WO1990009384A1 - Phosphoric acid esters, their preparation and their use for the preparation of biocompatible surfaces - Google Patents

Phosphoric acid esters, their preparation and their use for the preparation of biocompatible surfaces Download PDF

Info

Publication number
WO1990009384A1
WO1990009384A1 PCT/GB1990/000237 GB9000237W WO9009384A1 WO 1990009384 A1 WO1990009384 A1 WO 1990009384A1 GB 9000237 W GB9000237 W GB 9000237W WO 9009384 A1 WO9009384 A1 WO 9009384A1
Authority
WO
WIPO (PCT)
Prior art keywords
group
compound
preparation
formula
compound according
Prior art date
Application number
PCT/GB1990/000237
Other languages
French (fr)
Inventor
Shiv S. Sandhu
Ajay K. Luthra
Original Assignee
Biocompatibles Limited
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 Biocompatibles Limited filed Critical Biocompatibles Limited
Publication of WO1990009384A1 publication Critical patent/WO1990009384A1/en

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
    • A61L33/0076—Chemical modification of the substrate
    • A61L33/0082—Chemical modification of the substrate by reacting with an organic compound 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/06—Phosphorus compounds without P—C bonds
    • C07F9/08—Esters of oxyacids of phosphorus
    • C07F9/09—Esters of phosphoric acids
    • C07F9/10—Phosphatides, e.g. lecithin
    • 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
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/22—Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes

Definitions

  • the present invention relates to compounds for use in treating polymer and glass surfaces to render the surfaces biocompatible, to processes for producing the compounds and biocompatibilising the surfaces and to surfaces treated with the compounds.
  • prosthetic devices such as artificial vascular grafts having high tensile strength, high elongation, superior toughness and satisfactory abrasion resistance.
  • biocompatibility of the surfaces of known structural materials The asymmetric structure of biomembranes are crucial in the maintenance of homeostasis between cell-cell interactions. These are particularly important features of blood cells (eg. erythrocytes and leucocytes). Studies of cell systems have shown that the lipids which occur on the inner cell surface are procoagulant, whilst those on the outer surface are thromboresi ⁇ tant (Zwaal, RFA,
  • the lipid matrix on the outer surface comprises mainly the
  • the present invention provides compounds which are glycerophosphoryl choline derivatives having
  • the compounds of the invention are those of formula (I)
  • X is oxygen or -NH- and is
  • R 3 is hydrogen or methyl
  • R 2 is as defined above
  • R 4 is or -( CH 2 ) n -
  • n 2 or 3
  • R 2 is as defined above
  • Preferred compounds of formula (I) are those wherein one of A 1 and A 2 is hydrogen and those wherein A 1 and A 2 are the same groups
  • GPC glycerophosphorylcholine
  • Compounds of formula (I) can be produced by derivatising glycerophosphoryl choline by treatment with appropriate reactive intermediates which are readily available from commercial sources.
  • the reactions are generally conducted in water or a suitable solvent at ambient or elevated temperature. Suitable reactive
  • intermediates include succinic anhydride, ethane diamine and polymethylene di-isocyanates which will respectively generate the side chains A 1 and/or A 2 wherein R 1 is
  • GPC and the compounds of formula (I) are used to treat surfaces which are required to have improved
  • carboxylic groups and reaction with the compounds of formula (I) or GPC can be induced by readily available techniques such as the use of ionising radiation, peroxide formation, active vapour activation and UV grafting, any of which will initiate coupling of GPC or the compound of formula (I) to the reactive groups on the surface by free radical grafting processes.
  • the surface reactive groups may be derivatised by treatment with, for instance, carbodiimides, to give O-acylisoureas to which any of GPC and the
  • compounds of formula (I) may be coupled.
  • amino-carboxyl and hydroxyl groups on the surface of the material may be activated by treatment with
  • the present invention provides a process for biocompatibilising a surface comprising contacting the surface with GPC or a compound of formula (I) as hereinbefore defined under appropriate coupling conditions.
  • the invention further provides a material having the residues of GPC and/or one or more compounds of formula (I) coupled to its surface thereby rendering the material Biocompatible.
  • the material is a pre-formed prosthetic device such as an implant or
  • bis-UGPC bis-(undecylinoyl)glycero- phosphoryl choline
  • 1643 C C; 1241, 1178, 1092 C-O; 824, 767 P-O.
  • EDC 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
  • Hydrated contacted lenses were successively dipped into mixtures containing water and acetone with increasing acetone concentration and then into pure acetone. 1 mmole carbonyldiimidazole was dissolved in 5 mis dry acetone. The contact lenses were dipped into the dry acetone solution containing carbonyldiimidazole for 30 seconds and then successively dipped into mixtures

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Molecular Biology (AREA)
  • Organic Chemistry (AREA)
  • Surgery (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Materials For Medical Uses (AREA)

Abstract

A compound of formula (I), wherein each of A?1 and A2¿ is, independently, hydrogen or a group (a), in which R1 is selected from (i) certain radicals containing (b), in which R3 is hydrogen or methyl, (ii) -CH¿2?-CH2-COOH, (iii) -NH-CH2-CH2-NH2, or (iv) -NH-(CH2)t-NCO, in which t is 1 to 14. A process for its preparation and its use in rendering a surface biocompatible are also disclosed.

Description

PHOSPHORIC ACID ESTERS, THEIR PREPARATION AND THEIR USE FOR
THE PREPARATION OF BIOCOMPATIBLE SURFACES
The present invention relates to compounds for use in treating polymer and glass surfaces to render the surfaces biocompatible, to processes for producing the compounds and biocompatibilising the surfaces and to surfaces treated with the compounds.
For implantation in the human or animal body devices must be biocompatible in the sense that interaction with the living tissue should not cause damaging biological response (such as protein adhesion leading to thrombus formation) and the performance of the device should not be impaired once implanted (i.e. it should be non-degradable and have appropriate mechanical properties).
There are many known materials which have
the necessary mechanical properties to perform as
prosthetic devices, such as artificial vascular grafts having high tensile strength, high elongation, superior toughness and satisfactory abrasion resistance.
However it is still a major cause of concern that prosthetic devices generally have poor biological
compatibility. As a consequence, there has been intensive research into the development of biocompatible materials. The present inventors' approach is to devise improved surface treatments suitable for improving the
biocompatibility of the surfaces of known structural materials. The asymmetric structure of biomembranes are crucial in the maintenance of homeostasis between cell-cell interactions. These are particularly important features of blood cells (eg. erythrocytes and leucocytes). Studies of cell systems have shown that the lipids which occur on the inner cell surface are procoagulant, whilst those on the outer surface are thromboresiεtant (Zwaal, RFA,
Comfuriu, P and Van Deenen, LMM, Membrane asymmetry and blood coagulation, Nature 1977, 268, 358-360). The lipid matrix on the outer surface comprises mainly the
zwitterionic head grouping of phosphorylcholine.
Figure imgf000004_0001
The present invention provides compounds which are glycerophosphoryl choline derivatives having
particularly useful properties for treating surfaces in this way. The compounds of the invention are those of formula (I)
Figure imgf000004_0002
wherein one of A1 and A2 is a group and
Figure imgf000004_0003
the other is the same or a different group or is
Figure imgf000005_0001
hydrogen and the or each group R1 is selected from
(i)
Figure imgf000005_0002
wherein m is 0 to 3
X is oxygen or -NH- and is
Figure imgf000005_0003
in which R3 is hydrogen or methyl.
(ii)
Figure imgf000005_0004
wherein R2 is as defined above,
R4 is or -( CH2 )n -
Figure imgf000005_0005
in which n is 2 or 3
and Y is oxygen, -NH-,
or
Figure imgf000005_0006
or
Figure imgf000005_0007
in which p is 2 or 3
or
Figure imgf000005_0008
or
Figure imgf000005_0009
in which q is 1 to 3
(iii) -(CH2)8-R2
wherein s is 1 to 9
and R2 is as defined above
(iv) -CH2 -CH2 -COOH
(v) -NH-CH2 -CH2 -NH2 and
(vi) -NH-(CH2)t-NCO in which t is 1 to 14.
Preferred compounds of formula (I) are those wherein one of A1 and A2 is hydrogen and those wherein A1 and A2 are the same groups
Figure imgf000006_0001
The most preferred compound for use in accordance with the invention is glycerophosphorylcholine (GPC) itsel'f, but GPC is a known compound and so has not been included in formula (I).
Compounds of formula (I) can be produced by derivatising glycerophosphoryl choline by treatment with appropriate reactive intermediates which are readily available from commercial sources. The reactions are generally conducted in water or a suitable solvent at ambient or elevated temperature. Suitable reactive
intermediates include succinic anhydride, ethane diamine and polymethylene di-isocyanates which will respectively generate the side chains A1 and/or A2 wherein R1 is
-CH2-CH2-COOH, -NH-CH2-CH2-NH2 or -NH-(CH2)t-NCO
respectively.
GPC and the compounds of formula (I) are used to treat surfaces which are required to have improved
biocompatibility. Almost all such surfaces contain free reactive groups such as alcohol, amine, amide and
carboxylic groups and reaction with the compounds of formula (I) or GPC can be induced by readily available techniques such as the use of ionising radiation, peroxide formation, active vapour activation and UV grafting, any of which will initiate coupling of GPC or the compound of formula (I) to the reactive groups on the surface by free radical grafting processes.
Alternatively the surface reactive groups may be derivatised by treatment with, for instance, carbodiimides, to give O-acylisoureas to which any of GPC and the
compounds of formula (I) may be coupled. Alternatively, amino-carboxyl and hydroxyl groups on the surface of the material may be activated by treatment with
carbonyldiimidazole; GPC and all the compounds of formula (I) except for the isocyanate derivatives (definition (vi) of group R1) may be coupled in this way. Materials having amino or carboxyl surface groups may also be
activated using halo isocyanateε; free radical coupling processes are initiated by homolytic cleavage of the carbon-halogen bond of the halo isocyanate. This method is suitable for use with all those compounds of formula (I) wherein one or both A1 and A2 contain a group R2, i.e, definitions (i) to (iii) of group R1.
In further aspects the present invention provides a process for biocompatibilising a surface comprising contacting the surface with GPC or a compound of formula (I) as hereinbefore defined under appropriate coupling conditions. The invention further provides a material having the residues of GPC and/or one or more compounds of formula (I) coupled to its surface thereby rendering the material Biocompatible. Preferably the material is a pre-formed prosthetic device such as an implant or
ophthalmic contact lens.
The invention will now be illustrated by the following Examples.
EXAMPLE 1
Synthesis of bis-(undecylinoyl)glycerophosphorylcholine
Figure imgf000008_0001
The synthesis of bis-(undecylinoyl)glycero- phosphoryl choline (bis-UGPC) involved a two step process. In the first step the corresponding anhydride was prepared and was followed by coupling of the anhydride to glycerophosphorylcholine (GPC).
1. Anhydride Preparation
To a stirred solution containing undecylinic acid (0.1 mole, 18.4g), in dried chloroform (400ml) was added dicyclohexyl carbodiimide (DCC) (0.056 mole, 11.55g) at room temperature. The reaction was stopped after 3 hrs and the precipitate, dicyclohexylurea was removed and the solvent rotary evaporated. The resulting pale yellow residue was treated with dry acetone (50ml) and stored at 4ºC for 3hrs. A precipitate was formed and isolated. This step was repeated until no further precipitate was formed. Acetone was removed from the liquor by rotary yield of product = 12.3g (70%).
2. Bis-(undecylinoyl)glycerophosphorylcholine (bis-UGPC)
GPC (3g; 0.012 moles) was suspended in dry chloroform (100ml) under an atmosphere of nitrogen. The reaction flask (500ml) was covered to protect the reaction solvent from light. The undecylinic anhydride (10.52 g; 0.03 moles) was added to the reaction mixture followed by the addition of 4-dimethylamino-pyridine (DMAP) (2.85g; 0.023 moles). The nitrogen supply was isolated and the reaction flask sealed. The reaction mixture was stirred for 30hrs at ambient temperature. On completion of the
reaction the unreacted glycerophosphorylcholine was
filtered off; the solvent rotary evaporated, and an orange yellow residue was obtained. The residue was treated with dry acetone (50ml) and kept at -11ºC for 24hrs. A white precipitate was formed and was isolated and washed with cold acetone. The product was found to be highly
hydroscopic. Yield = 5.26g (74%).
I.R. analysis 3078 =CH; 2926, 2855 CH; 1738 C=O;
1643 C=C; 1241, 1178, 1092 C-O; 824, 767 P-O.
EXAMPLE 2
Grafting of bis-UGPC to the hydroxyl groups of a contact lens.
UGPC (29.5 mmole) was added to deionised water (5mls) containing one contact lens. The temperature of the solution was brought up to 58º C after which 18.2 μmoles of eerie ammonium nitrate was added to the solution and the temperature of the reaction was maintained at 58ºC for 30 minutes. After this the contact lens was removed from solution and washed several times in deionised water and finally placed in phosphate buffer pH7.4 and analysed for lysozyme absorption. EXAMPLE 3
Coupling of GPC to the lens by use of a water soluble carbodiimide.
Contact lenses were removed from their phosphate buffered saline environment and placed in a vial containing 1 mmole GPC in 5ml of deionised water. The lenses were equilibrated with GPC for lhr after which 1 mmole of
1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) was added to the vials. The vials were agitated in a shaking water bath for one hour at 25º C. The vials were then removed and stored in a refrigerator at 4ºC for 16 hours. The lenses were washed several times with distilled water and then finally equilibrated in phosphate buffered saline (pH7.4) and assayed for lysozyme absorption.
EXAMPLE 4
Coupling of GPC to the lens by use of carbonyldiimidazole
Hydrated contacted lenses were successively dipped into mixtures containing water and acetone with increasing acetone concentration and then into pure acetone. 1 mmole carbonyldiimidazole was dissolved in 5 mis dry acetone. The contact lenses were dipped into the dry acetone solution containing carbonyldiimidazole for 30 seconds and then successively dipped into mixtures
containing water and acetone with increasing water content and finally in pure water. The lenses were then incubated at room temperature in 5mls bicarbonate buffer (pH8) containing 1mmole GPC for 16 hours. The lenses were removed and washed several times with water and finally equilibrated in phosphate buffer (pH 7.4) and assayed for lysozyme absorption.

Claims

1. A compound of formula (I) :
Figure imgf000013_0001
wherein each of A1 and A2 is, independently, hydrogen or a group in which R1 is selected from
Figure imgf000013_0002
Figure imgf000013_0003
wherein m is 0 to 3,
X is oxygen or -NH- and
Figure imgf000013_0004
in which R3 is hydrogen or methyl,
Figure imgf000013_0005
wherein R2 is as defined above,
R4 is
Figure imgf000013_0006
in which n is 2 or 3
and Y is oxygen, -NH-,
or
Figure imgf000013_0007
or
Figure imgf000013_0008
in which p is 2 or 3
or
Figure imgf000014_0001
or
Figure imgf000014_0002
in which q is 1 to 3
(iii) —(CH2)S—R2
wherein s is 1 to 9
and R2 is as defined above
(iv) —CH2—CH2—COOH
(V) —NH—CH2—CH2—NH2
and
(vi) —NH—(CH2)t—NCO in which t is 1 to 14.
2. A compound according to claim 1 wherein one of A1 and A2 is hydrogen and the other is a group
—
Figure imgf000014_0003
3. A compound according to claim 1 wherein A1 and A2, which may be the same or different, are each a group
Figure imgf000014_0004
4. A compound according to claim 1 wherein each of A1 and A2 is a group in which R1 is independently
Figure imgf000015_0001
selected from
Figure imgf000015_0002
Figure imgf000015_0003
5. A compound according to claim 1 wherein each of A1 and A2 is the same group
Figure imgf000015_0004
6. A compound according to claim 5 wherein the group R1 is NH—CH2CH2—NH2
7. A compound according to claim 5 wherein the group R1 is NH—(CH2)t—NCO.
8. A process for the preparation of a compound of formula (I) as defined in claim 1 which comprises
derivatising glycerophosphoryl choline by treatment with a reactive intermediate which will generate the groups A1 and A2 as defined in claim 1.
9. A process according to claim 8 wherein the reactive compound is succinic anhydride, ethane diamine or a
polymethylene di-isocyanate.
10. A process for rendering a surface biocompatible which comprises contacting the surface with
glycerophosphoryl choline, or a compound as claimed in any one of claims 1 to 7 , under appropriate coupling
conditions.
11. An article to be introduced into the human or animal body or having a surface which is to be brought into contact with body fluids or cells or tissues, which article has been treated with glycerophosphoryl choline or at least one compound of formula (I) as defined in claim 1.
PCT/GB1990/000237 1989-02-14 1990-02-14 Phosphoric acid esters, their preparation and their use for the preparation of biocompatible surfaces WO1990009384A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB898903314A GB8903314D0 (en) 1989-02-14 1989-02-14 Biocompatibilising precursors
GB8903314.6 1989-02-14

Publications (1)

Publication Number Publication Date
WO1990009384A1 true WO1990009384A1 (en) 1990-08-23

Family

ID=10651664

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1990/000237 WO1990009384A1 (en) 1989-02-14 1990-02-14 Phosphoric acid esters, their preparation and their use for the preparation of biocompatible surfaces

Country Status (2)

Country Link
GB (1) GB8903314D0 (en)
WO (1) WO1990009384A1 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992006719A1 (en) * 1990-10-22 1992-04-30 Biocompatibles Limited Non-thrombogenic surfaces
WO1993005081A1 (en) * 1991-08-30 1993-03-18 Biocompatibles Ltd. Polymer treatments
WO1996029102A1 (en) * 1995-03-17 1996-09-26 Regents Of The University Of Minnesota Biocompatible materials

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0032622A1 (en) * 1979-12-20 1981-07-29 Dennis Chapman Polymerisable phospholipids and polymers thereof, methods for their preparation, methods for their use in coating substrates and forming liposomes and the resulting coated substrates and liposome compositions

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0032622A1 (en) * 1979-12-20 1981-07-29 Dennis Chapman Polymerisable phospholipids and polymers thereof, methods for their preparation, methods for their use in coating substrates and forming liposomes and the resulting coated substrates and liposome compositions

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
Chemical Abstracts, (Columbus, Ohio, US), Tenth Collective Index,Chemical Substances, 1982, page 20075CS, see reg. no. 563-24-6, 34688-34-1, 28319-77-9 and 4217-84-9 *
Chemical Abstracts, vol. 105, 1986, (Columbus, Ohio, US), Toyo Soda Mfg. Co., Ltd.: "Manufacture of polymerizable phospholipids", abstract 153302m, & Jpn. Kokai Tokkyo Koho JP 60 67,489 /85 67,489/ *
Chemical Abstracts, vol. 55, 1961, (Columbus, Ohio, US), F. Kögl et al: "Metabolism and functions of phosphatides. The preparation of a series of L-.-lecithins", column 2500h, (reg no 110440-24-9), & Rec. trav. chim. 79,661-74 (1969) *
Chemical Abstracts, vol. 55, 1961, (Columbus, Ohio, US), L.L.M. van Deenen et al: "Hydrolysis of synthetic phosphatides by Clostridium welchii (perfringens) phosphatidase", columns 21241i-21242b, (reg no 107423-73-4), & Biochem.Biophys. Research Communs. 4, 183-8 (1961) *
Chemical Abstracts, vol. 86, 1977, (Columbus, Ohio, US), Brain F.H. et al: "Preparation of 1-acyl-2-succinyl glycero-3- -phosphorylcholine and evidence against its involvement in succinate dehydrogenase action", abstract 39249p, (reg no 61510-03-0), & Chem. Phys. Lipids 1976, 17(4), 407-15 *
Chemical Abstracts, vol. 94, 1981, (Columbus, Ohio, US), Caffrey M et al: "Fluorescence quenching of model membranes. 3. Relationship between calcium adenosinetriphosphate enzyme acti- vity and the affinity of the protein for phospha- tidylcholines with different acyl chain character- istics", abstract 187754e (reg no 76743-19-6) & Biochemistry 1981, 20(7), 1949-61 *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1992006719A1 (en) * 1990-10-22 1992-04-30 Biocompatibles Limited Non-thrombogenic surfaces
US6521283B1 (en) 1990-10-22 2003-02-18 Biocompatibles Limited Non-thrombogenic surfaces
WO1993005081A1 (en) * 1991-08-30 1993-03-18 Biocompatibles Ltd. Polymer treatments
US5453467A (en) * 1991-08-30 1995-09-26 Biocompatibles Limited Polymer treatments
EP0891998A1 (en) * 1991-08-30 1999-01-20 Biocompatibles Limited Graft polymers
WO1996029102A1 (en) * 1995-03-17 1996-09-26 Regents Of The University Of Minnesota Biocompatible materials
US5711959A (en) * 1995-03-17 1998-01-27 Regents Of The University Of Minnesota Biocompatible materials

Also Published As

Publication number Publication date
GB8903314D0 (en) 1989-04-05

Similar Documents

Publication Publication Date Title
JP2741378B2 (en) Improved biocompatibility of solid surfaces
US10821211B2 (en) Coatings and biomedical implants formed from keratin biomaterials
JP7010700B2 (en) Modified collagen, its manufacturing method
US4820302A (en) Bio compatible and blood compatible materials and methods
US6177514B1 (en) Blocked functional reagants for cross-linking biological tissues
US4828561A (en) Bio compatible and blood compatible materials and methods
EP0803257B1 (en) Biomolecule attachment
EP0637309B1 (en) Metal coatings
US5645883A (en) Zwitterionic materials
JP2855224B2 (en) Preparation of polymer surface
JP2004511267A (en) Antithrombogenic membrane mimetic compositions and methods
FR2692582A1 (en) Novel crosslinkable collagen derivatives, process for obtaining same and their application to the preparation of biomaterials
US5711959A (en) Biocompatible materials
US5853744A (en) Solid-phase method for attaching a biomolecule to a substrate surface with a photoreactive crosslinking agent
EP0275293B1 (en) Polyesters
US5599587A (en) Phosphoric acid esters and their use in the preparation of biocompatible surfaces
HU208840B (en) Process for crosslinking collagens with diphenyl phosphoryl azide
WO1990009384A1 (en) Phosphoric acid esters, their preparation and their use for the preparation of biocompatible surfaces
US20070042015A1 (en) Coating composition for polymeric surfaces comprising serpin or serpin derivatives
US6890998B2 (en) Thiol activation of polyurethanes and methods of making the same
CA3152373A1 (en) Steam sterilization of hydrogels crosslinked by beta-eliminative linkers
US4748152A (en) Succinylated atelocollagen solution for use in viscosurgery and as a vitreous substitute
JP3376591B2 (en) Protein C activation promoter
KR100312712B1 (en) method for immobilizing on the surface of a living body materials
JP2743479B2 (en) Antithrombotic polyurethane

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB IT LU NL SE