Patent Application
20240423613
The present invention relates generally to systems and methods for tuning absorption pathways in bioabsorbable materials via chemical backbones and/or coatings.
Surgical staplers are used in surgical procedures to close openings in tissue, blood vessels, ducts, shunts, or other objects or body parts involved in the particular procedure. The openings can be naturally occurring, such as passageways in blood vessels or an internal organ like the stomach, or they can be formed by the surgeon during a surgical procedure, such as by puncturing tissue or blood vessels to form a bypass or an anastomosis, or by cutting tissue during a stapling procedure.
Most staplers have a handle (some of which are directly user operable, others of which are operable by a user via a robotic interface) with an elongate shaft extending from the handle and having a pair of movable opposed jaws formed on an end thereof for holding and forming staples therebetween. The staples are typically contained in a staple cartridge, which can house multiple rows of staples and is often disposed in one of the two jaws for ejection of the staples to the surgical site. In use, the jaws are positioned so that the object to be stapled is disposed between the jaws, and staples are ejected and formed when the jaws are closed, and the device is actuated. Some staplers include a knife configured to travel between rows of staples in the staple cartridge to longitudinally cut and/or open the stapled tissue between the stapled rows.
There is provided, in accordance with an example of the present invention, a bioabsorbable material configured to be delivered to tissue. The material can include a first polymerizable compound and a second polymerizable compound. The first polymerizable compound can include a reaction product of a polyol and an isocyanate and can be configured to degrade according to a first degradation profile. The second polymerizable compound can be configured to degrade according to a second degradation profile different than the first degradation profile. The material can undergo a phase transition in response to exposure to a fluid comprising at least one of a predetermined temperature, an enzyme-catalyst, and a predetermined pH.
There is provided, in accordance with an example of the present invention, a bioabsorbable material configured to be delivered to tissue. The material can include a copolymer backbone. The copolymer backbone can include a first polymerizable compound and a second polymerizable compound. The first polymerizable compound can include a reaction product of a polyol and an isocyanate and can be configured to degrade according to a first degradation profile. The second polymerizable compound can be configured to degrade according to a second degradation profile different than the first degradation profile. The material can undergo a phase transition in response to exposure to the fluid comprising a predetermined temperature.
There is provided, in accordance with an example of the present invention, a bioabsorbable material configured to be delivered to tissue. The material can include a first polymerizable compound and a second polymerizable compound. The first polymerizable compound can include a reaction product of a polyol and an isocyanate and can be configured to degrade according to a first degradation profile. The second polymerizable compound can coat the first polymerizable compound such that the coating can prevent the first polymerizable compound from exposure to a fluid ingress for a predetermined period of time. The material can undergo a phase transition in response to exposure to the fluid comprising a predetermined pH.
This invention will be more fully understood from the following detailed description taken in conjunction with the accompanying drawings, in which:
The following detailed description should be read with reference to the drawings, in which like elements in different drawings are identically numbered. The drawings, which are not necessarily to scale, depict selected embodiments and are not intended to limit the scope of the invention. The detailed description illustrates by way of example, not by way of limitation, the principles of the invention. This description will clearly enable one skilled in the art to make and use the invention, and describes several embodiments, adaptations, variations, alternatives and uses of the invention, including what is presently believed to be the best mode of carrying out the invention.
As used herein, the terms “about” or “approximately” for any numerical values or ranges indicate a suitable dimensional tolerance that allows the part or collection of components to function for its intended purpose as described herein. More specifically, “about” or “approximately” may refer to the range of values±10% of the recited value, e.g., “about 90%” may refer to the range of values from 81% to 99%.
As used herein, “degradation” refers to a process of breaking down of a polymer chain for absorption as atoms, molecules, or ions into the surroundings (e.g., tissue, cells, fluid, and the like). Degradation includes breaking primary and secondary bonds via thermal degradation, photodegradation, catalytic or enzymatic degradation, oxidative degradation, ion degradation, and biodegradation.
The term “polymerizable compound” means a compound containing one or more polymerizable groups. The term encompasses, for instance, monomers, macromers, oligomers, prepolymers, cross-linkers, and the like.
As used herein, “polymerizable groups” are groups that can undergo chain growth polymerization, such as free radical and/or cationic polymerization, for example a carbon-carbon double bond which can polymerize when subjected to radical polymerization initiation conditions. Non-limiting examples of free radical polymerizable groups include (meth)acrylates, styrenes, vinyl ethers, (meth)acrylamides, N-vinyllactams, N-vinylamides, O-vinylcarbamates, O-vinylcarbonates, and other vinyl groups. Preferably, the free radical polymerizable groups comprise (meth)acrylate, (meth)acrylamide, N-vinyl lactam, N-vinylamide, polyester polyols, poloxamers, and styryl functional groups, and mixtures of any of the foregoing. Preferably, the free radical polymerizable groups include (meth)acrylates, (meth)acrylamides, polyester polyols, poloxamers, and mixtures thereof. The polymerizable group may be unsubstituted or substituted. For instance, the nitrogen atom in (meth)acrylamide may be bonded to a hydrogen, or the hydrogen may be replaced with alkyl or cycloalkyl (which themselves may be further substituted).
The term “polyurethane,” as used herein, refers to a polymeric reaction product of an isocyanate and a polyol, and is not limited to those polymers which include only urethane or polyurethane linkages. It is well understood by those of ordinary skill in the art of preparing polyurethanes that the polyurethane polymers may also include linkages such as allophanate, carbodiimide, and other linkages described herein in addition to urethane linkages.
Any type of free radical polymerization may be used including but not limited to bulk, solution, suspension, and emulsion as well as any of the controlled radical polymerization methods such as stable free radical polymerization, nitroxide-mediated living polymerization, atom transfer radical polymerization, reversible addition fragmentation chain transfer polymerization, organotellurium mediated living radical polymerization, and the like.
The expressions “reaction system,” “reactive formulation,” “reaction product,” and “reactive mixture” are interchangeably used herein, and all refer to a combination of reactive compounds used to make the bioabsorbable material according to the disclosure.
The term “room temperature” refers to temperatures of about 20° C., this means referring to temperatures in the range 18° C. to 25° C. Such temperatures will include 18° C., 19° C., 20° C., 21° C., 22° C., 23° C., 24° C. and 25° C.
Unless otherwise expressed, the “weight percentage” (indicated as % wt. or wt. %) of a component in a composition refers to the weight of the component over the total weight of the composition in which it is present and is expressed as percentage.
“Glass transition temperature” and “Tg” as referred to herein refers to the temperature at which a reversible transition from a hard glass condition into a rubber-elastic condition occurs.
Surgical stapling assemblies and methods for manufacturing and using the same are provided. In general, a surgical stapling assembly can include a staple cartridge having staples disposed therein and an adjunct configured to be releasably retained on the staple cartridge. As discussed herein, the various adjuncts provided can be configured to compensate for variations in tissue properties, such as variations in tissue thickness, and/or to promote tissue ingrowth when the adjuncts are stapled to tissue. As discussed herein, an adjunct can include a bioabsorbable material, such as a foam.
An exemplary stapling assembly can include a variety of features to facilitate application of a surgical staple, as described herein and illustrated in the drawings. However, a person skilled in the art will appreciate that the stapling assembly can include only some of these features and/or it can include a variety of other features known in the art. The stapling assemblies described herein are merely intended to represent certain exemplary examples. Moreover, while the adjuncts are described in connection with surgical staple cartridge assemblies, the adjuncts can be used in connection with staple reloads that are not cartridge based or any type of surgical instrument.
In various instances, the end effector 106 can be manipulated by a handle 112 connected to the elongate shaft 108. The handle 112 can include user controls such as a rotation knob 114 that rotates the elongate shaft 108 and the end effector 106 about a longitudinal axis (Ls) of the elongate shaft 108 and an articulation control 115 that can articulate the end effector 106 about an articulate axis (TA) that is substantially transverse to the longitudinal axis (Ls) of the elongate shaft 108. Further controls include a closure trigger 116 which can pivot relative to a pistol grip 118 to close the end effector 106. A closure release button 120 can be outwardly presented on the handle 112 when the closure trigger 116 is clamped such that the closure release button 120 can be depressed to unclamp the closure trigger 116 and open the end effector 106, for example. Handle 112 may also take the form of an interface for connection to a surgical robot.
In some examples, a firing trigger 122, which can pivot relative to the closure trigger 116, can cause the end effector 106 to simultaneously sever and staple tissue clamped therein. The firing trigger 122 may be powered, require force from a user to engage, or some combination thereof. A manual firing release lever 126 can allow the firing system to be retracted before full firing travel has been completed, if desired, and, in addition, the firing release lever 126 can allow a surgeon, or other clinician, to retract the firing system in the event that the firing system binds and/or fails.
Additional details on the surgical stapling and severing device 100 and other surgical stapling and severing devices suitable for use with the present disclosure are described, for example, in U.S. Pat. No. 9,332,984 and in U.S. Patent Publication No. 2009/0090763, the disclosures of which are incorporated herein by reference in their entireties. Further, the surgical stapling and severing device need not include a handle, but instead can have a housing that is configured to couple to a surgical robot, for example, as described in U.S. Patent Publication No. 2019/0059889, the disclosure of which is incorporated herein by reference in its entirety.
As further shown in
The illustrated staple cartridge 200 includes staple cavities 212, 214 defined therein, in which each staple cavity 212, 214 is configured to removably house at least a portion of a staple (not shown). The number, shape, and position of the staple cavities can vary and can depend at least on the size and shape (e.g., mouth-like shape) of the staples to be removably disposed therein. In this illustrated example, the staple cavities are arranged in two sets of three longitudinal rows, in which the first set of staple cavities 212 is positioned on a first side of the longitudinal slot 210 and the second set of staple cavities 214 is positioned on a second side of the longitudinal slot 210. On each side of the longitudinal slot 210, and thus for each set of rows, a first longitudinal row of staple cavities 212a, 214a extends alongside the longitudinal slot 210, a second row of staple cavities 212b, 214b extends alongside the first row of staple cavities 212a, 214a, and a third row of staple cavities 212c, 214c extends alongside the second row of staple cavities 212b, 214b. Each row may be approximately parallel and the staple cavities that make up the rows may be approximately parallel in orientation with the longitudinal slot 210. As shown in
The staples releasably stored in the staple cavities 212, 214 can have a variety of configurations. An exemplary staple 300 that can be releasably stored in each of the staple cavities 212, 214 is illustrated in
In use, staples 300 can be deformed from an unfired position into a fired position such that the staple legs 304 move through the staple cavities 212, 214, penetrate tissue positioned between the anvil 102 and the staple cartridge 200, and contact the anvil 102. As the staple legs 304 are deformed against the anvil 102, the legs 304 of each staple 300 can capture a portion of the tissue within each staple 300 and apply a compressive force to the tissue. Further, the legs 304 of each staple 300 can be deformed downwardly toward the crown 302 of the staple 300 to form a staple entrapment area in which the tissue can be captured therein. In various instances, the staple entrapment area can be defined between the inner surfaces of the deformed legs and the inner surface of the crown of the staple. The size of the entrapment area for a staple can depend on several factors such as the length of the legs, the diameter of the legs, the width of the crown, and/or the extent in which the legs are deformed, for example.
In some examples, all of the staples disposed within the staple cartridge 200 can have the same unfired (pre-deployed, unformed) configuration. In other examples, the staples can include at least two groups of staples each having a different unfired (pre-deployed, unformed) configuration, e.g., varying in height and/or shape, relative to one another, etc.
Referring back to
With reference to
In use, the anvil 102 in
To deploy staples from the staple cartridge, as discussed above, the sled 500 in
As indicated above, the stapling device can be used in combination with a compressible adjunct. A person skilled in the art will appreciate that, while adjuncts are shown and described below, the adjuncts disclosed herein can be used with other surgical instruments and need not be coupled to a staple cartridge as described. Further, a person skilled in the art will also appreciate that the staple cartridges need not be replaceable.
As discussed above, with some surgical staplers, a surgeon is often required to select the appropriate staples having the appropriate staple height for tissue to be stapled. For example, a surgeon will utilize tall staples for use with thick tissue and short staples for use with thin tissue. In some instances, however, the tissue being stapled does not have a consistent thickness and thus, the staples cannot achieve the desired fired configuration for every section of the stapled tissue (e.g., thick and thin tissue sections). The inconsistent thickness of tissue can lead to undesirable leakage and/or tearing of tissue at the staple site when staples with the same or substantially greater height are used, particularly when the staple site is exposed to intra-pressures at the staple site and/or along the staple line.
Accordingly, various examples of adjuncts are provided that can be configured to compensate for varying thickness of tissue that is captured within fired (deployed) staples to avoid the need to take into account staple height when stapling tissue during surgery. That is, the adjuncts described herein can allow a set of staples with the same or similar heights to be used in stapling tissue of varying thickness (e.g., from thin to thick tissue) while also, in combination with the adjunct, providing adequate tissue compression within and between fired staples. Thus, the adjuncts described herein can maintain suitable compression against thin or thick tissue stapled thereto to thereby minimize leakage and/or tearing of tissue at the staple sites. In addition, exemplary adjuncts described herein may be configured to be absorbed in the body over a period of 100 to 300 days depending on implanted location and tissue health.
Alternatively, or in addition, the adjuncts can be configured to promote tissue ingrowth. In various instances, it is desirable to promote the ingrowth of tissue into an implantable adjunct, to promote the healing of the treated tissue (e.g., stapled and/or incised tissue), and/or to accelerate the patient's recovery. More specifically, the ingrowth of tissue into an implantable adjunct may reduce the incidence, extent, and/or duration of inflammation at the surgical site. Tissue ingrowth into and/or around the implantable adjunct may, for example, manage the spread of infections at the surgical site. The ingrowth of blood vessels, especially white blood cells, for example, into and/or around the implantable adjunct may fight infections in and/or around the implantable adjunct and the adjacent tissue. Tissue ingrowth may also encourage the acceptance of foreign matter (e.g., the implantable adjunct and the staples) by the patient's body and may reduce the likelihood of the patient's body rejecting the foreign matter. Rejection of foreign matter may cause infection and/or inflammation at the surgical site.
In general, the adjuncts provided herein are designed and positioned atop a staple cartridge, like staple cartridge 200. When the staples are fired (deployed) from the cartridge, the staples penetrate through the adjunct and into tissue. As the legs of the staple are deformed against the anvil that is positioned opposite the staple cartridge, the deformed legs capture a portion of the adjunct and a portion of the tissue within each staple. That is, when the staples are fired into tissue, at least a portion of the adjunct becomes positioned between the tissue and the fired staple. While the adjuncts described herein can be configured to be attached to a staple cartridge, it is also contemplated herein that the adjuncts can be configured to mate with other instrument components, such as an anvil of a surgical stapler. A person of ordinary skill will appreciate that the adjuncts provided herein can be used with replaceable cartridges or staple reloads that are not cartridge based.
In various embodiments, the adjunct or bioabsorbable materials disclosed herein can be comprised of an absorbable polymer. In certain embodiments, an adjunct can be comprised of foam, film, fibrous woven, fibrous non-woven polyurethane, polyether urethane, polyester urethane, polyester urea, polyester, polycarbonate, polyorthoester, polyanhydride, polyesteramide, polyphosphazenes, polyphosphoesters, polysaccharides, and/or polyoxaester. In other embodiments, an adjunct can be a copolymer including, for example, PGA (polyglycolic acid), PGA/PCL (poly(glycolic acid-co-caprolactone)), PLA/PCL (poly(lactic acid-co-polycaprolactone)), PLLA/PCL, PGA/TMC (poly(glycolic acid-co-trimethylene carbonate)), PDS, PEPBO, and the like. In various embodiments, an adjunct can include an organic material such as, for example, carboxymethyl cellulose, sodium alginate, hyaluronic acid, and/or oxidized regenerated cellulose. In various embodiments, an adjunct has a durometer in the 3-7 Shore A (30-50 Shore OO) ranges with a maximum stiffness of 15 Shore A (65 Shore OO). In certain embodiments, an adjunct can undergo 40% compression under 3 lbf load, 60% compression under 6 lbf load, and/or 80% compression under 20 lbf load, for example. In certain embodiments, one or more gasses, such as air, nitrogen, carbon dioxide, and/or oxygen, for example, can be bubbled through and/or contained within the adjunct.
In the illustrated example, the adjunct 604 can be mated to at least a portion of the top surface or deck surface 206 of the staple cartridge 602. In some examples, the top surface 206 of the staple cartridge 200 can include one or more surface features which can be configured to engage the adjunct 604 to avoid undesirable movements of the adjunct 604 relative to the staple cartridge 200 and/or to prevent premature release of the adjunct 604 from the staple cartridge 200. Exemplary surface features are described further below and in U.S. Pat. No. 10,052,104, which is incorporated by reference herein in its entirety.
The adjunct 604 is compressible to permit the adjunct to compress to varying heights to thereby compensate for different tissue thickness that are captured within a deployed staple. The adjunct 604 has an uncompressed (undeformed), or pre-deployed, height and is configured to deform to one of a plurality of compressed (deformed), or deployed, heights. For example, the adjunct 604 can have an uncompressed height which is greater than the fired height of the staples 300 disposed within the staple cartridge 200 (e.g., the height (H) of the fired staple 300a in
In use, once the surgical stapling and severing device, like device 100 in
As shown in
Referring to
The cartridge 200 has a height CH of about 6.3 mm to about 8.1 mm, a width CW of about 8.9 mm to about 14 mm, and a length CL of about 80 mm to about 90 mm such as about 86.7 mm.
The staple cartridge 200 may include one or more raised ledges 804 along one or more sides of the adjunct 604 to help align the adjunct 604 on the deck of the staple cartridge 200. Although not shown in
Balancing mechanical property depletion with backbone absorption of the adjunct after delivery may be improved with a dual phase degradation mechanism. As described above, the end effector 106 (shown in
Turning to
In some embodiments, the first polymerizable compound can be a reaction product of a polyol and an isocyanate, forming a polyurethane or polyurethane derivate. The polyurethane is configured to degrade according to a first degradation profile. An aliphatic polyurethane primarily undergoes oxidative and/or enzymatic mechanisms of absorption. To maintain the mechanical properties when firing the staples while tuning the absorption profile after minutes, hours, days, or weeks after delivery, a second polymerizable compound is added. The second polymerizable compound is configured to degrade according to a second degradation profile. In some examples, the second polymerizable compound can adjust an induction period for absorption, thereby delaying bulk absorption of the adjunct 604. In some instances, the physiological conditions at the delivery site can be used to accelerate absorption of at least one of the first polymerizable compound and/or the second polymerizable compound.
As described herein, the surgical adjunct 604 can be tuned for the particular purpose before, during, and after surgical procedures. The adjunct 604 includes a first polymerizable compound that has a first degradation profile and a second polymerizable compound with a second degradation profile different than the first. In particular, the adjunct 604 described can be a polymer with tunable absorption properties via an alternating copolymer, a random copolymer, a block copolymer, a multiblock copolymer architecture, a terpolymer, a graft copolymer (monomer backbone with pendant chains of a different monomer), a bulk homopolymer coated with a second homopolymer, and the like.
In some embodiments, the second polymerizable compound can be a polyester, a poloxamer, a polymethacrylate, a polyether, a polydioxanone, a polyanhydride, a hydroxypropyl methylcellulose acetate succinate, a cellulose acetate phthalate, a cellulose acetate trimellitate, a hydroxypropyl methylcellulose phthalate, a polyvinyl acetate phthalate, a poly(trimethylene carbonate), a poly(beta-thioether ester ketal), a polypropylene fumarate, a poly(ester urea), a poly(ester amide).
In some embodiments, the first polymerizable compound alone has a suitable degradation profile for healing tissue within approximately 6 weeks. In some embodiments, it is desirable to tune the degradation profile of the adjunct 604 for longer degradation profiles. In some embodiments, the bioabsorption rate of the adjunct 604 can be tuned by adding more or less of the second polymerizable compound to the first polymerizable compound. In general, the adjunct 604 can have approximately equal parts of the first polymerizable compound to second polymerizable compound. In certain other embodiments, the volumetric ratio of first polymerizable compound to second polymerizable compound can range from about 10:0.1 to about 0.1:10. For instance, when it is desirable to have a longer degradation profile, the volumetric ratio can be approximately 10:1, about 10:2, about 10:3, or about 10:4. As another non-limiting example, to tune the degradation profile to shorter periods of time, the volumetric ratio can be approximately 1:10, approximately 2:10, approximately 3:10, or approximately 4:10. As would be appreciated by one of skill in the relevant art, tuning the degradation profile of the adjunct as a whole can be done through adjusting the type, molecular weight, and quantity of first polymerizable compound to second polymerizable compound.
In some embodiments, the second polymerizable compound can be added to the polyurethane backbone such that the first and second polymerizable compounds together form a copolymer backbone. When the second polymerizable compound is added to the polyurethane backbone, the second polymerizable compound can be one of the polyol or the isocyanate. For instance, the second polymerizable compound can be a polyester polyol that when added to the first polymerizable compound, the polyester polyol can replace the polyol of the polyurethane reaction product to form a block copolymer or an alternating copolymer. Alternatively, or in addition thereto, the polyester polyol can be in addition to the polyol of the polyurethane reaction product such that more than one type of polyol monomer is introduced into the backbone of the polyurethane, such as in a block copolymer (A-B-A style) or a random copolymer.
The inclusion of an aliphatic polyester polyol as the second polymerizable compound, can add another degree of freedom in a polyurethane backbone to tune the absorption and mechanical properties of the adjunct 604. Above a certain molecular weight, mechanical toughening can occur through crystallization that effectively adds crosslinks to the polyurethane system and thus allow for lower covalent crosslinks overall. In general, reducing the number of covalent crosslinks can result in an accelerated degradation profile of the adjunct 604.
In addition to the change in crosslinking density, the addition of the second polymerizable compound such as polyester polyols, can increase the backbone susceptibility to hydrolysis mechanism of absorption. Under a hydrolysis mechanism pathway, the sensitivity to acidic conditions could be used to preferentially increase the absorption rate or degradation profile of the adjunct 604 in the presence of lower pH.
The typical polyester polyol is branched with a weight average molecular weight (Mw) of 2,000-10,000. Polyester polyols are typically made from mixtures of diols, triols, and dibasic acids or anhydrides. Polyether polyols are made by the reaction of epoxides with compounds having active hydrogen atom. Polyester polyols are made by the polycondensation reaction of multifunctional carboxylic acids and polyhydroxyl compounds. Example polyester polyol monomers include, without limitation, poly(hexamethylene adipate) (PHA), aminocaproic acid, hexamethylenediamine adipate (1:1), 6-aminiohexanoate, 1,4-butanediamine adipate, hexanedioic acid undecane-1,11-diamine, 6-diaminohexanoic acid, calcium bis(6-aminohexanoate), 6-aminohexanoyloxidanium, 6-aminohexanoic acid, octane-1,8-diamine hexanedioic acid, ethane-1,1,2-triamine hexanedioic acid, pentane-1,5-diamine heptanedioic acid, hexane-1,1-diamine hexanedioic acid, butane-1,1-diamine hexanedioic acid, (2S)-2,6-diaminohexanoic acid hexanedioic acid, heptane-1,6-diamine hexanedioic acid, 2-aminoacetic acid 2,6-diaminohexanoic acid, 2,6-diaminohexanoic acid hexanedioic acid, 2-aminoacetic acid (2S)-2,6-diaminohexanoic acid, cadaverine adipate, cadaverine adipate dihydrate, hexanedioic acid nonane-1,9-diamine, 6-aminocaproic acid-d6, 6-amino-2,2,6,6-tetradeuteriohexanoic acid, 6-aminohexanoic acid butanedioic acid, 6-amino-6,6-dideuteriohexanoic acid, 6-amino-2,2-dideuteriohexanoic acid, hexanedioic acid propan-1-amine, hexane-1,6-diamine octanedioic acid, 6-aminohexanoic acid hexanedioic acid, 6-(6-aminohexanoyloxy)-6-oxohexanoic acid, hexan-1-amine hexanedioic acid, 6-aminohexanoic acid carbamic acid, 2-aminoacetic acid 6-aminohexanoic acid, 6-aminohexanoic acid 3-aminopropanoic acid, ethane-1,2-diamine hexanedioic acid, 7-aminoheptanoic acid hexane-1,6-diamine, 6-aminohexanoic acid (2s)-2,6-diaminohexanoic acid, 6-aminohexanoic acid 3-aminopropanoic acid, butane-1,4-diamine heptanedioic acid, 6-amino-6-oxohexanoic acid hexane-1,6-diamine, acetic acid 6-aminohexanoic acid, 6-aminohexanoic acid azane, ethanamine hexanedioic acid, 4-aminobutanoic acid 6-aminohexanoic acid, 6-aminohexanoyl 6-aminohexaneperoxoate, 6-aminohexanoic acid ethane-1,2-diamine, 5-azaniumylpentylazanium hexanedioate, heptane-1,1-diamine hexanedioic acid, amino hexanoate 6-aminohexanoic acid, decane-1,10-diamine hexanedioic acid, ethane-1,2-diamine hexanedioic acid, 6-azaniumylhexylazanium hexanedioate hexanedioic acid, 6-(dideuterioamino) hexanoic acid, 7-aminoheptanoic acid 6-aminohexanoic acid, hexane-1,5-diamine hexanedioic acid, 6-aminohexanoic acid hexanoic acid, hexamethylendiammonium-adipat-dihydrat, tetramethylene diammonium adipate, 6-aminohexanoic acid hexane-1,6-diamine, 6-(4-aminobutylamino)oxy-6-oxohexanoic acid, hexane-1,6-diamine 6-hydroxyhexanoic acid, 6-azaniumylhexylazanium hexanedioate hydrate, 6-aminohexanoic acid hydrate, 6-aminohexanoic acid methylideneazanium, 6-aminohexanoic acid ethane molecular hydrogen, 6-aminohexanoic acid methanamine, heptane-1,7-diamine heptanedioic acid, 6-aminohexanoic acid ethane fermium cyanide, 5-carboxypentylazanide, 6-(6-aminohexylamino)oxy-6-oxohexanoic acid, 6-aminohexanoic acid zinc, octanedioic acid pentane-1,5-diamine, azanium 6-aminohexanoic acid, 6-aminohexanoic acid 2,6-diaminohexanoic acid, carbamic acid hexane-1,6-diamine hexanedioic acid, 6-(6-aminohexylamino)oxy-6-oxohexanoic acid methane, azanium 6-azaniumylhexylazanium hexanedioate, butan-1-amine hexanedioic acid, heptan-1-amine hexanedioic acid, 6-aminohexanoic acid 8-aminooctanoic acid, 7-aminoheptanoic acid heptanedioic acid, hexanedioic acid pentane-1,1-diamine, N-(6-aminohexyl) hydroxylamine hexanedioic acid, 6-azaniumylhexylazanium hexanedioic acid, 6-aminohexanoic acid ethane, 6-aminohexanoic acid hydrate, 7-azaniumylheptylazanium hexanedioate, butane-1,4-diamine hexanoic acid, 4-aminobutanoic acid; 6-aminohexanoic acid; 3-aminopropanoic acid, and 6-aminohexanoate.
In some embodiments, an adjunct 604 that has a hydroxy-terminated polymer chain can enhance the biodegradation profile. A stoichiometric excess of hydroxyl over carboxylic acid functionality ensures that the finished polymer is hydroxy-terminated, whereas a carboxyl excess leads to carboxylic acid-terminated polyesters. Branching can be incorporated into the polyester backbone using trifunctional monomers such as trimethylolpropane, 2,2-di(hydroxymethyl)-1-butanol, or trimellitic anhydride.
Polyether polyols are the most common type of polyols. Polyether polyols are made by the reaction of epoxides with compounds having active hydrogen atom. The typical polyester polyol. Polyether polyols have low glass transition temperature (Tg), which imparts good retention of physical properties and impact resistance at very low temperatures. In general polyether-based polyurethanes exhibit higher rebound (resilience) compared to polyester-based polyurethanes. Example polyether polyol monomers include, without limitation, polyethylene glycol, polytetramethylene ether glycol, polypropylene oxide glycol, polybutylene oxide glycol, triethylene glycol monoethyl ether, 1,2-diethoxyethane 2-[2-(2-methoxyethoxy)ethoxy]ethanol, 1,2-diethoxyethane 2-methoxyethanol, 2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethanol methane, 1-ethoxy-2-methoxyethane 2-methoxyethanol, methane 2-[2-(2-methoxyethoxy)ethoxy]ethanol hydrate, methanol 2-[2-(2-methoxyethoxy)ethoxy]ethanol, 2-(2-(2-(2-(2-(2-ethoxyethoxy)ethoxy)ethoxy)ethoxy)ethoxy)ethanol, 2-[2-(2-ethoxyethoxy)ethoxy]ethanol hydrate, 2,5,8,11-tetraoxatridecan-13-ol, 2-(2-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-ethoxy)-ethanol, 2,5,8,11,14,17-hexaoxanonadecan-19-ol, 3,6,9,12-tetraoxatetradecan-1-ol, 3,6,9,12,15-pentaoxaheptadecan-1-ol, 4,7,10,13-tetraoxa-1-oxoniacyclopentadecane, pentaethylene glycol-water, 2-[2-[2-[2-(2-ethoxyethoxy)ethoxy]ethoxy]ethoxy]ethanol, butane ethane-1,2-diol 2-propoxyethanol, butane 2-ethoxyethanol, ethanol, 2,2′-[1,2-ethanediylbis(oxy)]bis-, mixt. with 2,2′-oxybis [ethanol], 3,6,9,12,15-pentaoxaoctadecan-1-ol, 3,6,9,12-tetraoxapentadecan-1-ol, 2-(2-(2-propoxyethoxy)ethoxy) ethanol, pentaethylene glycol, hexaethylene glycol, tetraethylene glycol, triethylene glycol monomethyl ether, sodium 1,4,7,10,13,16-hexaoxoniacyclooctadecane, sodium 1,4,7,10,13-pentaoxoniacyclopentadecane, sodium 1,4,7,10-tetraoxoniacyclododecane, potassium 1,4,7,10,13-pentaoxoniacyclopentadecane, ytterbium 2-methoxyethoxide, cerium 2-methoxyethoxide, 2-[2-[2-(2-propoxyethoxy)ethoxy]ethoxy]ethanol, neodymium methoxyethoxide, erbium methoxyethoxide, ethanol 2-(2-hydroxyethoxy) ethanol pentane, butyl carbitol water, 2-[2-[2-(2-hydroxyethoxy)ethoxy]ethoxy]ethyl hypofluorite, lanthanum methoxyethoxide, 2-[2-(2-butoxyethoxy)ethoxy]ethanol propane, potassium 1,4,7,10,13,16-hexaoxoniacyclooctadecane, 2-[2-[2-[2-(2-hydroxyethynoxy)ethoxy]ethoxy]ethoxy]ethanol, 3,6,9,12,15,18-hexaoxahenicosan-1-ol, triethylene glycol-water, yttrium methoxyethoxide, heptaethylene glycol monomethyl ether, 2-(2-(2-ethoxyethoxy)ethoxy), 3,6,9,12,15,18-hexaoxaicosane-1,20-diol, 3,6,9,12,15-pentaoxanonadecan-1-ol, 3,6,9,12-tetraoxahexadecan-1-ol, triethylene glycol monobutyl ether, and the like.
Adding portions of the adjunct 604 with varying degrees of hydrophilicity can allow the adjunct to undergo a phase change upon exposure to a fluid. As the hydrophilicity increases, the adjunct will move from surface to bulk degradation due to the increased water ingress. In some examples, as the fluid swells the network, a material having the same polarity as the polymer may pass through a lower critical solution temperature (LCST). In general, the LCST is the critical temperature below which the components of a mixture are miscible in all proportions. In some embodiments, the polymer system in solution has an LCST at a temperature higher than the upper critical solution temperature (UCST), meaning that there is a temperature interval of complete miscibility, with partial miscibility at both higher and lower temperatures. The UCST is the critical temperature above which the components of a mixture are miscible in all proportions.
For polymers in a solution or fluid, the LCST depends on the polymer's degree of polymerization, polydispersity, branching, composition, and architecture. At temperatures below the LCST, portions of the polymer in solution or fluid are completely miscible in all proportions, whereas above the LCST, partial liquid miscibility occurs.
In some embodiments, adjunct 604 can include certain segments of a block copolymer that have an LCST ranging from approximately 20° C. to approximately 35° C. This allows at least a portion of the adjunct to undergo a phase transition at lower temperatures compared to a polyurethane backbone. Upon passing through the LCST, one of the polar or non-polar portions of the adjunct can micellize and form effective crosslinks within the system. In this manner, the fluid content increase due to fluid ingress can cause the adjunct to undergo a phase transition from one to two phases and then back to one phase. During the one phase, miscible period, the adjunct 604 has a low mechanical strength, which is desirable during deployment. During the two phase, immiscible period, fluid is absorbed into the adjunct 604 and the mechanical strength increases due to the effective increase in crosslinking that counterbalances the breakdown of the adjunct 604. Once a critical level is reached, the crosslinks can be disrupted, and the mechanical strength of the adjunct will decrease. This phase change allows for both low deployment forces and faster absorbing adjuncts since the critical phase of the healing process has reversible crosslinks.
In some embodiments, the second polymerizable compound can be a poloxamer added into the backbone of the polyurethane. Poloxamers are a class of water-soluble nonionic triblock copolymers formed by polar (polyethylene oxide) and non-polar (polypropylene oxide) blocks. Poloxamers can result in amphiphilic and surface-active properties to the polymer backbone. In some embodiments, increasing the water ingress into the polar portion of the adjunct 604 can promote faster absorption kinetics. The LCST is dependent on the polypropylene oxide segment length and relative water content.
In any of the embodiments described herein, the second polymerizable compound can be added as pendant groups to the first polymerizable compound backbone such that the second polymerizable compound forms a coating. The coating can act to prevent or delay the fluid ingress to the first polymerizable compound.
In some embodiments, the second polymerizable compound can act as an enteric coating in the presence of gastric fluid, or near an infection. The coating can be resistant or substantially resistant to absorption at certain pH, such as, for example, acidic conditions (pH<7) such that the coating can be used for tissue at or near the stomach. In other examples, the coating can delay absorption time for a predetermined timeframe and prevent the bulk material of the adjunct from contacting fluids. Gastric and infected fluids tend to have a lower pH than other locations in the body. Using an adjunct 604 with a second polymerizable compound that is resistant to degradation under acidic conditions can be beneficial when treating tissue near stomach, gastrointestinal tract, or other acidic areas of the body. In general, the retention of mechanical strength of the adjunct 604 is a function of absorption and fluid ingress. The second polymerizable compound can prevent or slow fluid penetration at lower pH's. As the pH increases, fluid is allowed to pass through the coating and initiate the degradation of the first polymerizable compound. The second polymerizable compound can be tailored to have a specific induction period based on pH by adjusting the composition, thickness, branching, and the like.
In some embodiments, the second polymerizable compound can be a polymethacrylate based copolymer with specific carboxylic acid functionalization. In addition, the second polymerizable compound can also include as a copolymer with or without the polymethacrylate, without limitation, a polydioxanone, a polyanhydride, a hydroxypropyl methylcellulose acetate succinate, a cellulose acetate phthalate, a cellulose acetate trimellitate, a hydroxypropyl methylcellulose phthalate, a polyvinyl acetate phthalate, a poly(trimethylene carbonate), a poly(beta-thioether ester ketal), a polypropylene fumarate, a poly(ester urea), a poly(ester amide), or combinations thereof.
In addition to a single enteric coating layer, the second polymerizable compound also forms a multilayer construct to provide additional advantages independent of the local pH environment. In some embodiments, the second polymerizable compound can form an acid-generating surface of the adjunct such that the enteric coating is maintained as additional protons or acid species are generated. This would extend the induction period provided by the enteric coating and further prevent any fluid ingress. As the surface eroding polymer degrades to a critical point, such as when the enteric coating is in the presence of a neutral pH, fluid ingress may proceed and allow for stapling implant absorption. In some embodiments, a multilayer construct may exist as a bilayer. In any embodiment described herein, the bilayer or multilayer construct can include active pharmaceutical ingredients (API's) that could be released as the surface eroding polymer degrades. Example acid-generating polymers can include, without limitation, polyanhydrides such as poly(carboxyphenoxy hexane-sebacic acid), poly(fumaric acid-sebacic acid), poly(imide-sebacic acid), and poly(imide-carboxyphenoxy hexane). Other acid-generating polymers can include 3-iodopropyl acetal moieties.
In some embodiments, when the second polymerizable compound forms a coating, the composition and/or thickness of the coating can provide an induction period for the absorption and/or degradation process. The initial thickness of the second polymerizable compound coating prior to delivery and/or an induction period can range from about 20 μm to about 100 μm (e.g., from about 30 μm to about 90 μm, from about 40 μm to about 60 μm, from about 45 μm to about 50 μm, and any range in between). Upon exposure to a temperature or a pH, the thickness of the second polymerizable compound coating may increase depending on the compression of the tissue required to reach a hemostatic seal.
As would be appreciated by one of skill in the art, the addition of the second polymerizable compound can be done with spatial control for optimal absorption, tissue in-growth, and/or hemostatic behavior. Further, the composition of the first and second polymerizable compound can be a gradient along a portion of the adjunct 604 (e.g., along a length, at a central point, at the ends, along the staple line, etc.,) with a varying bio-absorption profile. In general, a short-term absorption profile may be preferred to address hemostasis while a long-term absorption profile may address better tissue healing without leakages.
In some embodiments, adding the second polymerizable compound to the backbone, as pendant groups to the first polymerizable compound, or as a coating, can be done through any suitable technique including, without limitation, inkjet printing, direct deposition, thermal spraying, cold dynamic spraying, cold spraying, electro spraying, ultrasonic spray coating, dip coating, screen printing, spin coating, solution deposition, stereolithography, exterior lamination, and the like.
In some embodiments, the change in crosslink density between the first polymerizable compound and the second polymerizable compound forms a gradient of compression strength along a portion of the adjunct 604. In general, the adjunct 604 may have a compression strength of about 20 kPa to about 70 kPa, such as about 30 kPa to about 60 kPa (e.g., about 42 kPa), about 30 kPa to about 50 kPa, about 32.5 kPa to about 37.5 kPa. In some embodiments, the adjunct 604 may have a compression strength of about 20 kPa to about 70 kPa due to a portion of the adjunct 604 having the first polymerizable compound, and a compression strength of about 15 kPa to about 50 kPa due to a portion of the adjunct 604 having the second polymerizable compound.
In some examples, the adjunct 604 may have a tensile strength of about 30 kPa to about 90 kPa such as about 45 kPa to about 85 kPa or about 55 kPa to about 75 kPa. In some examples, the adjunct 604 will have tensile strength of about 110 kPa to about 150 kPa.
In any of the embodiments disclosed herein, the adjunct having a block copolymer having the first polymerizable compound and the second polymerizable compound can modulate the degradation profile of the adjunct (and the mechanical properties of the bioabsorbable material) for a predetermined time frame. For instance, a phase change may occur over several seconds or minutes such that during delivery, the porous body is readily compressible, and the end effector is easily inserted through the trocar. After the induction period passes, the mechanical strength of the adjunct 604 increases to allow for a suitable hemostatic seal between the tissue. This increased mechanical strength after the induction period can range from approximately 10 minutes to approximately 6 weeks, the amount of time that may be necessary for the tissue to heal.
Turning back to
Specifically with respect to
As will be appreciated by one skilled in the art, The embodiments described above are cited by way of example, and the present invention is not limited by what has been particularly shown and described hereinabove. Rather, the scope of the invention includes both combinations and sub combinations of the various features described hereinabove, as well as variations and modifications thereof which would occur to persons skilled in the art upon reading the foregoing description and which are not disclosed in the prior art.
In some examples, disclosed devices (e.g., end effector, surgical adjunct, and/or staple cartridges) and methods involving one or more disclosed devices may involve one or more of the following clauses:
This application claims priority under 35 U.S.C. § 119 to U.S. Provisional Patent Application No. 63/522,660, filed Jun. 22, 2023, the entire contents of which are fully incorporated herein by reference.
| Number | Date | Country | |
|---|---|---|---|
| 63522660 | Jun 2023 | US |
