Compounds and compositions for delivering active agents

• US 6,090,958 A
• Filed: 02/07/1997
• Issued: 07/18/2000
• Est. Priority Date: 03/31/1995
• Status: Expired due to Term

• Current Assignee: NOVO Nordisk North America Operations A/S
• Original Assignee: Emisphere Technologies, Inc. (Novo Nordisk A/S)
• Inventors: Ho, Koc-Kan, Leone-Bay, Andrea, Sarubbi, Donald J., Leipold, Harry R.
• Primary Examiner(s): Carr, Deborah D.
• Application Number:
  US08/797,816
• Time in Patent Office: 1,257 Days
• Field of Search: 564/161, 554/112, 554/114, 514/532, 514/534, 514/557, 514/558, 514/561, 514/563, 424/451, 424/464
• US Class Current: 554/112
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• CPC Class Codes: A61K 38/29 Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/541 Organic ions forming an ion pair complex with the pharmacologically or therapeutically active agent
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0056 Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
• 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 233/34 having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
• CPC Class Codes: C07C 233/47 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 233/48 having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a saturated carbon skeleton containing rings
• CPC Class Codes: C07C 233/51 having the carbon atom of the carboxamide group bound to an acyclic carbon atom of a carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 233/52 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 233/54 having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
• 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 233/69 of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 233/81 : 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 233/83 : of an acyclic saturated carbon skeleton
• CPC Class Codes: C07C 233/84 : of a saturated carbon skeleton containing rings
• CPC Class Codes: C07C 233/87 : of a carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 235/12 : having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07C 235/24 : 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 235/34 : having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• 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 235/52 : having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07C 235/56 : 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 235/60 : having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• 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 235/66 : with carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings being part of condensed ring systems and singly-bound oxygen atoms, bound to the same carbon skeleton
• CPC Class Codes: C07C 235/74 : of a saturated carbon skeleton
• CPC Class Codes: C07C 235/82 : with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring
• CPC Class Codes: C07C 237/12 : having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups peptides C07K
• CPC Class Codes: C07C 237/20 : the carbon skeleton containing six-membered aromatic rings
• CPC Class Codes: C07C 237/36 : having the nitrogen atom of the carboxamide group bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
• CPC Class Codes: C07C 237/40 : having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 237/42 : having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
• CPC Class Codes: C07C 243/38 : with acylating carboxyl groups bound to carbon atoms of six-membered aromatic rings
• CPC Class Codes: C07C 259/06 : having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 271/28 : to a carbon atom of a non-condensed six-membered aromatic ring
• CPC Class Codes: C07C 271/54 : to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
• CPC Class Codes: C07D 209/48 : with oxygen atoms in positions 1 and 3, e.g. phthalimide
• CPC Class Codes: C07D 211/62 : attached in position 4
• CPC Class Codes: C07D 213/81 : Amides; Imides
• CPC Class Codes: C07D 213/82 : in position 3
• CPC Class Codes: C07D 239/42 : One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 241/24 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 257/04 : Five-membered rings
• CPC Class Codes: C07D 295/192 : from aromatic carboxylic acids
• CPC Class Codes: C07D 311/12 : substituted in position 3 and unsubstituted in position 7
• CPC Class Codes: C07D 311/24 : with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
• CPC Class Codes: C07D 311/30 : not hydrogenated in the hetero ring, e.g. flavones

Abstract

Carrier compounds and compositions therewith which are useful in the delivery of active agents are provided. Methods of administration and preparation are provided as well.

Claims

1. A compound having the formula ##STR9## or a salt thereof.

2. A method for preparing a composition, said method comprising mixing:

(A) at least one active agent;

(B) at least one compound as defined in claim 1; and

(C) optionally, a dosing vehicle.

15. A dosage unit form comprising:

(A) a composition as defined in claim 1; and

(B) (a) an excipient

(b) a diluent,

(c) a disintegrant,

(d) a lubricant,

(e) a plasticizer,

(f) a colorant,

(g) a dosing vehicle, or

(h) any combination thereof.

16. A composition as defined in claim 15;

wherein said active agent is selected from the group consisting of a biologically active agent, a chemically active agent, or a combination thereof.

17. A dosage unit form as defined in claim 16, wherein said biologically active agent comprises at least one peptide, mucopolysaccharide, carbohydrate, or lipid.

18. A dosage unit form as defined in claim 16, wherein said biologically active agent is selected from the group consisting of human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interferon, interleukin-II, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoclonal antibody, samatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, cromolyn sodium, vancomycin, parathyroid hormone, desferrioxamine (DFO), or any combination thereof.

19. A dosage unit form as defined in claim 18, wherein said biologically active agent comprises an interferon, interleukin-II, insulin, heparin, low molecular weight heparin, calcitbnin, oxytosin, vasopressin, vancomycin, DFO, parathyroid hormone, and combinations thereof.

20. A dosage unit form as defined in claim 15, wherein said biologically active agent comprises parathyroid hormone.

21. A dosage unit form as defined in claim 15, wherein said biologically active agent comprises recombinant human growth hormone.

22. A dosage unit form as defined in claim 15, wherein said biologically active agent agent comprises heparin.

23. A dosage unit form as defined in claim 15, wherein said biologically active agent comprises low molecular weight heparin.

24. A dosage unit form as defined in claim 15, in the form of a tablet, a capsule, or a liquid.

25. A dosage unit form as defined in claim 24, wherein said dosing vehicle is selected from the group consisting of water, 1,2-propane diol, ethanol, or any combination thereof.

3. A composition comprising:

(A) at least one active agent; and

(B) a carrier comprising a compound having the following formula ##STR10## or a salt thereof.

4. A composition as defined in claim 3, wherein said active agent is selected from the group consisting of a biologically active agent, a chemically active agent, or a combination thereof.

5. A composition as defined in claim 4, wherein said biologically active agent comprises at least one peptide, mucopolysaccharide, carbohydrate, or lipid.

6. A composition as defined in claim 4, wherein said biologically active agent is selected from the group consisting of human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interferon, interleukin-II, insulin, heparin, low molecular weight heparin, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoclonal antibody, samatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, cromolyn sodium, vancomycin, parathyroid hormone, desferrioxamine (DFO), or any combination thereof.

7. A composition as defined in claim 6, wherein said biologically active agent comprises an interferon, interleukin-II, insulin, heparin, low molecular weight heparin, calcitonin, oxytosin, vasopressin, vancomycin, DFO, parathyroid hormone, and combinations thereof.

8. A composition as defined in claim 4, wherein said biologically active agent comprises parathyroid hormone.

9. A composition as defined in claim 4, wherein said biologically active agent comprises recombinant human growth hormone.

10. A composition as defined in claim 4, wherein said biologically active agent agent comprises heparin.

11. A composition as defined in claim 4, wherein said biologically active agent comprises low molecular weight heparin.

12. A composition as defined in claim 3, wherein said carrier comprises a poly(amino acid).

13. A composition as defined in claim 3, wherein said carrier comprises a polypeptide.

14. A method for administering a biologically-active agent to an animal in need of said agent, said method comprising administering orally to said animal a composition as defined in claim 4.