Functionalized drugs and polymers derived therefrom

• US RE45,548 E1
• Filed: 10/09/2013
• Issued: 06/09/2015
• Est. Priority Date: 01/28/2005
• Status: Active Grant

• Current Assignee: Bezwada Biomedical, LLC
• Original Assignee: Bezwada Biomedical, LLC
• Inventors: Bezwada, Rao S.
• Primary Examiner(s): DICKINSON, PAUL W
• Application Number:
  US14/049,262
• Time in Patent Office: 608 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/185 Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids hydroxamic acids A61K31/16; peroxy acids A61K31/327
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/353 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/404 Indoles, e.g. pindolol
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 31/4164 1,3-Diazoles
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/535 having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• CPC Class Codes: A61K 31/7135 Compounds containing heavy metals
• CPC Class Codes: A61K 47/51 the non-active ingredient being a modifying agent
• CPC Class Codes: A61K 9/0058 : Chewing gums non-medicinal aspects, preparing chewing gum A23G4/00; chewing gum for care of the teeth or oral cavity, e.g. with breath freshener A61Q11/00
• CPC Class Codes: A61K 9/1647 : Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 31/10 : Macromolecular materials
• CPC Class Codes: C07C 69/734 : Ethers
• CPC Class Codes: C07C 69/92 : with etherified hydroxyl groups
• CPC Class Codes: C08G 18/3206 : aliphatic
• CPC Class Codes: C08G 18/711 : containing oxygen in addition to isocyanate oxygen
• CPC Class Codes: C08G 18/771 : oxygen
• CPC Class Codes: C08G 18/797 : containing carbodiimide and/or uretone-imine groups

Abstract

Compounds selected from:

where DRUG-OH, DRUG-COOH and DRUG-NH₂ are biologically active compounds; each X is independently selected from —CH₂COO— (glycolic acid moiety), —CH(CH₃)COO— (lactic acid moiety), —CH₂CH₂OCH₂COO— (dioxanone moiety), —CH₂CH₂CH₂CH₂CH₂COO— (caprolactone moiety), —(CH₂)_yCOO—, where y is 2-4 or 6-24 and —(CH₂CH₂O)_zCH₂C—, where z is 2-24; each Y is independently selected from —COCH₂O— (glycolic ester moiety), —COCH(CH₃)O— (lactic ester moiety), —COCH₂OCH₂CH₂O— (dioxanone ester moiety), —COCH₂CH₂CH₂CH₂CH₂O— (caprolactone ester moiety), —CO(CH₂)_mO—, where m is 2-4 or 6-24 and —COCH₂O(CH₂CH₂O)_n— where n is between 2-24; R′ is hydrogen, benzyl or an alkyl group, the alkyl group being either straight-chained or branched; and p is 1-6. Multi-functional compounds and drug dimers, oligomers and polymers are also disclosed.

Claims

1. A compound selected from the group consisting of:

2. A compound according to claim 1 wherein each X is independently selected from the group consisting of:

—

CH₂COO—

(glycolic acid moiety),

—

CH(CH₃)COO—

(lactic acid moiety),

—

CH₂CH₂OCH₂COO—

(dioxanone moiety), and

—

CH₂CH₂CH₂CH₂CH₂COO—

(caprolactone moiety); and

each Y is independently selected from the group consisting of;

—

COCH₂O—

(glycolic ester moiety);

—

COCH(CH₃)O—

(lactic ester moiety);

—

COCH₂OCH₂CH₂O—

(dioxanone ester moiety); and

—

COCH₂CH₂CH₂CH₂CH₂O—

(caprolactone ester moiety).

3. A composition comprising two or more different species of the compound according to claim 1.

4. An anti-inflammatory composition comprising an effective amount of at least one compound of claim 1, wherein DRUG-OH, DRUG-COOH and DRUG-NH₂ have has anti-inflammatory properties;

a pharmaceutically acceptable excipient; and

optionally further comprising a second anti-inflammatory agent.

5. A pain-reducing composition comprising an effective amount of at least one compound of claim 1, wherein DRUG-OH, DRUG-COOH and DRUG-NH₂ have has pain-reducing properties;

a pharmaceutically acceptable excipient; and

optionally further comprising a second pain-reducing agent.

6. A bioactive composition comprising an effective amount of at least one compound of claim 1 and a pharmaceutically acceptable excipient, wherein said composition is in a form suitable for oral, enteral, parenteral, topical, transdermal, ocular, vitreal, rectal, nasal, pulmonary, or vaginal administration.

7. A pharmaceutical composition comprising an effective amount of at least one compound of claim 1 and a pharmaceutically acceptable excipient.

8. A method for the reduction of pain which comprises administering to a subject in need thereof by means of controlled release drug delivery a therapeutically effective amount of at least on compound the pain-reducing composition of claim 5.

9. A method for the treatment of inflammation which comprises administering to a subject in need thereof by means of controlled drug delivery a therapeutically effective amount of at least one compound the anti-inflammatory composition of claim 4.

19. The compound of claim 1, wherein said NSAIDs and pain-reducing agents are selected from the group consisting of Aceclofenac, Acemetacin, Alminoprofen, Amodiaquine, Anileridine, Aspirin, Balsalazide, Capsaicin, Carprofen, Cinmetacin, Clometacin, Diclofenac, Diflunisal, Eprosartan, Fenbufen, Fendosal, Flubiprofen, Flufenamic acid, Ibuprofen, Indometacin, Ketorolac, Ketobemidone, Ketoprofen, Levorphanol, Loxoprofen, Mefenamic acid, Mesalazine, Nabumetone, Naproxen, Paracetamol, Phenacetin, Phenazocine, Salicylic acid, Salsalate, Salazofulfapyridine, Sulindac, Suprofen, Tiaprofenic acid, and Tolmetin and Salazosulfapyridine.

10. A compound having the formula:

11. A compound according to claim 10 wherein each X is independently selected from the group consisting of:

—

CH₂COO—

(glycolic acid moiety),

—

CH(CH₃)COO—

(lactic acid moiety),

—

CH₂CH₂OCH₂COO—

(dioxanone moiety), and

—

CH₂CH₂CH₂CH₂CH₂COO—

(caprolactone moiety).

12. A composition comprising two or more different species of the compound according to claim 10.

13. An anti-inflammatory composition comprising:

(a) an effective amount of at least one compound of claim 10;

the formula;

14. A pain-reducing composition comprising:

(a) an effective amount of at least one compound of claim 10;

the formula;

15. A bioactive composition comprising an effective amount of at least one compound of claim 10 and a pharmaceutically acceptable excipient, wherein said composition is in a form suitable for oral, enteral, parenteral, topical, transdermal, ocular, vitreal, rectal, nasal, pulmonary, or vaginal administration.

16. A pharmaceutical composition comprising an effective amount of at least one compound of claim 10 and a pharmaceutically acceptable excipient.

17. A method for the reduction of pain which comprises administering to a subject in need thereof by means of controlled release drug delivery a therapeutically effective amount of at least one compound the pain-reducing composition of claim 14.

18. A method for the treatment of inflammation which comprises administering to a subject in need thereof by means of controlled drug delivery a therapeutically effective amount of at least one compound the anti-inflammatory composition of claim 13.

20. The compound anti-inflammatory composition of claim 10 13, wherein said NSAIDs are selected from the group consisting of Aceclofenac, Acemetacin, Alminoprofen, Aspirin, Balsalazide, Carprofen, Cinmetacin, Clometacin, Diclofenac, Diflunisal, Fenbufen, Fendosal, Flubiprofen, Flufenamic acid, Ibuprofen, Indometacin Indomethacin, Ketorolac, Ketoprofen, Loxoprofen, Mefenamic acid, Naproxen, Salicylic acid, Salsalate, Salazofulfapyridine Salazosulfapyridine, Sulindac, Suprofen, Tiaprofenic acid, and Tolmetin.

24. The anti-inflammatory composition of claim 13, wherein said second anti-inflammatory agent (c) is represented by the formula of compound (a).

25. The pain-reducing composition of claim 14, wherein said second pain-reducing agent (c) is represented by the formula of compound (a).

26. The pain-reducing composition of claim 14, wherein said NSAIDs are selected from the group consisting of Aceclofenac, Acemetacin, Alminoprofen, Aspirin, Balsalazide, Carprofen, Cinmetacin, Clometacin, Diclofenac, Diflunisal, Fenbufen, Fendosal, Flubiprofen, Flufenamic acid, Ibuprofen, Indomethacin, Ketorolac, Ketoprofen, Loxoprofen, Mefenamic acid, Naproxen, Salicylic acid, Salsalate, Salazosulfapyridine, Sulindac, Suprofen, Tiaprofenic acid, and Tolmetin.

21. A bioactive composition comprising:

(a) an effective amount of at least one compound having the formula;

22. A method for the reduction of pain which comprises administering to a subject in need thereof by means of controlled release drug delivery a therapeutically effective amount of at least one compound having the formula:

23. A method for the treatment of inflammation which comprises administering to a subject in need thereof by means of controlled release drug delivery a therapeutically effective amount of at least one compound having the formula: