Phospholipid derivatized with PEG bifunctional linker and liposome containing it

• US 5,556,948 A
• Filed: 01/19/1994
• Issued: 09/17/1996
• Est. Priority Date: 01/22/1993
• Status: Expired due to Fees

• Current Assignee: Mitsubishi Chemical Corporation (Mitsubishi Chemical Group Corp.)
• Original Assignee: Mitsubishi Chemical Corporation (Mitsubishi Chemical Group Corp.)
• Inventors: Nagaike, Kazuhiro, Tagawa, Toshiaki, Awane, Kaoru
• Primary Examiner(s): Kim, Kay K. A.
• Application Number:
  US08/182,832
• Time in Patent Office: 972 Days
• Field of Search: 424/450, 424/178.4, 548/119, 530/391.9, 530/391.1
• US Class Current: 530/391.9
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: C07F 9/5537 the heteroring containing the structure -C(=O)-N-C(=O)- (both carbon atoms belong to the heteroring)

Abstract

A phospholipid derivative of the following formula (I): ##STR1## wherein A is a residue of a phospholipid having a phosphatidylethanolamine moiety, and B is a linking group having a polyalkylene glycol moiety.

Claims

1. A phospholipid derivative of formula (I):

##STR5## wherein A has the following formula (II);

##STR6## wherein each of R¹ and R², which are independent of each other, is a C₁₁ -C₁₉ alkyl group or a C₁₁ -C₁₉ alkenyl group, and D is a single bond, --C═

(NH₂⁺)(CH₂)_0-10 --, --CO(CH₂)_0-10 -- or --CH₂ (CH₂)_0-10 --, and B is a linking group having the following formula (III);

space="preserve" listing-type="equation">J-PEG-L (III)

wherein each of J and L, which are independent of each other, is a single bond, --CO(CH₂)_0-10 --, --(CH₂)_0-10 CO--, --NHCO(CH₂)_0-10 --, --(CH₂)_0-10 CONH-- or --CH₂ (CH₂)_0-10 --, and PEG is a polyethylene glycol residue.

2. A liposome comprising the phospholipid derivative of claim 1.

3. The liposome according to claim 2 further comprising a drug.

4. The liposome according to claim 1, wherein a protein having a thiol group is reacted with a double bond of a maleimide group of the phospholipid derivative.

5. The liposome according to claim 4, wherein the protein having a thiol group is an antibody wherein endogenous dithiol groups in cysteine residues thereof have been reduced to thiol groups.