# US 2016/0354596 A1 · Active-agent inserts for connectors and related methods

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- Number: US 2016/0354596 A1
- Document ID: US20160354596A1
- Status: Published application
- Kind: A1
- Application number: 15/111,971
- Filed: 2015-01-16
- Published: 2016-12-08
- Earliest claimed: 2014-01-16
- Assignees: Attwill Medical Solutions Steriflow L.P.
- Applicants: Attwill Medical Solutions Steriflow L.P.
- Inventors: Attilio DiFiore
- Web page: https://patentgrep.com/patent/US20160354596A1

## CPC

- A61M 39/162: {with antiseptic agent incorporated within the connector}
- A61M 25/0017: {specially adapted for long-term hygiene care, e.g. urethral or indwelling catheters to prevent infections}
- A61M 39/10: Tube connectors or tube couplings
- A61M 39/12: for joining a flexible tube to a rigid attachment
- A61M 39/18: Methods or apparatus for making the connection under sterile conditions, i.e. sterile docking
- A61M 39/20: Closure caps or plugs for connectors or open ends of tubes
- A61M 2025/0019: {Cleaning catheters or the like, e.g. for reuse of the device, for avoiding replacement}
- A61M 2025/0056: {provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir}
- A61M 2039/1077: {Adapters, e.g. couplings adapting a connector to one or several other connectors}
- A61M 2205/0205: Materials having antiseptic or antimicrobial properties, e.g. silver compounds, rubber with sterilising agent
- A61M: DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY (introducing media into or onto the bodies of animals A61D7/00; means for inserting tampons A61F13/26; devices for administering food or medicines orally A61J; containers for collecting, storing or administering blood or medical fluids A61J1/05); DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY (surgery A61B; chemical aspects of surgical articles A61L); DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR {(Electrotherapy, e.g. producing anaesthesia by the use of alternating or intermittent currents A61N1/36021)}

## Abstract

A method of tuning the release of an active agent from a cartridge disposed in a catheter and related cartridges are disclosed herein. In one embodiment, a method of tuning the release of an active agent from a cartridge disposed in a catheter convector is provided. The method can include establishing a desired release profile for an active agent to be delivered into a catheter, and disposing a cartridge having the active agent associated therewith into a fluid pathway of a catheter connector of the catheter. Thus, when an aqueous solution contacts and passes by the cartridge, the active agent is released from the cartridge at the desired release profile.

## Claims

### Claim 1

A method of tuning the release of an active agent from a cartridge adapted for insertion into a catheter connector, comprising:
establishing a desired release profile for an active agent to be delivered into a catheter; and
disposing a cartridge having the active agent associated therewith into a fluid pathway of a catheter connector of the catheter, wherein when an aqueous solution contacts and passes by the cartridge, the active agent is released from the cartridge at the desired release profile.

### Claim 2 (depends on 1)

The method of claim 1, wherein the active agent includes an antimicrobial agent, an antiviral agent, an antifungal agent, an antithrombotic agent, or combinations thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the active agent is a pharmaceutical agent.

### Claim 4 (depends on 3)

The method of claim 3, wherein the pharmaceutical agent is a chemotherapeutic agent.

### Claim 5 (depends on 1)

The method of claim 1, wherein the active agent is chemically modified to alter the solubility of the active agent in order to provide the desired release profile of the active agent from the cartridge.

### Claim 6 (depends on 5)

The method of claim 5, wherein the active agent is chemically modified to reduce the solubility of the active agent.

### Claim 7 (depends on 5)

The method of claim 5, wherein the active agent is chemically modified to increase the solubility of the active agent.

### Claim 8 (depends on 1)

The method of claim 1, wherein the active agent is associated with the cartridge by a lyophilization process

### Claim 9 (depends on 1)

The method of claim 1, wherein the active agent is associated with the cartridge such that at least a portion of the active agent is coated with a coating layer that delays the release of the active agent from the cartridge following exposure of the cartridge to the aqueous solution.

### Claim 10 (depends on 9)

The method of claim 9, wherein the coating layer is a water soluble sugar-based coating.

### Claim 11 (depends on 9)

The method of claim 9, wherein the coating layer includes a carbohydrate.

### Claim 12 (depends on 9)

The method of claim 9, wherein the coating layer includes a sugar or a sugar alcohol.

### Claim 13 (depends on 9)

The method of claim 9, wherein the coating layer includes a glycol or a water soluble polymer.

### Claim 14 (depends on 9)

The method of claim 9, wherein the thickness of the coating layer affects the delay in release of the active agent, and wherein the delay in release is measured with respect to the volume of fluid passed primarily through the cartridge.

### Claim 15 (depends on 1)

The method of claim 1, wherein the active agent is associated with the cartridge such that at least a portion of the cartridge is coated with a coating layer and is further undercoated with respect to the active agent.

### Claim 16 (depends on 1)

The method of claim 1, wherein porosity of the cartridge is adapted to delay release of the active agent.

### Claim 17 (depends on 1)

The method of claim 1, wherein the active agent is absorbed beneath a surface of the cartridge.

### Claim 18 (depends on 1)

The method of claim 1, wherein the cartridge associated with the active agent is adapted to include at least two of the following properties:
i) the cartridge has a porosity configured to delay or modulate the release of the active agent;
ii) the active agent is chemically modified to alter its solubility in a predetermined flushing or locking solution;
iii) the active agent is lyophilized on or into a surface of the cartridge;
iv) a coating layer is included on the cartridge that delays or modulates the release of the active agent from the cartridge;
v) the active agent is absorbed beneath a surface of the cartridge; and
vi) the active agent is in solution and is passed through an agent that slows the release of the active agent.

### Claim 19 (depends on 18)

The method of claim 18, wherein the agent that slows the release of the active agent is activated carbon or silica.

### Claim 20 (depends on 1)

The method of claim 1, wherein the cartridge is adapted to be positioned primarily within a lumen of the catheter connector.

### Claim 21 (depends on 1)

The method of claim 1, wherein the active agent is chlorhexidine gluconate or derivative thereof.

### Claim 22

An insert for a luer-type catheter connection, comprising a cartridge adapted for insertion into a fluid pathway of a catheter connector, the cartridge having a lyophilized active agent associated therewith, wherein the cartridge is configured to release the lyophilized active agent into the catheter when fluid is passed along or through the cartridge.

### Claim 23 (depends on 22)

The insert of claim 22, further comprising:
a male end configured for insertion into a female luer fitting of a catheter;
a female end configured to receive a male luer nozzle of a fluid delivery device; and
a fluid pathway connecting the female end and the male end,
wherein the cartridge is positioned such that the fluid pathway is fluidly coupled to the cartridge.

### Claim 24 (depends on 23)

The insert of claim 23, wherein the fluid pathway is primarily between the cartridge and an interior wall of the catheter.

### Claim 25 (depends on 23)

The insert of claim 23, wherein the fluid pathway is primarily through the cartridge.

### Claim 26 (depends on 22)

The insert of claim 22, wherein the active agent is deposited on a surface of the cartridge.

### Claim 27 (depends on 22)

The insert of claim 22, wherein the active agent is absorbed beneath a surface of the cartridge.

### Claim 28 (depends on 22)

The insert of claim 22, wherein the active agent includes an antimicrobial agent, an antiviral agent, an antifungal agent, a chemotherapeutic agent, an antithrombotic agent, or combinations thereof.

### Claim 29 (depends on 22)

The insert of claim 22, wherein the active agent is a pharmaceutical agent.

### Claim 30 (depends on 29)

The insert of claim 29, wherein the pharmaceutical agent is a chemotherapeutic agent.

### Claim 31 (depends on 22)

The insert of claim 22, wherein the active agent is lyophilized to a surface of the cartridge by contacting the cartridge with an active agent-containing solution, and lyophilizing the solution in the presence of the cartridge.

### Claim 32 (depends on 22)

The insert of claim 22, wherein lyophilization occurs at a temperature ranging from −30° C. to −80° C., and at a vacuum pressure of 10 to 50 millitorr.

### Claim 33

An insert for a luer-type catheter connection, comprising a cartridge adapted for insertion into a fluid pathway of a catheter connector, the cartridge having a chemically modified active agent associated therewith, wherein the chemically modified active agent is modified to alter a release profile compared to an unmodified active agent, and wherein the cartridge is configured to release the chemically modified active agent into the catheter when fluid is passed along or through the cartridge.

### Claim 34 (depends on 33)

The insert of claim 33, further comprising:
a male end configured for insertion into a female luer fitting of a catheter;
a female end configured to receive a male luer nozzle of a fluid delivery device; and
a fluid pathway connecting the female end and the male end,
wherein the cartridge is positioned such that the fluid pathway is fluidly coupled to the cartridge.

### Claim 35 (depends on 34)

The insert of claim 34, wherein the fluid pathway is primarily between the cartridge and an interior wall of the catheter.

### Claim 36 (depends on 34)

The insert of claim 34, wherein the fluid pathway is primarily through the cartridge.

### Claim 37 (depends on 33)

The insert of claim 33, wherein the active agent is deposited on a surface of the cartridge.

### Claim 38 (depends on 33)

The insert of claim 33, wherein the active agent is absorbed beneath a surface of the cartridge.

### Claim 39 (depends on 33)

The insert of claim 33, wherein the active agent includes an antimicrobial agent, an antiviral agent, an antifungal agent, a chemotherapeutic agent, an antithrombotic agent, or combination thereof.

### Claim 40 (depends on 33)

The insert of claim 33, wherein the active agent is a pharmaceutical agent.

### Claim 41 (depends on 40)

The insert of claim 40, wherein the pharmaceutical agent is a chemotherapeutic agent.

### Claim 42 (depends on 33)

The insert of claim 33, wherein the chemically modified active agent is modified to delay release of the active agent compared to an unmodified active agent.

### Claim 43 (depends on 33)

The insert of claim 33, wherein the chemically modified active agent is modified to hasten release of the active agent compared to an unmodified active agent.

### Claim 44 (depends on 33)

The insert of claim 33, wherein the chemically modified active agent is modified to modulate or change the release profile compared to an unmodified active agent.

### Claim 45 (depends on 33)

The insert of claim 33, wherein the active agent is chlorhexidine gluconate or derivative thereof.

### Claim 46

An insert for a luer-type catheter connection, comprising a cartridge adapted for insertion into a fluid pathway of a catheter connector, the cartridge having an active agent associated therewith and a coating layer applied to one or both of the cartridge or the active agent, wherein the coating layer is adapted or formulated to control release of the active agent into the catheter when fluid is passed along or through the cartridge.

### Claim 47 (depends on 46)

The insert of claim 46, further comprising:
a male end configured for insertion into a female luer fitting of a catheter;
a female end configured to receive a male luer nozzle of a fluid delivery device; and
a fluid pathway connecting the female end and the male end,
wherein the cartridge is positioned such that the fluid pathway is fluidly coupled to the cartridge.

### Claim 48 (depends on 47)

The insert of claim 47, wherein the fluid pathway is primarily between the cartridge and an interior wall of the catheter.

### Claim 49 (depends on 47)

The insert of claim 47, wherein the fluid pathway is primarily through the cartridge.

### Claim 50 (depends on 46)

The insert of claim 46, wherein the coating layer includes a carbohydrate.

### Claim 51 (depends on 46)

The insert of claim 46, wherein the coating layer includes a sugar or a sugar alcohol.

### Claim 52 (depends on 46)

The insert of claim 46, wherein the coating layer includes a glycol or a water soluble polymer.

### Claim 53 (depends on 46)

The insert of claim 46, wherein the coating layer is applied at a thickness from 0.01 to 100 μm.

### Claim 54 (depends on 46)

The insert of claim 46, wherein the active agent is deposited on a surface of the cartridge and the coating layer is overcoated with respect to the active agent.

### Claim 55 (depends on 46)

The insert of claim 46, wherein the active agent is absorbed beneath a surface of the cartridge and the coating layer is overcoated with respect to the active agent.

### Claim 56 (depends on 46)

The insert of claim 46, wherein the coating layer is coated on the cartridge and is undercoated with respect to the active agent.

### Claim 57 (depends on 46)

The insert of claim 46, wherein the active agent includes an antimicrobial agent, an antiviral agent, an antifungal agent, a chemotherapeutic agent, an antithrombotic agent, or combination thereof.

### Claim 58 (depends on 46)

The insert of claim 46, wherein the active agent is a pharmaceutical agent.

### Claim 59 (depends on 58)

The insert of claim 58, wherein the pharmaceutical agent is a chemotherapeutic agent.

### Claim 60 (depends on 46)

The insert of claim 46, wherein the coating layer is adapted to delay release of the active agent compared to an uncoated cartridge.

### Claim 61 (depends on 47)

The insert of claim 47, wherein the coating layer is adapted to hasten release of the active agent compared to an uncoated cartridge.

### Claim 62 (depends on 46)

The insert of claim 46, wherein the coating layer is adapted to modulate or change the release profile compared to an uncoated cartridge.

### Claim 63 (depends on 46)

The insert of claim 46, wherein the active agent is dichlorhexidine gluconate or derivative thereof.

### Claim 64

An insert for a luer-type catheter connection, comprising a cartridge adapted for insertion into a fluid pathway of a catheter connector, the cartridge having an active agent associated therewith, wherein the cartridge has a porosity configured to control release of the active agent into the catheter when fluid is passed along or through the cartridge.

### Claim 65 (depends on 64)

The insert of claim 64, further comprising:
a male end configured for insertion into a female luer fitting of a catheter;
a female end configured to receive a male luer nozzle of a fluid delivery device; and
a fluid pathway connecting the female end and the male end,
wherein the cartridge is positioned such that the fluid pathway is fluidly coupled to the cartridge.

### Claim 66 (depends on 65)

The insert of claim 65, wherein the fluid pathway is primarily between the cartridge and an interior wall of the catheter.

### Claim 67 (depends on 65)

The insert of claim 65, wherein the fluid pathway is primarily through the cartridge.

### Claim 68 (depends on 64)

The insert of claim 64, wherein the cartridge comprises a porous polymeric, sponge, ceramic, or fibrous material.

### Claim 69 (depends on 64)

The insert of claim 64, wherein the cartridge has a bulk volume of 25% to 75%.

### Claim 70 (depends on 64)

The insert of claim 64, wherein the active agent is deposited on a surface of the cartridge.

### Claim 71 (depends on 64)

The insert of claim 64, wherein the active agent is absorbed beneath a surface of the cartridge.

### Claim 72 (depends on 64)

The insert of claim 64, wherein the active agent includes an antimicrobial agent, an antiviral agent, an antifungal agent, a chemotherapeutic agent, an antithrombotic agent, or combination thereof.

### Claim 73 (depends on 64)

The insert of claim 64, wherein the active agent is a pharmaceutical agent.

### Claim 74 (depends on 73)

The insert of claim 73, wherein the pharmaceutical agent is a chemotherapeutic agent.

### Claim 75 (depends on 64)

The insert of claim 64, wherein the active agent is chlorhexidine gluconate or derivative thereof.

### Claim 76

An insert for a luer-type connection, comprising a cartridge adapted for insertion into a fluid pathway of a catheter or fluid directing device, the cartridge having a pharmaceutical agent associated therewith, wherein the cartridge is adapted to release pharmaceutical agent into the catheter or fluid directing device when fluid is passed along or through the cartridge.

### Claim 77 (depends on 76)

The insert of claim 76, further comprising:
a male end configured for insertion into a female luer fitting of a catheter or fluid directing device;
a female end configured to receive a male luer nozzle of a fluid delivery device; and
a fluid pathway connecting the female end and the male end,
wherein the cartridge is positioned such that the fluid pathway is fluidly coupled to the cartridge.

### Claim 78 (depends on 77)

The insert of claim 77, wherein the fluid pathway is primarily between the cartridge and an interior wall of the catheter.

### Claim 79 (depends on 77)

The insert of claim 77, wherein the fluid pathway is primarily through the cartridge.

### Claim 80 (depends on 76)

The insert of claim 76, wherein the cartridge is adapted for controlled release of the pharmaceutical agent over a predetermined period of time from the cartridge.

### Claim 81 (depends on 76)

The insert of claim 76, wherein the cartridge is adapted for delivering a bolus of the pharmaceutical agent from the cartridge.

### Claim 82 (depends on 76)

The insert of claim 76, wherein the pharmaceutical agent is a chemotherapeutic agent.

### Claim 83 (depends on 76)

The insert of claim 76, wherein the insert is adapted for safety to reduce the risk of contact between a medical practitioner and the pharmaceutical agent.

### Claim 84 (depends on 76)

The insert of claim 76, wherein the catheter or fluid directing device is the catheter and is adapted for transcutaneous or direct vascular or ductal access to a subject or patient.

### Claim 85 (depends on 76)

The insert of claim 76, wherein the catheter or fluid directing device is the fluid directing device and is adapted for delivery to a fluid container or substrate for subsequent oral, topical, intravenous, intramuscular, ocular, anal, vaginal, mucosal, or transdermal preparation or delivery.

### Claim 86 (depends on 76)

The insert of claim 76, wherein the cartridge comprises a porous polymeric, sponge, ceramic, or fibrous material.

### Claim 87 (depends on 76)

The insert of claim 76, wherein the cartridge has a bulk volume of 25% to 75%.

### Claim 88 (depends on 76)

The insert of claim 76, wherein the pharmaceutical agent is deposited on a surface of the cartridge.

### Claim 89 (depends on 76)

The insert of claim 76, wherein the pharmaceutical agent is absorbed beneath a surface of the cartridge.

### Claim 90

A method of tuning the release of an active agent from a cartridge adapted for insertion into a catheter connector, comprising:
determining a desired release profile for an active agent to be delivered into or through a catheter when contacted with a predetermined aqueous solution;
obtaining a cartridge configured to be disposed into a catheter connector along a fluid pathway of the catheter; and
associating the active agent with the cartridge to provide the release profile upon flow of the predetermined aqueous solution in contact with the cartridge.

### Claim 91 (depends on 90)

The method of claim 90, wherein the active agent includes an antimicrobial agent, an antiviral agent, an antifungal agent, an antithrombotic agent, or combination thereof.

### Claim 92 (depends on 90)

The method of claim 90, wherein the active agent is a pharmaceutical agent.

### Claim 93 (depends on 92)

The method of claim 92, wherein the pharmaceutical agent is a chemotherapeutic agent.

### Claim 94 (depends on 90)

The method of claim 90, wherein the active agent is chemically modified to alter the solubility of the active agent in order to provide the desired release profile of the active agent from the cartridge.

### Claim 95 (depends on 90)

The method of claim 90, wherein the active agent is associated with the cartridge by a lyophilization process.

### Claim 96 (depends on 0)

The method of claim 0, wherein the lyophilization process is carried out by freezing the active agent in the presence of the cartridge at a temperature ranging from −30 C to −80 C, and vacuuming the cartridge 10 to 50 millitorr.

### Claim 97 (depends on 90)

The method of claim 90, wherein at least a portion of one or both of the cartridge or the active agent is coated with a coating layer that is adapted to delay the release of the active agent from the cartridge following exposure of the cartridge to the aqueous solution.

### Claim 98 (depends on 90)

The method of claim 90, wherein porosity of the cartridge is adapted to delay release of the active agent.

### Claim 99 (depends on 90)

The method of claim 90, wherein the active agent is deposited on a surface of the cartridge.

### Claim 100 (depends on 90)

The method of claim 90, wherein the active agent is absorbed beneath a surface of the cartridge.

### Claim 101 (depends on 90)

The method of claim 90, wherein the cartridge associated with the active agent is adapted to include at least two of the following properties:
i) the cartridge has a porosity configured to delay or modulate the release of the active agent;
ii) the active agent is chemically modified to alter its solubility in a predetermined flushing or locking solution;
iii) the active agent is lyophilized on or into a surface of the cartridge;
iv) a coating layer is included on the cartridge that delays or modulates the release of the active agent from the cartridge;
v) the active agent is absorbed beneath a surface of the cartridge; and
vi) the active agent is in solution and is passed through an agent that slows the release of the active agent.

### Claim 102 (depends on 101)

The method of claim 101, wherein the agent that slows the release of the active agent is activated carbon or silica.

### Claim 103 (depends on 90)

The method of claim 90, wherein the cartridge is adapted to be positioned primarily within a lumen of the catheter connector.

### Claim 104 (depends on 90)

The method of claim 90, further comprising the step of disposing the cartridge into the catheter connector.

### Claim 105 (depends on 104)

The method of claim 104, further comprising the step of flowing the predetermined aqueous solution in contact with the cartridge.

### Claim 106 (depends on 105)

The method of claim 105, further comprising the step of flowing the predetermined aqueous solution at a predetermined volume.

### Claim 107 (depends on 106)

The method of claim 106, wherein the release profile is such that at least 80 wt % of the active agent content associated with the cartridge is delivered from the cartridge within the first 20 wt % of the predetermined volume.

### Claim 108 (depends on 106)

The method of claim 106, wherein the release profile is such that less than 20 wt % of the active agent content associated with the cartridge is delivered from the cartridge within the first 80 wt % of the predetermined volume.

### Claim 109 (depends on 106)

The method of claim 106, wherein the cartridge is adapted for a catheter locking application.

### Claim 110 (depends on 109)

The method of claim 109, wherein the release profile is such that at least 90 wt % of the active agent content associated with the cartridge is delivered from the cartridge based on a total volume representing a catheter luminal fixed volume downstream from the cartridge.

### Claim 111 (depends on 106)

The method of claim 106, wherein the cartridge is adapted for a catheter flushing application.

### Claim 112 (depends on 111)

The method of claim 111, wherein the release profile is such that a volume of a flush through a lumen is greater than a fixed volume of the lumen, and wherein at least 90% of the agent is released from the cartridge within the last 10% of the flush volume lumen.

### Claim 113 (depends on 90)

The method of claim 90, wherein the desired release profile is such that when 20 mL of the aqueous solution is passed along or through the cartridge within the lumen of a 10 French diameter catheter, no more than 5 wt % of the active agent is released in the first 18 mL of the aqueous solution.

### Claim 114 (depends on 90)

The method of claim 90, wherein the desired release profile is such that when 20 mL of the aqueous solution is passed along or through the cartridge within the lumen of a 10 French diameter catheter, no more than 5 wt % of the active agent is released in the first 15 mL of the aqueous solution.

### Claim 115 (depends on 90)

The method of claim 90, wherein the desired release profile is such that when 20 mL of the aqueous solution is passed along or through the cartridge within the lumen of a 10 French diameter catheter, no more than 10 wt % of the active agent is released in the first 15 mL of the aqueous solution.

### Claim 116 (depends on 90)

The method of claim 90, wherein the desired release profile is such that when 20 mL of the aqueous solution is passed along or through the cartridge within the lumen of a 10 French diameter catheter, no more than 5 wt % of the active agent is released in the first 2 mL of the aqueous solution.

### Claim 117 (depends on 90)

The method of claim 90, wherein the desired release profile is such that when 3.0 mL of the aqueous solution is passed along or through the cartridge within the lumen of a 10 French diameter catheter, at least 95 wt % of the active agent is released in the last 2 mL of the aqueous solution.

### Claim 118 (depends on 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88)

A method of delivering an active agent into the lumen of a catheter or a patient, comprising flowing an aqueous solution in contact with the insert of any one of claims 21-88 to cause the active agent to enter the lumen of the catheter and/or the patient.