.

Pharmaceutical Business Intelligence

  • Anticipate P&T budget requirements
  • Evaluate market entry opportunities
  • Find generic sources and suppliers
  • Predict branded drug patent expiration

► Plans and Pricing

Upgrade to enjoy subscriber-only features like email alerts and data export. See the Plans and Pricing

DrugPatentWatch Database Preview

Details for Patent: 5,693,338

« Back to Dashboard

Details for Patent: 5,693,338

Title: Diketopiperazine-based delivery systems
Abstract:Compositions useful in the delivery of active agents are provided. These delivery compositions include (a) an active agent; and either (b)(1) a carrier of (i) at least one amino acid and (ii) at least one diketopiperazine or (b)(2) at least one mono-N-substituted, di-N-substituted, or unsubstituted diketopiperazine. Methods for preparing these compositions and administering these compositions are also provided.
Inventor(s): Milstein; Sam J. (Larchmont, NY)
Assignee: Emisphere Technologies, Inc. (Hawthorne, NY)
Filing Date:Sep 29, 1994
Application Number:08/315,200
Claims:1. A delivery composition comprising:

(a) an active agent;

(b) a diketopiperazine having the formula: ##STR5## wherein R.sup.1, R.sup.2, or R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1 -C.sub.24 alkyl, C.sub.1 -C.sub.24 alkenyl, phenyl, naphthyl, (C.sub.1 -C.sub.10 alkyl)phenyl, (C.sub.1 -C.sub.10 alkenyl)phenyl, (C.sub.1 -C.sub.10 alkyl)naphthyl, (C.sub.1 -C.sub.10 alkenyl)naphthyl, phenyl (C.sub.1 -C.sub.10 alkyl), phenyl (C.sub.1 -C.sub.10 alkenyl), naphthyl (C.sub.1 -C.sub.10 alkyl), and naphthyl (C.sub.1 -C.sub.10 alkenyl);

R.sup.1 or R.sup.2, or both R.sup.1 and R.sup.2, optionally, are independently substituted with C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkenyl, C.sub.1 -C.sub.4 alkoxy, --OH, --SH, and --CO.sub.2 R.sup.3 or any combination thereof; wherein R.sup.3 is hydrogen, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkenyl;

R.sup.1, R.sup.2, or R.sup.1 and R.sup.2 , optionally, are independently interrupted by oxygen, nitrogen, sulfur, or any combination thereof;

said phenyl, naphthyl, or phenyl and naphthyl groups, optionally, are independently substituted by C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkoxy, --OH, --SH, or CO.sub.2 R.sup.4 wherein R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, or C.sub.1 -C.sub.6 alkenyl; and

R.sup.1 and R.sup.2 are not both hydrogen; and

(c) an enzyme inhibitor selected from the group consisting aprotinin, Bowman-Birk inhibiting actinonin, or any combination of the foregoing.

2. A delivery composition as defined in claim 1, comprising a microsphere.

3. A delivery composition as defined in claim 2, wherein said microsphere comprises a microcapsule.

4. A delivery composition as defined in claim 2, wherein said microsphere has a diameter of less than about 10 .mu.m.

5. A delivery composition as defined in claim 1, wherein said active agent comprises a fragrance.

6. A delivery composition as defined in claim 1, wherein said active agent comprises a biologically active agent.

7. A delivery composition as defined in claim 6, wherein said biologically active agent is selected from the group consisting of a peptide, a mucopolysaccharide, a carbohydrate, a lipid, a pesticide, or any combination thereof.

8. The delivery composition as defined in claim 7, 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, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoolonal antibody, somatostatin, adrenocorticotropin, gonadotropin releasing hormone, oxytocin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine (DFO), or any combination of any of the foregoing.

9. A delivery composition as defined in claim 8, wherein said biologically-active agent is selected from the group consisting of an interferon, interleukin-II, insulin, heparin, calcitonin, oxytocin, vasopressin, cromolyn sodium, vancomycin, DFO, or any combination of any of the foregoing.

10. A delivery composition as defined in claim 1, wherein said diketopiperazine is derived from two .alpha.-amino acids.

11. A delivery composition as defined in claim 10, wherein said two .alpha.-amino acids from which said diketopiperazine is derived are independently selected from the group consisting of glutamic acid, aspartic acid, tyrosine, phenylalanine, and optical isomers thereof.

12. A delivery composition as defined in claim 10, wherein said two .alpha.-amino acids from which said diketopiperazine is derived are the same.

13. A delivery composition as defined in claim 10, wherein said diketopiperazine is prepared by the thermal condensation of said two .alpha.-amino acids from which said diketopiperazine is derived.

14. A pharmacological composition comprising:

(a) at least one pharmacologically active agent; and

(b) a diketopiperazine having the formula: ##STR6## wherein R.sup.1, R.sup.2, or R.sup.1 and R.sup.2 independently are hydrogen, C.sub.1 -C.sub.24 alkyl, C.sub.1 -C.sub.24 alkenyl, phenyl, naphthyl, (C.sub.1 -C.sub.10 alkyl)phenyl, (C.sub.1 -C.sub.10 alkenyl)phenyl, (C.sub.1 -C.sub.10 alkyl)naphthyl, (C.sub.1 -C.sub.10 alkenyl)naphthyl, phenyl (C.sub.1 -C.sub.10 alkyl), phenyl (C.sub.1 -C.sub.10 alkenyl), naphthyl (C.sub.1 -C.sub.10 alkyl), and naphthyl (C.sub.1 -C.sub.10 alkenyl);

R.sup.1 or R.sup.2, or both R.sup.1 and R.sup.2, optionally, are independently substituted with C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkenyl, C.sub.1 -C.sub.4 alkoxy, --OH, --SH, and --CO.sub.2 R.sup.3 or any combination thereof; wherein R.sup.3 is hydrogen, C.sub.1 -C.sub.4 alkyl, or C.sub.1 -C.sub.4 alkenyl;

R.sup.1, R.sup.2, or R.sup.1 and R.sup.2, optionally, are independently interrupted by oxygen, nitrogen, sulfur, or any combination thereof;

said phenyl, naphthyl, or phenyl and naphthyl groups, optionally, are independently substituted by C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkoxy, --OH, --SH, or CO.sub.2 R.sup.4 wherein R.sup.4 is hydrogen, C.sub.1 -C.sub.6 alkyl, or C.sub.1 -C.sub.6 alkenyl; and

R.sup.1 and R.sup.2 are not both hydrogen; and

(c) an enzyme inhibitor selected from the group consisting aprotinin, Bowman-Birk inhibiting actinonin, or any combination of the foregoing.

15. A dosage unit form comprising:

(A) a delivery 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 dosage unit form as defined in claim 14, comprising an oral dosage unit form.

17. A dosage unit form as defined in claim 15, selected from the group consisting of a tablet, a capsule, and a liquid.

18. A method for administering a biologically active agent to an animal in need of such agent, said method comprising administering orally to said animal, a composition as defined in claim 1.

19. A delivery composition comprising:

(a) an active agent;

(b) a diketopiperazine having the formula ##STR7## (c) an enzyme inhibitor selected from the group consisting aprotinin, Bowman-Birk inhibiting actinonin, or any combination of the foregoing.

20. A delivery composition as defined in claim 19, comprising a microsphere.

21. A delivery composition as defined in claim 20, wherein said microsphere comprises a microcapsule.

22. A delivery composition as defined in claim 20, wherein said microsphere has a diameter of less than about 10 .mu.m.

23. A delivery composition as defined in claim 19, wherein said active agent comprises a fragrance.

24. A delivery composition as defined in claim 19, wherein said active agent comprises a biologically active agent.

25. A delivery composition as defined in claim 24, wherein said biologically active agent is selected from the group consisting of a peptide, a muco-polysaccharide, a carbohydrate, a lipid, a pesticide, or any combination of any of the foregoing.

26. A delivery composition as defined in claim 24, wherein said biologically-active agent is selected from the group consisting of human growth hormone, bovine growth hormone, growth hormone-releasing hormone, an interfer-on, interleukin-II, insulin, heparin, calcitonin, erythropoietin, atrial naturetic factor, an antigen, a monoclonal antibody, somatostatin, adrenocorticotropin, gonadotro-pin releasing hormone, oxytocin, vasopressin, cromolyn sodium, vancomycin, desferrioxamine (DFO), or any combination of any of the foregoing.

27. A delivery composition as defined in claim 26, wherein said biologically-active agent is selected from the group consisting of an interferon, interleukin-II, insulin, heparin, calcitonin, oxytocin, vasopressin, cromolyn sodium, vancomycin, DFO, or any combination of any of the foregoing.

28. A pharmacological composition comprising:

(A) at least one pharmacologically active agent;

(B) a carrier comprising a diketopiperazine having the formula: ##STR8## (c) an enzyme inhibitor selected from the group consisting aprotinin, Bowman-Birk inhibiting actinonin, or any combination of the foregoing.

29. A dosage unit form comprising:

(A) a delivery composition as defined in claim 19; 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.

30. A dosage unit form as defined in claim 29, comprising an oral dosage unit form.

31. A dosage unit form as defined in claim 29, selected from the group consisting of a tablet, a capsule, and a liquid.

32. A method for administering a biologically active agent to an animal in need of such agent, said method comprising administering orally to said animal, a delivery composition as defined in claim 19.
« Back to Dashboard

For more information try a trial or see the database preview and plans and pricing

How are People Using DrugPatentWatch?

Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verifification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.

`abc