EP0354855A2
Expired / Lapsed
EP
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Liposomes on which adsorption of proteins is inhibited
Assignee: Terumo Corp
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Filing: 1989-08-11
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Granted: —
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Expires: 2009-08-11
Abstract
Abstract Agents for inhibiting adsorption of proteins on the liposome surface and liposomes which are agglutination-free by binding said inhibiting agent on the surface are disclosed. The above-mentioned inhibiting agents comprise a hydrophobic moiety and a hydrophilic macromolecular chain moiety. Adsorption of plasma proteins on the liposomes is inhibited due to the hydrophilic moiety exposed on the liposome surface with a result that agglutination of the liposomes in plasma is prevented. Therefore, there is no danger of embolism in blood vessels inhibiting blood flow when the liposomes are introduced into the living body. Accordingly, the liposomes are especially highly useful as artificial erythrocytes for which a large dose of liposomes is needed for administration. Moreover, when liposomes are introduced into the living body, antibody protein (immunoglobulin) to the liposome which is an antigen will be adsorbed on the liposome to produce foreign body recognition in the phagocytes (macrophage) with a result that the liposome will be included in the macrophage and disappear within a short period of time. Thus, inhibition of the protein adsorption on liposome can delay disappearance of the liposome in plasma. In addition, a method for preparing the above-described liposomes is disclosed.
Inventors
- 👤 Hiroshi Yoshida
- 👤 Hiroshi Goto
Bibliographic Details
Application Number
—
Jurisdiction
EP
Data Source
google_patents
Last Synchronized
2026-10-23 16:31
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K9/1272; A61P; A61P7/00; A61P7/08; Y; Y10; Y10T; Y10T428/00; Y10T428/29; Y10T428/2982; Y10T428/2984
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
32 words
1) An agent for inhibiting adsorption of proteins on the liposome surface comprising a compound having a hydrophobic moiety at one end and a hydrophilic macromolecular chain moiety at the other end.
Claim 2
Dependent Claim
32 words
1) An agent for inhibiting adsorption of proteins on the liposome surface comprising a compound having a hydrophobic moiety at one end and a hydrophilic macromolecular chain moiety at the other end.
Claim 3
Dependent Claim
29 words
2) An agent for inhibiting adsorption of proteins on the liposome surface according to Claim 1 wherein the hydrophobic moiety and the hydrophilic macromolecular chain moiety are covalently bound.
Claim 4
Dependent Claim
31 words
3) An agent for inhibiting adsorption of proteins on the liposome surface according to Claim 1 wherein degree of polymerization for the hydrophilic macromolecular chain moiety is 5 - 1000 moles.
Claim 5
Dependent Claim
26 words
4) An agent for inhibiting adsorption of proteins on the liposome surface according to Claim 1 wherein the hydrophilic macromolecular chain moiety consists of polyethylene glycol.
Claim 6
Dependent Claim
32 words
5) An agent for inhibiting adsorption of proteins on the lipsome surface according to Claim 1 wherein the hydrophobic moiety and the hydrophilic macromolecular chain moiety are bound via an ether bond.
Claim 7
Dependent Claim
44 words
6) An agent for inhibiting adsorption of proteins on the liposome surface according to Claim 5 wherein the hydrophilic macromolecular chain moiety is bound with an alcoholic radical of a long chain-aliphatic alcohol, a sterol, a polyoxypropylene alkyl or a glycerin fatty acid ester.
Claim 8
Dependent Claim
33 words
7) An agent for inhibiting adsorption of proteins on the liposome surface according to Claims 1 - 4 wherein the hydrophilic macromolecular chain moiety is bound with the hydrophilic group of a phospholipid.
Claim 9
Dependent Claim
21 words
8) An agent for inhibiting adsorption of proteins on the liposome surface according to Claim 7 wherein the phospholipid is phosphatidylethanolamine.
Claim 10
Dependent Claim
25 words
9) An agent for inhibiting adsorption of proteins on the liposome surface according to Claim 7 wherein the bond is formed via a triazine ring.
Claim 11
Dependent Claim
25 words
10) An agent for inhibiting adsorption of proteins on the liposome surface according to Claim 7 wherein the bond is formed via an amide bond.
Claim 12
Dependent Claim
46 words
11) A liposome in which the hydrophobic moiety of the agent for inhibiting adsorption of proteins on the liposome surface according to Claims 1 - 10 is fixed to the liposome membrane-constituting lipid layer and the hydrophilic macromolecular chain moiety externally extends from the liposome surface.
Claim 13
Dependent Claim
14 words
12) A liposome according to Claim 11 wherein hemoglobin is enclosed within the liposome.
Claim 14
Dependent Claim
45 words
13) A method for preparing liposomes on which adsorption of proteins is inhibited which comprises adding an agent for inhibiting adsorption of proteins on the liposome surface according to Claims 1 - 10 to a liposome suspension and then collecting the liposomes from said suspension.
Claim 15
Dependent Claim
41 words
14) A method for preparing liposomes on which adsorption of proteins is inhibited which comprises uniformly mixing an agent for inhibiting adsorption of proteins on the liposome surface with a liposome membrane-forming lipid and forming liposomes using the mixture thus obtained.
Claim 16
Dependent Claim
41 words
14) A method for preparing liposomes on which adsorption of proteins is inhibited which comprises uniformly mixing an agent for inhibiting adsorption of proteins on the liposome surface with a liposome membrane-forming lipid and forming liposomes using the mixture thus obtained.
Claim 17
Dependent Claim
36 words
15) A liposome on which adsorption of proteins is inhibited comprising one end of a hydrophilic macromolecular chain moiety directly bound with a liposome membrane-constituting lipid and the other end externally extending from the liposome surface.
Claim 18
Dependent Claim
36 words
15) A liposome on which adsorption of proteins is inhibited comprising one end of a hydrophilic macromolecular chain moiety directly bound with a liposome membrane-constituting lipid and the other end externally extending from the liposome surface.
Claim 19
Dependent Claim
67 words
16) A method for preparing liposomes on which adsorption of proteins is inhibited which comprises adding a hydrophilic macromolecular compound activated so as to bind with a liposome membrane-constituting lipid to a liposome suspension and allowing to react in such a way that one end of the hydrophilic macromolecule is bound with the liposome membrane-constituting lipid and the other end is extended externally from the liposome surface.
Claim 20
Dependent Claim
67 words
16) A method for preparing liposomes on which adsorption of proteins is inhibited which comprises adding a hydrophilic macromolecular compound activated so as to bind with a liposome membrane-constituting lipid to a liposome suspension and allowing to react in such a way that one end of the hydrophilic macromolecule is bound with the liposome membrane-constituting lipid and the other end is extended externally from the liposome surface.
References Cited (Backward Citations)
No citation records indexed.
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