Surface treatment system and method for a subcutaneous device

Abstract

Methods of modifying medical devices and methods of manufacturing medical devices are disclosed. One embodiment of a method of modifying a medical device includes treating a portion of the medical device with a cold plasma and functionalizing the plasma treated portion with a polymer. One embodiment of a method of manufacturing a medical device includes providing a subcutaneous component configured to be positioned subcutaneously under a user and performing a surface treatment on a portion of the subcutaneous component.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to U.S. Provisional Patent Application No. 63 / 132,071, filed December 30, 2020, entitled “Surface Treatment System and Method for Subcutaneous Devices,” the contents of which are incorporated herein by reference in their entirety. Technical Field

[0003] This disclosure relates to a subcutaneous device, and more specifically, to a subcutaneous device having a treated surface. Background Technology

[0004] Insertor devices, which may be referred to as inserters or syringes, can be used in the medical field to implant medical devices (e.g., infusion sets, sensors, etc.) through a patient's skin in a more or less automated manner.

[0005] In some cases, when using an inserter, the user (e.g., a patient or treatment provider) must apply force to the user's skin surface to inject the medical device or a component of the device in the form of a needle, cannula, sensor, etc. This can cause physical or psychological pain and / or discomfort and may lead to inappropriate administration of the medical device. Many people fear sharp objects, such as needles and other puncture devices used for medical procedures and treatments. This fear can be irrational and may hinder proper medical treatment. In one example, in cases of self-medication, insufficient administration of the appropriate dose of the required drug composition can lead to potentially life-threatening complications. In another example, when treating diabetes (e.g., in adolescents), there is a risk that the required insulin dose may not be administered by the individual due to irrational fear of needles and / or a general lack of knowledge and awareness of the consequences of neglecting the correct administration of the device and dosage.

[0006] Another issue with medical device implantation is the risk of contamination of the puncture component before or during administration. This can lead to patient infection (e.g., infection via a contaminated insertion needle). The longer the needle is exposed, the higher the risk of accidental contamination, which can result from finger contact with the needle, contact with unclean surfaces, airborne contamination, aerosol contamination, etc. Depending on the nature of the contamination (e.g., contamination from viruses, bacteria, fungi, yeast, and / or prions) and the patient's overall health condition, the resulting infection can rapidly escalate into a life-threatening condition.

[0007] Because contact with contaminated insertion needles can be life threatening, especially in a hospital setting, the risk of accidental exposure to contaminated material in the form of used insertion needles should be minimized. Therefore, there is a need in the art for a robust, reliable, accurate, safe, sanitary, and user-friendly inserter device that addresses the aforementioned problems.

[0008] Some inserter devices include a cannula and / or needle disposed within a body segment for implantation into a subcutaneous layer of skin. In at least some cases, the cannula can remain in place for up to three days, or possibly longer. If the cannula remains in a location in the subcutaneous layer of skin for more than about three days, the patient's body can recognize the cannula as a foreign object and react by rejecting the cannula. Rejection of the foreign object can result in reduced absorption of any medication administered through the cannula. It can therefore be advantageous to provide a solution that allows for an increased length of time before the body begins to reject the cannula. It can even be more desirable to provide a cannula and related components that can remain undetected by the patient's body when the cannula is implanted subcutaneously. SUMMARY

[0009] The present disclosure can include one or more of the following features, alone or in combination.

[0010] According to one aspect of the present disclosure, a method of modifying a medical device can include treating a portion of the medical device with cold plasma and functionalizing the plasma-treated portion with a polymer.

[0011] In some embodiments, the polymer can include a zwitterionic polymer.

[0012] In some embodiments, the zwitterionic polymer can be a sulfobetaine polymer or a carboxybetaine polymer.

[0013] In some embodiments, the polymer can include a phosphorylcholine species.

[0014] In some embodiments, the polymer can include a compound having the following formula:

[0015]

[0016] In some embodiments, the polymer can be a hyaluronic acid species.

[0017] In some embodiments, the polymer can include a compound having the following formula:

[0018]

[0019] In some embodiments, the plasma-treated portion of the medical device can be disposed at least partially along a surface of a subcutaneous component of the medical device, the surface being configured for positioning subcutaneously in a user.

[0020] In some embodiments, the plasma treated portion of the medical device can be defined at least in part along a surface of the cannula and configured for positioning subcutaneously in a user.

[0021] In some embodiments, the polymer can comprise a hyaluronic acid species and the plasma treated portion of the medical device can be defined at least in part along a surface of the cannula and configured for positioning subcutaneously in a user.

[0022] In some embodiments, the polymer can comprise a hyaluronic acid species and the plasma treated portion of the medical device can be defined at least in part along a surface of the cannula and configured for positioning subcutaneously in a user.

[0023] In some embodiments, treating the portion of the medical device can comprise treating the portion at a temperature of about 0-60 degrees Celsius.

[0024] In some embodiments, treating the portion of the medical device can comprise treating the portion at a pressure of about 1 atmosphere.

[0025] In some embodiments, treating the portion of the medical device can comprise treating the portion at a temperature of about 0-60 degrees Celsius and a pressure of about 1 atmosphere.

[0026] In some embodiments, functionalizing the plasma treated portion with a polymer can comprise functionalizing the plasma treated portion after treating the portion of the medical device.

[0027] In some embodiments, functionalizing the plasma treated portion with a polymer can comprise functionalizing the plasma treated portion simultaneously with treating the portion of the medical device.

[0028] In some embodiments, the method can comprise immobilizing biomolecules via a linking molecule on a surface of the plasma treated portion by generating a non-thermal atmospheric pressure plasma at a temperature equal to or below about 60 °C and maintaining the non-thermal atmospheric pressure plasma at the temperature equal to or below about 60 °C and can deposit the linking molecule onto the plasma treated portion by exposing the plasma treated portion to a first plasma jet and the linking molecule, thereby forming a linking layer on the plasma treated portion.

[0029] In some embodiments, the method can comprise depositing biomolecules on the linking layer by exposing the linking layer to a second plasma jet and the biomolecules.

[0030] In some embodiments, the biomolecules can comprise a phosphatidylcholine species.

[0031] In some embodiments, the biomolecule can include a compound having the following formula:

[0032]

[0033] In some embodiments, the biomolecule can include a hyaluronic acid species.

[0034] In some embodiments, the biomolecule can include a compound formulation having the following formula:

[0035]

[0036] In some embodiments, the polymer can include a methacrylated hyaluronic acid (HLA).

[0037] In some embodiments, the polymer can include a methacrylated hyaluronic acid compound having the following formula:

[0038]

[0039] In some embodiments, the polymer can include one or more hydrophilic polyalkylene glycol polymers.

[0040] In some embodiments, the one or more hydrophilic polyalkylene glycol polymers can include PEG or related PEG-like polymers having different structures.

[0041] In some embodiments, the structures can be one or more of a network structure, a branched structure, a dendritic structure, a hyperbranched structure.

[0042] According to another aspect of the disclosure, a method of manufacturing a medical device can include providing a subcutaneous component configured to be positioned subcutaneously in a user and performing a surface treatment on a portion of the subcutaneous component. Performing the surface treatment on the portion of the subcutaneous component can include exposing a treated portion of the subcutaneous component to a cold atmospheric plasma to form a linking layer on the treated portion and functionalizing the linking layer with a biomolecule configured to reduce a foreign body response to the subcutaneous component when the subcutaneous component is positioned subcutaneously in the user.

[0043] In some embodiments, prior to performing the surface treatment on the portion of the subcutaneous component, the method can include forming one or more holes through the subcutaneous component, and performing the surface treatment on the portion of the subcutaneous component does not close the one or more holes.

[0044] In some embodiments, the biomolecule can include a phosphatidylcholine species.

[0045] In some embodiments, the biomolecule can include a compound having the following formula:

[0046]

[0047] In some embodiments, the biomolecule can include a hyaluronic acid species.

[0048] In some embodiments, the biomolecule can include a compound having the formula:

[0049]

[0050] According to another aspect of the disclosure, a method of manufacturing a medical device can include providing a subcutaneous component configured to be positioned subcutaneously in a user and performing a surface treatment on a portion of the subcutaneous component. Performing the surface treatment on the portion of the subcutaneous component can include exposing a treated portion of the subcutaneous component to a cold atmospheric plasma to form a linking layer on the treated portion, functionalizing the linking layer with a biomolecule configured to reduce a foreign body reaction to the subcutaneous component when the subcutaneous component is positioned subcutaneously in a user, and immobilizing the biomolecule through a linking molecule located on a surface of the treated portion.

[0051] In some embodiments, immobilizing the biomolecule through the linking molecule can include generating a non-thermal atmospheric plasma at a temperature equal to or less than about 60 °C and maintaining the non-thermal atmospheric plasma at the temperature equal to or less than about 60 °C.

[0052] In some embodiments, immobilizing the biomolecule through the linking molecule can include depositing the linking molecule on the treated portion by exposing the treated portion to a first plasma jet and the linking molecule, thereby forming the linking layer on the plasma treated portion.

[0053] In some embodiments, the method can include depositing the biomolecule on the linking layer by exposing the linking layer to a second plasma jet and the biomolecule.

[0054] In some embodiments, prior to performing the surface treatment on the portion of the subcutaneous component, the method can include forming one or more holes through the subcutaneous component, and performing the surface treatment on the portion of the subcutaneous component does not close the one or more holes.

[0055] These and other features of the present disclosure will become more apparent with reference to the following description of illustrative embodiments. BRIEF DESCRIPTION OF DRAWINGS

[0056] The application described herein is illustrated by way of example and not by way of limitation in the accompanying drawings. For simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements are exaggerated relative to the other elements. Further, where considered appropriate, reference labels have been repeated among the figures for elements that are the same or similar.

[0057] Figure 1 Perspective view of the assembled inserter device;

[0058] Figure 2A Perspective view of the assembled inserter device; Figure 1 Front perspective view of the housing of the inserter device shown;

[0059] Figure 2B Cross-sectional view of the housing along the axis J-J;

[0060] Figure 2C End view of the housing as seen from its proximal end;

[0061] Figure 3A Front perspective view of the outer part of the inserter device shown; Figure 1 Cross-sectional view of the outer part taken along the axis L-L;

[0062] Figure 3B End view of the outer part as seen from its distal end;

[0063] Figure 4A Front perspective view of the first part of the inserter device shown; Figure 1 Cross-sectional view of the first part taken along the axis K-K;

[0064] Figure 4B End view of the first part as seen from its distal end;

[0065] Figure 4C Front perspective view of the second part of the inserter device shown;

[0066] Figure 5A Cross-sectional view of the second part taken along the axis of the connecting and locking member of the second part; Figure 1

[0067] Figure 5B

[0068] Figure 6 Perspective view of one embodiment of an infusion port hub adapted for use with the inserter device shown; Figure 1

[0069] Cross-sectional view of the inserter device shown in the idle position; Figure 7 Figure 1

[0070] Figure 8 ​​​​in the inserted position Figure 1 cross-sectional view of the inserter device shown in the inserted position;

[0071] Figure 9 in the retracted position Figure 1 cross-sectional view of the inserter device shown in the retracted position;

[0072] Figure 10A in a first state after insertion of the insertion needle Figure 1 perspective view of the first and second parts of the inserter device shown in a first state after insertion of the insertion needle;

[0073] Figure 10B in a second state after insertion of the insertion needle Figure 1 perspective end view of the first and second parts of the inserter device shown in a second state after insertion of the insertion needle;

[0074] Figure 10C in a third state after insertion of the insertion needle Figure 1 perspective view of the first and second parts of the inserter device shown in a third state after insertion of the insertion needle;

[0075] Figure 11A in a state just before retraction of the insertion needle Figure 1 perspective view of the first and second parts of the inserter device shown in a state just before retraction of the insertion needle;

[0076] Figure 11B in another state just before retraction of the insertion needle Figure 1 perspective end view of the first and second parts of the inserter device shown in another state just before retraction of the insertion needle;

[0077] Figure 11C in a further state just before retraction of the insertion needle Figure 1 perspective view of the first and second parts of the inserter device shown in a further state just before retraction of the insertion needle;

[0078] Figure 12 simplified flowchart of a surface treatment method; and

[0079] Figure 13 perspective view of one embodiment of a subcutaneous device having one or more holes or slits defined therethrough. DETAILED DESCRIPTION

[0080] While the concepts of the present disclosure can be susceptible to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and will be described in detail herein. However, it should be understood that the concepts of the present disclosure are not intended to be limited to the particular forms disclosed, but on the contrary, are intended to cover all modifications, equivalents and alternatives falling within the scope of the present disclosure and the appended claims.

[0081] As used in the specification and the claims, the phrase “one embodiment,” “an embodiment,” “an illustrative embodiment,” etc. indicates that the embodiment described can include a particular feature, structure, or characteristic, but is not necessarily one of the only implementations. Further, multiple embodiments can be described, but do not necessarily have to dwell on single embodiments, or implementations that might not be necessary for a particular implementation. Additionally or alternatively, features, structures, or characteristics can be universal among some or all embodiments. Finally, when a particular feature, structure, or characteristic is described in connection with an embodiment, it is submitted that it is within the knowledge of those in the art to effect such feature, structure, or characteristic in connection with other embodiments whether or not explicitly described or claimed. Additionally, it should be understood that the listed items presented in the following manner are merely examples of lists of items. The items can be combined in a single package, or multiple items can be spread across several packages. Additionally, items can optionally be included or excluded from a package or group of packages. Further, the items can be combined in a package or group, which can be sold or distributed through retail sales facilities 2002, 2004, and 2006, and / or can otherwise be obtained by way of a computer- based service as described herein such as via the Internet or over a mobile phone network.

[0082] In the drawings, certain features or structures, like those of apparatuses, modules, instruction blocks, and data elements, can be shown in particular arrangements and / or order to facilitate description. However, it should be understood that such particular arrangements and / or order can not be required. Rather, in some embodiments, these features can be arranged / arranged differently than shown in the illustrative drawings. Moreover, inclusion of a feature in a particular drawing does not imply that such feature is necessary in all embodiments, and in some embodiments, such a feature can not be included or such a feature can be combined with other features.

[0083] In some embodiments, illustrative elements used to represent methods can be implemented by users in a manual manner. In other embodiments, these illustrative elements can be implemented using any appropriate form of machine-readable instructions (e.g., software or firmware applications, programs, functions, modules, routines, processes, procedures, plug-ins, applets, widgets, code fragments, and / or others) in an automated manner, and each such instruction can be implemented using any appropriate programming language, library, application programming interface (API), and / or other software development tool. For example, in some embodiments, illustrative elements can be implemented using Java, C++, and / or other programming languages. Similarly, illustrative elements used to represent data or information can be implemented using any appropriate electronic arrangement or structure (e.g., registers, data stores, tables, records, arrays, indexes, hashes, mappings, trees, lists, graphs, files (any file type), folders, directories, databases, and / or others).

[0084] Furthermore, in the drawings, connecting elements, such as lines or arrows or the like, indicate connections, relationships or associations between two or more other illustrative elements, and absence of any such connecting elements does not imply absence of a connection, relationship or association between two or more elements. In other words, some connections, relationships or associations between elements can not be shown in the drawings in order not to obscure the disclosure. In addition, for ease of illustration, a single connecting element can be used to represent multiple connections, relationships or associations between elements. For example, where a connecting element represents a communication of signals, data or instructions, it will be understood by those skilled in the art that such element can represent one or more signal paths (for example, buses), as can be needed, to effect the communication.

[0085] Reference will now be made to Figure 1 , showing an embodiment of an inserter device 100 having the functionality of automatic insertion and automatic retraction of an insertion needle 102. The inserter device 100 is used to place an infusion port hub 104, in combination with a subcutaneous component 106 (see Figures 7-9 ), in the subcutis of a patient. At least in some embodiments, the infusion port hub 104 can be used for injection of a portion of a medicament over a period of time, for example, up to a period of 3 days. The infusion port hub 104 can comprise or otherwise embody an infusion device, a sensor device, a patch device, or the like.

[0086] Figure 1 The shown inserter device 100 is in an assembled, idle state. In this illustrative embodiment, the inserter device 100 comprises an outer component 300 and a housing 200, and the housing 200 is partially covered by the outer component 300. Functional components are housed inside the housing 200. The illustrative functional components include a first component 400, a second component 500, an insertion spring 402, a retraction spring 502, and an insertion needle 102 attached to the second component 500. The inserter device 100 is adapted for use with an infusion port hub 104 (e.g., an infusion device) attached thereto, but it will be understood that other suitable infusion sites / closed infusion devices fully implanted in the human body can also be used. Throughout this specification, the term "distal" refers to the end / surface / element that is farthest from the infusion port hub 104, and the term "proximal" refers to the end / surface / element that is closest to the infusion port hub 104. In addition, for the purposes of this disclosure, a discussion of a "vertical" plane / direction refers to a plane / direction that extends parallel to the insertion needle 102, and a discussion of a "horizontal" plane / direction refers to a plane / direction that is parallel to the surface of the patient's skin, which is perpendicular to the vertical plane / direction.

[0087] In this illustrative embodiment, Figure 2A a front view of the housing 200 is shown, Figure 2B a cross-sectional view of the housing 200 along axis J-J is shown, Figure 2CA view of the housing 200 is shown from the proximal end 201. The shape and / or diameter of the proximal end 201 can have different designs depending on the infusion port hub 104 attached to the proximal end 201, and it should be understood that the present disclosure is not limited to the depicted shape and / or diameter. Rather, the proximal end 201 can have various dimensions and be shaped in one or more suitable geometric forms depending on the infusion port hub 104.

[0088] The exemplary housing 200 comprises or otherwise embodies an elongated tube comprising a sidewall 203 having an inner surface forming a cavity. The housing 200 has an oval shape to ensure that the first component 400 cannot be rotated in a horizontal plane before, during or after activation of the inserter device 100. Of course, in a number of other embodiments, it should be understood that the housing 200 can be shaped in other suitable geometric forms.

[0089] The housing 200 illustratively comprises two proximal protrusions 202 positioned opposite each other at a distal end 205 of the housing 200. The proximal protrusions 202 are adapted to engage (e.g., be received in) two corresponding openings 304 in the outer component 300. The housing 200 additionally comprises two openings 204 positioned generally opposite each other at a (e.g., longitudinal) middle position of the housing 200. The openings 204 are adapted to engage with the locking elements 312 on the outer component 300. The proximal protrusions 202 and the openings 204 are aligned in pairs along a vertical axis extending from the proximal end 201 to the distal end 205, thus extending in a direction parallel to the insertion direction.

[0090] In this illustrative embodiment, on the inside of the housing 200, a housing guide member 206 is provided extending from the proximal end 201 to about the middle (e.g., longitudinally) of the housing 200. The housing guide member 206 extends along an axis parallel to the vertical axis defined by the pair of proximal protrusions 202 and openings 204, and is circumferentially displaced about 80-110 degrees relative to the vertical axis defined by the pair of proximal protrusions 202 and openings 204. The housing guide member 206 is adapted to be received by the slot 412 of the first component 400, and the housing guide member 206 is dimensioned such that when the guide member 206 is received in the slot 412, a portion of the guide member 206 extends through the slot 412 and into the interior of the first component 400.

[0091] Figure 3A a front view of the outer component 300 is shown, Figure 3BA cross-sectional view of the outer part 300 along the axis L-L is shown. The outer part 300 illustratively comprises and otherwise embodies a first section 302 and a second section 303. The first section 302 comprises two openings 304 provided at a distal end 306 of the first section 302. The two openings 304 are dimensioned to interact with the corresponding proximal protrusions 202 of the housing 200, thereby interlocking the housing 200 and the outer part 300. On the inside of the distal end 306 a protruding annular collar 314 is provided, which is inserted around by the distal end of the insertion spring 402. As a result, the insertion spring 402 cannot move horizontally before, during and / or after insertion and / or retraction of the insertion needle 102.

[0092] The second section 303 illustratively comprises two outwardly extending arms 307, an engagement means 310, a release element 308 and a locking element 312. The arms 307 are positioned opposite to each other in a horizontal plane and are directly attached at their distal ends to the first section 302. The engagement means 310 is illustratively embodied as a ring, which can be circular or elliptical. Of course, in other embodiments the engagement means 310 can take other suitable geometric forms. The release element 308 extends partly along the arms 307 and partly along the engagement means 310.

[0093] In this illustrative embodiment, the locking element 312 comprises two inwardly pointing parts for engaging with the openings 204 on the housing 200. The locking elements 312 are positioned opposite to each other on the engagement means 310 and are circumferentially offset by approximately 90 degrees with respect to the release element 308 and the arms 307. The locking elements 312 ensure that the insertion spring 402 stays in the preloaded position before the introducer device 100 is activated by engaging with the corresponding locking members 410 on the first part 400, thereby fixing the first part 400 at the top of the distal end 205 of the housing 200 and above the top of the locking elements 312.

[0094] Figure 4A A front view of the first part 400 is shown, Figure 4B A cross-sectional view of the first part 400 along the axis K-K is shown, Figure 4C A view of the first part 400 as seen from the distal end 401 is shown. The first part 400 illustratively comprises a tube, which comprises a first section 404 and a second section 408. The outer diameter of the first section 404 is smaller than the outer diameter of the second section 408, thereby forming a bearing surface 403. One end of the insertion spring 402 rests on the bearing surface 403.

[0095] The first section 404 illustratively includes two release slots 406 for engaging with corresponding locking members 508, 508' of the second component 500. Each release slot 406 extends from a distal end 401 along a vertical axis parallel to the insertion direction. The first section 404 also includes a recess 405 on its inner surface to facilitate interaction with an inclined guide member 510 of the second component 500.

[0096] In this exemplary embodiment, the second segment 408 has locking members 410 (such as two protrusions) arranged opposite each other on the outer side of the second segment 408 in a horizontal plane. Figure 7 In the preloaded idle position shown, locking member 410 engages with locking element 312 of external component 300. This interaction secures insertion spring 402 in the preloaded position to prevent insertion pin 102 from being activated during transport. Slot 412 is arranged between the two locking members 410 for receiving inner housing guide member 206 of housing 200 during activation of inserter device 100.

[0097] An exemplary proximal surface 414 of the first component 400 is provided with a central annular opening 416 (see...). Figure 4B and Figure 7 The insertion needle 102 passes through the opening when the subcutaneous component 106 is inserted into the patient. The opening 416 is illustratively sized to allow only the insertion needle 102 to pass through. In some cases, the diameter of the opening 416 is only 10-20% larger than the diameter of the insertion needle 102. This helps prevent the user from accidentally inserting their fingers through the opening 416 and coming into contact with the insertion needle 102 while using the inserter device 100. Furthermore, due to the small opening 416, the insertion needle 102 is almost invisible, which may have a positive psychological effect on patients / users who are afraid of needles.

[0098] The inner side of the second section 408 has an opening 418 for engaging with the corresponding locking members 508, 508' of the second component 500. In the idle and inserted positions, the locking members 508, 508' of the second component 500 are supported by the support edge 419, thereby fixing the retraction spring 502 and the second component 500 in a preloaded state. The annular recess 420 (see...) Figure 4B and 7 It is disposed on the proximal surface 422 to accommodate one end of the retraction spring 502, thereby ensuring that it does not shift horizontally before, during or after insertion and / or retraction.

[0099] When the insertion needle 102 is inserted, in this illustrative embodiment, the proximal surface 414 exerts pressure on the subcutaneous component 106, thereby locking the subcutaneous body component 110 within the cavity of the infusion port hub 104. Moreover, because after the insertion needle 102 is inserted, the first component 400 is pressed against the distal surface 114 of the subcutaneous component 106 due to the relaxed insertion spring 402, the proximal surface 414 helps release the subcutaneous component 106 from the insertion needle 102 when the insertion needle 102 is retracted into the inserter device 100.

[0100] Optionally, in some embodiments, the first component 400 can be provided with additional mechanisms for releasing the subcutaneous component 106 from the insertion needle 102. In one example, these mechanisms can take the form of distance pieces that ensure that the subcutaneous component 106 is pushed down into the opening of the infusion port hub 104 with a force that causes the subcutaneous component 106 to contact or position beyond the locking mechanism within the opening of the infusion port hub 104. In particular, one mechanism for releasing the subcutaneous component 106 includes a leaf spring disposed between the proximal surface 414 of the first component 400 and the distal surface 114 of the subcutaneous component 106. In at least some embodiments, the leaf spring is attached to or part of the first component 400 at one end. When the first component 400 is pushed toward the infusion port hub 104 by the insertion spring 402, the leaf spring will be loaded when the first component 400 is close enough to the infusion port hub 104. The leaf spring will then exert pressure on the subcutaneous component 106 to lock the subcutaneous body component 110 within the opening of the infusion port hub 104.

[0101] Figure 5A is a front view of the second component 500, Figure 5B is a cross-sectional view of the second component 500 along the axis connecting the locking members 508, 508'. The second component 500 includes a relatively small, elongated tube sized to fit inside the first component 400. The second component 500 includes a first section 504 and a second section 506. The outer diameter of the first section 504 is larger than the outer diameter of the second section 506 to form a bearing surface (as shown at Figure 10C and 11C to ensure that the retraction spring 502 is always positioned around the second section 506 at one end.

[0102] The locking members 508, 508' (in this embodiment two protrusions) disposed outside the first section 504 are configured to slide within corresponding release slots 406 on the first component 400 during activation of the inserter device 100. An inclined guide member 510 is located between the locking members 508, 508'. The second component 500 includes a recess 512 for guiding the second component 500 relative to the first component 400 during use of the inserter device 100. The insertion needle 102 is attached to the second component 500 and extends vertically upward within the generally solid second component 500. Of course, it should be understood that in some embodiments the positions of the first component 400 and the second component 500 can be reversed.

[0103] Figure 6 An embodiment of an exemplary port 104 (e.g., infusion port) is depicted, wherein the subcutaneous component 106 includes a cannula 108 and a body component 110. The body component 110 is shaped to secure the subcutaneous component 106 in the port 104 when the subcutaneous component 106 is inserted into the patient's skin 112. The subcutaneous component 106 is positioned on the insertion needle 102 and is held in place due to friction between the insertion needle 102 and the soft contact portion (e.g., cannula 108) of the subcutaneous component 106. The insertion needle 102 can be inside, beside, or outside the cannula 108.

[0104] In some embodiments, one or more surfaces of the port 104 and / or the subcutaneous component 106 can include a treated portion 116. The treated portion 116 can be disposed along a surface of the port 104 and / or the subcutaneous component 106 that directly contacts the user and / or is in place under the user's skin. The treated portion 116 can undergo a surface treatment process to introduce special performance characteristics into the treated portion 116. Thus, interfacial phenomena (e.g., lubricity, wettability, or adhesion) can be controlled without changing the overall properties of the underlying port 104 and / or subcutaneous component 106, such as tensile strength or flexibility. The surface treatment process can be a cost-effective mechanism for introducing active agents, such as drugs, antimicrobial agents, or peptides, in minimal amounts that are confined to only the surfaces (i.e., treated portion 116) where they are needed. For the subcutaneous component 106, the treated portion 116 can include a polymer form to make the subcutaneous component 106 less susceptible to foreign body reactions, thereby increasing tolerability for longer wear times.

[0105] In one aspect of the present disclosure, the surface treatment method of the treated portion 116 can utilize a cold atmospheric plasma. Cold atmospheric plasma surface treatment methods can provide a versatile and mild process that can be implemented under mild process conditions. For example, cold atmospheric plasma can be run at room temperature (i.e., about 10-30 degrees Celsius) and atmospheric conditions (i.e., 1 atmosphere, no vacuum). Thus, as used herein, the term“surface treatment method” includes any cold atmospheric plasma method. One example contemplated herein implements a two-step method that immobilizes biomolecules via a linking molecule on the surface of the treated portion 116 by generating and sustaining a non-thermal atmospheric plasma at a temperature of about room temperature to about 60 °C. In one embodiment, the biomolecules can be biopolymers or biocompatible polymers.

[0106] Cold plasma, which can be referred to as non-thermal or non-equilibrium plasma, refers to a low-temperature plasma formed at atmospheric pressure. It should be understood that a cold plasma is a plasma that is not in thermodynamic equilibrium because the electron temperature is higher than the temperature of the heavy species (e.g., ions and neutral particles) in the plasma. In some cases, a cold plasma can be produced when a sufficient amount of energy (e.g., above the ionization energy) is added to gaseous atoms and / or molecules, causing ionization and subsequently producing free electrons, photons, free radicals, and ion species. The excitation energy supplied to the gas to form the cold plasma can originate from a discharge, direct current, radio frequency, microwave, or other forms of electromagnetic radiation. By selecting the reaction conditions (e.g., activation energy, pressure, power input, carrier gas, and initial organic compounds such as polymers or monomers) accordingly, a suitable modified surface can be produced for different applications or requirements. Non-limiting examples of cold plasma technology and methods for producing cold plasma include atmospheric pressure plasma jet, dielectric barrier discharge, direct current (DC) glow discharge, discharge plasma, microwave discharge, pulsed power discharge, radio frequency (RF) discharge, and the like.

[0107] Surface polymerization in any of the embodiments described herein can include or otherwise embody any suitable polymerization process, such as conventional condensation, addition, or free radical graft polymerization (FRGP), or controlled radical polymerization (CRP) (e.g., ATRGP, RAFT, or NMGP). Surface reactivity can be controlled by adjusting plasma operating parameters, such as plasma source, plasma precursors and carrier gas, gas flow rate, gas partial pressure, high frequency power and applied voltage, as well as surface treatment time and preparation of the substrate surface.

[0108] In some embodiments, the cold plasma is a cold atmospheric plasma (CAP). In at least some embodiments, the cold plasma is an atmospheric pressure discharge cold plasma.

[0109] In some embodiments, the cold atmospheric pressure plasma has a pressure in the range of about 50 kPa to 150 kPa. Further, in some embodiments, the pressure at which the CAP is present is in the range of about 60 kPa to 140 kPa, in the range of about 70 kPa to 130 kPa, or in the range of about 80 kPa to 120 kPa. Further, in some embodiments, the pressure at which the CAP is present is in the range of about 100 kPa to 103 kPa. However, in various other embodiments, the cold plasma can be applied at a reduced pressure, for example, below 50 kPa (e.g., in the range of 0.01 kPa to 40 kPa or in the range of 0.1 kPa to 25 kPa).

[0110] In some embodiments, the cold plasma stream is applied to the surface to induce formation of surface-bound active sites that act as polymerization initiators or covalent binding sites. At least in some embodiments, the active sites can facilitate formation of a dense array of grafted polymers covalently bound to the surface of the substrate when contacted with a polymer, monomer, or monomer solution.

[0111] The surface of the medical device (e.g., the inserter device 100) can be in direct contact with the plasma as it is generated, or placed in a separate post-plasma region. If the surface is in direct contact with the plasma during generation, such placement can occur in the plasma reactor. For the purposes of the present disclosure, a post-plasma (post-discharge) region refers to a region external to the plasma, downstream of the plasma formation gas stream, in which active species such as free radicals still exist. This post-plasma region is particularly useful for delicate substrate surfaces such as polymers.

[0112] At least in some embodiments, the cold plasma treatment can be performed at an RF power of at least 1 W, 5 W, 10 W, 15 W, or at least 20 W. Further, in some embodiments, the cold plasma treatment can be performed at an RF power of no more than 2000 W, 1500 W, 1000 W, 500 W, 400 W, 300 W, 200 W, 100 W, 90 W, 80 W, 70 W, or no more than 60 W. Further, in some embodiments, the treatment can be performed at an RF power of about 20 W to 60 W.

[0113] In some embodiments, the cold plasma can have a temperature of at least 5 °C or at least 10 °C. At least in some embodiments, the cold plasma can have a temperature of no more than 60 °C or no more than 50 °C. Further, in some embodiments, the cold plasma is at ambient temperature, for example, in the range of 15 °C to 35 °C.

[0114] In some embodiments, the cold plasma treatment can be performed for at least 1 second, at least 2 seconds, at least 3 seconds, at least 4 seconds, at least 5 seconds, or at least 10 seconds. Further, in some embodiments, the cold plasma treatment can be performed for no more than 240 seconds, no more than 180 seconds, or no more than 120 seconds. Further, in some embodiments, the treatment can be performed for about 5 seconds to 120 seconds.

[0115] In some embodiments, the cold plasma treatment can be performed at an RF power of about 10 W to about 60 W and for a time of about 5 seconds to about 120 seconds. Further, in some embodiments, the cold plasma treatment can be performed using the foregoing RF and time ranges with a precursor gas selected from the group consisting of hydrogen, oxygen, nitrogen, argon, or helium.

[0116] In Figure 12 In one embodiment shown, the surface treatment method 1200 includes a first block 1202 and a second block 1204, which can be performed sequentially or simultaneously. In the first block 1202, a linking layer is created on the treated portion 116 by exposing the treated portion 116 to a first plasma jet and a linking molecule, thereby depositing the linking molecule on the treated portion 116. In the second block 1204 of the method 1200, a biomolecule is deposited on the linking layer by exposing the linking layer to a second plasma jet and the biomolecule. International Publication Nos. WO2020099434A1, WO2019243631A1, and WO2019038378A1 (all naming Molecular Plasma Group SA as applicant) discuss surface treatment methods contemplated herein and are hereby incorporated by reference in their entireties.

[0117] The surface treatment methods contemplated herein can be implemented on any treated portion 116 to, among other things, reduce foreign body reactions. In one aspect of the present disclosure, the biomolecule deposited on the linking layer can include phosphorylcholine to mimic the natural chemistry of cell phospholipid membranes. In this example, an active phosphorylcholine species (e.g., acrylate-functionalized phosphorylcholine) is dispersed into a gas stream and then combined with a cold, atmospheric pressure plasma. When the plasma-activated surface reacts with the phosphorylcholine species, the active species / plasma are directed onto the treated portion 116 to be modified, thereby creating covalent bonds and creating a surface chemically functionalized with phosphorylcholine moieties. According to one illustrative aspect herein, an exemplary phosphorylcholine species is:

[0118]

[0119] The above methods can improve the efficiency of the amount of phosphorylcholine required compared to dip coating methods. Further, it should be appreciated that all exposed surfaces of the treated portion 116 can be functionalized in one pass without the need to add a layer of material that can seal any desired pores.

[0120] In one aspect of the disclosure, the biomolecule deposited on the connecting layer can include hyaluronic acid. Hyaluronic acid is a molecule that can be particularly effective in reducing a foreign body response. More specifically, any treated portion 116 with hyaluronic acid can avoid activating macrophages responsible for initiating a foreign body response. In one example, a reactive hyaluronic acid species is dispersed into a gas stream and then combined with a cold atmospheric plasma. When the plasma-activated surface reacts with the hyaluronic acid species, the reactive species / plasma are directed onto the treated portion 116 to be modified, resulting in covalent bonds and creating a surface chemically functionalized with hyaluronic acid moieties. One illustrative example of a hyaluronic acid species according to the disclosure is:

[0121]

[0122] In one embodiment, the biomolecule polymer can be a biopolymer or a biocompatible polymer. The polymer can be a homopolymer or a copolymer. Examples of biopolymers can include glycosaminoglycans or mixtures thereof. Glycosaminoglycans are naturally occurring polysaccharides containing hexosamine and disaccharide repeating units of hexose or hexuronic acid and can contain one or more sulfate groups or can be non-sulfated. Typically, glycosaminoglycans are non-sulfated. Glycosaminoglycans can be anionic, cationic, or non-ionic. Typically, glycosaminoglycans are anionic. In one particular embodiment, the glycosaminoglycan is an anionic, non-sulfated glycosaminoglycan or mixtures thereof.

[0123] The disclosure contemplates the use of glycosaminoglycans of any known size, type, or form. The molecular weight of the glycosaminoglycan can be in the range of about 5,000 Da (Daltons) to about 20,000,000 Da, about 10,000 Da to about 12,000,000 Da, or about 1,000,000 Da to about 10,000,000 Da, among other ranges.

[0124] Glycosaminoglycans can be provided in free acid or salt form. Glycosaminoglycans can be combined with any suitable cation, including but not limited to: alkali metals, such as sodium and potassium, alkaline earth metals; nitrogen-containing cations, such as ammonium, substituted ammonium, and quaternized derivatives thereof; and other suitable cations. Preferred salts of glycosaminoglycans and derivatives thereof include alkali or alkaline earth glycosaminoglycan salts. Glycosaminoglycans can be provided in pure form, as mixtures of glycosaminoglycans with proteins and natural substances derived from the production of glycosaminoglycans from natural materials, or as chemically modified glycosaminoglycan derivatives. Mixtures of such glycosaminoglycans can also be provided.

[0125] Representative glycosaminoglycans include hyaluronic acid or derivatives thereof, such as Hylan, heparin, heparan sulfate, chondroitin, keratin, dermatan, and sulfates of such materials. A particularly preferred glycosaminoglycan is hyaluronic acid and derivatives thereof, which comprise repeating disaccharide structures of D-glucuronic acid and 2-acetamido-2-deoxy-D-glucose, bound by alternating β1→3 glucuronic acid and β1→4 glucosamine linkages. Representative hyaluronic acid and derivatives thereof that can be provided include, but are not limited to: Biomatrix's Hyaluronic acid, such as that described in U.S. Patent No. 4,303,676 (Balazs), which is incorporated herein by reference; Biomatrix's Hylan, such as that described in British Published Patent Application No. 2,172,295A (Balazs et al.), which is incorporated herein by reference; and substantially pure hyaluronic acid, such as that described in U.S. Patent No. 4,141,973 (Balazs), which is incorporated herein by reference.

[0126] In some embodiments, the polymer can be biocompatible. The biocompatible polymer can be a polymer having a phospholipid group, typically a phosphatidylcholine group. The presence of the phospholipid group can mimic the natural chemistry of a cell phospholipid membrane.

[0127] In at least some embodiments, the biomolecule polymer can also be any hydrophilic polyalkylene glycol polymer. Such biomolecule polymer can be PEG having different structures (reticular structure, branched structure, dendritic structure, hyperbranched structure, etc.) or related PEG-like polymers having different structures (reticular structure, branched structure, dendritic structure, hyperbranched structure, etc.).

[0128] In another example, the biomolecule polymer can include a methacrylated HLA, such as:

[0129]

[0130] In some embodiments, the biocompatible polymer can be obtained / obtainable by synthesizing a monomer having a phosphorylcholine structure and polymerizing it with a (meth)acrylic monomer. In the case of (meth)acrylate monomers, alkyl methacrylates and alkyl acrylates of 1 to 20 carbon atoms can be used. In the case of copolymer production or (meth)acrylate monomers, alkyl methacrylates and alkyl acrylates of 1 to 8 alkyl esters can typically be used. Specific examples of (meth)acrylate monomers include methyl acrylate, ethyl acrylate, butyl acrylate, 2-ethylhexyl acrylate (2-ethylhexyl acrylate), lauryl acrylate, and stearyl acrylate, alkyl esters of methacrylic acid and methyl methacrylate, such as methyl methacrylate, ethyl methacrylate, butyl methacrylate, 2-ethylhexyl methacrylate (2-ethylhexyl methacrylate), lauryl methacrylate, and stearyl methacrylate. As used herein, the term “(meth)acrylic acid” refers to either acrylic acid or methacrylic acid, typically acrylic acid, which is commonly used in biological applications.

[0131] In various embodiments, the biocompatible polymer can have a molecular weight of about 5,000 Da (Daltons) to about 20,000,000 Da, about 10,000 Da to about 12,000,000 Da, or about 1,000,000 Da to about 10,000,000 Da.

[0132] Although phosphorylcholine and hyaluronic acid are specifically discussed herein as the portion of the biomolecule deposited on the junction layer during the surface treatment process, other molecules are contemplated by the present disclosure. For example, other peptides, proteins, polysaccharides, and hydrophilic polymers (e.g., poly(ethylene oxide)) are also contemplated herein as the biomolecule deposited on the junction layer during the surface treatment process.

[0133] Referring now to Figure 13 One embodiment of the subcutaneous device contemplated herein includes a cannula 108 having a plurality of holes or slits 1302 therethrough. The holes or slits 1302 can be configured to provide a flow path for the delivery of a drug or the like to a user through the cannula 108. The holes or slits 1302 can be laser cut into the cannula 108 through the treated portion 116. While dip coating Figure 13 of the cannula 108 is one possible way to introduce a coating to the surface thereof, such a process can potentially result in the coating sealing the holes or slits 1302, thereby affecting their ability to function as intended. Accordingly, the present disclosure also envisions a surface treatment method 1200 as described herein that instead utilizes a cold atmospheric plasma process to surface treat the cannula 108 at the molecular level. Such a method can be implemented without the risk of sealing any holes or slits 1302 in the cannula 108.

[0134] In some embodiments, the surface treatment method includes introducing a phosphorylcholine species, such as an acrylate-functionalized phosphorylcholine, to the treated portion 116. The surface treatment method can include introducing other phosphorylcholine species or other phospholipid materials as biomolecules to the treated portion 116 as well. In some embodiments, the hydrophilic material includes, for example, polyvinyl chloride (PVC) plasticized with dioctyl terephthalate (bis(2-ethylhexyl) benzene-1,4-dicarboxylate) or bis(2-ethylhexyl) terephthalate, i.e., (DOTP) or (DEHT), respectively. In some embodiments, the hydrophilic material incorporated into the TPE can include a polyolefin-based synthetic thermoplastic polyolefin elastomer containing a hydrophilic additive.

[0135] In some embodiments, the treatment process can introduce a hydrogel material including polyvinyl poly-pyrrolidone (PVPP) and / or polyvinyl pyrrolidone (PVP) as biomolecules to the treated portion 116. In some embodiments, the silver or silver chloride material can be any one or more of those described in U.S. Patent Application No. 11 / 194,951 and U.S. Patent No. 6,451,003, the entire contents of both of which are incorporated herein by reference.

[0136] In Figures 7-9 embodiments, the inserter device 100 is shown in a cross-sectional view along line A-A. In some embodiments, the four portions of the inserter device 100 (i.e., the housing 200, the outer member 300, the first member 400, and the second member 500) are constructed of a hard plastic that can incorporate segments of a softer material to prevent breakage of these members during the activation of the inserter device 100. The insertion spring 402 and the retraction spring 502 can have a metal construction, although other types of materials can be used.

[0137] Figure 7 The inserter device 100 is shown in an idle state prior to activation of the inserter device 100. Both springs 402, 502 are in a pre-loaded position. The insertion spring 402 and the first member 400 are fixed in the pre-loaded idle position by the locking element 312, which prevents the first member 400 from shifting relative to the housing 200. The second member 500 is held in the pre-loaded idle position by the locking members 508, 508' engaging the two openings 418 and the support rim 419 on the inside of the first member 400. The pre-loading of both springs 402, 502 in the idle state ensures a favorable compact design of the inserter device 100.

[0138] Figure 8An inserter device 100 in the insertion position is shown, with a cannula 108 inserted into the patient's skin 112 and a body component 110 secured within an infusion port 104. The infusion port 104 includes a proximal surface 118 configured to contact the patient's skin 112. In some embodiments, a treated portion 116 is located on the proximal surface 118 of the infusion port 104.

[0139] like Figure 7 As shown, the infusion port 104 includes an inner surface 120 and an outer surface 122. The inner surface 120 includes a surface arranged around the body member 110 when the body member 110 is inserted into the cavity of the infusion port 104. The inner surface 120 also includes a surface defining an opening in the infusion port 104 through which the cannula 108 extends. The remaining surfaces of the infusion port 104 define the outer surface 122 (including the proximal surface 118). The processed portion 116 may include any one or both of the surface 120 and the outer surface 122 of the infusion port 104.

[0140] For reference Figure 9 The sleeve 108 includes an inner surface 124 and an outer surface 126. The inner surface is configured to contact the insertion needle 102 to hold the insertion needle 102 in place due to friction therebetween as described above. The outer surface 126 is positioned relative to the inner surface 124. A processed portion 116 may be located on one or both of the inner surface 124 and the outer surface 126 of the sleeve 108.

[0141] like Figure 7 As shown, the body component 110 may include an outer surface 128, which includes a ribbed portion configured to retain the body component 110 within the cavity of the infusion port 104. Furthermore, the body component 110 may include an inner surface 130 configured to receive an external device, such as an injection needle or its support structure. The processed portion 116 may include any one or both of the inner surface 130 and the outer surface 128 of the body component 110.

[0142] In some embodiments, the infusion port 104 includes an adhesive surface for releasably attaching the infusion port 104 to the patient's skin 112. A release liner can be removed from the infusion port 104 before it is placed on the patient's skin 112. In such embodiments, the adhesive material may be part of the treated portion, or may be separate from and / or different from the treated surface.

[0143] exist Figure 8 In the insertion position shown, the insertion needle 102 is still inserted into the patient's body and has not yet returned to the retracted position. The insertion spring 402 is in the relaxed position, while the retraction spring 502 is still in the preloaded position.

[0144] Figure 9 The inserter device 100 is shown in the retracted position, at which time the cannula 108 has been inserted into the patient's skin 112 and the insertion needle 102 attached to the second part 500 has been retracted to a position at the distal end 205 of the housing 200, so that the insertion needle is no longer located within the first part 400. The retraction spring 502 is in a relaxed position, at which position it cannot be reloaded again if the inserter device 100 is not disassembled. This ensures that the insertion needle 102 is contained within the inserter device 100 and cannot be extended outside of it.

[0145] Insertion of the subcutaneous part 106 into the patient's skin 112 is accomplished by placing the inserter device 100 on the patient's skin 112 with the infusion port hub 104 directly on top of the patient's skin 112 and then activating the inserter device 100. Typically, prior to placing the infusion port hub 104 on the patient's skin 112, the protective release paper must be removed from the infusion port hub 104, thereby exposing the adhesive layer underneath the infusion port hub 104 for fastening the infusion port hub 104 to the patient's skin 112.

[0146] Activation of the inserter device 100 is accomplished by exerting pressure on the two release elements 308 on the outer part 300, i.e. by deforming the engagement means 310 by pressing the two release elements 308 closer together. The distance between the locking elements 312 is thus increased, so that there is sufficient space to allow the locking members 410 on the first part 400 to pass the locking elements 312 with the help of the insertion spring 402, which in this way is allowed to relax.

[0147] By contrast Figure 10A -C and Figure 11A -C, in particular by contrast Figure 10A -B and Figure 11A -B, it can be observed that the second part 500 is urged to rotate clockwise by advancing the housing guide member 206 within the slot 412 and rotating the inclined guide member 510. From Figure 10C and 11C The release of the locking members 508, 508' from the inner opening 418 is most clearly seen in Figure 10C The locking members 508, 508' are shown fixed underneath the inner opening 418, Figure 11C The locking members 508, 508' are shown located in the release slot 406 of the first part 400, thereby allowing the retraction spring 502 to relax, thereby pushing the second part 500 to the retracted position, at which the second part is no longer contained within the first part 400.

[0148] When the second part 500 is released from the first part 400, the second part 500 is generally rotated 10-40 degrees relative to the first part.

[0149] The construction of the inserter device 100 is such that it can only be used once, since it is not possible to reload the springs 402, 502 after the inserter device 100 has been activated. This is advantageous in that the user is not tempted to use the device more than once and thereby expose him / herself to unnecessary health risks.

[0150] The construction of the inserter device 100, which is combined from essentially four interconnected parts: the housing 200, the outer part 300, the first part 400, the second part 500, and two springs 402, 502, and one insertion needle 102, allows for a simple construction and a rather compact device can be obtained. This reduces the production costs.

[0151] Normally, the inserter device 100 is contained in a protective bag during transport. The conditions inside the bag are sterile, thereby ensuring that the inserter device 100 can be kept sterile until it is to be used. The only time the insertion needle 102 is exposed is during the short moment of insertion. This makes the inserter device 100 safe to handle, since the user cannot come into contact with the insertion needle 102 before the device is activated and / or after the insertion needle 102 is automatically retracted. Thus, it is safe to dispose of the inserter device 100 with the normal household garbage without having to protect it beforehand.

[0152] The user can achieve both the automatic insertion and the automatic retraction of the insertion needle 102 by exerting pressure in the horizontal plane, since this mainly involves one movement. Furthermore, since the insertion procedure does not involve exerting pressure in the direction towards the skin, the procedure is more attractive to users who are afraid of injection needles and other piercing devices, since these users often find it much more difficult to insert an insertion needle if they have to exert pressure towards the skin at the same time.

[0153] Various plasma coating types (e.g. PEG, phosphocholine (PC) and hyaluronic acid (HLA)) were applied to PTFE sleeves. The results are summarized in Table 1 below.

[0154]

[0155] Table 1

[0156] 3EGDVE = 3 (Ethylene Glycol) Divinyl Ether (CAS 765-12-8). Precursor for plasma deposition of antifouling PEG-based coatings. 3 EG units. Vinyl groups tend to increase grafting and deposition rate.

[0157] MA-PC = 2-methacryloyloxyethylphosphocholine (CAS 67881-98-5) at 10 wt% in EGDMA / EtOH 50 / 50. Methacrylate functionalized phosphocholine. Suggested by ConvaTec to mimic cell wall. MA-PC is poorly soluble in EGDMA (crosslinker). It is very soluble in ethanol. It was then decided to dissolve 10 wt% of MA-PC in a mixture of 50 / 50 (wt) EGDMA and ethanol. Plasma deposition of this formulation should result in a MA-PC rich, EGDMA based plasma polymer matrix.

[0158] HAM-20k / EGDMA = HAM-20k = methacrylated hyaluronic acid (molecular weight 20,000-30,000) at 2 wt% in aqueous solution / H20. HAM-20k is only soluble in water. We also tried to dissolve it in EtOH and EGDMA, but were not successful. It was then decided to use separate atomizers to co-inject the HAM-20k solution and EGDMA simultaneously. Plasma co-deposition of the aqueous based HAM-20k solution and EGDMA should result in a HAM-20k rich, EGDMA based plasma polymer matrix.

[0159] UV1 and UV2 = Rhodamine 6G (R6G) used as UV tracer for Q&D tests. UV1 solution was prepared by adding 0.1 wt% of R6G to a 3EGDVE / EtOH 90 / 10 (wt) solution. EtOH was added to completely dissolve the R6G. UV2 solution was prepared by adding 1 wt% of R6G to an EGDMA / EtOH 80 / 20 (wt) solution.

[0160] • MPG's The equipment used for all treatments (see Figure 2). A special nozzle (reference number: 20000 106) designed and printed by the MPG was able to treat the outer wall of the cannula homogeneously. The cannula was mounted on a rotating (about 5 RPM) sample holder system by means of a long, gauge 27 needle (OD = 0.4 mm) that went through the cannula. The plasma head was then scanned over the surface to be treated.

[0161] - In the case of 3EGDVE, the plasma power was fixed at 300 W (see experimental table above). This value should result in the best grafting and highest crosslinking degree of the PEG-like plasma coating. For the cases of MA-PC and HAM-20k / EGDMA, two different plasma power settings were tested: 300 W and 450 W.

[0162] - The linear speed was arbitrarily set to 0.6 meters / minute, the number of passes ( Coating thickness) was arbitrarily set to a relatively high value of 20 (10 back-and-forth scans). Coating thickness can be optimized later in the study.

[0163] The "Precursor Flow" parameter controls the mass feed of precursor. In the case of 3EGDVE, this parameter was fixed to the known optimal precursor feed, while in the other cases this parameter was varied / different. Nitrogen (N2; 80 slm) was the primary plasma and carrier gas.

[0164] The ratio between power and precursor feed, in other words, energy per molecule, influences the retention of key chemical moieties as well as the degree of cross-linking. While higher power potentially induces more cross-linking and better grafting plasma coatings, it also leads to more fragmentation of the precursor, thus losing chemical moieties.

[0165] "Sheet WCA" was measured immediately after treatment, on a flat PTFE sheet that was treated the same way as the sleeve. "Sleeve WCA" was measured on the sleeve itself. Between treatment and measurement, the sleeve was stored in the lab for approximately 7 months.

[0166] Q&D test:

[0167] During the exploratory dates, several trials were performed at MPG. A portable water contact angle (WCA) apparatus was used to evaluate the hydrophilicity of the treated model PTFE surface (PTFE tape). In addition, additional sacrificial samples (with UV tracers) were produced, as requested by ConvaTec, to evaluate the uniformity of the coating and resistance to silicone / poly-siloxane / silicone block penetration tests.

[0168] • WCA: Values were recorded in the experimental table for each precursor and test condition.

[0169] 0 Untreated PTFE tape: 105°-110°; Carbon dioxide activated PTFE tape: 85°-90°.

[0170] 0 Without considering the activation step, 3EGDVE resulted in a WCA value of approximately 27°-28°.

[0171] 0 MA-PC based coatings resulted in angles in the range of 40°-45°. Higher power and higher precursor flow conditions #5 resulted in a slight increase in WCA, 45°-50°.

[0172] 0 HAM-20k: Condition #7 (moderate power, lower precursor flow) resulted in a WCA in the range of 33°-35°. Increasing power and precursor flow resulted in a slight increase in WCA, 40°-45°.

[0173] 0Important note: After the samples were cycled wet and dry, we rechecked the WCA values. The measured WCA values remained in the same range as freshly treated. This indicates that the plasma coating is grafted well and does not release / dissolve upon wetting, or at least not completely.

[0174] • Qualitative "silicone block" test: Additional samples were prepared using chemical precursors doped with UV tracers (UV1 and UV2, see experimental section). The UV-tracers enable to assess the homogeneity of the coating, as well as their resistance against permeation / penetration in a silicone block. As shown in Figure 3, both PEG-based and EGDMA-type plasma coatings show significant resistance against permeation, even without a CO2 plasma activation step.

[0175] Conclusion:

[0176] • Successful deposition of all types of chemicals; all conditions resulted in a durable wettable surface.

[0177] • Silicone block test showed that the coatings have very good resistance against permeation, even without a plasma pre-activation step. ConvaTec considers this very promising.

[0178] • The samples to be tested at ConvaTec will be produced as follows:

[0179] 0 20 replicates (9 mm cannula) for PEG-based coatings, conditions #1 and #2.

[0180] 0 For the other two chemicals (MA-PC and HAM-20k), 6 replicates (6 mm cannula) per condition.

[0181] 0 3 replicates of UV1 and UV2 type coatings are also included in the package (6 mm cannula).

[0182] 0 A total of 94 cannulas were processed, and will be tested by ConvaTec.

[0183] While the present disclosure has been described with respect to at least one embodiment, the present disclosure can be further modified within the spirit and scope of the disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the disclosure using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which the disclosure pertains and fall within the limits of the appended claims.

Claims

1. A method of modifying a subcutaneous medical device, the method comprising: treating a portion of a subcutaneous medical device with a cold plasma; functionalizing the plasma-treated portion with a polymer; and immobilizing a biomolecule through a linking molecule located on a surface of the plasma-treated portion, wherein: immobilizing the biomolecule through the linking molecule comprises generating a non-thermal atmospheric pressure plasma at a temperature equal to or less than 60 °C and maintaining the non-thermal atmospheric pressure plasma at the temperature equal to or less than 60 °C; and depositing the linking molecule on the plasma-treated portion by exposing the plasma-treated portion to a first plasma jet and the linking molecule, thereby forming a linking layer on the plasma-treated portion, wherein the biomolecule comprises a hyaluronic acid species of Formula (II):

2. The method of claim 1, further comprising depositing the biomolecule on the linking layer by exposing the linking layer to a second plasma jet and the biomolecule.

3. A method of manufacturing a subcutaneous medical device, the method comprising: providing a subcutaneous component configured to be positioned subcutaneously in a user; and performing a surface treatment on a portion of the subcutaneous component, wherein performing the surface treatment on the portion of the subcutaneous component comprises: exposing the treated portion of the subcutaneous component to a cold atmospheric pressure plasma to form a linking layer on the treated portion; functionalizing the linking layer with a biomolecule configured to reduce a foreign body reaction to the subcutaneous component when the subcutaneous component is positioned subcutaneously in a user; and immobilizing the biomolecule through a linking molecule located on a surface of the treated portion, wherein immobilizing the biomolecule through the linking molecule comprises generating a non-thermal atmospheric pressure plasma at a temperature equal to or less than 60 °C and maintaining the non-thermal atmospheric pressure plasma at the temperature equal to or less than 60 °C, wherein immobilizing the biomolecule through the linking molecule comprises depositing the linking molecule on the treated portion by exposing the treated portion to a first plasma jet and the linking molecule, thereby forming the linking layer on the plasma-treated portion, wherein the biomolecule comprises a hyaluronic acid species of Formula (II):

4. The method of claim 3, further comprising depositing the biomolecule on the linking layer by exposing the linking layer to a second plasma jet and the biomolecule.

5. The method of claim 3, prior to performing the surface treatment on the portion of the subcutaneous component, the method further comprising forming one or more holes through the subcutaneous component, wherein performing the surface treatment on the portion of the subcutaneous component does not occlude the one or more holes. ​

Images