INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

FIELD

Described herein are devices for delivering therapeutic fluids, and more particularly small, disposable, portable infusion devices and methods that can be used to transcutaneously deliver fluids safely and simply to a patient.

BACKGROUND

During drug delivery, it is often desirable to bypass the digestive system of a patient to avoid degradation of the drug's active ingredients that can be caused by the catalytic enzymes in the digestive tract and liver. Delivery of a drug other than by way of the intestines is known as parenteral delivery. Parenteral delivery of drugs in liquid form is often desired to enhance the effect of the substance being delivered, insuring that the unaltered medicine reaches its intended site at a significant concentration. Moreover, undesired side effects associated with other routes of delivery, such as systemic toxicity, can potentially be avoided by parenteral delivery. Further, many medicines are only available in liquid form, and/or the liquid may have desirable characteristics that cannot be achieved with solid or pill form. Delivery of liquid medicines may best be accomplished by infusing directly into the cardiovascular system via veins or arteries, into the subcutaneous tissue, or directly into organs, tumors, cavities, bones, or other site-specific locations within the body.

Parenteral delivery of liquid medicines into the body is often accomplished by administering bolus injections using a needle and reservoir or continuously by gravity driven dispensers or transdermal patch technologies. Bolus injections often imperfectly match the clinical needs of the patient and usually require larger individual doses than are desired at the specific time they are given. Continuous delivery of medicine through gravity feed systems compromise the patient's mobility and lifestyle and limit the therapy to simplistic flow rates and profiles. Transdermal patches have special requirements of the medicine being delivered, particularly as it relates to the molecular structure, and similar to gravity feed systems, the control of the drug administration is severely limited.

Ambulatory infusion pumps have been developed for delivering liquid medicaments to a patient. These infusion devices have the ability to offer sophisticated fluid delivery profiles that can provide bolus delivery, continuous infusion, and variable flow rate delivery. Ambulatory infusion pumps, however, can be problematic, as the user is generally forced to choose between a soft delivery cannula, which tends to have high initial failure rates and is prone to kinking, or a steel needle set, which has a lower initial failure rate but is associated with increased pain and shortened time of use. Additionally, the challenge with current infusion sets is that the 90-degree (i.e., rigid cannula) infusion sets, which are easiest to insert, are also associated with the highest rates of failure, partially due to needle breakage and/or fluid leaking out of the relatively short insertion path. Further, infusion sets with a soft cannula, however, tend to be harder to insert and/or are associated with increased apprehension/intimidation.

Moreover, a necessary and important step in preparing an infusion set for use is filling the tubing with liquid medicament, such as insulin to be delivered to a person with diabetes. This is often done by attaching the infusion set tubing to either the insulin pump reservoir or the insulin pump reservoir adaptor (e.g., a device that holds the reservoir into the pump). The pump is then programmed to fill the tubing with insulin. This is not an automatic process. The user is typically either asked to hold down a button until the tubing is filled or to program an amount believed to be sufficient to fill the tubing. The user is instructed not to move on to another step until they observe insulin drops exiting the distal end of the tubing to infusion site connection or the distal end of the infusion cannula. The observation confirms that the tubing has been filled.

Tube filling carries two risk cases. The first risk case is when the user attempts to fill the tube and makes the mistake of connecting the tube to an infusion set that has already been inserted into their body. This would prevent the user from knowing when the tube had been completely filled and would result in any excess insulin delivered in an attempt to fill the tube to be delivered to the pump user, resulting in an over delivery. Over delivery carries with it a significant risk of hypoglycemia (low blood glucose levels). The second risk case is incomplete filling of the tubing. Failure to completely fill the tubing can lead to under delivery of insulin. This in turn can lead to hyperglycemia (elevated glucose levels). The amount of missed insulin (10 to 15 units) can be approximately 25 to 50% of a typical pump user's daily dose (˜42 units) but could exceed the total daily dose of a pump user with higher than typical insulin sensitivity. In many cases, the missed insulin associated with a non-filled or partially filled tube causes a significant health risk to the pump user. Filling the tubing is not an easy task, especially for those with any macular degeneration, as is often associated with diabetes progression.

Accordingly, an ambulatory infusion pump set that is efficient, safe, effective, easy to insert into a patient, and easy/safe to fill is desired.

SUMMARY OF THE DISCLOSURE

In general in one embodiment, a device for delivering fluid to a patient includes a housing assembly, a subcutaneous infusion cannula assembly extending from the housing, an insertion mechanism, and a fluid connection port. The insertion mechanism is configured to extend the infusion cannula in a helical path from the housing assembly. The fluid connection port is configured to connect the device to a source of delivery fluid.

This and other embodiments can include one or more of the following features. The infusion cannula can have a pre-set curved shape. The device can further include a sharp inner stylet configured to extend through the infusion cannula. The sharp inner stylet can have a pre-set curved shape. The insertion mechanism can further include mechanical features to define or limit the depth of extension of the infusion cannula from the housing assembly. The insertion mechanism can further include a rotational drive mechanism configured to rotate the infusion cannula as the cannula is extended from the housing assembly. The rotational drive mechanism can be a spring. The housing can include an adhesive on at least one surface thereof configured to attach the device to skin of the patient. The subcutaneous infusion cannula can be flexible. The cannula can include an outer tube and an inner reinforcement coil. The cannula can include two or more fluid exit holes at or near the distal end thereof. The insertion mechanism can include an automatic retraction mechanism for moving the stylet from the advanced position to the retracted position on completion of the insertion cycle. The housing assembly can contain a releasable fluid interconnect assembly to connect the subcutaneous cannula assembly to the source of fluid.

In some embodiments, a system for delivering fluid to a user transcutaneously includes a subcutaneous infusion cannula base assembly, a cannula inserter assembly and a fluid connection assembly. The subcutaneous infusion cannula base assembly is configured to be located on the user's skin. The cannula inserter assembly is coupled to the cannula base assembly and is configured to drive an infusion cannula through the user's skin in a nominally helical trajectory. The fluid connection assembly is configured to fluidically connect the cannula base assembly to a source of delivery fluid.

In some of the above embodiments, the inserter assembly is removably coupled to the cannula base assembly. The system may further comprise a sharp inner stylet configured to extend through the infusion cannula. The sharp inner stylet may have a pre-set curved shape. In some embodiments, the cannula base assembly includes an adhesive on at least one surface thereof configured to attach the cannula base assembly to the user's skin. In some embodiments, the subcutaneous infusion cannula is flexible. The cannula may include an outer tube and an inner reinforcement coil. In some embodiments, the cannula includes two or more fluid exit holes at or near the distal end thereof.

In some embodiments, the inserter assembly includes an automatic retraction mechanism configured to move the stylet from an advanced position to a retracted position after completion of a cannula insertion cycle. The inserter assembly may also include an automatic release mechanism configured to decouple the inserter assembly from the cannula base assembly after completion of a stylet retraction cycle. The inserter assembly may be configured to automatically perform the cannula insertion cycle, the stylet retraction cycle and a release cycle in succession after a single trigger event without further interaction from the user. In some embodiments, the inserter assembly includes a single drive spring configured to supply all energy required to drive the cannula insertion cycle, the stylet retraction cycle and the release cycle. The system may further comprise packaging for enclosing at least the inserter assembly before use. The inserter assembly may include at least one drive spring, and the inserter assembly may be configured to automatically charge the drive spring as the packaging is being opened.

In some embodiments, the fluid connection assembly of the infusion system includes tubing and an element or assembly that changes color when the tubing has been primed with fluid. The fluid connection assembly may include a releasable fluid interconnect assembly configured to releasably connect the cannula base assembly to the source of delivery fluid, and the source of delivery fluid may be external to the cannula base assembly. The releasable fluid interconnect assembly may include a needle and a septum, and the fluid interconnect assembly may be configured to insert an end of the needle through the septum after a cannula stylet is withdrawn from the septum.

In some embodiments, a system for delivering fluid to a user transcutaneously includes a subcutaneous infusion cannula base assembly, a cannula inserter assembly and a fluid connection assembly. The cannula base assembly is configured to be located on the user's skin and includes an infusion cannula having a central lumen therethrough. The cannula includes a reinforcing coil extending along a portion of the central lumen. The coil has at least two different pitches along its length. The cannula inserter assembly is coupled to the cannula base assembly and includes a sharp stylet configured to pass through the central lumen of the cannula. The inserter assembly is configured to drive the stylet and infusion cannula together through the user's skin without a needle placed over the cannula. The fluid connection assembly is configured to fluidically connect the cannula base assembly to a source of delivery fluid.

In some of the above embodiments, the reinforcing coil has a first section with a first coil pitch and a second section with a second coil pitch, the first section being located more distally in the cannula than the second section. In these embodiments, the first coil pitch is greater than the second coil pitch. In some embodiments, the first coil pitch is an open pitch and the second coil pitch is a closed pitch. In some embodiments, the first section includes a plurality of holes though a side wall of the cannula. The inserter assembly may be configured to drive the stylet and infusion cannula together through the user's skin at a 90 degree angle. The inserter assembly may be configured to drive the stylet and infusion cannula together through the user's skin at an angle of less than 45 degrees.

In some embodiments, a system for delivering fluid to a user transcutaneously includes a subcutaneous infusion cannula base assembly, a cannula inserter assembly and a fluid connection assembly. The cannula base assembly is configured to be located on the user's skin and includes an infusion cannula formed from a polyether block amide thermoplastic elastomer having a central lumen therethrough. The cannula has a nominal outside diameter no greater than 0.56 mm. The cannula includes a reinforcing coil extending along a portion of the central lumen. The reinforcing coil has a nominal inside diameter and a nominal outside diameter. The nominal outside diameter is the same as a nominal inside diameter of the central lumen it resides in. The reinforcing coil has a first section with a first coil pitch and a second section with a second coil pitch. The first coil section is located more distally in the cannula than the second section. The first coil pitch is an open pitch and the second coil pitch is a closed pitch. The first section includes a plurality of holes though a side wall of the cannula. The cannula includes a distalmost section having an outer taper of between 10 and 30 degrees and no reinforcing coil located in the distalmost section. A portion of the cannula is siliconized to reduce insertion force. The cannula inserter assembly is coupled to the cannula base assembly and includes a sharp stylet configured to pass through the central lumen of the cannula. The stylet has a nominal outside diameter that is the same as the nominal inside diameter of the reinforcing coil. The stylet has a sharpened distal tip that extends from the distalmost section of the cannula. The inserter assembly is configured to drive the stylet and cannula together through the user's skin without a needle placed over the cannula. The fluid connection assembly is configured to fluidically connect the cannula base assembly to a source of delivery fluid.

