NZ757861B2 - Catheter tubing with tailored modulus response - Google Patents
Catheter tubing with tailored modulus response Download PDFInfo
- Publication number
- NZ757861B2 NZ757861B2 NZ757861A NZ75786118A NZ757861B2 NZ 757861 B2 NZ757861 B2 NZ 757861B2 NZ 757861 A NZ757861 A NZ 757861A NZ 75786118 A NZ75786118 A NZ 75786118A NZ 757861 B2 NZ757861 B2 NZ 757861B2
- Authority
- NZ
- New Zealand
- Prior art keywords
- catheter tubing
- elastic modulus
- catheter
- thermoplastic polyurethane
- polyurethane
- Prior art date
Links
- 229920002803 Thermoplastic polyurethane Polymers 0.000 claims abstract description 95
- 239000004433 Thermoplastic polyurethane Substances 0.000 claims abstract description 95
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 17
- 239000011780 sodium chloride Substances 0.000 claims description 17
- TZCXTZWJZNENPQ-UHFFFAOYSA-L Barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 claims description 16
- 239000004970 Chain extender Substances 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 125000005442 diisocyanate group Chemical group 0.000 claims description 13
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- GLQBXSIPUULYOG-UHFFFAOYSA-M Bismuth oxychloride Chemical compound Cl[Bi]=O GLQBXSIPUULYOG-UHFFFAOYSA-M 0.000 claims description 8
- WMWLMWRWZQELOS-UHFFFAOYSA-N Bismuth(III) oxide Chemical compound O=[Bi]O[Bi]=O WMWLMWRWZQELOS-UHFFFAOYSA-N 0.000 claims description 8
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- MGLUJXPJRXTKJM-UHFFFAOYSA-L bismuth subcarbonate Chemical compound O=[Bi]OC(=O)O[Bi]=O MGLUJXPJRXTKJM-UHFFFAOYSA-L 0.000 claims description 4
- 229940036358 bismuth subcarbonate Drugs 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 claims description 4
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- QZWKEPYTBWZJJA-UHFFFAOYSA-N 3,3'-Dimethoxybenzidine-4,4'-diisocyanate Chemical compound C1=C(N=C=O)C(OC)=CC(C=2C=C(OC)C(N=C=O)=CC=2)=C1 QZWKEPYTBWZJJA-UHFFFAOYSA-N 0.000 description 2
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- UPMLOUAZCHDJJD-UHFFFAOYSA-N Diphenylmethane p,p'-diisocyanate Chemical compound C1=CC(N=C=O)=CC=C1CC1=CC=C(N=C=O)C=C1 UPMLOUAZCHDJJD-UHFFFAOYSA-N 0.000 description 2
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- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
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- 150000004985 diamines Chemical class 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
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- 239000000945 filler Substances 0.000 description 2
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- 239000004416 thermosoftening plastic Substances 0.000 description 2
- RUELTTOHQODFPA-UHFFFAOYSA-N toluene 2,6-diisocyanate Chemical compound CC1=C(N=C=O)C=CC=C1N=C=O RUELTTOHQODFPA-UHFFFAOYSA-N 0.000 description 2
- 229940035437 1,3-propanediol Drugs 0.000 description 1
- SBJCUZQNHOLYMD-UHFFFAOYSA-N 1,5-Naphthalene diisocyanate Chemical compound C1=CC=C2C(N=C=O)=CC=CC2=C1N=C=O SBJCUZQNHOLYMD-UHFFFAOYSA-N 0.000 description 1
- ALQSHHUCVQOPAS-UHFFFAOYSA-N 1,5-Pentanediol Chemical compound OCCCCCO ALQSHHUCVQOPAS-UHFFFAOYSA-N 0.000 description 1
- XXMIOPMDWAUFGU-UHFFFAOYSA-N 1,6-Hexanediol Chemical compound OCCCCCCO XXMIOPMDWAUFGU-UHFFFAOYSA-N 0.000 description 1
- CHUGKEQJSLOLHL-UHFFFAOYSA-N 2,2-Bis(bromomethyl)propane-1,3-diol Chemical compound OCC(CO)(CBr)CBr CHUGKEQJSLOLHL-UHFFFAOYSA-N 0.000 description 1
- SLCVBVWXLSEKPL-UHFFFAOYSA-N 2,2-dimethylpropane-1,3-diol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 description 1
- CTNICFBTUIFPOE-UHFFFAOYSA-N 2-(4-hydroxyphenoxy)ethane-1,1-diol Chemical compound OC(O)COC1=CC=C(O)C=C1 CTNICFBTUIFPOE-UHFFFAOYSA-N 0.000 description 1
- QWGRWMMWNDWRQN-UHFFFAOYSA-N 2-methylpropane-1,3-diol Chemical compound OCC(C)CO QWGRWMMWNDWRQN-UHFFFAOYSA-N 0.000 description 1
- 231100000716 Acceptable daily intake Toxicity 0.000 description 1
- 210000004369 Blood Anatomy 0.000 description 1
- 229920002068 Fluorinated ethylene propylene Polymers 0.000 description 1
- HCDGVLDPFQMKDK-UHFFFAOYSA-N Hexafluoropropylene Chemical group FC(F)=C(F)C(F)(F)F HCDGVLDPFQMKDK-UHFFFAOYSA-N 0.000 description 1
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- 238000010521 absorption reaction Methods 0.000 description 1
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- VSSAZBXXNIABDN-UHFFFAOYSA-N cyclohexylmethanol Chemical compound OCC1CCCCC1 VSSAZBXXNIABDN-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent Effects 0.000 description 1
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- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
- CGNJFUJNEYIYRZ-UHFFFAOYSA-N nonane-1,3-diol Chemical compound CCCCCCC(O)CCO CGNJFUJNEYIYRZ-UHFFFAOYSA-N 0.000 description 1
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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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
-
- 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
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/42—Anti-thrombotic agents, anticoagulants, anti-platelet agents
-
- 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
- A61L29/02—Inorganic materials
-
- 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
- A61L29/049—Mixtures of macromolecular compounds
-
- A—HUMAN NECESSITIES
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- 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
- A61L29/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
-
- 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
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/16—Biologically active materials, e.g. therapeutic substances
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- A—HUMAN NECESSITIES
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- 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
- A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
- A61L29/18—Materials at least partially X-ray or laser opaque
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0043—Catheters; Hollow probes characterised by structural features
- A61M2025/0059—Catheters; Hollow probes characterised by structural features having means for preventing the catheter, sheath or lumens from collapsing due to outer forces, e.g. compressing forces, or caused by twisting or kinking
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- A—HUMAN NECESSITIES
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- A61M25/00—Catheters; Hollow probes
- A61M25/0043—Catheters; Hollow probes characterised by structural features
- A61M2025/006—Catheters; Hollow probes characterised by structural features having a special surface topography or special surface properties, e.g. roughened or knurled surface
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- A61M25/00—Catheters; Hollow probes
- A61M25/0043—Catheters; Hollow probes characterised by structural features
- A61M2025/0063—Catheters; Hollow probes characterised by structural features having means, e.g. stylets, mandrils, rods or wires to reinforce or adjust temporarily the stiffness, column strength or pushability of catheters which are already inserted into the human body
- A61M2025/0064—Catheters; Hollow probes characterised by structural features having means, e.g. stylets, mandrils, rods or wires to reinforce or adjust temporarily the stiffness, column strength or pushability of catheters which are already inserted into the human body which become stiffer or softer when heated
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- A—HUMAN NECESSITIES
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- A61M25/00—Catheters; Hollow probes
- A61M25/0043—Catheters; Hollow probes characterised by structural features
- A61M2025/0063—Catheters; Hollow probes characterised by structural features having means, e.g. stylets, mandrils, rods or wires to reinforce or adjust temporarily the stiffness, column strength or pushability of catheters which are already inserted into the human body
- A61M2025/0065—Catheters; Hollow probes characterised by structural features having means, e.g. stylets, mandrils, rods or wires to reinforce or adjust temporarily the stiffness, column strength or pushability of catheters which are already inserted into the human body which become stiffer or softer when becoming wet or humid, e.g. immersed within a liquid
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- A—HUMAN NECESSITIES
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- A61M25/00—Catheters; Hollow probes
- A61M25/0009—Making of catheters or other medical or surgical tubes
- A61M25/0012—Making of catheters or other medical or surgical tubes with embedded structures, e.g. coils, braids, meshes, strands or radiopaque coils
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- A—HUMAN NECESSITIES
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- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0017—Catheters; Hollow probes specially adapted for long-term hygiene care, e.g. urethral or indwelling catheters to prevent infections
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0021—Catheters; Hollow probes characterised by the form of the tubing
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M25/00—Catheters; Hollow probes
- A61M25/0043—Catheters; Hollow probes characterised by structural features
- A61M25/0054—Catheters; Hollow probes characterised by structural features with regions for increasing flexibility
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/30—Low-molecular-weight compounds
- C08G18/32—Polyhydroxy compounds; Polyamines; Hydroxyamines
- C08G18/3203—Polyhydroxy compounds
- C08G18/3206—Polyhydroxy compounds aliphatic
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/48—Polyethers
- C08G18/4854—Polyethers containing oxyalkylene groups having four carbon atoms in the alkylene group
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
- C08G18/66—Compounds of groups C08G18/42, C08G18/48, or C08G18/52
- C08G18/6666—Compounds of group C08G18/48 or C08G18/52
- C08G18/667—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38
- C08G18/6674—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/3203
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/74—Polyisocyanates or polyisothiocyanates cyclic
- C08G18/76—Polyisocyanates or polyisothiocyanates cyclic aromatic
- C08G18/7657—Polyisocyanates or polyisothiocyanates cyclic aromatic containing two or more aromatic rings
- C08G18/7664—Polyisocyanates or polyisothiocyanates cyclic aromatic containing two or more aromatic rings containing alkylene polyphenyl groups
- C08G18/7671—Polyisocyanates or polyisothiocyanates cyclic aromatic containing two or more aromatic rings containing alkylene polyphenyl groups containing only one alkylene bisphenyl group
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L75/00—Compositions of polyureas or polyurethanes; Compositions of derivatives of such polymers
- C08L75/04—Polyurethanes
Abstract
Catheter tubing comprises: an elongate body comprising a base thermoplastic polyurethane; and a compounded thermoplastic polyurethane co-extruded with the base thermoplastic polyurethane to provide a section of catheter tubing discrete from the elongate body, the compounded thermoplastic polyurethane comprising a thermoplastic polyurethane and a radiopaque material, wherein the catheter tubing comprises a first elastic modulus under first conditions prior to entry into a patient; and wherein when exposed to second conditions comprising two or more in vivostimuli for a duration of time the catheter tubing comprises a second elastic modulus that is not more than fifty percent of the first modulus. The first elastic modulus is at least 1300 MPa. e comprising a thermoplastic polyurethane and a radiopaque material, wherein the catheter tubing comprises a first elastic modulus under first conditions prior to entry into a patient; and wherein when exposed to second conditions comprising two or more in vivostimuli for a duration of time the catheter tubing comprises a second elastic modulus that is not more than fifty percent of the first modulus. The first elastic modulus is at least 1300 MPa.
Description
CATHETER TUBING WITH TAILORED MODULUS RESPONSE
TECHNICAL FIELD
The present disclosure relates generally to devices, systems, and methods
in the medical field including catheter tubing comprising a thermoplastic polyurethane
having a softening profile where the tubing softens only upon exposure to in vivo stimuli.
BACKGROUND
Thermoplastic polyurethane materials are some of the most commonly
used biomaterial polymer for various medical applications. Some thermoplastic
polyurethane materials are stiff and their flexibility may not be controllable. This limits
their use in many types of polyurethane medical applications, especially for long-term
medical uses. In some cases, these materials are not able to maintain their original
stiffness or other physical property and their physical properties change too quickly.
For medication infusion or injection, an invasive medical device is
typically used to create a fluid channel from a medication reservoir to the patient, usually
to vascular vessels or subcutaneous tissue. To ensure success of insertion to the body
tissue of a target area, the entry portion of the device needs to be stiff enough for
minimum pain. Intravascular catheters, for example, are currently utilized in a wide
variety of minimally invasive medical procedures. Generally, an intravascular catheter
allows a clinician to remotely perform a medical procedure by inserting the catheter into
the patient’s vascular system. Typically, the practice is to insert a flexible catheter tube
into a vein and leave the catheter tube in such a position for purposes such as periodically
administering fluids, transfusions and medication, collecting of blood samples, and the
like. The catheter tube may remain in place for days or weeks at a time. After the distal
portion of the catheter tube has entered the patient’s vascular system, the clinician may
advance the distal tip forward by applying longitudinal forces to the proximal portion of
the catheter and bend force to the catheter tube body. For the catheter tubing to
effectively communicate these longitudinal forces, it is desirable that the catheter tube
has a high level of pushability, which can be translated to a material property of high
stiffness of catheter tube. In some countries, nursing practices prior to insertion of IV
catheter include pre-priming the IV catheters in 25°C (or ambient) saline, which can
cause the tubing to soften such that insertion becomes difficult. Once reaching the tissue,
such as a blood vessel, the part of the device that remains in the tissue needs to be soft
enough to minimize potential complications, such as mechanical phlebitis, and improve
patient comfort. In some instances, a catheter may cause phlebitis, which is an
inflammation of a vein, due to local trauma to the vein in which the catheter is inserted.
Harder catheters in the vein can be more likely to cause such trauma.
There remains a need for polyurethanes for catheter manufacture that are
stiff under ambient conditions for catheter insertion but which becomes soft and pliable
for positioning and indwelling only upon exposure to more than one in vivo stimuli.
SUMMARY
Provided are medical devices, for example, catheter tubing. Non-limiting
examples of catheter tubing include: peripheral intravenous (IV) catheters; intravascular
catheters; central venous catheters including tri-lumen, bi-lumen, and single lumen;
midline catheters; and urinary catheters. Vascular access devices may use catheter tubing
as disclosed herein in conjunction with one or more components such as needles and/or
guidewires.
In an embodiment, a catheter tubing comprises: an elongate body
comprising a base thermoplastic polyurethane; and a compounded thermoplastic
polyurethane co-extruded with the base thermoplastic polyurethane to provide a section
of catheter tubing discrete from the elongate body, the compounded thermoplastic
polyurethane comprising a thermoplastic polyurethane and a radiopaque material;
wherein the catheter tubing comprises a first elastic modulus under first conditions prior
to entry into a patient; and wherein when exposed to second conditions comprising two or
more in vivo stimuli for a time, the catheter tubing comprises a second elastic modulus
that is not more than fifty percent of the first modulus.
The thermoplastic polyurethane of the compounded thermoplastic
polyurethane may be a different formulation from the base thermoplastic polyurethane.
The section discrete from the elongate body may comprise one or more elongate stripes
comprising the compounded thermoplastic polyurethane, integrally formed with the
elongate body. The catheter tubing of may have a cross-sectional area that comprises the
base thermoplastic polyurethane in an amount in the range of 60% to 80% and the
compounded thermoplastic polyurethane in an amount in the range of 20% to 40%.
The first conditions may comprise: a temperature in the range of 20 to
°C and a relative humidity in the range of 0 to 90%. The first elastic modulus may be
at least 1300 MPa. The first elastic modulus may be the range of 1300 to 2200 MPa.
The two or more in vivo stimuli of the second conditions may comprise a
temperature in the range of about 36 to about 40°C, and one or more of: saline, plasma,
white blood cells, platelets, red blood cells, water, absence of light, antibodies, and
enzymes. The second elastic modulus may be at most 650 MPa, 400 MPa, 200 MPa, or
100 MPa. The second elastic modulus may be in the range of 10 to 650 MPa, 10 to 400
MPa, 10 to 200 MPa, or 10 to 100 MPa. The second elastic modulus may be reached
after exposure to the second conditions for about 30 minutes or less. The second elastic
modulus may be reached after exposure to the second conditions for about 5 to about 10
minutes.
The radiopaque material of the compounded thermoplastic polyurethane
may comprise bismuth oxychloride (BiOCl), bismuth trioxide (Bi O ), bismuth
subcarbonate (Bi O CO ), barium sulfate (BaSO ), tungsten (W), or combinations
2 2 3 4
thereof.
The base thermoplastic polyurethane, the compounded thermoplastic
polyurethane, or both may further comprise an antithrombogenic agent, an antimicrobial
agent, a lubricant, a colorant, an active pharmaceutical, or combinations thereof.
In a detailed aspect, a catheter tubing comprises: an elongate body
comprising a base thermoplastic polyurethane that is a product from a reaction of: a
diisocyanate, a diol chain extender, at least one polyglycol, and optionally, an amine-
terminated polyether, the base thermoplastic polyurethane optionally further comprising
an antithrombogenic agent, an antimicrobial agent, a lubricant, a colorant, an active
pharmaceutical, or combinations thereof; and one or more elongate stripes co-extruded
with the base thermoplastic polyurethane, the elongate stripes comprising a compounded
thermoplastic polyurethane comprising a thermoplastic polyurethane and a radiopaque
material; wherein the catheter tubing comprises a first elastic modulus under first
conditions prior to entry into a patient; and wherein when exposed to second conditions
comprising two or more in vivo stimuli for a time, the catheter tubing comprises a second
elastic modulus that is not more than fifty percent of the first modulus.
The first conditions may comprise: a temperature in the range of 20 to
°C and a relative humidity in the range of 0 to 90% and the two or more in vivo stimuli
of the second conditions comprise a temperature in the range of about 36 to about 40°C,
and one or more of: saline, plasma, white blood cells, platelets, red blood cells, water,
absence of light, antibodies, and enzymes.
The first elastic modulus may be in the range of 1300 to 2200 MPa and the
second elastic modulus is the range of 10 to 650 MPa, 10 to 400 MPa, 10 to 200 MPa, or
to 100 MPa.
The second elastic modulus may be reached after exposure to the second
conditions for about 30 minutes or less. The second elastic modulus may be reached after
exposure to the second conditions for about 5 to about 10 minutes.
An aspect is a vascular access device comprising any catheter tubing
disclosed herein in combination with one or more components, wherein the vascular
access device is selected from the group consisting of: a central venous catheter, a
peripherally-inserted central catheter, a midline catheter and a peripheral intravenous
catheter.
An aspect is a method of making a medical device including a catheter
tubing comprising: designing an elongate body having a section of catheter tubing
discrete from the elongate body to form the catheter tubing such that the catheter tubing
comprises a first elastic modulus under first conditions prior to entry into a patient; and
wherein when exposed to second conditions comprising two or more in vivo stimuli for a
time, the catheter tubing comprises a second elastic modulus that is not more than fifty
percent of the first modulus.
The designing of the elongate body having the section of catheter tubing
discrete from the elongate body may comprise: providing a base polyurethane; providing
a compounded polyurethane comprising a thermoplastic polyurethane and a radiopaque
material; and co-extruding the base polyurethane and the compounded polyurethane to
form the elongate body of the base polyurethane and the section discrete from the
elongate body of the compounded thermoplastic polyurethane. The method may further
comprise combining the catheter tubing with one or more components to form the
medical device. The one or more components may include a needle and the medical
device may be a vascular access device. The vascular access device may be selected
from the group consisting of: a central venous catheter, a peripherally-inserted central
catheter, a midline catheter, and a peripheral intravenous catheter.
A further aspect is a method of delivering a medical fluid to a patient
comprising: obtaining a catheter tubing; inserting the catheter tubing into a patient under
first conditions when the catheter tubing comprises a first elastic modulus; and indwelling
the catheter tubing for a duration under second conditions when the catheter tubing is
exposed to two or more in vivo stimuli and the catheter tubing comprises a second elastic
modulus that is not more than fifty percent of the first modulus. The catheter tubing may
comprise: an elongate body comprising a base thermoplastic polyurethane; and one or
more sections discrete from the elongate body comprising a compounded polyurethane
comprising a thermoplastic polyurethane and a radiopaque material.
The first conditions may comprise: a temperature in the range of 20 to
°C and a relative humidity in the range of 0 to 90% and the two or more in vivo stimuli
of the second conditions may comprise a temperature in the range of about 36 to about
40°C, and one or more of: saline, plasma, white blood cells, platelets, red blood cells,
water, absence of light, antibodies, and enzymes.
The first elastic modulus may be in the range of 1300 to 2200 MPa and the
second elastic modulus may be in the range of 10 to 650 MPa, 10 to 400 MPa, 10 to 200
MPa, or 10 to 100 MPa. The second elastic modulus may be reached after exposure to
the second condition for about 5 to about 10 minutes.
BRIEF DESCRIPTION OF THE DRAWINGS
provides a schematic cross-section view of an exemplary vascular
access device; and
is plan view of an exemplary catheter.
DETAILED DESCRIPTION
Before describing several exemplary embodiments of the invention, it is to
be understood that the invention is not limited to the details of construction or process
steps set forth in the following description. The invention is capable of other
embodiments and of being practiced or being carried out in various ways.
Provided are medical devices, for example, catheter tubing, that provide
both high inherent stiffness of polyurethane under environmental conditions and
flexibility after being exposed to two or more in vivo stimuli. The devices are a
composite assembly, comprising a base thermoplastic polyurethane and a compounded
thermoplastic polyurethane co-extruded with the base thermoplastic polyurethane. The
base thermoplastic polyurethane and the compounded thermoplastic polyurethane form
discrete sections of the tubing. The compounded thermoplastic polyurethane may form
one or more elongate stripes on or within a body composed of the base polyurethane.
The thermoplastic polyurethane of the compounded thermoplastic polyurethane may be
the same formulation as the base thermoplastic polyurethane, or it may be different
depending on the application. By using a composite system, the tubing herein provides a
nuanced softening profile in a way that unitary systems cannot.
Elastic modulus is a property of a thermoplastic material that indicates a
degree of stiffness or softness of the material. A catheter of stiffer materials at insertion
decreases the likelihood of a failure IV catheter insertion due to catheter failures such as
catheter tip peel back and catheter tubing accordion. An elastic modulus of at least about
400 MPa is a non-limiting target for effective insertion. Upon insertion, softening of the
materials is desirable for comfort and minimizing potential complications. An elastic
modulus that is about 400 MPa may be tolerable for indwelling, but an elastic modulus
that is lower than 400 MPa is desirable for indwelling. For example, relatively low
elastic modulus values in the non-limiting range of less than about 100 MPa may be
desired. As discussed, higher modulus for insertion is desired in combination with lower
modulus for indwelling.
Advantageously, the polyurethane-based catheter tubing of the present
disclosure, which has discrete sections, e.g., stripes, in combination with a body, softens
to an elastic modulus after insertion and exposure to two or more in vivo stimuli that is
reduced by fifty percent or more compared to the elastic modulus prior to insertion. In
one or more embodiments, the tubing has modulus of 500 MPa or greater, or 1300 MPa
or greater, at all environmental conditions encountered during insertions of IV catheters;
however, it will decrease its modulus (for example to 650 MPa or less, or 400 MPa or
less, or 200 MPa or less, or 100 MPa or less) during a relatively short duration (e.g., 30
minutes or less, 10 minutes or less, or about 5 minutes) upon exposure to multiple stimuli
(such as body temperature, saline, plasma, white blood cells and platelets, red blood cells,
water, absence of light, antibodies, certain enzymes, etc.) when in the vein to reduce
catheter related complications like phlebitis, infiltration, and extravasation. In some
countries, nursing practices prior to insertion of IV catheter include pre-priming the IV
catheters in 25°C (or ambient) saline. The catheter tubing of the present disclosure
maintains a high elastic modulus (e.g., 500 MPa or greater, or 1300 MPa or greater),
which is a higher modulus than current commercially available materials within expected
pre-priming to insertion time range (0-10 minutes) to ensure successful insertion of the
IV catheters. That is, upon exposure to only a single in vivo condition, as simulated, for
example, by saline, the tubing of the present disclosure remains stiff enough for insertion.
Upon entry into the body environment and exposure to a second in vivo condition, the
tubing becomes softer.
Prior art in catheter tubing materials have historically focused on the
compositions of polyurethane materials without recognizing particular properties of the
materials properties that facilitate successful with IV catheter placement and monitoring
by a clinician. Until the present disclosure, there was not consideration of properties of
the materials at different environment temperature and humidity or pre-priming
scenarios. The present disclosure has identified that reduction of polyurethane material
modulus only when a combination of multiple stimuli that are unique in the body
environment (e.g., the veins) facilitates successful with IV catheter placement and
monitoring by a clinician.
Elastic modulus as used herein is the pressure at which the catheter tubing
bends, measured in MPa by techniques known in the art. A Dynamic Mechanical
Analyzer (DMA) from TA Instrument model Q800 may be used to measure elastic
modulus.
In vivo stimulus or stimuli refer to actual or simulated condition(s) that
exist in the environment of the body including but not limited to temperature in the range
of about 36 to about 40°C; exposure to: saline, plasma, white blood cells, platelets, red
blood cells, water, antibodies, and enzymes; and absence of light. In vivo stimuli may be
simulated by ex vivo experiments that approximate stimuli that exist in the environment
of the body. This may be done, for example, by exposing tubing to a saline bath with a
temperature in the range of about 36 to about 40°C. Exposure to in vivo stimulus or
stimuli begins when the tubing is securely placed in vivo and achieves the temperature of
the environment of the body. For simulation purposes, exposure to in vivo stimulus or
stimuli begins when the tubing is under steady state in vivo conditions.
Radiopaque materials may be included in compounded polyurethanes to
render them X-ray detectable. Most commonly used radiopaque fillers are one or more
of: bismuth oxychloride (BiOCl), bismuth trioxide (Bi O ), bismuth subcarbonate
(Bi O CO ), barium sulfate (BaSO ), and tungsten (W).
2 2 3 4
POLYURETHANES
Polyurethane materials disclosed herein have controlled and desirable
stiffness and flexibility. The stiffness and flexibility of this polyurethane may be tailored
and purposely varied to fit different practical needs. Medical devices formed of these
polyurethane materials are used to create a fluid channel from a medication reservoir to a
patient in need thereof, where the fluid channel may be inserted into and in fluid
communication with vascular vessels, or subcutaneous tissue, where the invasive medical
device comprises any of the polyurethane materials as described herein.
Thermoplastic polyurethanes (TPUs) suitable for medical devices are
typically synthesized from three basic components, a diisocyanate, a polyglycol, and a
chain extender, usually a low molecular weight diol, diamine, or water. If the chain
extender is a diol, the polyurethane consists entirely of urethane linkages. If the extender
is water or diamine, both urethane and urea linkages are present, which results in a
polyurethaneurea (PUU). Inclusion of an amine-terminated polyether to the polyurethane
synthesis also results in a polyurethaneurea (PUU). Device applications for thermoplastic
polyurethanes include central venous catheters (CVCs), peripherally inserted central
catheter (PICCs), and peripheral intravenous catheters (PIVCs). Thermoplastic
polyurethanes chain extended with diols used in medical devices are disclosed in the
following co-owned patents: U.S. Patent Nos. 5,545,708; 5,226,899; 5,281,677; and
,266,669.
Polyurethane and polyurea chemistries are based on the reactions of
isocyanates with other hydrogen-containing compounds, where isocyanates are
compounds having one or more isocyanate group (-N=C=O). Isocyanate compounds can
be reacted with water (H O), alcohols (R-OH), carboxylic acids (R-COOH), amines (R -
NH ), ureas (R-NH-CONH ), and amides (R-CONH ). Certain polyurethanes may be
(3-x) 2 2
thermoplastic elastomers (TPE), whereas other compositions may be highly cross-linked.
Thermoplastic polyurethanes comprise two-phases or microdomains
conventionally termed hard segments and soft segments, and as a result are often referred
to as segmented polyurethanes. The hard segments, which are generally of high
crystallinity, form by localization of the portions of the polymer molecules which include
the diisocyanate and chain extender(s). The soft segments, which are generally either
non-crystalline or of low crystallinity, form from the polyglycol or the optional amine-
terminated polyether. The hard segment content is determined by the weight percent of
diisocyanate and chain extender in the polyurethane composition, and the soft segment
content is the weight percent of polyglycol or polydiamine. The thermoplastic
polyurethanes may be partly crystalline and/or partly elastomeric depending on the ratio
of hard to soft segments. One of the factors which determine the properties of the
polymer is the ratio of hard and soft segments. In general, the hard segment contributes
to hardness, tensile strength, impact resistance, stiffness and modulus while the soft
segment contributes to water absorption, elongation, elasticity and softness.
Polyurethane materials may be used as raw materials for catheter tubing
via extrusion or molding, where the formed catheter tubing is capable of improving the
success of insertion due to increased initial tubing stiffness, and/or significantly
extending the catheter tubing’s indwelling and reducing catheter tubing induced clinical
complications because of its greater flexibility and antimicrobial activity. The medical
device may have a predetermined balance of stiffness for insertion and pliability for
threading through a blood vessel.
Stiffness, flexibility, and softening in response to environmental changes
depend on the polyurethane's molecular structure and polymerization methods controlled
by adjusting the balance of the hydrophobicity and hydrophilicity of the material. One of
the solutions to control polyurethane stiffness and flexibility is to determine an
appropriate balance between hydrophobicity and hydrophilicity. This may be achieved
by selecting a particular type of isocyanate, polyol, chain extender, and their composition,
to produce an intended combination of properties appropriate for the specific application.
A thermoplastic polyurethane may be produced by the reaction of: a
diisocyanate, a diol chain extender, at least one polyglycol, and optionally, an amine-
terminated polyether. The thermoplastic polyurethane may optionally further comprise
an antithrombogenic agent, an antimicrobial agent, a lubricant, a colorant, an active
pharmaceutical, or combinations thereof. The polyurethane may have a hard segment
content between about 50% and about 70% by weight, where a hard segment is the
portion(s) of the polymer molecules which include the diisocyanate and the extender
components, which are generally highly crystalline due to dipole-dipole interactions
and/or hydrogen bonding. In contrast, the soft segments form from the polyglycol
portions between the diisocyanate of the polymer chains and generally are either
amorphous or only partially crystalline due to the characteristics of the polyglycol(s).
Polymerization of the polyurethane may be a one-step bulk polymerization
without requiring a catalyst or other additives.
A polyglycol is a polymer derived from an alkylene oxide containing
ether-glycol linkages which contains a chain of repeating units with a distribution of a
number of repeating units. Polyglycols include polyetherglycols.
A chain extender is a discrete hydroxyl- and/or amine-terminated
compounds used during polymerization to impart desired properties to a polymer.
With respect to polyurethane chemistry:
Isocyanate index= _Isocyanate equivalents
polyol equivalents
The isocyanate equivalent is defined as the weight of sample which will combine with 1
g equivalent weight of the aromatic diisocyanate. The sample is generally a polyol,
amine or other compound that possesses groups capable of reacting with an isocyanate.
See C. Hepburn “Polyurethane Elastomers ” 2nd Edition, Springer, pages 42-43, (1992).
In general, the polyurethane becomes harder with an increasing isocyanate index. There
is, however, a point beyond which the hardness does not increase and the other physical
properties begin to deteriorate. Polyurethane materials provided herein have an
isocyanate index in the range of 1 to 1.4.
The diisocyanate may be an aromatic diisocyanate. In various
embodiments, the aromatic isocyanate may be selected from the group consisting of 4,4'-
diphenylmethane diisocyanate (MDI) (Formula I), 2,2'-dimethyl- 4,4'-
biphenyldiisocyanate (Formula II), 3,3'-dimethyl-4,4'-diphenyl diisocyanate (TODI)
(Formula III), 2,4-toluene diisocyanate, 2,6-toluene diisocyanate (TDI), 1,5-naphthalene
diisocyanate (NDI), 4,6'-xylylene diisocyanate (XDI), 3,3'-dimethyl-diphenylmethane
4,4'-diisocyanate (DMMDI), dianisidine diisocyanate (DADI), and their blends.
(I), (II), and (III).
The at least one polyglycol may be a polytetramethylene ether glycol. The
polytetramethylene ether glycol (PTMEG) may be PTMEG250, PTMEG650,
PTMEG1000, PTMEG1450, PTMEG1800, PTMEG2000, and PTMEG2900. PTMEG
having the formula: HO(CH CH CH CH -O-) H, which may have an average value of n
2 2 2 2 n
in the range of 3 to 40. A blend of two or more PTMEG250, PTMEG650, PTMEG1000,
PTMEG1450, PTMEG1800, PTMEG2000, and PTMEG2900 may be used such. A
preferred an average molecular weight of the combination is about 1000 Da. In one or
more embodiments, the polyols is a blend of two or more PTMEG having the formula:
HO(CH CH CH CH -O-) H, where n has an average value in the range of 3 to 40 and an
2 2 2 2 n
average molecular weight of the combination being 1000 Da or less.
Additional polyglycols may be present in the polyurethane material,
including but not limited to: polyethylene oxide glycol (PEG), polypropylene oxide
glycol (PPG), polyester glycol, silicone glycol, polycarbonate glycol, and combinations
thereof. The additional polyglycols may be selected from: PEG 8000, PPG PT3000, or
combinations thereof. PEG 8000 is a polyethylene glycol having a formula weight of
7,000-9,000. PPG PT3000 is a polypropylene glycol having an average molecular weight
of 3,000. A polycarbonate glycol having an average molecular weight of 350 to 1000
may be used.
A diol may be linear, comprising one or more of: butane diol (BDO),
ethylene glycol, diethylene glycol, triethylene glycol, l,2-propane diol, 1,3-propane diol,
1,5-pentanediol, 1,6-hexane diol, l,4-bis hydroxymethyl cyclohexane, hydroquinone
dihydroxyethyl ether. A diol may be side-branching, comprising one or more of: 2,2-
dimethyl-1,3-propanediol (NPG), 2-methyl-1,3-propanediol, 2-butylethyl-1,3-
propanediol (BEPD), 1,3-Dibromo-2,2-dimethylolpropane (BBMPD).
The polyurethane may further comprise a polyetheramine. Suitable
polyetheramines include but are not limited to amine-terminated polyethers having
repeating units of polyethylene oxide, polypropylene oxide or polytetramethylene oxide
and having a molecular weight in the range of about 400 to 8,000. Preferred
polyetheramines have polypropylene oxide repeating units. Jeffamine® D4000 is a
specific polyetheramine, an amine-terminated polyoxypropylene glycol, having an
average molecular weight of about 4000.
The polyurethanes described herein may be fabricated into film, tubing,
and other forms by conventional thermoplastic fabricating techniques including melt
casting, extrusion, molding, etc. The polyurethane described herein may be used for
PICCs, PIVCs, and CVCs. The polymer may have incorporated therein, as desired,
conventional stabilizers. The amounts of these materials will vary depending upon the
application of the polyurethane, but they are typically present in amounts so ranging from
0.1 to 50 weight percent of the polymer.
The stiffness, flexibility and polyurethane’s softening are dependent of its
molecular structure and its environment. Polyurethane’s flexibility can be changed by a
change of its environment, and controlled by adjusting the balance of its hydrophobicity
and hydrophilicity of the material. The hydrophobicity and hydrophilicity depends on its
molecular structure and composition.
GENERAL PROCEDURE FOR POLYURETHANE SYNTHESIS
The polyurethanes discussed here were prepared by “one shot” bulk
synthesis process. The polyol(s) and chain extender(s) were mixed thoroughly with
vacuum stripping first and then with nitrogen gas purging for 12 to 24 hours. At ambient
temperature, a calculated quantity of diisocyanate was added all at once with very
vigorous stirring. Vigorous stirring was conducted, then the mixture was poured into a
Teflon-lined tray and immediately placed in an oven for post curing.
Table 1. Exemplary Formulations of Polyurethanes with the proviso that
the ingredients total 100%.
Table 1 1-A 1-B 1-C
Reactant by weight by weight by weight
Diisocyanate 30-60% 35-55% 40-50%
Total Polyglycol 10-44.9% 15-39.9 22-34.9
Polyetheramine MW230-4000 0-30% 0-25% 0-20%
Diol Chain Extender 0.1-25% 5-20% 12-18%
Hard Segment % 50-75% 52-68% 55-65%
Table 2. Exemplary Formulations of Compounded Polyurethanes with the
proviso that the ingredients total 100%.
Table 2 2-A 2-B 2-C
Reactant by weight by weight by weight
Diisocyanate 20-45% 25-40% 29-39%
Total Polyglycol 10-39.9% 11-35.9 12-29.9
Polyetheramine MW230-4000 0-20% 0-15% 0-10%
Diol Chain Extender 0.1-20% 5-18% 6-15%
Radiopaque Material 10%-50% 15-50% 15-45%
GENERAL PROCEDURE FOR FORMATION OF VASCULAR ACCESS
DEVICES
Vascular access devices include but are not limited to catheter tubing.
Exemplary devices are: central venous catheters, peripherally-inserted central catheters,
and peripheral intravenous catheters. Catheter tubing can be formed through
compounding and extrusion or coextrusion processes. During the compounding,
granulates of synthesized polyurethanes described herein and radiopaque filler are added
into a compounder simultaneously. The mix ratio can be controlled and adjusted by a
gravimetric multiple-feeder system. The mixed polyurethane melt continuously passes
through a die in the front of the compounder, passes through a quench tank, and is cut
into regular-sized pellets by a puller-pelletizer. The collected pellets are used to be fed
into an extruder/coextruder to form a catheter tube, depending on tubing’s specific
configuration.
Embodiments of catheter tubing based on polyurethanes discussed herein
can be varied by changing and selecting of extruder/coextruders, extrusion dies, the
number of stripes and layers, the volume percentage of stripe material and the type of
radiopaque agent.
Turning to the figures, provides a schematic cross-section of an
exemplary vascular access device in the form of catheter tubing 100, which comprises a
body 122 of a base polyurethane and one or more stripes 112 of a compounded
polyurethane throughout the body 122. The body 122 is clear and the stripes 112 are
opaque and positioned to permit visual feedback in the areas of the catheter body 122
where there are not stripes. The compounded polyurethane of the stripes 112 may
according to any of the exemplary formulations of Table 2, including radiopaque
material(s) 111. The stripe 112 may include the same base polyurethane as body 122 or
the stripe 112 may include a different polyurethane compared to the base polyurethane of
body 122. The stripes 112 are generally elongate along the tubing. In this embodiment,
there are six stripes 112 of oval cross-section, which are substantially evenly distributed
throughout the body 122. Distance of the stripe to the tubing outer surface is d1 and
distance of the stripe to the tubing inner surface is d2. The stripes 112 in one or more
embodiments are spaced to be equidistant between the tubing inner and outer surfaces
(d1=d2). The body 122 defines a lumen 115. To form the striped tubing of the
compounded polyurethane is coextruded with the base polyurethane and processed
through a cross-head die to form an integral tubing having stripes.
In one or more embodiments, a cross-sectional area of the tubing
comprises the base thermoplastic polyurethane in an amount in the range of 60% to 80%
and the compounded thermoplastic polyurethane in an amount in the range of 20% to
40%. In an embodiment, the cross-sectional area comprises 35±3% stripes. In another
embodiment, the cross-sectional area comprises 25±3% stripes.
The catheter tubing disclosed herein demonstrates a first elastic modulus
under first conditions prior to entry into a patient. The first elastic modulus may be at
least 500 MPa, or 600 MPa, or 700 MPa, or 800 MPa, or 900 MPa, or 1000 MPa, or 1100
MPa, or 1200 MPa, or 1300 MPa or greater. The first elastic modulus may be in the
range of 500 to 2200 MPa or 1300 MPa to 2200 MPa.
The catheter tubing disclosed herein demonstrates a second elastic
modulus after exposure for a duration to second conditions comprising two or more in
vivo stimuli after to entry into a patient. The second elastic modulus is not more than
fifty percent of the first modulus. That is, the second elastic modulus is reduced by more
than fifty percent after exposure to the second conditions for a duration. The second
elastic modulus may be at most 650 MPa, or 600 MPa, or 550 MPa, or 500 MPa, or 450
MPa, or 400 MPa, or 350 MPa, or 300 MPa, or 250 MPa, or 200 MPa, or 150 MPa, or
100 MPa, or 50 MPa, or 10 MPa, or less. The second elastic modulus may be in the
range of 10 to 650 MPa and ranges and sub-ranges in between. The second elastic
modulus may be reached after a duration of about 30 minutes or less, 25 minutes or less ,
minutes or less, 15 minutes or less, or 10 minutes or less. The second elastic modulus
may be reached after a duration in the range of about 5 to 30 minutes, about 5 to 25
minutes, about 5 to 20 minutes, or about 5 to 10 minutes.
In an exemplary catheter is illustrated. Catheter tubing as
disclosed herein forms the catheter, which is shaped as needed to receive other
components for forming vascular access devices. Catheter 10 comprises a primary
conduit 12, which is tubing in its as-extruded form. At a distal end, a tip 14 is formed by
a tipping process. At a proximal end, a flange 16 is formed as needed for receipt of other
components including but not limited to catheter adapters. Exemplary vascular access
devices may include a needle further to the catheter for access to blood vessels.
EMBODIMENTS
Various embodiments are listed below. It will be understood that the
embodiments listed below may be combined with all aspects and other embodiments in
accordance with the scope of the invention.
Embodiment 1. A catheter tubing comprising: an elongate body
comprising a base thermoplastic polyurethane; and a compounded thermoplastic
polyurethane co-extruded with the base thermoplastic polyurethane to provide a section
of catheter tubing discrete from the elongate body, the compounded thermoplastic
polyurethane comprising a thermoplastic polyurethane and a radiopaque material;
wherein the catheter tubing comprises a first elastic modulus under first conditions prior
to entry into a patient; and wherein when exposed to second conditions comprising two or
more in vivo stimuli for a time, the catheter tubing comprises a second elastic modulus
that is not more than fifty percent of the first modulus.
Embodiment 2. The catheter tubing of embodiment 1, wherein the
thermoplastic polyurethane of the compounded thermoplastic polyurethane is a different
formulation from the base thermoplastic polyurethane.
Embodiment 3. The catheter tubing of one of embodiments 1 to 2, wherein
the section discrete from the elongate body comprises one or more elongate stripes
comprising the compounded thermoplastic polyurethane, integrally formed with the
elongate body.
Embodiment 4. The catheter tubing of one of embodiments 1 to 3 having a
cross-sectional area that comprises the base thermoplastic polyurethane in an amount in
the range of 60% to 80% and the compounded thermoplastic polyurethane in an amount
in the range of 20% to 40%.
Embodiment 5. The catheter tubing of one of embodiments 1 to 4, wherein
the first conditions comprise: a temperature in the range of 20 to 30°C and a relative
humidity in the range of 0 to 90%.
Embodiment 6. The catheter tubing of one of embodiments 1 to 5, wherein
the first elastic modulus is at least 1300 MPa.
Embodiment 7. The catheter tubing of one of embodiments 1 to 6, wherein
the first elastic modulus is the range of 1300 to 2200 MPa.
Embodiment 8. The catheter tubing of one of embodiments 1 to 7, wherein
the two or more in vivo stimuli of the second conditions comprise a temperature in the
range of about 36 to about 40°C, and one or more of: saline, plasma, white blood cells,
platelets, red blood cells, water, absence of light, antibodies, and enzymes.
Embodiment 9. The catheter tubing of one of embodiments 1 to 8, wherein
the second elastic modulus is at most 650 MPa, at most 400 MPa, at most 200 MPa, or at
most 100 MPa.
Embodiment 10. The catheter tubing of one of embodiments 1 to 9,
wherein the second elastic modulus is the range of 10 to 650 MPa, 10 to 400 MPa, 10 to
200 MPa, or 10 to 100 MPa.
Embodiment 11. The catheter tubing of one of embodiments 1 to 10,
wherein the second elastic modulus is reached after exposure to the second conditions for
about 30 minutes or less.
Embodiment 12. The catheter tubing of embodiment 11, wherein the
second elastic modulus is reached after exposure to the second conditions for about 5 to
about 10 minutes.
Embodiment 13. The catheter tubing of one of embodiments 1 to 12,
wherein the radiopaque material of the compounded thermoplastic polyurethane
comprises bismuth oxychloride (BiOCl), bismuth trioxide (Bi O ), bismuth subcarbonate
(Bi O CO ), barium sulfate (BaSO ), tungsten (W), or combinations thereof.
2 2 3 4
Embodiment 14. The catheter tubing of one of embodiments 1 to 13,
wherein the base thermoplastic polyurethane, the compounded thermoplastic
polyurethane, or both further comprise an antithrombogenic agent, an antimicrobial
agent, a lubricant, a colorant, an active pharmaceutical, or combinations thereof.
Embodiment 15. A catheter tubing comprising: an elongate body
comprising a base thermoplastic polyurethane that is a product from a reaction of: a
diisocyanate, a diol chain extender, at least one polyglycol, and optionally, an amine-
terminated polyether, the base thermoplastic polyurethane optionally further comprising
an antithrombogenic agent, an antimicrobial agent, a lubricant, a colorant, an active
pharmaceutical, or combinations thereof; and one or more elongate stripes co-extruded
with the base thermoplastic polyurethane, the elongate stripes comprising a compounded
thermoplastic polyurethane comprising a thermoplastic polyurethane and a radiopaque
material; wherein the catheter tubing comprises a first elastic modulus under first
conditions prior to entry into a patient; and wherein when exposed to second conditions
comprising two or more in vivo stimuli for a time, the catheter tubing comprises a second
elastic modulus that is not more than fifty percent of the first modulus.
Embodiment 16. The catheter tubing of embodiment 15, wherein the first
conditions comprise: a temperature in the range of 20 to 30°C and a relative humidity in
the range of 0 to 90% and the two or more in vivo stimuli of the second conditions
comprise a temperature in the range of about 36 to about 40°C, and one or more of:
saline, plasma, white blood cells, platelets, red blood cells, water, absence of light,
antibodies, and enzymes.
Embodiment 17. The catheter tubing of one of embodiments 15 to 16,
wherein the first elastic modulus is the range of 1300 to 2200 MPa; and the second elastic
modulus is the range of 10 to 650 MPa, 10 to 400 MPa, 10 to 200 MPa, or 10 to 100
MPa.
Embodiment 18. The catheter tubing of one of embodiments 15 to 17,
wherein the second elastic modulus is reached after exposure to the second conditions for
about 30 minutes or less.
Embodiment 19. The catheter tubing of embodiment 18, wherein the
second elastic modulus is reached after exposure to the second conditions for about 5 to
about 10 minutes.
Embodiment 20. A vascular access device comprising the catheter tubing
of one of embodiments 1 to 19 in combination with one or more components, wherein the
vascular access device is selected from the group consisting of: a central venous catheter,
a peripherally-inserted central catheter, a midline catheter and a peripheral intravenous
catheter.
Embodiment 21. A method of making a medical device including a
catheter tubing comprising: designing an elongate body having a section of catheter
tubing discrete from the elongate body to form the catheter tubing such that the catheter
tubing comprises a first elastic modulus under first conditions prior to entry into a patient;
and wherein when exposed to second conditions comprising two or more in vivo stimuli
for a time, the catheter tubing comprises a second elastic modulus that is not more than
fifty percent of the first modulus.
Embodiment 22. The method of embodiment 21 wherein the designing of
the elongate body having the section of catheter tubing discrete from the elongate body
comprises: providing a base polyurethane; providing a compounded polyurethane
comprising a thermoplastic polyurethane and a radiopaque material; and co-extruding the
base polyurethane and the compounded polyurethane to form the elongate body of the
base polyurethane and the section discrete from the elongate body of the compounded
thermoplastic polyurethane.
Embodiment 23. The method of one of embodiments 21 to 22 further
comprising combining the catheter tubing with one or more components to form the
medical device.
Embodiment 24. The method of embodiment 23, wherein the one or more
components includes a needle and the medical device is a vascular access device.
Embodiment 25. The method of embodiment 24, wherein the vascular
access device is selected from the group consisting of: a central venous catheter, a
peripherally-inserted central catheter, a midline catheter, and a peripheral intravenous
catheter.
Embodiment 26. A method of delivering a medical fluid to a patient
comprising: obtaining a catheter tubing; inserting the catheter tubing into a patient under
first conditions when the catheter tubing comprises a first elastic modulus; and indwelling
the catheter tubing for a duration under second conditions when the catheter tubing is
exposed to two or more in vivo stimuli and the catheter tubing comprises a second elastic
modulus that is not more than fifty percent of the first modulus.
Embodiment 27. The method of embodiment 26, wherein the catheter
tubing comprises: an elongate body comprising a base thermoplastic polyurethane; and
one or more sections discrete from the elongate body comprising a compounded
polyurethane comprising a thermoplastic polyurethane and a radiopaque material.
Embodiment 28. The method of one of embodiments 26 to 27, wherein the
first conditions comprise: a temperature in the range of 20 to 30°C and a relative
humidity in the range of 0 to 90% and the two or more in vivo stimuli of the second
conditions comprise a temperature in the range of about 36 to about 40°C, and one or
more of: saline, plasma, white blood cells, platelets, red blood cells, water, absence of
light, antibodies, and enzymes.
Embodiment 29. The method of one of embodiments 26 to 28, wherein the
first elastic modulus is the range of 1300 to 2200 MPa and the second elastic modulus is
the range of 10 to 650 MPa, 10 to 400 MPa, 10 to 200 MPa, or 10 to 100 MPa.
Embodiment 30. The method of one of embodiments 26 to 29, wherein the
second elastic modulus is reached after exposure to the second conditions for about 5 to
about 10 minutes.
EXAMPLES
Composite catheter tubing according to Comparative Examples A-C and
inventive Examples 1-3 was made by the following procedure. A first melt stream of a
first base polyurethane from a primary extruder and a second melt stream of a
compounded polyurethane from a secondary extruder were maintained separately until
combined as continuous layers in a forward, downstream portion of an extruder head.
From the extruder head, the streams subsequently passed through and emerged from a
tube die (coaxial or cross-head) as an integral tubing member. The encapsulated stripes
were made from the compounded polyurethane and the rest of the tubing body was made
from the first base polyurethane only. The geometries of COMPARATIVE Examples A-
C and Examples 1-3 were identical. The compounded polyurethane of the stripes were
identical among Examples 1-3. The base polyurethane of the tubing bodies varied among
Examples 1-3.
A Dynamic Mechanical Analyzer (DMA) from TA Instrument model
Q800 was used to measure elastic modulus .
COMPARATIVE Example A
A commercially-available aromatic polyether polyurethane was used as a
first base polyurethane, having a hard segment content of about 60% by weight. A slab
of the first base polyurethane was ground into granulates, which were then converted to
pellets by a traditional conventional compounding machine to result in a transparent
polyurethane.
A compounded polyurethane was made from the first base polyurethane in
combination with a radiopaque material. A slab of the first base polyurethane was
ground into granulates, which were then compounded with barium sulfate by a traditional
conventional compounding machine to result in a compounded polyurethane that was
radiopaque.
In this example, the body and the stripes contained the same underlying
polyurethane material. A composite catheter having a body and stripes was then
fabricated.
COMPARATIVE Example B
The commercially-available polyurethane of COMPARATIVE Example
A was used as a first base polyurethane.
A compounded polyurethane was made from the first base polyurethane in
combination with a radiopaque material, and an additive to increase stiffness. A slab of
the first base polyurethane was ground into granulates, which were then compounded
with both the additive and barium sulfate by a traditional conventional compounding
machine to result in a compounded polyurethane that was radiopaque.
In this example, the body and the stripes contained the same underlying
polyurethane materials. A composite catheter having a body and stripes was then
fabricated.
COMPARATIVE Example C
The commercially-available polyurethane of COMPARATIVE Example
A was used as a first base polyurethane.
A compounded polyurethane was made from a second base polyurethane
and a radiopaque material. The second base polyurethane was different from the first
base polyurethane in that it had about 70% hard segment. A slab of the second base
polyurethane was ground into granulates, which were then compounded with barium
sulfate by a traditional conventional compounding machine to result in a compounded
polyurethane that was radiopaque.
In this example, the body and the stripes contained different underlying
polyurethane materials. A composite catheter having a body and stripes was then
fabricated.
COMPARATIVE Example D
A commercially-available striped hexafluoropropylene and
tetrafluoroethylene (FEP) catheter tubing was obtained.
Example 1
A first base polyurethane was made by the “one shot” bulk polymerization
process (no catalyst) in accordance with Exemplary Formulation C as shown in Table 1
using MDI as the aromatic diisocyanate with and the polyglycol PTMEG of varying
molecular weights (Nominal MW < 1000 and Nominal 1000 = MW =2900). The chain
extender was 1,4 butanediol. A slab of the first base polyurethane was ground into
granulates, which were then converted to pellets by a traditional conventional
compounding machine to result in a transparent polyurethane.
A compounded polyurethane was made from a second base polyurethane
and a radiopaque material. The second base polyurethane was made by the “one shot”
bulk polymerization process (no catalyst), utilizing MDI as the aromatic diisocyanate and
the polyglycol PTMEG with a wider PTMEG molecular weight distribution relative to
the first base polyurethane and 1,4 butanediol as the chain extender. A slab of the second
base polyurethane was ground into granulates, which were then compounded with barium
sulfate by a traditional conventional compounding machine to result in a compounded
polyurethane that was radiopaque.
In this example, the body and the stripes contained different underlying
polyurethane materials. A composite catheter having a body and stripes was then
fabricated according to the procedure provided above.
Example 2
The second base polyurethane of Example 1 as used as a first base
polyurethane in Example 2.
The compounded polyurethane of Example 2 was the same as that of
Example 1.
In this example, the body and the stripes contained the same underlying
polyurethane material. A composite catheter having a body of the first base polyurethane
and stripes of the compounded polyurethane was then fabricated according to the
procedure provided above.
Example 3
The commercially-available polyurethane of COMPARATIVE Example
A was used as a first base polyurethane.
The compounded polyurethane of Example 3 was the same as that of
Examples 1-2.
In this example, the body and the stripes contained different underlying
polyurethane materials. A composite catheter having a body of the first base
polyurethane and stripes of the compounded polyurethane was then fabricated according
to the procedure provided above.
Example 4
TESTING
Elastic modulus of tubing according to Comparative Examples A-D and
Inventive Examples 1-3 was measured under environmental temperatures (25°C and
°C) and various nominal relative humidity (RH) values, the results for which are
summarized in Tables 3-4.
Table 3 20% RH 40% RH 60% RH 90% RH
Modulus at Insertion
°C
EXAMPLE MPa MPa MPa MPa
Example 1 2015 1828 1559 1062
Example 2 1749 1653 1506 1162
Example 3 1429 1328 1191 926
Comparative Example A 566 515 446 335
Comparative Example B 1042 967 863 663
Comparative Example C 1228 1154 1046 926
Comparative Example D 445 446 446 445
Table 4 20% RH 40% RH 60% RH 90% RH
Modulus at Insertion
°C
EXAMPLE MPa MPa MPa MPa
Example 1 1373 1085 772 320
Example 2 1467 1267 1025 638
Example 3 2263 1018 853 560
Comparative Example A 472 393 322 218
Comparative Example B 867 754 649 432
Comparative Example C 849 754 649 476
Comparative Example D 583 580 579 579
The results of Tables 3-4 indicate a substantially linear response of elastic
modulus as changing with respect to a single variable, namely relative humidity. For
Examples 1-3 and A-C, as relative humidity increases, the elastic modulus decreases. For
Example D, there is not a significant change in elastic modulus over different relative
humidity values.
Elastic modulus results of tubing according to Comparative Examples A-
D and Inventive Examples 1-3 under varying temperatures (25°C, 30°C, 35°C, and 40°C)
and 0% relative humidity are summarized in Table 5.
Table 5 25°C 30°C 35°C 40°C
Modulus at Various
Temperatures
0% RH
EXAMPLE MPa MPa MPa MPa
Example 1 2129 1587 1249 904
Example 2 1811 1614 1464 1112
Example 3 1491 1237 1178 904
Comparative Example A 572 537 469 434
Comparative Example B 1061 989 813 728
Comparative Example C 1239 929 834 734
Comparative Example D 439 587 501 564
The results of Table 5 indicate varying responses of elastic modulus as
changing with respect to a single variable, namely temperature. For Examples 1-3 and A-
C, as temperature increases, the elastic modulus decreases. For Example D, the change in
elastic modulus over different temperatures is not linear.
Elastic modulus results of tubing according to Comparative Examples A-
D and Inventive Examples 1-3 under various recommended storage conditions (for real-
time studies) as defined by climatic zones by World Health Organization (WHO) are
summarized in Table 6.
Table 6 Zone II Zone III Zone IV
°C 30°C 30°C
60% RH 35% RH 70% RH
EXAMPLE MPa MPa MPa
Example 1 1559 1085 614
Example 2 1506 1267 897
Example 3 1191 1019 761
Comparative Example A 447 393 290
Comparative Example B 863 755 576
Comparative Example C 1046 754 594
Comparative Example D 446 580 579
: Zone III is defined as 30°C 35% RH. Data was collected at 40% RH due to parameters
of testing equipment.
The results of Table 6 demonstrate the widely varying elastic modulus
based on storage conditions. Stiffness for insertion can therefore vary widely depending
on conditions that catheters are exposed to prior to insertion.
Example 5
TESTING
Elastic modulus of tubing according to Comparative Examples A-D and
Inventive Examples 1-3 was measured after exposure to a single in vivo stimulus for a
duration of time, the results for which are summarized in Table 7. In Table 7, time 0
corresponds to when the saline in which the tubing was soaking achieved steady state
°C.
Table 7 0 6 10
Modulus at Indwell minutes minutes minutes
(single stimulus pre-
priming)
°C MPa MPa MPa
EXAMPLE
Example 1 2233 1944 1790
Example 2 1202 805 667
Example 3 1070 712 569
Comparative Example A 462 286 221
Comparative Example B 770 532 430
Comparative Example C 809 601 509
Comparative Example D 445 455 456
The results of Table 7 show modest softening over time for Examples 1-3.
Comparative Examples A-C also modestly soften over time. Comparative Example D
shows no significant change.
Example 6
TESTING
Elastic modulus of tubing according to Comparative Examples A-D and
Inventive Examples 1-3 was measured after exposure to two in vivo stimuli for a duration
of time, the results for which are summarized in Table 8. In Table 8, time 0 corresponds
to when the saline in which the tubing was soaking achieved steady state 37°C.
Table 8 0 5 15 30
Modulus at Indwell minutes minutes minutes minutes
(Soaked in 37°C Saline)
EXAMPLE MPa MPa MPa MPa
Example 1 805 203 38 26
Example 2 740 231 61 52
Example 3 688 245 81 61
Comparative Example A 128 115 109 106
Comparative Example B 230 151 137 130
Comparative Example C 497 283 206 192
Comparative Example D 468 466 471 473
The results of Table 8 show that Examples 1-3 have significant softening
in a relatively short duration of time when exposed to two in vivo stimuli. That is, a non-
linear response is achieved with the inventive tubing. It is advantageous to have catheter
materials that reduce their modulus only upon exposure to multiple stimuli that are
unique to the human veins. In Examples 1-3 the presence of both stimuli (37°C and
saline) are required for the modulus to decrease. Comparative Example D shows no
significant change upon exposure to multiple stimuli. Comparative Examples A-B show
only a modest reduction in elastic modulus. Comparative Example C shows softening
but not as quickly as Examples 1-3. The examples achieved steady state after about 30
minutes of indwelling.
Overall, the higher modulus at all insertion environments (pre-prime and
humidity) of Inventive Examples 1-3 ensure higher likelihood of insertion success while
the softer modulus when exposed to more than one stimulus in the body environment will
facilitate a reduction in catheter-related complications like phlebitis, infiltration, and
extravasation.
Reference throughout this specification to “one embodiment,” “certain
embodiments,” “one or more embodiments” or "an embodiment" means that a particular
feature, structure, material, or characteristic described in connection with the embodiment
is included in at least one embodiment of the invention. Thus, the appearances of the
phrases such as “in one or more embodiments,” “in certain embodiments,” “in one
embodiment” or “in an embodiment” in various places throughout this specification are
not necessarily referring to the same embodiment of the invention. Furthermore, the
particular features, structures, materials, or characteristics may be combined in any
suitable manner in one or more embodiments.
Although the invention herein has been described with reference to
particular embodiments, it is to be understood that these embodiments are merely
illustrative of the principles and applications of the present invention. It will be apparent
to those skilled in the art that various modifications and variations can be made to the
method and apparatus of the present invention without departing from the spirit and
scope of the invention. Thus, it is intended that the present invention include
modifications and variations that are within the scope of the appended claims and their
equivalents.
Claims (23)
1. A catheter tubing comprising: an elongate body comprising a base thermoplastic polyurethane; and a compounded thermoplastic polyurethane co-extruded with the base thermoplastic polyurethane to provide a section of catheter tubing discrete from the elongate body, the compounded thermoplastic polyurethane comprising a thermoplastic polyurethane and a radiopaque material; wherein the catheter tubing comprises a first elastic modulus under first conditions prior to entry into a patient; wherein when exposed to second conditions comprising two or more in vivo stimuli for a time, the catheter tubing comprises a second elastic modulus that is not more than fifty percent of the first elastic modulus; and wherein the first elastic modulus is at least 1300 MPa.
2. The catheter tubing of claim 1, wherein the thermoplastic polyurethane of the compounded thermoplastic polyurethane is a different formulation from the base thermoplastic polyurethane.
3. The catheter tubing of claim 1, wherein the section discrete from the elongate body comprises one or more elongate stripes comprising the compounded thermoplastic polyurethane, integrally formed with the elongate body.
4. The catheter tubing of claim 1 having a cross-sectional area that comprises the base thermoplastic polyurethane in an amount in a range of 60% to 80% and the compounded thermoplastic polyurethane in an amount in a range of 20% to 40%.
5. The catheter tubing of claim 1, wherein the first conditions comprise: a temperature in the range of 20 to 30°C and a relative humidity in the range of 0 to 90%.
6. The catheter tubing of claim 1, wherein the first elastic modulus is in the range of 1300 to 2200 MPa.
7. The catheter tubing of claim 1, wherein the two or more in vivo stimuli of the second conditions comprise a temperature in the range of about 36 to about 40°C, and one or more of: saline, plasma, white blood cells, platelets, red blood cells, water, absence of light, antibodies, and enzymes.
8. The catheter tubing of claim 1, wherein the second elastic modulus is at most 650 MPa.
9. The catheter tubing of claim 1, wherein the second elastic modulus is in the range of 10 to 650 MPa.
10. The catheter tubing of claim 1, wherein the second elastic modulus is reached after exposure to the second conditions for about 30 minutes or less.
11. The catheter tubing of claim 10, wherein the second elastic modulus is reached after exposure to the second conditions for about 5 to about 10 minutes.
12. The catheter tubing of claim 1, wherein the radiopaque material of the compounded thermoplastic polyurethane comprises bismuth oxychloride (BiOCl), bismuth trioxide (Bi O ), bismuth subcarbonate (Bi O CO ), barium sulfate (BaSO ), 2 3 2 2 3 4 tungsten (W), or combinations thereof.
13. The catheter tubing of claim 1, wherein the base thermoplastic polyurethane, the compounded thermoplastic polyurethane, or both further comprise an antithrombogenic agent, an antimicrobial agent, a lubricant, a colorant, an active pharmaceutical, or combinations thereof.
14. A catheter tubing comprising: an elongate body comprising a base thermoplastic polyurethane that is a product from a reaction of: a diisocyanate, a diol chain extender, and at least one polyglycol, and optionally further, an amine-terminated polyether, the base thermoplastic polyurethane optionally further comprising an antithrombogenic agent, an antimicrobial agent, a lubricant, a colorant, an active pharmaceutical, or combinations thereof; and one or more elongate stripes co-extruded with the base thermoplastic polyurethane, the elongate stripes comprising a compounded thermoplastic polyurethane comprising a thermoplastic polyurethane and a radiopaque material; wherein the catheter tubing comprises a first elastic modulus under first conditions prior to entry into a patient; wherein when exposed to second conditions comprising two or more in vivo stimuli for a time, the catheter tubing comprises a second elastic modulus that is not more than fifty percent of the first elastic modulus; and wherein the first elastic modulus is the range of 1300 to 2200 MPa.
15. The catheter tubing of claim 14, wherein the first conditions comprise: a temperature in a range of 20 to 30°C and a relative humidity in a range of 0 to 90% and the two or more in vivo stimuli of the second conditions comprise a temperature in a range of about 36 to about 40°C, and one or more of: saline, plasma, white blood cells, platelets, red blood cells, water, absence of light, antibodies, and enzymes.
16. The catheter tubing of claim 14, wherein the second elastic modulus is the range of 10 to 650 MPa.
17. The catheter tubing of claim 14, wherein the second elastic modulus is reached after exposure to the second conditions for about 30 minutes or less.
18. The catheter tubing of claim 17, wherein the second elastic modulus is reached after exposure to the second conditions from about 5 to about 10 minutes.
19. A vascular access device comprising the catheter tubing of claim 1 in combination with one or more components, wherein the vascular access device is selected from the group consisting of: a central venous catheter, a peripherally-inserted central catheter, a midline catheter and a peripheral intravenous catheter.
20. A method of making a medical device including a catheter tubing comprising: producing an elongate body having a section of catheter tubing discrete from the elongate body to form the catheter tubing such that the catheter tubing comprises a first elastic modulus under first conditions prior to entry into a patient; wherein the producing comprises: providing a base polyurethane; providing a compounded polyurethane comprising a thermoplastic polyurethane and a radiopaque material; and co-extruding the base polyurethane and the compounded polyurethane to form the elongate body of the base polyurethane and the section discrete from the elongate body of the compounded thermoplastic polyurethane such that the first elastic modulus is at least 1300 MPa; wherein when exposed to second conditions comprising two or more in vivo stimuli for a time, the catheter tubing comprises a second elastic modulus that is not more than fifty percent of the first elastic modulus.
21. The method of claim 20 further comprising combining the catheter tubing with one or more components to form the medical device.
22. The method of claim 21, wherein the one or more components includes a needle and the medical device is a vascular access device.
23. The method of claim 22, wherein the vascular access device is selected from the group consisting of: a central venous catheter, a peripherally-inserted central catheter, a midline catheter, and a peripheral intravenous catheter. 1 100 00 d1 1 111 11 1 115 15 1 122 22 FIG. 2
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15/489,109 US10596302B2 (en) | 2017-04-17 | 2017-04-17 | Catheter tubing with tailored modulus response |
US15/489,109 | 2017-04-17 | ||
PCT/US2018/026250 WO2018194840A1 (en) | 2017-04-17 | 2018-04-05 | Catheter tubing with tailored modulus response |
Publications (2)
Publication Number | Publication Date |
---|---|
NZ757861A NZ757861A (en) | 2020-10-30 |
NZ757861B2 true NZ757861B2 (en) | 2021-02-02 |
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