Classifications

• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
  • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
  • C12Q1/56—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T428/00—Stock material or miscellaneous articles
  • Y10T428/31504—Composite [nonstructural laminate]
  • Y10T428/31652—Of asbestos
  • Y10T428/31663—As siloxane, silicone or silane
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T428/00—Stock material or miscellaneous articles
  • Y10T428/31504—Composite [nonstructural laminate]
  • Y10T428/31855—Of addition polymer from unsaturated monomers
  • Y10T428/31935—Ester, halide or nitrile of addition polymer
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T428/00—Stock material or miscellaneous articles
  • Y10T428/31504—Composite [nonstructural laminate]
  • Y10T428/31855—Of addition polymer from unsaturated monomers
  • Y10T428/31938—Polymer of monoethylenically unsaturated hydrocarbon

Definitions

• the instant invention is directed to a method for reducing the tendency of blood to coagulate when brought into contact with foreign surfaces and to a method for treating a foreign surface to render it nonthrombogenic.
• the citrate When blood is stored, sodium citrate is often added to retard coagulation. The citrate, however, may produce undesirable physiological effects during blood transfusions and often interferes with blood analyses. It would be advantageous if such difficulties could be avoided by storing blood in such a way as to prevent contact between the blood and surfaces which have a tendency to promote coagulation.
• the term foreign surfaces refers to surfaces of a material, other than body tissue, which normally induces coagulation or thrombosis of blood.
• the principal object of this invention is to pro vide surfaces which do not promote coagulation.
• Another object of the invention is to provide a means for preventing or diminishing blood coagulation induced by contact with foreign surfaces.
• a further object of the invention is to provide a method for treating a surface to reduce the incidence of blood coagulation seen in the absence of conventional anticoagulants.
• a still further object of the invention is to provide a method for binding a conventional anticoagulant to a foreign surface, thereby providing a nonthrombogenic surface.
• Another object of the invention is to provide instruments, conduits, containers, membranes, and the like, suitable for use in contact with blood.
• a method which comprises treating a surface with a surface-active agent at an elevated temperature whereby the hydrocarbon portion of the surface-active agent is bound to the surface.
• the treated surface is further treated with or exposed to a conventional anticoagulant, such as heparin and other sulfuric acid esters of mucopolysaccan'des.
• a conventional anticoagulant such as heparin and other sulfuric acid esters of mucopolysaccan'des.
• a paraffin surface which has been treated with a cationic surface-active agent having an excess of positive hydrophilic groups is characterized by a prolonged coagulation time in vitro. It has also been discovered that the coagulation time can be further increased by subsequent treatment of the surface with an anticoagulant, such as heparin.
• the most important natural anticoagulant occurs in the body as its sodium salt.
• the active component of heparin is a negative ion having a large number of sulfate and sulfonate groups. It has now been found possible to bind heparin, by chemisorption, to a surface which bears positive hydrophilic groups.
• an anticoagulant having positively charged active groups can be fixed to a surface having negatively charged groups, e.g., by means of an anionic surface-active agent.
• Surface-active agents e.g., anionic and cationic surfactants
• the elevated temperature is believed to increase the permeability of the molecular structure of the plastic.
• the increased permeability allows the hydrophobic end of the molecule, e.g., the alkyl chain of the surface-active molecule, to become primarily fixed to the plastic surface.
• Subsequent reduction of the penneability of the plastic surface by lowering the temperature, causes the primarily fixed molecules of the surface-active agent to become permanently bound to the plastic surface.
• the surface-active agent thus fixed to the plastic surface cannot be dislodged by normal mechanical methods or by washing the surface with a solvent at temperatures below the fixing temperature. it is possible, however, to remove the surface-aetive agent by bringing the plastic surface into contact with a solvent or the surface-active agent at a temperature which is approximately equal to or higher than the temperature utilized for fixing the surface, active materials to the
• the method of this invention is applicable to the treatment of a wide variety of materials including glass and metal surfaces.
• Glass and metal articles are first coated with suitable plastics before treatment.
• the preferred materials are plastics, including polyethylene, polypropylene, polyvinyl chloride, polystyrene, polytetrafluorethylene, and the like. It is possible to utilize this invention in the treatment of articles comprising inert polyolefins and also of the general class of thermoplastics. Elastomers and cellulose derivatives can also be rendered nonthrombogenic by this invention.
• a surface-active agent containing an alkyl chain of at least four carbon atoms In order to form a firm bond between the surface and the surface-active agent it is preferred to use a surface-active agent containing an alkyl chain of at least four carbon atoms.
• Surfaceactive agents having a long hydrocarbon chain are preferred, particularly those containing a hydrocarbon chain of from about 12 to about 18 carbon atoms.
• Suitable cationic surface-active agents can be of a varied nature and include primary, secondary, tertiary amines, and their salts, as well as quaternary ammonium compounds, pyridinium, and guanidium salts which have at least one alkyl group with a chain length longer than two carbon atoms and preferably longer than about eight carbon atoms.
• the nitrogen atom can bear one, two and three hydrocarbon atoms, such as a lower alkyl group, e.g., methyl, ethyl, or propyl; a benzyl, or an alkylol group, or the nitrogen atom can bear one or two hydrocarbon groups having an arbitrary chain length.
• a lower alkyl group e.g., methyl, ethyl, or propyl
• a benzyl, or an alkylol group or the nitrogen atom can bear one or two hydrocarbon groups having an arbitrary chain length.
• alkyl ammonium salts of the formula:
• X is a halogen and y is a number of at least about 4 and preferably from about 8 to 18 Since primary amines provide stronger heparin complexes than other ammonium salts of equivalent chain length, it is preferred to use primary amines as the surface-active agents in the treatment of chemically inert plastics.
• the primary amines are generally employed in the salt form, i.e., as a salt made by adding HCl, HBr or H].
• Water solutions of salts of primary amines are preferred since the amine molecules absorbed onto the plastic surface from these solutions are to a large extent ionized whereas this is not normally the case for solutions formed by dissolving amine in e.g., organic solvents.
• the Krafft point is the temperature at which the solubility of the surface-active agent suddenly increases and provides homogeneous solutions. Absorbed amine molecules are more difficult to rinse off. Accordingly, if water or an aqueous solution is used for rinsing the plastic articles after treatment with the surface-active agent, the temperature of the water should preferably be above the Krafft point of the surface-active agent.
• the surfaceactive agent When using an anticoagulant having positively charged reactive groups, e.g., protamine hydrochloride, the surfaceactive agent should be anionic. For instance, a surface can be treated with sodium cetyl sulfate and subsequently treated with protamine hydrochloride.
• the surface-active agent can be used in the form of an aqueous solution.
• an article having a plastic surface and the aqueous solution of the surface-active agent are heated, if necessary in an autoclave, to an elevated temperature near or above the softening temperature of the pl&tic.
• the temperature should preferably be at least about 80C.
• the concentration of the surface-active agent in the aqueous solution in equilibrium with the surface-active agent absorbed onto the surface of the plastic article should preferably be higher than about one-third the so-called critical micelle concentration which is characteristic of the surfaceactive agent. This assures that a monolayer of high concentration of the surface-active agent is provided on the surface.
• an aqueous solution containing from about 4 to about 10 4 moles of surface-active agent per liter of solution.
• the aqueous solution of the surface-active material should preferably be degassed at a temperature of about 100C. In order to remove oxygen and other gases which might impair absorption. Degassing is particularly important when treatment is conducted in an autoclave, as otherwise an undesired oxidation of a polymer surface might occur at this high temperature.
• Water solutions of primary amines preferably have a pH above about 4 at about 55C. when the concentration is 0.005 moles per liter.
• Suitable solutions can be prepared by dissolv ing a sufficient amount of an amine salt in water or by neutralizing the free amine, e.g., in an aqueous solution with an aqueous acid. [fit is desired to transform the entire amount of free amine to the salt form, precautions should be taken to avoid use of excessive amounts of acid, which, if present during treatment of the surface, may interfere with absorption of the surface-active molecule.
• Suitable solutions can be prepared by dissolving the amine, preferably a primary amine, in a small volume of ethanol, and adding the resulting solution, at room temperature with vigorous stirring to an aqueous solution containing an equivalent amount of acid. Stirring is continued for about 10 minutes at room temperature to disperse the entire amount of amine in the liquid and neutralize it with the acid. The temperature is then raised to a temperature above the Krafft point of the actual ammonium salt, at which point heating may be stopped. However, it is preferred to heat the solution to about 90C., so that dissolved gases, e.g., oxygen and carbon dioxide, are removed.
• dissolved gases e.g., oxygen and carbon dioxide
• washing of the plastic surface with an organic solvent facilitates fixing of the surface-active agent to the surface, probably due to cleaning or swelling of the plastic surface as a result of contact with the organic solvent.
• an organic solvent of hydrophobic character it is preferred to rinse the washed plastic surface with a hydrophilic organic solvent, e.g., acetone, before treatment of the plastic surface with the aqueous solution of the surface-active agent.
• a plastic surface with a liquid which is not a true solution of the surface-active agent but rather a dispersion of the surface-active material, i.e., an emulsion or suspension.
• the surface-active agent may be dispersed in water or an organic liquid, preferably a lower alcohol.
• the plastic surface is treated with the dispersion of the surface-active agent at an elevated temperature for a time sufficient to insure fixing of the desired concentration of surfaceactive molecules on the surface.
• the temperature is reduced to ensure firm bonding of the surface-active molecules to the surface.
• the temperature should be reduced by at least about C., and it is preferred to reduce the temperature to a level of from about 40 C. to about 50 C.
• the reduction in temperature may be accomplished while the plastic article is immersed in the dispersion or solution or the article may be removed from the liquid and allowed to cool in air.
• a suitable nonthrombogenic surface can be provided by treating the plastic surface, with a surfaccactive agent anticoagulant complex prepared by reacting a surface-active agent, preferably a cationic agent, with an anticoagulant. to form a complex compound.
• the treatment of the surface is conducted at elevated temperatures, as discussed herein. Formation of the complex does not significantly impair the thrombosis-retarding capacity of the anticoagulant.
• a blood anticoagulant such as heparin, is a polyelectrolyte having a large number or ionic groups to which the surface-active molecules can be attached.
• the ionic groups of heparin occur in a regular pattern and it is a theory of ours that the positions of the ionic groups of the surface-active molecules should be consistent with the regular pattern of the ionic groups of the heparin molecule if a maximum amount of heparin is to be bound to a surface having a given number of surface-active molecules.
• This consistency may not always be obtained if the surface is first treated with the surface-active agent alone, as these molecules may become fixed to the surface in an irregular pattern, especially at a low surface concentration of the surfaceactive agent.
• the anticoagulant By reacting the anticoagulant with the surfaceactive agent in an aqueous solution to form an emulgated or dispersed complex and fixing the complex to the surface, this irregularity can be diminished.
• heparin can be reacted with cetyltrimethylammonium bromide and a plastic article can be treated with an aqueous dispersion of the resulting complex compound. Binding of the complex compound to the plastic is effected by penetration of the plastic surface by the hydrocarbon chains of the cetyltrimethylammonium portion of the molecule.
• the concentration of heparin on the surface of the plastic article shall be at least 0.1 lntemational Unit (lU) per square centimeter. Consequently, the concentration of heparin in the aqueous dispersion or emulsion of a cationheparin complex compound should preferably be so high that said surface concentration is obtained.
• the ratio of cationic surface agent to heparin should preferably be from about 10' to 10 mole of surface-active agent per lntemational Unit of heparin.
• Suitable cationic surface-active agents include monoamines having a long hydrocarbon chain, in acid solution, alkyl pyridinium chloride and alkyl trimethyl ammonium halides, e.g., chloride bromide or iodide, containing a long chain alkyl radical.
• the surface-active agent consisted of an alkyl-ammonium salt of the type where'R is a hydrocarbon chain having at least 12 carbon atoms, as shown, X is a negative monovalent ion, e.g., chlorine or bromine, and R,, R and R can be the same or different members of the group consisting of hydrogen, and lower alkyl.
• the surface-active agent consisted of an alkyl ammonium salt of the type RNH Cl, where R is a hydrocarbon chain with not more than six carbon atoms, and in experiment 9, the surface-active agent was comprised of an alkyl ammonium salt of the formula:
• the results are given in table 1, which states the type of radicals, the treatment time, the treatment temperature, the concentration of the surface-active agent in the solution, and the results of measurement of radioactivity as the number of decays observed per minute.
• the radioactivity values represent a measure of the quantity of heparin bound to the plastic surface.
• R1:R1 CH1 0 118 0. 001 2, 040
• Table 3 shows some examples of suitable plastics and suitable treatment time and temperature for such plastics.
• plastic plates were treated with an aqueous solution of cetyltrimethylammonium bromide.
• the concentration of the solution was 3-l0 m0l/l., except for the first two plastics mentioned in the table for which a concentration of 710 mol/ l. was used. In general, a somewhat higher concentration is to be preferred, viz, about 10 to about 10 mol/l.
• the cetyltrimethylammonium bromide was labeled with radioac tive isotope C14, which made it possible to determine the quantity of surface-active agents fastened to the surface. Any quantity of surface-active agent loosely adhering to the surface was first removed by thorough washing. Table 3 shows the result of the radioactivity measurement, as number of decays per minute. The results obtained for one plastic are not directly comparable to that of another plastic due to differences in surface area.
• metal articles can be provided with a coating of a plastic, and such plastic surface subsequently treated to make it coagulation retarding.
• EXAMPLE 1 Small tubes of polyethylene are treated with an aqueous solution of cetyltrimethylammonium bromide having a concentration of 0.0005 mole per liter, for 24 hours at 100 C. The tubes are allowed to cool down at 70 C. in the solution.
• EXAMPLE 2 Small tubes of polypropylene are treated with an acidified aqueous solution of cetylamine, having a concentration of 0.1 mole per liter, for 24 hours at 150 C. The tubes are rinsed five times with distilled water and are treated with a solution of heparin, having a concentration of 200 IU per milliliter for 15 minutes. The treated tubes are rinsed five times with an isosmotic solution of sodium chloride. Blood in contact with the tubes, thus treated, does not coagulate after 1 hour.
• EXAMPLE 3 Two milliliters of an aqueous solution of heparin having a concentration of 5,000 IU per milliliter are added, with stirring, to l liter of an aqueous solution of cetylpyridinium bromide having a concentration of 0.001 mole per liter. A polyethylene surface having a size of 20 square decimeters is treated in the emulsion thus prepared for 24 hours at 83 C. The surface is now repeatedly rinsed with an isosmotic solution of sodium chloride. Blood is brought into contact with the surface thus treated in an experiment in vitro. No coagulation can be found after 2 hours. After having been in contact with said surface and having been transferred to a container of a material, such as glass, which promotes coagulation, the blood will coagulate after -15 minutes.
• a material such as glass
• EXAMPLE 4 Two milliliters of an aqueous solution of heparin containing 5,000 [U per milliliter are added, while stirring, to 1 liter of an aqueous solution of cetyltrimethylammonium bromide having a concentration of 0.001 mole per liter. A polypropylene surface having a size of 17 square decimeters is treated in the emulsion thus prepared for 2 hours at 165 C. The surface is now repeatedly rinsed with an isosmotic solution of sodium chloride. Blood is brought into contact with the surface thus treated in an experiment in vitro. No coagulation can be found after 2 hours. After having been in contact with said surface and having been transferred to a container of a material, such as glass, which promotes coagulation, the blood will coagulate after 10l5 minutes.
• a material such as glass
• EXAMPLE 5 Small tubes of polyethylene are treated for 36 hours at 93 C. with an emulsion prepared by mixing 500 milliliters of a heparin solution containing 40.000 IU of heparin and 500 milliliters of an aqueous solution of cetyltrimethylammonium bromide having a concentration of 0.002 mole per liter. The tubes are allowed to cool down in the emulsion to 45 C., and are subsequently rinsed one time with an aqueous solution of cetylpyridinium bromide having a concentration of 0.1 mole per liter and 10 times with distilled water. Blood is stored in the tubes thus treated. No coagulation can be found after 2 hours. After having been transferred from tubes thus treated into a glass container, the blood will coagulate in the normal time.
• EXAMPLE 6 Small tubes of polypropylene are treated with an emulsion as described in example 5, except that the temperature is 1 50 C. After cooling the tubes are rinsed 10 times with distilled water and one time with an isosmotic solution of sodium chloride. No coagulation can be found in blood having been stored for 2 hours in tubes thus treated. After having been transferred to a glass container the blood will coagulate in the normal time.
• EXAMPLE 7 Five hundred milliliters of an aqueous solution of cetyltn'methylammonium bromide having a concentration of 0.002 mole per liter are mixed with 500 milliliters of a solution of heparin containing 40,000 [U of heparin. Small containers of polystyrene are treated with the emulsion thus prepared for 2 hours at C. The containers are allowed to cool down in the emulsion, and are now rinsed 10 times with distilled water and two times with an isosmotic solution of sodium chloride. When stored in such containers blood will begin to coagulate after approximately 80 minutes.
• EXAMPLE 8 An emulsion is prepared as described in example 7. Tubes of polyvinyl chloride are treated in the emulsion for 15 minutes at C., and are subsequently rinsed 10 times with distilled water and two times with an isosmotic solution of sodium chloride. When stored in such tubes blood will begin to coagulate after approximately 60 minutes.
• EXAMPLE 9 Small tubes of polyethylene are treated with an acidified aqueous solution of octadecylamine (0.005 mole) for 17 hours at 98 C. The tubes are allowed to cool down to 50 C. in the solution of the surface-active agent. They are now rinsed four times, 10 minutes at a time, with 50 C. isosmotic solution of sodium chloride. The tubes are then treated for 4 hours at 70 C. with an isosmotic sodium chloride solution containing 2.5 [U of heparin per milliliter and then rinsed for 1 hour at 40 C. with an isosmotic salt solution. Blood stored in these tubes shows no signs of coagulation after 3 hours storage and gives, when transferred to glass tubes, normal coagulation times.
• EXAMPLE 10 Small tubes of polypropylene are treated with a 0.005-mo1ar cetylammonium chloride aqueous solution for 15 hours at C. After cooling in the solution the tubes are rinsed four times, 10 minutes at a time, with an isosmotic salt solution at 40 C. The tubes are then treated for 2 hours at 70 C. with an isosmotic salt solution containing a 2 IU of heparin per milliliter. The tubes are then treated for 1 hour at 40 C. with an aqueous solution containing a cetylammonium chloride (0.01 weight percent) and sodium chloride (0.9 weight percent). The tubes are then rinsed five times with a 40 C. isosmotic salt solution.
• Blood is stored in these tubes for 2 hours. There is no sign of coagulation.
• the tubes are now carefully rinsed 10 times with an isosmotic salt solution. Fresh blood is then again brought into contact with the surface. After 2 hours storage without coagulation this blood is poured out and the tubes are again rinsed 10 times with an isosmotic salt solution and more blood is brought into contact with the treated tubes. After a 2-hour storage period the blood in these tubes is transferred, without coagulation, to untreated glass tubes. A normal coagulation time is now obtained.
• EXAMPLE 11 Tubes of polycarbonate were treated for 3 hours at about 1 12 C. in a water solution of octadecylamine. The amine concentration was 0.002-molar and the amine was neutralized with hydrochloric acid to a pH of 7. The amine solution was poured off at 60 C. and the tubes were immediately rinsed four times with 60 C. isotonic salt solution, once with 60 C. 0.0l-molar hydrochloric acid, and five times with 60 C. isotonic salt solution. The tubes were treated for 2 hours at 60 C. with an isotonic salt solution containing 2.5 lU per mole of heparin and afterwards the tubes were rinsed times with 40 C. isotonic salt solution. The tubes were then filled with blood. No coagulation was observed after 3 hours storage at 37 C.
• tubes were now treated for 4 hours at 70 C. with an isotonic salt solution containing 2.5 [U per milliliter of heparin.
• the tubes were rinsed 10 times with a 40 C., 10 percent sodium chloride solution.
• the tubes were now filled with blood. No coagulation was observed after 3 hours storage at 37 C.
• EXAMPLE l3 Plates of silicone resin were treated for 14 hours at 160 C. with a 0.005-molar cetylamine hydrochloride aqueous solution. The solution was allowed to cool to 60 C., and the plates were immediately rinsed three times at 50 C. for 10 minutes with an isotonic salt solution and then 10 times with a 40 C. isotonic salt solution. The plates were divided into two groups and now treated with heparin solutions in two different ways:
• the other group of plates was treated for 4 hours at 70 C. in a dispersion of complex compound of heparin-cetylammonium chloride.
• the complex compound was produced by reacting an aqueous solution containing 12 [U per milliliter of heparin with a 0.0003-molar cetylamine-hydrochloride aqueous resulting in a heparin having three-fourths of its negative groups bound as a complex compound.
• the heparin was labeled with tritium.
• EXAMPLE l4 Woven articles of fibers of polytetrafluorethylene were treated in a 0.005-molar cetylamine hydrochloride aqueous solution either for 4 hours at 230 or for 18 hours at l95 C.
• the amine solution in both series was allowed to cool to 60 C.
• the articles were now rinsed 20 times with 50 C. isotonic salt solution.
• the articles of both series were treated with heparin solutions as described in paragraphs (a) and (b) of example 13, and were subsequently rinsed as described in said example. In all articles thus produced the heparin was firmly adsorbed to the surface.
• EXAMPLE 15 An artificial heart valve consisted of parts of tantalum meta, woven pieces of polytetrafluoroethylene and a bail made from a silicone resin. The parts were treated in the following way in an aqueous 0.005 molar cetylamine hydrochloride solution.
• the silicone resin ball was treated in a solution at C. for 14 hours.
• the tantalum and the polytetrafluoroethylene parts were treated in the solution at C. for 14 hours.
• the amine solution was allowed to cool to 60 C., and the parts were carefully rinsed 15 times with an isotonic salt solution at 50 C.
• the parts were now assembled to form two artificial valves. One of these valves was now treated for 4 hours at 70 C. in an isotonic salt solution containing 2.5 lU per milliliter of heparin.
• valves were treated in an aqueous dispersion of a complex compound of heparin and cetylammonium chloride containing 12 IU per milliliter of heparin and 310 moles per milliliter of cetylammonium chloride.
• the values were now carefully rinsed 10 times with an isotonic salt solution at 40 C. Experiments in vivo revealed that both valves had a nonthrombogenic surface.
• the tubes were then divided into four groups.
• One group of tubes was heparinized for 2 hours at 40 C. with an isotonic salt solution containing 2.5 lU per milliliter of heparin.
• a second group of tubes was heparinized for 2 hours at 70 C. with an isotonic salt solution containing 10 IU per milliliter of heparin.
• a third group of the tubes was heparinized for 2 hours at 70 C. with an isotonic salt solution containing 100 IU per milliliter of heparin.
• a fourth group of the tubes was heparinized for 2 hours at 20 C. with an isotonic salt solution containing 100 IU or milliliter of heparin. All tubes were rinsed 20 times with 40 C. isotonic salt solution after the heparin treatment.
• none of the series produced any signs of coagulation in human blood having been stored for 2 hours in the tubes.
• EXAMPLE 1 Polyethylene catheters (length 6080 centimeters, diameter 2.5 millimeter) were under sterile conditions inserted via a vein in the backbone of a dog up into Vena Cava Inferior to a level with the heart. Eight catheters had been treated in distilled water for 17 hours at 98 C. (so-called nontreated catheters) and eight catheters had been treated l7 hours at 98 C. in a water solution containing heparin-CTAB-complex produced by reacting 40 IU of heparin per milliliter with 10" 5 moles of CTAB per milliliter, i.e., three-fourths of the heparin negative groups are neutralized.
• a method for retarding coagulation of blood in contact with a plastic surface which comprises treating such plastic surface with a cationic surface-active agent in an aqueous medium at a temperature sufficiently elevated so as to cause absorption of the cationic agent onto the surface, and treating such plastic surface with heparin.
• the cationic surface-active agent is a member of the group consisting of primary, secondary and tertiary amines and salts thereof and quatemary ammonium compounds.
• plastic surface is treated with an aqueous solution containing the surface-active agent in a concentration of at least about moles per liter and subsequently treated with an aqueous solution containing the heparin.
• a plastic article suitable for use in contact with blood without significant coagulation said article having a plastic surface which is to contact the blood, said surface having been treated with a cationic surface-active agent and heparin by the method of claim 1.
• thermoplastic is a thermoplastic
• a plastic article as described in claim 13 wherein the surface-active agent has an alkyl chain of about l2 to about 18 carbon atoms.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Life Sciences & Earth Sciences (AREA)
• Health & Medical Sciences (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Zoology (AREA)
• Wood Science & Technology (AREA)
• Engineering & Computer Science (AREA)
• Microbiology (AREA)
• Neurosurgery (AREA)
• Biotechnology (AREA)
• Immunology (AREA)
• Analytical Chemistry (AREA)
• Molecular Biology (AREA)
• Physics & Mathematics (AREA)
• Biophysics (AREA)
• Hematology (AREA)
• Biochemistry (AREA)
• Bioinformatics & Cheminformatics (AREA)
• General Engineering & Computer Science (AREA)
• General Health & Medical Sciences (AREA)
• Genetics & Genomics (AREA)
• Materials For Medical Uses (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=20300376

Family Applications (1)

Country Status (2)

Cited By (54)

• 1964
  • 1964-12-17 SE SE15249/64A patent/SE306597B/xx unknown
• 1968
  • 1968-06-21 US US738826A patent/US3634123A/en not_active Expired - Lifetime

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events