Biocompatible surfaces

• US 4,348,329 A
• Filed: 12/22/1980
• Issued: 09/07/1982
• Est. Priority Date: 12/20/1979
• Status: Expired due to Term

• Current Assignee: Biocompatibles Ltd (Abbott Laboratories)
• Original Assignee: Dennis Chapman
• Inventors: Chapman, Dennis
• Primary Examiner(s): Niebling, John F.
• Application Number:
  US06/218,556
• Time in Patent Office: 624 Days
• Field of Search: 260/403, 260/945
• US Class Current: 554/80
• CPC Class Codes: A61K 9/1273 Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances polymers grafted or coated on phosphatidyl liposomes A61K9/1271, on non-phosphatidyl liposomes A61K9/1272
• CPC Class Codes: A61L 15/44 Medicaments
• CPC Class Codes: A61L 2300/626 Liposomes, micelles, vesicles
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 33/00 Antithrombogenic treatment of surgical articles, e.g. sutures, catheters, prostheses, or of articles for the manipulation or conditioning of blood; Materials for such treatment
• CPC Class Codes: A61L 33/064 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L33/062 takes precedence
• CPC Class Codes: B01D 2323/30 Cross-linking
• CPC Class Codes: B01D 2323/34 Use of radiation
• CPC Class Codes: B01D 67/0088 Physical treatment with compounds, e.g. swelling, coating or impregnation
• CPC Class Codes: B01D 67/00933 by addition of a layer chemically bonded to the membrane
• CPC Class Codes: C07C 51/353 by isomerisation; by change of size of the carbon skeleton
• CPC Class Codes: C07C 57/18 with only carbon-to-carbon triple bonds as unsaturation
• CPC Class Codes: C07F 9/10 Phosphatides, e.g. lecithin
• CPC Class Codes: C08F 38/00 Homopolymers and copolymers of compounds having one or more carbon-to-carbon triple bonds
• CPC Class Codes: C08L 43/02 Homopolymers or copolymers of monomers containing phosphorus
• CPC Class Codes: C08L 49/00 Compositions of homopolymers or copolymers of compounds having one or more carbon-to-carbon triple bonds; Compositions of derivatives of such polymers
• CPC Class Codes: Y10S 623/92 Method or apparatus for preparing or treating prosthetic

Abstract

New phospholipids containing a conjugated di-yne system have the formula: ##STR1## wherein at least one of B₁ and B₂ is a group of the formula

--(CO).sub.p --X.sub.1 --C.tbd.C--C.tbd.C--Y.sub.1

wherein p is 0 or 1, X₁ is a direct bond or a divalent aliphatic or cycloaliphatic group, Y₁ is H or a monovalent aliphatic or cycloaliphatic group, the total number of carbon atoms in X₁ and Y₁ in each of B₁ and/or B₂ being 8 to 26; and the other of B₁ and B₂ is either (a) the same or a different group of the formula:

--(CO).sub.p --X.sub.1 --C.tbd.C--C.tbd.C--Y.sub.1

where X₁, Y₁ or p are as defined above;

or (b) is an aliphatic or cycloaliphatic group containing at least 8 carbon atoms; n is 0 or 1, m is 2, 3 or 4 and each R independently represents an alkyl group containing 1 to 4 carbon atoms, and are prepared by esterification and/or etherification of glycerol by conventional techniques. The conjugated di-yne systems can be cross-linked by actinic radiation to give intermolecular and, in certain cases, also intramolecular cross-linking. Thin layers of the phospholipids can be coated onto substrates subsequently to be brought into contact with blood or other body fluids and then cross-linked to give polymer coated surfaces which have a reduced tendency to initiate blood coagulation, for example, compared to untreated surfaces. Artificial lenses for the human eye treated in this way have a reduced tendency to cause endothelial damage. The phospholipids of the invention can also be formed into liposomes and the conjugated di-yne system then cross-linked. Physiologically active materials such as drugs, enzymes or antigens can be incorporated into the liposomes which can then be used as prolonged release formulations.

Claims

1. A conjugated di-yne of the general formula:

##STR13## wherein at least one of B₁ and B₂ is a group of the formula

space="preserve" listing-type="equation">--(CO).sub.p --X.sub.1 --C.tbd.C--C.tbd.C--Y.sub.1

wherein p is 0 or 1, X₁ is a direct bond or a divalent aliphatic or cycloaliphatic group, Y₁ is H or a monovalent aliphatic or cycloaliphatic group, the total number of carbon atoms in X₁ and Y₁ in each of B₁ and/or B₂ being 8 to 26; and

the other of B₁ and B₂ is either (a) the same or a different group of the formula;

space="preserve" listing-type="equation">--(CO).sub.p --X.sub.1 --C.tbd.C--C.tbd.C--Y.sub.1

where X₁, Y₁ or p are as defined above;

or (b) is an aliphatic or cycloaliphatic group containing at least 8 carbon atoms;

n is 0 to 1, m is 2, 3 or 4 and each R independently represents an alkyl group containing 1 to 4 carbon atoms.

2. A di-yne according to claim 1 wherein B₁ and B₂ are identical or different groups of the formula:

space="preserve" listing-type="equation">--CO--X.sub.1 --C.tbd.C--C.tbd.C--Y.sub.1.

3. A di-yne according to claim 1 or 2 wherein X₁ and Y₁ are both saturated unbranched hydrocarbon chains, each pair of X₁ and Y₁ groups containing 10 to 16 carbon atoms.

4. A di-yne according to claim 2 wherein the number of carbon atoms in each X₁ is such that the di-yne will undergo both intramolecular and intermolecular crosslinking on exposure to actinic radiation.

5. A di-yne according to claims 1 or 2 wherein n is 1, m is 2 and each R is methyl.

6. A di-yne of the formula:

##STR14## wherein q is 9 to 11.

7. A di-yne of the formula:

##STR15##

8. A di-yne of the formula:

##STR16##