WO2022150498A1 - Compositions et procédés de fixation de cathéter - Google Patents

Compositions et procédés de fixation de cathéter Download PDF

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Publication number
WO2022150498A1
WO2022150498A1 PCT/US2022/011471 US2022011471W WO2022150498A1 WO 2022150498 A1 WO2022150498 A1 WO 2022150498A1 US 2022011471 W US2022011471 W US 2022011471W WO 2022150498 A1 WO2022150498 A1 WO 2022150498A1
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WO
WIPO (PCT)
Prior art keywords
catheter
adhesive composition
cyanoacrylate
vascular access
radiation
Prior art date
Application number
PCT/US2022/011471
Other languages
English (en)
Inventor
Sheng Zhang
Amanda Guido
Original Assignee
Adhezion Biomedical, Llc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US17/569,168 external-priority patent/US20220218951A1/en
Application filed by Adhezion Biomedical, Llc filed Critical Adhezion Biomedical, Llc
Priority to CN202280019370.2A priority Critical patent/CN117062636A/zh
Priority to EP22703470.9A priority patent/EP4274628A1/fr
Publication of WO2022150498A1 publication Critical patent/WO2022150498A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
    • A61L29/04—Macromolecular materials
    • A61L29/041—Macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds

Definitions

  • One of the most common complications associated with catheter insertion includes migration, dislodgement, micromovement, and infiltration.
  • Patient movement and frequent dressing changes can cause large-scale movement of the catheter, sometimes resulting in dislodgement and requiringa new catheter to be inserted.
  • Small-scale catheter movement also known as “pistoning,” irritatesthe vessel wall and is believed to lead to the development of phlebitis, the most common complication associated with catheter use.
  • catheter failure rate is as high as 50%. Reducing the frequency of complications associated with catheter movement can, in turn, reduce the occurrence of needle stick injuries forhealth care workers and prevent otherwise unnecessary costs for hospital stays.
  • CBSI catheter-related bloodstream infections
  • Common skin microbes including coagulase-negative staphylococci, S. aureus , and enterococci, can migrate to the catheter insertion site and colonize the catheter hub and tubing.
  • Astudy conducted on 1,681 IV catheters found that after their use 33.8% were colonized and 12.3% were infected, with roughly a third of the infected catheters corresponding to a bloodstream infection.
  • HAI Hospital-acquired infections
  • the severity of bleeding from the insertion site varies at different insertion site locations. As an example, bleeding complications for central venous catheters (CVC) are reported in up to 1.6% of cases that frequently require medical intervention.
  • CVC central venous catheters
  • the current standard of care if bleeding occurs at the insertion site is to utilize gauze compressions and frequent dressing changes until the bleeding subsides.
  • the ability to provide hemostasis at the insertion site has the potential to increase patient comfort while decreasing the overall length and cost associated with hospital stays. Therefore, it would be desirable to find a solution that can not only secure the intravascular catheter tubing and hub but also provide a hemostatic effect at the insertion site.
  • This invention provides compositions and methods which can significantly increase the securement strength of catheters, the peel strength of transparent dressing products over catheters, provide antibacterial property and thus potentially reduce blood stream infections, are capable of providing effective hemostasis and sealing at the catheter insertion site, and have a shelf life stability of at least 24 months post gamma and ETO sterilization.
  • compositions and methods disclosed in this invention can be applied to devices including, but are not limited to, connector fittings, catheter systems (e.g., including catheters, catheter hubs, catheter adaptors, catheter tubing, etc.), fluid supply lines, inserted ports, other similar articles, or combinations thereof.
  • catheter systems e.g., including catheters, catheter hubs, catheter adaptors, catheter tubing, etc.
  • fluid supply lines e.g., inserted ports, other similar articles, or combinations thereof.
  • the liquid adhesive disclosed in this invention provides a much stronger securement strength in terms of catheter securement.
  • the catheter securement strength of liquid adhesive compositions disclosed in this invention is about 10 times stronger than some of the competitor products, indicating the significant advantage of liquid adhesive disclosed in this invention over conventional catheter dressing products.
  • the significantly stronger securement strength of the liquid adhesive composition disclosed in this invention can inhibit and/or reduce catheter movement, migration, and dislodgement of the catheter, which is a significant benefit of the liquid adhesive compositiondisclosed in this invention over the conventional and commercially available catheter dressing products.
  • Applying the liquid adhesive composition disclosed in the present patent underneath the dressingproducts can further significantly increase the securement strength of catheters.
  • Applying the liquid adhesive composition disclosed in this invention underneath the catheter insertion tube, catheter hub, catheter wings, and transparent dressing product can provide a securement strength of at least 11 lbf to the catheter being secured, which is up to 36 times stronger compared to the securement strength provided by some of conventional dressing or tape products used alone.
  • the securement strength of the liquid adhesive composition disclosed in the present patent can maintain over a period of time. An in vitro study demonstrated that the securement strength of theliquid adhesive composition disclosed in this invention can provide the effective securement for at least 7 days.
  • liquid adhesive composition disclosed in this invention can secure the catheter insertion tubeand seal the insertion site, while conventional catheter dressing products can only secure the catheter hub/wing but leave the insertion tube unsecured and the insertion site unsealed, which is the most vulnerable part of the entire vascular access system.
  • Liquid adhesive composition disclosed in this invention can provide an effective and water- resistant seal on the catheter insertion site.
  • the effective and water-resistant seal on the catheter insertion site of the liquid adhesive composition disclosed in this invention was evaluated by a liquid dye penetration method.
  • the liquid adhesive composition disclosed in this invention provides hemostasis and stops bleeding at the catheter insertion site.
  • the hemostatic property of the liquid adhesive composition disclosed in the present patent was confirmed by both modified activated clotting time assay and blood flow inhibition assay methods.
  • the liquid adhesive composition disclosed in this invention can provide antibacterial and bacteriaimmobilization properties, which are beneficial to catheter securement in terms of potentially inhibiting or reducing the known complication of the catheter related blood stream infection (CRB SI).
  • liquid adhesive compositions disclosed in this invention can seal vascular access sites and securevascular access devices providing antibacterial properties and hemostatic properties at or around vascular access sites, which typically requires the use of three or more different conventional products to achieve.
  • Sterilization of the liquid adhesive composition disclosed herein can be accomplished by any method, including, but not limited to chemical, physical and irradiation techniques.
  • Liquid adhesive composition disclosed in this invention maintain a shelf life of at least 24 months post sterilization as evaluated by real time shelf life stability study.
  • the method described herein provides for securing a vascular access device which has a tube that has been inserted into a vascular system of a patient at a vascular access point.
  • the method includes applying a first amount of a radiation-sterilized cyanoacrylate adhesive composition over the vascular access point. This first amount is allowed to cure to create a first cured radiation-sterilized cyanoacrylate adhesive composition.
  • This first cured radiation-sterilized cyanoacrylate adhesive composition is transparent and provides a water-resistant seal bander, a hemostatic effect on the vascular access point, an antimicrobial function to immobilize and eliminate bacteria at and around vascular access point. It also secures the insertion tube to the vascular access site.
  • a second amount of the radiation-sterilized cyanoacrylate adhesive composition is applied under a portion of the vascular access device at a site remote from the vascular access point. This second amount is allowed to cure thereby securing the vascular access device to the patient with a secured strength greater than 2 pounds of force (lbf).
  • the water-resistant seal barrier lasts for more than 3 days.
  • the vascular access device is a catheter and the first cured radiation-sterilized cyanoacrylate adhesive composition further inhibits complications associated with catheter insertion selected from the group consisting of catheter dislodgement, catheter infiltration, catheter migration, catheterocclusion, catheter-related phlebitis, and catheter-related infections.
  • the first cured radiation-sterilized cyanoacrylate adhesive composition further prevents bleeding at the vascular access point.
  • the first cured radiation-sterilized cyanoacrylate adhesive composition immobilizes bacteria at the vascular access point.
  • the first cured radiation-sterilized cyanoacrylate adhesive composition is an antimicrobial that provides at least a 6 log reduction of gram-positive bacteria, gram-negative bacteria, yeast, and fungi 3 minutes after curing.
  • the portion of the vascular access device under which second amount of the radiation-sterilized cyanoacrylate adhesive composition are wings.
  • the secured strength of the secured vascular access device to the patient is greater than 3 lbfs or 5 lbfs.
  • the vascular access device is selected from a group consisting of:
  • the radiation-sterilized cyanoacrylate adhesive composition comprises a mixture of stabilized and sterile polymerizable monomers.
  • the polymerizable monomers comprise a cyanoacrylate with straight chain or branched chain alkyl or alkoxyalkyl groups having 4 to 20 carbon atoms, including but not limited to, 2-octyl cyanoacrylate, dodecyl cyanoacrylate, undecyl cyanoacrylate, decyl cyanoacrylate, butyl cyanoacrylate, nonyl cyanoacrylate, heptyl cyanoacrylate, hexyl cyanoacrylate, pentyl cyanoacrylate, propyl cyanoacrylate, ethyl cyanoacrylate, 2-ethylhexyl cyanoacrylate, methyl cyanoacrylate, 3- methoxybutyl cyanoacrylate, 2-butoxyethyl
  • the radiation-sterilized cyanoacrylate adhesive composition may be stabilized by free radical stabilizers and anionic stabilizers.
  • the radiation-sterilized cyanoacrylate adhesive composition may be sterilized by irradiation methods and/or chemical sterilization methods.
  • the radiation-sterilized cyanoacrylate adhesive composition may have a shelf life of at least 24 months post sterilization evaluated by real time shelf stability studies.
  • the vascular access device is selected from a group consisting of peripheral IV catheters, PICC catheters, and CVC catheters.
  • the radiation-sterilized cyanoacrylate adhesive provides securement of the vascular access device to the patient for up to 7 days.
  • the radiation-sterilized cyanoacrylate adhesive is packaged in an applicator.
  • the applicator may be fabricated from a material that is substantially impermeable to moisture and air.
  • the adhesive composition disclosed in the present patent can be accurately dispensed and appliedto the catheter insertion site, on and underneath the catheter tubing, and underneath the catheter hub, which conventional catheter dressing products cannot achieve.
  • Liquid adhesive dispensed bythe applicator provides an effective securement of catheters such as intravenous (IV) catheters; peripheral venous catheters (PVCs), central venous catheters (CVCs), peripherally inserted central catheters (PICCs), arterial catheters, urinary catheters, and dialysis catheters.
  • IV intravenous
  • PVCs peripheral venous catheters
  • CVCs central venous catheters
  • PICCs peripherally inserted central catheters
  • arterial catheters urinary catheters, and dialysis catheters.
  • the adhesive composition disclosed in the present patent will be applied to devices including, butare not limited to, connector fittings, catheter systems (e.g., including catheters, catheter hubs, catheter adaptors, catheter tubing, etc.), fluid supply lines, inserted ports, other similar articles, orcombinations thereof.
  • catheter systems can include, but are not limited to, intravenous (IV) catheters; peripheral venous catheters (PVCs), central venous catheters (CVCs), peripherally inserted central catheters (PICCs), arterial catheters, urinary catheters, and dialysis catheters.
  • peripheral catheters include, but are not limitedto, Insyte Autoguard from BD, Nexiva IV catheter from BD, BD Saf-T-Intima, Jelco Viavalve safety Iv Catheter, Excel Safelet Catheters, Retractable Technologies VanishPoint catheters, Smiths Medical Protectiv Safety IV catheter, McKesson Select catheter, Bard Access Accucath, Terumo Medical Surflo, and B Braun Introcan Safety IV Catheter.
  • the most common commercially available midline peripheral catheters include, but are not limited to, Silicon First Midcath by Med Alliance Group, Argon Medical Midline Single Lumen, Bard Power Glide Midline, First Midcath, and Arrowg+ard Blue advance midline.
  • the most common commercially available PICC include, but are not limited to, PowerPicc by BD, BioFlo PICC by Angiodynamics, Argyle PICC by Covidien, and Arrow International PICC TwinCath.
  • the catheter, tubing, or medical line can be secured to the patient with the adhesive compositions, which is simple to use while providing reliable fixation of the catheter to the skin of the patient.
  • the liquid adhesives disclosed in the present patent provide a much stronger securement strength in terms ofcatheter securement.
  • the liquid adhesive compositions disclosed in the present patent provided much stronger securement strength in terms of securing BD Nexiva catheter when compared to conventional transparent dressing or tape products.
  • Table 1 indicates the securement strength is about 10 times stronger than some of the competitor products indicating the significant advantage of liquid adhesive disclosed in the present patent over conventional catheter dressing products.
  • Table 1 shows the securement strength of the liquid adhesive compositions disclosed in the present patent versus conventional catheter securement dressing products after 30 minutes while securing Nexiva catheters.
  • the significantly stronger securement strength of the liquid adhesive composition disclosed in the presentpatent can inhibit and/or reduce catheter movement, migration, and dislodgement of the catheter, which is a significant benefit of the liquid adhesive composition disclosed in the present patent over the conventional and commercially available catheter dress products, which include, but not limited to, TegadermTM, Opsite, HubGuard®, Durapore, 3M PICC/CVC Securement, SorbaviewShield, Sorbaview Ultimate Window Dressing product line, Sure View IV Securement TransparentFilm Dressing, Venti-Gard, UltraDrape -UGPIV Barrier and Securement, Securis Stabilization Device.
  • Tegaderm is the most popular film dressing product line.
  • Tegaderm products are Tegaderm CHG 1659 IV Securement Dressing, Tegaderm CHG 1658 IV Securement Dressing, Tegaderm 1683 IV Advanced Securement Dressing, Tegaderm 1685 IV Advanced Securement Dressing, Tegaderm 1688 IV Advanced Securement Dressing, Tegaderm 1689 IV Advanced Securement Dressing, Tegaderm 1680 IV Advanced Securement Dressing for Pediatrics, Tegaderm 1682 IV Advanced Securement for Pediatrics, Tegaderm Roll Film dressing, and Tegaderm HP 9519HP.
  • Conventional catheter stabilization devices that are commercially available are, GRIP-LOK by Baxter, WingGuard Catheter Securement Device, Grip-Lok by TidiProducts, and the StatLock product line.
  • liquid adhesive composition disclosed in the present patent can secure the catheter insertion tube and seal the insertion site, while conventional catheter dressing products can only secure the catheter hub/wing but leave the insertion tube unsecured and the insertion site unsealed, which is the most vulnerable part of the entire vascular access system. Unsecured insertion tube and unsealed catheter insertion site could be the most obvious reason that would cause migration, dislodgement, micromovement, phlebitis, and catheter-related blood stream infections (CRBSI).
  • CBSI catheter-related blood stream infections
  • the securement strength of the liquid adhesive composition disclosed in the present patent can maintain over a period of time.
  • the liquid adhesive composition disclosed in the present patent can provide the effective securement for at least 1 day.
  • the securement strength of the liquid adhesive composition disclosed in the present patent can provide the effective securement for at least 3 days.
  • the securement strength of the liquid adhesive composition disclosed in the present patent can provide the effective securement for at least 5 days, and in one more preferred embodiment, the securement strength of the liquid adhesive composition disclosed in the present patent can provide the effective securement for at least 7 days.
  • the securement strength of the liquid adhesive composition disclosed in the present patent evaluated at time intervals of 1 day, 3 days, and 7 days was 3.06 lbf, 3.02 lbf, and 3.72 lbf, respectively.
  • liquid adhesive composition disclosed in the present patent are also compatible with conventional catheter dressing products, which include, but are not limited to, TegadermTM, Opsite, HubGuard®, Durapore, 3M PICC/CVC Securement, Sorbaview Shield, Sorbaview Ultimate Window Dressing product line, Sure View IV Securement Transparent Film Dressing, Venti-Gard, UltraDrape - UGPIV Barrier and Securement, Securis Stabilization Device.
  • conventional catheter dressing products include, but are not limited to, TegadermTM, Opsite, HubGuard®, Durapore, 3M PICC/CVC Securement, Sorbaview Shield, Sorbaview Ultimate Window Dressing product line, Sure View IV Securement Transparent Film Dressing, Venti-Gard, UltraDrape - UGPIV Barrier and Securement, Securis Stabilization Device.
  • the effective securement strength of the liquid adhesive composition disclosed in the present patent was also confirmed by an in vivo model.
  • a total of six canines were divided into 3 groups with 2 animal per group to evaluate the stress of Autoguard IV catheters, Power PICC catheters, or Arrowguard CVC catheters secured by the liquid adhesive composition disclosed in the presentpatent.
  • the dynamic challenge was to pull on the cannula 10 times each hour for 6 hours.
  • the study showed no securement failure for each of the cannula tested at any time interval, which demonstrated that the liquid adhesive composition disclosed in the present patent successfully secured all three types of catheters tested in peripheral and central veins.
  • liquid adhesive composition disclosed in the present patent can alsosignificantly increase the peel strength of transparent dressing products, which include, but are notlimited to, Tegaderm dressing products, Opsite, Sorbaview Shield, Sorbaview Ultimate Window Dressing product line, Sure View IV Securement Transparent Film Dressing, Venti-Gard, 3M PICC/CVC Securement, UltraDrape - UGPIV Barrier and Securement, and Securis Stabilization Device.
  • transparent dressing products include, but are notlimited to, Tegaderm dressing products, Opsite, Sorbaview Shield, Sorbaview Ultimate Window Dressing product line, Sure View IV Securement Transparent Film Dressing, Venti-Gard, 3M PICC/CVC Securement, UltraDrape - UGPIV Barrier and Securement, and Securis Stabilization Device.
  • Tegaderm dressing products include, but are not limited to, Tegaderm CHG 1659 IV Securement Dressing, Tegaderm CHG 1658 IV Securement Dressing, Tegaderm 1683 IV Advanced Securement Dressing, Tegaderm 1685 IV Advanced Securement Dressing, Tegaderm 1688 IV Advanced Securement Dressing, Tegaderm 1689 IV Advanced Securement Dressing, Tegaderm 1680 IV Advanced Securement Dressing for Pediatrics, Tegaderm 1682 IV Advanced Securement for Pediatrics, Tegaderm Roll Film dressing, and Tegaderm HP 9519HP.
  • the liquid adhesive composition disclosed in the present patent can be applied partially or entirely underneath the dressing products.
  • the peel strength of the transparent dressing products with the liquid adhesive composition disclosed in the present patent applied underneath is about 2 times stronger than that of the transparent dressing product alone. In another embodiment, the peel strength of the transparent dressing products with the liquid adhesive composition disclosed in the present patent applied underneath is about 4 times stronger than that of the transparent dressing product alone. In a preferred embodiment, the peel strength of the transparent dressing products with the liquid adhesive composition disclosed in the present patent applied underneath is about 8 times stronger than that of the transparent dressing product alone. In a more preferred embodiment, the peel strength of the transparent dressing products with the liquid adhesive composition disclosed in the present patent applied underneath is about 8 times stronger than that of the transparent dressing product alone.
  • Applying the liquid adhesive composition disclosed in the present patent underneath the dressingproducts can also significantly increase the securement strength of catheters that include, but are not limited to peripheral intravenous catheters (PICs), central venous catheters (CVCs), peripherally inserted central catheters (PICCs), arterial catheters, urinary catheters, and dialysis catheters, as demonstrated by Table 3 below.
  • PICs peripheral intravenous catheters
  • CVCs central venous catheters
  • PICCs peripherally inserted central catheters
  • arterial catheters urinary catheters
  • dialysis catheters as demonstrated by Table 3 below.
  • applying the liquid adhesive composition disclosed in the present patent underneath the catheter insertion tube, catheter hub, catheter wings, and transparent dressing product can provide a securement strength of at least 5 lbf to the catheter being secured.
  • applying the liquid adhesive composition disclosed in the present patent underneath the catheter insertion tube, catheter hub, catheter wings, and transparent dressing product can provide a securement strength of at least 6 lbf to the catheter being secured.
  • applying the liquid adhesive composition disclosed in the present patent underneath the catheter insertion tube, catheter hub, catheter wings, and transparent dressing product can provide a securement strength of at least 8 lbf to the catheter being secured.
  • applying the liquid adhesive composition disclosed in the present patent underneath the catheter insertion tube, catheter hub, catheter wings, and transparent dressingproduct can provide a securement strength of at least 10 lbf to the catheter being secured.
  • applying the liquid adhesive composition disclosed in the present patent underneath the catheter insertion tube, catheter hub, catheter wings, and transparent dressing product can provide a securement strength of at least 11 lbf to the catheter being secured.
  • Table 3 shows securement strength of transparent dressing product 5 alone, and transparent dressingproduct 5 plus adhesive composition disclosed in the present patent with additional drops of adhesive composition applied directly under transparent dressing product 5 while securing BD Nexiva catheters onto pig skin for 30 minutes.
  • the liquid adhesive composition disclosed in the present patent can provide the effective and water-resistant seal on the catheter insertion site for at least 1 day.
  • the securement strength of the liquid adhesive composition disclosed in the present patent can provide the effective and water-resistant seal on the catheter insertion site for at least 3 days.
  • the securement strength of the liquid adhesive compositiondisclosed in the present patent can provide the effective and water-resistant seal on the catheter insertion site for at least 5 days, and in one more preferred embodiment, the securement strength of the liquid adhesive composition disclosed in the present patent can provide the effective and water-resistant seal on the catheter insertion site at least 7 days.
  • the effective and water-resistant seal on the catheter insertion site of the liquid adhesive composition disclosed in the present patent was evaluated by a liquid dye penetration method. Once the catheters have been inserted into the skin, they are secured to the skin by applying the liquid adhesive composition disclosed in the present patent. Once the appropriate amount of time has passed, a total of thirty minutes, the aqueous liquid dye is applied on top of the point in which the catheter tubing is inserted into the skin. Once this is completed the liquid dye rested for certain time intervals, the aqueous liquid dye solution was completely removed from the testing articles secured by the liquid adhesive composition disclosed in the present patent by using a spray bottle filled with water. Observations were recorded after initial removal of the dye, underneath the hub, and on the insertion point.
  • the adhesive composition of the present invention has shown significant resistance to water penetration tested by the hydrostatic pressure impact test.
  • the adhesive composition of the presentinvention provides an effective barrier against aqueous solutions, and the sealant integrity of the adhesive film layer once applied to the catheter stays intact with no pinholes.
  • the water- based liquid dye did not penetrate the adhesive film at the junction of the catheter and the skin; therefore, the adhesive composition of the present invention provides securement to the catheter while providing a proficient sealant layer for the insertion site as well as the catheter hub.
  • liquid adhesive composition disclosed in the present patent Compared to conventional and commercially available catheter dressing products, yet another advantage of the liquid adhesive composition disclosed in the present patent is that the liquid compositions disclosed herein provide hemostasis to the catheter insertion site.
  • the hemostatic property of the liquid adhesive composition disclosed in the present patent was confirmed by bothmodified activated clotting time assay and blood flow inhibition assay methods.
  • An experiment was conducted to determine the hemostatic properties of the liquid adhesive composition disclosed in the present patent through means of customized modified activated clotting time (mACT).
  • mACT customized modified activated clotting time
  • the liquid adhesive composition disclosed in the present patent was used to study the hemostatic properties while in contact with blood or plasma. Saline was the negative control used in all experiments.
  • test group was evaluated when in contact with citrated whole blood (diluted 1:1 with saline), platelet poor plasma (prepared via centrifugation of citrated whole blood at 2500 X g for 20 minutes at 21°c), and non-anti coagulated whole blood (diluted 1:1 with saline) each from four healthy donors.
  • a clotting analyzer was used on blood samples collected into sodium citrate anticoagulant or non-additive vacutainer tubes to evaluate the effects of the liquid adhesive composition disclosed in the present patent on mACT assay.
  • a certain amount of diluted whole blood (WB) or neat platelet poor plasma (PPP) were added to each well.
  • a control standard prothrombin time (PT) test with normal pooled plasma and Neoplastine Cl plus regent was performed each day of testing for control.
  • test strip was placed for about 3 minutes before being transferred to the test wells.
  • the test was initiated with a maximum time limit of 180 seconds.
  • thromboplastin or tissue factor
  • WB was also placed into contact with Neoplastine Cl plus reagent. This test was performed with results presented as the amount of time (seconds) it took to achieve hemostasis with the liquid adhesive composition disclosed in the present patent in the presence of WB or other blood products.
  • the liquid adhesive composition disclosed in the present patent is significantly faster to achieve hemostasis of whole blood (WB), neat platelet poor plasma (PPP) or other blood products, than other blood coagulation agents including but not limited to Thrombopastin.
  • the liquid adhesive compositiondisclosed in the present patent is at least 3 times faster to achieve hemostasis than other blood coagulation agents.
  • the liquid adhesive composition disclosed in the present patent is at least 6 times faster to achieve hemostasis than other blood coagulation agents.
  • the liquid adhesive composition disclosed in the present patent is at least 9 times faster to achieve hemostasis than other blood coagulation agents.
  • the liquid adhesive composition disclosed in the present patent is at least 12 times faster to achieve hemostasis than other blood coagulation agents.
  • the hemostatic properties of the liquid adhesive composition disclosed in the present patent was also evaluated by blood flow inhibition (BFI) assay.
  • BFI blood flow inhibition
  • Three sodium citrate vacutainer tubes or onenon-additive tube were used to collect blood.
  • a peristaltic pump was installed with two pieces of four-inch C-flex tubing added to the distal and proximal ends of the peristaltic pump tube, which contains a 1.5mL Eppendorf tube.
  • One milliliter of citrated diluted whole blood (WB), non- anti coagulated WB, or Platelet-Poor Plasma (PPP) was perfused through the tubing until the blood reached the distal end.
  • WB citrated diluted whole blood
  • PPP Platelet-Poor Plasma
  • the liquid adhesive composition disclosed in the present patent is statistically significant in halting excessive blood flow compared to the control or no treatment group.
  • the swine were induced under general anesthesia; the hair located on the dorsal- lateral back was removed; and fluids were administered to maintain or increase systolic blood pressure, thereby achieving adequate blood flow. Heparin was administered to achieve adequate blood flow from each incision.
  • the spot for each incision was outlined on the back of each swine using a marker and ruler. There were thirty sites located on each side of the back for each pig; the incisions were lined in three rows of ten.
  • the treatments that each incision site received were rotated in a repeating order as follows: Sham Control, Gelfoam ® Powder, Kaltostat ® , and the liquid adhesive composition disclosed in the present patent. The rotation continued until all incisions were treated.
  • the bleeding scores prior to the treatment serve as a baseline for start of bleeding to determine the effect the different articles have on improving hemostasis of the incisions.
  • the average incision bleeding score was 2.3 ⁇ 1.0, while the bleeding score was significantly dropped to 0.2 ⁇ 0.4 after treating the incision with the liquid adhesive composition disclosed in the present patent.
  • the statistical analysis preformed shows that the liquid adhesive composition disclosed in the present patent is statistically equivalent to Gelfoam® and Kaltostat® in terms of providing hemostatic effect on swine full thickness incisions.
  • the liquid adhesive composition disclosed in the present patent can provide the antibacterial and bacteria immobilization property, which is beneficial to catheter securement in terms of potentially inhibiting or reducing the known complication of the catheter related blood stream infection (CRB SI).
  • CB SI catheter related blood stream infection
  • Microorganisms chosen for examination individually in these experiments include, but are not limited to, Methicillin Resistant Staphylococcus Aureus (MRSA), S. epidermidis, Pseudomonas aeruginosa, Candida albicans and Corynebaterium species.
  • MRSA Methicillin Resistant Staphylococcus Aureus
  • S. epidermidis S. epidermidis
  • Pseudomonas aeruginosa Candida albicans
  • Corynebaterium species The experiments demonstrated that the
  • the liquid adhesive composition disclosed in the present patent was tested in its liquid state against the challenge microorganisms such as Escherichia coli, Klebsiella pheumoniae, Stphylococcus epidermidis, and Staphylococcus aureus subs. Aureus (MRSA).
  • the liquid adhesive composition disclosed in the present patent was determined to be an effective antimicrobial agent.
  • the kill level observed for the liquid adhesive composition disclosed in the present patent after a three-minute contact time can be about five log reduction.
  • the kill level observed for the liquid adhesive composition disclosed in the present patent after a three-minute contact time can be about 6 log reduction.
  • the kill level observed for the liquid adhesive composition disclosed in the present patent after a three-minute contact time can be about 7 log reduction. In a preferred embodiment, the kill level observed for the liquid adhesive composition disclosed in the present patent after a three-minute contact time can be about 8 log reduction. In a more preferred embodiment, the kill level observed for the liquidadhesive composition disclosed in the present patent after a three- minute contact time can be about 9 log reduction.
  • the liquid adhesive compositions disclosed in this invention can seal vascular access sites and secure vascular access devices providing antibacterial property and stopping bleeding at or aroundvascular access sites, which requires three or more different conventional products to achieve.
  • the liquid adhesive compositions disclosed in this invention possess several characteristics that are critical for the maintenance and care of the vascular access sites and the stabilization and securement of vascular access devices.
  • the liquid adhesive compositions disclosed in this invention can provide a water-resistant seal and barrier to the vascular access site up to 7 days while ensuring the vascular access sites visible during entire time of securement.
  • the conventional catheter dressing products could not seal the vascular access sites, but leave the vulnerable vascular access sites open instead.
  • liquid adhesive compositions disclosed in this invention provide significantly stronger securement strength to the catheters than that provided by the conventional securement methods using the dressing products or stabilization devices, which can inhibit, reduce, or prevent catheter-related complications such as catheter dislodgement, catheter infiltration, catheter migration/movement, catheter occlusion, catheter-related phlebitis, or catheter-related infections.
  • the adhesive composition disclosed in the present patent is used to apply liquid sealant to secure catheters on human skin.
  • Preferred adhesive compositions are readily polymerizable, e.g., anionically polymerizable and/or free radical polymerizable.
  • the adhesive compositions are preferably a 1,1-di substituted ethylene monomer, e.g., a cyanoacrylate monomer.
  • the adhesive compositions are based upon one or more polymerizable cyanoacrylate monomers, and/or reactive oligomers of cyanoacrylate.
  • Such cyanoacrylate monomers are readily polymerizable, e.g., anionically polymerizable and/or free radical polymerizable, to form polymers.
  • Cyanoacrylate monomers suitable for use in accordance with the present invention include, but are not limited to, 1,1-di substituted ethylene monomers of the formula:
  • Preferred monomers of Formula I for use in this invention are alpha-cyanoacrylates. These monomers are known in the art and have the formula:
  • R 2 is hydrogen and R 3 is a hydrocarbyl or substituted hydrocarbyl group; a group having the formula , wherein is a 1,2-alkylene group having 2-4 carbon atoms, R 5 is an alkylene group having 2-12 carbon atoms, and R 6 is an alkyl group having 1-6 carbon atoms; or a group having the formula:
  • R 7 is: wherein n is 1-14, preferably 1-8 carbon atoms and R 8 is an organic moiety.
  • suitable hydrocarbyl and substituted hydrocarbyl groups include straight chain or branched chain alkyl groups having 1-16 carbon atoms; straight chain or branched chain Cl- 06 alkyl groups substituted with an acyloxy group, a haloalkyl group, an alkoxy group, a halogen atom, a cyano group, or a haloalkyl group, straight chain or branched chain alkenyl groups having 2 to 16 carbon atoms, straight chain or branched chain alkynyl groups having 2 to 12 carbon atoms cycloalkyl groups; arylalkyl groups; alkylaryl groups; and aryl groups.
  • Table 4 lists a few examples of securement strength of different cyanoacrylate compositions used for securing BD Autoguard catheters.
  • the organic moiety R may be substituted or unsubstituted and may be a straight chain, branchedor cyclic, saturated, unsaturated, or aromatic.
  • organic moieties include C1-C8 alkyl moieties, C2-C8 alkenyl moieties, C2-C8 alkynyl moieties, C3-C12 cycloaliphatic moieties, aryl moieties such as phenyl and substituted phenyl, and arylalkyl moieties such as benzyl, methylbenzyl, and phenylethyl.
  • organic moieties include substituted hydrocarbon moieties, such as halo (e.g., chloro-, fluoro-, and bromo-substituted hydrocarbons) and oxy- (e.g., alkoxy substituted hydrocarbons) substituted hydrocarbon moieties.
  • Preferred organic radicals are alkyl, alkenyl and alkynyl moieties having from 1 to about 8 carbon atoms, and halo- sub stitutedderivatives thereof. Particularly preferred are alkyl moieties of 4 to 8 carbon atoms.
  • R is preferably an alkyl group having 1-10 carbon atomsor a group having the formula —AO R ⁇ , wherein A is a divalent straight or branched chain alkyleneor oxyalkylene moiety having 2-8 carbon atoms, and is a straight or branched alkyl moiety having 1-8 carbon atoms.
  • the preferred alpha-cyanoacrylate monomers used in this invention are 2-octyl cyanoacrylate, dodecyl cyanoacrylate, 2-ethylhexyl cyanoacrylate, butyl cyanoacrylate, methyl cyanoacrylate, 3-methoxybutyl cyanoacrylate, 2-butoxy ethyl cyanoacrylate, 2- isopropoxy ethyl cyanoacrylate, or l-methoxy-2-propyl cyanoacrylate, or a combination thereof.
  • the cyanoacrylate monomers can be prepared according to methods known in the art. Reference is made, for example, to U.S. Pats. No. 2,721,858 and No. 3,254,111, each of which is hereby incorporated in its entirety by reference.
  • One such process includes, for example, reacting a cyanoacetate with formaldehyde in the presence of a basic condensation catalyst at an elevated temperature to produce a low molecular weight polymer.
  • a de-polymerization (or cracking) step is followed under high temperature and high vacuum in the presence of acidic and anionic inhibitors, yielding a crude monomer that can be distilled under high temperature and high vacuum in the presence of radical and acidic inhibitors.
  • the distilled cyanoacrylate monomers can be filtered through one or multiple filters in order to reduce the bioburden level of the cyanoacrylate composition and remove any immiscible impurities or contaminants. If filtered, the cyanoacrylate monomers may be filtered through any suitable sized filters known in the art. For example, in a multiple step filtration process, the cyanoacrylate monomers may be filtered through a primary filter and one or more additional or secondary filters.
  • the size of the primary filter may range, for example, on the order of about 0.01 to about 0.8 pm, preferably in the range of about 0.01 to about 0.6 pm, and more preferably in the range of about 0.03 to about 0.6 pm.
  • the size of the additional or secondary filters may range, for example, on the order of about 1 to about 200 pm, preferably in the range of about 1 to about 150 pm, and more preferably in the range of about 1 to about 100 pm.
  • cyanoacrylate monomer was produced with a high purity.
  • the purity of cyanoacrylate in this invention is at least about 97% by weight, preferably at least about 98% by weight, and more preferably at least about 99% by weight.
  • the purity of cyanoacrylate monomer was measured during and/or after distillation process.
  • the highpurity of cyanoacrylate monomer was obtained by multiple distillations under high vacuum and high temperature.
  • the vacuum for distilling cyanoacrylate monomer is in the range of about 0.02Torr to about 15 Torr, preferably in the range of about 0.05 Torr to about 10 Torr, and more preferably in the range of about 0.1 Torr to about 10 Torr.
  • the distillation temperature is in the range of about 100 °C to about 180 °C, preferably in the range of about 100 °C to about 160 °C, and more preferably in the range of about 100 °C to about 150 °C.
  • basic polymers or copolymers may be applied to reduce the amount of contaminants and extraneous additives in the cyanoacrylate monomer, but this can leadto several problems including premature polymerization.
  • Some basic polymers or copolymers arenot soluble in cyanoacrylate but are mixed with the monomer adhesive in mutual contact until theadhesive is destabilized. In order to achieve the mutual contact, such polymers or copolymers aremixed with the cyanoacrylate monomer for a minimum of 3 hours, which may remove possible acid residues to destabilize the adhesive. The solid powder of such polymer is then removed from cyanoacrylate adhesive by filtering.
  • a proper amount of both free radical and anionic stabilizers has to be included into said adhesive compositions in order to ensurethat the inventive compositions do not cure upon sterilization, and further ensure that the inventive compositions can provide a stable shelf life of at least 24 months.
  • the inventive compositions should be stabilized via the combination of free radical and anionic stabilizers.
  • free radical stabilizers include without limitation, hydroquinone; catechol; hydroquinone monomethyl ether and hindered phenols such as butylated hydroxyanisol; 4-ethoxyphenol; butylated hydroxytoluene (BHT, 2,6-di-tert-butyl butylphenol), 4-methoxyphenol (MP); 3- methoxyphenol;2-tertbutyl- 4methoxy phenol; 2-tert-butyl-4-methoxyphenol; 2,2- methylene-bis-(4-methyl-6-tert-butylphenol).
  • the preferred anoinic stabilizer is sulfur dioxide.
  • anionic stabilizers may be a very strong acid including without limitationperchloric acid, hydrochloric acid, hydrobromic acid, toluenesulfonic acid, fluorosulfonic acid, phosphoric acid, ortho, meta, or para-phosphoric acid, trichloroacetic acid, and sulfuric acid.
  • the compositions may optionally contain thickening agents.
  • Suitable thickening agents include polycyanoacrylate, partial polymer of cyanoacrylate, polycaprolactone, copolymers of alkylacrylate and vinyl acetate, polyalkyl methacrylates, polyalkyl acrylates, lactic-glycolic acid copolymers, lactic acid-caprolactone copolymers, polyorthoesters, copolymers of alkyl methacrylates and butadiene, polyoxalates, and triblock copolymers of polyoxypropylene flanked by two hydrophilic chains of polyoxyethylene.
  • a plasticizer may be included in the inventive cyanoacrylate compositions.
  • the plasticizing agent preferably does not contain any moisture and should not adversely affect the stability of the cyanoacrylate compositions.
  • suitable plasticizers include, but are not limited to, tributyl citrate (TBC), acetyl tributyl citrate (ATBC), dimethyl sebacate, diethylsebacate, triethyl phosphate, tri(2-ethyl-hexyl)phosphate, tri(p- cresyl) phosphate, diisodecyl adipate (DIDA), glyceryl triacetate, glyceryl tributyrate, dioctyl adipate (DICA), isopropyl myrisate, butyl sterate, lauric acid, trioctyl trimelliate, dioctyl glutatrate (DICG) and mixtures thereof.
  • TBC tributyl citrate
  • ATBC acetyl tributyl citrate
  • DIDA diis
  • Tributyl citrate, diisodecyl adipate and acetyl tributyl citrate are preferred plasticizers used in an amount of 0 to 30%, preferably 1% to 20%, and more preferably 2 % to 10 %.
  • compositions of this invention may further contain small amounts of colorants such as dyes, pigments, and pigment dyes.
  • Suitable dyes include derivatives of anthracene and other complex structures. These dyes include without limitation, l-hydroxy-4-[4methylphenylamino]- 9,10 anthracenedione (D&C violet No. 2); 9-(o-carboxyphenyl)-6-hydroxy2,4,5,7-tetraiodo-3H- xanthen-3-one-, disodium salt, monohydrate (FD&C Red No. 3); disodium salt of 6-hydroxy-5- [(4-sulfophenyl)axo]-2-naphthalene-sulfonic acid (FD&C Yellow No.
  • the liquid adhesive composition disclosed in thepresent patent should be sterile. Sterilization of the liquid adhesive composition disclosed herein can be accomplished by any method, including, but not limited to chemical, physical and irradiation techniques. Examples of chemical methods include, but are not limited to, exposure to ethylene oxide and hydrogen peroxide. Examples of physical methods include, but are not limited to, sterilization by heat (dry or moist) or retort canning. Examples of irradiation methods include, but are not limited to, gamma irradiation, electron beam irradiation, X-ray irradiation and microwave irradiation.
  • Preferred methods of sterilization are irradiation methods, including but not limited to, electron beam (E-beam), gamma irradiation and X-Ray.
  • E-beam electron beam
  • gamma irradiation gamma irradiation
  • X-Ray X-Ray
  • the dose applied which is sufficient enough to sterilize the adhesive compositions typically, ranges from about 5 kGy to 50 kGy, andmore preferably from about 5 kGy to 25 kGy.
  • E-beam irradiation is preferably conducted at ambient atmosphere conditions and the exposure time to the irradiation is preferably within 60 seconds.
  • Any standard power source is suitable, including a linear accelerator, which produces irradiation measured in kilo watts (KW). The larger the beam power, the more product volume can be processed.
  • the inventive cyanoacrylate adhesive compositions are irradiated at a beam power ranging from about 2 KW to about 30 KW, preferably about 5 KW to about 20 KW, and more preferably about 10 KW to about 20 KW.
  • E-beam irradiation typically involves the use of high- energy electrons.
  • the beam energy ranges from 1 million to 10 million electron volts (MeV), preferably 3 MeV to 10 MeV, and more preferably 5 MeV to 10 MeV.
  • the dose of Gamma irradiation to the liquid adhesive composition disclosed in the present patent is in the range of about 5 kGy to about 40 kGy, preferably in the range of about 5 kGy to about 30kGy, more preferably about 5 kGy to about 25 kGy, and most preferably about 5 kGy to about 20kGy.
  • the dose of X-ray irradiation to cyanoacrylate compositions with naphthoquinone 2,3-oxide is in the range of about 5 kGy to about 40 kGy, preferably in the range of about 5 kGy to about 30 kGy, more preferably about 5 kGy to about 25 kGy, and most preferably about 5 kGy to about 20kGy.
  • High energy electrons are used in the instant method of x-ray sterilization of liquid adhesive compositions.
  • X-rays are generated as high-frequency and short- wavelength electromagnetic photons. Conventional x-ray technology is suitable in the instant invention.
  • the X-ray energy used in the present invention ranges from 1 million to 10 million electron volts (MeV), preferably 3MeV to lOMeV, and more preferably 3 to 7.5MeV.
  • the dose of gamma irradiation desirably ranges from about 5 to about 25 kGy, preferably in the range of about 5 to about 20 kGy, and morepreferably in the range of about 5 to about 15 kGy.
  • Standard Cobalt Co- 60 may be used as the gamma ray source in sterilizing the compositions and packages of the present invention.
  • the viscosity of the cyanoacrylate composition may change, including an increase or decrease.
  • the change in viscosity of the cyanoacrylate adhesive compositions, after the sterilization may vary, for example, depending on the original viscosity and the presence of additives such as a polymerization accelerator, a medicament, or stabilizers.
  • the increase in viscosity of the composition after is within about 1% to about 200%, preferably within about 1% to about 80%, and more preferably within about 1% to about 60% of the initial viscosity of the composition, before sterilization.
  • the viscosity of the composition after sterilization is within about 5% to about 300% of the initial viscosity of the composition, before sterilization.
  • the viscosity may change about 5% to about 10%, about 5% to about 15%, about 5% to about 20%, about 7% to about 10%, about 7% to about 15%, about 8% to about 12%, about 8% to about 15%, about 8% to about 20%, about 10% to about 100%, about 10% to about 80%, about 10% to about 60%, about 10% to about 40%, about 10% to about 30%, about 10% to about 20%, about 20% to about 100%, about 20% to about 60%, about 20% to about 50%, about 20% to about 40%, about 20% to about 30%, about 30% to about 300%, about 30% to about 200%, about 30% to about 150%, about 30% to about 100%, about 30% to about 50%, about 40% to about 300%, about 40% to about 200%, about 40% to about 150%, about 40% to about 100%, about 40% to about 80%, about 40% to about 80%, about 50% to about 300%, about 50% to about 30
  • shelf-life refers to the amount of time the composition therein can be held at ambient conditions (approximately room temperature) or less, without degradation of the composition occurring to the extent that the composition cannot be used in the manner and for the purpose for which they were intended. Thus, while some degradation to the composition can occur, it must not be to such an extent that the composition is no longer useable.
  • extended shelf-life refers to a shelf-life of at least 12 months, preferably at least 18 months, and more preferably at least 24 months.
  • Stability refers to theresultant composition maintaining a commercially acceptable form for the prescribed amount of time. That is, the composition does not prematurely polymerize or otherwise change form or degrade to the point that the composition is not useful for its intended purpose. Thus, while some polymerization or thickening of the composition may occur, such as can be measured by changes in viscosity of the composition, such change is not so extensive as to destroy or significantly impair the usefulness of the composition.
  • the accelerated aging test was performed in the oven at 80 °C for a period of 13 days. Based on calculations, 13 days accelerated aging at 80 °C is equal to 2 years of shelf life, and 1 day of accelerated aging at 80 °C is equal to 56 days.
  • the stability of the liquid adhesive composition disclosed in the present patent after sterilization can also be evaluated by the real time assessment.
  • the real time aging study was conducted at room temperature by keeping the cyanoacrylate compositions in the suitable package afterirradiation sterilization in a designated environment where the temperature and humidity are monitored by a chart recorder. The temperature was controlled at 22 °C ⁇ 5 °C and the humidity cannot exceed 80%.
  • Viscosity, curing speed, and purity of the cyanoacrylate adhesive compositions in the suitable package after irradiation sterilization were evaluated at day 0, month 12, and 24 or other intervals between day 0 and month 24 to assess the performance and stability of the adhesive compositions. The viscosity was used to evaluate the stability of the adhesive compositions.
  • the present invention further provides a kit for applying the cyanoacrylate adhesive composition, including an applicator containing therein an effective amount of the cyanoacrylate composition.
  • the applicators are designed to be safe and easy to use, with a tapered tip and the ability to controlthe flow rate of an adhesive or sealant material for the purpose of precise control.
  • the applicator is also compatible with radiation sterilization techniques.
  • the containers for the adhesive and sealant material of the applicators are made of materials with high moisture and air barrier properties such as cyclic olefin copolymers or acrylonitrile copolymers so that the adhesiveand sealant material can be sterilized by radiation and thereafter provide longterm shelf stability.
  • the present invention includes: a body, a container for containing an adhesive material, and a rigid tapered tip.
  • Adhesives may be pre-packaged in the applicator in the container, for example, sealed within the container by a frangible foil or a membrane, which may be hermetically sealed.
  • the container for adhesives can be fabricated from a multi-layer sheetmateriai, and the inner layer of the container, which contacts the adhesive, can be fabricated ffoma cyclic olefin copolymer.
  • the container thereby constructed is compatible with radiati onsteri lization, such as electron beam, gamma, or x-ray sterilization, so that adhesives inside the applicator can be sterilized via radiation without diminished shelf stability (e.g., without prematurely polymerizing).
  • the long-term shelf life stability of adhesive packaged in the applicators may be provided after radiation sterilization,
  • the container comprises a plurality of walls that define a chamber that is preferably open at the distal end, which may be closed off by at least one seal, for example, a frangible seal.
  • the frangibleseal is heat sealed to the container for storing the adhesive.
  • Suitable materials for the frangible seal may include, but are not limited to, aluminum foil, plastic membrane, laminated aluminum foil, plastic wrap, waxed paper, oiled paper, or the like.
  • Laminated aluminum foil may be composed of at least two layers of different materials which include, but are not limited to, aluminum, acrylonitrile copolymer, low density polyethylene, low density polypropylene, polyethylene teraphthalate, cyclic olefin copolymer, and the like.
  • Suitable materials for the container should have a desired barrier property for moisture and air so that the premature polymerization of the adhesive can be prevented or inhibited.
  • the exceptionalbarrier properties offered by preferred materials of this invention make them ideal materials for use in construction of the packaging bodies in accordance with the present invention.
  • Preferred materials of this invention offer a high barrier to oxygen at all levels of relative humidity. This ensures that a consistently high barrier to oxygen is maintained, regardless of the humidity of the surrounding environment.
  • the water vapor barrier properties of the preferred materials of this invention make them desirable materials for packaging and sterilizing cyanoacrylate-based adhesive materials in accordance with the present invention.
  • Suitable materials for the container include, but are not limited to, high density polyethylene (HDPE), polypropylene, polyvinylchloride, acrylonitrile copolymer, polycarbonate, polytetrafluoroethylene (PFTE), cyclicolefin copolymer, and the like.
  • HDPE high density polyethylene
  • polypropylene polypropylene
  • polyvinylchloride polyvinylchloride
  • acrylonitrile copolymer polycarbonate
  • PFTE polytetrafluoroethylene
  • cyclicolefin copolymer cyclicolefin copolymer
  • Suitable materials for the container and the inner layer of the frangible seal include unsaturated cyclic monomers and one or more unsaturated linear monomer.
  • Unsaturated linear monomers include without limitation aikenes having 1 to 20, preferably from 1 to 12 carbon atoms, most preferably from 1 to 6 carbon atoms, such as for example alpha-olefins, for example ethylene, propylene, and butylene.
  • Unsaturated cyclic monomers include without limitation, cyclopentadiene and derivatives thereof such as for example dicyclopentadiene and 2,3- dihydrocyclopentadiene; 5,5-dimethyl-2-norbomene, 5-butyl -2-norbomene, 5-ethylidene-2- norbornene, norbomene and derivatives thereof, 2-norbomene, 5-methy!-2 ⁇ norbomene, 5- methoxycarbonyl -2-norbomene, 5-eyano-2-norbornene, 5-methyl-5-methoxycarbonyl-2- norbornene, and 5-phenyl-2-norbomene, and combinations of two or more thereof.
  • un saturated linear monomers may be chosen from 1 -butene, 4-methyl- 1-pentene, 1 -hexene, 1- octene, 1-decene, 1-dodecene, 1 -tetradecene, 1-hexadecene, 1-octadecene and 1-ei eocene, cydopentene, cydohexane, 3 -methyl cyclohexene, cyclooctene, 1,4-hexadiene, 4-methyl- 1 ,4- hexadiene, 5-methyl- 1,4-hexadiene, 1 ,7-octadiene, dicyclopentadiene, 5-ethylidene-2-norbomene, 5-vinyl -2-norbomene, tetracyclododecene, 2-methyltetracyclododecene, and 2- ethyltetracycl
  • the unsaturated linear monomer is 1 -hexene, butylene, propylene, and ethylene.
  • the copolymer is cyclopentadiene-ethylene copolymer, cyclopentadiene-butylene copolymer, cyclopentadiene- hexene copolymer, cyclopentadiene-propylene copolymer, cyclopentadiene-octene copolymer, dicyclopentadiene-ethylene copolymer, dicyclopentadiene-butylene copolymer, dicyclopentadiene-hexene copolymer, dicyclopentadiene-propylene copolymer, dicyclopentadiene-octene copolymer, norbomene-ethylene copolymer, norbomene-propylene copolymer, norbornene-butylene copolymer, norborene-hexene copolymer, 5-
  • the applicator body may be fabricated from any suitable materials.
  • a cutting portion inside the applicator body is designed to be sharp and strong so as to readily break the frangible seal for dispensing adhesive inside the container.
  • the grip section should be flexible and soft enough to make squeezing readily possible. Therefore, the material of the applicator body is specifically designed for the applicator body. Suitable materials for the applicator body include but are not limited to polyethylene (PE), polypropylene, polyvinylchloride, polycarbonate, polytetrafluoroethylene (PFTE), polystyrene (PS), and polymethylpentene with a certain percentage of thermoplastic elastomers (TPE).
  • PE polyethylene
  • PFTE polytetrafluoroethylene
  • PS polystyrene
  • TPE thermoplastic elastomers
  • TPE may be present in the materials used for constructing the applicator body in the amount of 2% to 70%, preferably 3% to 60%, and more preferably 5% to 50%. Without including TPE, the applicator body is too hard to be squeezed to dispense and control the flow of the adhesive. If too much TPE is present in the applicator body, the cutting portion becomes too soft to puncture through the frangible seal for dispensing adhesive inside the container.
  • the composition is sterilized to provide a Sterility Assurance Level (SAL) of at least 10 3 .
  • SAL Sterility Assurance Level
  • the sterility assurance level may be at least 10 4 , 10 5 , or 10 6 .
  • TegadermTM 9525HP Securement strength of TegadermTM 9525HP vs. the liquid adhesive composition disclosed in the present patent for Securing BD Nexiva Catheters after 6 hours. Porcine skin was prepared and cleaned with isopropyl alcohol. Measure and mark a spot to insert the catheter in thecenter of the skin. Inject the IV Catheter needle into the skin as to leave the IV Catheter resting flush against the skin and the catheter tube injected into the skin. To secure the BD Nexiva Catheter with TegadermTM 9525HP, apply TegadermTM 9525HP per IFU. To secure the BD Nexiva Catheterwith the liquid adhesive composition disclosed in the present patent, apply the adhesive under the catheter hub, tubing, and insertion site.
  • This study is to evaluate the securement strength of BD Nexiva Catheters secured to porcine skin by the liquid adhesive composition disclosed in the present patent plus TegadermTM9525HP with additional drops of the liquid adhesive composition disclosed in the present patent applied under the entire area of the TegadermTM9525HP dressing.
  • prepare porcine skin by cutting and cleaning the skin with isopropyl alcohol. Measure and mark a spot to insert the catheter in the center of the skin. Inject the IV Catheter needle into the skin as to leave the IV Catheter resting flush against the skin and the catheter tube injected into the skin.
  • To secure the BD Nexiva Catheter apply the liquid adhesive composition disclosed in the present patent under the catheter hub, tubing and insertion site.
  • liquid adhesive composition disclosed in the present patent provides an effective barrier against aqueous solutions for up to 7 days.
  • the catheter securement capability of the liquid adhesive composition disclosed inthe present patent was also evaluated in the canine model on securing three different types of cannulas in peripheral and central veins.
  • a total of six dogs were enrolled in this study and divided into 3 groups with two animals per group.
  • Either Insyte Autoguard IV Catheters, Power PICC Dual-Lumen Catheters, or Arrowgard Coated Polyurethane CVCs were implanted into the animals representing the three different groups.
  • Each animal had two of the same type catheters implanted in either jugular veins (Power PICC or Arrowgard) or cephalic veins (Autoguard) and the liquid adhesive composition disclosed in the present patent was applied to each insertion site to secure the catheter.
  • the TSA plates were challenged with -100- 500cfu (10 pL) of the challenge organism and the liquid adhesive composition disclosed in the present patent was immediately applied over the challenge organism.
  • the inoculum and glue wereallowed to dry and were then incubated, at 30-35°C ( Escherichia coli and Proteus mirabilis) and 20-25°C ( ⁇ Serratia marcescens).
  • a positive control and a negative control were also tested and all plates were monitored for up to 48hrs.
  • the mm of horizontal growth/spread were measured for thetest article and the positive control.
  • the positive control demonstrated the movement of the challenge organisms with results of 1.5mm.
  • the liquid adhesive composition disclosed in the present patent has the potential to mitigate the risk of infection at the insertion site, near open wounds or damaged skin providing protection to the overall vascular access site.
  • the average viscosity and set time for the liquid adhesive composition was 6.0 cps, and 18 seconds, respectively, at day 0, which were slightly increased to 48.4 cps and 44 seconds, respectively, at real time shelf month 24. Both the viscosity and set time throughout the 24 months of real tie shelf life have remained within the specifications (200 cps, and 90 seconds, respectively).
  • the average viscosity and set time for the liquid adhesive composition was 5.33 cps, and 17.5 seconds, respectively, at day 0, which were slightly increased to 9.35 cps and 35 seconds, respectively, at real time shelf month 24. Both the viscosity and set time throughout the 24 months of real tie shelf life have remained within the specifications (200 cps, and 90 seconds, respectively).

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
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Abstract

Compositions et procédés de fixation de cathéter procurant une fixation extrêmement solide, un joint résistant à l'eau, une hémostase efficace et des propriétés antibactériennes au niveau et autour de sites d'accès vasculaire. Par fixation du site d'insertion et du raccord à la peau, la composition et le procédé réduisent des complications telles qu'un délogement de cathéter, une infiltration de cathéter, une migration de cathéter, une occlusion de cathéter, une phlébite associée à un cathéter et des infections associées à un cathéter.
PCT/US2022/011471 2021-01-07 2022-01-06 Compositions et procédés de fixation de cathéter WO2022150498A1 (fr)

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US63/134,888 2021-01-07
US17/569,168 2022-01-05
US17/569,168 US20220218951A1 (en) 2021-01-07 2022-01-05 Catheter securement compositions and methods providing significantly strong securement, water resistant seal, effective hemostatis, and antibacterial properties at and around vascular access sites

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140163610A1 (en) * 2008-10-31 2014-06-12 Adhezion Biomedical, Llc Sterilized liquid compositions of cyanoacrylate monomer mixtures
US20150283290A1 (en) * 2014-04-02 2015-10-08 Adhezion Biomedical, Llc Sterilized compositions of cyanoacrylate monomers and naphthoquinone 2,3-oxides
US20160158499A1 (en) * 2009-10-29 2016-06-09 Robert E. Helm Two-Part Multi-Function Vascular Catheter And Integrated Circumferentially Sealing Securement Dressing
WO2018186979A1 (fr) * 2017-04-07 2018-10-11 Becton, Dickinson And Company Dispositif de fixation de cathéter avec fenêtre
WO2019099352A1 (fr) * 2017-11-14 2019-05-23 Adhezion Biomedical, Llc Dispositif et compositions liquides pour fixer des cathéters ayant une pointe effilée rigide

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20140163610A1 (en) * 2008-10-31 2014-06-12 Adhezion Biomedical, Llc Sterilized liquid compositions of cyanoacrylate monomer mixtures
US20160158499A1 (en) * 2009-10-29 2016-06-09 Robert E. Helm Two-Part Multi-Function Vascular Catheter And Integrated Circumferentially Sealing Securement Dressing
US20150283290A1 (en) * 2014-04-02 2015-10-08 Adhezion Biomedical, Llc Sterilized compositions of cyanoacrylate monomers and naphthoquinone 2,3-oxides
WO2018186979A1 (fr) * 2017-04-07 2018-10-11 Becton, Dickinson And Company Dispositif de fixation de cathéter avec fenêtre
WO2019099352A1 (fr) * 2017-11-14 2019-05-23 Adhezion Biomedical, Llc Dispositif et compositions liquides pour fixer des cathéters ayant une pointe effilée rigide

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