Modified amino acids for drug delivery

• US 6,180,140 B1
• Filed: 06/02/1995
• Issued: 01/30/2001
• Est. Priority Date: 04/22/1994
• Status: Expired due to Term

• Current Assignee: NOVO Nordisk North America Operations A/S
• Original Assignee: Emisphere Technologies, Inc. (Novo Nordisk A/S)
• Inventors: Leone-Bay, Andrea, Wang, Nai Fang
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): CHANNAVAJJALA, LAKSHMI SARADA
• Application Number:
  US08/460,265
• Time in Patent Office: 2,069 Days
• Field of Search: 424/451, 424/489, 424/464, 424/499, 424/490, 514/553, 514/561
• US Class Current: 424/489
• CPC Class Codes: A61K 31/16 Amides, e.g. hydroxamic acids
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 38/212 IFN-alpha
• CPC Class Codes: A61K 38/23 Calcitonins
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: C07C 229/42 with carboxyl groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by saturated carbon chains
• CPC Class Codes: C07C 233/55 having the carbon atom of the carboxamide group bound to a carbon atom of an unsaturated carbon skeleton
• CPC Class Codes: C07C 233/63 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07C 233/87 of a carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 235/38 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/64 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/84 with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 237/22 having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated peptides C07K
• CPC Class Codes: C07C 2601/02 with a three-membered ring
• CPC Class Codes: C07C 2601/08 the ring being saturated
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 2601/18 with a ring being at least seven-membered
• CPC Class Codes: C07C 279/14 : being further substituted by carboxyl groups
• CPC Class Codes: C07K 1/1077 : by covalent attachment of residues other than amino acids or peptide residues, e.g. sugars, polyols, fatty acids
• CPC Class Codes: C07K 5/06043 : Leu-amino acid
• CPC Class Codes: C07K 5/06095 : Arg-amino acid

Abstract

The present invention relates to an oral delivery system, and in particular to modified amino acids or peptides for use as a delivery system of sensitive agents such as bioactive peptides. The modified amino acids or peptides can form non-covalent mixtures or microspheres with active biological agents. These mixtures or microspheres are suitable for oral administration of biologically active agents to animals. Methods for the preparation of such amino acids and peptides are also disclosed.

Claims

1. A compound having the formula

wherein A is arginine, or citrulline.

2. A compound according to claim 1, wherein A is acylated at two or more functional groups.

3. A compound according to claim 1, wherein A is arginine.

4. A compound according to claim 2, wherein A is arginine.

5. A compound according to claim 2, wherein A is tryptophan.

6. A compound according to claim 1, wherein A is citrulline.

7. A compound according to claim 2, wherein A is citrulline.

8. A compound having the formula

wherein A and B independently are arginine or leucine.

9. A compound according to claim 8, wherein if A, B or A and B are arginine , A, B, or A and B are acylated at two or more functional groups.

10. A compound having the formula

wherein A is arginine.

11. A compound according to claim 10, wherein A is acylated at two or more functional groups.

12. A compound having the formula

wherein A is leucine.

13. A compound having the formula

wherein A is phenylglycine.

14. A compound having the formula

wherein A is phenylglycine.