Aminocarnitine directed pharmaceutical agents

• US 4,866,040 A
• Filed: 01/15/1987
• Issued: 09/12/1989
• Est. Priority Date: 01/06/1986
• Status: Expired due to Term

• Current Assignee: CepTor Corp. (Xechem International, Inc.)
• Original Assignee: Alfred Stracher, Leo Kesner
• Inventors: Kesner, Leo, Stracher, Alfred
• Primary Examiner(s): Lovering, Richard D.
• Application Number:
  US07/003,888
• Time in Patent Office: 971 Days
• Field of Search: 514/547, 514/305, 514/535, 514/547, 514/556, 514/821, 514/2, 514/17, 428/402.2, 530/330
• US Class Current: 514/16.4
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 47/542 Carboxylic acids, e.g. a fatty acid or an amino acid
• CPC Class Codes: A61K 9/127 Liposomes
• CPC Class Codes: C07C 229/22 the carbon skeleton being further substituted by oxygen atoms
• CPC Class Codes: C07C 229/26 having more than one amino group bound to the carbon skeleton, e.g. lysine
• CPC Class Codes: C07C 279/12 being further substituted by nitrogen atoms not being part of nitro or nitroso groups
• CPC Class Codes: C07C 323/58 with amino groups bound to the carbon skeleton
• CPC Class Codes: C07K 5/0205 containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
• CPC Class Codes: C07K 5/06043 Leu-amino acid
• CPC Class Codes: Y10T 428/2984 Microcapsule with fluid core [includes liposome]

Abstract

Carnitine, aminocarnitine and cysteic acid serve as carriers to bring pharmaceutically active compounds to desired sites in the body, e.g. skeletal muscle or the heart. The pharmaceutically active compound can be a protease inhibitor, a cardioactive drug for combating arrythmia, etc. The linkage is chemical through one or more alcohol, carboxyl or amine groups using reagents such as glutaraldehyde, dicarboxylic acid anhydrides and acid halides and carbodiimides. Carnitine derivatives are also incorporated into liposomes which are then used as carriers of active pharmaceutical agents.

Claims

1. A compound comprising aminocarnitine covalently bonded through an alcohol, carboxyl or amine group to a pharmaceutically active compound.

2. A compound according to claim 1, wherein the pharmaceutically active compound is a protease inhibitor.

3. A compound according to claim 1, wherein the pharmaceutically active compound is pepstatin or leucylargininal.

4. A pharmaceutical composition preferentially deliverable to cardiac and skeletal muscle comprising a pharmaceutically effective amount of the compound of claim 3 effective therefor and a pharmaceutically acceptable diluent.

5. A compound according to claim 1, wherein the pharmaceutically active compound is cardioactive.

6. A compound according to claim 1, wherein the active compound is active against arrythmia.

7. A pharmaceutical composition preferentially deliverable to cardiac and skeletal muscle comprising a pharmaceutically effective amount of the compound of claim 6 effective therefor and a pharmaceutically acceptable diluent.

8. A compound according to claim 1, wherein the bond is through a bifunctional radical.

9. A compound according to claim 1, wherein the bond is through at least on bifunctional radical of a dialdehyde, carbodiimide, dicarboxylic acid or aminoacid.

10. A compound according to claim 1, wherein the pharmaceutically active compound is procainamide.

11. In the treatment of a muscle disorder in a patient wherein a pharmaceutically active compound is administered to such patient, the improvement which comprises administering said compound covalently bonded through an alcohol, carboxyl or amine group to aminocarnitine.

12. The method according to claim 11, wherein the muscle being treated is a skeletal muscle.

13. The method according to claim 12, wherein the pharmaceutically active compound is a protease inhibitor.

14. The method according to claim 11, wherein the muscle being treated is the heart.

15. The method according to claim 14, wherein the pharmaceutically active compound is active against arrythmia.

16. The method according to claim 11, wherein the pharmaceutically active compound is procainamide.