Classifications

• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B5/00—Measuring for diagnostic purposes; Identification of persons
  • A61B5/145—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue
  • A61B5/14525—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using microdialysis
  • A61B5/14528—Measuring characteristics of blood in vivo, e.g. gas concentration or pH-value ; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid or cerebral tissue using microdialysis invasively
• • 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
• • 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
  • A61M25/0009—Making of catheters or other medical or surgical tubes

Definitions

• the present invention relates to a catheter according to the preamble of claim 1 and a method for producing such a catheter according to the preamble of claim 18.
• a generic catheter for microdialysis is known from WO 99/41606.
• This catheter each has a feed channel and a discharge channel made of a semipermeable membrane for a dialysis fluid, which are arranged in a microchip. Both channels are connected to each other by a hairpin-shaped area which protrudes from the microchip and through which the exchange of substances between the dialysis and body fluids takes place.
• the discharge channel is integrally connected to a likewise 'embedded in the microchip analysis unit for monitoring the composition of the dialysis liquid after the mass transfer.
• This analysis unit is composed of a reservoir with a reference substance, a reference electrode or ion-sensitive electrode and a sensor, for example an ion-sensitive field effect transistor (ISFET).
• ISFET ion-sensitive field effect transistor
• This catheter has an inner tubular part and an outer tubular part surrounding it in the form of a hollow fiber membrane.
• the inner tubular part encloses a discharge channel.
• the outer wall of the inner tubular part and the inner wall of the outer tubular part delimit a feed channel.
• spacing means are provided which support the inner wall of the outer tubular part with respect to the outer wall of the inner tubular part.
• Another catheter for microdialysis is disclosed in DE 33 42 170 C2.
• This catheter has a tubular or tubular dialysis membrane, for example a hollow fiber membrane, accommodated in a metal housing.
• a tubular or tubular dialysis membrane for example a hollow fiber membrane
• the manufacture of such a catheter is complex because, given the dimensions required, a very fine tube has to be inserted very precisely into a housing.
• the hose tends to lean against the inner housing wall and thus block part of the membrane, which results in unpredictable exchange services.
• the object of the present invention is therefore to provide a catheter of the type mentioned above, which is easy to manufacture and can be easily implanted and explanted.
• the solution consists in a catheter with the features of claim 1 and in a method with the features of claim 18.
• the catheter according to the invention thus has an angle of about 180 °, i.e. about U-shaped curved hollow fiber membrane, with the two legs of the U as close together as possible. Normally, this would cause the hollow fiber membrane to kink, which would interrupt the passage of liquid through the lumen.
• the anisotropic use of heat or solvents at least in this area changes the structure of the hollow fiber membrane in such a way that the hollow fiber membrane can be bent by approximately 180 ° without kinking, i.e. without the lumen closing.
• connections of the catheter according to the invention are actually two tubes that can be easily connected.
• the dialysis fluid enters the hollow fiber membrane at one end and exits at the other end.
• the cathode for microdialysis according to the invention has a very small overall diameter.
• the catheter according to the invention is therefore not only very easy to implant and to explant, it also offers significantly improved wearing comfort and significantly reduced dead times compared to the prior art.
• the inventive method is characterized in that the hollow fiber membrane is heat-treated at least in the area to be bent or is treated with at least one solvent.
• the anisotropic introduction of heat or the anisotropic treatment with at least one solvent changes the structure of the hollow fiber membrane in such a way that it can be bent approximately U-shaped with a minimum overall diameter of the catheter without kinking and closing the lumen.
• the hollow fiber membrane only has to be processed from the outside in order to produce a catheter according to the invention for microdialysis. It was also shown that it is not necessary to support the lumen as it is e.g. Example at Bending of metallic pipes by filling with sand is state of the art. Furthermore, it is no longer necessary to insert a tube or another part into the interior of a hollow fiber membrane or to insert a membrane tube into a housing. There is also no longer any danger of damaging the inner separating layer of the hollow fiber membrane.
• the distance (a) between the two legs of the hollow fiber membrane should preferably be less than 50% of the diameter (d) of the hollow fiber membrane.
• the total diameter of the catheter should advantageously be less than 2.5 times the diameter of the hollow fiber membrane. This results in the smallest possible size and a particularly small overall diameter of the finished catheter.
• the hollow fiber membrane is further preferably bent in the U-shaped area by 180 ° +/- 5 ° and can have a reinforcement to improve the tensile strength. The use of a reinforcement further simplifies the explantation since the risk of losing the membrane or membrane parts is further reduced.
• the reinforcement can be, for example, a wire, a thread and / or a strand, which can be guided, for example, parallel to the two legs and connected to them, for example glued or welded.
• the reinforcement can consist of a metal, a metal alloy or a plastic. Wires made of stainless steel, a precious metal or monofilament polymer fibers, threads made of polymer fibers or strands made of several thin metallic threads are well suited.
• the catheter according to the invention can have a liquid-impermeable zone in the area of the inflow and / or outflow of the dialysis fluid, which zone can also serve as a “shaft” for the connection of the ends.
• the hollow fiber membrane can furthermore have at least at least one radiation-absorbing substance, such as dyes and / or pigments, in order to increase the absorption of the radiation and thus the heat input when heat is introduced by electromagnetic radiation.
• the action of solvents is preferably carried out by applying a small drop of a suitable solvent or solvent mixture.
• the size of the drop depends on the diameter and the wall thickness of the hollow fiber membrane.
• the volume should be sufficient to fill the pore structure of the membrane over a length corresponding to one to one and a half times the diameter and approximately 50% of the membrane circumference.
• Suitable solvents are those which dissolve or soften the polymer of the membrane and cause it to shrink, e.g. Dimethylfor amide, dimethyl sulfoxide, dimethylacetamide or tetrahydrofuran. Chlorinated hydrocarbons e.g. Trichlorethylene is not preferred for environmental reasons. Solvents or solvent mixtures which can be easily removed by evaporation are particularly preferred, e.g. Mixtures of isopropanol and tetrahydrofuran.
• the introduction of heat via direct contact with an electrically heated wire has proven to be particularly suitable.
• the introduction of heat by electromagnetic radiation is also possible, for example by laser radiation, microwave radiation or high-frequency radiation, provided that the radiation is absorbed by the hollow fiber membrane at least in the curved region.
• Commercial dialysis hollow fibers for example made of polyamides, polyamide S, polyaryl ether sulfones, poly methacrylate, polysulfones or polycarbonate-polyether block copolymers (for example available under the trade name Gambrane) are suitable as the hollow fiber membrane.
• Hollow fiber membranes with an asymmetrical structure are particularly suitable in such a way that the lumen is surrounded by a fine-pored separating layer, while the wall has increasingly larger and / or open pores to the outside.
• the outside diameter of the hollow fiber membrane should not exceed 600 ⁇ m, better still less than 300 ⁇ m and particularly preferably less than 200 ⁇ m.
• Hollow fiber membranes with a small diameter for example an inner diameter in the range from 50 to 100 ⁇ m, preferably 60 to 90 ⁇ m and a small wall thickness, for example 20 to 80 ⁇ m, preferably 40 ⁇ m are also suitable. The latter can be processed into catheters according to the invention with a particularly small overall diameter.
• the reinforcement can be glued by applying a thin layer of adhesive to the reinforcement and then connecting it to the hollow fiber membrane.
• Suitable adhesives are reactive adhesives such as cyanoacrylate adhesives or polyurethane adhesives as well as solvent-based adhesives or radiation-activatable adhesives or thermally activatable polymers or adhesives (hot-melt adhesives) such as ethylene / ethyl acrylate copolymers, ethylene / vinyl acrylate copolymers, polyamides, polyesters, polyisobutylene or polyvinyl butyrates and the membrane materials themselves.
• a drop of a reactive polymer mixture on the front i.e. be applied to the bent end of the catheter, which further improves the adhesion between the membrane and the reinforcement and also closes any weak points and leaks in the membrane in the bent area.
• the adhesives already mentioned can also be used for this.
• the liquid-impermeable zone in the region of the inflow and / or outflow of the catheter according to the invention can be created, for example, by impregnating the hollow fiber membrane with a suitable polymer or a polymer mixture, for example an adhesive, which can then be cured thermally or reactively.
• a suitable polymer or a polymer mixture for example an adhesive
• This is accompanied by a shrinkage of the hollow fiber membrane, which in addition to reducing the wall thickness also results in a reduction in the inner diameter.
• the advantage of this procedure is that by reducing the inside diameter Hollow fiber membrane, the dead volume of the catheter according to the invention is reduced. This in turn reduces the dwell time of a sample in the area of the inflow and / or outflow, and a measurement variable, for example a change in the glucose content in the tissue, can
• the thermal treatment in the area of the inflow and / or outflow can take place by the action of hot air, by partial introduction of the catheter into a hot chamber or between two heated jaws or by the action of radiation.
• IR radiation is particularly well suited for the precise spatial shaping of the catheter if it is ensured that the radiation is only absorbed in the segments to be heated. This can be done by adding suitable radiation-absorbing substances such as dyes or pigments.
• the design of the inflow and / or outflow of the catheter according to the invention is selected such that the two ends of the hollow fiber membrane are present separately from one another. They can then be inserted into recesses in a hose or in a carrier plate with miniaturized flow paths in a manner known per se and then glued in place.
• the reinforcement can then be attached in a manner known per se or to a hose or a support plate with miniaturized flow paths, for example in a recess or on a surface of the support plate, for. Eg glued in.
• Figure 1 is a schematic representation, not to scale, of a hollow fiber membrane for a catheter according to the invention after bending;
• Figure 2a shows the rear part of a hollow fiber membrane from Figure 1 with a reinforcement;
• Figure 2b shows the hollow fiber membrane of Figure 1 with a reinforcement in its entirety
• FIG. 3 shows a schematic cross section through the hollow fiber membrane from FIGS. 2a and 2b.
• the hollow fiber membrane piece is placed in the center on an electrically heatable constantan wire with a diameter of 250 ⁇ m.
• the two ends of the hollow fiber membrane are loaded with a force of 1 mg.
• This wire is heated electrically.
• a current of 1.7 A flows from a current-regulated power supply over a period of 2x2 seconds.
• the hollow fiber membrane deforms at the contact point and bends.
• the two legs form an angle of 15 ° to 30 °. By squeezing gently at the moment the power is turned off in the second cycle, the angle can be reduced to practically zero.
• FIG. 1 schematically shows such a U-shaped hollow fiber membrane 10 with two legs 11, 13, which each lead to an inflow 12 or outflow 14 and a curved region 15.
• the direction of flow of the dialysis fluid is indicated by arrows.
• the distance a between the legs 11, 13 is less than 50% of the diameter d of the hollow fiber membrane 10 " .
• In the area of Inflow 12 and outflow 14 each have a liquid-impermeable area 12 ', 14'.
• Another liquid-impermeable area 15 ' is located in the curved area 15, which is impregnated with an adhesive.
• a PAS hollow fiber membrane from Gambro Dialysatoren, Hechingen, Germany, with an inner diameter of 214 ⁇ m and a wall thickness of 43 ⁇ m is cut to a length of 50 mm and placed on a support.
• the support has a narrow, straight recess in the middle in which an electrically heatable constantan wire with a diameter of 250 ⁇ m oriented perpendicular to the surface is guided in a uniform movement at approx. 10 mm / s.
• a current of -1.7 A flows through the wire.
• the wire hits the hollow fiber membrane in the middle and drags it along. To the side of the travel path of the wire are walls, the distance from the path of the wire is reduced asymptotically to 500 ⁇ m.
• the entrained hollow fiber bends in the desired manner.
• the angle between the two legs can be reduced to practically zero.
• the movements of the wire and jaws and the current flow are controlled automatically. This enables a reproducible shaping of the bend without any problems.
• a wire made of stainless steel material no. 1.4301, Fe / Crl8 / Nil0, degree of hardness: annealed, diameter: 0.05 mm
• the wire is covered with a thin layer of a polyamide.
• the wire is drawn through a coating nozzle (diameter 300 ⁇ m) at a speed of 3.1 m / min and coated on all sides with a layer of a solution of 15% by weight Trigamid T3000, manufacturer Creanova, Mari, Germany, 7% by weight .-% PVP Plasdone C-15, manufacturer ISP Technologies, Inc., Wayne, USA and 78 wt .-% NMP (N-methyl-2-pyrrolidone), manufacturer Merck, Darmstadt, Germany.
• the wire thus coated is drawn through a water bath to wash out the solvent. A solid white layer with a thickness of approx. 100 ⁇ m is formed. After drying in air, the coated reinforcement wire can be used.
• Treated hollow fiber membrane is wrapped around a practically endless reinforcing wire as treated under 2 in such a way that the two legs of the hollow fiber membrane lie close together and together form a turn with a pitch of 5 to 10 mm per turn.
• the bend is pressed directly onto the wire, while the beginning and end of the hollow fiber membrane protrude from the wire by about 3 mm each.
• An electrical current of 0.2 A is passed through the wire over a period of 3.5 seconds.
• the wire heated by the current melts the coating of the reinforcing wire and the hollow fiber membrane on the outside. After the power is turned off, the wire cools and the hollow fiber membrane adheres firmly.
• FIGS. 2a and 2b schematically show a hollow fiber membrane 10 reinforced as in 3. which is wound around a reinforcing wire 20.
• the bent region 15 is connected to the reinforcement wire 20, while the inflow 12 and the outflow 14 project from the reinforcement wire 20, for example, over the length of the impermeable regions 12 ′ and 14 ′.
• Hoses 21, 22, into which the inflow 12 and the outflow 14 are glued, are also indicated.
• Figure 3 shows a cross section along the line III-III in Figure 2a. It can be seen that the coating 20 'of the reinforcing wire 20 is melted and fused to the outer region of the hollow fiber membrane.
• a catheter manufactured as under 4. is flowed through with distilled water at a flow of 0.1 ⁇ l / min and placed in a beaker with 200 mg / dl glucose.
• a glucose content in the dialysis fluid of 199 mg / dl is measured at the exit of the catheter. 6. Measurement of dead time (95)
• dead time (95) denotes the dead time until a signal change of 95% is reached.
• a catheter manufactured as under 4. is combined with a suitable flow refractive index measuring cell and flowed through with distilled water at a flow of 0.1 ⁇ l / min.
• the catheter is alternately placed in beakers with 200 mg / dl glucose and with distilled water.
• the glucose concentration in the measuring cell follows the concentration in the beaker with a time delay. After subtracting the delay caused by the volume of the measuring cell and its supply line, 252 seconds remain for the dead time (95) of the catheter.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Biophysics (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Biomedical Technology (AREA)
• Heart & Thoracic Surgery (AREA)
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• Public Health (AREA)
• Pulmonology (AREA)
• Optics & Photonics (AREA)
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• Hematology (AREA)
• Anesthesiology (AREA)
• Molecular Biology (AREA)
• External Artificial Organs (AREA)
• Separation Using Semi-Permeable Membranes (AREA)
• Artificial Filaments (AREA)
• Materials For Medical Uses (AREA)
• Media Introduction/Drainage Providing Device (AREA)

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• 2001
  • 2001-08-30 SE SE0102879A patent/SE519630C2/sv not_active IP Right Cessation
• 2002
  • 2002-08-30 DE DE50211650T patent/DE50211650D1/de not_active Expired - Lifetime
  • 2002-08-30 US US10/488,135 patent/US20050015044A1/en not_active Abandoned
  • 2002-08-30 EP EP02797654A patent/EP1423160B1/de not_active Expired - Lifetime
  • 2002-08-30 WO PCT/EP2002/009686 patent/WO2003020352A2/de not_active Ceased
  • 2002-08-30 ES ES02797654T patent/ES2299629T3/es not_active Expired - Lifetime
  • 2002-08-30 AT AT02797654T patent/ATE385428T1/de not_active IP Right Cessation
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