Infusion system with extended duration

Abstract

An extended duration infusion device / system suitable for transdermal delivery of a therapeutic fluid to a subject is described. The infusion device reduces and delays the formation of fibrotic envelopes on and around the infusion cannula, and significantly increases the useful life of the infusion device. The infusion device includes a deflectable treatment reservoir to "actively" diffuse insulin and eliminate the effects of foreign body reactions (FBR).

Description

Technical Field

[0001] The present invention relates to an infusion device. The present invention also relates to a method of transdermally infusing a fluid such as insulin or glucagon into a subject. Background Art

[0002] Drug infusion devices provide a way to deliver drugs to a subject percutaneously. The infusion device includes a small infusion device cannula attached to a cannula housing, which is attached to the patient's body (e.g., arm or abdomen). The infusion device also includes a pump and associated catheters to deliver the drug from a reservoir to the cannula for infusion. The cannula is implanted percutaneously in the subject. The cannula is typically part of a wearable device (e.g., an infusion device or a patch pump device) and can be used to deliver drugs to a subject continuously or at predetermined time intervals. Diabetics typically use them to deliver insulin.

[0003] A very common problem associated with current infusion devices is foreign body reaction, which results in the formation of a fibrotic layer or capsule on and around the infusion cannula, leading to occlusion. This typically occurs within 4 days of implantation, which means the cannula must be removed and discarded (often prematurely) and a new cannula implanted in a different location. Blockages can also occur due to improper insertion technique, resulting in kinking of the cannula. Another problem with these devices is that pressure can build up in the infusion cannula because the fibrotic capsule can cause the release of large doses of medication. In the case of insulin infusion devices, this large dose release can cause hypoglycemia in the subject. Failure of insulin delivery can result in hyperglycemia and ketoacidosis.

[0004] Some companies have attempted to passively eliminate this response by increasing the diffusion area by increasing the number of holes in the cannula through which insulin can diffuse. This approach can provide some small enhancement in maintaining insulin diffusion over time. However, this augmentation method is passive and ultimately limits its effectiveness in overcoming fiber obstruction and achieving long-term drug diffusion efficacy.

[0005] It is an object of the present invention to overcome at least one of the above problems. Summary of the invention

[0006] The problems of the prior art are solved by providing an infusion device that includes a deflectable therapeutic reservoir to "actively" diffuse insulin and eliminate the effects of a foreign body reaction (FBR). The deflectable therapeutic reservoir compresses to push the fluid (therapeutic) in the therapeutic reservoir down the length of the connected cannula lumen. This compression of the therapeutic reservoir is controlled by customizing, for example, the pressure, ramp rate, and actuation curve of a second "actuating" reservoir that uses a gas, fluid, or solid to implement multiple diffusion schemes to deflect the therapeutic reservoir, thereby overcoming the effects of the fibrous capsule over time during drug diffusion. By eliminating the effects of this FBR, preset doses of drug can be continuously delivered to surrounding tissues, changing the area of ​​tissue to which these doses are delivered, and continuously addressing the positioning of the cannula lumen, for example, straightening it when it is kinked. The cannula lumen can have a defined hole along its length, or can be completely porous. Providing a drug reservoir with a fluid deflector provides a more controllable actuation mechanism, allowing for more finely tuned and responsive drug delivery from the cannula.

[0007] In a first aspect, there is provided an infusion device adapted for transdermal delivery of a therapeutic fluid to a subject, comprising:

[0008] A small infusion set cannula comprising a hollow body defining a central lumen, a fluid inlet, and a plurality of infusion outlets (8) in fluid communication with the central lumen;

[0009] a treatment fluid chamber, the treatment fluid chamber including a fluid outlet, the fluid outlet being in fluid communication with a fluid inlet and a fluid inlet of the cannula of the small infusion set;

[0010] a therapeutic fluid supply conduit in fluid communication with a fluid inlet of the therapeutic fluid chamber;

[0011] a fluid deflector comprising an actuation chamber, an actuation fluid storage reservoir, an actuation fluid supply conduit fluidly connecting the actuation fluid storage reservoir to the actuation chamber, and an actuation fluid pump operable to pump actuation fluid from the actuation fluid storage reservoir into the actuation chamber;

[0012] an elastically deformable deflectable membrane separating a therapeutic fluid in the therapeutic fluid chamber from an actuation fluid in the actuation chamber; and

[0013] a controller operatively connected to the actuation fluid pump and configured to control actuation of the fluid deflector through actuation of the actuation fluid pump,

[0014] The fluid deflector is generally configured to deflect the elastically deformable deflectable membrane upon actuation to push therapeutic fluid from the therapeutic fluid chamber into the central lumen of the small infusion set cannula and expel the therapeutic fluid through the infusion outlet.

[0015] The infusion device of the present invention allows for the pumping of medication from a reservoir into an implanted infusion device cannula at a predetermined rate and also addresses the problem of fibrous capsule formation by providing a fluid deflector to apply an additional "push" to the medication at certain time intervals and at a specified pressure, which has been found to significantly reduce the rate of fibrous capsule formation. In addition, the infusion device of the present invention allows for the fluid deflector to be positioned near the cannula, which is advantageous because it is in line with the therapeutic flow in the infusion system.

[0016] In any embodiment, the infusion set includes a therapeutic fluid storage container and a therapeutic fluid pump configured to pump therapeutic fluid from the therapeutic fluid storage container to the small infusion set cannula via the therapeutic fluid supply conduit and the therapeutic fluid chamber.

[0017] In any embodiment, the therapeutic fluid chamber comprises the elastically deformable deflectable membrane.

[0018] In any embodiment, the therapeutic fluid chamber is contained within the actuation chamber.

[0019] In any embodiment, the therapeutic fluid chamber and the actuation chamber are connected to the proximal end of the small infusion set cannula.

[0020] In any embodiment, the treatment fluid chamber and the actuation chamber are configured to be disposed on a skin surface.

[0021] In any embodiment, the elastically deformable deflectable membrane has a convex configuration prior to fluid deflection.

[0022] In any embodiment, the small infusion set cannula has an axial length of 5-20 mm.

[0023] In any embodiment, the controller is configured to control an actuation parameter of the fluid deflector, the parameter being selected from an actuation frequency of the fluid deflector, a pressure in the therapeutic fluid chamber during actuation of the fluid deflector, a rate of change of pressure in the therapeutic fluid chamber during actuation, and the actuation curve / waveform.

[0024] In either embodiment, the controller is preprogrammed to actuate the fluid deflector at timed intervals during delivery of a dose of drug.

[0025] In any embodiment, the controller is preprogrammed to actuate the fluid deflector according to a square wave actuation profile with an on time of 4-8 seconds and an off time of 4-8 seconds.

[0026] In any embodiment, the controller is preprogrammed to actuate the fluid deflector at an amplitude of 0.5-15, 2-12, or 4-8 psi.

[0027] In any embodiment, the infusion set (30) includes a body parameter sensor.

[0028] In any embodiment, the body parameter sensor is operably connected to the controller, and wherein the controller is configured to actuate the fluid deflector in response to measurements received from the sensor.

[0029] In any embodiment, the plurality of infusion outlets are arranged along the length of the small infusion set cannula.

[0030] In either embodiment, the small infusion set cannula is flexible.

[0031] In any embodiment, the infusion device comprises:

[0032] a small infusion set cannula having a hollow body defining a central lumen, the central lumen including a plurality of infusion outlets in fluid communication with the central lumen;

[0033] a therapeutic fluid chamber including a fluid outlet in fluid communication with an inlet of the central lumen of the small infusion set cannula;

[0034] therapeutic fluid storage containers;

[0035] a therapeutic fluid supply conduit providing fluid communication between the therapeutic fluid storage container and the fluid inlet of the therapeutic fluid chamber;

[0036] a therapeutic fluid pump configured to pump therapeutic fluid from the therapeutic fluid storage container to the therapeutic fluid chamber through the therapeutic fluid supply conduit;

[0037] a fluid deflector comprising an actuation chamber, an actuation fluid storage container fluidly connected to the actuation chamber, and an actuation fluid pump operable to pump actuation fluid from the actuation fluid storage container to the actuation chamber; and

[0038] a controller operably connected to the actuation fluid pump and configured to control actuation of the actuation fluid pump,

[0039] Typically, the treatment fluid chamber comprises an elastically deformable deflectable membrane separating a treatment fluid in the treatment fluid chamber from an actuation fluid in the actuation fluid chamber.

[0040] In any embodiment, the infusion device comprises:

[0041] a small infusion set cannula having a hollow body defining a central lumen having a plurality of infusion outlets in fluid communication with the central lumen;

[0042] a therapeutic fluid chamber including a fluid outlet in fluid communication with an inlet of the central lumen of the cannula of the small infusion set;

[0043] a therapeutic fluid supply conduit in fluid communication with the fluid inlet of the therapeutic fluid chamber;

[0044] a fluid deflector comprising an actuation chamber, an actuation fluid storage container fluidly connected to the actuation chamber, and an actuation fluid pump operable to pump actuation fluid from the actuation fluid storage container to the actuation chamber; and

[0045] an elastically deformable deflectable membrane that separates a therapeutic fluid in the therapeutic fluid chamber from an actuation fluid in the actuation chamber; and

[0046] a controller operably connected to the actuation fluid pump and configured to control the fluid deflector by actuating the actuation fluid pump,

[0047] Typically, the controller is preprogrammed to actuate the fluid deflector at timed intervals during delivery of a dose of drug.

[0048] In any embodiment, the infusion device comprises:

[0049] a small infusion set cannula having a hollow body defining a central lumen having a plurality of infusion outlets in fluid communication with the central lumen;

[0050] a therapeutic fluid chamber including a fluid outlet in fluid communication with an inlet of the central lumen of the small infusion set cannula;

[0051] a therapeutic fluid supply conduit in fluid communication with a fluid inlet of the therapeutic fluid chamber;

[0052] a fluid deflector comprising an actuation chamber, an actuation fluid storage container fluidly connected to the actuation chamber, and an actuation fluid pump operable to pump actuation fluid from the actuation fluid storage container to the actuation chamber; and

[0053] an elastically deformable deflectable membrane separating a therapeutic fluid in the therapeutic fluid chamber from an actuation fluid in the actuation chamber; and

[0054] a controller operatively connected to the actuation fluid pump and configured to control the fluid deflector through actuation of the actuation fluid pump,

[0055] Typically, the controller is configured to actuate the fluid deflector with a square wave actuation profile.

[0056] In another aspect, an infusion cannula device adapted for transcutaneously delivering a therapeutic fluid to a subject is provided, comprising:

[0057] a small infusion set cannula having a hollow body defining a central lumen having a plurality of infusion outlets in fluid communication with the central lumen;

[0058] a therapeutic fluid chamber defined at least in part by a resiliently deformable deflectable membrane, the therapeutic fluid chamber including a fluid outlet in fluid communication with an inlet of a central lumen of a small infusion set cannula;

[0059] a therapeutic fluid supply conduit in fluid communication with the fluid inlet of the therapeutic fluid chamber;

[0060] a fluid deflector comprising an actuation chamber configured to be pneumatically or hydraulically pressurized by an actuation fluid pump; and

[0061] a controller operably connected to the fluid deflector and operable to control actuation of the fluid deflector,

[0062] Typically, the therapeutic fluid chamber is contained within the actuation chamber such that during use, pressurization of the actuation chamber causes the elastically deformable deflectable membrane to deflect to push the therapeutic fluid from the therapeutic fluid chamber into the hollow body of the small infusion set cannula and expel the therapeutic fluid through the infusion opening.

[0063] In another aspect, an infusion cannula device adapted for transcutaneously delivering a therapeutic fluid to a subject is provided, comprising:

[0064] a small infusion set cannula having a hollow body defining a central lumen, the central lumen including a plurality of infusion outlets in fluid communication with the central lumen;

[0065] therapeutic fluid storage containers;

[0066] a therapeutic fluid supply conduit providing fluid communication between the therapeutic fluid storage container and the fluid inlet of the small infusion set cannula;

[0067] a therapeutic fluid pump (19) configured to pump therapeutic fluid from a therapeutic fluid storage container (18) to a small infusion set cannula (6) via a therapeutic fluid supply conduit (15);

[0068] Characterized in that the infusion device comprises an actuation module, wherein the actuation module comprises:

[0069] A fluid deflector comprising an actuation chamber (11), an actuation fluid storage container (20) fluidly connected to the actuation chamber (11), and an actuation fluid pump (21) operable to pump the actuation fluid from the actuation fluid storage container (20) to the actuation chamber (11) to pressurize the actuation chamber (11);

[0070] a compressible therapeutic fluid chamber (10) arranged in series in a therapeutic fluid supply conduit (15); and

[0071] a controller operatively connected to the actuation fluid pump (21) and configured to control actuation of the actuation fluid pump (21),

[0072] The compressible therapeutic fluid chamber (10) is arranged in the actuation chamber, whereby the actuation chamber (11) causes the compressible therapeutic fluid chamber (10) to compress when pressurized, so as to push the therapeutic fluid from the therapeutic fluid chamber (10) into the hollow body of the small infusion device sleeve (6) and discharge the therapeutic fluid through the infusion opening (8).

[0073] In another aspect, an infusion device is provided, the infusion device comprising an infusion device cannula suitable for delivering a therapeutic fluid, such as a drug, percutaneously to a subject. The term "therapeutic fluid" should be understood to include fluids used for therapeutic or diagnostic purposes. An infusion device generally comprises:

[0074] an infusion set cannula having a hollow body (typically flexible) defining a central lumen having distal and proximal ends and a plurality of infusion openings in fluid communication with the central lumen;

[0075] a therapeutic fluid reservoir comprising a deflectable membrane and in fluid communication with the central lumen of the flexible hollow body;

[0076] a therapeutic fluid supply conduit in fluid communication with the therapeutic fluid reservoir; and

[0077] A deflector is configured to be actuated to deflect the deflectable membrane, thereby pushing therapeutic fluid from the therapeutic fluid reservoir into the flexible hollow body of the infusion cannula and expelling the therapeutic fluid through the infusion opening.

[0078] Typically, the therapeutic fluid reservoir is disposed at the proximal end of the hollow tube. In these embodiments, the therapeutic fluid reservoir forms part of the implantable portion of the cannula. In other embodiments, it is distal to the hollow tube and connected to the hollow tube by a fluid conduit. In these embodiments, the therapeutic fluid reservoir is typically located outside the body.

[0079] In any embodiment, the therapeutic fluid reservoir is an elastically deformable chamber. In any embodiment, the therapeutic fluid reservoir is a soft robotic capsule. In any embodiment, the deflectable membrane is deformable, typically elastically deformable.

[0080] In any embodiment, the cannula includes an actuation chamber, and the therapeutic fluid reservoir is disposed within the actuation chamber.

[0081] In either embodiment, the deflector is a fluid deflector.

[0082] In any embodiment, the fluid deflector includes a deflector chamber, a deflector fluid supply conduit fluidly connected to the deflector chamber, and a first pump operable to pump the deflector fluid into the deflector chamber, whereby supplying the deflector fluid to the deflector chamber causes the size of the deflector chamber to increase and achieve deflection of the deflectable membrane.

[0083] In either embodiment, the therapeutic fluid reservoir and the deflection chamber are separated by a deflectable membrane.

[0084] In any embodiment, the deflector is configured to mechanically deflect the deflectable membrane.

[0085] In any embodiment, the deflector is configured to electrically deflect the deflectable membrane.

[0086] In any embodiment, the deflector is configured to magnetically deflect the deflectable membrane.

[0087] In either embodiment, the deflector is configured to thermally deflect the deflectable film (eg, photothermally actuated or electrothermally actuated).

[0088] In either embodiment, the deflectable membrane has a convex configuration.

[0089] In either embodiment, the deflectable membrane can be deflected from a convex configuration to a planar or concave configuration.

[0090] In any embodiment, the deflectable membrane is deflectable from a planar configuration to a concave configuration.

[0091] In any embodiment, the treatment fluid supply conduit includes a lumen disposed within the deflector fluid supply conduit.

[0092] In any embodiment, the deflector fluid supply conduit includes a lumen disposed within the treatment fluid supply conduit.

[0093] In any embodiment, the plurality of infusion openings are arranged along a side wall of the flexible hollow body.

[0094] In any embodiment, the plurality of infusion openings is provided by at least a portion of a hollow body formed of a material permeable to the therapeutic fluid. Such a porous material may be formed by, for example, salt leaching.

[0095] In either embodiment, the infusion cannula is sized for percutaneous implantation to deliver the drug into subcutaneous or adipose tissue.

[0096] In any embodiment, the infusion cannula has an axial length of 5-20 mm, such as 5-10 mm, 10-20 mm, 10-15 mm, or 15-20 mm.

[0097] In any embodiment, the infusion cannula has an inner diameter of 0.1 to 1.0 mm or 0.1 to 0.5 mm.

[0098] In either embodiment, the system of the present invention is wearable.

[0099] In any embodiment, the system includes a therapeutic fluid storage container fluidly connected to the proximal end of the therapeutic fluid supply conduit.

[0100] In any embodiment, the system includes a second pump configured to pump therapeutic fluid from the therapeutic fluid storage container to the deflectable therapeutic fluid reservoir when actuated.

[0101] In any embodiment, the system includes a controller operably connected to the deflector and operable to control actuation of the deflector. The controller is configured to control the actuation rate of the fluid deflector (e.g., the frequency at which it is actuated). The controller can be configured to control the pressure in the therapeutic fluid reservoir during deflection, the rate of change of pressure, and the actuation profile / waveform (see Figure 7 E).

[0102] In one embodiment, the controller is preprogrammed to actuate the deflector according to a sequence of steps.

[0103] In any embodiment, at least two consecutive steps include different deflection waveforms.

[0104] In either embodiment, the controller is configured to perform the sequence of steps multiple times per day at predetermined time intervals.

[0105] In any embodiment, the system includes a body parameter sensor. The body parameter sensor can be a blood or body fluid sensor. The sensor can be configured to detect a parameter of the body fluid, such as temperature, pH, oxygen, or the level of a component in the body fluid (e.g., a metabolite such as glucose).

[0106] In either embodiment, the sensor is operably connected to the controller, and wherein the controller is configured to actuate the sequence of steps in response to measurements received from the sensor.

[0107] In either embodiment, the sensor is a glucose sensor configured to measure glucose in the blood or interstitial fluid of the subject, wherein the glucose sensor is operably connected to the controller, and wherein the controller is configured to actuate the sequence of steps in response to a blood glucose measurement received from the sensor.

[0108] In either embodiment, the sensor is configured for manual actuation of the pump. This is useful for diabetics, for example, who may wish to actuate the system to deliver a bolus dose of a fluid such as insulin before a meal.

[0109] The present invention also relates to the use of an infusion device as described herein to deliver fluids to a subject via cannula infusion, typically percutaneous infusion.

[0110] The present invention also relates to a method of diffusing a fluid into a subject (in one embodiment, the method employs an infusion device of the present invention), the method comprising the steps of:

[0111] implanting an infusion set cannula having an infusion outlet into tissue of a subject (e.g., percutaneously);

[0112] actuating the therapeutic fluid pump to advance the therapeutic fluid through the therapeutic fluid supply conduit and into the therapeutic fluid chamber; and

[0113] The fluid deflector is actuated by a controller to deflect an elastically deformable deflectable membrane in fluid communication with the therapeutic fluid in the therapeutic fluid chamber, thereby pushing the therapeutic fluid from the therapeutic fluid chamber into the infusion set cannula and out through the infusion outlet.

[0114] In either embodiment, the infusion set cannula is implanted percutaneously into the patient.

[0115] In any embodiment, the fluid deflector includes an actuation chamber and means for fluidly pressurizing the actuation chamber with an actuation fluid to fluidly deflect the elastically deformable deflectable membrane, wherein the method includes actuating an actuation fluid pump to fluidly pressurize the actuation chamber.

[0116] In any embodiment, the method includes delivering a defined dose of a therapeutic fluid to the subject.

[0117] In any embodiment, the elastically deformable deflectable membrane forms part of a therapeutic fluid chamber, wherein the method comprises subcutaneously implanting the therapeutic fluid chamber and the actuation chamber.

[0118] In any embodiment, the method includes modifying at least one deflection parameter of the fluid deflector during delivery of the defined dose of the therapeutic fluid.

[0119] In any embodiment, the deflection parameter is selected from the group consisting of pressure in the therapeutic fluid chamber during actuation of the fluid deflector, a rate of change of pressure in the therapeutic fluid chamber during actuation, and an actuation curve / waveform.

[0120] In any embodiment, the method includes actuating the fluid deflector according to a sequence of steps, wherein at least two of the sequence of steps include different values ​​of the deflection parameter. For example, if the parameter is a waveform of the fluid deflector, the first step may be a square actuation waveform and the second step may be a triangular actuation waveform.

[0121] In any embodiment, the sequence of steps includes at least three steps, wherein each step includes a different actuation waveform.

[0122] In any embodiment, the method includes modifying a rate of change of pressure in the therapeutic fluid chamber during actuation during delivery of a defined dose of the therapeutic fluid.

[0123] In any embodiment, the infusion device includes a controller operably connected to the actuation fluid pump and configured to control actuation of the actuation fluid pump during delivery of a defined dose of the therapeutic fluid.

[0124] In any embodiment, the fluid includes a pharmaceutically active agent.

[0125] In either embodiment, the pharmaceutically active agent is insulin or glucagon.

[0126] In either embodiment, the inflation fluid is a gas such as air or a liquid such as saline.

[0127] Further aspects and preferred embodiments of the invention are defined and described in the further claims set out herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0128] FIG. 1(A) shows an infusion cannula system of the present invention.

[0129] FIG. 1(B) : illustrates an implantable infusion cannula which forms part of the infusion cannula system of the present invention and comprises a hollow tube and an actuation chamber.

[0130] FIG. 2 : shows an infusion cannula with a therapeutic fluid reservoir during filling with therapeutic fluid: (A) before filling; (B) during filling; and (C) after filling.

[0131] FIG3: shows an infusion cannula with a deflection chamber and a therapeutic fluid reservoir (delivering therapeutic fluid through the cannula) during actuation: (A) the therapeutic fluid reservoir is filled with therapeutic fluid; (B) the deflection chamber is filled with fluid, causing the deflectable membrane of the therapeutic fluid reservoir to deflect, thereby pushing the therapeutic fluid into the cannula and out through the hole to enter the tissue; and (C) after the therapeutic fluid reservoir is refilled with therapeutic fluid.

[0132] Figure 4: shows examples of different embodiments of the present invention, including (A) a fluid deflector for a deflectable membrane; (B) an electric, magnetic or acoustic deflector for a deflectable membrane; (C) a mechanical deflector for a deflectable membrane; (D) a photothermal deflector for a deflectable membrane; (E) an electrothermal deflector for a deflectable membrane.

[0133] Figure 5 : shows a diagram of a system of the present invention, which includes an infusion cannula system, a glucose monitor, and a mobile device configured to communicate with the sensor and control system and control the operation of the cannula based on data received from the glucose sensor.

[0134] Figure 6: shows (A) a comparison of active and passive diffusion in terms of the drop in blood glucose levels over time, and separate passive (B) and active (C) diffusion blood glucose curves over time.

[0135] Figure 7 (A): Shown is the diffusion of the drug analog through the fibrous capsule formed around the device over time at 4 and 20 days after implantation.

[0136] Figure 7 (B) shows the diffusion of the drug analog through the fibrous capsule formed around the device 21 days after subcutaneous implantation in rats (shown in red), where the drug analog is concentrated in the reservoir of the device (white dashed line) before actuation and diffuses into the surrounding tissue after actuation.

[0137] Figure 7 (C) shows the diffusion area (cm) for passive diffusion (blue line) and actuated-assisted diffusion (red line). 2 ) is quantified with respect to time.

[0138] Figure 7 (D) shows the diffusion area (cm) of the drug analog before and after actuation and during passive diffusion alone. 2 ), where the bars correspond to the matching colors in part C.

[0139] Figure 7 (E): Waveform showing that varying the actuation regime gives a high level of control over the drug delivery profile. DETAILED DESCRIPTION

[0140] All publications, patents, patent applications, and other references mentioned herein are hereby incorporated by reference in their entirety to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated by reference and were incorporated by reference in its entirety.

[0141] Definition and general preferences

[0142] As used herein, unless otherwise indicated, the following terms are intended to have the following meanings, in addition to any broader (or narrower) meaning that a term may have in the art:

[0143] Unless the context requires otherwise, the singular as used herein shall be understood to include the plural, and vice versa. The terms "a" or "an" used in relation to an entity shall be understood to refer to one or more of that entity. Thus, the terms "a" (or "an"), "one or more" and "at least one" are used interchangeably herein.

[0144] As used herein, the term "comprise" or variations thereof (e.g., "includes" or "comprising") should be understood to mean the inclusion of any described integers (e.g., features, elements, characteristics, properties, method / process steps, or limitations) or groups of integers (e.g., features, elements, characteristics, properties, method / process steps, or limitations), but not the exclusion of any other integers or groups of integers. Thus, as used herein, the term "comprises" is inclusive or open-ended, and does not exclude additional, unrecited integers or method / process steps.

[0145] As used herein, the term "disease" is used to define any abnormal condition that impairs physiological function and is associated with specific symptoms. The term is broadly used to include any disorder, disease, abnormality, pathology, morbidity, condition or syndrome in which physiological function is impaired, regardless of the nature of the etiology (or whether an etiological basis for the disease is actually established). Thus, it includes conditions caused by infection, trauma, injury, surgery, radioablation, age, poisoning or nutritional deficiency.

[0146] As used herein, the term "treatment" or "treating" refers to an intervention (e.g., administering a pharmaceutical agent to a subject) that cures, improves or alleviates disease symptoms or eliminates (or alleviates) its cause (e.g., an increase in tight junction protein levels). In this case, the term is synonymous with the term "therapy".

[0147] In addition, the term "treatment" or "treatment" refers to an intervention (e.g., administering a pharmaceutical agent to a subject) that prevents or delays the onset or progression of a disease or reduces (or eradicates) its incidence in the treated population. In this case, the term "treatment" is synonymous with the term "prophylaxis".

[0148] As used herein, an effective amount or therapeutically effective amount of a drug is defined as an amount that can be administered to a subject without excessive toxicity, irritation, allergic reaction or other problems or complications, comparable to a reasonable benefit / risk ratio, but sufficient to provide the desired effect, such as treatment or prevention manifested by permanent or temporary improvement of the subject's condition. Depending on the age and general condition of the individual, the mode of administration and other factors, the amount will vary from individual to individual. Therefore, although it is impossible to determine an exact effective amount, those skilled in the art are able to determine the appropriate "effective" amount in any individual case using routine experiments and background common sense. In this case, the therapeutic outcome includes eradication or alleviation of symptoms, alleviation of pain or discomfort, extension of survival time, improvement of activity and other clinical signs of improvement. The therapeutic outcome is not necessarily a complete cure. Improvements can be observed in biological / molecular markers, clinical or observed improvements. In a preferred embodiment, the method of the present invention is applicable to humans, large competition animals (horses, camels, dogs) and domestic companion animals (cats and dogs).

[0149] In the context of treatment and effective amounts defined above, the term "subject" (which, where the context permits, is to be understood to include "individual," "animal," "patient," or "mammal") defines any subject in need of treatment, particularly a mammalian subject. Mammalian subjects include, but are not limited to, humans, livestock, farm animals, zoo animals, sports animals, pets (such as dogs, cats, guinea pigs, rabbits, rats, mice, horses, camels, bison, cattle, cows), primates (such as apes, monkeys, gorillas, and chimpanzees), canines (such as dogs and wolves), felines (such as cats, lions, and tigers), equines (such as horses, donkeys, zebras, etc.), food animals (such as cattle, pigs, and sheep), ungulates (such as deer and giraffes), and rodents (e.g., mice, rats, hamsters, and guinea pigs). In a preferred embodiment, the subject is a human. As used herein, the term "horse" refers to equine mammals, including horses, donkeys, asses, kiangs, and zebras.

[0150] "Infusion set cannula" refers to an implantable cannula with a hollow body having an infusion outlet configured to allow the liquid in the hollow body to enter the surrounding tissue implanted by the cannula. An infusion cannula is typically a small infusion set cannula (e.g., having an axial length less than 30 or 25 mm and / or an inner diameter less than 1.5, 1.0, 0.75, 0.5 or 0.3 mm), such as a percutaneous infusion set cannula typically having a length of 6-20 mm and an inner diameter of 0.15-1.0 mm. In one embodiment, the cannula is a 25G cannula. Compared with a larger cannula (e.g., a central line cannula), the infusion set cannula is more likely to be blocked due to fibrosis wrapping. The infusion set cannula is typically flexible. The cannula can be formed by any suitable material, and its details are known to those skilled in the art. Examples of materials include silicone, polyurethane, polyethylene, polyvinyl chloride, PTFE and nylon. In one embodiment, the infusion set cannula is not an intravenous cannula. The cannula typically has an open distal end sized to permit axial advancement of the delivery needle through the lumen of the cannula during implantation of the infusion cannula.

[0151] "Percutaneous" as applied to an infusion set cannula refers to an infusion set cannula that is configured for administration through the skin and is implanted in the subcutaneous or subcutaneous fat layer. Percutaneous infusion cannulas are typically designed to be administered by the patient using an applicator (e.g., Medtronic MINIMED TM The device is self-implanted using an infusion device and does not require a doctor to implant it.

[0152] "Infusion outlet" refers to a hole that allows fluid to be infused from the lumen of the cannula to the surrounding tissue. The hole is usually a small hole formed on the side wall of the cannula, which is usually at least coextensive with the distal end of the balloon and the entire length. These holes are usually arranged on one side of the cannula, and optionally also arranged at the distal end of the cannula. In the embodiment shown, the cannula has two groups of four infusion openings, which are axially arranged on opposite sides of the cannula side wall. It should be understood that the infusion openings can be provided in any number or arrangement. The size of the opening can range from 5-300 μm. The hole can be configured so that the cannula has a porosity of 5% to 95% (i.e., the percentage of area of ​​the cannula side wall opened due to the hole). The infusion opening can also be of any shape, including a circular hole or an elongated slit. The infusion opening can have the same inner diameter from the inside to the outside, or it can be a cone with an inlet larger than an outlet, or vice versa. In some embodiments, the cannula can be formed of a porous material itself, wherein the hole provides an infusion opening. The porous sleeve can be formed by porogen leaching technology (Jeffrey A. Coffer et al., PSS Vol 202, published on June 8, 2005). The porous sleeve can be made of silicone, Pebax, polyurethane, polytetrafluoroethylene, PTFE, nylon elastomer, Dacron and other thermoplastic elastomers.

[0153] A "therapeutic fluid chamber" refers to a chamber having a deflectable membrane, an inlet fluidically connected to a therapeutic fluid supply conduit, and an outlet fluidically connected to the inner cavity of an infusion set cannula. The chamber is typically disposed at the proximal end of the infusion set cannula and is integrally formed with the infusion set cannula and is configured for implantation with the infusion set cannula. In other embodiments, the chamber is remote from the infusion set cannula and is connected thereto by a section of tubing. The chamber is typically in the form of a soft robotic capsule including an elastically deformable deflectable membrane. The deflectable membrane may be convex and configured to be deflected into a planar or concave configuration by a fluid deflector.

[0154] A "fluid deflector" refers to a device configured to deflect a deflectable membrane of a therapeutic fluid reservoir when actuated. Typically, the fluid deflector includes an actuation chamber fluidically connected to an actuation fluid supply conduit. An actuation fluid, typically a liquid such as saline, is pumped into the chamber, causing the deflectable membrane of the therapeutic fluid reservoir to deflect and push the therapeutic fluid into the hollow tube of the infusion cannula. The deflectable membrane can be convex (e.g., dome-shaped). The deflectable membrane can be deflected from a convex shape to a flat or concave shape (or a less convex shape). The actuation chamber can include an actuation fluid reservoir that is fluidically connected to the actuation fluid supply conduit and is configured to abut the deflectable membrane when the actuation fluid is pumped into the actuation fluid reservoir. In other embodiments, the deflector can be an electrical or electromechanical device configured to deflect the deflectable membrane when actuated. In other embodiments, the deflector may form part of the deflectable membrane and may be actuated by electrical, magnetic, acoustic or thermal (photothermal or electrothermal) means to deflect the membrane. In one embodiment, the deflectable membrane comprises a dielectric elastomer or a piezoelectric material.

[0155] "Fluid" means air, gas or liquid or a mixture thereof. When the deflector is fluid, the fluid is typically a liquid such as saline, but may also be air. The therapeutic fluid is typically a medication, such as a self-administered drug such as insulin or a diagnostic agent. Other types of medications that may be self-administered are anti-inflammatory drugs, antimicrobial drugs, analgesics, and chemotherapy drugs. The medication is typically a fluid and may be a solution or a suspension.

[0156] "Controller" refers to a device operably connected to an actuating fluid pump and configured to control actuation of the pump. The system typically includes a pump for the actuating fluid supply conduit (actuating fluid pump) and a separate pump for the therapeutic fluid supply conduit (therapeutic fluid pump). The controller can be configured to actuate the pump to refill the therapeutic fluid reservoir after the reservoir has been emptied. The controller can be configured to actuate the actuating fluid pump to push the therapeutic fluid into the infusion set conduit. The controller can be configured to control one or more of the following actuation parameters: actuation time; actuation frequency; ramp rate of actuation; maximum actuation pressure (Pmax) and Pmax time. In one embodiment, the controller is configured to actuate the actuating fluid pump to perform a series of actuation steps. Typically, at least two (preferably all) actuation steps have different actuation profiles. The actuation profiles of the actuation steps may differ in actuation waveform (see Figure 5 E), which can be selected from square, triangle, trapezoid.

[0157] The controller may be programmable to actuate the system at a predetermined time (e.g., once a day, several times a day, or upon user request). In addition, actuation parameters (e.g., the volume of drug to be delivered, the drug infusion time, the pressure of drug delivery, and the time period between balloon expansion and balloon contraction) may be controlled by the controller. The controller typically includes a processor operably connected to the controller. The processor may be preprogrammable. The controller may include a graphical display. The controller may include a user interface. The controller and the processor may be contained in the same housing. The controller is typically wearable. The controller may include a wireless communication module configured to communicate with an independent processor. The independent processor may be a mobile communication device including software that includes instructions for the processor to control the operation of the controller. The software may be downloadable software (e.g., a mobile communication "app"). The software may be configured to graphically display data related to the operation of the system on a screen of the controller or mobile communication device.

[0158] A "sensor" refers to a device capable of measuring a body parameter, such as pH, or the presence or abundance of an element (e.g., a drug or metabolite) in the body, particularly in a body fluid such as blood or interstitial fluid. The sensor may be implantable. Examples include sensors (e.g., glucose sensors) for detecting metabolite levels in body fluids such as blood or interstitial fluid. The system of the present invention may include a sensor, or be configured to be operably connected to a sensor. A controller forming part of the system of the present invention may be operably connected to the sensor and actuate the system in response to data received from the sensor. The controller may be configured to actuate the system of the present invention when the metabolite level reaches a threshold level. For example, when the system of the present invention is used to infuse insulin, the system may be configured to actuate in response to data from a sensor indicating that the glucose level has reached a defined threshold level.

[0159] Example

[0160] The present invention will now be described with reference to specific examples. These examples are merely exemplary and are for illustrative purposes only: they are not intended to limit the scope of the claimed patent or the described invention in any way. These embodiments constitute the best mode of currently implementing the present invention.

[0161] 1 to 3, there is shown an infusion device of the present invention for transdermal infusion of insulin into a subject and generally indicated by reference numeral 1. The infusion device 1 includes an infusion device cannula 6, an actuation module 9, a drug supply module 4, an actuation fluid supply module 5, and a fluid supply conduit 3.

[0162] The infusion set cannula 6 comprises a flexible tube having an inner lumen 7 and an exit hole 8. In this embodiment, the infusion set cannula 1 has a length of about 3 cm and a width of about 0.3 cm. Therefore, it will be described as a small infusion set cannula. The infusion set cannula 1 is sized to be implanted subcutaneously in a patient and to deliver a drug subcutaneously when activated.

[0163] The actuation module 9 is connected to the proximal end of the cannula 6 and includes an actuation chamber 11 and a drug chamber 10. The actuation chamber 11 is fluidly connected to the actuation fluid supply module 5 (described below). The drug chamber 10 is fluidly connected to the drug supply module 4 (described below) at one end and is fluidly connected to the lumen 7 of the cannula 6 at the opposite end. The drug chamber 10 is arranged in contact with the actuation chamber 11 and includes a dome-shaped (convex) elastically deformable deflectable membrane 13, which separates the drug in the drug chamber 10 from the actuation fluid in the actuation chamber 11. Figure 3A and Figure 3B As shown, when the actuating fluid enters the actuating chamber 11 to pressurize the chamber, the elastically deformable membrane 13 is pressed from the convex shape ( Figure 3A ) deflects to concave ( Figure 3B ). This has the effect of pushing the drug from the drug chamber into the sleeve 6, such as Figure 3B shown.

[0164] Specific reference Figure 1A , the fluid supply conduit 3 connects the infusion set cannula 6 (located under the skin when in use) with the rest of the system (arranged outside the body). The conduit 3 includes a drug supply conduit 15 that fluidically connects the drug chamber 10 with the drug supply module 4, and an actuating fluid supply conduit 16 that fluidically connects the actuating chamber 11 with the actuating fluid supply module 5. The drug supply module 4 includes a drug storage container 18 and a drug pump 19, which is configured to pump the drug from the storage chamber 18 to the cannula 6 via the drug reservoir 10 when actuated. The actuating fluid supply module 5 includes an actuating fluid storage container 20 and an actuating fluid pump 21, which is configured to pump the actuating fluid from the storage container 20 to the actuating chamber 11 when actuated.

[0165] In use, referring to FIGS. 2 and 3 , when the drug pump 19 is actuated, the drug is pumped from the storage chamber 18 to the drug reservoir 10 to fill the reservoir with the drug, such as Figure 2C Although not shown, the drug will continue to flow to the cannula 6 and out of the outlet 8. The pump 19 is configured to deliver the drug to the cannula 6 at a set flow rate until a predetermined dose has been delivered. The actuation fluid pump 21 is then actuated to pump the actuation fluid into the actuation chamber 11, which pressurizes the chamber and causes the deflectable membrane 13 to move from the cannula 6 to the outlet 8. Figure 3A The dome shape shown deflects to Figure 3BThe concave shape shown in the figure pushes the drug into the sleeve 6 and is discharged through the infusion outlet 8. During the delivery of a predetermined dose of the drug, the pump is intermittently actuated to intermittently pressurize the actuation chamber with a defined frequency, amplitude (chamber pressure) and waveform. For example, in one embodiment, the actuation chamber is pressurized with an amplitude of 6 psi (e.g., the pressure in the actuation chamber) according to a square wave (6 seconds on, 6 seconds off). It should be understood that the pressurization curve of the actuation chamber can adopt different amplitudes and different waveforms and frequencies depending on the degree of obstruction of the sleeve and other parameters (e.g., the drug infusion rate or the size of the infusion area). The pressurization curve of the actuation chamber can be controlled by a controller, which is operably connected to the actuation fluid pump 21 and is configured to actuate the pump by selecting one or more preset actuation frequencies, actuation waveforms and actuation amplitudes.

[0166] Figure 4 shows different embodiments of the infusion device of the present invention, including: (A) a fluid deflector for a deflectable membrane; (B) an electric, magnetic or acoustic deflector for a deflectable membrane; (C) a mechanical deflector for a deflectable membrane; (D) a photothermal deflector for a deflectable membrane; (E) an electrothermal deflector for a deflectable membrane.

[0167] Figure 5 An infusion device of the present invention is shown, which is generally indicated by reference numeral 30, wherein components identified with reference to the previous embodiments are given the same reference numerals. The system includes the above-mentioned infusion device 1, a wearable glucose sensor 31 configured to measure the blood glucose level of a subject, and a controller 32 configured to wirelessly receive data from the sensor and then actuate the infusion device 1 based on the received data. In this embodiment, the controller 32 is provided by a mobile phone having control software running on the device. The software can be downloadable software (e.g., "app"). The software can include program instructions to instruct the device to wirelessly communicate with the sensor and the two pumps 19, 21 of the infusion device 11, so as to actuate the actuation pump according to a preprogrammed sequence of steps. The sequence selected by the controller can be determined by data received from the sensor, or determined according to the drug being delivered. The controller can control the actuation of the infusion cannula, such as when it is actuated (e.g., at what time of day, how many times a day) and how it is actuated (e.g., actuation mode). The controller can be wearable. The system of the present invention can be wearable. For example, the controller can be configured to actuate the infusion cannula in a sequence of actuation steps, such as 2-100 consecutive actuation steps. The sequence of steps can be performed over a period of time, such as 1-60 minutes. At least two actuation steps (or most or all) can have different actuation profiles, such as square, triangle, trapezoid.

[0168] Equivalent

[0169] The foregoing description describes in detail the currently preferred embodiments of the present invention. Based on these descriptions, those skilled in the art may conceive of many modifications and variations in its practice. These modifications and variations are intended to be included in the appended claims.

Claims

1. An infusion device (1) suitable for transdermal delivery of a therapeutic fluid to a subject, comprising: A small infusion set cannula (6), the small infusion set cannula (6) comprising a hollow body defining a central lumen (7), a fluid inlet, and a plurality of infusion outlets (8) in fluid communication with the central lumen; a treatment fluid chamber (10), the treatment fluid chamber (10) comprising a fluid outlet, the fluid outlet being in fluid communication with a fluid inlet and a fluid inlet of the small infusion set cannula (6); a treatment fluid supply conduit (15) in fluid communication with a fluid inlet of the treatment fluid chamber (10); A fluid deflector comprising an actuation chamber (11), an actuation fluid storage container (20), an actuation fluid supply conduit (16) fluidly connecting the actuation fluid storage container (20) to the actuation chamber (11), and an actuation fluid pump (21) operable to pump actuation fluid from the actuation fluid storage container (20) into the actuation chamber (11); an elastically deformable deflectable membrane (13) which separates a treatment fluid in the treatment fluid chamber (10) from an actuation fluid in the actuation chamber (11); and a controller operatively connected to the actuation fluid pump (21) and configured to control actuation of the fluid deflector by actuation of the actuation fluid pump (21), The fluid deflector is configured to deflect the elastically deformable deflectable membrane (13) when actuated to push the therapeutic fluid from the therapeutic fluid chamber (10) into the central lumen (7) of the small infusion set cannula (6) and discharge the therapeutic fluid through the infusion outlet (8).

2. The infusion device according to claim 1 comprises a therapeutic fluid storage container (18) and a therapeutic fluid pump (19), wherein the therapeutic fluid pump (19) is configured to pump the therapeutic fluid from the therapeutic fluid storage container (18) to the small infusion device cannula (6) via the therapeutic fluid supply conduit (15) and the therapeutic fluid chamber (10).

3. The infusion device according to claim 1 or 2, wherein: The therapeutic fluid chamber (10) comprises the elastically deformable deflectable membrane (13).

4. An infusion device according to any one of the preceding claims, wherein The treatment fluid chamber (10) is contained within the actuation chamber (11).

5. An infusion device according to any one of the preceding claims, wherein The treatment fluid chamber (10) and the actuation chamber (11) are connected to the proximal end of the small infusion set cannula (6).

6. The infusion device according to claim 5, wherein: The treatment fluid chamber (10) and the actuation chamber (11) are configured to be arranged on the surface of the skin when the small infusion set cannula (6) is implanted under the skin.

7. An infusion device according to any one of the preceding claims, wherein The elastically deformable deflectable membrane (13) has a convex configuration prior to fluid deflection.

8. An infusion device according to any one of the preceding claims, wherein The small infusion set cannula (6) has an axial length of 5-20 mm.

9. An infusion device according to any one of the preceding claims, wherein The controller is configured to control an actuation parameter of the fluid deflector, the actuation parameter being selected from an actuation frequency of the fluid deflector, a pressure in the treatment fluid chamber during actuation of the fluid deflector, a rate of change of pressure in the treatment fluid chamber during actuation, and an actuation curve / waveform.

10. An infusion device according to any one of the preceding claims, wherein The controller is preprogrammed to actuate the fluid deflector at timed intervals during delivery of a dose of drug.

11. The infusion device according to claim 10, wherein: The controller is preprogrammed to actuate the fluid deflector according to a square wave actuation profile with an on time of 4-8 seconds and an off time of 4-8 seconds.

12. The infusion device according to claim 10, wherein: The controller is preprogrammed to actuate the fluid deflector at an amplitude of 4-8 psi.

13. The infusion device (30) according to any of the preceding claims, comprising a body parameter sensor (31 ).

14. The infusion device according to claim 13, wherein: The body parameter sensor (31) is operably connected to the controller (32), and wherein the controller is configured to actuate the fluid deflector in response to measurements received from the sensor.

15. An infusion device according to any one of the preceding claims, wherein The plurality of infusion outlets (8) are arranged along the length of the small infusion set cannula (6).

16. An infusion device according to any one of the preceding claims, wherein The small infusion set cannula (6) is connected to the treatment fluid chamber (10) and the actuation chamber (11) via a flexible or rigid fluid conduit.

17. The infusion device (1) according to claim 1, comprising: A small infusion set cannula (6) having a hollow body defining a central lumen (7), the central lumen (7) including a plurality of infusion outlets (8) in fluid communication with the central lumen; a treatment fluid chamber (10) comprising a fluid outlet in fluid communication with the inlet fluid of the central lumen of the small infusion set cannula (6); a therapeutic fluid storage container (18); a therapeutic fluid supply conduit (15) providing fluid communication between a therapeutic fluid storage container (16) and a fluid inlet of the therapeutic fluid chamber (10); a therapeutic fluid pump (19) configured to pump therapeutic fluid from the therapeutic fluid storage container (18) to the therapeutic fluid chamber (10) through the therapeutic fluid supply conduit; A fluid deflector comprising an actuation chamber (11), an actuation fluid storage container (20) fluidly connected to the actuation chamber (11), and an actuation fluid pump (21) operable to pump actuation fluid from the actuation fluid storage container (20) to the actuation chamber (11); and a controller operatively connected to the actuation fluid pump (21) and configured to control actuation of the actuation fluid pump (21), in: The treatment fluid chamber (10) comprises an elastically deformable deflectable membrane (13) which separates a treatment fluid in the treatment fluid chamber from an actuating fluid in the actuating fluid chamber (11).

18. The infusion device according to claim 1, comprising: A small infusion set cannula (6) having a hollow body defining a central lumen (7) having a plurality of infusion outlets (8) in fluid communication with the central lumen; a treatment fluid chamber (10) comprising a fluid outlet in fluid communication with an inlet fluid of a central lumen (7) of the cannula (6) of the small infusion set; a treatment fluid supply conduit (15) in fluid communication with a fluid inlet of the treatment fluid chamber (10); A fluid deflector comprising an actuation chamber (11), an actuation fluid storage container (20) fluidly connected to the actuation chamber (11), and an actuation fluid pump (21) operable to pump actuation fluid from the actuation fluid storage container (20) to the actuation chamber (11); and an elastically deformable deflectable membrane (13) which separates a treatment fluid in the treatment fluid chamber (10) from an actuation fluid in the actuation chamber (11); and a controller operatively connected to the actuation fluid pump (21) and configured to control the fluid deflector by actuation of the actuation fluid pump (21), Wherein the controller is preprogrammed to actuate the fluid deflector at timed intervals during delivery of a dose of the drug.

19. The infusion device according to claim 1, comprising: A small infusion set cannula (6) having a hollow body defining a central lumen (7) having a plurality of infusion outlets (8) in fluid communication with the central lumen; a treatment fluid chamber (10) comprising a fluid outlet in fluid communication with an inlet fluid of a central lumen (7) of the cannula (6) of the small infusion set; a treatment fluid supply conduit (15) in fluid communication with a fluid inlet of the treatment fluid chamber (10); A fluid deflector comprising an actuation chamber (11), an actuation fluid storage container (20) fluidly connected to the actuation chamber (11), and an actuation fluid pump (21) operable to pump actuation fluid from the actuation fluid storage container (20) to the actuation chamber (11); and an elastically deformable deflectable membrane (13) which separates a treatment fluid in the treatment fluid chamber (10) from an actuation fluid in the actuation chamber (11); and a controller operatively connected to the actuation fluid pump (21) and configured to control the fluid deflector by actuation of the actuation fluid pump (21), Wherein the controller is configured to actuate the fluid deflector with a square wave actuation curve.

20. An infusion cannula device (1) suitable for transcutaneously delivering a therapeutic fluid to a subject, comprising: A small infusion set cannula (6) having a hollow body defining a central lumen, the central lumen having a plurality of infusion outlets (8) in fluid communication with the central lumen; a therapeutic fluid chamber (10) at least partially defined by an elastically deformable deflectable membrane (13) and including a fluid outlet in fluid communication with an inlet of the central lumen of the small infusion set cannula (6); a treatment fluid supply conduit (15) in fluid communication with a fluid inlet of the treatment fluid chamber (10); A fluid deflector comprising an actuation chamber (11) configured to be pneumatically or hydraulically pressurized by an actuation fluid pump (21); and a controller operably connected to the fluid deflector and operable to control actuation of the fluid deflector, The therapeutic fluid chamber (10) is contained within the actuation chamber (11), so that during use, pressurization of the actuation chamber (11) causes the elastically deformable deflectable membrane (13) to deflect, thereby pushing the therapeutic fluid from the therapeutic fluid chamber (10) into the hollow body of the small infusion set cannula (6) and expelling the therapeutic fluid through the infusion opening (8).

21. The infusion device (1) according to claim 1, comprising: A small infusion set cannula (6) having a hollow body defining a central lumen (7), the central lumen (7) including a plurality of infusion outlets (8) in fluid communication with the central lumen; a therapeutic fluid storage container (18); a therapeutic fluid supply conduit (15) providing fluid communication between a therapeutic fluid storage container (16) and a fluid inlet of the small infusion set cannula (6), the therapeutic fluid supply conduit (15); a therapeutic fluid pump (19) configured to pump therapeutic fluid from the therapeutic fluid storage container (18) to the small infusion set cannula (6) via the therapeutic fluid supply conduit (15); Characterized in that: the infusion device comprises an actuation module, and the actuation module comprises: A fluid deflector comprising an actuation chamber (11), an actuation fluid storage container (20) fluidly connected to the actuation chamber (11), and an actuation fluid pump (21) operable to pump actuation fluid from the actuation fluid storage container (20) to the actuation chamber (11) to pressurize the actuation chamber (11); a compressible therapeutic fluid chamber (10) disposed in the therapeutic fluid supply conduit (15); and a controller operatively connected to the actuation fluid pump (21) and configured to control actuation of the actuation fluid pump (21), wherein the compressible treatment fluid chamber (10) is arranged in the actuation chamber, whereby the actuation chamber (11) When pressurized, the compressible treatment fluid chamber (10) is compressed to push the treatment fluid from the treatment fluid chamber (10) into the hollow body of the small infusion set cannula (6) and discharge the treatment fluid through the infusion opening (8).

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