inlet configured to receive into the connector a volume of a medical fluid; andan outlet configured to dispense a volume of the medical fluid out of the connector in at least a first stage and a second stage, the medical fluid connector being configured to move at least a portion of the medical fluid through the connector along a different fluid path in the second stage than in the first stage,wherein in the first stage, the connector is configured to dispense the medical fluid out of the connector without a therapeutic additive or at least without a clinically significant concentration of the therapeutic additive; and wherein in the second stage, the connector is configured to dispense the medical fluid out of the connector with a therapeutic additive of a clinically significant concentration, andwherein the connector is configured to automatically increase the concentration of additive in the dispensed medical fluid within the second stage initiated by stopping the flowing of the medical fluid into the inlet of the connector.
  • 14. The medical fluid connector of claim 13, wherein the medical fluid connector is configured to dispense the medical fluid during the second stage even after the medical fluid is no longer being received into the connector.
  • 15. A medical fluid-modifying device configured to modify a medical fluid by inserting an additive into the medical fluid, the medical fluid-modifying device comprising: an upstream connector;a downstream connector;a main fluid pathway; anda secondary fluid pathway that is different from the main fluid pathway, wherein at a diversion region between the main fluid pathway and the secondary fluid pathway, the main fluid pathway stays open to a flow of the medical fluid, and wherein at the diversion region between the main fluid pathway and the secondary fluid pathway, the main fluid pathway has a first cross-sectional area and the secondary fluid pathway has a second cross-sectional area, the first cross-sectional area being at least about four times larger than the second cross-sectional area;wherein the main fluid pathway is configured to convey unchanged a portion of the medical fluid that is inserted into the fluid-modifying device from the upstream connector to the downstream connector, andwherein the secondary fluid pathway is configured to add an additive into a portion of the medical fluid that is inserted into the fluid-modifying device.
  • 16. The medical fluid-modifying device of claim 15, wherein the unchanged portion of the medical fluid is configured to be conveyed through the medical fluid-modifying device before the portion of the medical fluid in which the additive is added.
  • 17. The medical fluid-modifying device of claim 15, wherein the unchanged portion of the medical fluid is configured to have a sufficient volume to flush out a patient catheter to be used with the medical fluid-modifying device before a clinically significant amount of additive is added to the medical fluid by the medical fluid-modifying device.
  • 18. The combination of the medical fluid-modifying device of claim 17 and the patient catheter.
  • 19. The fluid-modifying device of claim 16, wherein the secondary fluid pathway includes a carrier of additive.
  • 20. The fluid-modifying device of claim 19, wherein the carrier of additive is configured to change the volume within the secondary fluid pathway.
PRIORITY CLAIM AND INCORPORATION BY REFERENCE

This application claims the benefit under 35 U.S.C. § 120 and 35 U.S.C. § 365(c) as a continuation of International Application No. PCT/US2018/030015, designating the United States, with an international filing date of Apr. 27, 2018, titled “MEDICAL FLUID CONNECTORS AND METHODS FOR PROVIDING ADDITIVES IN MEDICAL FLUID LINES,” which claims the benefit under 35 U.S.C. § 119(e) of U.S. Provisional Patent Application No. 62/492,887, filed on May 1, 2017, U.S. Provisional Patent Application No. 62/520,300, filed on Jun. 15, 2017, U.S. Provisional Patent Application No. 62/558,618, filed on Sep. 14, 2017, and U.S. Provisional Patent Application No. 62/662,149, filed on Apr. 24, 2018, which are hereby incorporated by reference herein in their entireties, forming part of the present disclosure. Any feature, structure, material, method, or step that is described and/or illustrated in any embodiment in any of the foregoing provisional patent applications can be used with or instead of any feature, structure, material, method, or step that is described and/or illustrated in the following paragraphs of this specification or the accompanying drawings.

US Referenced Citations (943)
Number Name Date Kind
382297 Fry May 1888 A
559697 Tiugti et al. May 1896 A
877946 Overton Feb 1908 A
975939 William et al. Nov 1910 A
1445642 O'Neill Feb 1923 A
1793068 Dickinson Feb 1931 A
2098340 Henahan Nov 1937 A
2436297 Guarnaschelli Feb 1948 A
2457052 Le Clair Dec 1948 A
2771644 Martin Nov 1956 A
2842382 Franck Jul 1958 A
2968497 Treleman Jan 1961 A
3127892 Bellamy, Jr. et al. Apr 1964 A
3262448 Ring et al. Jul 1966 A
3270743 Gingras Sep 1966 A
3301392 Eddingfield Jan 1967 A
3304047 Martin Feb 1967 A
3334860 Bolton, Jr. Aug 1967 A
3411665 Blum Nov 1968 A
3484121 Quinton Dec 1969 A
3485416 Fohrman Dec 1969 A
3538950 Porteners Nov 1970 A
3595241 Sheridan Jul 1971 A
3604582 Boudin Sep 1971 A
3707972 Villari et al. Jan 1973 A
3729031 Baldwin Apr 1973 A
3882858 Klemm May 1975 A
3977401 Pike Aug 1976 A
3977517 Kadlecik et al. Aug 1976 A
3987930 Fuson Oct 1976 A
3993066 Virag Nov 1976 A
4041934 Genese Aug 1977 A
4046889 Ondetti et al. Sep 1977 A
4052511 Cushman et al. Oct 1977 A
4053052 Jasper Oct 1977 A
4053651 Ondetti et al. Oct 1977 A
4066067 Micheli Jan 1978 A
4076285 Martinez Feb 1978 A
4078686 Karesh et al. Mar 1978 A
4079738 Dunn et al. Mar 1978 A
4095810 Kulle Jun 1978 A
4113751 Arnold Sep 1978 A
4121585 Becker, Jr. Oct 1978 A
4129571 Ondetti et al. Dec 1978 A
4133441 Mittleman et al. Jan 1979 A
4143853 Abramson Mar 1979 A
4150845 Kopacz et al. Apr 1979 A
4154840 Ondetti et al. May 1979 A
4154960 Ondetti et al. May 1979 A
4192443 McLaren Mar 1980 A
4194509 Pickering et al. Mar 1980 A
4195632 Parker et al. Apr 1980 A
4233982 Bauer et al. Nov 1980 A
4243035 Barrett Jan 1981 A
4245635 Kontos Jan 1981 A
4264664 Kunz Apr 1981 A
4280632 Yuhara Jul 1981 A
4294370 Toeppen Oct 1981 A
4317446 Ambrosio et al. Mar 1982 A
4324239 Gordon et al. Apr 1982 A
4325368 Kaemmerer Apr 1982 A
4331783 Stoy May 1982 A
4334551 Pfister Jun 1982 A
4335756 Sharp et al. Jun 1982 A
4337327 Stoy Jun 1982 A
4340049 Munsch Jul 1982 A
4340052 Dennehey et al. Jul 1982 A
4354490 Rogers Oct 1982 A
4369294 Stoy Jan 1983 A
4370451 Stoy Jan 1983 A
4379458 Bauer et al. Apr 1983 A
4379874 Stoy Apr 1983 A
4384589 Morris May 1983 A
4387879 Tauschinski Jun 1983 A
4390016 Riess Jun 1983 A
4397442 Larkin Aug 1983 A
4402691 Rosenthal et al. Sep 1983 A
4405312 Gross et al. Sep 1983 A
4417890 Dennehey et al. Nov 1983 A
4420589 Stoy Dec 1983 A
4427126 Ostrowsky Jan 1984 A
4430073 Bemis et al. Feb 1984 A
4432764 Lopez Feb 1984 A
4432766 Bellotti et al. Feb 1984 A
4436125 Blenkush Mar 1984 A
4439179 Lueders et al. Mar 1984 A
4439184 Wheeler Mar 1984 A
4440207 Genatempo et al. Apr 1984 A
4444310 Odell Apr 1984 A
4446967 Halkyard May 1984 A
4447419 Quadro May 1984 A
4457749 Bellotti et al. Jul 1984 A
4461368 Plourde Jul 1984 A
4461896 Portlock Jul 1984 A
4480940 Woodruff Nov 1984 A
4507111 Gordon et al. Mar 1985 A
4511359 Vaillancourt Apr 1985 A
4534764 Mittleman et al. Aug 1985 A
4538836 Kruetten Sep 1985 A
4559043 Whitehouse Dec 1985 A
4568675 Bush et al. Feb 1986 A
4585758 Huang et al. Apr 1986 A
4602042 Chantler et al. Jul 1986 A
4610469 Wolff-Mooij Sep 1986 A
4619640 Potolsky et al. Oct 1986 A
4623332 Lindmayer et al. Nov 1986 A
4624664 Peluso et al. Nov 1986 A
4626545 Taub Dec 1986 A
4629159 Wellenstam Dec 1986 A
4631188 Stoy Dec 1986 A
4642091 Richmond Feb 1987 A
4660803 Johnston et al. Apr 1987 A
4662878 Lindmayer May 1987 A
4666057 Come et al. May 1987 A
4666427 Larsson et al. May 1987 A
4671306 Spector Jun 1987 A
4671412 Gatten Jun 1987 A
4681886 Haugwitz et al. Jul 1987 A
4692458 Ryan et al. Sep 1987 A
4692459 Ryan et al. Sep 1987 A
4700744 Rutter et al. Oct 1987 A
4703762 Rathbone et al. Nov 1987 A
4705790 Hubele et al. Nov 1987 A
4723603 Plummer Feb 1988 A
4728075 Paradis Mar 1988 A
4728321 Chen Mar 1988 A
4738668 Bellotti et al. Apr 1988 A
4745950 Mathieu May 1988 A
4747502 Luenser May 1988 A
4748160 Bennion et al. May 1988 A
4752983 Grieshaber Jun 1988 A
4769013 Lorenz et al. Sep 1988 A
4774964 Bonaldo Oct 1988 A
4774965 Rodriguez et al. Oct 1988 A
4778447 Velde et al. Oct 1988 A
4781702 Herrli Nov 1988 A
4799926 Haber Jan 1989 A
4804015 Albinsson Feb 1989 A
4808158 Kreuzer et al. Feb 1989 A
4810241 Rogers Mar 1989 A
4811847 Reif et al. Mar 1989 A
4813933 Turner Mar 1989 A
4816024 Sitar et al. Mar 1989 A
4834271 Litwin May 1989 A
4862913 Wildfang Sep 1989 A
4874366 Zdeb Oct 1989 A
4883483 Lindmayer Nov 1989 A
4889255 Schiemann et al. Dec 1989 A
4894056 Bommarito Jan 1990 A
4898580 Crowley Feb 1990 A
4915687 Sivert Apr 1990 A
4917669 Bonaldo Apr 1990 A
4919658 Badia Apr 1990 A
4927019 Haber et al. May 1990 A
4935010 Cox et al. Jun 1990 A
4941873 Fischer Jul 1990 A
4950260 Bonaldo Aug 1990 A
4957637 Cornell Sep 1990 A
4963132 Gibson Oct 1990 A
D313277 Haining Dec 1990 S
D314050 Sone Jan 1991 S
4983161 Dadson et al. Jan 1991 A
4985017 Theeuwes Jan 1991 A
4989733 Patry Feb 1991 A
4991629 Ernesto et al. Feb 1991 A
4997371 Fischer Mar 1991 A
4999210 Solomon Mar 1991 A
5002964 Loscalzo Mar 1991 A
5006114 Rogers et al. Apr 1991 A
5015238 Solomon et al. May 1991 A
5019096 Fox, Jr. et al. May 1991 A
5021059 Kensey et al. Jun 1991 A
5024657 Needham et al. Jun 1991 A
5025001 Loscalzo et al. Jun 1991 A
5026359 Burroughs Jun 1991 A
5031622 LaHaye Jul 1991 A
5033961 Kandler et al. Jul 1991 A
5047021 Utterberg Sep 1991 A
5049139 Gilchrist Sep 1991 A
5059186 Yamamoto et al. Oct 1991 A
5065783 Ogle, II Nov 1991 A
5070885 Bonaldo Dec 1991 A
5071411 Hillstead Dec 1991 A
5071413 Utterberg Dec 1991 A
5098385 Walsh Mar 1992 A
5108376 Bonaldo Apr 1992 A
5122123 Vaillancourt Jun 1992 A
5127626 Hilal et al. Jul 1992 A
5129824 Keller Jul 1992 A
5139483 Ryan Aug 1992 A
5143104 Iba et al. Sep 1992 A
5147333 Raines Sep 1992 A
5154703 Bonaldo Oct 1992 A
5154920 Flesher et al. Oct 1992 A
5184742 DeCaprio et al. Feb 1993 A
5190534 Kendell Mar 1993 A
5195957 Tollini Mar 1993 A
RE34223 Bonaldo Apr 1993 E
5199948 McPhee Apr 1993 A
5201725 Kling Apr 1993 A
5203775 Frank et al. Apr 1993 A
5205820 Kriesel Apr 1993 A
5205821 Kruger et al. Apr 1993 A
5207706 Menaker May 1993 A
5211634 Vaillancourt May 1993 A
5212204 Keefer et al. May 1993 A
5215537 Lynn et al. Jun 1993 A
5240675 Wilk et al. Aug 1993 A
5242421 Chan Sep 1993 A
5246011 Caillouette Sep 1993 A
5250550 Keefer et al. Oct 1993 A
5251873 Atkinson et al. Oct 1993 A
D342134 Mongeon Dec 1993 S
5269771 Thomas et al. Dec 1993 A
5278192 Fung et al. Jan 1994 A
5281206 Lopez Jan 1994 A
5284475 Mackal Feb 1994 A
5295657 Atkinson Mar 1994 A
5297310 Cox et al. Mar 1994 A
5301686 Newman Apr 1994 A
5304130 Button Apr 1994 A
5306243 Bonaldo Apr 1994 A
5312377 Dalton May 1994 A
5324270 Kayan et al. Jun 1994 A
5324647 Rubens et al. Jun 1994 A
5330426 Kriesel et al. Jul 1994 A
5330450 Lopez Jul 1994 A
5330899 Devaughn et al. Jul 1994 A
5337730 Maguire Aug 1994 A
5344414 Lopez et al. Sep 1994 A
5352410 Hansen et al. Oct 1994 A
5354267 Niermann et al. Oct 1994 A
5356396 Wyatt et al. Oct 1994 A
5360413 Leason et al. Nov 1994 A
5366505 Farber Nov 1994 A
5366997 Keefer et al. Nov 1994 A
5370614 Amundson et al. Dec 1994 A
5370636 Von Witzleben Dec 1994 A
5370640 Kolff Dec 1994 A
5375589 Bhatta Dec 1994 A
5380306 Brinon Jan 1995 A
5380758 Stamler et al. Jan 1995 A
5391150 Richmond Feb 1995 A
5402826 Molnar et al. Apr 1995 A
5405331 Behnke et al. Apr 1995 A
5405333 Richmond Apr 1995 A
5405919 Keefer et al. Apr 1995 A
5407807 Markus Apr 1995 A
5409012 Sahatjian Apr 1995 A
5411499 Dudar et al. May 1995 A
5417673 Gordon May 1995 A
5425465 Healy Jun 1995 A
5428070 Cooke et al. Jun 1995 A
5433330 Yatsko et al. Jul 1995 A
5433705 Giebel et al. Jul 1995 A
5439451 Collinson et al. Aug 1995 A
5441487 Vedder Aug 1995 A
5445623 Richmond Aug 1995 A
5456668 Ogle, II Oct 1995 A
5456675 Wolbring et al. Oct 1995 A
5464399 Boettger Nov 1995 A
5470307 Lindall Nov 1995 A
5470327 Helgren et al. Nov 1995 A
5471706 Wallock et al. Dec 1995 A
5474536 Bonaldo Dec 1995 A
5480393 Bommarito Jan 1996 A
5492147 Challender et al. Feb 1996 A
5496288 Sweeney Mar 1996 A
5501426 Atkinson et al. Mar 1996 A
5507733 Larkin et al. Apr 1996 A
5507744 Tay et al. Apr 1996 A
5514177 Kurz et al. May 1996 A
5518026 Benjey May 1996 A
5520665 Fleetwood May 1996 A
5520666 Choudhury et al. May 1996 A
5485827 Zapol et al. Jun 1996 A
5525357 Keefer et al. Jun 1996 A
5531695 Swisher Jul 1996 A
5533708 Atkinson et al. Jul 1996 A
5533983 Haining Jul 1996 A
5535785 Werge et al. Jul 1996 A
5536241 Zapol Jul 1996 A
5536258 Folden Jul 1996 A
5540661 Tomisaka et al. Jul 1996 A
5545614 Stamler et al. Aug 1996 A
5549566 Elias et al. Aug 1996 A
5549651 Lynn Aug 1996 A
5552115 Malchesky Sep 1996 A
5552118 Mayer Sep 1996 A
5554127 Crouther et al. Sep 1996 A
5554135 Menyhay Sep 1996 A
5555908 Edwards et al. Sep 1996 A
5569235 Ross et al. Oct 1996 A
5573516 Tyner Nov 1996 A
5575769 Vaillancourt Nov 1996 A
5578059 Patzer Nov 1996 A
5580530 Kowatsch et al. Dec 1996 A
5584819 Kopfer Dec 1996 A
5591137 Stevens Jan 1997 A
5591143 Trombley, III et al. Jan 1997 A
5597536 Mayer Jan 1997 A
5599352 Dinh et al. Feb 1997 A
5605696 Eury et al. Feb 1997 A
5607072 Rigney et al. Mar 1997 A
5613615 Zeyfang et al. Mar 1997 A
5616130 Mayer Apr 1997 A
5620088 Martin et al. Apr 1997 A
5620427 Werschmidt et al. Apr 1997 A
5624402 Imbert Apr 1997 A
5628733 Zinreich et al. May 1997 A
RE35539 Bonaldo Jun 1997 E
5645538 Richmond Jul 1997 A
5665077 Resen et al. Sep 1997 A
5674206 Allton et al. Oct 1997 A
5676346 Leinsing Oct 1997 A
5685866 Lopez Nov 1997 A
5685868 Lundquist Nov 1997 A
5688253 Lundquist Nov 1997 A
5694978 Heilmann et al. Dec 1997 A
5699821 Paradis Dec 1997 A
5700248 Lopez Dec 1997 A
5702017 Goncalves Dec 1997 A
5716339 Tanaka et al. Feb 1998 A
5722537 Sigler Mar 1998 A
5735826 Richmond Apr 1998 A
5738144 Rogers Apr 1998 A
5743892 Loh et al. Apr 1998 A
5749861 Guala et al. May 1998 A
5763409 Bayol et al. Jun 1998 A
5770645 Stamler et al. Jun 1998 A
5776116 Lopez Jul 1998 A
5782808 Folden Jul 1998 A
5782816 Werschmidt et al. Jul 1998 A
5785693 Haining Jul 1998 A
5792120 Menyhay Aug 1998 A
5797887 Rosen et al. Aug 1998 A
5806831 Paradis Sep 1998 A
5810792 Fangrow, Jr. et al. Sep 1998 A
5814024 Thompson et al. Sep 1998 A
5814666 Green et al. Sep 1998 A
5820601 Mayer Oct 1998 A
5820604 Fox et al. Oct 1998 A
5827244 Boettger Oct 1998 A
5839715 Leinsing Nov 1998 A
5848994 Richmond Dec 1998 A
5902631 Wang et al. May 1999 A
5941857 Nguyen et al. Aug 1999 A
5947954 Bonaldo Sep 1999 A
5951519 Utterberg Sep 1999 A
5954957 Chin-Loy et al. Sep 1999 A
5971972 Rosenbaum Oct 1999 A
D416086 Parris et al. Nov 1999 S
5989229 Chiappetta Nov 1999 A
5994444 Trescony Nov 1999 A
6029946 Doyle Feb 2000 A
6036171 Weinheimer et al. Mar 2000 A
6041805 Gydesen et al. Mar 2000 A
6045539 Menyhay Apr 2000 A
6045623 Cannon Apr 2000 A
6050978 Orr et al. Apr 2000 A
6059107 Nosted et al. May 2000 A
6063062 Paradis May 2000 A
6068011 Paradis May 2000 A
6068475 Stoyka, Jr. et al. May 2000 A
6068617 Richmond May 2000 A
6071413 Dyke Jun 2000 A
6079432 Paradis Jun 2000 A
6087479 Stamler et al. Jul 2000 A
6093743 Lai et al. Jul 2000 A
6095356 Rits Aug 2000 A
6099519 Olsen et al. Aug 2000 A
6105812 Riordan Aug 2000 A
6106502 Richmond Aug 2000 A
6113068 Ryan Sep 2000 A
6113572 Gailey et al. Sep 2000 A
6116468 Nilson Sep 2000 A
6117114 Paradis Sep 2000 A
6126640 Tucker et al. Oct 2000 A
6142446 Leinsing Nov 2000 A
6143318 Gilchrist et al. Nov 2000 A
6146363 Giebel et al. Nov 2000 A
6152913 Feith et al. Nov 2000 A
6158614 Haines et al. Dec 2000 A
6170522 Tanida Jan 2001 B1
6171287 Lynn et al. Jan 2001 B1
6174539 Stamler et al. Jan 2001 B1
6179141 Nakamura Jan 2001 B1
6183450 Lois Feb 2001 B1
6202870 Pearce Mar 2001 B1
6202901 Gerber et al. Mar 2001 B1
6206134 Stark et al. Mar 2001 B1
6206860 Richmond Mar 2001 B1
6207855 Toone et al. Mar 2001 B1
6217564 Peters et al. Apr 2001 B1
6227391 King May 2001 B1
6232406 Stoy May 2001 B1
6232434 Stamler et al. May 2001 B1
6237800 Barrett et al. May 2001 B1
6242393 Ishida et al. Jun 2001 B1
6245048 Fangrow et al. Jun 2001 B1
6245056 Walker et al. Jun 2001 B1
6248380 Kocher et al. Jun 2001 B1
6250315 Ernster Jun 2001 B1
6255277 Stamler et al. Jul 2001 B1
6267754 Peters Jul 2001 B1
6299132 Weinheimer et al. Oct 2001 B1
6315113 Britton et al. Nov 2001 B1
6315761 Shcherbina et al. Nov 2001 B1
6359167 Toone et al. Mar 2002 B2
6359182 Stamler et al. Mar 2002 B1
6375231 Picha et al. Apr 2002 B1
6379660 Saavedra et al. Apr 2002 B1
6379691 Tedeschi et al. Apr 2002 B1
6394983 Mayoral et al. May 2002 B1
6402207 Segal et al. Jun 2002 B1
6403759 Stamler et al. Jun 2002 B2
6409716 Sahatjian et al. Jun 2002 B1
6428520 Lopez Aug 2002 B1
6431219 Redler et al. Aug 2002 B1
6444318 Guire et al. Sep 2002 B1
6468259 Djokic et al. Oct 2002 B1
6471978 Stamler et al. Oct 2002 B1
6488951 Toone et al. Dec 2002 B2
6491965 Berry et al. Dec 2002 B1
6499719 Clancy et al. Dec 2002 B1
6508792 Szames et al. Jan 2003 B2
6508807 Peters Jan 2003 B1
6538116 Stamler et al. Mar 2003 B2
6541802 Doyle Apr 2003 B2
6543745 Enerson Apr 2003 B1
6550493 Williamson et al. Apr 2003 B2
6555504 Ayai et al. Apr 2003 B1
6562781 Berry et al. May 2003 B1
6581906 Pott et al. Jun 2003 B2
6583311 Toone et al. Jun 2003 B2
6585691 Vitello Jul 2003 B1
6595964 Finley et al. Jul 2003 B2
6595981 Huet Jul 2003 B2
6605294 Sawhney Aug 2003 B2
6605751 Gibbins et al. Aug 2003 B1
6609696 Enerson Aug 2003 B2
6632199 Tucker et al. Oct 2003 B1
6634498 Kayerod et al. Oct 2003 B2
6656217 Herzog, Jr. et al. Dec 2003 B1
6666852 Niedospial, Jr. Dec 2003 B2
6673891 Stamler et al. Jan 2004 B2
6679395 Pfefferkorn et al. Jan 2004 B1
6679870 Finch et al. Jan 2004 B1
6681803 Taneya et al. Jan 2004 B2
6685694 Finch et al. Feb 2004 B2
6692468 Waldenburg Feb 2004 B1
6695817 Fangrow Feb 2004 B1
6716396 Anderson Apr 2004 B1
6722705 Korkor Apr 2004 B2
6725492 Moore et al. Apr 2004 B2
6745998 Doyle Jun 2004 B2
6786884 DeCant, Jr. et al. Sep 2004 B1
6808510 DiFiore Oct 2004 B1
6827766 Carnes et al. Dec 2004 B2
6840501 Doyle Jan 2005 B2
6871087 Hughes et al. Mar 2005 B1
6875205 Leinsing Apr 2005 B2
6875840 Stamler et al. Apr 2005 B2
6887994 Stamler et al. May 2005 B2
6899315 Mailville et al. May 2005 B2
6911025 Miyahar Jun 2005 B2
6916051 Fisher Jul 2005 B2
6929005 Sullivan et al. Aug 2005 B2
6943035 Davies et al. Sep 2005 B1
6955669 Curutcharry Oct 2005 B2
6964406 Doyle Nov 2005 B2
7004934 Vaillancourt Feb 2006 B2
7015347 Toone et al. Mar 2006 B2
7030238 Stamler et al. Apr 2006 B2
7037302 Vaillancourt May 2006 B2
7040598 Raybuck May 2006 B2
7044441 Doyle May 2006 B2
7045585 Berry et al. May 2006 B2
7049308 Stamler et al. May 2006 B2
7052711 West et al. May 2006 B2
7056308 Utterberg Jun 2006 B2
7067659 Stamler et al. Jun 2006 B2
7081109 Tighe et al. Jul 2006 B2
7083605 Miyahara Aug 2006 B2
7087709 Stamler et al. Aug 2006 B2
7097850 Chappa et al. Aug 2006 B2
7100891 Doyle Sep 2006 B2
7125396 Leinsing et al. Oct 2006 B2
7140592 Phillips Nov 2006 B2
7147625 Sarangapani et al. Dec 2006 B2
7160272 Eyal et al. Jan 2007 B1
7182313 Doyle Feb 2007 B2
7195615 Tan Mar 2007 B2
7198611 Connell et al. Apr 2007 B2
7244249 Leinsing et al. Jul 2007 B2
7259250 Stamler et al. Aug 2007 B2
7279176 West et al. Oct 2007 B1
7282186 Lake, Jr. et al. Oct 2007 B2
7306197 Parrino et al. Dec 2007 B2
7306198 Doyle Dec 2007 B2
7306566 Raybuck Dec 2007 B2
7309326 Fangrow, Jr. Dec 2007 B2
7316669 Ranalletta Jan 2008 B2
7347458 Rome et al. Mar 2008 B2
7347853 DiFiore et al. Mar 2008 B2
7350764 Raybuck Apr 2008 B2
7361164 Simpson et al. Apr 2008 B2
7417109 Stamler et al. Aug 2008 B2
7431712 Kim Oct 2008 B2
7442402 Chudzik et al. Oct 2008 B2
7452349 Miyahar Nov 2008 B2
7485107 DiFiore et al. Feb 2009 B2
7491192 DiFiore Feb 2009 B2
7497484 Ziman Mar 2009 B2
7516846 Hansen Apr 2009 B2
7588563 Guala Sep 2009 B2
7611505 Ranalletta et al. Nov 2009 B2
7614426 Kitani et al. Nov 2009 B2
7615034 DiFiore Nov 2009 B2
7625907 Stamler et al. Dec 2009 B2
7635344 Tennican et al. Dec 2009 B2
D607325 Rogers et al. Jan 2010 S
7645274 Whitley Jan 2010 B2
7651481 Raybuck Jan 2010 B2
7666170 Guala Feb 2010 B2
7708714 Connell et al. May 2010 B2
7731678 Tennican et al. Jun 2010 B2
7731679 Tennican et al. Jun 2010 B2
7749189 Tennican et al. Jul 2010 B2
7753891 Tennican et al. Jul 2010 B2
7758530 DiFiore et al. Jul 2010 B2
7758566 Simpson et al. Jul 2010 B2
7762524 Cawthon et al. Jul 2010 B2
7763006 Tennican Jul 2010 B2
7766182 Trent et al. Aug 2010 B2
7766897 Ramsey et al. Aug 2010 B2
7776011 Tennican et al. Aug 2010 B2
7780794 Rogers et al. Aug 2010 B2
7785616 Stamler et al. Aug 2010 B2
7794675 Lynn Sep 2010 B2
7799010 Tennican Sep 2010 B2
7803139 Fangrow, Jr. Sep 2010 B2
7803140 Fangrow, Jr. Sep 2010 B2
7815614 Fangrow, Jr. Oct 2010 B2
7857793 Raulerson et al. Dec 2010 B2
7922701 Buchman Apr 2011 B2
7922711 Ranalletta et al. Apr 2011 B2
7928079 Hrabie et al. Apr 2011 B2
7938795 DiFiore et al. May 2011 B2
7956062 Stamler et al. Jun 2011 B2
7959026 Bertani Jun 2011 B2
7963565 Suter Jun 2011 B2
7972137 Rosen Jul 2011 B2
7972322 Tennican Jul 2011 B2
7981090 Plishka et al. Jul 2011 B2
7985302 Rogers et al. Jul 2011 B2
7993309 Schweikert Aug 2011 B2
7998134 Fangrow et al. Aug 2011 B2
8034454 Terry Oct 2011 B2
8065773 Vaillancourt et al. Nov 2011 B2
8066670 Cluff et al. Nov 2011 B2
8069523 Vaillancourt et al. Dec 2011 B2
8113837 Zegarelli Feb 2012 B2
8146757 Abreu et al. Apr 2012 B2
8162899 Tennican Apr 2012 B2
8167847 Anderson et al. May 2012 B2
8172825 Solomon et al. May 2012 B2
8177761 Howlett et al. May 2012 B2
8177772 Christensen et al. May 2012 B2
8197749 Howlett et al. Jun 2012 B2
8206514 Rogers et al. Jun 2012 B2
8231587 Solomon et al. Jul 2012 B2
8231602 Anderson et al. Jul 2012 B2
8252247 Ferlic Aug 2012 B2
8262628 Fangrow, Jr. Sep 2012 B2
8262643 Tennican Sep 2012 B2
8273303 Ferlic et al. Sep 2012 B2
8281824 Molema et al. Oct 2012 B2
8328767 Solomon et al. Dec 2012 B2
8336152 Kerr et al. Dec 2012 B2
8343112 Solomon et al. Jan 2013 B2
8361408 Lynn Jan 2013 B2
8372045 Needle et al. Feb 2013 B2
8377040 Burkholz et al. Feb 2013 B2
8414547 DiFiore et al. Apr 2013 B2
8419713 Solomon et al. Apr 2013 B1
8454579 Fangrow, Jr. Jun 2013 B2
8480968 Lynn Jul 2013 B2
8491546 Hoang et al. Jul 2013 B2
8500717 Becker Aug 2013 B2
8506527 Carlyon Aug 2013 B2
8506538 Chelak Aug 2013 B2
8523798 DiFiore Sep 2013 B2
8523830 Solomon et al. Sep 2013 B2
8523831 Solomon et al. Sep 2013 B2
8533887 Hirst Sep 2013 B2
8545479 Kitani et al. Oct 2013 B2
8568371 Siopes et al. Oct 2013 B2
8622995 Ziebol et al. Jan 2014 B2
8622996 Ziebol et al. Jan 2014 B2
8641681 Solomon et al. Feb 2014 B2
8641684 Utterberg et al. Feb 2014 B2
8647308 Solomon et al. Feb 2014 B2
8647326 Solomon et al. Feb 2014 B2
8651271 Shen Feb 2014 B1
8671496 Kerr et al. Mar 2014 B2
8740864 Hoang et al. Jun 2014 B2
8758307 Grimm et al. Jun 2014 B2
8777504 Shaw et al. Jul 2014 B2
8791073 West et al. Jul 2014 B2
8845593 Anderson et al. Sep 2014 B2
8877231 Rosen Nov 2014 B2
8910919 Bonnal et al. Dec 2014 B2
8920404 DiFiore et al. Dec 2014 B2
8968268 Anderson et al. Mar 2015 B2
8981139 Schoenfisch et al. Mar 2015 B2
8999073 Rogers et al. Apr 2015 B2
9022984 Ziebol et al. May 2015 B2
9072296 Mills et al. Jul 2015 B2
9072868 Ziebol et al. Jul 2015 B2
9078992 Ziebol et al. Jul 2015 B2
9089680 Ueda et al. Jul 2015 B2
9095500 Brandenburger et al. Aug 2015 B2
9095667 Von Schuckmann Aug 2015 B2
9101685 Li et al. Aug 2015 B2
9101750 Solomon et al. Aug 2015 B2
9114915 Solomon et al. Aug 2015 B2
9125600 Steube et al. Sep 2015 B2
9149624 Lewis Oct 2015 B2
9180252 Gelblum et al. Nov 2015 B2
9192449 Kerr et al. Nov 2015 B2
9205248 Wu et al. Dec 2015 B2
9216440 Ma et al. Dec 2015 B2
9233208 Tekeste Jan 2016 B2
9242084 Solomon et al. Jan 2016 B2
9248093 Kelley, III et al. Feb 2016 B2
9248229 Devouassoux et al. Feb 2016 B2
9259284 Rogers et al. Feb 2016 B2
9259535 Anderson et al. Feb 2016 B2
9283367 Hoang et al. Mar 2016 B2
9283368 Hoang et al. Mar 2016 B2
9283369 Ma et al. Mar 2016 B2
9289588 Chen Mar 2016 B2
9296525 Murphy et al. Mar 2016 B2
9302049 Tekeste Apr 2016 B2
9320858 Grimm et al. Apr 2016 B2
9320859 Grimm et al. Apr 2016 B2
9320860 Grimm et al. Apr 2016 B2
9352080 Goodall et al. May 2016 B2
9352140 Kerr et al. May 2016 B2
9352141 Wong May 2016 B2
9352142 Ziebol et al. May 2016 B2
9381339 Wu et al. Jul 2016 B2
9399125 Burkholz Jul 2016 B2
9408971 Carlyon Aug 2016 B2
9527660 Tennican Dec 2016 B2
9592375 Tennican Mar 2017 B2
9700676 Anderson et al. Jul 2017 B2
9700677 Anderson et al. Jul 2017 B2
9700710 Anderson et al. Jul 2017 B2
9707348 Anderson et al. Jul 2017 B2
9707349 Anderson et al. Jul 2017 B2
9707350 Anderson et al. Jul 2017 B2
9809355 Solomon et al. Nov 2017 B2
9849276 Ziebol et al. Dec 2017 B2
9867975 Gardner et al. Jan 2018 B2
9907617 Rogers Mar 2018 B2
9933094 Fangrow Apr 2018 B2
9999471 Rogers et al. Jun 2018 B2
10016587 Gardner et al. Jul 2018 B2
10046156 Gardner et al. Aug 2018 B2
10159829 Ziebol et al. Dec 2018 B2
10166381 Gardner et al. Jan 2019 B2
10195000 Rogers et al. Feb 2019 B2
10201692 Chang Feb 2019 B2
10328207 Anderson et al. Jun 2019 B2
10525250 Ziebol et al. Jan 2020 B1
10695550 Gardner et al. Jun 2020 B2
10744316 Fangrow Aug 2020 B2
10806919 Gardner et al. Oct 2020 B2
10821278 Gardner et al. Nov 2020 B2
11160932 Anderson et al. Nov 2021 B2
11229746 Anderson et al. Jan 2022 B2
20020077693 Barclay et al. Jun 2002 A1
20020082682 Barclay et al. Jun 2002 A1
20020098278 Bates et al. Jun 2002 A1
20030039697 Zhao et al. Feb 2003 A1
20030062376 Sears et al. Apr 2003 A1
20030072783 Stamler et al. Apr 2003 A1
20030153865 Connell et al. Aug 2003 A1
20030199835 Leinsing et al. Oct 2003 A1
20030208165 Christensen et al. Nov 2003 A1
20040034042 Tsuji et al. Feb 2004 A1
20040034329 Mankus et al. Feb 2004 A1
20040037836 Stamler et al. Feb 2004 A1
20040048542 Thomaschefsky et al. Mar 2004 A1
20040052689 Yao Mar 2004 A1
20040052831 Modak et al. Mar 2004 A1
20040156908 Polaschegg et al. Aug 2004 A1
20040210201 Farnan Oct 2004 A1
20040215148 Hwang et al. Oct 2004 A1
20040247640 Zhao et al. Dec 2004 A1
20040249337 DiFiore Dec 2004 A1
20040249338 DeCant, Jr. et al. Dec 2004 A1
20050013836 Raad Jan 2005 A1
20050015075 Wright et al. Jan 2005 A1
20050065479 Schiller et al. Mar 2005 A1
20050098527 Yates et al. May 2005 A1
20050124942 Richmond Jun 2005 A1
20050124970 Kunin et al. Jun 2005 A1
20050147524 Bousquet Jul 2005 A1
20050147525 Bousquet Jul 2005 A1
20050148930 Hseih et al. Jul 2005 A1
20050152891 Toone et al. Jul 2005 A1
20050171493 Nicholls Aug 2005 A1
20050214185 Castaneda Sep 2005 A1
20050220882 Pritchard et al. Oct 2005 A1
20050228362 Vaillancourt Oct 2005 A1
20050228482 Herzog et al. Oct 2005 A1
20050256461 DiFiore et al. Nov 2005 A1
20050265958 West et al. Dec 2005 A1
20050267421 Wing Dec 2005 A1
20050271711 Lynch Dec 2005 A1
20050288551 Callister et al. Dec 2005 A1
20060004316 DiFiore et al. Jan 2006 A1
20060024372 Utterberg et al. Feb 2006 A1
20060058734 Phillips Mar 2006 A1
20060096348 DiFiore May 2006 A1
20060118122 Martens et al. Jun 2006 A1
20060129109 Shaw et al. Jun 2006 A1
20060142730 Proulx et al. Jun 2006 A1
20060149191 DiFiore Jul 2006 A1
20060161115 Fangrow Jul 2006 A1
20060195117 Rucker et al. Aug 2006 A1
20060202146 Doyle Sep 2006 A1
20060206178 Kim Sep 2006 A1
20060253084 Nordgren Nov 2006 A1
20060261076 Anderson Nov 2006 A1
20070003603 Karandikar et al. Jan 2007 A1
20070088292 Fangrow Apr 2007 A1
20070088293 Fangrow Apr 2007 A1
20070088294 Fangrow Apr 2007 A1
20070106205 Connell et al. May 2007 A1
20070167910 Tennican et al. Jul 2007 A1
20070179453 Lim et al. Aug 2007 A1
20070187353 Fox et al. Aug 2007 A1
20070212381 DiFiore et al. Sep 2007 A1
20070231315 Lichte et al. Oct 2007 A1
20070248676 Stamler et al. Oct 2007 A1
20070249996 Tennican et al. Oct 2007 A1
20070265578 Tennican et al. Nov 2007 A1
20070287989 Crawford et al. Dec 2007 A1
20080027399 Harding et al. Jan 2008 A1
20080027401 Ou-Yang Jan 2008 A1
20080033371 Updegraff et al. Feb 2008 A1
20080039803 Lynn Feb 2008 A1
20080058733 Vogt et al. Mar 2008 A1
20080093245 Periasamy et al. Apr 2008 A1
20080095680 Steffens et al. Apr 2008 A1
20080097315 Miner et al. Apr 2008 A1
20080097407 Plishka Apr 2008 A1
20080103485 Kruger May 2008 A1
20080287920 Fangrow et al. May 2008 A1
20080014005 Shirley Jun 2008 A1
20080128646 Clawson Jun 2008 A1
20080147047 Davis et al. Jun 2008 A1
20080161763 Harding et al. Jul 2008 A1
20080172007 Bousquet Jul 2008 A1
20080177250 Howlett et al. Jul 2008 A1
20080187460 Utterberg et al. Aug 2008 A1
20080188791 DiFiore et al. Aug 2008 A1
20080190485 Guala Aug 2008 A1
20080262465 Zinger et al. Oct 2008 A1
20080318333 Nielsen et al. Dec 2008 A1
20080319423 Tanghoj et al. Dec 2008 A1
20090008393 Howlett et al. Jan 2009 A1
20090012426 Tennican Jan 2009 A1
20090024096 Hai et al. Jan 2009 A1
20090028750 Ryan Jan 2009 A1
20090062766 Howlett et al. Mar 2009 A1
20090093757 Tennican Apr 2009 A1
20090126867 Decant, Jr. et al. May 2009 A1
20090137969 Colantonio et al. May 2009 A1
20090149820 DiFiore Jun 2009 A1
20090163876 Chebator et al. Jun 2009 A1
20090205151 Fisher et al. Aug 2009 A1
20090205656 Nishibayashi et al. Aug 2009 A1
20090247485 Ahmed et al. Oct 2009 A1
20090259194 Pinedjian et al. Oct 2009 A1
20090270832 Vancaillie et al. Oct 2009 A1
20090293882 Terry Dec 2009 A1
20100004510 Kuroshima Jan 2010 A1
20100049170 Solomon et al. Feb 2010 A1
20100050351 Colantonio et al. Mar 2010 A1
20100064456 Ferlic Mar 2010 A1
20100074932 Talsma Mar 2010 A1
20100137472 Ou-Yang Jun 2010 A1
20100143427 King et al. Jun 2010 A1
20100152670 Low Jun 2010 A1
20100160894 Julian et al. Jun 2010 A1
20100172794 Ferlic et al. Jul 2010 A1
20100242993 Hoang et al. Sep 2010 A1
20100253070 Cheon et al. Oct 2010 A1
20100280805 DiFiore Nov 2010 A1
20100292673 Korogi et al. Nov 2010 A1
20100292674 Jepson et al. Nov 2010 A1
20100306938 Rogers et al. Dec 2010 A1
20100318040 Kelley, III et al. Dec 2010 A1
20110030726 Vaillancourt et al. Feb 2011 A1
20110044850 Solomon et al. Feb 2011 A1
20110046564 Zhong Feb 2011 A1
20110046603 Felsovalyi et al. Feb 2011 A1
20110062703 Lopez Mar 2011 A1
20110064512 Shaw et al. Mar 2011 A1
20110071475 Horvath et al. Mar 2011 A1
20110082431 Burgess et al. Apr 2011 A1
20110184338 McKay Jul 2011 A1
20110184382 Cady Jul 2011 A1
20110208128 Wu et al. Aug 2011 A1
20110217212 Solomon et al. Sep 2011 A1
20110276031 Hoang et al. Nov 2011 A1
20110282302 Lopez et al. Nov 2011 A1
20110311602 Mills et al. Dec 2011 A1
20110314619 Schweikert Dec 2011 A1
20120022469 Albert et al. Jan 2012 A1
20120031904 Kuhn et al. Feb 2012 A1
20120039764 Solomon et al. Feb 2012 A1
20120083730 Rush et al. Apr 2012 A1
20120083750 Sansoucy Apr 2012 A1
20120157965 Wotton et al. Jun 2012 A1
20120191029 Hopf et al. Jul 2012 A1
20120195807 Ferlic Aug 2012 A1
20120216359 Rogers et al. Aug 2012 A1
20120216360 Rogers et al. Aug 2012 A1
20120220955 Maseda et al. Aug 2012 A1
20120283696 Cronenberg et al. Nov 2012 A1
20120302968 Tennican Nov 2012 A1
20120302970 Tennican Nov 2012 A1
20120302997 Gardner et al. Nov 2012 A1
20120315201 Ferlic et al. Dec 2012 A1
20130030414 Gardner et al. Jan 2013 A1
20130035667 Anderson et al. Feb 2013 A1
20130039953 Dudnyk et al. Feb 2013 A1
20130053751 Holtham Feb 2013 A1
20130072908 Solomon et al. Mar 2013 A1
20130085313 Fowler et al. Apr 2013 A1
20130085474 Charles et al. Apr 2013 A1
20130098398 Kerr et al. Apr 2013 A1
20130098938 Efthimiadis Apr 2013 A1
20130102950 DiFiore Apr 2013 A1
20130123754 Solomon et al. May 2013 A1
20130134161 Fogel et al. May 2013 A1
20130138085 Tennican May 2013 A1
20130144258 Ziebol et al. Jun 2013 A1
20130150795 Snow Jun 2013 A1
20130164189 Hadden Jun 2013 A1
20130171030 Ferlic et al. Jul 2013 A1
20130183635 Wilhoit Jul 2013 A1
20130197485 Gardner et al. Aug 2013 A1
20140042116 Shen et al. Feb 2014 A1
20140048079 Gardner et al. Feb 2014 A1
20140052074 Tekeste Feb 2014 A1
20140101876 Rogers et al. Apr 2014 A1
20140155868 Nelson et al. Jun 2014 A1
20140227144 Liu et al. Aug 2014 A1
20140228775 Burkholz et al. Aug 2014 A1
20140228809 Wong Aug 2014 A1
20140243797 Jensen et al. Aug 2014 A1
20140249476 Grimm et al. Sep 2014 A1
20140249477 Grimm et al. Sep 2014 A1
20140249486 Grimm et al. Sep 2014 A1
20140336610 Michel Nov 2014 A1
20140339812 Carney et al. Nov 2014 A1
20140339813 Cederschiöld et al. Nov 2014 A1
20150141934 Gardner et al. May 2015 A1
20150148287 Woo et al. May 2015 A1
20150165127 Haefele et al. Jun 2015 A1
20150217106 Banik et al. Aug 2015 A1
20150231380 Hoang et al. Aug 2015 A1
20150237854 Mills et al. Aug 2015 A1
20150238703 Glocker Aug 2015 A1
20150258324 Chida et al. Sep 2015 A1
20150273199 Adams et al. Oct 2015 A1
20150297455 Sanders et al. Oct 2015 A1
20150297881 Sanders et al. Oct 2015 A1
20150306367 DiFiore Oct 2015 A1
20150306369 Burkholz et al. Oct 2015 A1
20150314119 Anderson et al. Nov 2015 A1
20150320926 Fitzpatrick et al. Nov 2015 A1
20150320992 Bonnet et al. Nov 2015 A1
20150343174 Ziebol et al. Dec 2015 A1
20150374968 Solomon et al. Dec 2015 A1
20160001056 Nelson et al. Jan 2016 A1
20160001058 Ziebol et al. Jan 2016 A1
20160015863 Gupta et al. Jan 2016 A1
20160015931 Ryan et al. Jan 2016 A1
20160015959 Solomon et al. Jan 2016 A1
20160045629 Gardner et al. Feb 2016 A1
20160067365 Ma et al. Mar 2016 A1
20160067471 Ingram et al. Mar 2016 A1
20160088995 Ueda et al. Mar 2016 A1
20160089530 Sathe Mar 2016 A1
20160101223 Kelley, III et al. Apr 2016 A1
20160101276 Tekeste Apr 2016 A1
20160106969 Neftel Apr 2016 A1
20160121097 Steele May 2016 A1
20160144118 Solomon et al. May 2016 A1
20160158520 Ma et al. Jun 2016 A1
20160158521 Hoang et al. Jun 2016 A1
20160158522 Hoang et al. Jun 2016 A1
20160184527 Tekeste Jun 2016 A1
20160213912 Daneluzzi Jul 2016 A1
20160250420 Maritan et al. Sep 2016 A1
20160354596 DiFiore Dec 2016 A1
20170020911 Berry et al. Jan 2017 A1
20170042636 Young Feb 2017 A1
20170143447 Rogers et al. May 2017 A1
20170182241 DiFiore Jun 2017 A1
20170203092 Ryan et al. Jul 2017 A1
20170239443 Abitabilo et al. Aug 2017 A1
20170361023 Anderson et al. Dec 2017 A1
20180028403 Fangrow Feb 2018 A1
20180200500 Ziebol et al. Jul 2018 A1
20180214684 Avula et al. Aug 2018 A1
20180369562 Gardner Dec 2018 A1
20190038888 Gardner Feb 2019 A1
20190111245 Gardner et al. Apr 2019 A1
20190201681 Ziebol et al. Jul 2019 A1
20190282795 Fangrow Sep 2019 A1
20200085690 Fangrow Mar 2020 A1
20200139037 Ziebol et al. May 2020 A1
20200139101 Ziebol et al. May 2020 A1
20200139102 Ziebol et al. May 2020 A1
20200139103 Ziebol et al. May 2020 A1
20200139104 Ziebol et al. May 2020 A1
20200155794 Ziebol May 2020 A1
20200324102 Fangrow Oct 2020 A1
20200330741 Fangrow Oct 2020 A1
20200406020 Fangrow Dec 2020 A1
20210093791 Anderson Apr 2021 A1
20210162194 Gardner Jun 2021 A1
20210205596 Ziebol et al. Jul 2021 A1
20210308442 Gardner Oct 2021 A1
Foreign Referenced Citations (127)
Number Date Country
2 148 847 Dec 1995 CA
2825217 Mar 2007 CA
2 841 832 Jun 2019 CA
2402327 Oct 2000 CN
2815392 Sep 2006 CN
201150420 Nov 2008 CN
201519335 Jul 2010 CN
106902402 Jun 2017 CN
3515665 May 1986 DE
89 06 628 Sep 1989 DE
43 34 272 Apr 1995 DE
29617133 Jan 1997 DE
0 088 341 Sep 1983 EP
0 108 785 May 1984 EP
0 174 162 Mar 1986 EP
0 227 219 Jul 1987 EP
0 237 239 Sep 1987 EP
0 245 872 Nov 1987 EP
0 257 485 Mar 1988 EP
0 639 385 Feb 1995 EP
0 734 721 Oct 1996 EP
0 769 265 Apr 1997 EP
1 061 000 Oct 2000 EP
1 331 020 Jul 2003 EP
1 471 011 Oct 2004 EP
1 442 753 Feb 2007 EP
1 813 293 Aug 2007 EP
1 977 714 Oct 2008 EP
2 444 117 Apr 2012 EP
2 606 930 Jun 2013 EP
2 671 604 Dec 2013 EP
2 731 658 May 2014 EP
2 493 149 May 1982 FR
2 506 162 Nov 1982 FR
2 782 910 Mar 2000 FR
123221 Feb 1919 GB
2 296 182 Jun 1996 GB
2 333 097 Jul 1999 GB
2 387 772 Oct 2003 GB
57-131462 Aug 1982 JP
04-99950 Feb 1992 JP
09-216661 Aug 1997 JP
2000-157630 Jun 2000 JP
2002-234567 Aug 2002 JP
2002-291906 Oct 2002 JP
2005-218649 Aug 2005 JP
2006-182663 Jul 2006 JP
2011-036691 Feb 2011 JP
2011-528647 Nov 2011 JP
2013-520287 Jun 2013 JP
2014-117461 Jun 2014 JP
2 246 321 Feb 2005 RU
WO 8303975 Nov 1983 WO
WO 8505040 Nov 1985 WO
WO 9320806 Oct 1993 WO
WO 9507691 Mar 1995 WO
WO 9635416 Nov 1996 WO
WO 9638136 Dec 1996 WO
WO 199719701 Jun 1997 WO
WO 9812125 Mar 1998 WO
WO 199944665 Sep 1999 WO
WO 200170199 Sep 2001 WO
WO 200205188 Jan 2002 WO
WO 200247581 Jun 2002 WO
WO 200249544 Jun 2002 WO
WO 2003015677 Feb 2003 WO
WO 2003070296 Aug 2003 WO
WO 2004035129 Apr 2004 WO
WO 2004112846 Dec 2004 WO
WO 2005112954 Dec 2005 WO
WO 2005112974 Dec 2005 WO
WO 2006007690 Jan 2006 WO
WO 2006044236 Apr 2006 WO
WO 2006102756 Oct 2006 WO
WO 2007008511 Jan 2007 WO
WO 2007056773 May 2007 WO
WO 2007137056 Nov 2007 WO
WO 2008042285 Apr 2008 WO
WO 2008086631 Jul 2008 WO
WO 2008089196 Jul 2008 WO
WO 2008100950 Aug 2008 WO
WO 2008140807 Nov 2008 WO
WO 2009002474 Dec 2008 WO
WO 2009060322 May 2009 WO
WO 2009117135 Sep 2009 WO
WO 2009123709 Oct 2009 WO
WO 2009136957 Nov 2009 WO
WO 2009153224 Dec 2009 WO
WO 2010002757 Jan 2010 WO
WO 2010002808 Jan 2010 WO
WO 2010011616 Jan 2010 WO
WO 2010034470 Apr 2010 WO
WO 2010039171 Apr 2010 WO
WO 2010062589 Jun 2010 WO
WO 2011028722 Mar 2011 WO
WO 2011053924 May 2011 WO
WO 2011106374 Sep 2011 WO
WO 2011119021 Sep 2011 WO
WO 2012118829 Sep 2012 WO
WO 2012162006 Nov 2012 WO
WO 2013009998 Jan 2013 WO
WO 2013023146 Feb 2013 WO
WO 2012184716 Dec 2013 WO
WO 2013192574 Dec 2013 WO
WO 2014074929 May 2014 WO
WO 2014140949 Sep 2014 WO
WO 14159346 Oct 2014 WO
WO 2015074087 May 2015 WO
WO 2015119940 Aug 2015 WO
WO 2015120336 Aug 2015 WO
WO 2015164129 Oct 2015 WO
WO 2015168677 Nov 2015 WO
WO 2015174953 Nov 2015 WO
WO 2016025775 Feb 2016 WO
WO 2016182822 Nov 2016 WO
WO 2017015047 Jan 2017 WO
WO 2017127364 Jul 2017 WO
WO 2017127365 Jul 2017 WO
WO 2018009653 Jan 2018 WO
WO 2018071717 Apr 2018 WO
WO 2018204206 Nov 2018 WO
WO 2018237090 Dec 2018 WO
WO 2018237122 Dec 2018 WO
WO 2019178560 Sep 2019 WO
WO 2019246472 Dec 2019 WO
WO 2020097366 May 2020 WO
WO 2020251947 Dec 2020 WO
Non-Patent Literature Citations (25)
Entry
Invitation to Pay Additional Search Fees in corresponding International Patent Application No. PCT/US2018/030015, dated Jun. 19, 2018, in 2 pages.
International Search Report and Written Opinion in corresponding International Patent Application No. PCT/US2018/030015, dated Aug. 27, 2018, in 12 pages.
Antibiotic Lock Therapy Guidline, Stanford Hospital and Clinics, Pharmacy Department Policies and Procedures, issued Jun. 2011.
“Small-bore connectors for liquids and gases in healthcare applications—Part : Connectors for intravascular or hypodermic applications,” ISO 80369-7, Corrected version dated Dec. 1, 2016 (50 pages).
Hospira, “You Work in Neverland,” Lifeshield Product Brochure in 2 pages, Published 2009.
Baxter Minicap: Photographs of the Baxter Minicap (Sep. 1, 1998) (4 pages).
Baxter, “Peritoneal Dialysis Patient Connectology,” Product Descriptions in 1 page, downloaded Jul. 1, 2011.
Beta Cap II Advertisement from Quinton Instrument Co. (Aug. 1981).
Catheter Connections, “Introducing DualCap,” Product Brochure in 1 page, Copyright 2011.
Charney, “Baxter Healthcare InterlinkTM IV Access System” in 1 page, from Handbook of Modern Hospital Safety. Published Mar. 1999.
Clave® Needlefree Connector, icumedial, human connections, 2 page brochure. 2012, M1-1065 Rev. 04.
Conical Fittings: International Standard, “Conical fittings with 6% (Luer) Taper for Syringes, Needles and certain Other Medical Equipment—Part 2: Lock Fittings”, Ref. No. ISO 594-2:1998. International Organization for Standardization (Sep. 1, 1998) 2nd ed. (16 pages).
Devine, Redacted version of letter from David A. Divine, Esq. of Lee & Hayes, dated May 16, 2011 (3 pages).
Devine, Redacted version of letter from David A. Divine, Esq. of Lee & Hayes, dated May 27, 2011 (3 pages).
Du. Y, et al. Protein adsorption on polyurethane catheters modified with a novel antithrombin-heparin covalent complex, Journal of Biomedical Materials Research Part A, 2006, 216-225.
Holmer, E. et al. The molecular-weight dependence of the rate-enhancing effect of heparin on the inhibition of thrombin, Factor Xa, Factor IXa, Factor XIa, Factor XIIa and kallikrein by antithrombin, Biochem. J. (1981) 193, 395-400.
Hyprotek, “Port Protek,” Product Brochure in 1 page, downloaded Sep. 19, 2011 from http://www.hyprotek.com/products.html.
ICU Medical Antimicrobial Microclave, first sold Jan. 21, 2010, p. 1-2.
Klement, P. et al. Chronic performance of polyurethane catheters covalently coated with ATH complex: A rabbit jugular vein model, Biomaterials, (2006), 27, 5107-5117.
Menyhay et al., “Disinfection of Needleless Catheter Connectors and Access Ports with Alcohol May Not Prevent Microbial Entry: The Promise of a Novel Antiseptic-Barrier Cap” Infection Control Hospital and Epidemiology, vol. 27, No. 1 (Jan. 2006) (5 pages).
Otto, Mosby's Pocket Guide to Infusion Therapy. Elsevier Health Sciences, 2004. Pages 65-66. Accessed at: http://books.google.com/books?id=j8T14HwWdS4C&lpg=PP1&pg=PP1#v=onepage&f=false (Year: 2004).
Photographs of the Baxter Minicap (Sep. 1, 1998) (4 pages).
Quinton Beta Capp II advertisement, in 3 pages.
V-Link Luer Activated Device, with VitalShield Protective Coating, 2 page brochure, Baxter Dec. 2009.
International Preliminary Report on Patentability, re PCT Application No. PCT/US2018/030015, dated Mar. 10, 2020.
Related Publications (1)
Number Date Country
20200069931 A1 Mar 2020 US
Provisional Applications (4)
Number Date Country
62662149 Apr 2018 US
62558618 Sep 2017 US
62520300 Jun 2017 US
62492887 May 2017 US
Continuations (1)
Number Date Country
Parent PCT/US2018/030015 Apr 2018 US
Child 16669303 US