Self-lubricating backflow infusion catheter

Abstract

The present disclosure relates to a self-lubricating cannula for delivering a fluid drug to a subcutaneous site. The self-lubricating cannulas include a polyether block polyamide and an additive that are configured to facilitate the manufacture of tip self-lubricating cannulas. The present disclosure also provides a method of making the self-lubricating cannula and a method of administering insulin using the self-lubricating cannula.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 641,341, filed May 1, 2024, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This technology relates generally to medical devices, and more specifically to self-lubricating infusion cannulas for administering medications to individuals (such as insulin to diabetic patients). Background Technology

[0004] Millions of individuals with diabetes require insulin therapy to control uncontrolled blood glucose levels (i.e., blood glucose levels). As an alternative to multiple daily injections (syringe or pen), many rely on small, wearable insulin infusion devices to manage their blood sugar. Typically, an infusion device includes a pump (which comprises controls, a processing module, and a battery), a reservoir that holds the fluid medication (e.g., insulin), and an infusion kit / subsystem. The infusion kit / subsystem includes a cannula constructed for subcutaneous insertion into the individual's body and a tubing system that connects the reservoir to the cannula. When the tubing in the infusion subsystem is minimal and the pump adheres to the skin, the pump system is wearable and is called a patch pump. The cannula and tubing are part of the infusion subsystem in a patch pump. Infusion devices where the pump is not worn against the skin but is tethered by a longer tubing are called tethered pumps, and the cannula and tubing are called infusion kits. In patch pumps or tethered pumps, the cannula is inserted subcutaneously and remains at the infusion site for several days to enable the delivery of the fluid medication. Cannulation provides a pathway for subcutaneous delivery of medication to an individual.

[0005] The manufacturing process of cannulas involves modifying the distal end of the cannula, making it "tip-shaped" or "tip-formed" to facilitate penetration into an individual's tissues. Tipping involves modifying the distal end of the cannula to reduce the force required to penetrate into body tissues and minimize damage to those tissues. In the tipping process, the cannula is pressed into a heated mold, which takes on the shape and features of the mold. For example, the heated mold may feature a narrowed cannula tip with rounded edges. The geometry of the cannula tip is optimized to reduce penetration effort and discomfort for the patient during insertion into the body. Tipping is common for cannulas configured to receive a needle within their lumen.

[0006] The most popular and widely used catheters are made of polytetrafluoroethylene (PTFE) and fluoroethylene propylene (FEP). These biocompatible polymers are lubricating and allow for easy manufacturing, including the formation of the tip geometry. Catheters made from these polymers can reliably deliver insulin to an individual for several days before performance degradation, and the catheters must be removed and replaced.

[0007] However, a drawback of using PTFE and FEP polymers is that they consist of perfluoroalkyl and polyfluoroalkyl substances (PFAS), which are long-lasting chemicals associated with adverse effects on human health and are difficult to break down. Because PFAS are not easily degraded, they can accumulate over time and build up in the body and environment. Studies have shown a correlation between exposure to certain PFAS and adverse effects on fertility, developmental delays in children, increased cancer risk, reduced immune system function against infections, interference with the body's natural hormones, increased cholesterol levels, and increased risk of obesity.

[0008] There is a need for biocompatible cannulas made of PFAS-free materials, suitable for advanced manufacturing processes, and capable of delivering insulin to individual tissues within days while maintaining good performance. Such cannulas should be reliably made from materials that are readily compatible with advanced manufacturing processes. PFAS-free cannulas would benefit not only the millions of diabetic patients requiring subcutaneous insulin infusion, but also any individual requiring subcutaneous fluid medication infusion. Summary of the Invention

[0009] This disclosure provides a PFAS-free self-lubricating cannula configured for subcutaneous insertion and exhibiting desired properties such as reflux and self-lubrication. The self-lubricating cannula described herein includes a tip formed by a process involving a heated mold and resists adhesion to the heated mold. Furthermore, this disclosure discloses a method for preparing and using the self-lubricating cannula, which includes administering insulin to a diabetic individual.

[0010] In one aspect, this disclosure provides a self-lubricating cannula comprising a polyether block polyamide and an additive, wherein the self-lubricating cannula is configured for delivering insulin to an individual in need, and the self-lubricating cannula resists adhesion to a heated mold. A self-lubricating cannula for delivering insulin to an individual in need is also provided.

[0011] In one aspect, this disclosure provides a method for preparing a self-lubricating cannula, the method comprising the steps of: combining a polyether block polyamide and an additive to form a mixture, extruding the mixture to form a cannula, cutting the cannula to a desired length, and treating the distal end of the cannula with a heated mold to form a tip; wherein the self-lubricating cannula is used for delivering insulin to an individual in need, and the self-lubricating cannula resists adhesion to the heated mold. In another aspect, a self-lubricating cannula formed by any of the methods described herein is provided.

[0012] In another aspect, this disclosure provides a method for administering insulin to an individual in need, the method comprising: providing a self-lubricating cannula as described herein; inserting the self-lubricating cannula into the individual; and delivering insulin to the individual in need via the self-lubricating cannula.

[0013] In another aspect, this disclosure provides an infusion device comprising: a housing configured to be positioned on the skin at an infusion site of a patient; a reservoir configured to store a fluid drug, the reservoir being received by the housing; and a cannula configured for subcutaneous insertion into the patient's tissue at the infusion site, wherein the cannula is configured to be self-lubricating and comprises a polyether block polyamide and an additive.

[0014] The various implementation schemes disclosed herein are provided as examples and do not limit the technology of this subject. Attached Figure Description

[0015] Figure 1 Some general aspects of the example cannula shown as opening onto the bushing or needle guide are outlined.

[0016] Figure 2 The illustration shows an example of the entire cannula and cannula tip manufacturing process.

[0017] Figure 3 This is a photograph of an exemplary cannula with a needle inside the tip cannula.

[0018] Figure 4A and Figure 4B The image shows photographs of cannulas prepared after tip forming, which contain polyether block polyamides without siloxanes. Figure 4A ) and polyether block polyamides containing 1.5% siloxane ( Figure 4B ).

[0019] Figure 5 This is a diagram illustrating an example of intubation. Detailed Implementation

[0020] I. Overview of Intubation

[0021] Cannulas are a key component of infusion therapy and serve as the junction between the infusion device and the patient's subcutaneous tissue. Cannulas provide the ability to deliver fluid medications, such as insulin, to a target location (i.e., the infusion site) on an individual's body over a period of several days (e.g., 1 to 2 days, 2 to 3 days, or up to 6 to 7 days). Some cannulas are for subcutaneous insertion and can be 22 to 30 standard measurements. Some cannulas are made of synthetic polymers and may also be referred to as plastic catheters.

[0022] Figure 1 This is an illustration of a cannula that mates with a bushing, which serves as a needle guide. The bushing connects the cannula to the rest of the infusion device. Together, the bushing and cannula provide a sealed fluid delivery pathway for drugs (e.g., insulin) into the subcutaneous tissue of a patient (e.g., a diabetic patient).

[0023] A. Foreign body reaction and intubation-related complications

[0024] Implantation of a cannula into human tissue triggers an immune response known as a foreign body reaction. This reaction manifests as an acute inflammatory response at the insertion site and can encompass the epidermis, dermis, and subcutaneous adipose tissue. In addition to the immune response, the insertion process itself can induce mechanical trauma. This trauma can affect cells and connective tissue along the cannula's path, potentially damaging the basement membrane, extracellular matrix, and structural proteins. Disruption of the vascular network (including lymphatic vessels, arterioles, capillaries, and venules) can further impair the tissue microenvironment and lead to fluid buildup and potential coagulation.

[0025] Another complication associated with cannulation is infusion site loss or reduction. This phenomenon is thought to be mediated in part by the encapsulation of the cannula by fibrous tissue. The quality of insulin infusion can be affected by the interaction between insulin and the materials it comes into contact with (e.g., the reservoir and fluid pathways in contact during storage, filling, and delivery). The encapsulation process can lead to inconsistent and unreliable drug delivery. In cases of inconsistent insulin, individuals may experience changes in blood glucose. The exact mechanisms of site loss / reduction remain unclear, but may involve complex interactions between factors such as local inflammation, intraluminal coagulation within the cannula, and progressive fibrotic tissue proliferation. Additionally, cannula movement during daily activities can exacerbate host responses and contribute to persistent tissue stimulation.

[0026] The aforementioned immune responses, tissue trauma, and infusion site loss lead to cannula failure, loss of effective insulin delivery, and ultimately uncontrolled blood glucose levels. To deliver insulin effectively and control blood glucose levels, the infusion kit is replaced, which typically involves removing the failed cannula at a different infusion site and inserting a new one. One way to extend cannula lifespan is by optimizing the cannula tip to reduce or minimize foreign body reactions, mechanical trauma, and infusion site loss.

[0027] B. Intubation characteristics

[0028] The self-lubricating cannula material is rigid to facilitate penetration and insertion into patient tissue and resists bends or kinks that could obstruct insulin flow. The material is compliant enough to expand and conform to the liner or needle guide, yet flexible enough to form a fluid-impermeable seal around the liner or needle guide. The self-lubricating cannula material does not react with patient tissue.

[0029] The in vivo performance of self-lubricating cannulas is influenced by their surface microstructure. Smooth surfaces reduce protein adhesion to the cannula, potential occlusion, and minimize inflammatory responses. Smooth surfaces also reduce friction during insertion, which helps reduce insertion force and tissue trauma. Compared to rougher surfaces, smoother cannula surfaces prolong consistent insulin delivery and avoid prolonged periods of infusion site loss. Surface smoothness can be assessed visually using microscopes, SEM, etc.

[0030] The quality of self-lubricating cannula tips is critical for the penetration and lifespan of intracorporeal catheters. The tip geometry is optimized for minimal penetration force and minimal patient discomfort. To increase intracorporeal catheter lifespan, the tip needs to strike a balance between sharpness and bluntness. A sharp tip reduces the force required to pierce tissue, thus minimizing discomfort during insertion. A degree of bluntness in the tip after insertion helps reduce tissue damage during any subsequent movement of the tip within the body. Including an optional silicone oil coating to reduce the effects of micromovements within the body can further increase catheter lifespan.

[0031] The opening of the self-lubricating cannula is large enough to deliver fluid medications (e.g., insulin) without causing obstruction, and narrow enough to minimize trauma to patient tissues during insertion and placement at the infusion site. Additionally, the cannula's fill volume is minimized to reduce the amount of insulin wasted after disposal of the used cannula.

[0032] C. General manufacturing process

[0033] An overview of conventional cannula manufacturing and tip forming is shown in Figure 2The conventional cannulation manufacturing process begins with the addition of raw material (i.e., a premixed copolymer / additive mixture) to the feed hopper of a screw extruder. The screw rotates at a predetermined speed, and a temperature controller connected to heating / cooling elements on the barrel maintains the temperature at a set point. The extrudate exits the die, which can be shaped or altered, then shaped, and the resulting cannula is cooled. The term "cannula" is used interchangeably with "cannula" as used herein. Cannulas can be extruded on conventional manufacturing equipment, and specific processing parameters related to a particular resin are available from the supplier. The extruded cannula is then cut to a length and opened onto a bushing fitted with a mandrel via an interference fit (also known as a friction fit or press fit). The distal end of the cannula is then tipped using a heated and lubricated die. The tipping process requires a heated die, which is typically lubricated to prevent cannula sticking. Finally, the tip cannula is treated with a lubricant.

[0034] In the above manufacturing process, polyether block polyamide resin and additives are combined and thoroughly premixed, and then added to the feed hopper of a screw extruder. The integration of additives throughout the tube material is important for the self-lubricating and recirculating properties exhibited by the tube.

[0035] The most critical and challenging process step is the tip forming process. The tip forming mold determines the geometry of the distal portion of the cannula, such as the characteristics of a rounded tip or a tapered shape. This mold is designed to provide an optimized tip catheter, where the shape and size facilitate insertion into the body and minimize tissue trauma. The tip forming process requires preheating the tip forming mold to a predetermined temperature to allow the resin in the tubing to flow back and force the tip of the tubing to conform to the shape of the mold. A silicone / siloxane lubricant is applied to the mold surface before tip forming. The distal end of the cannula (also known as the catheter tubing) is forced and pressed into the mold. During tip forming, a mandrel is used to hold, guide, and align the cannula with the mold. The distal end is held in the mold for a predetermined dwell time so that the distal end of the cannula can contact the mold for flow back and conform to the mold's dimensions. After the predetermined dwell time, the cannula is retracted from the mold. A successfully formed tip will have a smooth surface while also conforming to the dimensions of the molded surface.

[0036] D. PFAS-free cannulation alternatives

[0037] Polytetrafluoroethylene (PTFE) and fluorinated ethylene propylene (FEP) are already the preferred materials for cannulation. PTFE can be reflowed when heated and is more lubricating than other resins, thus conforming to the shape of the mold and reducing the chance of adhesion to the molded surface. Although PTFE is lubricating, the mold surface is usually lubricated during manufacturing to facilitate tip forming and reduce cannulation adhesion to the mold.

[0038] PTFE and FEP belong to the hundreds of chemicals classified as perfluoroalkyl and polyfluoroalkyl substances (PFAS). PFAS are characterized by carbon atom chains bonded to fluorine atoms and are known as "permanent chemicals" due to their persistence and resistance to degradation. There is a growing awareness of the accumulation of PFAS in soil, water, and living organisms. The extent of the adverse effects of permanent chemicals on human health and the environment is a subject of ongoing research. This disclosure provides alternatives to currently commercially available PTFE and FEP cannulas. In some embodiments, the self-lubricating cannulas described herein are PFAS-free.

[0039] Suitable alternatives to PFAS-free materials are not readily apparent, and numerous manufacturing and mechanical reasons make a material unsuitable for infusion catheters. Therefore, PTFE and FEP catheters and tubing have become popular. Unlike PTFE and FEP, many other resins do not reflow well when heated or become very "sticky" and adhere to molded surfaces. Some materials are inferior because they lack sufficient rigidity and will cause kinking or buckling within the catheter during insertion, damaging it. Some materials may not be flexible enough, which can lead to tissue trauma and inflammation due to catheter movement during implantation. Other resins may not be biocompatible and may react with the patient's tissues.

[0040] Materials (such as polyether block polyamide, and also under trade names) Arkema (well-known) has been excluded from cannula manufacturing, despite the fact that these materials are biocompatible and have proven in vivo properties due to poor reflux and viscosity upon heating, which would contaminate the tip forming process. Suitable cannulas made of polyether block polyamides for use in insulin infusion devices are unavailable because their manufacture is considered infeasible.

[0041] This disclosure provides cannulas comprising polyether block polyamide and additives, wherein these cannulas exhibit self-lubricating and reflux properties. Due to the inclusion of additives, resins previously not considered suitable materials for cannula production can now be used to prepare cannulas as described herein.

[0042] The term "self-lubricating" refers to the ability of a cannula to provide the inherent lubrication or smoothing properties of the cannula material. This self-lubricating property allows the cannula to be formed using a heated mold without sticking to the mold upon release from the mold surface. The self-lubricating properties of the self-lubricating cannulas disclosed herein are attributed to the inherent properties of the cannula material, which is a combination of polyether block polyamide and additives, rather than a separate coating of lubricant onto the cannula surface.

[0043] In some implementations, the tip forming process does not require lubrication of the heated mold or the surface of the untipped cannula, thereby reducing the number of steps and the amount of lubricating material required in the tip forming process.

[0044] The term "reflow" refers to the process of melting the insert material in a tip forming process. When processed with a heated mold, the insert melts, conforms to the mold size, and then solidifies upon cooling.

[0045] The combination of polyether block polyamide and additives disclosed herein provides self-lubricating and reflow properties that facilitate tip forming processes. After a predetermined residence time in the mold, the tip can be removed from the mold without adhering to or sticking to the mold surface, thus maintaining the integrity of the newly formed tip. The result is a self-lubricating cannula with a regular and smooth tip surface. Without the additives, the tip forming process causes the cannula to stick to the mold and results in poor tip forming. The resulting tip may have, for example, irregular edges, a rough surface, or deviate from the mold dimensions.

[0046] In some implementations, the surface of the self-lubricating cannula that comes into contact with the heated mold is smoother than the surface of a similar additive-free cannula that comes into contact with the heated mold.

[0047] In some implementations, the surface of the self-lubricating cannula that comes into contact with the lubricated heated mold is smoother than the surface of a similar additive-free cannula that comes into contact with the lubricated heated mold.

[0048] E. Polyether block polyamide

[0049] The self-lubricating cannula disclosed herein comprises polyether block polyamide and additives. Polyether block polyamide is a block copolymer composed of rigid polyamide blocks and soft polyether blocks. Polyether block polyamide is also known as PEBA, poly(ether-block-amide), polyether polyamide block copolymer, polyether polyamide copolymer, polyamide block polyether, polyamide polyether block copolymer, and polyamide polyether copolymer. The term "copolymer" refers to any polymer formed from two or more monomers. Polyether block polyamide is a thermoplastic elastomer and is an example of a copolymer.

[0050] Polyether block polyamides are obtained through the polycondensation of carboxylic acid polyamides and alcohol-terminated polyethers. The general chemical structure of polyether block polyamides is:

[0051]

[0052] The repeating units of the polyamide component (PA) in block copolymers can have different carbon chain lengths, such as 6 carbons (PA6, Nylon 6), 11 carbons (Nylon 11), or 12 carbons (PA12, Nylon 12). For example:

[0053]

[0054] Polyether block polyamides can be substituted, for example, with methyl or acetyl N-substituted groups. The polyether component (PE) of the block copolymer can have different monomer carbon chain lengths, such as 2 carbons or 4 carbons, and examples include polytetramethylene ether glycol (PTMG) and poly(ethylene oxide) (PEO), as shown below:

[0055]

[0056] The terms “n”, “x”, and “y” refer to integers and indicate the number of repeating units.

[0057] The raw material used in the preparation of self-lubricating cannulas is polyether block polyamide resin. Polyether block polyamide can be marketed under various trade names. Purchased from the manufacturer Arkema, and can be sold under the trade name E-purchased from Evonik Industries. The resin contains no plasticizers. Table 1 lists a series of eight types. Block copolymers and their physical properties.

[0058] Table 1.

[0059]

[0060]

[0061] N: No fracture; C: Complete fracture; P: Partial fracture

[0062] Polyether block polyamides such as It possesses measurable physical properties, such as Shore hardness, density, melting point, moisture content, absorbency, water absorption, flexural modulus, and tensile modulus, as listed in Table 1. These properties can be measured using standardized tests, such as those developed by ASTM International, ISO, and IEC.

[0063] In some implementations, polyether block polyamide is It can be obtained as a resin from commercial suppliers such as Arkema. In some embodiments, the polyether block polyamide is selected from... 2533 3533 4033 4533、 5533 6333、 7033 and The group consisting of 7233 or combinations thereof. In some embodiments, the polyether block polyamide is selected from... 3533 5533 and A group consisting of 7233.

[0064] In some embodiments, the polyether block polyamides disclosed herein have physical property characteristics including two or more physical properties listed in Table 1 (e.g., Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus, and tensile modulus), wherein such physical property characteristics are equivalent to those described in Table 1. Physical properties of polyether block polyamides. In some embodiments, the polyether block polyamides disclosed herein have physical properties including two or more physical properties listed in Table 1 (e.g., Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus, and tensile modulus), wherein the physical properties are equivalent to those described in Table 1. 3533 5533 or The physical properties of 7233. In some of the aforementioned embodiments, the physical properties consist of three or more, four or more, five or more, six or more, or seven or more of the aforementioned physical properties.

[0065] In some embodiments, the polyether block polyamide has the properties selected from... 2533 3533 4033 4533、 5533 6333、 7033 and The group consisting of 7233 The physical properties of polyether block polyamides are equivalent to those of polyether block polyamides. The properties are listed in Table 1. In some embodiments, the polyether block polyamide disclosed herein may have the same properties as... 3533 5533 and The physical properties of 7233 are equivalent to those of other physical properties, among which... The properties and characteristics are listed in Table 1.

[0066] As used herein, “equivalent” is the value listed in Table 1 plus or minus 0.1% to 20%, plus or minus 0.1% to 10%, plus or minus 0.1% to 5%, or plus or minus 0.1% to 2%. In some embodiments, the term “equivalent” is replaced by “about”.

[0067] F. Additives

[0068] The self-lubricating cannulas described herein contain additives. These additives provide the cannulas with self-lubricating properties. In one aspect, the additives are introduced early in the cannulas manufacturing process, whereby the additives are combined with a polyether block polyamide resin to form a paste. Thus, the additives and the polyether block polyamide are tightly combined and mixed. The resulting catheter (which subsequently undergoes a tip-forming process) contains additives incorporated throughout the self-lubricating cannulas, a crucial feature as it provides the desired reflow and non-stick qualities during the tip-forming process. If the additives are not incorporated into the cannulas material along with the polyether block polyamide, simply lubricating the surface of a heated mold or an untipped cannulas with siloxane and then pressing the cannulas into the mold results in poor tip-forming. In one embodiment, the self-lubricating cannulas comprises a homogeneous mixture of polyether block polyamide and additives.

[0069] Examples of additives are siloxanes or silicones, which are compounds having alternating silicon (Si) and oxygen (O) atoms. An example of a siloxane's chemical formula is -(R₂SiO). n - where n is the number of repeating units, and R is an organic substituent, such as methyl, ethyl, propyl, phenyl, etc., or R is, for example, an aminoalkyl, hydroxyl, hydrogen, or vinyl group. Siloxanes can be linear, cyclic, branched, or cross-linked. Siloxanes include oligomers and polymeric structures (polysiloxanes).

[0070] The macromolecular backbone of polysiloxanes consists of Si-O-Si units. The Si atoms are replaced by organic groups such as C1-C10 hydrocarbon groups. An example of a polysiloxane is polydimethylsiloxane (PDMS), in which two methyl groups are bonded to each Si atom.

[0071] High molecular weight polysiloxanes refer to polysiloxanes having a weight-average molecular weight (Mw) of at least 5000 Da, at least 10,000 Da, at least 30,000 Da, at least 50,000 Da, at least 100,000 Da, at least 500,000 Da, at least 1,000,000 Da, or at least 2,000,000 Da. In some embodiments, a high molecular weight polysiloxane is a polysiloxane with a Mw of at least 50,000 Da. In some embodiments, a high molecular weight polysiloxane is a polysiloxane with a Mw of at least 100,000 Da. In some embodiments, a high molecular weight polysiloxane is a polysiloxane with a Mw of at least 500,000 Da. In some embodiments, a high molecular weight polysiloxane is a polysiloxane with a Mw of at least 1,000,000 Da. Mw can be determined by molecular weight characteristic data obtained by gel permeation chromatography analysis. In some implementations, the Mw of the polysiloxane is similar to that of the polysiloxane Multibase. TM MB50-017 masterbatch.

[0072] Polysiloxane can be marketed under the trade name Multibase TM Purchased from manufacturer DuPont. An example of polysiloxane is Dow Corning MB50-017 masterbatch (equivalent to the renamed Multibase). TM MB50-017 masterbatch is a granulation formulation of ultra-high molecular weight siloxane polymers dispersed in a thermoplastic polyurethane carrier. Dow Corning MB50-017 contains 50% siloxane.

[0073] Other Multibase TM Polysiloxanes include MB50-001, MB50-001 G2, HMB-0221, HMB-6301, MB25-501, MB50-002, MB25-035, MB25-502, AMB-12235, MB25-235, MB50-313, MB50-321, MB50-801, MB50-802, MB50-314, MB50-320, MB50-004, MB50-007, MB50-008, MB40-006, HMB-1103, MB50-011, MB50-320, HMB-1103, MB50-010, MB50-012, MB50-315, and HMB-1903.

[0074] The additive may be dispersed in a polymer carrier to facilitate its binding with the polyether block polyamide during manufacturing. Examples of polymer carriers include thermoplastic polyurethane, polypropylene homopolymer (PPH), low-density polyethylene (LDPE), linear low-density polyethylene (LLDPE), high-density polyethylene (HDPE), ethylene-vinyl acetate (EVA), high-impact polystyrene (HIPS), acrylonitrile butadiene styrene (ABS), styrene-acrylonitrile (SAN), polyoxymethylene (POM), ethylene methyl acrylate copolymer (EMA), nylon 6 (PA6), copolyester ether (COPE), polyethylene terephthalate (PET), and polycarbonate (PC), or combinations thereof.

[0075] In some embodiments, the additive promotes the backflow of the self-lubricating cannula and reduces adhesion of the self-lubricating cannula surface to the heated mold. In some embodiments, the additive is a siloxane. In some embodiments, the siloxane is a polysiloxane. In some embodiments, the polysiloxane is a high molecular weight siloxane polymer. In some embodiments, the additive is an alkylated polysiloxane. In some embodiments, the additive is polydimethylsiloxane. In some embodiments, the additive is Multibase. TM MB50-017 masterbatch. In some embodiments, the additive is dispersed in a polymer carrier, such as in thermoplastic polyurethane.

[0076] The amount of additives disclosed herein in the self-lubricating cannulas is sufficient to provide self-lubricating qualities (e.g., non-adhesion to heated molds, promoting smooth, regular surfaces) and maintain other desired properties of the cannulas, such as rigidity. It is also desirable to minimize the concentration of the additives to avoid any possible leaching from the self-lubricating cannulas into the fluid path or to avoid any possible reaction with individual tissues.

[0077] In some embodiments, the self-lubricating cannula contains: less than 10% by weight, less than 7% by weight, less than 5% by weight, less than 3% by weight, less than 2% by weight, less than 1.5% by weight, or less than 1% by weight of an additive, and contains at least 0.1% by weight of an additive.

[0078] In some embodiments, the self-lubricating cannula comprises: 0.1 wt% to 10 wt%, 0.1 wt% to 7 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 3 wt%, 0.1 wt% to 2 wt%, 0.1 wt% to 1.5 wt%, 0.1 wt% to 1 wt%, 0.5 wt% to 10 wt%, 0.5 wt% to 7 wt%, 0.5 wt% to 5 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1 wt%. 0.5% by weight, 0.5% to 1% by weight, 0.7% to 10% by weight, 0.7% to 7% by weight, 0.7% to 5% by weight, 0.7% to 3% by weight, 0.7% to 2% by weight, 0.7% to 1.5% by weight, 0.7% to 1% by weight, 1% to 10% by weight, 1% to 7% by weight, 1% to 5% by weight, 1% to 3% by weight, 1% to 2% by weight, or 1% to 1.5% by weight of additives.

[0079] In some embodiments, the self-lubricating cannula comprises: about 10% by weight, about 9.5% by weight, about 9% by weight, about 8.5% by weight, about 8% by weight, about 7.5% by weight, about 7% by weight, about 6.5% by weight, about 6% by weight, about 5.5% by weight, about 5% by weight, about 4.5% by weight, about 4% by weight, about 3.5% by weight, about 3% by weight, about 2.5% by weight, about 2% by weight, about 1.5% by weight, about 1% by weight, or about 0.5% by weight of an additive.

[0080] G. Constructing a self-lubricating cannula with a needle.

[0081] The needle can optionally be used to facilitate cannulation by puncturing an individual's tissue (e.g., skin) to allow the cannula to be inserted and positioned at the intended site. The cannula can be configured to surround the outer surface of the needle. For example, Figure 3 A photograph is shown of a needle located inside the lumen of a cannula. Alternatively, the needle may be configured to surround the outer surface of the cannula.

[0082] In some embodiments, the self-lubricating cannula also includes a needle located within the cannula. In some embodiments, the self-lubricating cannula also includes a needle located on the outside of the self-lubricating cannula. In some embodiments, the self-lubricating cannula is configured for subcutaneous insertion into the tissue of a diabetic patient. In some embodiments, the cannula is part of an infusion kit / subsystem.

[0083] In some embodiments, the self-lubricating cannula comprises a polyether block polyamide and a siloxane, wherein: the self-lubricating cannula is configured to deliver insulin to an individual in need; the self-lubricating cannula resists adhesion to a heated mold; and the siloxane is a high molecular weight polysiloxane (such as Multibase). TMMB50-017); Polyether block polyamide is (such as) 3533, 5533 and 7233); and the amount of siloxane is from 0.1% to 5% by weight (such as about 2%, 1.5% and about 1% by weight).

[0084] In some embodiments, the self-lubricating cannula comprises a polyether block polyamide and a siloxane, wherein: the self-lubricating cannula is configured to deliver insulin to an individual in need; the self-lubricating cannula resists adhesion to a heated mold; and the siloxane is a high molecular weight polysiloxane (such as Multibase). TM MB50-017); Polyether block polyamides have physical property characteristics including three or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus, and tensile modulus; physical property characteristics are as described in Table 1. Polyether block polyamide (e.g., 3533, 5533 and The physical properties of 7233 are equivalent; and the amount of siloxane is from 0.1 wt% to 5 wt% (such as about 2 wt%, 1.5 wt% and about 1 wt%).

[0085] In some embodiments, the self-lubricating cannula comprises a polyether block polyamide and a siloxane, wherein: the self-lubricating cannula is configured to deliver insulin to an individual in need; the self-lubricating cannula resists adhesion to a heated mold; and the siloxane is a high molecular weight polysiloxane (such as Multibase). TM MB50-017), wherein the Mw of the polysiloxane is at least 10,000 Da, 50,000 Da, 100,000 Da, or 500,000 Da; the polyether block polyamide has physical property characteristics including three or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus, and tensile modulus; the physical property characteristics are as described in Table 1. Polyether block polyamide (e.g., 3533, 5533 and The physical properties of 7233 are equivalent; and the amount of siloxane is from 0.1 wt% to 5 wt% (such as about 2 wt%, 1.5 wt% and about 1 wt%).

[0086] In some implementations, the polyether block polyamide and siloxane are a homogeneous mixture.

[0087] II. Methods for delivering fluid drugs using self-lubricating cannulas

[0088] This disclosure provides a method for administering a fluid drug to an individual in need using the self-lubricating cannula described herein. An individual in need refers to a subject requiring subcutaneous infusion of a fluid drug (e.g., insulin), and includes humans, pigs, and dogs.

[0089] Fluid medications can be any drug intended for subcutaneous delivery. Examples of subcutaneous administration include insulin, growth hormone, adrenaline, opioids, heparin, and allergy medications. Medications requiring long-term delivery to an individual over a period of several days may benefit from the use of self-lubricating cannulas.

[0090] The administration of fluid medications can be performed using an infusion device that houses a cannula. The infusion device includes a pump (which includes controls, a processing module, and a battery), a reservoir containing the fluid medication (e.g., insulin), an infusion kit / subsystem for subcutaneous insertion into the individual (which includes the cannula described herein), and a tubing system connecting the reservoir to the cannula. An infusion kit refers to both an external infusion kit and an internal infusion kit, the external infusion kit connecting the tethered pump to the cannula via a long tubing, and the internal infusion kit, such as a patch pump worn on the body (i.e., the pump, cannula, and tubing are all located within the patch device).

[0091] In some embodiments, this disclosure provides a method for administering insulin to an individual in need, the method comprising: providing a self-lubricating cannula as described herein; inserting the self-lubricating cannula into the individual; and delivering insulin to the individual in need via the self-lubricating cannula.

[0092] The self-lubricating cannula is subcutaneously inserted into an infusion site located in the abdomen, thigh, hip, upper arm, lower back, or buttocks of the individual in need. During insertion into the individual, the self-lubricating cannula resists tugging or kinking. Insertion results in the cannula being implanted into the individual. During this period, the individual may continue to “wear” the self-lubricating cannula. As used herein, the term “wear” refers to the implantation of the cannula into the individual after insertion.

[0093] Once implanted, the self-lubricating cannula should remain in contact with the individual in need (i.e., implanted) for at least 3 consecutive days, at least 4 consecutive days, at least 5 consecutive days, at least 6 consecutive days, at least 7 consecutive days, at least 8 consecutive days, at least 9 consecutive days, or at least 10 consecutive days before replacement or removal. The implantation of the self-lubricating cannula should be maintained as long as the flow of the fluid medication (e.g., insulin) is sufficient to facilitate drug administration to the individual. In individuals with diabetes, beneficial insulin administration results in effective control of blood glucose levels. When a foreign body reaction, inflammatory response, coagulation, or any other adverse reaction occurs leading to infusion site failure, blood glucose levels will rise despite the administration of a larger dose of insulin. This is a signal that the individual is no longer benefiting from infusion therapy and the cannula should be removed with the insertion of a new cannula at a different infusion site. Currently, manufacturers recommend removing the cannula every 3 days and inserting it at a different site in the body, and some cannulas are left in place for up to 7 days. Exceeding this time increases the chances of tissue damage, infection, scarring, and elevated blood glucose.

[0094] In some implementations, the individual in need is a human. In some implementations, the individual is a diabetic patient. In some implementations, the individual is a diabetic pig.

[0095] In some embodiments, the distal end of the self-lubricating cannula includes a tip configured to penetrate the skin of the individual in need. In some embodiments, the self-lubricating cannula is configured to be worn (i.e., implanted) at a single site on the diabetic patient for at least 2 days, at least 3 days, or at least 3 days. In some embodiments, the self-lubricating cannula is in contact with the individual in need for at least 3 consecutive days, at least 4 consecutive days, at least 5 consecutive days, at least 6 consecutive days, at least 7 consecutive days, at least 8 consecutive days, at least 9 consecutive days, or at least 10 consecutive days before being replaced or removed.

[0096] In some embodiments, a self-lubricating cannula is used to deliver fluid medications to an individual in need. In some embodiments, a self-lubricating cannula is used to deliver insulin. In some embodiments, a self-lubricating cannula is a fluid tubing for fluid medications. In some embodiments, a self-lubricating cannula is used to deliver insulin to a diabetic subject at a single infusion site for a period of time (e.g., 1 to 2 days, 2 to 3 days, at least 6 to 7 days, at least 10 days).

[0097] III. Evaluate intubation performance

[0098] Examples of assessing cannulation performance include monitoring the total daily insulin dose (TDD) and determining the patient’s level of comfort during cannulation or insulin infusion.

[0099] TDD (Total Dependence Discharge) is the amount of insulin required to maintain an individual's blood glucose at a desired level. Foreign body reactions, tissue damage, and infusion site issues arising from the use of infusion devices (i.e., cannulation and insulin infusion) can reduce effective insulin delivery. As the body begins to react at the insertion site, the amount of insulin required to maintain a patient's normal blood glucose level will start to increase. Eventually, the amount of insulin will not be sufficient to lower glucose levels, at which point the infusion kit must be removed and a new infusion site is required. Therefore, monitoring insulin TDD can be used to assess cannulation performance.

[0100] Subjective levels of comfort and discomfort during cannulation can be assessed by providing test subjects with a questionnaire. Immediately after each cannulation, a Lickitt comfort / discomfort scale (very uncomfortable, uncomfortable, neutral, comfortable, and very comfortable) is presented to each study participant. Patients indicate which level is closest to the level perceived during cannulation and their responses are recorded. The word "pain" is avoided to prevent influencing the participants' perception. At the end of the test, the data are listed and analyzed using... Software pairwise analysis (“standard techniques” and “emergency techniques”).

[0101] Where the context permits, singular or plural terms may also include plural or singular terms, respectively. While specific implementations and examples of this technology have been described above for illustrative purposes, those skilled in the art will recognize that various equivalent modifications can be made within the scope of this technology.

[0102] As used herein, the terms “generally,” “substantially,” “about,” and similar terms are used as approximate terms rather than terms of degree, and are intended to take into account the inherent biases of the measured or calculated values ​​that will be recognized by one of ordinary skill in the art. As used herein, the term “about” is used synonymously with the term “approximately.” Illustratively, the use of the term “about” with respect to quantity indicates a value slightly different from the stated value, for example, plus or minus 0.1% to 10%, plus or minus 0.1% to 5%, or plus or minus 0.1% to 2%. In some embodiments, the term “about” indicates a value plus or minus 10% of the stated value. In some embodiments, the term “about” indicates a value plus or minus 5% of the stated value. In some embodiments, the term “about” indicates a value plus or minus 2% of the stated value. In some embodiments, the term “about” indicates a value plus or minus 1% of the stated value.

[0103] Furthermore, unless the word “or” is explicitly limited to meaning only a single item excluding other items when referring to a list having two or more items, its use in such a list should be interpreted as including (a) any single item in the list, (b) all items in the list, or (c) any combination of items in the list. Additionally, the term “including” throughout the text is used to mean at least the described features, such that no larger number of the same features and / or other features of additional types are excluded.

[0104] IV. Exemplary Implementation

[0105] Some implementation schemes disclosed herein relate to Implementation Scheme I, as follows:

[0106] Implementation Scheme I-1. A self-lubricating cannula comprising polyether block polyamide and additives, wherein the self-lubricating cannula is configured to deliver insulin to an individual in need, and the self-lubricating cannula resists adhesion to a heated mold.

[0107] Implementation Scheme I-2. The self-lubricating cannula according to Implementation Scheme I-1, wherein the additive is a siloxane.

[0108] Implementation Scheme I-3. The self-lubricating cannula according to Implementation Scheme I-1 or I-2, wherein the additive is a polysiloxane.

[0109] Implementation Scheme I-4. The self-lubricating cannula according to Implementation Scheme I-3, wherein the polysiloxane is a high molecular weight polysiloxane.

[0110] Implementation Scheme I-5. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-4, wherein the additive is polydimethylsiloxane.

[0111] Implementation Scheme I-6. A self-lubricating cannula according to any one of Implementation Schemes I-1 to I-5, wherein the additive is Multibase TM MB50-017.

[0112] Implementation Scheme I-7. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-6, wherein the self-lubricating cannula comprises: less than 10% by weight, less than 7% by weight, less than 5% by weight, less than 3% by weight, less than 2% by weight, less than 1.5% by weight, or less than 1% by weight of an additive, and comprises at least 0.1% by weight of an additive.

[0113] Implementation Scheme I-8. A self-lubricating cannula according to any one of Implementation Schemes I-1 to I-6, wherein the self-lubricating cannula comprises: 0.1 wt% to 10 wt%, 0.1 wt% to 7 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 3 wt%, 0.1 wt% to 2 wt%, 0.1 wt% to 1.5 wt%, 0.1 wt% to 1 wt%, 0.5 wt% to 10 wt%, 0.5 wt% to 7 wt%, 0.5 wt% to 5 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 0.5 wt% % to 2 wt%, 0.5 wt% to 1.5 wt%, 0.5 wt% to 1 wt%, 0.7 wt% to 10 wt%, 0.7 wt% to 7 wt%, 0.7 wt% to 5 wt%, 0.7 wt% to 3 wt%, 0.7 wt% to 2 wt%, 0.7 wt% to 1.5 wt%, 0.7 wt% to 1 wt%, 1 wt% to 10 wt%, 1 wt% to 7 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, or 1 wt% to 1.5 wt% of additives.

[0114] Implementation Scheme I-9. A self-lubricating cannula according to any one of Implementation Schemes I-1 to I-8, wherein the self-lubricating cannula comprises about 10% by weight, about 9.5% by weight, about 9% by weight, about 8.5% by weight, about 8% by weight, about 7.5% by weight, about 7% by weight, about 6.5% by weight, about 6% by weight, about 5.5% by weight, about 5% by weight, about 4.5% by weight, about 4% by weight, about 3.5% by weight, about 3% by weight, about 2.5% by weight, about 2% by weight, about 1.5% by weight, about 1% by weight, or about 0.5% by weight of an additive.

[0115] Implementation Scheme I-10. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-9, wherein the self-lubricating cannula further comprises thermoplastic polyurethane.

[0116] Implementation Scheme I-11. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-10, wherein the polyamide block polyether is

[0117] Implementation Scheme I-12. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-11, wherein: the polyamide block polyether is selected from... 3533 5533 and Groups consisting of 7233 or combinations thereof.

[0118] Implementation Scheme I-13. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-10, wherein: the polyamide block polyether has a physical property characteristic including two or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus and tensile modulus; and the physical property characteristic is consistent with that described in Table 1. The physical properties of polyether block polyamides are equivalent.

[0119] Implementation Scheme I-14. A self-lubricating cannula according to any one of Implementation Schemes I-1 to I-10, wherein: the polyamide block polyether has a physical property characteristic comprising two or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus, and tensile modulus; and the physical property characteristic is consistent with that described in Table 1. 3533 5533 or The physical properties of 7233 are identical.

[0120] Implementation Scheme I-15. The self-lubricating cannula according to Implementation Scheme I-13 or I-14, wherein: the polyamide block polyether has physical property characteristics including three or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorption rate, water absorption rate, flexural modulus and tensile modulus.

[0121] Implementation Scheme I-16. The self-lubricating cannula according to Implementation Scheme I-13 or I-14, wherein: the polyamide block polyether has physical property characteristics including four or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorption rate, water absorption rate, flexural modulus and tensile modulus.

[0122] Implementation Scheme I-17. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-16, wherein after the self-lubricating cannula comes into contact with the heated mold, the surface of the self-lubricating cannula in contact with the heated mold is smoother than the surface of a similar additive-free cannula in contact with the heated mold.

[0123] Implementation Scheme I-18. A self-lubricating cannula according to any one of Implementation Schemes I-1 to I-17, wherein the distal end of the self-lubricating cannula includes a tip configured to penetrate the skin of the individual in need.

[0124] Implementation Scheme I-19. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-18, wherein the self-lubricating cannula does not contain polyfluoroalkyl substances (PFAS).

[0125] Implementation Scheme I-20. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-19, wherein the self-lubricating cannula further includes a needle located within the self-lubricating cannula.

[0126] Implementation Scheme I-21. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-19, wherein the self-lubricating cannula further comprises a needle located on the outside of the self-lubricating cannula.

[0127] Implementation Scheme I-22. A self-lubricating cannula according to any one of Implementation Schemes I-1 to I-21, wherein the individual in need is a diabetic patient.

[0128] Implementation Scheme I-23. A self-lubricating cannula according to any one of Implementation Schemes I-1 to I-22, wherein the self-lubricating cannula is configured for subcutaneous insertion into the tissue of a diabetic patient.

[0129] Implementation Scheme I-24. The self-lubricating cannula according to Implementation Scheme I-23, wherein the self-lubricating cannula is configured to be implanted at a single site in the diabetic patient for at least 2 days prior to removal.

[0130] Implementation Scheme I-25. A self-lubricating cannula according to any one of Implementation Schemes I-1 to I-24, wherein the cannula has dimensional features including two or more, three or more, four or more, five or more, six or more, or seven or more sizes within the size range in Table 3.

[0131] Implementation Scheme I-26. The self-lubricating cannula according to any one of Implementation Schemes I-1 to I-25, wherein the cannula has a size falling within all the size ranges provided in Table 3.

[0132] Implementation Scheme I-27. A method for preparing a self-lubricating cannula, the method comprising the steps of: combining a polyether block polyamide and an additive to form a mixture, extruding the mixture to form a cannula, cutting the cannula to a desired length, and treating the distal end of the cannula with a heated mold to form a tip; wherein the self-lubricating cannula is used for delivering insulin to an individual in need, and the self-lubricating cannula resists adhesion to the heated mold.

[0133] Implementation Scheme I-28. The method according to Implementation Scheme I-27, wherein the heated mold is optionally lubricated before the distal end of the cannula is treated with the heated mold to form a tip.

[0134] Implementation Scheme I-29. The method according to Implementation Scheme I-27 or I-28, wherein the additive is a siloxane.

[0135] Implementation Scheme I-30. The method according to any one of Implementation Schemes I-27 to I-29, wherein the additive is a polysiloxane.

[0136] Implementation Scheme I-31. The method according to Implementation Scheme I-30, wherein the polysiloxane is a high molecular weight polysiloxane.

[0137] Implementation Scheme I-32. The method according to any one of Implementation Schemes I-27 to I-31, wherein the additive is polydimethylsiloxane.

[0138] Implementation Scheme I-33. The method according to any one of Implementation Schemes I-27 to I-31, wherein the additive is Multibase TM MB50-017.

[0139] Implementation Scheme I-34. The method according to any one of Implementation Schemes I-27 to I-33, wherein the self-lubricating cannula comprises: less than 10% by weight, less than 7% by weight, less than 5% by weight, less than 3% by weight, less than 2% by weight, less than 1.5% by weight, or less than 1% by weight of an additive, and comprises at least 0.1% by weight of an additive.

[0140] Implementation Scheme I-35. The method according to any one of Implementation Schemes I-27 to I-33, wherein the self-lubricating cannula comprises: 0.1 wt% to 10 wt%, 0.1 wt% to 7 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 3 wt%, 0.1 wt% to 2 wt%, 0.1 wt% to 1.5 wt%, 0.1 wt% to 1 wt%, 0.5 wt% to 10 wt%, 0.5 wt% to 7 wt%, 0.5 wt% to 5 wt%, 0.5 wt% to 3 ... % to 2 wt%, 0.5 wt% to 1.5 wt%, 0.5 wt% to 1 wt%, 0.7 wt% to 10 wt%, 0.7 wt% to 7 wt%, 0.7 wt% to 5 wt%, 0.7 wt% to 3 wt%, 0.7 wt% to 2 wt%, 0.7 wt% to 1.5 wt%, 0.7 wt% to 1 wt%, 1 wt% to 10 wt%, 1 wt% to 7 wt%, 1 wt% to 5 wt%, 1 wt% to 3 wt%, 1 wt% to 2 wt%, or 1 wt% to 1.5 wt% of additives.

[0141] Implementation Scheme I-36. The method according to any one of Implementation Schemes I-27 to I-33, wherein the self-lubricating cannula comprises about 10% by weight, about 9.5% by weight, about 9% by weight, about 8.5% by weight, about 8% by weight, about 7.5% by weight, about 7% by weight, about 6.5% by weight, about 6% by weight, about 5.5% by weight, about 5% by weight, about 4.5% by weight, about 4% by weight, about 3.5% by weight, about 3% by weight, about 2.5% by weight, about 2% by weight, about 1.5% by weight, about 1% by weight, or about 0.5% by weight of an additive.

[0142] Implementation Scheme I-37. The method according to any one of Implementation Schemes I-27 to I-36, wherein the additive is dispersed in thermoplastic polyurethane.

[0143] Implementation Scheme I-38. The method according to any one of Implementation Schemes I-27 to I-37, wherein the polyamide block polyether is

[0144] Implementation Scheme I-39. The method according to any one of Implementation Schemes I-27 to I-38, wherein the polyamide block polyether is selected from 3533 5533 and Groups consisting of 7233 or combinations thereof.

[0145] Implementation Scheme I-40. The method according to any one of Implementation Schemes I-27 to I-39, wherein: the polyamide block polyether has a physical property characteristic comprising two or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus and tensile modulus; and the physical property characteristic is consistent with that described in Table 1. The physical properties of polyether block polyamides are equivalent.

[0146] Implementation Scheme I-41. The method according to any one of Implementation Schemes I-27 to I-40, wherein: the polyamide block polyether has a physical property characteristic comprising two or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus and tensile modulus; and the physical property characteristic is consistent with that described in Table 1. 3533 5533 or The physical properties of 7233 are identical.

[0147] Implementation Scheme I-42. The method according to Implementation Scheme I-40 or I-41, wherein: the polyamide block polyether has physical property characteristics including three or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus and tensile modulus.

[0148] Implementation Scheme I-43. The method according to Implementation Scheme I-40 or I-41, wherein: the polyamide block polyether has physical property characteristics including four or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus and tensile modulus.

[0149] Implementation Scheme I-44. The method according to any one of Implementation Schemes I-27 to I-43, wherein the surface of the self-lubricating cannula in contact with the heated mold is smoother than the surface of a similar additive-free cannula in contact with the heated mold.

[0150] Implementation Scheme I-45. The method according to any one of Implementation Schemes I-27 to I-44, wherein the distal end of the self-lubricating cannula includes a tip configured to penetrate the skin of the individual in need.

[0151] Implementation Scheme I-46. The method according to any one of Implementation Schemes I-27 to I-45, wherein the self-lubricating cannula does not contain polyfluoroalkyl substances (PFAS).

[0152] Implementation Scheme I-47. The method according to any one of Implementation Schemes I-27 to I-46, wherein the self-lubricating cannula further includes a needle located within the self-lubricating cannula.

[0153] Implementation Scheme I-48. The method according to any one of Implementation Schemes I-27 to I-46, wherein the self-lubricating cannula further includes a needle located on the outside of the self-lubricating cannula.

[0154] Implementation Scheme I-49. The method according to any one of Implementation Schemes I-27 to I-48, wherein the individual in need is a diabetic patient.

[0155] Implementation Scheme I-50. The method according to any one of Implementation Schemes I-27 to I-49, wherein the self-lubricating cannula is configured for subcutaneous insertion into the tissue of a diabetic patient.

[0156] Implementation Scheme I-51. The method according to Implementation Scheme I-50, wherein the self-lubricating cannula is configured to be implanted at a single site in the diabetic patient for at least 3 days prior to removal.

[0157] Implementation Scheme I-52. A self-lubricating cannula, said self-lubricating cannula being formed by the method according to any one of claims 27-51.

[0158] Implementation Scheme I-53. A self-lubricating cannula for delivering insulin to an individual in need, according to any one of Implementation Schemes I-1 to I-26 or I-52.

[0159] Implementation Scheme I-54. A method of administering insulin to an individual in need, the method comprising: providing a self-lubricating cannula according to any one of Implementation Schemes I-1 to I-26, I-52 or I-53; inserting the self-lubricating cannula into the individual; and delivering insulin to the individual in need via the self-lubricating cannula.

[0160] Implementation Scheme I-55. The method according to Implementation Scheme I-54, wherein the self-lubricating cannula is inserted into the subcutaneous tissue of the abdomen, thigh, hip, upper arm, lower back or buttocks of the individual in need.

[0161] Implementation Scheme I-56. The method according to Implementation Scheme I-53 or I-54, wherein the self-lubricating cannula resists bundles or kinks during insertion into the individual in need.

[0162] Implementation Scheme I-57. The method according to any one of Implementation Schemes I-53 to I-56, wherein the self-lubricating cannula is implanted in the individual in need for at least 3 consecutive days, at least 4 consecutive days, at least 5 consecutive days, at least 6 consecutive days, at least 7 consecutive days, at least 8 consecutive days, at least 9 consecutive days, or at least 10 consecutive days before the cannula is replaced or removed.

[0163] Implementation Scheme I-58. The method according to any one of Implementation Schemes I-53 to I-57, wherein the total daily dose (TDD) of insulin delivered to the individual in need does not increase by more than 25% over a continuous period of 10 days.

[0164] Implementation Scheme I-59. The method according to any one of Implementation Schemes I-53 to I-58, wherein the cannula is fluidly connected to the insulin infusion device.

[0165] Implementation Scheme I-60. An infusion device comprising: a housing configured to be positioned on the skin of a patient at an infusion site; a reservoir configured to store a fluid drug, the reservoir being received by the housing; and a cannula configured for subcutaneous insertion into the patient's tissue at the infusion site, wherein the cannula is configured to be self-lubricating and comprises a polyether block polyamide and an additive.

[0166] Implementation Scheme I-61. The infusion device according to Implementation Scheme I-60, wherein the cannula is a self-lubricating cannula according to any one of Implementation Schemes I-1 to I-26, I-52 or I-53.

[0167] V. Example

[0168] The following specific embodiments should be understood as merely illustrative and not as limiting the remainder of this disclosure in any way.

[0169] Example 1: General process for preparing the cannula

[0170] This embodiment describes the general process for preparing the self-lubricating cannula described herein.

[0171] Polyether block amides (e.g., A combination of resin and siloxane additives (e.g., 3% by weight of DowCorning MB50-017 masterbatch) is used and blended to incorporate the siloxane into the entire polymer material. A feedstock containing 1.5% by weight of siloxane is added to the feed hopper and extruded on a conventional screw extruder. Specific processing parameters for the particular resin are obtained from the supplier. The extruded conduit is cut to a specified length and opened onto a bushing fitted with a mandrel by an interference fit. The distal end of the conduit is then tip-formed using a heated and lubricated die. This process requires preheating the tip-forming die to a predetermined temperature to allow resin recirculation and force the tip of the conduit to conform to the shape of the die. A silicone / siloxane lubricant is applied to the heated die surface just before tip-forming. The distal end of the conduit is forced and pressed into the heated die. During tip-forming, a mandrel is used to hold, guide, and align the conduit with the heated die. The distal end is held in the mold for a predetermined dwell time to allow backflow of the distal end of the conduit in contact with the mold and to conform to the mold size. After the predetermined dwell time, the tip-shaped cannula is retracted from the mold.

[0172] Used for preparing catheters The type of resin partially determines molding conditions, such as mold temperature. For example, Table 2 contains various... Molding conditions.

[0173] Table 2.

[0174]

[0175] *: Desiccant dryer (dew point ≤ -25℃)

[0176] Example 2: Comparison of polyether block polyamides with and without siloxanes

[0177] This embodiment compares self-lubricating cannulas with those formed without additives. In particular, visual inspection of the tipped surfaces and forms reveals different results due to the tipping process.

[0178] As described in Example 1, a polyether block polyamide was prepared. The cannula contains 5533) and 1.5% by weight of a siloxane polymer (3% of Dow Corning MB50-017 masterbatch, which consists of ultra-high molecular weight polysiloxane dispersed in thermoplastic polyurethane, wherein the siloxane content is 50%).

[0179] Similar cannulas were also prepared under the same conditions but without the additives. It was noted that the cannula tips without additives adhered to the mold and could not be retracted without damage, even when a siloxane lubricant was applied to the heated mold before tip forming. The cannula tips were visually examined using an optical microscope.

[0180] Figure 4 shows a magnified photograph of the tip of the polyether block polyamide cannula. The tip of the cannula without additives ( Figure 4A It has a rough and irregular surface. The tip of the pointed end is uneven. Conversely, Figure 4B The self-lubricating cannula shown contains 1.5% polysiloxane and has a relatively smooth surface and a uniformly rounded tip.

[0181] Polyether block polyamides are known to be inherently sticky materials. As observed in this example, when used alone to form cannulas, polyether block polyamides adhere to the heated mold during the tip forming process, resulting in poor tip forming—the surface and edges are rough, irregular, and inconsistent. Even when excessive lubricant is added to the mold, cannulas formed solely from polyether block polyamides adhere to the tip forming mold.

[0182] like Figure 4B As observed in the photograph, incorporating 1.5% by weight of siloxane into the cannula material improves manufacturability and cannula quality. This example illustrates the feasibility of manufacturing cannulas using polyether block polyamide and a small amount of siloxane additives under existing manufacturing processes. With the siloxane, the cannula exhibits improved reflow characteristics while not adhering to the molded surface during tip forming.

[0183] Example 3: Exemplary cannulation specifications

[0184] This embodiment provides a dimensional description of the exemplary cannula disclosed herein. Table 3 provides... Figure 5The dimensions of various parameters of the cannula and bushing / needle guide are shown. Feature 1 shows the proximal end of the cannula opening onto the needle guide / bushing, which is labeled Feature 2, and is the fluid inlet of the cannula.

[0185] Table 3.

[0186]

[0187] In some embodiments, this disclosure provides a self-lubricating cannula having dimensional features of two or more, three or more, four or more, five or more, six or more, or seven or more sizes included in the size ranges in Table 3. In some embodiments, the self-lubricating cannula has sizes falling within all the size ranges provided in Table 3.

[0188] Example 4: Preclinical testing of cannulation in a diabetic pig model

[0189] Example 3: Preclinical testing of cannulation in a diabetic pig model

[0190] The performance of the prototype self-lubricating cannula for insulin infusion can be evaluated in a diabetic pig model over a period of time (e.g., 10 days). Commercially available infusion devices can be modified to accommodate the test cannula. The performance of the prototype cannula can be tested against commercially available cannula standards, such as Medtronic Extended. TM Infusion kit (EIS).

[0191] Animal subjects were fasted for at least 12 hours prior to the test. On day 0, pigs were fed a standard diet at the prescribed time. While the subjects were under general anesthesia, a cannula was subcutaneously inserted into the abdominal tissue. A glucose sensor was also implanted at least 5 cm from the cannula. Blood glucose levels were measured five times daily at prescribed times (i.e., 07:30, 09:30, 11:30, 14:30, and 16:30). An infusion device was used to deliver Novolog insulin to the subjects.

[0192] Establish a basal delivery rate for Day 0, which represents the basal delivery rate required to maintain blood glucose concentration within a desired range (e.g., 100 mg / dL to 400 mg / dL). The infusion device delivers large doses of insulin as needed, such as after a meal when blood glucose concentration increases beyond the desired range. The infusion kit is considered ineffective when blood glucose concentration does not respond to changes in insulin dosage, such as when administering an increased dose of insulin fails to lower or control blood glucose concentration.

[0193] Calculate the amount of insulin administered over a 24-hour period, the total daily dose (TDD), and the duration of the test, or until the infusion kit fails. Animal survival rates and changes in insulin TDD over the test duration can be compared. Increases in insulin TDD over time can indicate deterioration of the infusion site. If the change in insulin TDD is small, it indicates successful insulin delivery and that blood glucose concentrations are maintained at the desired level. Furthermore, the performance of the cannulation test can be compared to that of commercially available standards.

[0194] in conclusion

[0195] While embodiments of the present disclosure have been shown and described herein, those skilled in the art will understand that such embodiments are provided by way of example only. Numerous variations, modifications, and substitutions can be made by those skilled in the art without departing from the invention. It should be understood that various alternatives to the embodiments of the invention described herein can be employed in the practice of this invention. For example, although the steps are presented in a given order, alternative embodiments may perform the steps in a different order. The various embodiments described herein can also be combined to provide further embodiments. It is contemplated that the following claims define the scope of the invention and thus cover the methods and structures within the scope of these claims and their equivalents.

[0196] It should also be understood that specific embodiments have been described herein for illustrative purposes, but various modifications may be made without departing from the present technology. Furthermore, while advantages associated with certain embodiments of the present technology have been described in the context of those embodiments, other embodiments may also exhibit such advantages, and not all embodiments need to exhibit such advantages to fall within the scope of the present technology. Therefore, this disclosure and associated technology may cover other embodiments not explicitly shown or described herein.

Claims

1. A self-lubricating cannula comprising a polyether block polyamide and an additive, wherein the self-lubricating cannula is configured to deliver insulin to an individual in need, and wherein the self-lubricating cannula resists adhesion to a heated mold.

2. The self-lubricating cannula according to claim 1, wherein the additive is a polysiloxane.

3. The self-lubricating cannula according to claim 2, wherein the polysiloxane is a high molecular weight polysiloxane.

4. The self-lubricating cannula according to claim 1, wherein the self-lubricating cannula comprises: 0.1 wt% to 10 wt%, 0.1 wt% to 7 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 3 wt%, 0.1 wt% to 2 wt%, 0.1 wt% to 1.5 wt%, 0.1 wt% to 1 wt%, 0.5 wt% to 10 wt%, 0.5 wt% to 7 wt%, 0.5 wt% to 5 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1.5 wt%, 0.5 wt% to 1 wt%, 0.7 wt% to 10 wt%, 0.7 wt% to 7 wt%, 0.7 wt% to 5 wt%, 0.7 wt% to 3 wt%, 0.7 wt% to 2 wt%, 0.7 wt% to 1.5 wt%, 0.7 wt% to 1 wt%, The additives are present in amounts of 1% to 10% by weight, 1% to 7% by weight, 1% to 5% by weight, 1% to 3% by weight, 1% to 2% by weight, or 1% to 1.5% by weight.

5. The self-lubricating cannula according to claim 1, wherein the self-lubricating cannula further comprises thermoplastic polyurethane.

6. The self-lubricating cannula according to claim 1, wherein the polyamide block polyether is 7. The self-lubricating cannula according to claim 1, wherein: The polyamide block polyether has physical properties including two or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus, and tensile modulus; and The physical properties described in Table 1 are consistent with those in Table 1. The physical properties of polyether block polyamides are equivalent.

8. The cannula according to claim 1, wherein the self-lubricating cannula does not contain polyfluoroalkyl substances (PFAS).

9. The self-lubricating cannula of claim 1, wherein the self-lubricating cannula is configured for subcutaneous insertion into the tissue of a diabetic patient.

10. A method for preparing a self-lubricating cannula, the method comprising the following steps: Polyether block polyamides and additives are combined to form a mixture. The mixture is extruded to form a cannula. Cut the cannula to the desired length, and The distal end of the cannula is treated with a heated mold to form a tip; The self-lubricating cannula is used to deliver insulin to individuals in need, and the self-lubricating cannula resists adhesion to the heated mold.

11. The method of claim 10, wherein the additive is a polysiloxane.

12. The method of claim 10, wherein the self-lubricating cannula comprises: 0.1 wt% to 10 wt%, 0.1 wt% to 7 wt%, 0.1 wt% to 5 wt%, 0.1 wt% to 3 wt%, 0.1 wt% to 2 wt%, 0.1 wt% to 1.5 wt%, 0.1 wt% to 1 wt%, 0.5 wt% to 10 wt%, 0.5 wt% to 7 wt%, 0.5 wt% to 5 wt%, 0.5 wt% to 3 wt%, 0.5 wt% to 2 wt%, 0.5 wt% to 1.5 wt%, 0.5 wt% to 1 wt%, 0.7 wt% to 10 wt%, 0.7 wt% to 7 wt%, 0.7 wt% to 5 wt%, 0.7 wt% to 3 wt%, 0.7 wt% to 2 wt%, 0.7 wt% to 1.5 wt%, 0.7 wt% to 1 wt%, The additives are present in amounts of 1% to 10% by weight, 1% to 7% by weight, 1% to 5% by weight, 1% to 3% by weight, 1% to 2% by weight, or 1% to 1.5% by weight.

13. The method of claim 10, wherein the additive is dispersed in thermoplastic polyurethane.

14. The method of claim 10, wherein: The polyamide block polyether has physical properties including two or more physical properties selected from the group consisting of Shore hardness, density, melting point, humidity, absorbance, water absorption, flexural modulus, and tensile modulus; and The physical properties described in Table 1 are consistent with those in Table 1. The physical properties of polyether block polyamides are equivalent.

15. The method of claim 10, wherein the self-lubricating cannula does not contain polyfluoroalkyl substances (PFAS).

16. A method for administering insulin to an individual in need, the method comprising: Provide a self-lubricating cannula as described in claim 1; The self-lubricating cannula is inserted into the individual's body; as well as Insulin is delivered to the individual in need via the self-lubricating cannula.

17. The method of claim 16, wherein the self-lubricating cannula is implanted in the individual in need for at least 3 consecutive days, at least 4 consecutive days, at least 5 consecutive days, at least 6 consecutive days, at least 7 consecutive days, at least 8 consecutive days, at least 9 consecutive days, or at least 10 consecutive days before the cannula is replaced or removed.

18. The method of claim 16, wherein the total daily dose (TDD) of insulin delivered to the individual in need does not increase by more than 25% over a continuous period of 10 days.

19. An infusion device, the infusion device comprising: A housing configured to be positioned on the skin at the infusion site of the patient; A reservoir configured to store a fluid drug, the reservoir being configured to be received by the housing; and A cannula configured for subcutaneous insertion into the patient's tissue at the infusion site, wherein the cannula is configured to be self-lubricating and comprises polyether block polyamide and additives.

20. The infusion device according to claim 19, wherein the cannula is the self-lubricating cannula according to claim 1.

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