EP0486625A1 - Verfahren zur herstellung einer bioverträglichen oberfläche - Google Patents
Verfahren zur herstellung einer bioverträglichen oberflächeInfo
- Publication number
- EP0486625A1 EP0486625A1 EP90917894A EP90917894A EP0486625A1 EP 0486625 A1 EP0486625 A1 EP 0486625A1 EP 90917894 A EP90917894 A EP 90917894A EP 90917894 A EP90917894 A EP 90917894A EP 0486625 A1 EP0486625 A1 EP 0486625A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- phospholipid
- coated
- blood
- solvent
- bath
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
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.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AUPJ513989 | 1989-07-07 | ||
AU5139/89 | 1989-07-07 | ||
AU59502/90A AU631903B2 (en) | 1989-07-07 | 1990-07-06 | A method for producing a biocompatible surface |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0486625A4 EP0486625A4 (de) | 1992-04-01 |
EP0486625A1 true EP0486625A1 (de) | 1992-05-27 |
Family
ID=25632425
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP90917894A Withdrawn EP0486625A1 (de) | 1989-07-07 | 1990-07-06 | Verfahren zur herstellung einer bioverträglichen oberfläche |
Country Status (2)
Country | Link |
---|---|
EP (1) | EP0486625A1 (de) |
WO (1) | WO1991000745A1 (de) |
Families Citing this family (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5282850A (en) * | 1989-07-25 | 1994-02-01 | Smith & Nephew Richards, Inc. | Artificial heart components with wear resistant coatings of reduced thrombogenicity |
GB9022938D0 (en) | 1990-10-22 | 1990-12-05 | Biocompatibles Ltd | Non-thrombogenic surfaces |
GB9112267D0 (en) * | 1991-06-07 | 1991-07-24 | Biocompatibles Ltd | Polymeric coating |
US5217743A (en) * | 1992-02-07 | 1993-06-08 | Paradigm Biotechnologies Partnership | Biomaterials of enhanced biocompatibility |
US5798117A (en) * | 1992-04-24 | 1998-08-25 | Biocompatibles Limited | Method of reducing microorganism adhesion |
EP0637309B1 (de) * | 1992-04-24 | 1999-03-31 | Biocompatibles Limited | Metall beschichtungen |
US5824359A (en) * | 1997-06-30 | 1998-10-20 | Becton Dickinson And Company | Medical device lubricant containing lecithin |
GB9920547D0 (en) | 1999-08-31 | 1999-11-03 | Destiny Pharma Ltd | Coated implant |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0032622B1 (de) * | 1979-12-20 | 1985-08-14 | Dennis Chapman | Polymerisationsfähige Phospholipide und deren Polymere, Verfahren zu deren Herstellung, Verfahren zu deren Verwendung für die Bildung von Überzugschichten auf Substraten und zum Bilden von Liposomen und die daraus entstehenden Liposomzusammensetzungen und Substrate mit Überzugschichten |
US4426330A (en) * | 1981-07-20 | 1984-01-17 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
US4725442A (en) * | 1983-06-17 | 1988-02-16 | Haynes Duncan H | Microdroplets of water-insoluble drugs and injectable formulations containing same |
GB8527071D0 (en) * | 1985-11-04 | 1985-12-11 | Biocompatibles Ltd | Plastics |
US4803075A (en) * | 1986-06-25 | 1989-02-07 | Collagen Corporation | Injectable implant composition having improved intrudability |
-
1990
- 1990-07-06 WO PCT/AU1990/000292 patent/WO1991000745A1/en not_active Application Discontinuation
- 1990-07-06 EP EP90917894A patent/EP0486625A1/de not_active Withdrawn
Non-Patent Citations (2)
Title |
---|
No further relevant documents have been disclosed. * |
See also references of WO9100745A1 * |
Also Published As
Publication number | Publication date |
---|---|
WO1991000745A1 (en) | 1991-01-24 |
EP0486625A4 (de) | 1992-04-01 |
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Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 19920115 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB IT LI LU NL SE |
|
17Q | First examination report despatched |
Effective date: 19931209 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 19940201 |