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
  • A61L33/0041—Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate characterised by the choice of an antithrombatic agent other than heparin
• • 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

Definitions

• the present invention relates to methods for producing biocompatible surfaces by coating them with phospholipid and binding the phospholipid to the surface by means of ultrasonication.
• the formation of blood clots on the surfaces of these instruments is dangerous and may prove fatal if the clots are washed off by the blood flow into the vascular system.
• US Patent 4 426 330 discloses a chemically modified phospholipid for more stable coatings.
• US Patent 4 438 329 discloses a phospholipid chemically bonded to a polymer for coating surfaces.
• the introduction of new, chemically modified phospholipids into a human body or blood stream may have unforseen - 2 -
• the present invention concerns a method for producing a biocompatible surface, by coating the surface with phospholipid characterised by immersing the surface to be coated in a bath containing a suspension of phospholipid in a liquid in which it is sparingly soluble, and then ultrasonicating the bath to coat the surface with phospholipid.
• Another aspect of the invention concerns pre-treating the surface to be coated.
• the surface is firstly immersed in a phospholipid solution.
• the solution comprises phospholipid substantially dissolved in a solvent in which it is soluble, such as ethanol or chloroform.
• the surface is then removed from the solution and the solvent allowed to evaporate off.
• the dry surface is then subjected to the ultrasonication process described above.
• Any suitable surface may be coated, such as metal, glass, plastics or ceramics. Any phospholipid may be used and some examples are described in Table 1. TABLE 1
• Phosphoglycerides phosphatidic acids cytidylic phosphoglycerides (CDP diglyceride) choline phosphoglycerides ethanolamine phosphoglycerides
• Phosphoglycolipids diacyl glycerylphosphoryldiglucosyl
• Phosphodiol lipids acyl dihydroxyacetone phosphate alkyl dihydroxyacetone phosphate
• the preferred phospholipid is phosphatidylcholine, (lecithin) .
• the ultrasonic treatment is conducted in the normal manner using commercially available ultrasonic equipment. - 4 - '
• the suspension of phospholipid used in the bath comprises preferably finely divided phospholipid suspended in a liquid in which it is only sparingly soluble.
• the suspension is preferably an aqueous suspension.
• Phospholipid is added to the suspension in solid form and is suspended by an initial ultrasonication to form liposomes.
• the phospholipid is preferably suspended at a concentration of 0.1 to 10% w/v, most preferably 1 to 2% w/v.
• the liquids that may be used to suspend the phospholipid in accordance with the present invention include water and physiological saline solutions.
• Any ultrasound device can be used in accordance with the present invention, such as the Model G112SPIT (serial No. 11254) produced by Laboratory Supplies Co. Inc., New York.
• the method of coating a surface with phospholipid may also comprise a pre-treatment step, which involves dissolving phospholipid in a solvent; placing the surface to be coated into the phospholipid/solvent solution to allow initial gross deposition of phospholipid onto the surface; removing the coated surface from the phospholipid solvent solution; evaporating off residual solvent on the coated surface; placing the coated surface into the suspension; and ultrasonicating the coated surface as described previously.
• a pre-treatment step which involves dissolving phospholipid in a solvent; placing the surface to be coated into the phospholipid/solvent solution to allow initial gross deposition of phospholipid onto the surface; removing the coated surface from the phospholipid solvent solution; evaporating off residual solvent on the coated surface; placing the coated surface into the suspension; and ultrasonicating the coated surface as described previously.
• the phospholipid is suspended in the solvent by stirring. Any solvent that dissolves phospholipid may be used in accordance with the present invention, such as chloroform or methanol.
• the pre-treatment by immersion in the dissolved phospholipid may involve the gross deposition of phospholipid from a solution with a low degree of supersaturation.
• the ultrasonication of the coated surface orientates and consolidates the phospholipid that was deposited on the surface to be coated from the solution.
• the slow deposition of the phospholipid from the solution with a low degree of supersaturation onto the surface to be coated enables the phospholipid to be deposited with a better orientation and thus gives an effective coating.
• the methods of the present invention enable the rapid and successful coating of surfaces with phospholipid.
• the methods may be used to coat the surfaces of medical instruments, thereby making the surfaces non-thrombogenic.
• the present invention is particularly applicable for the production of coated catheters for which the surfactant properties of lubrication and release are ideal. It may also be used to produce pacemakers and prosthetic devices which are less likely to be rejected by the body's immune system. The invention may also be applied to ceramic prosthesis to reduce their permeability.
• the present invention has found that surfaces having phospholipid adhered to them seem to be less likely to generate an antibody response than uncoated materials. Similarly, the formation of blood clots is greatly reduced on such coated surfaces.
• heparin which can now be grafted to certain surfaces to render then non-thrombogenic.
• One of the features of grafted heparin is the number of negative charges which they impart, indicating that they might function by providing a site most conducive to the adsorption of the endogenous surfactants, such as phospholipids, which are then the true interface with blood or other body fluids.
• the experiment was performed by solvent depositing soya lecithin in chloroform. Whilst these rods showed less clotting than the uncoated control rod, they were found to be less effective than the rods of comparative example 1 and markedly less effective than the rods coated using ultrasound..
• Example 2 The Experiments 2 and 3 were repeated, but the surfaces were allowed to dry before being placed in the bath and ultrasonicated as described in Example 1. The glass rods resulting were placed in blood as described in Example 1. The rods thus treated were clean of blood, amd the incidence of clotting was less than in Example 2 or 3.

Landscapes

• Health & Medical Sciences (AREA)
• Epidemiology (AREA)
• Hematology (AREA)
• Surgery (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Materials Engineering (AREA)
• Engineering & Computer Science (AREA)
• Chemical & Material Sciences (AREA)
• Materials For Medical Uses (AREA)

Applications Claiming Priority (3)

Publications (2)

Family

ID=25632425

Family Applications (1)

Country Status (2)

Families Citing this family (8)

Family Cites Families (5)

• 1990
  • 1990-07-06 WO PCT/AU1990/000292 patent/WO1991000745A1/en not_active Ceased
  • 1990-07-06 EP EP90917894A patent/EP0486625A1/de not_active Withdrawn

Non-Patent Citations (2)

Also Published As

Similar Documents

Legal Events