WO1979000638A1 - A method of producing thrombosis-resistant surfaces - Google Patents

A method of producing thrombosis-resistant surfaces Download PDF

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Publication number
WO1979000638A1
WO1979000638A1 PCT/SE1979/000035 SE7900035W WO7900638A1 WO 1979000638 A1 WO1979000638 A1 WO 1979000638A1 SE 7900035 W SE7900035 W SE 7900035W WO 7900638 A1 WO7900638 A1 WO 7900638A1
Authority
WO
WIPO (PCT)
Prior art keywords
heparin
hirudin
salt
metal
palladium
Prior art date
Application number
PCT/SE1979/000035
Other languages
English (en)
French (fr)
Inventor
A Bergstroem
B Soedervall
Original Assignee
Thin Conductive Coating Oester
A Bergstroem
B Soedervall
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Thin Conductive Coating Oester, A Bergstroem, B Soedervall filed Critical Thin Conductive Coating Oester
Publication of WO1979000638A1 publication Critical patent/WO1979000638A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS 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
    • A61L33/00Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
    • A61L33/0005Use of materials characterised by their function or physical properties
    • A61L33/0011Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
    • A61L33/0017Anticoagulant, 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.

Landscapes

  • 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)
PCT/SE1979/000035 1978-02-17 1979-02-16 A method of producing thrombosis-resistant surfaces WO1979000638A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE7801853 1978-02-17
SE7801853 1978-02-17

Publications (1)

Publication Number Publication Date
WO1979000638A1 true WO1979000638A1 (en) 1979-09-06

Family

ID=20334023

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE1979/000035 WO1979000638A1 (en) 1978-02-17 1979-02-16 A method of producing thrombosis-resistant surfaces

Country Status (4)

Country Link
EP (1) EP0015909A1 (da)
JP (1) JPS55500091A (da)
DK (1) DK427079A (da)
WO (1) WO1979000638A1 (da)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0357242A1 (en) * 1988-08-03 1990-03-07 New England Deaconess Hospital Corporation A biocompatible, thromboresistant substance comprising hirudin, analogs or fragments thereof, and methods of producing the same
EP0367489A2 (en) * 1988-11-01 1990-05-09 Baxter International Inc. Thromboresistant materials and methods for making same
WO1991002750A1 (en) * 1989-08-18 1991-03-07 Biogen, Inc. Novel inhibitors of thrombin
EP0442843A1 (de) * 1990-02-14 1991-08-21 Pentapharm A.G. Inhibitoren zur antikoagulierenden Vorbehandung von Blutproben
WO1992005749A1 (en) * 1990-10-04 1992-04-16 New England Deaconess Hospital Corporation Soluble thrombogenesis inhibitor conjugates
US5112615A (en) * 1988-08-03 1992-05-12 New England Deaconess Hospital Corporation Soluble hirudin conjugates
US5135516A (en) * 1989-12-15 1992-08-04 Boston Scientific Corporation Lubricious antithrombogenic catheters, guidewires and coatings
WO1993010827A1 (en) * 1991-11-29 1993-06-10 William Cook Europe A/S A process for hydrophilic coating of metal surfaces
US5281662A (en) * 1988-08-03 1994-01-25 New England Deaconess Hospital Corporation Anthraquinone dye treated materials
CN112043877A (zh) * 2020-08-06 2020-12-08 苏州大学 一种蚕丝抗凝血管支架覆膜及其制备方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3819079A1 (de) * 1988-06-04 1989-12-07 Hoechst Ag Hirudin-derivate mit verzoegerter wirkung

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2702253A (en) * 1950-11-01 1955-02-15 Gasaccumulator Svenska Ab Surface metallizing method
US3549409A (en) * 1969-04-28 1970-12-22 Cordis Corp Production of nonthrombogenic plastics

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2702253A (en) * 1950-11-01 1955-02-15 Gasaccumulator Svenska Ab Surface metallizing method
US3549409A (en) * 1969-04-28 1970-12-22 Cordis Corp Production of nonthrombogenic plastics

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Chalmers. Tidskrift utgiven av Chalmers Tekniska Hogskola, No. 2 1971, issued 1971 (Goteborg, Sweden) "Heparin", see pages 4 to 6. *
Journal of Biomedical Materials Research, Volume 6, Pt 1, issued 1972 (New York), M F DYCK, "Inorganic Heparin Complexes for the Preparation of Nonthrombogenic Surfaces", see pages 115 to 141. *

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5112615A (en) * 1988-08-03 1992-05-12 New England Deaconess Hospital Corporation Soluble hirudin conjugates
US5281662A (en) * 1988-08-03 1994-01-25 New England Deaconess Hospital Corporation Anthraquinone dye treated materials
US5167960A (en) * 1988-08-03 1992-12-01 New England Deaconess Hospital Corporation Hirudin-coated biocompatible substance
EP0357242A1 (en) * 1988-08-03 1990-03-07 New England Deaconess Hospital Corporation A biocompatible, thromboresistant substance comprising hirudin, analogs or fragments thereof, and methods of producing the same
EP0367489A3 (en) * 1988-11-01 1991-07-31 Baxter International Inc. Thromboresistant materials and methods for making same
EP0367489A2 (en) * 1988-11-01 1990-05-09 Baxter International Inc. Thromboresistant materials and methods for making same
WO1991002750A1 (en) * 1989-08-18 1991-03-07 Biogen, Inc. Novel inhibitors of thrombin
US5135516A (en) * 1989-12-15 1992-08-04 Boston Scientific Corporation Lubricious antithrombogenic catheters, guidewires and coatings
EP0442843A1 (de) * 1990-02-14 1991-08-21 Pentapharm A.G. Inhibitoren zur antikoagulierenden Vorbehandung von Blutproben
WO1992005749A1 (en) * 1990-10-04 1992-04-16 New England Deaconess Hospital Corporation Soluble thrombogenesis inhibitor conjugates
EP0551286A1 (en) * 1990-10-04 1993-07-21 New England Deaconess Hospital Soluble hirudin conjugates
EP0551286A4 (en) * 1990-10-04 1993-11-03 New England Deaconess Hospital Soluble hirudin conjugates
WO1993010827A1 (en) * 1991-11-29 1993-06-10 William Cook Europe A/S A process for hydrophilic coating of metal surfaces
CN112043877A (zh) * 2020-08-06 2020-12-08 苏州大学 一种蚕丝抗凝血管支架覆膜及其制备方法

Also Published As

Publication number Publication date
EP0015909A1 (en) 1980-10-01
JPS55500091A (da) 1980-02-14
DK427079A (da) 1979-10-10

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