Conjugate of adriamycin and cyclodextrin

• US 5,183,883 A
• Filed: 09/27/1991
• Issued: 02/02/1993
• Est. Priority Date: 09/28/1990
• Status: Expired due to Fees

• Current Assignee: Mercian Corporation (Kirin Holdings Company Limited)
• Original Assignee: Mercian Corporation (Kirin Holdings Company Limited)
• Inventors: Nishida, Hiroshi, Shirai, Masataka, Yamamoto, Reijko, Okajima, Yasuo, Tone, Hiroshi, Tanaka, Hiroshi, Kominato, Kaichiro, Yoshioka, Takeo, Iguchi, Hiroshi, Hirano, Shin-ichi, Okamoto, Rokuro
• Primary Examiner(s): Rollins, John W.
• Assistant Examiner(s): Peselev, Elli
• Application Number:
  US07/766,791
• Time in Patent Office: 494 Days
• Field of Search: 536/6.9, 536/112, 519/34
• US Class Current: 536/6.4
• CPC Class Codes: A61K 47/6951 using cyclodextrin cyclodextrins used as simple excipients A61K47/40
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07H 15/252 Naphthacene radicals, e.g. daunomycins, adriamycins
• CPC Class Codes: C08B 37/0012 Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof

Abstract

Adriamycin derivatives represented by formula (I) ##STR1## wherein R denotes a divalent hydrocarbon group,

CD denotes a cyclodextrin residue,

m is 1 to 8, and

n is 0 to 8.

The compounds exhibit excellent anti-cancer activity over a wide administration range, have low toxicity and sustained release, and maintain activity for a long period of time; thus, they are quite useful as an anti-cancer agent.

Claims

1. A compound of formula (I) ##STR7## wherein R is a divalent hydrocarbon group selected from the group consisting of C₁ -C₆ alkylene, --C═

C--, C₅ -C₇ cycloalkylene, 1,2-phenylene and 2,3- and 1,8-naphthalene,

CD is a cyclodextrin residue,

m is 1 to 8, and

n is 0 to 8.

2. The compound of claim 1 wherein R is ethylene, 1,2- or 1,3-propylene, 1,2-, 1,3- or 1,4-butylene, 1,2-cyclohexylene, 1,2-phenylene, or 2,3- or 1,8-naphthalene.

3. The compound of claim 1 wherein CD is a γ

-cyclodextrin residue.

4. The compound of claim 1 wherein m is 1 or 2, and n is 0 to 2.

5. The compound of claim 1 wherein R is ethylene, CD is a γ

-cyclodextrin residue, m is 1, and n is 0.

6. The compound of claim 1 wherein R is 1,2-phenylene, CD is a γ

-cyclodextrin residue, m is 1 or 2, and n is 0.

7. The compound of claim 1 wherein R is 2,3- or 1,8-naphthalene, CD is a γ

-cyclodextrin residue, n is 1, and n is 0.

8. The compound of claim 1 wherein R is 1,2-cyclohexylene, CD is a γ

-cyclodextrin residue, m is 1, and n is 0.