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
  • A61L33/00—Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
  • A61L33/0005—Use of materials characterised by their function or physical properties
  • A61L33/0011—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
  • A61L33/0017—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate using a surface active agent

Definitions

• the present invention relates to a novel method of effect ⁇ ively treating surfaces with heparin, hirudin and other anticoagulant proteins for the purpose of rendering said surfaces resistant to thrombosis.
• the method comprises the treatment of said surface with a palladium salt or a rhodium salt prior to heparising said surface.
• Heparin which is a mucopolysaccharide from D-glucoseamine and glucuronic acid with a molecular weight of about 17000, has the ability of preventing the aforementioned formation of a thrombus. It is essential that a heparinized surface is stable and that the heparin is firmly bound to the surface of the object.
• -stage method of heparinizing a surface which method, in addition to washing stages, comprises treating the surface with hexadecyl amine hydrochloride heparin, an aminesoluti t glutaraldehyde and cooking salt.
• the product is considerab better than one whose surfaces have not been treated.
• the layers produced when applying this method tend to be uneve and are also liable to be washed-off by the blood flowing thereagainst, consequently, there is a need of improving the method.
• Heparin shares this property with hirudin and other anticoagulant proteins.
• Hirudin is a protein having a molecular weight of 16000 - 1000.
• the surface to be treated may be of practically any materi whatsoever, although preferably the surface is of metal, such as a stainless steel, a plastics material, such as polyvinyl chloride, polyolefins, acryl resins and co-poly ⁇ mers thereof, silicon plastics, rubber, particularly butyl rubber, and fluorocarbon plastics.
• metal such as a stainless steel
• plastics material such as polyvinyl chloride, polyolefins, acryl resins and co-poly ⁇ mers thereof, silicon plastics, rubber, particularly butyl rubber, and fluorocarbon plastics.
• the treatment metal may be one of a number of different metals. Those metals tested in particular included palladium, rhodium, nickel, cobalt and copper. Among these metals palladium and rhodium take a particular position, owing to the fact that peptide hydrogen ionisation takes place at an optimal pH range of 3-4. The pH range in the case of nickel is 4-6, in the case of cobalt 6-8 and in the case of copper 8-10. With regard to these properties see E.W. Wilson and R.B. Martin, Inorg. Chem 9, page 528 (1970).
• the well-cleaned, and optionally etched surface is treated with a solution of a metal salt of the metal soluble in the solvent used, with a preferably pharmaceutically acceptable acid.
• a suitable solvent there can be mentioned primarily water, and water in mix ⁇ tures with a polar solvent m-iscible therewith.
• Polar organic solvents can also be used. Among those polar solvents which can be used are alkanols, such as methanol and ethanol.
• Suitable salts are primarily chlorides, sul ⁇ phates, nitrates, acetates, citrates, although it lies within the expertise of one skilled in this art to select other suitable soluble salts of the metal used.
• Rhodium can be used in the same manner.
• the treatment with the metal salt takes only some seccnds up to some minutes, depending upon the temperature of the solution and its pH, and takes place at an ion strength o 0.3-3 mmol metal salt per litre, which in the case of the mentioned palladium salts corresponds to 0.1-0.5 grams of salt per litre.
• the temperature may be room temperature, although a temperature of 50-80 c C is preferred.
• the surface is treated with a heparin solution containing 1000-10000 IE heparin per litre.
• the solution contains mainly water and other suitable substances such as sodium chloride and glucose.
• the treatment time also varies here, although normally requires a treatment time 15-45 minutes. Glucose can be added to stabilise the solu tion.
• the treatment method proposed in accordance with the in ⁇ vention results in the formation of a heparin layer which, has been judged, on the tests carried out, to be some ten times better than a heparin layer produced in accordance with the present standpoint of technics. It is assumed th palladium binds to the amine group in the glucose amine part of the heparin molecule, possibly in combination with van den Waals bonds to oxygen atoms in the heparin chain and in the sulphone group which is bound to the amine gro in the glucose amine part of the molecule.

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• Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Animal Behavior & Ethology (AREA)
• Engineering & Computer Science (AREA)
• Hematology (AREA)
• Surgery (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Materials Engineering (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Materials For Medical Uses (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 1979
  • 1979-02-16 WO PCT/SE1979/000035 patent/WO1979000638A1/en unknown
  • 1979-02-16 JP JP50042479A patent/JPS55500091A/ja active Pending
  • 1979-09-11 EP EP19790900219 patent/EP0015909A1/en not_active Withdrawn
  • 1979-10-10 DK DK427079A patent/DK427079A/da not_active Application Discontinuation

Non-Patent Citations (1)

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